@article {pmid38587941, year = {2024}, author = {Michaud, NL and Bouton, ME}, title = {An analysis of reinstatement after extinction of a conditioned taste aversion.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {50}, number = {2}, pages = {144-160}, doi = {10.1037/xan0000378}, pmid = {38587941}, issn = {2329-8464}, support = {/NH/NIH HHS/United States ; }, abstract = {Taste aversion learning has sometimes been considered a specialized form of learning. In several other conditioning preparations, after a conditioned stimulus (CS) is conditioned and extinguished, reexposure to the unconditioned stimulus (US) by itself can reinstate the extinguished conditioned response. Reinstatement has been widely studied in fear and appetitive Pavlovian conditioning, as well as operant conditioning, but its status in taste aversion learning is more controversial. Six taste-aversion experiments with rats therefore sought to discover conditions that might encourage it there. The results often yielded little to no evidence of reinstatement, and we also found no evidence of concurrent recovery, a related phenomenon in which responding to a CS that has been conditioned and extinguished is restored if a second CS is separately conditioned. However, a key result was that reinstatement occurred when the conditioning procedure involved multiple closely spaced conditioning trials that could have allowed the animal to learn that a US presentation signaled or set the occasion for another trial with a US. Such a mechanism is precluded in many taste aversion experiments because they often use very few conditioning trials. Overall, the results suggest that taste aversion learning is experimentally unique, though not necessarily biologically or evolutionarily unique. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38562680, year = {2024}, author = {Taxier, LR and Flanigan, ME and Haun, HL and Kash, TL}, title = {Retrieval of an ethanol-conditioned taste aversion promotes GABAergic plasticity in the insular cortex.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.20.585950}, pmid = {38562680}, abstract = {UNLABELLED: Blunted sensitivity to ethanol's aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuit's potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic activity onto IC-BLA projections would be facilitated following the retrieval of an ethanol-conditioned taste aversion (CTA). Consistent with this hypothesis, frequency of mIPSCs was increased following retrieval of an ethanol-CTA across cell layers in IC-BLA projection neurons. This increase in GABAergic plasticity occurred in both a circuit-specific and learning-dependent manner. Additionally, local inhibitory inputs onto layer 2/3 IC-BLA projection neurons were greater in number and strength following ethanol-CTA. Finally, DREADD-mediated inhibition of IC parvalbumin-expressing cells blunted the retrieval of ethanol-CTA in male, but not female, mice. Collectively, this work implicates a circuit-specific and learning-dependent increase in GABAergic tone following retrieval of an ethanol-CTA, thereby advancing our understanding of how the aversive effects of ethanol are encoded in the brain.

SIGNIFICANCE STATEMENT: Sensitivity to the aversive properties of ethanol contributes to motivation to consume alcohol. However, the plasticity-associated mechanisms through which ethanol's aversive effects are represented within neural circuits are largely unidentified. In the present study, we used whole-cell patch clamp electrophysiology combined with synaptic input mapping to identify alterations in GABAergic plasticity within the insula, and within cells projecting from the insula to the basolateral amygdala. We demonstrate learning and circuit-specific alterations in GABAergic tone following retrieval of an ethanol-conditioned taste aversion, as well as a male-specific role for Parvalbumin-expressing interneurons in modulating the strength of an ethanol-conditioned taste aversion. Combined, these findings provide novel insights into how the aversive properties of ethanol are encoded within brain circuitry.}, } @article {pmid38492666, year = {2024}, author = {Trevisonno, J and Venter, C and Pickett-Nairne, K and Bégin, P and Cameron, SB and Chan, ES and Cook, VE and Factor, JM and Groetch, M and Hanna, MA and Jones, DH and Wasserman, RL and Mack, DP}, title = {Food aversion and anxiety represent primary patient barriers to food oral immunotherapy.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaip.2024.03.014}, pmid = {38492666}, issn = {2213-2201}, abstract = {While oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and evaluated the role of healthcare professionals, especially dietitians METHODS: A survey in Canada and the US involved families currently enrolled in food OIT programmes RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with slower buildup (p=0.02), and reduction in dose (p=0.002). Taste aversion was a strongly age-dependent barrier for initiation (p<0.001) and continuation (p<0.002), with older children over 6 years of age reporting it as a very significant barrier (p<0.001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (p<0.05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (p<0.001) CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age-dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.}, } @article {pmid38471095, year = {2024}, author = {Osler, AL and Alfredo, KA and Mihelcic, JR}, title = {Chlorine Water Taste Threshold and Acceptability among Indigenous and Non-Indigenous Populations in Rural Panama.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.3c05630}, pmid = {38471095}, issn = {1520-5851}, abstract = {Although gains in access to water services over the past two decades have been large, more than two billion people still lack access to safely managed drinking water. This study examines and compares free chlorine taste and acceptability thresholds of rural Indigenous Ngäbe and rural Latino Panamanians to study if taste aversion may be a limiting factor in chlorination of community systems in Panama using the three-alternative forced choice test methodology. This study is the first to establish a best-estimate taste threshold for a rural Indigenous group and the only study in Latin America to report best-estimate taste thresholds using those methods. Median taste thresholds were 0.87 mg/L Cl2 for Indigenous Ngäbe participants (n = 82) and 1.64 mg/L Cl2 for Latino participants (n = 64), higher than both the minimum concentration for biologically safe water (0.2 mg/L) and the recommended concentration range in Panama (0.3-0.8 mg/L). Median acceptability thresholds were established much higher than taste thresholds at 3.45 mg/L Cl2. The results show that the ability to accurately taste chlorine may not be the limiting factor for adoption of safe water initiatives in remote and Indigenous communities.}, } @article {pmid38383904, year = {2024}, author = {Ramirez, LA and Przybysz, KR and Pitock, JR and Starr, EM and Yang, H and Glover, EJ}, title = {Attenuated incubation of ethanol-induced conditioned taste aversion in a model of dependence.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, pmid = {38383904}, issn = {1432-2072}, support = {AA029130/AA/NIAAA NIH HHS/United States ; AA022538/AA/NIAAA NIH HHS/United States ; AA024208/AA/NIAAA NIH HHS/United States ; AA026577/AA/NIAAA NIH HHS/United States ; }, abstract = {RATIONALE: Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning.

OBJECTIVES: This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound.

METHODS: CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0 g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure.

RESULTS: Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0 g/kg producing greater CTA than 1.5 g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was largely absent in CIE-exposed rats. Re-conditioning after vapor exposure facilitated increased CTA magnitude to a similar degree in AIR- and CIE-exposed males. In contrast, CTA magnitude was unchanged by re-conditioning in females.

CONCLUSIONS: These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion.}, } @article {pmid38332437, year = {2024}, author = {Boakes, RA and Badolato, C and Rehn, S}, title = {Taste aversion learning during successive negative contrast.}, journal = {Learning & behavior}, volume = {}, number = {}, pages = {}, pmid = {38332437}, issn = {1543-4508}, support = {ARC DP17010392//Australian Research Council/ ; }, abstract = {Previous experiments found that acceptance of saccharin by rats was reduced if they had prior experience of sucrose or some other highly palatable solution. This study tested whether such successive negative contrast (SNC) effects involve acquisition of an aversion to the new taste. In three experiments, rats were switched from sucrose exposure in Stage 1 to a less palatable solution containing a new taste in Stage 2. In Experiments 1 and 2, a novel flavor was added to a saccharin solution at the start of Stage 2. In Experiment 1, preference tests revealed a weak aversion to the added vanilla flavor in the Suc-Sacch group, while in Experiment 2 an aversion was found in the Suc-Sacch group to the salty flavor that was used, compared with controls given access either saccharin or water in Stage 1. In Experiment 3, the Suc-Quin group, given quinine solution in Stage 2, displayed a greater aversion to quinine than a Water-Quin control group. These results support the suggestion that taste aversion learning plays a role in the initial suppression of intakes in a qualitative consummatory SNC effect. However, in the light of other evidence, it seems that the unusual persistence of successive negative contrast when rats are switched from sucrose to saccharin is not due to a long-lasting reduction in the value of saccharin.}, } @article {pmid38303664, year = {2024}, author = {Przybysz, KR and Ramirez, LA and Pitock, JR and Starr, EM and Yang, H and Glover, EJ}, title = {A translational rodent model of individual differences in sensitivity to the aversive properties of ethanol.}, journal = {Alcohol, clinical & experimental research}, volume = {}, number = {}, pages = {}, doi = {10.1111/acer.15267}, pmid = {38303664}, issn = {2993-7175}, support = {AA022538/AA/NIAAA NIH HHS/United States ; AA024208/AA/NIAAA NIH HHS/United States ; AA026577/AA/NIAAA NIH HHS/United States ; AA029130/AA/NIAAA NIH HHS/United States ; }, abstract = {BACKGROUND: A strong relationship exists between individual sensitivity to the aversive properties of ethanol and risk for alcohol use disorder (AUD). Despite this, our understanding of the neurobiological mechanisms underlying the subjective response to ethanol is limited. A major contributor to this lack of knowledge is the absence of preclinical models that enable exploration of this individual variability such as is possible in studies of humans.

METHODS: Adult male and female Long-Evans rats were trained to associate a novel tastant (saccharin) with acute exposure to either saline or ethanol (1.5 g/kg or 2.0 g/kg i.p.) over three conditioning days using a standard conditioned taste aversion (CTA) procedure. Variability in sensitivity to ethanol-induced CTA was phenotypically characterized using a median split across the populations studied.

RESULTS: When examining group averages, both male and female rats exposed to saccharin paired with either dose of ethanol exhibited lower saccharin intake relative to saline controls indicative of ethanol-induced CTA. Examination of individual data revealed a bimodal distribution of responses uncovering two distinct phenotypes present in both sexes. CTA-sensitive rats exhibited a rapid and progressive reduction in saccharin intake with each successive ethanol pairing. In contrast, saccharin intake was unchanged or maintained after an initial decrease from baseline levels in CTA-resistant rats. While CTA magnitude was similar between male and female CTA-sensitive rats, among CTA-resistant animals females were more resistant to the development of ethanol-induced CTA than males. Phenotypic differences were not driven by differences in baseline saccharin intake.

CONCLUSIONS: These data parallel work in humans by revealing individual differences in sensitivity to the aversive properties of ethanol that emerge immediately after initial exposure to ethanol in both sexes. This model can be used in future studies to investigate the neurobiological mechanisms that confer risk for AUD.}, } @article {pmid38298775, year = {2024}, author = {Douton, JE and Carelli, RM}, title = {Unraveling Sex Differences in Affect Processing: Unique Oscillatory Signaling Dynamics in the Infralimbic Cortex and Nucleus Accumbens Shell.}, journal = {Biological psychiatry global open science}, volume = {4}, number = {1}, pages = {354-362}, doi = {10.1016/j.bpsgos.2023.08.011}, pmid = {38298775}, issn = {2667-1743}, abstract = {BACKGROUND: Negative affect is prevalent in psychiatric diseases such as depression and addiction. Projections from the infralimbic cortex (IL) to the nucleus accumbens shell (NAcSh) are causally linked to learned negative affect as 20 Hz optogenetic stimulation of this circuit reduces conditioned taste aversion (CTA) in male but not female rats. However, the prior study did not provide insight into how innate versus learned negative affect are processed in these areas across sex.

METHODS: To address this issue, local field potential activity was simultaneously recorded in the IL and NAcSh in response to intraoral infusion of rewarding (saccharin) and aversive (quinine) tastants and following induction of a CTA in male and female Sprague Dawley rats.

RESULTS: Local field potential oscillatory activity within each brain region to saccharin varied across sex. In males, CTA increased IL resting-state power, which was correlated with the strength of the learned aversion, and reduced beta power and IL-NAcSh coherence. In females, CTA increased gamma power in the NAcSh. Similar effects were observed in males and females after CTA in theta-low gamma phase-amplitude coupling. Finally, while quinine produced similar effects in oscillatory power across sex, females showed differences in phase-amplitude coupling within the NAcSh that may be linked to aversion resistance.

CONCLUSIONS: We revealed sex-specific hedonic processing in the IL and NAcSh and how oscillatory signaling is disrupted in learned negative affect, revealing translationally relevant insight into potential treatment strategies that can help to reduce the deleterious effects of learned negative affect in psychiatric illnesses.}, } @article {pmid38215678, year = {2023}, author = {Yoshida, Y and Fujishiro, S and Kawai, R and Kawabata, F}, title = {Characterization of taste sensitivities to amino acids and sugars by conditioned taste aversion learning in chickens.}, journal = {Animal : an international journal of animal bioscience}, volume = {18}, number = {2}, pages = {101050}, doi = {10.1016/j.animal.2023.101050}, pmid = {38215678}, issn = {1751-732X}, abstract = {Taste plays an essential role in regulating the feeding behaviors of animals. The present study aimed to characterize the taste sensory profiles of amino acids and sugars in chickens. To achieve this, we employed a conditioned taste aversion learning method, which is characterized by a specific pairing of gastrointestinal malaise and taste perception. Our findings revealed that chickens were able to learn to avoid L-Val, L-Lys, and L-His through conditioned taste aversion learning, and exhibited a strong aversion to L-Arg. These results suggest that chickens are primarily sensitive to basic amino acids, including L-Lys, which is a crucial limiting amino acid in feeds. Interstingly, this sensitivity to basic amino acids in chickens contrasts with humans, who are mainly sensitive to acidic amino acids as umami taste. Furthermore, despite the absence of a mammalian sweet taste receptor gene in the chicken genome, we demonstrated that chickens learned to avoid glucose, galactose, sucrose, and maltose by conditioned taste aversion learning. Taken together, the present study provides the idea that chickens possess a gustatory perception toward specific amino acids and sugars for the detection of beneficial nutrients in their feeds.}, } @article {pmid38211776, year = {2024}, author = {Briones-Vidal, MG and Reyes-García, SE and Escobar, ML}, title = {NEUROTROPHIN-3 INTO THE INSULAR CORTEX STRENGTHENS CONDITIONED TASTE AVERSION MEMORY.}, journal = {Behavioural brain research}, volume = {}, number = {}, pages = {114857}, doi = {10.1016/j.bbr.2024.114857}, pmid = {38211776}, issn = {1872-7549}, abstract = {Memory consolidation is an essential process of long-term memory formation. Neurotrophins have been suggested as key regulators of activity dependent changes in the synaptic efficacy and morphology, which are considered the downstream mechanisms of memory consolidation. The neurotrophin 3 (NT-3), a member of the neurotrophin family, and its high affinity receptor TrkC, are widely expressed in the insular cortex (IC), a region with a critical role in the consolidation of the conditioned taste aversion (CTA) paradigm, in which an animal associates a novel taste with nausea. Nevertheless, the role of this neurotrophin in the cognitive processes that the IC mediates remains unexamined. To answer whether NT-3 is involved in memory consolidation at the IC, adult male Wistar rats were administered with NT-3 or NT-3 in combination with the Trk receptors inhibitor K252a into the IC, immediately after CTA acquisition under two different conditions: a strong-CTA (0.2M lithium chloride i.p.) or a weak-CTA (0.1M lithium chloride i.p.). Our results show that NT-3 strengthens the memory trace of CTA, transforming a weak conditioning into a strong one, in a Trk-dependent manner. The present evidence suggests that NT-3 has a key role in the consolidation process of an aversive memory in a neocortical region.}, } @article {pmid38204574, year = {2023}, author = {Zhang, FX and Xie, XH and Guo, ZX and Wang, HD and Li, H and Wu, KLK and Chan, YS and Li, YQ}, title = {Evaluating proxies for motion sickness in rodent.}, journal = {IBRO neuroscience reports}, volume = {15}, number = {}, pages = {107-115}, pmid = {38204574}, issn = {2667-2421}, abstract = {Motions sickness (MS) occurs when the brain receives conflicting sensory signals from vestibular, visual and proprioceptive systems about a person's ongoing position and/or motion in relation to space. MS is typified by symptoms such as nausea and emesis and implicates complex physiological aspects of sensations and sensorimotor reflexes. Use of animal models has been integral to unraveling the physiological causality of MS. The commonly used rodents (rat and mouse), albeit lacking vomiting reflex, reliably display phenotypic behaviors of pica (eating of non-nutritive substance) and conditioned taste aversion (CTAver) or avoidance (CTAvoi) which utilize neural substrates with pathways that cause gastrointestinal malaise akin to nausea/emesis. As such, rodent pica and CTAver/CTAvoi have been widely used as proxies for nausea/emesis in studies dealing with neural mechanisms of nausea/emesis and MS, as well as for evaluating therapeutics. This review presents the rationale and experimental evidence that support the use of pica and CTAver/CTAvoi as indices for nausea and emesis. Key experimental steps and cautions required when using rodent MS models are also discussed. Finally, future directions are suggested for studying MS with rodent pica and CTAver/CTAvoi models.}, } @article {pmid38161042, year = {2023}, author = {Lockwood, DR and Cassell, JA and Smith, JC and Houpt, TA}, title = {Patterns of ingestion of rats during chronic oral administration of lithium chloride.}, journal = {Physiology & behavior}, volume = {}, number = {}, pages = {114454}, doi = {10.1016/j.physbeh.2023.114454}, pmid = {38161042}, issn = {1873-507X}, abstract = {Chronic lithium administration to rodents is used to explore the potential neural mechanisms of mood stabilization, as well as to model the side effects of chronic lithium on multiple organ systems. Oral administration of lithium in the maintenance diet or drinking water is convenient, but lithium can acutely affect intake and it can mediate acquisition of conditioned taste aversions. We compared ad libitum food and fluid intake by male rats with LiCl or NaCl solutions as their sole source of fluid across 20 days, with a commonly used dosage of LiCl (24 mM: 1 g / L LiCl). To quantify the pattern of intake, rats were housed in cages equipped with lickometers to detect licks and infrared photobeams to detect food access with 6-s resolution. To determine if rats formed a CTA to LiCl, they were subsequently tested with access to NaCl. Rats showed an immediate avoidance of the LiCl solution, as seen on the first day of access by an increased latency to initiate drinking and a decreased size of drinking bouts. Rats showed a differential response to LiCl vs. NaCl after as few as 5 licks. Chronic consumption of LiCl solution led to significantly decreased food and fluid intake compared to baseline, with concomitant weight loss. The decreased intake was realized by marked changes in the pattern of drinking and feeding bouts: a decrease in per-lick volume and a decrease in licks per drinking bout, and an increase in feeding bout duration resulting in an overall decrease in eating rate. Conversely, chronic NaCl access led to an increase in drinking bout number and licks/bout. The avoidance of LiCl was likely a combination of toxic effects of ingested LiCl and rapid acquisition of a learned aversion to the taste of LiCl, as shown by an extinguishable generalized aversion to NaCl solution during subsequent NaCl test days. The marked effect of chronic oral LiCl on ingestion may impact the oral dosing of lithium as well as the rat's metabolic status.}, } @article {pmid38154277, year = {2023}, author = {Gradowski, L}, title = {From fringe to mainstream: The Garcia effect.}, journal = {Studies in history and philosophy of science}, volume = {103}, number = {}, pages = {114-122}, doi = {10.1016/j.shpsa.2023.12.004}, pmid = {38154277}, issn = {0039-3681}, abstract = {The rejection of research results is sometimes thought to be justified in cases of individuals embracing fringe ideas that depart significantly from prevailing orthodoxy, or in cases of individuals who lack appropriate expertise or credentials. The case of John Garcia exhibits both of these dimensions, and illustrates that such rejection can delay scientific advancements. Garcia's work decisively challenged what was the orthodoxy in psychology in the midcentury: behaviorism. Behaviorist learning theorists suffered from theory-entrenchment insofar as they failed to acknowledge Garcia's anomalous research findings that ran counter to their theoretical expectations. The case study also illustrates that theories on the margins can become embraced as a result of advancements in adjacent research fields. Studying how Garcia's work moved from fringe to mainstream results in lessons for the philosophy of science and epistemology more generally. Only when we see the mechanisms of exclusion at work can we understand how science and other knowledge production systems can inadvertently act counterproductively via gatekeeping practices that filter out unorthodox points of view.}, } @article {pmid38048984, year = {2023}, author = {Dornellas, APS and Thiele, TE and Navarro, M}, title = {Chemogenetic inhibition of locus coeruleus to rostromedial tegmental nucleus noradrenergic pathway increases light cycle ethanol drinking in male and female mice and blunts ethanol-induced CTA.}, journal = {Neuropharmacology}, volume = {}, number = {}, pages = {109809}, doi = {10.1016/j.neuropharm.2023.109809}, pmid = {38048984}, issn = {1873-7064}, abstract = {We recently showed that chemogenetic activation of the locus coeruleus (LC) to the rostromedial tegmental nucleus (RMTg) noradrenergic (NE) pathway significantly blunted binge-like ethanol drinking and induced aversive-like behaviors in mice. The aim of the present study is to determine if silencing this TH + LC → RMTg noradrenergic pathway promotes increased levels of binge-like ethanol intake and reduced ethanol-induced conditioned taste aversion (CTA). To this end, both male and female TH-ires-cre mice on a C57BL/6 J background were cannulated in the RMTg and injected in the LC with rAVV viruses that encode cre-dependent Gi-expressing designer receptor exclusively activated by designer drugs (DREADDs), or its control, to directly control the activity of NE neurons. Inhibition of the LC to RMTg pathway had no effect on the binge-ethanol drinking in a "drinking-in-the-dark" (DID) paradigm. However, when using this paradigm during the light cycle, silencing of this circuit significantly increased ethanol intake without altering sucrose drinking. Moreover, we found that inhibition of this circuit significantly attenuated an ethanol-induced CTA. In addition, when compared to control animals, pairing RMTg-directed Clozapine N-oxide (CNO) with an i.p. injection of 1.5 g/kg ethanol reduced c-Fos activation in the LC, and increased c-Fos expression in the ventral tegmental area (VTA) in Gi-expressing mice. Our data show that inhibition of the TH + LC to the RMTg pathway significantly increased ethanol drinking as well as attenuated ethanol-induced CTA, supporting the involvement of the LC to RMTg noradrenergic circuit as an important protective mechanism against excessive ethanol consumption.}, } @article {pmid37989122, year = {2023}, author = {Dong, XC and Xu, DY}, title = {Research progress on the role and mechanism of GDF15 in body weight regulation.}, journal = {Obesity facts}, volume = {}, number = {}, pages = {}, doi = {10.1159/000535089}, pmid = {37989122}, issn = {1662-4033}, abstract = {BACKGROUND: Growth differentiation factor-15 (GDF-15) is a member of the growth differentiation factor subfamily in the transforming growth factor beta superfamily. GDF15 has multiple functions and can regulate biological processes. High levels of GDF15 in the circulation can affect metabolic processes. Studies have shown that GDF15 is associated with changes in body weight.

SUMMARY: This review reviews the current knowledge on the relationship between GDF15 and body weight change, focusing on the role and mechanism of GDF15 in body weight regulation. GDF15 plays an important role in reducing food intake, improving insulin resistance, and breaking down fat, suggesting that GDF15 has an important regulatory effect on body weight. The mechanism by which GDF15 causes reduced food intake may be related to changes in food preference, delayed gastric emptying, and conditioned taste aversion. GDF15 can combat insulin resistance induced by inflammation or protect β-cell from apoptosis. GDF15 probably promote lipolysis through a brain-somatic tissue circuit. Several factors and related signaling pathways are also mentioned that can contribute to the effects of GDF15 on reducing weight.

KEY MESSAGE: GDF15 plays an important role in weight regulation and provides a new direction for the treatment of obesity. Its effects on resisting obesity are of great significance to inhibiting the progression of metabolic diseases. It is expected to become a new target for regulating body weight, improving obesity, and treating metabolic diseases such as diabetes.}, } @article {pmid37883032, year = {2023}, author = {Rehn, S and Boakes, RA and Dwyer, DM}, title = {Switching from sucrose to saccharin: Extended successive negative contrast is not maintained by hedonic changes.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {49}, number = {4}, pages = {289-295}, doi = {10.1037/xan0000362}, pmid = {37883032}, issn = {2329-8464}, support = {//Experimental Psychology Society/ ; }, abstract = {Previous experiments found that acceptance of saccharin by rats was reduced if they had prior experience of sucrose or some other highly palatable solution. This reduction in saccharin consumption was particularly extended after a switch from sucrose. On the surface, this seems to correspond to a successive negative contrast (SNC) effect. This term was coined by C. F. Flaherty to describe the situation where consumption of a target solution is reduced by prior experience of a more valuable solution, typically a more concentrated version of the target solution. However, SNC effects are normally transient and assessed relative to a nonshifted control. Here, we confirm that the reduction in consumption seen when shifting from sucrose to saccharin is persistent and is seen relative to the traditional unshifted control. In addition, an analysis of licking microstructure showed that the shift from sucrose to saccharin suppressed the hedonic value of saccharin relative to controls, but this effect was less persistent than consumption suppression. Interestingly, a similar dissociation is observed in extinction of conditioned taste aversion (CTA): suppression of consumption produced by CTA is far more persistent than suppression of hedonic value. The comparison of results across procedures suggests that persistent SNC produced by a qualitative downshift from sucrose to saccharin appears different from quantitative downshifts in the concentration of a single solution, and qualitative downshift effects may involve CTA. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37882427, year = {2023}, author = {Expósito, AN and Vázquez-Agredos, A and Menchén, S and Gámiz, F and Gallo, M}, title = {Taste Neophobia, Latent Inhibition of Taste Aversion and Object Recognition Memory in Adolescent Rats.}, journal = {Psicothema}, volume = {35}, number = {4}, pages = {423-431}, doi = {10.7334/psicothema2022.256}, pmid = {37882427}, issn = {1886-144X}, abstract = {BACKGROUND: Adolescence in mammals is a period marked by increased novelty-seeking and enhanced responsiveness to the stressful properties of novel stimuli. Despite the need to taste potentially toxic novel foods during the adolescent growth spurt, there has been little study of taste neophobia and its attenuation.

METHOD: Four experiments were carried out to compare taste neophobia and related memory processes in male and female adolescent (PND28) and adult (PND70) Wistar rats. Experiments 1 and 2 evaluated attenuation of taste neophobia to cider vinegar (3%) and sodium saccharin (0.1%) solutions were evaluated. Additionally, to test the role of memory in neophobia during adolescence, latent inhibition of taste aversion and object recognition memory were assessed in Experiment 3 and Experiment 4, respectively.

RESULTS: Adolescent and adult rats exhibited taste neophobia to the saccharin solution but adolescent rats required more exposure trials than adults to recognize the vinegar solution as safe. Both groups exhibited similar latent inhibition of taste aversion and object recognition memory. No sex effect was significant.

CONCLUSIONS: Contrary to the accepted view associating adolescence with reduced neophobia, adolescent rats exhibited taste neophobia which even increased when sour tastes were encountered.}, } @article {pmid37818887, year = {2023}, author = {Chikamoto, N and Fujimoto, K and Nakai, J and Totani, Y and Hatakeyama, D and Ito, E}, title = {Expression Level Changes in Serotonin Transporter are Associated with Food Deprivation in the Pond Snail Lymnaea stagnalis.}, journal = {Zoological science}, volume = {40}, number = {5}, pages = {382-389}, doi = {10.2108/zs230027}, pmid = {37818887}, issn = {0289-0003}, abstract = {In the pond snail Lymnaea stagnalis, serotonin (5-HT) plays an important role in feeding behavior and its associated learning (e.g., conditioned taste aversion: CTA). The 5-HT content in the central nervous system (CNS) fluctuates with changes in the nutritional status, but it is also expected to be influenced by changes in the serotonin transporter (SERT) expression level. In the present study, we identified SERT in Lymnaea and observed its localization in 5-HTergic neurons, including the cerebral giant cells (CGCs) in the cerebral ganglia and the pedal A cluster neurons and right and left pedal dorsal 1 neurons in the pedal ganglia by in situ hybridization. Real-time PCR revealed that the SERT mRNA expression level was lower under severe food deprivation than under mild food deprivation in the whole CNS as well as in a single CGC. These results inversely correlated with previous data that the 5-HT content in the CNS was higher in the severely food-deprived state than in the mildly food-deprived state. Furthermore, in single CGCs, we observed that the 5-HT level was significantly increased in the severely food-deprived state compared with the mildly food-deprived state. Our present findings suggest that changes in the SERT expression level associated with food deprivation may affect 5-HT signaling, probably contributing to learning and memory mechanisms in Lymnaea.}, } @article {pmid37816597, year = {2023}, author = {Hurley, SW and Douton, JE and Carelli, RM}, title = {Neuronal Ensembles in the Infralimbic Cortex Dynamically Process Distinct Aspects of Hedonic Value.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.0253-23.2023}, pmid = {37816597}, issn = {1529-2401}, abstract = {Hedonic processing is critical for guiding appropriate behavior, and the infralimbic cortex (IL) is a key neural substrate associated with this function in rodents and humans. We used deep brain, in vivo calcium imaging and taste reactivity (TR) in freely behaving male and female Sprague Dawley rats to examine whether the infralimbic cortex is involved in encoding innate versus conditioned hedonic states. In experiment 1, we examined the IL neuronal ensemble responsiveness to intraoral innately rewarding (sucrose) versus aversive (quinine) tastants. Most IL neurons responded to either sucrose only or both sucrose and quinine, with fewer neurons selectively processing quinine. Among neurons that responded to both stimuli, some appear to encode hedonic processing. In experiment 2, we examined how IL neurons process devalued sucrose using conditioned taste aversion (CTA). We found that neurons that responded exclusively to sucrose were disengaged while additional quinine-exclusive neurons were recruited. Moreover, tastant-specific neurons that did not change their neuronal activity after CTA appeared to encode objective hedonic value. However, other neuronal ensembles responded to both tastants and appear to encode distinct aspects of hedonic processing. Specifically, some neurons responded differently to quinine and sucrose and shifted from appetitive-like to aversive-like activity after CTA, thus encoding the subjective hedonic value of the stimulus. Conversely, neurons that responded similarly to both tastants were heightened after CTA. Our findings show dynamic shifts in IL ensembles encoding devalued sucrose and support a role for parallel processing of objective and subjective hedonic value.Significance StatementDisrupted affective processing contributes to psychiatric disorders including depression, substance use disorder, and schizophrenia. We assessed how the infralimbic cortex, a key neural substrate involved in affect generation and affect regulation, processes innate and learned hedonic states using deep brain in vivo calcium imaging in freely behaving rats. We report that unique infralimbic cortex ensembles encode stimulus subjective and objective hedonic value. Further, our findings support similarities and differences in innate versus learned negative affective states. This study provides insight into the neural mechanisms underlying affect generation and help establish a foundation for the development of novel treatment strategies to reduce negative affective states that arise in many psychiatric disorders.}, } @article {pmid37806503, year = {2023}, author = {Ranmal, SR and Nhouchi, Z and Keeley, A and Adler, L and Lavarde, M and Pensé-Lhéritier, AM and Tuleu, C}, title = {Taste assessment for Paediatric Drug Development: A Comparison of Bitterness Taste Aversion in Children versus Naïve and Expert Young Adult Assessors.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {123494}, doi = {10.1016/j.ijpharm.2023.123494}, pmid = {37806503}, issn = {1873-3476}, abstract = {Medicines for children often taste bitter, presenting a significant challenge to treatment compliance. However, most studies on paediatric drug development rely on adult volunteers for sensory research, and the level of expertise required from these assessors is unclear. This study aimed to address this gap by investigating perceived bitterness aversion to taste strips impregnated with different concentrations of quinine hydrochloride in 439 school-aged children. Expert (n=26) and naïve (n=65) young adult assessors evaluated quinine solutions as well as taste strips, for methodological bridging purposes. All assessors differentiated the aversiveness of the taste strips in a dose dependent manner. Younger children aged 4-8 years had difficulty discriminating higher bitter concentrations, whereas pre-adolescents 9-11 years and naive adults showed better discrimination at the top of the scale. Naive assessors showed similar bitter perception as children. However, the results were slightly different between strips and solution in adults. These findings highlight the key role that adult panels can play in paediatric formulation development. Taste strips show promise as a safe and pragmatic tool for sensory pharmaceutical evaluations, though further studies are warranted to establish the relationship between age and hedonic taste perception using compounds with diverse physicochemical and sensory qualities.}, } @article {pmid37805008, year = {2023}, author = {Kobayashi, S and Kajiwara, M and Cui, Y and Sako, T and Sasabe, T and Hayashinaka, E and Wada, Y and Kobayashi, M}, title = {Activation of multiple neuromodulatory systems in alert rats acquiring conditioned taste aversion revealed by positron emission tomography.}, journal = {Brain research}, volume = {}, number = {}, pages = {148617}, doi = {10.1016/j.brainres.2023.148617}, pmid = {37805008}, issn = {1872-6240}, abstract = {Conditioned taste aversion (CTA) is an essential ability for animals to consume food safely and is regulated by neuromodulatory systems including the dopamine, noradrenaline, serotonin, and acetylcholine systems. However, because few studies focused on a comprehensive understanding of whole-brain activities, how these neuromodulators contribute to the process of CTA remains an open issue. [18]F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can visualize activated regions within the whole brain simultaneously and noninvasively. This study aimed to understand the mechanisms of CTA, especially focusing on the retrieval process after CTA acquisition by FDG-PET imaging. CTA was established in rats who received an intraoral application of saccharin solution (IOAS) on the first day (Day1), a LiCl i.p. injection after an IOAS on Day2, and an IOAS on Day3 (CTA group). The subtraction images of Day3 of the SHAM group, which received a 0.9% NaCl (saline) injection instead of a LiCl on Day2, from those of Day3 of the CTA group revealed increases in FDG signals in multiple brain regions including the substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and nucleus basalis magnocellularis, in addition to the hippocampus and nociception-related regions, including the parabrachial nucleus and solitary nucleus. On the other hand, the visceral pain induced by the LiCl injection increased FDG signals in the primary and secondary somatosensory and insular cortices in addition to the parabrachial nucleus and solitary nucleus. These results suggest that the retrieval process of CTA induces brain regions producing neuromodulators and pain-related brainstem.}, } @article {pmid37805119, year = {2023}, author = {Gutiérrez-Vera, B and Reyes-García, SE and Escobar, ML}, title = {Brief environmental enrichment elicits metaplasticity on the insular cortex in vivo and reduces the strength of conditioned taste aversion.}, journal = {Neurobiology of learning and memory}, volume = {}, number = {}, pages = {107840}, doi = {10.1016/j.nlm.2023.107840}, pmid = {37805119}, issn = {1095-9564}, abstract = {Environmental enrichment (EE) is known to improve memory and cognition and modulate the impact of aversive stimuli in animals, promoting the development of resilience to stressful situations. Likewise, it is known that EE can modulate synaptic plasticity as is the case of long-term potentiation (LTP). These findings have been described initially in ex vivo preparations, suggesting that the effects of EE are the result of an early modification of the synaptic excitability and transmission. In this regard, it is known that metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. In addition, we have shown that CTA extinction allows the induction but not the maintenance of IC-LTP of the Bla-IC pathway. Recently, we also showed that prior exposure to environmental enrichment for three weeks reduces the strength of CTA, restoring the brain-derived neurotrophic factor (BDNF) levels in the IC. The present study aimed to analyze the effects of brief exposure to an enriched environment on the strength of aversive memory, as well as on the in vivo IC-LTP. To do so, adult rats were exposed for seven days to an EE, either before CTA training or LTP induction in the Bla-IC pathway. Our results demonstrate that a seven-day exposure to an enriched environment attenuates the aversive response to a strong CTA and allows the induction but not the maintenance of LTP in the insular cortex. These findings provide evidence that metaplastic regulation in a neocortical region takes part in the mechanisms through which brief exposure to enriched environments attenuates an aversive response.}, } @article {pmid37774959, year = {2023}, author = {Lamb, RJ and Schindler, CW and Ginsburg, BC}, title = {Effects of an Ethanol-Paired Conditioned Stimulus on Responding for Ethanol Suppressed by a Conditioned-Taste-Aversion.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.alcohol.2023.09.008}, pmid = {37774959}, issn = {1873-6823}, abstract = {Ethanol-Paired Conditioned Stimuli (CS) can increase ethanol responding either in extinction or occurring at low rates late in a session. To examine the generality of CS induced increases in ethanol-responding, we examined if a CS could increase responding suppressed by Conditioned-Taste-Aversion (CTA), which presumably suppresses responding by changing ethanol's valence from positive to negative. Rats were trained to respond for ethanol under a Random Interval (RI) schedule. We then removed the lever and paired Random-Time ethanol deliveries with illumination of a stimulus light (i.e., CS) for ten sessions. Results were compared with a Truly Random Control group, in which the light and ethanol deliveries occurred independently. In a subsequent experiment, rats were treated similarly, except the light served as a discriminative stimulus, as the lever was extended and ethanol deliveries were available under a RI during light presentations. After this training, the lever was returned and rats again responded for ethanol. Subsequently, sessions were followed by LiCl administration. When responding reached low levels, LiCl administration stopped and the light was occasionally illuminated during the session. Responding during the light presentation was compared to responding during the period preceding light presentation. Responding partially recovered across ten sessions and was greater during light presentations than in the period before it in all three groups. Increases were not reliably different between the groups indicating that explanations for these increases such as CS-induced increases in motivation or approach towards the light are unlikely to be correct. The most likely explanation for these light-induced increases is that during sessions in which the light had been presented previously, LiCl had never been presented and thus, the light had come to signal that ethanol was safe to drink.}, } @article {pmid37759600, year = {2023}, author = {Nakai, J and Namiki, K and Fujimoto, K and Hatakeyama, D and Ito, E}, title = {FOXO in Lymnaea: Its Probable Involvement in Memory Consolidation.}, journal = {Biology}, volume = {12}, number = {9}, pages = {}, doi = {10.3390/biology12091201}, pmid = {37759600}, issn = {2079-7737}, support = {JPMJSP2128//Japan Science and Technology Agency/ ; none//Waseda University/ ; }, abstract = {Food deprivation activates forkhead box O (FOXO), a transcription factor downstream of insulin receptors. In the pond snail Lymnaea stagnalis, insulin signaling and food deprivation improve memory consolidation following conditioned taste aversion (CTA) learning. We investigated the subcellular localization of FOXO in Lymnaea and changes in its expression levels following food deprivation, CTA learning, and insulin administration. Immunohistochemistry revealed that Lymnaea FOXO (LymFOXO) was located in the central nervous system (CNS) neuronal cytoplasm in food-satiated snails but was mainly in neuronal nuclei in food-deprived snails. Following CTA acquisition, LymFOXO translocated to the nuclei in food-satiated snails and remained in the nuclei in food-deprived snails. Contrary to our expectations, insulin administered to the CNS did not induce LymFOXO translocation into the nuclei in food-satiated snails. Real-time PCR was used to quantify LymFOXO mRNA levels, its target genes, and insulin signaling pathway genes and revealed that LymFOXO mRNA was upregulated in food-deprived snails compared to food-satiated snails. Insulin applied to isolated CNSs from food-satiated snails increased LymFOXO compared to vehicle-treated samples. Food deprivation prepares FOXO to function in the nucleus and enhances CTA learning in snails. Insulin application did not directly affect LymFOXO protein localization. Thus, insulin administration may stimulate pathways other than the LymFOXO cascade.}, } @article {pmid37745477, year = {2023}, author = {Ramirez, LA and Przybysz, KR and Pitock, JR and Starr, EM and Yang, H and Glover, EJ}, title = {Attenuated incubation of ethanol-induced conditioned taste aversion in a model of dependence.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.13.557582}, pmid = {37745477}, abstract = {RATIONALE: Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning.

OBJECTIVES: This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound.

METHODS: CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0 g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure.

RESULTS: Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0 g/kg producing greater CTA than 1.5 g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was absent in CIE-exposed rats. These group differences were eliminated upon re-conditioning after vapor exposure.

CONCLUSIONS: These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather, attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion.}, } @article {pmid37713319, year = {2023}, author = {Barnhart, WR and Dial, LA and Jordan, AK and Studer-Perez, EI and Kalantzis, MA and Musher-Eizenman, DR}, title = {Higher meal disengagement and meal presentation are uniquely related to psychological distress and lower quality of life in undergraduate students.}, journal = {Journal of American college health : J of ACH}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/07448481.2023.2245912}, pmid = {37713319}, issn = {1940-3208}, abstract = {Objective: Picky eating, which occurs in emerging adulthood and is associated with psychological distress and quality of life, has historically been conceptualized as unidimensional despite research suggesting it is a multifaceted construct. Participants: An undergraduate sample (N = 509; Mage = 19.96). Methods: A cross-sectional survey assessed picky eating facets (food variety, meal disengagement, meal presentation, and taste aversion), disordered eating, anxiety, depression, stress, obsessive compulsive disorder (OCD), and social phobia symptoms, and quality of life. Results: Meal disengagement was uniquely related to higher anxiety, depression, stress, and social phobia symptoms and lower quality of life, whereas meal presentation was uniquely related to higher anxiety, stress, and OCD symptoms, beyond covariates and disordered eating. Food variety and taste aversion were not uniquely related to outcomes. Conclusions: Considering picky eating multidimensionally may yield important insights beyond the broader construct in terms of its relationship with psychological well-being in undergraduates.}, } @article {pmid37626986, year = {2023}, author = {Rivi, V and Batabyal, A and Lukowiak, K and Benatti, C and Rigillo, G and Tascedda, F and Blom, JMC}, title = {LPS-Induced Garcia Effect and Its Pharmacological Regulation Mediated by Acetylsalicylic Acid: Behavioral and Transcriptional Evidence.}, journal = {Biology}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/biology12081100}, pmid = {37626986}, issn = {2079-7737}, support = {L.R. N. 20/2002 PROGETTI DI RICERCA SUI METODI ALTERNATIVI ALL'UTILIZZO DI ANIMALI//Regione Emilia Romagna/ ; FAR 2016//Department of Life Sciences - University of Modena and Reggio Emilia/ ; 227993-2019//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Lymnaea stagnalis learns and remembers to avoid certain foods when their ingestion is followed by sickness. This rapid, taste-specific, and long-lasting aversion-known as the Garcia effect-can be formed by exposing snails to a novel taste and 1 h later injecting them with lipopolysaccharide (LPS). However, the exposure of snails to acetylsalicylic acid (ASA) for 1 h before the LPS injection, prevents both the LPS-induced sickness state and the Garcia effect. Here, we investigated novel aspects of this unique form of conditioned taste aversion and its pharmacological regulation. We first explored the transcriptional effects in the snails' central nervous system induced by the injection with LPS (25 mg), the exposure to ASA (900 nM), as well as their combined presentation in untrained snails. Then, we investigated the behavioral and molecular mechanisms underlying the LPS-induced Garcia effect and its pharmacological regulation by ASA. LPS injection, both alone and during the Garcia effect procedure, upregulated the expression levels of immune- and stress-related targets. This upregulation was prevented by pre-exposure to ASA. While LPS alone did not affect the expression levels of neuroplasticity genes, its combination with the conditioning procedure resulted in their significant upregulation and memory formation for the Garcia effect.}, } @article {pmid37190662, year = {2023}, author = {Gao, ZY and Huang, CM and Cheng, CN and Huang, AC}, title = {D2 Receptors and Sodium Ion Channel Blockades of the Basolateral Amygdala Attenuate Lithium Chloride-Induced Conditioned Taste Aversion Applying to Cancer Chemotherapy Nausea and Vomiting.}, journal = {Brain sciences}, volume = {13}, number = {4}, pages = {}, pmid = {37190662}, issn = {2076-3425}, support = {NSTC 111-2410-H-431-010//National Science and Technology Council/ ; YSVH110-09//Taipei Veterans General Hospital/ ; }, abstract = {Cancer patients regularly suffer from the behavioral symptoms of chemotherapy-induced nausea and vomiting. Particularly, it is involved in Pavlovian conditioning. Lithium chloride (LiCl) was used as the unconditioned stimulus (US) and contingent with the tastant, for example, a saccharin solution (i.e., the conditioned stimulus; CS), resulted in conditioned taste aversion (CTA) to the CS intake. The present study employed an animal model of LiCl-induced CTA to imitate chemotherapy-induced nausea and vomiting symptoms. Recently, the basolateral amygdala (BLA) was shown to mediate LiCl-induced CTA learning; however, which brain mechanisms of the BLA regulate CTA by LiCl remain unknown. The present study was designed to test this issue, and 4% lidocaine or D2 blocker haloperidol were microinjected into BLA between the 0.1% saccharin solution intake and 0.15M LiCl. The results showed lidocaine microinjections into the BLA could attenuate the LiCl-induced CTA. Microinjections of haloperidol blunted the CTA learning by LiCl. Altogether, BLA via the sodium chloride ion channel and D2 receptors control LiCl-induced conditioned saccharin solution intake suppression. The findings can provide some implications and contributions to cancer chemotherapy-induced nausea and vomiting side effects, and will help to develop novel strategies to prevent the side effects of cancer chemotherapy.}, } @article {pmid36635250, year = {2023}, author = {Kolatt Chandran, S and Yiannakas, A and Kayyal, H and Salalha, R and Cruciani, F and Mizrahi, L and Khamaisy, M and Stern, S and Rosenblum, K}, title = {Intrinsic Excitability in Layer IV-VI Anterior Insula to Basolateral Amygdala Projection Neurons Correlates with the Confidence of Taste Valence Encoding.}, journal = {eNeuro}, volume = {10}, number = {1}, pages = {}, pmid = {36635250}, issn = {2373-2822}, mesh = {Mice ; Animals ; *Basolateral Nuclear Complex/physiology ; Amygdala/physiology ; Taste/physiology ; Avoidance Learning/physiology ; Neurons ; }, abstract = {Avoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. However, the perceived valence of sensory information can change following conflicting experiences. Pleasurability and aversiveness are two crucial parameters defining the perceived valence of a taste and can be impacted by novelty. Importantly, the ability of a given taste to serve as the conditioned stimulus (CS) in conditioned taste aversion (CTA) is dependent on its valence. Activity in anterior insula (aIC) Layer IV-VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlated with and necessary for CTA learning and retrieval, as well as the expression of neophobia toward novel tastants, but not learning taste familiarity. Yet, the cellular mechanisms underlying the updating of taste valence representation in this specific pathway are poorly understood. Here, using retrograde viral tracing and whole-cell patch-clamp electrophysiology in trained mice, we demonstrate that the intrinsic properties of deep-lying Layer IV-VI, but not superficial Layer I-III aIC-BLA neurons, are differentially modulated by both novelty and valence, reflecting the subjective predictability of taste valence arising from prior experience. These correlative changes in the profile of intrinsic properties of LIV-VI aIC-BLA neurons were detectable following both simple taste experiences, as well as following memory retrieval, extinction learning, and reinstatement.}, } @article {pmid37406868, year = {2023}, author = {Nakajima, S and Umemoto, S and Nagaishi, T}, title = {Food avoidance learning based on swimming in laboratory mice (Mus musculus).}, journal = {Behavioural processes}, volume = {}, number = {}, pages = {104910}, doi = {10.1016/j.beproc.2023.104910}, pmid = {37406868}, issn = {1872-8308}, abstract = {Although it is now well documented that laboratory rats learn to avoid the flavored substance consumed immediately before running in activity wheels or swimming in water buckets, research on this activity-based flavor avoidance learning in other species is limited. Recently, running-based flavor avoidance learning has been demonstrated in laboratory mice by employing a method of resistance-to-habituation of neophobic reaction to novel food; mice that repeatedly experience running after encountering a novel food have a prolonged tendency to reject that food compared to control mice without paired running. The present article reports a series of attempts to obtain evidence of flavor avoidance learning based on swimming rather than running using this resistance-to-habituation method. Swimming-based flavor avoidance was clearly demonstrated in a differential conditioning paradigm; however, its demonstration in a simple conditioning paradigm requires a post-training choice test of the target food and another type of food. These results are likely due to the short swimming time (20min) and the formation of weak flavor aversion.}, } @article {pmid37382606, year = {2023}, author = {Kagan, D and Hollings, J and Batabyal, A and Lukowiak, K}, title = {Five-minute exposure to a novel appetitive food substance is sufficient time for a microRNA-dependent long-term memory to form.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {}, number = {}, pages = {}, pmid = {37382606}, issn = {1432-1351}, support = {227993-2019//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {The Garcia effect is a unique form of conditioned taste aversion which requires that a novel food stimulus be followed sometime later by a sickness state associated with the novel food stimulus. The long-lasting associative memory resulting from the Garcia effect ensures that organisms avoid toxic foods in their environment. Considering its ecological relevance, we sought to investigate whether a brief encounter (5 min) with a novel, appetitive food stimulus can cause a persisting long-term memory (LTM) to form that would in turn block the Garcia effect in Lymnaea stagnalis. Furthermore, we wanted to explore whether that persisting LTM could be modified by the alteration of microRNAs via an injection of poly-L-lysine (PLL), an inhibitor of Dicer-mediated microRNA biogenesis. The Garcia effect procedure involved two observations of feeding behavior in carrot separated by a heat stress (30 °C for 1 h). Exposing snails to carrot for 5 min caused a LTM to form and persist for 1 week, effectively preventing the Garcia effect in snails. In contrast, PLL injection following the 5-min carrot exposure impaired LTM formation, allowing the Garcia effect to occur. These results provide more insight into LTM formation and the Garcia effect, an important survival mechanism.}, } @article {pmid37352906, year = {2023}, author = {Su, S and Wei, Z and Huang, H and Yoshizawa, T and Inui, T and Funahashi, M}, title = {Conditioned nausea induced by cisplatin and emetine identified by a taste reactivity test in rats.}, journal = {Physiology & behavior}, volume = {}, number = {}, pages = {114278}, doi = {10.1016/j.physbeh.2023.114278}, pmid = {37352906}, issn = {1873-507X}, abstract = {No prior studies have shown that gaping reactions are produced with the avoidance of conditioned taste caused by cisplatin and emetine. Therefore, we tried to demonstrate it using a taste reactivity test in rats and found the gaping reactions induced when saccharin is readministered after gustatory conditioning that paired saccharin with cisplatin or emetine. Since conditioned gaping reactions indicate the aversion to saccharin taste and conditioned nausea, the present study suggest that the taste aversion is induced by cisplatin and emetine. It was also found that with intraperitoneal injections of emetine alone, gaping almost never occurs.}, } @article {pmid37333122, year = {2023}, author = {Przybysz, KR and Ramirez, LA and Pitock, JR and Starr, EM and Yang, H and Glover, EJ}, title = {A translational rodent model of individual differences in sensitivity to the aversive properties of ethanol.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.06.08.544209}, pmid = {37333122}, abstract = {BACKGROUND: A strong relationship exists between individual sensitivity to the aversive properties of ethanol and risk for alcohol use disorder (AUD). Despite this, our understanding of the neurobiological mechanisms underlying subjective response to ethanol is relatively poor. A major contributor to this is the absence of preclinical models that enable exploration of this individual variability similar to studies performed in humans.

METHODS: Adult male and female Long-Evans rats were trained to associate a novel tastant (saccharin) with acute exposure to either saline or ethanol (1.5 g/kg or 2.0 g/kg i.p.) over three conditioning days using a standard conditioned taste aversion (CTA) procedure. Variability in sensitivity to ethanol-induced CTA was phenotypically characterized using a median split across the populations studied.

RESULTS: When examining group averages, both male and female rats that had saccharin paired with either dose of ethanol exhibited reduced saccharin intake relative to saline controls of ethanol-induced CTA. Examination of individual data revealed a bimodal distribution of responses uncovering two distinct phenotypes present in both sexes. CTA-sensitive rats exhibited a rapid and progressive reduction in saccharin intake with each successive ethanol pairing. In contrast, saccharin intake was unchanged or maintained after an initial decrease from baseline levels in CTA-resistant rats. While CTA magnitude was similar between male and female CTA-sensitive rats, CTA-resistant females were more resistant to the development of ethanol-induced CTA than their male counterparts. Phenotypic differences were not driven by differences in baseline saccharin intake. CTA sensitivity correlated with behavioral signs of intoxication in only a subset of rats.

CONCLUSIONS: These data parallel work in humans by revealing individual differences in sensitivity to the aversive properties of ethanol that emerge immediately after initial exposure to ethanol in both sexes. This model can be leveraged in future studies to investigate the neurobiological mechanisms that confer risk for AUD.}, } @article {pmid37306398, year = {2023}, author = {Cote, JM and Hood, A and Kwon, B and Smith, JC and Houpt, TA}, title = {Behavioral and neural responses to high strength magnetic fields are reduced in otolith mutant mice.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpregu.00317.2022}, pmid = {37306398}, issn = {1522-1490}, abstract = {Static high magnetic fields (MFs) interact with the vestibular system of humans and rodents. In rats and mice, exposure to MFs causes perturbations such as head movements, circular locomotion, suppressed rearing, nystagmus, and conditioned taste aversion acquisition. To test the role of otoconia, two mutant mouse models were examined: head-tilt Nox3[het] (het) and tilted Opt1[tlt] (tlt), with mutations respectively in Nox3, encoding the NADPH oxidase 3 enzyme, and Opt1, encoding the opterin1 proton channel, which are normally expressed in the otolith organs, and are critical for otoconia formation. Consequently, both mutants show a near complete loss of otoconia in the utricle and saccule, and are non-responsive to linear acceleration. Mice were exposed to a 14.1 T MF for 30 min. After exposure, locomotor activity, conditioned taste aversion and c-Fos (in het) were assessed. Wild-type mice exposed to the MF showed suppressed rearing, increased latency to rear, locomotor circling, and c-Fos in brainstem nuclei related to vestibular processing (prepositus, spinal vestibular, and supragenual nuclei). Mutant het mice showed no response to the magnet and were similar to sham animals in all assays. Unlike het, tlt mutants exposed to the MF showed significant locomotor circling and suppressed rearing compared to sham controls, although they failed to acquire a taste aversion. The residual responsiveness of tlt vs het mice might reflect a greater semicircular deficit in het mice. These results demonstrate the necessity of the otoconia for the full effect of exposure to high MFs, but also suggest a semicircular contribution.}, } @article {pmid37113545, year = {2023}, author = {Yu, YH and Tsai, AC and Ou, CY and Cheng, CN and Chang, FC and Shyu, BC and Huang, ACW}, title = {Optogenetic stimulation in the medial prefrontal cortex modulates stimulus valence from rewarding and aversive to neutral states.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1119803}, pmid = {37113545}, issn = {1664-0640}, abstract = {INTRODUCTION: Understanding the modulations of the medial prefrontal cortex (mPFC) in the valence of the stimulus from rewarding and aversive status to neutral status is crucial for the development of novel treatments for drug addiction. This study addressed this issue and examined whether optogenetic ChR2 photostimulation in the cingulate, prelimbic, and infralimbic cortices of the mPFC regulated the valence of saccharin solution consumption from the rewarding property, the aversive property induced by morphine's conditioning, and the neutral states via saccharin extinction processes after morphine's conditioning.

METHODS: All rats received virus infection, buried optical fiber, optical stimulation, water deprivation, and saccharin solution consumption phases. In Experiment 1, rats were given ChR2 virus infection into the cingulate cortex (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL) to influence the rewarding saccharin solution consumption under photostimulation. In Experiment 2, rats were given ChR2 or EYFP virus infection into the Cg1, PrL, and IL to alter the saccharin solution consumption in the morphine-induced aversively conditioned taste aversion (CTA) and the saccharin solution consumption in the neutral state following the extinction process under photostimulation. Later, the immunohistochemical staining with c-Fos protein was performed for the Cg1, IL, PrL, nucleus accumbens core, nucleus accumbens shell, central amygdala, basolateral amygdala, ventral tegmental area, and dentate gyrus.

RESULTS: The results showed that optogenetic PrL stimulation decreased the rewarding valence of saccharin solution consumption and increased the morphine-induced, aversive valence of saccharin solution consumption. PrL stimulation decreased the neutral valence of saccharin solution consumption via the extinction process. Cg1 optogenetic stimulation increased the rewarding valence of saccharin solution consumption and the aversive valence of saccharin solution consumption induced by morphine in conditioning. Optogenetic IL stimulation increased the aversive valence of saccharin solution consumption induced by morphine via conditioning.

CONCLUSION: Altogether, optogenetic stimulation in the subareas of the mPFC modulated the reward, aversion, and neutral valences of the stimulus and altered neuronal activity in the mPFC, amygdala, nucleus accumbens, and hippocampus. Notably, the change of valence was temporary alternation during light-on related to the light-off periods. However, the findings may provide insights in the development of novel treatments for addictive symptoms.}, } @article {pmid36906931, year = {2023}, author = {Chen, A and Wang, R and Kang, Y and Liu, J and Wu, J and Zhang, Y and Zhang, Y and Shao, L}, title = {Tongue-brain-transported ZnO NPs induced abnormal taste perception.}, journal = {Advanced healthcare materials}, volume = {}, number = {}, pages = {e2203316}, doi = {10.1002/adhm.202203316}, pmid = {36906931}, issn = {2192-2659}, abstract = {Nanoparticles (NPs) can be transported to the brain, especially the nerve, because of their small size and high biological activity. Our previous studies confirmed that zinc oxide (ZnO) NPs could enter the brain through the tongue-brain pathway, but it is unclear whether they would further affect synaptic transmission and brain perception. In this study, we found that tongue-brain-transported ZnO NPs could cause a decrease in taste sensitivity and taste aversion learning ability, indicating abnormal taste perception. Moreover, the release of miniature excitatory postsynaptic currents, the frequency of action potential release and the expression of c-fos were decreased, suggesting that the synaptic transmission was reduced. To further explore the mechanism, we carried out protein chip detection of inflammatory factors and found that neuroinflammation occurs. Importantly, we found that neuroinflammation originated from neurons. The JAK-STAT signaling pathway was activated, which inhibited the Neurexin1-PSD95-Neurologigin1 pathway and c-fos expression. Blocking the activation of the JAK-STAT pathway prevented neuroinflammation and the reduction in Neurexin1-PSD95-Neurologigin1. These results indicate that ZnO NPs could be transported by the tongue-brain pathway and lead to abnormal taste perception by neuroinflammation-induced deficits in synaptic transmission. Our study reveals the influence of ZnO NPs on neuronal function and provides a novel mechanism. This article is protected by copyright. All rights reserved.}, } @article {pmid36898644, year = {2023}, author = {Miranda, MI and Alcalá, A and Vera-Rivera, G and Rangel-Hernández, JA}, title = {Differential effects of thirst and satiety on conditioned taste aversion acquisition, retrieval, and memory extinction.}, journal = {Physiology & behavior}, volume = {}, number = {}, pages = {114143}, doi = {10.1016/j.physbeh.2023.114143}, pmid = {36898644}, issn = {1873-507X}, abstract = {Thirst is an essential motivational component that could modulate the strength of conditioning; pioneer studies show that the rats' sexual dimorphism observed in the rate of aversive memory extinction of conditioned taste aversion (CTA) is affected by the state of fluid deprivation. On the other hand, previous evidence suggests that fluid intake volume and temporal context before and during conditioning may influence CTA. Furthermore, although CTA has been demonstrated using various types of stimuli, neural processing and homeostatic regulation of water and nutritional balance may differ depending on the stimulus used and the conditioning stages. Therefore, this study explored the effects of state motivated by thirst and satiation, using saccharin, as a non-caloric sweet stimulus, during CTA and the aversive memory extinction process under similar contextual and temporal conditions. First, we implemented an ad libitum water protocol in male and female adult rats to evaluate saccharin aversive memory formation; we compared this with a traditional CTA with liquid deprivation in the same context and temporal consumption conditions. Furthermore, we evaluated whether liquid satiety affects the acquisition or the aversive memory retrieval differentially. Our results show that the ad libitum liquid regimen allows reliable quantifications of basal water consumption, monitored every hour for more than five days. We observed a reliable CTA, where the magnitude of aversive memory and its extinction is significantly higher in both male and female rats; the strong CTA observed is substantially due to the satiety state during taste aversion memory retrieval. Our data show that although liquid deprivation does not affect CTA acquisition, it does induce weakness in the magnitude of aversive retrieval expression and fast aversive memory extinction, similarly in male and females. Overall, the results indicate that the need to satiate the demand for liquids during retrieval prevails over the conditioned aversion learned, suggesting, that thirst is a source of temporary variables dominating the aversive responses during CTA retrieval.}, } @article {pmid36898496, year = {2023}, author = {Arthurs, J and Pauli, J and Palmiter, RD}, title = {Activation of parabrachial tachykinin 1 neurons counteracts some behaviors mediated by parabrachial CGRP neurons.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2023.03.003}, pmid = {36898496}, issn = {1873-7544}, abstract = {Many threats activate parabrachial neurons expressing calcitonin gene-related peptide (CGRP[PBN]) which transmit alarm signals to forebrain regions. Most CGRP[PBN] neurons also express tachykinin 1 (Tac1), but there are also Tac1-expressing neurons in the PBN that do not express CGRP (Tac1+;CGRP- neurons). Chemogenetic or optogenetic activation of all Tac1[PBN] neurons in mice elicited many physiological/behavioral responses resembling the activation of CGRP[PBN] neurons, e.g., anorexia, jumping on a hot plate, avoidance of photostimulation; however, two key responses opposed activation of CGRP[PBN] neurons. Activating Tac1[PBN] neurons did not produce conditioned taste aversion and it elicited dynamic escape behaviors rather than freezing. Activating Tac1+;CGRP- neurons, using an intersectional genetic targeting approach, resembles activating all Tac1[PBN] neurons. These results reveal that activation of Tac1+;CGRP- neurons can suppress some functions attributed to the CGRP[PBN] neurons, which provides a mechanism to bias behavioral responses to threats.}, } @article {pmid36856894, year = {2023}, author = {Muñiz Moreno, J and Loy, I}, title = {Taste aversion learning in the snail Cornu aspersum.}, journal = {Animal cognition}, volume = {}, number = {}, pages = {}, pmid = {36856894}, issn = {1435-9456}, abstract = {The present study was conducted to provide evidence of conditioned taste aversion learning (CTA) in the snail Cornu aspersum, using quinidine as the aversive stimulus in a procedure of Pavlovian Conditioning of Tentacle Lowering. Subjects were split into two groups: paired and unpaired. During the devaluation phase, subjects from the "paired group" received the US followed by the quinidine exposure, while subjects from the "unpaired group" received the quinidine and, 30 min later, the US. Subjects which had received the US paired with the quinidine showed a decrease of the conditioned response (CR), in contrast to subjects which had received the quinidine and the US unpaired. These results provide a useful CTA procedure in terrestrial snails. The implication of the results for learning and the physiological correlates is discussed.}, } @article {pmid36762112, year = {2023}, author = {Ou, CY and Yu, YH and Wu, CW and Kozłowska, A and Shyu, BC and Huang, ACW}, title = {Neuronal activity of the medial prefrontal cortex, nucleus accumbens, and basolateral amygdala in conditioned taste aversion and conditioned place preference induced by different doses of morphine administrations in rats.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1062169}, pmid = {36762112}, issn = {1663-9812}, abstract = {To re-examine the paradoxical effect hypothesis of abused drugs, the present study concerned whether different doses of morphine disparately affect neuronal activity and associations among the subareas of the medial prefrontal cortex (mPFC: cingulate cortex 1-Cg1, prelimbic cortex-PrL, infralimbic cortex-IL), the subregions of the nucleus accumbens (NAc; both core and shell), and the basolateral amygdala (BLA) following conditioned taste aversion (CTA) and conditioned place preference (CPP). All rats were given a 0.1% saccharin solution for 15-min, and they were intraperitoneally injected with saline or 20, 30, or 40 mg/kg morphine to form the aversive CTA learning. Later, half of the rats were tested for CPP (including the CTA and then CPP tests) for 30-min. Finally, the immunohistochemical staining with c-Fos was conducted after the behavioral test. After the CTA test, c-Fos (%) in the Cg1 and PrL (but not the IL) was more in 20-40 mg/kg of the morphine groups; c-Fos (%) in the NAc core, NAc shell, and BLA was more in the 30-40 mg/kg morphine group. After the CPP test, the Cg1, PrL, IL, and BLA showed more c-Fos (%) in 20 mg/kg morphine; the NAc core showed fewer in c-Fos (%) in the 30-40 mg/kg morphine groups. The mPFC subregions (e.g., Cg1, PrL, and IL), NAc subareas (e.g., NAc core and NAc shell), and BLA were involved in the different doses of morphine injections. The correlation analysis showed that a positive correlation was observed between PrL and IL with NAc core with low doses of morphine and with NAc shell with increasing doses of morphine after the CTA test. After the CPP, an association between PrL and NAc core and NAc shell at low doses and between IL and BLA and NAc shell with increasing doses of morphine. Therefore, different neural substrates and the neural connectivity are observed following different doses of morphine and after the CTA and CPP tests. The present data extend the paradoxical effect hypothesis of abused drugs.}, } @article {pmid36571995, year = {2022}, author = {Yuan, Y and Yan, Z and Lao, Q and Jiang, N and Wu, S and Lu, Q and Han, J and Zhao, S}, title = {Discovery of a potent and long-acting Xenopus GLP-1-based GLP-1/glucagon/Y2 receptor triple agonist.}, journal = {European journal of medicinal chemistry}, volume = {247}, number = {}, pages = {115036}, doi = {10.1016/j.ejmech.2022.115036}, pmid = {36571995}, issn = {1768-3254}, abstract = {The combination of incretin-based therapies and PYY analogue has shown great potential for the treatment of type 2 diabetes (T2DM) and obesity. In this study we developed the first example of a unimolecular triple agonist peptide to simultaneously target GLP-1, glucagon and Y2 receptors, aiming for superior weight loss and better glycemic control. The strategy for constructing such a unimolecular triple agonist peptide is the conjugation of the GLP-1R/GCGR dual-agonistic moiety and PYY moiety via maleimide-thiol specific reaction. A novel triple agonist peptide, 3b, was identified via stepwise structure optimization, long-acting modification and in vitro receptor screens. Peptide 3b exhibited potent and balanced GCGR and GLP-1R activities as well as potent and highly selective Y2R activity. Peptide 3b potently reduced food intake without triggering nausea associated behavior in kaolin consumption and conditioned taste aversion assays. In diet induced obesity (DIO) mice, a lower dose of 3b achieved significantly better effects on lipid metabolism, body weight, and glycemic control than higher dose of GLP-1R mono-agonist, GLP-1R/GCGR dual agonist and GLP-1R/Y2R dual agonist counterparts. Collectively, these data support the therapeutic potential of our GLP-1R/GCGR/Y2R triple agonist 3b as a novel anti-obesity and anti-diabetic agent. Targeting GLP-1R, GCGR and Y2R with unimolecular triple agonist peptide offers a route to develop new obesity and T2DM treatments.}, } @article {pmid36563678, year = {2022}, author = {Lavi, A and Sehgal, M and de Sousa, AF and Ter-Mkrtchyan, D and Sisan, F and Luchetti, A and Okabe, A and Bear, C and Silva, AJ}, title = {Local memory allocation recruits memory ensembles across brain regions.}, journal = {Neuron}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuron.2022.11.018}, pmid = {36563678}, issn = {1097-4199}, abstract = {Memories are thought to be stored in ensembles of neurons across multiple brain regions. However, whether and how these ensembles are coordinated at the time of learning remains largely unknown. Here, we combined CREB-mediated memory allocation with transsynaptic retrograde tracing to demonstrate that the allocation of aversive memories to a group of neurons in one brain region directly affects the allocation of interconnected neurons in upstream brain regions in a behavioral- and brain region-specific manner in mice. Our analysis suggests that this cross-regional recruitment of presynaptic neurons is initiated by downstream memory neurons through a retrograde mechanism. Together with statistical modeling, our results indicate that in addition to the anterograde flow of information between brain regions, the establishment of interconnected, brain-wide memory traces relies on a retrograde mechanism that coordinates memory ensembles at the time of learning.}, } @article {pmid36548243, year = {2022}, author = {Gore-Langton, JK and Varlinskaya, EI and Werner, DF and , }, title = {Ethanol-induced conditioned taste aversion and associated neural activation in male rats: Impact of age and adolescent intermittent ethanol exposure.}, journal = {PloS one}, volume = {17}, number = {12}, pages = {e0279507}, doi = {10.1371/journal.pone.0279507}, pmid = {36548243}, issn = {1932-6203}, abstract = {Individuals that initiate alcohol use at younger ages and binge drink during adolescence are more susceptible to developing alcohol use disorder. Adolescents are relatively insensitive to the aversive effects of alcohol and tend to consume significantly more alcohol per occasion than adults, an effect that is conserved in rodent models. Adolescent typical insensitivity to the aversive effects of alcohol may promote greater alcohol intake by attenuating internal cues that curb its consumption. Attenuated sensitivity to the aversive effects of alcohol is also retained into adulthood following protracted abstinence from adolescent intermittent ethanol (AIE) exposure. Despite these effects, much remains unknown regarding the neural contributors. In the present study, we used a conditioned taste aversion (CTA) paradigm to investigate neuronal activation in late-developing forebrain structures of male adolescents and adult cFos-LacZ transgenic rats as well as in AIE adults following consumption of 0.9% sodium chloride previously paired with an intraperitoneal injection of 0, 1.5 or 2.5 g/kg of ethanol. Adults that were non-manipulated or received water exposure during adolescence showed CTA to both ethanol doses, whereas adolescents displayed CTA only to the 2.5 g/kg ethanol dose. Adults who experienced AIE did not show CTA. Adults displayed increased neuronal activation indexed via number of β-galactosidase positive (β-gal+) cells in the prefrontal and insular cortex that was absent in adolescents, whereas adolescents but not adults had a reduced number of β-gal+ cells in the central amygdala. Adults also displayed greater cortical-insular functional connectivity than adolescents as well as insular-amygdalar and prefrontal cortex-accumbens core functional connectivity. Like adolescents, adults previously exposed to AIE displayed reduced prefrontal-insular cortex and prefrontal-accumbal core functional connectivity. Taken together, these results suggest that attenuated sensitivity to the aversive effects of ethanol is related to a loss of an insular-prefrontal cortex-accumbens core circuit.}, } @article {pmid36509179, year = {2022}, author = {Kikuchi, E and Inui, T and Su, S and Sato, Y and Funahashi, M}, title = {Chemogenetic inhibition of the bed nucleus of the stria terminalis suppresses the intake of a preferable and learned aversive sweet taste solution in male mice.}, journal = {Behavioural brain research}, volume = {}, number = {}, pages = {114253}, doi = {10.1016/j.bbr.2022.114253}, pmid = {36509179}, issn = {1872-7549}, abstract = {Conditioned taste aversion (CTA) is established by pairing a taste solution as a conditioned stimulus (CS) with visceral malaise as an unconditioned stimulus (US). CTA decreases the taste palatability of a CS. The bed nucleus of the stria terminalis (BNST) receives taste inputs from the brainstem. However, the involvement of the BNST in CTA remains unclear. Thus, this study examined the effects of chemogenetic inhibition of the BNST neurons on CS intake after CTA acquisition. An adeno-associated virus was microinjected into the BNST of male C57/BL6 mice to induce the inhibitory designer receptor hM4Di. The mice received a pairing of 0.2% saccharin solution (CS) with 0.3M lithium chloride (2% BW, intraperitoneal). After conditioning, the administration of clozapine-N-oxide (CNO, 1mg/kg) significantly enhanced the suppression of CS intake on the retrieval of CTA compared with its intake following saline administration (p < 0.01). We further assessed the effect of BNST neuron inhibition on the intake of water and taste solutions (saccharin, sucralose, sodium chloride, monosodium glutamate, quinine hydrochloride, and citric acid) using naïve (not learned CTA) mice. CNO administration significantly decreased the intake of saccharin and sucralose (p < 0.05). Our results indicate that BNST neurons mediate sweet taste and regulate sweet intake, regardless of whether sweets should be ingested or rejected. BNST neurons may be inhibited in the retrieval of CTA, thereby suppressing CS intake.}, } @article {pmid36508476, year = {2022}, author = {Hatakeyama, D and Chikamoto, N and Fujimoto, K and Kitahashi, T and Ito, E}, title = {Comparison between relative and absolute quantitative real-time PCR applied to single-cell analyses: Transcriptional levels in a key neuron for long-term memory in the pond snail.}, journal = {PloS one}, volume = {17}, number = {12}, pages = {e0279017}, doi = {10.1371/journal.pone.0279017}, pmid = {36508476}, issn = {1932-6203}, abstract = {Quantitative real-time PCR (qPCR) is a powerful method for measuring nucleic acid levels and quantifying mRNA levels, even in single cells. In the present study, we compared the results of single-cell qPCR obtained by different quantification methods (relative and absolute) and different reverse transcription methods. In the experiments, we focused on the cerebral giant cell (CGC), a key neuron required for the acquisition of conditioned taste aversion in the pond snail Lymnaea stagnalis, and examined changes in the mRNA levels of 3 memory-related genes, cAMP-response element binding proteins (LymCREB1 and LymCREB2) and CREB-binding protein (LymCBP), during memory formation. The results obtained by relative quantification showed similar patterns for the 3 genes. For absolute quantification, reverse transcription was performed using 2 different methods: a mixture of oligo d(T) primers and random primers (RT method 1); and gene-specific primers (RT method 2). These methods yielded different results and did not show consistent changes related to conditioning. The mRNA levels in the samples prepared by RT method 2 were up to 3.3 times higher than those in samples prepared by RT method 1. These results suggest that for qPCR of single neurons, the efficacy and validity do not differ between relative and absolute quantification methods, but the reverse transcription step critically influences the results of mRNA quantification.}, } @article {pmid36444166, year = {2022}, author = {Al-Kuraishy, HM and Al-Gareeb, AI and Alexiou, A and Papadakis, M and Nadwa, EH and Albogami, SM and Alorabi, M and Saad, HM and Batiha, GE}, title = {Metformin and growth differentiation factor 15 (GDF15) in type 2 diabetes mellitus: A hidden treasure.}, journal = {Journal of diabetes}, volume = {}, number = {}, pages = {}, doi = {10.1111/1753-0407.13334}, pmid = {36444166}, issn = {1753-0407}, abstract = {Type 2 diabetes mellitus (T2DM) is a chronic endocrine disorder due to the reduction of insulin sensitivity and relative deficiency of insulin secretion. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta (TGF-β) superfamily and was initially identified as macrophage inhibitory cytokine-1 (MIC-1). GDF15 is considered a cytokine with an anti-inflammatory effect and increases insulin sensitivity, reduces body weight, and improves clinical outcomes in diabetic patients. GDF15 acts through stimulation of glial-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), which is highly expressed in the brain stem to induce taste aversion. Metformin belongs to the group of biguanides that are derived from the plant Galega officinalis. It is interesting to note that metformin is an insulin-sensitizing agent used as a first-line therapy for T2DM that has been shown to increase the circulating level of GDF15. Thus, the present review aims to determine the critical association of the GDF15 biomarker in T2DM and how metformin agents affect it. This review illustrates that metformin activates GDF15 expression, which reduces appetite and leads to weight loss in both diabetic and nondiabetic patients. However, the present review cannot give a conclusion in this regard. Therefore, experimental, preclinical, and clinical studies are warranted to confirm the potential role of GDF15 in T2DM patients.}, } @article {pmid36439968, year = {2022}, author = {Panayi, MC and Killcross, S}, title = {Outcome devaluation by specific satiety disrupts sensory-specific Pavlovian-to-instrumental transfer.}, journal = {Frontiers in behavioral neuroscience}, volume = {16}, number = {}, pages = {983480}, pmid = {36439968}, issn = {1662-5153}, abstract = {Reward predictive cues can selectively motivate instrumental behaviors that predict the same rewarding outcomes, an effect known as specific Pavlovian-to-instrumental transfer (PIT). This selective effect is thought to be mediated by a representation of the sensory specific properties of an outcome, that has become associated with both the Pavlovian cue and the instrumental response during initial learning. Specific satiety is a common method of outcome devaluation that reduces an outcome's value but might also lead to the habituation of the outcome's sensory properties. Previous research has demonstrated that specific PIT is insensitive to changes in specific outcome value following taste aversion devaluation, as well as general satiety manipulations, and therefore specific satiety should not disrupt specific PIT by reducing outcome value. The present rodent experiments used a specific satiety devaluation procedure immediately prior to a specific PIT test to show that habituation of these outcome specific sensory representations can disrupt its efficacy as a stimulus and abolish the specific PIT effect. Experiment 1 employed a two-lever choice test to show that a non-devalued stimulus supports specific PIT, whereas a devalued stimulus abolished the specific PIT effect. Experiment 2 replicated this procedure while controlling for response competition by using a single-lever test to confirm that a devalued stimulus abolishes the specific PIT effect. These findings demonstrate that specific satiety can disrupt the ability of an outcome specific representation to support specific PIT. Given previous findings that specific PIT is insensitive to changes in outcome value by general satiety and taste aversion devaluation, this suggests that specific satiety devaluation might disrupt the use of sensory specific outcome representations to guide behavior via a mechanism that is independent of the outcome's current value.}, } @article {pmid36382058, year = {2022}, author = {Yoshida, Y and Tanaka, R and Fujishiro, S and Nishimura, S and Tabata, S and Kawabata, F}, title = {Conditioned Taste Aversion to L-Amino Acid Taste Stimuli and Oral Transcriptional Changes to Type 1 Taste Receptors T1R1 and T1R3 on Chronic Exposure to L-Alanine Solution in Chickens.}, journal = {The journal of poultry science}, volume = {59}, number = {4}, pages = {348-356}, pmid = {36382058}, issn = {1349-0486}, abstract = {Elucidating taste sensing systems in chickens is an important step toward understanding poultry nutrition. Amino acid taste receptors, type 1 taste receptors 1 and 3 (T1R1 and T1R3, respectively), are expressed in chicken taste cells, and chicken T1R1/T1R3 is activated by L-alanine (L-Ala) and L-serine (L-Ser), but not by L-proline (L-Pro). However, it is not clear whether chickens have a gustatory perception of L-amino acids. Here, we found that chickens conditioned to avoid either L-Ala, L-Ser, or L-Pro solutions could successfully learn to avoid the corresponding L-amino acid solution in the conditioned taste aversion (CTA) test. Because CTA is a well-established learning paradigm generated specifically by pairing gustatory perception and gastrointestinal malaise, the present study suggests that chickens can sense L-amino acids by gustatory perception. In addition, we found that the expression of the T1R1 and T1R3 genes was significantly downregulated in response to chronic exposure to L-Ala solution, but not to acute oral stimulation. Taken together, the present study suggests that chickens have a gustatory perception of L-amino acids, and the expression of T1R1/T1R3 mRNAs in the oral cavity can be regulated by L-amino acid intake. Since chickens can detect L-Pro solutions, additional amino acid receptors, other than T1R1/T1R3, may be involved in L-amino acid taste detection in chickens.}, } @article {pmid36368526, year = {2022}, author = {Reich, N and Hölscher, C}, title = {Beyond appetite: Acylated ghrelin as a learning, memory and fear behavior-modulating hormone.}, journal = {Neuroscience and biobehavioral reviews}, volume = {143}, number = {}, pages = {104952}, doi = {10.1016/j.neubiorev.2022.104952}, pmid = {36368526}, issn = {1873-7528}, mesh = {Humans ; *Ghrelin/metabolism ; *Memory/physiology ; Appetite ; Fear/physiology ; Amygdala/physiology ; Hippocampus/physiology ; }, abstract = {Although often referred to as a hunger hormone, recent evidence highlights a neuroprotective function of acylated ghrelin (AG) and a substantial role in the regulation of declarative and aversive memories as well as fear behavior. As such, in this review, we i) evaluate what specific stages and forms of memory, as well as which respective brain areas are affected by acylated ghrelin, ii) illustrate the plasticity-associated signaling pathways of AG in the hippocampus, also involving memory resolution-enhancing neurogenesis, iii) elucidate how the peptide modulates neurotransmitter systems (glutamate, γ-aminobutyric acid, dopamine, serotonin), iV) clarify the role of AG in conditioned taste aversion, novelty learning and the formation of spatial, recognition, auditory fear, contextual fear and passive avoidance memories in the hippocampus and amygdala as well as V) solve the mystery behind AG, its impact on the 5-HT system, the recently established link to post-traumatic stress disorder and the either fear-suppressing or fear-potentiating effects under neutral and acutely stressed conditions or chronic stress, respectively.}, } @article {pmid36261035, year = {2022}, author = {Staszko, SM and Boughter, JD and Fletcher, ML}, title = {The impact of familiarity on cortical taste coding.}, journal = {Current biology : CB}, volume = {32}, number = {22}, pages = {4914-4924.e4}, pmid = {36261035}, issn = {1879-0445}, support = {R01 DC016833/DC/NIDCD NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Cerebral Cortex/physiology ; *Taste/physiology ; Taste Perception/physiology ; Neurons/physiology ; Recognition, Psychology ; }, abstract = {The role of the gustatory region of the insular cortex in mediating associative taste learning, such as conditioned taste aversion, has been well studied. However, while associative learning plays a role in some taste behaviors, such as avoiding toxins, animals often encounter taste stimuli in their natural environment without explicit consequences. This type of inconsequential experience with sensory stimuli has been studied in other sensory systems, generally with the finding that neuronal responses habituate with repeated sensory exposure. This study sought to determine the effect of taste familiarity on population taste coding in the mouse gustatory cortex (GC). Using microendoscope calcium imaging, we studied the taste responses of visually identifiable neurons over 5 days of taste experience, during which animals could freely choose to consume taste stimuli. We found that the number of active cells in the insular cortex, as well as the number of cells characterized as taste-responsive, significantly decreased as animals became familiar with taste stimuli. Moreover, the magnitude of taste-evoked excited responses increased while inhibited responses decreased with experience. By tracking individual neurons over time, we identified a subpopulation of stable neurons present on all days of the taste familiarity paradigm and further characterized their taste coding properties. The population-level response across these stable cells was distinct for each taste quality when taste stimuli were novel, but population responses for readily consumed stimuli became more correlated as the stimuli became familiar. Overall, these results highlight the effects of familiarity on both taste-specific and non-taste responses in the gustatory cortex.}, } @article {pmid36248606, year = {2022}, author = {López, M and Dwyer, DM and Gasalla, P and Jove, C and Begega, A}, title = {Characterizing Hedonic Responses to Flavors Paired with Internal Pain and Nausea through the Taste Reactivity Test in Rats.}, journal = {Bio-protocol}, volume = {12}, number = {18}, pages = {}, pmid = {36248606}, issn = {2331-8325}, abstract = {Feeding behavior is a complex experience that involves not only sensory (i.e., visual, odor, taste, or texture) but also affective or emotional aspects (i.e., pleasure, palatability, or hedonic value) of foods. As such, behavioral tests that assess the hedonic impact of foods are necessary to fully understand the factors involved in ingestive behavior. In this protocol, we use the taste reactivity (TR) test to characterize the hedonic responses of rats to flavors paired with either lithium chloride-induced nausea or internal pain produced by hypertonic NaCl, two treatments that reduce voluntary consumption. This application of the TR test demonstrates how emetic and non-emetic (somatic pain in particular) treatments produce dissociable patterns of hedonic reactions to fluids: only emetic treatments result in the production of aversive orofacial responses, reflecting conditioned nausea, whereas somatic pain produces immobility, reflecting conditioned fear. Other methods, such as the microstructural analysis of licking behavior, do not reliably distinguish conditioned nausea and fear, a key advantage of the more selective TR procedure. This protocol also contains guidance for adaptation to other species and designs.}, } @article {pmid36190750, year = {2022}, author = {Buabang, EK and Boddez, Y and Wolf, OT and Moors, A}, title = {The role of goal-directed and habitual processes in food consumption under stress after outcome devaluation with taste aversion.}, journal = {Behavioral neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1037/bne0000439}, pmid = {36190750}, issn = {1939-0084}, abstract = {People are more likely to engage in various suboptimal behaviors such as overeating, addictive behaviors, and short-sighted financial decision-making when they are under stress. Traditional dual-process models propose that stress can impair the ability to engage in goal-directed behavior so that people have to rely on habitual behavior. Support for this idea comes from a study by Schwabe and Wolf (2010), in which stressed participants continued to perform a learned instrumental behavior leading to a liquid after the liquid was devalued with a satiation procedure. Based on these findings, suboptimal behavior under stress is often seen as habitual. In the present study, we conducted a conceptual replication of the study by Schwabe and Wolf (2010). Instead of using a satiation procedure to achieve the outcome devaluation, we devalued outcomes through taste aversion. We did not replicate the pattern of findings by Schwabe and Wolf (2010). Our results indicate instead that stressed participants were sensitive to outcome values when the outcomes became truly aversive and hence that their behavior was goal-directed. This suggests either that (a) habitual processes are subject to boundary conditions or (b) the processes responsible for the findings of Schwabe and Wolf (2010) were never habitual to begin with. This may have far-reaching implications for explaining suboptimal behavior under stress in general. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid36183862, year = {2022}, author = {Bishnoi, IR and Cloutier, CJ and Tyson, CD and Matic, VM and Kavaliers, M and Ossenkopp, KP}, title = {Infection, learning, and memory: Focus on immune activation and aversive conditioning.}, journal = {Neuroscience and biobehavioral reviews}, volume = {142}, number = {}, pages = {104898}, doi = {10.1016/j.neubiorev.2022.104898}, pmid = {36183862}, issn = {1873-7528}, mesh = {Animals ; *Lipopolysaccharides/pharmacology ; *Avoidance Learning ; Lithium Chloride/pharmacology ; Behavior, Animal/physiology ; Conditioning, Psychological/physiology ; Taste ; }, abstract = {Here we review the effects of immune activation primarily via lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, on hippocampal and non-hippocampal-dependent learning and memory. Rodent studies have found that LPS alters both the acquisition and consolidation of aversive learning and memory, such as those evoking evolutionarily adaptive responses like fear and disgust. The inhibitory effects of LPS on the acquisition and consolidation of contextual fear memory are discussed. LPS-induced alterations in the acquisition of taste and place-related conditioned disgust memory within bottle preference tasks and taste reactivity tests (taste-related), in addition to conditioned context avoidance tasks and the anticipatory nausea paradigm (place-related), are highlighted. Further, conditioned disgust memory consolidation may also be influenced by LPS-induced effects. Growing evidence suggests a central role of immune activation, especially pro-inflammatory cytokine activity, in eliciting the effects described here. Understanding how infection-induced immune activation alters learning and memory is increasingly important as bacterial and viral infections are found to present a risk of learning and memory impairment.}, } @article {pmid36056214, year = {2022}, author = {Liu, J and Wu, R and Johnson, B and Zhang, Y and Zhu, Q and Li, JX}, title = {Selective TAAR1 agonists induce conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {239}, number = {10}, pages = {3345-3353}, pmid = {36056214}, issn = {1432-2072}, support = {R01DA034806/DA/NIDA NIH HHS/United States ; R21DA040777/DA/NIDA NIH HHS/United States ; R01DA034806/DA/NIDA NIH HHS/United States ; R21DA040777/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Antipsychotic Agents/chemistry/pharmacology ; Aversive Agents/chemistry/pharmacology ; Humans ; Mammals ; Oxazoles ; Phenethylamines/pharmacology ; Rats ; *Receptors, G-Protein-Coupled/agonists ; Saccharin/pharmacology ; Sodium Chloride ; Taste/drug effects ; *Taste Perception/drug effects ; }, abstract = {RATIONALE: Trace amine-associated receptor 1 (TAAR1) is the best-studied receptor of trace amines, a group of biogenic amines expressed at a relatively low level in the mammalian brain. Growing evidence suggests that TAAR1 plays a critical role in various neuropsychiatric disorders. Given that selective TAAR1 agonists were shown to produce pro-cognition and antipsychotic-like effects as well as to suppress drug use and relapse, they have been proposed to be novel treatments for mental disorders such as schizophrenia and addiction. However, the aversive effects of selective TAAR1 agonists remain largely unknown.

OBJECTIVES: Here, we evaluated whether the selective TAAR1 full agonist RO5166017 and partial agonist RO5263397 could induce conditioned taste aversion (CTA).

RESULTS: We found that RO5166017 and RO5263397 produced significant aversions to both saccharin and NaCl taste novelty. Furthermore, RO5166017 produced CTA to saccharin in TAAR1 heterozygous knockout (taar1[±]) and wild-type rats but not in TAAR1 homozygous knockout rats (taar1[-/-]), suggesting that TAAR1 was sufficient for the taste aversive stimulus property of RO5166017.

CONCLUSIONS: Taken together, our data indicate that selective TAAR1 agonists could produce strong CTA. Our study urges careful evaluations of the aversive effects of TAAR1 agonists before translating them to clinical use for the treatment of mental disorders.}, } @article {pmid35944659, year = {2022}, author = {Niedringhaus, M and West, EA}, title = {Prelimbic cortex neural encoding dynamically tracks expected outcome value.}, journal = {Physiology & behavior}, volume = {256}, number = {}, pages = {113938}, doi = {10.1016/j.physbeh.2022.113938}, pmid = {35944659}, issn = {1873-507X}, support = {R00 DA042934/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Cerebral Cortex ; *Conditioning, Classical ; Cues ; Extinction, Psychological ; Rats ; *Reward ; }, abstract = {Animals must modify their behavior based on updated expected outcomes in a changing environment. Prelimbic cortex (PrL) neural encoding during learning predicts, and is necessary for, appropriately altering behavior based on a new expected outcome value following devaluation. We aimed to determine how PrL neural activity encodes reward predictive cues after the expected outcome value of those cues is decreased following conditioned taste aversion. In one post-devaluation session, rats were tested under extinction to determine their ability to alter their behavior to the expected outcome values (i.e., extinction test). In a second post-devaluation session, rats were tested with the newly devalued outcome delivered so that the rats experienced the updated outcome value within the session (i.e., re-exposure test). We found that PrL neural encoding of the cue associated with the devalued reward predicted the ability of rats to suppress behavior in the extinction test session, but not in the re-exposure test session. While all rats were able to successfully devalue the outcome during conditioned taste aversion, a subset of rats continued to consume the devalued outcome in the re-exposure test session. We found differential patterns of PrL neural encoding in the population of rats that did not avoid the devalued outcome during the re-exposure test compared to the rats that successfully avoided the devalued outcome. Our findings suggest that PrL neural encoding dynamically tracks expected outcome values, and differential neural encoding in the PrL to reward predictive cues following expected outcome value changes may contribute to distinct behavioral phenotypes.}, } @article {pmid35931277, year = {2022}, author = {Ascencio Gutierrez, V and Carrillo, AA and Boersma, GJ and Tamashiro, KLK and Moran, TH and Iñiguez, SD and Treesukosol, Y}, title = {Effect of early-life stress or fluoxetine exposure on later-life conditioned taste aversion learning in Sprague-Dawley rats.}, journal = {Neuroscience letters}, volume = {787}, number = {}, pages = {136818}, doi = {10.1016/j.neulet.2022.136818}, pmid = {35931277}, issn = {1872-7972}, support = {R16 GM145552/GM/NIGMS NIH HHS/United States ; SC2 GM109811/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adverse Childhood Experiences ; Animals ; Avoidance Learning ; Body Weight ; *Fluoxetine/pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Taste ; }, abstract = {In rodents, early-life exposure to environmental stress or antidepressant medication treatment has been shown to induce similar long-term consequences on memory- and depression-related behavior in adulthood. To expand on this line of work, we evaluated how juvenile exposure to chronic variable stress (CVS) or the selective serotonin reuptake inhibitor fluoxetine (FLX) influences conditioned taste aversion (CTA) learning in adulthood. To do this, in Experiment 1, we examined how adolescent CVS alone (postnatal day [PND] 35-48), or with prenatal stress (PNS) history (PNS + CVS), influenced the acquisition and extinction of CTA in adult male Sprague Dawley rats. Specifically, at PND70+ (adulthood), rats were presented with 0.15 % saccharin followed by an intraperitoneal (i.p.) injection of lithium chloride (LiCl) to induce visceral malaise. A total of four saccharin (conditioned stimulus) and LiCl (unconditioned stimulus) pairings occurred across the CTA acquisition phase. Next, saccharin was presented without aversive consequences, and intake was measured across consecutive days of the extinction phase. No differences in body weight gain across the experimental days, rate of CTA acquisition, or extinction of CTA, were observed among the experimental groups (control, n = 7; CVS, n = 12; PNS + CVS, n = 9). In Experiment 2, we evaluated if early-life FLX exposure alters CTA learning in adulthood. Specifically, adolescent stress naïve male and female rats received FLX (0 or 20 mg/kg/i.p) once daily for 15 consecutive days (PND35-49). During antidepressant exposure, FLX decreased body weight gain in both male (n = 7) and female rats (n = 7), when compared to respective controls (male control, n = 8; female control, n = 8). However, juvenile FLX exposure decreased body weight-gain in adult male, but not female, rats. Lastly, adolescent FLX history had no effect on CTA acquisition or extinction in adulthood (PND70), in neither male nor female rats. Together, the data indicate that juvenile FLX exposure results in a long-term decrease of body weight-gain in a male-specific manner. Yet, independent of sex, neither early-life stress nor FLX exposure alters CTA learning in adulthood.}, } @article {pmid35918017, year = {2022}, author = {Tachibana, T and Nakatani, A and Khan, S and Makino, R and Cline, MA}, title = {Effect of lithium chloride on food intake, cloacal temperature, voluntary activity, and crop-emptying rate in chicks.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {273}, number = {}, pages = {111284}, doi = {10.1016/j.cbpa.2022.111284}, pmid = {35918017}, issn = {1531-4332}, mesh = {Animals ; Anorexia ; *Chickens/physiology ; Eating ; Lipopolysaccharides/pharmacology ; Lithium/pharmacology ; *Lithium Chloride/pharmacology ; Mammals ; Taste ; Temperature ; Zymosan/pharmacology ; }, abstract = {Infections frequently accompany with non-specific symptoms such as anorexia and hyperthermia. In addition, there may be unpleasant sensations such as visceral discomfort during infection. Lipopolysaccharide (LPS), a Gram-negative bacteria cell wall component, is known to induce the unpleasant sensation of conditioned taste aversion in mammals. However, the relationship between unpleasant sensations and changes in behavior and physiological conditions has not been investigated extensively in birds. Lithium chloride (LiCl) is a compound that induces unpleasant sensations, including visceral discomfort, although its effects on behavior and physiological conditions have also not been investigated extensively in birds. Thus, the present study was aimed to investigate the effect of an intraperitoneal (IP) injection of LiCl on conditioned visual aversion, food intake, cloacal temperature, voluntary activity, crop-emptying rate, and blood constituents in chicks (Gallus gallus). We also examined the effect of IP injections of LPS and zymosan, a cell wall component of fungus, on conditioned visual aversion formation. First, IP injection of LiCl was confirmed to induce conditioned visual aversion in chicks. An IP injection of LiCl significantly decreased food intake, voluntary activity, and crop-emptying rate but did not affect the temperature. In addition, the injection of LiCl significantly increased plasma corticosterone concentration, indicating that LiCl serves as a stressor in chicks. Finally, IP injections of LPS and zymosan were found to induce conditioned visual aversion in chicks. Collectively, these results suggest that LiCl induces conditioned aversion, anorexia, hypoactivity, and inhibition of crop-emptying in chicks. In addition, LPS and zymosan would induce unpleasant sensations in chicks.}, } @article {pmid35913117, year = {2022}, author = {Bai, L and Sivakumar, N and Yu, S and Mesgarzadeh, S and Ding, T and Ly, T and Corpuz, TV and Grove, JCR and Jarvie, BC and Knight, ZA}, title = {Enteroendocrine cell types that drive food reward and aversion.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35913117}, issn = {2050-084X}, support = {RF1 NS116626/NS/NINDS NIH HHS/United States ; R01 DK106399/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cholecystokinin/metabolism ; *Enteroendocrine Cells/metabolism ; *Food ; Food Preferences ; Mice ; Reward ; Taste ; }, abstract = {Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here, we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.}, } @article {pmid35878079, year = {2022}, author = {Sánchez, J and Dwyer, DM and Honey, RC and de Brugada, I}, title = {Perceptual learning after rapidly alternating exposure to taste compounds: Assessment with different indices of generalization.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {48}, number = {3}, pages = {169-178}, doi = {10.1037/xan0000333}, pmid = {35878079}, issn = {2329-8464}, support = {/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Association Learning/physiology ; Conditioning, Classical ; *Discrimination Learning ; Generalization, Psychological ; Humans ; Learning ; Male ; Rats ; *Taste/physiology ; }, abstract = {Exposure to two similar stimuli (AX and BX; e.g., two tastes) reduces the extent to which a conditioned response later established to BX generalizes to AX. This example of perceptual learning is more evident when AX and BX are exposed in an alternating manner (AX, BX, AX, BX,…) than when AX and BX occur in separate blocks (e.g., AX, AX,…BX, BX,…). We examined in male rats (N = 126) the impact of rapid alternation to AX and BX on generalization of a taste aversion from BX to AX. Experiment 1 showed that such alternating presentations (with 5-min intervals between AX and BX) reduced generalization relative to blocked exposure; but only as assessed by consumption levels and not by lick cluster size (an index of hedonic reactions). Experiment 1 also showed that the nature of exposure did not affect how A influenced performance to a novel conditioned taste, Y. Experiment 2 replicated the pattern of results involving the different influences of rapidly alternating and blocked exposure on generalization from BX to AX, and showed that this effect was only evident when rats received access to water during the 5-min intervals between AX and BX. These results reinforce parallels between perceptual learning effects in rats and humans, both at empirical and theoretical levels. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35864815, year = {2022}, author = {Shanmugamprema, D and Muthuswamy, K and Ponnusamy, V and Subramanian, G and Velusamy, T and Krishnan, V and Subramaniam, S}, title = {CD36 and GPR120 mediated orogustatory perception of dietary lipids and its physiological implication in the pygmy mouse Mus booduga.}, journal = {Journal of animal physiology and animal nutrition}, volume = {106}, number = {6}, pages = {1408-1419}, doi = {10.1111/jpn.13755}, pmid = {35864815}, issn = {1439-0396}, mesh = {Mice ; Animals ; *Taste Buds/metabolism ; Dietary Fats/metabolism ; CD36 Antigens/genetics/metabolism ; Taste Perception/genetics ; Taste ; Linoleic Acid/metabolism ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {Fat taste perception has long been concerned in the regulation of dietary fat intake. Substantial experimental evidence defends fat as a sixth taste modality, but its allied peripheral mechanisms are not yet well established. The present study aimed to analyse the diet-induced changes in fat taste perception and its associated physiological variations in Mus booduga. Four groups of animals were used for the present study and were fed any one of the following diet; normal diet (10% fat), low-fat diet (4% fat), high-fat diet (36% fat), or high-fat diet (HFD) (36% fat) + rapeseed oil (HFRDO) (14%) for 9 weeks. The animals were then subjected to metabolic tolerance, fat preference, and conditioned taste aversion studies. Diet-induced alterations in the expression of genes associated with lipogenesis, inflammation, and fat taste (CD36 and GPR120) were analysed. Capacitative calcium signalling induced by both linoleic acid and grifolic acid in taste bud cells (TBCs) was also analysed. In result, both the HFD and HFDRO groups revealed deterioration in glucose homoeostasis and displayed decreased preference scores for fatty acids, which are associated with lower CD36 expression and increased GPR120 expression in TBCs. Furthermore, change in [Ca[2+] ]i induced by LA was also compromised in CD36 positive TBCs along with elevated systemic inflammatory and lipidemic responses in both these obese groups. Overall, for the first time, our results support that chronic HFD feeding alters the CD36 and GPR120 mediated fat taste perception in M. booduga.}, } @article {pmid35784020, year = {2022}, author = {Aiyer, A and Bunuba Rangers, and Bell, T and Shine, R and Somaweera, R and Bruny, M and Ward-Fear, G}, title = {Taking the bait: Developing a bait delivery system to target free-ranging crocodiles and varanid lizards with a novel conservation strategy.}, journal = {Ecology and evolution}, volume = {12}, number = {6}, pages = {e8933}, pmid = {35784020}, issn = {2045-7758}, abstract = {In tropical Australia, conditioned taste aversion (CTA) can buffer vulnerable native predators from the invasion of a toxic prey species (cane toads, Rhinella marina). Thus, we need to develop methods to deploy aversion-inducing baits in the field, in ways that maximize uptake by vulnerable species (but not other taxa). We constructed and field-tested baiting devices, in situ with wild animals. Apparatus were set next to waterbodies and baited concurrently at multiple locations (over water, water's edge, and on the bank). Baits were checked and replaced twice daily during the trial; remote cameras recorded visitation by native predators. Bait longevity was compared at sun-exposed and shaded locations over 12 h. The strength required to remove baits from apparatus was measured in varanids and crocodiles. The device promoted high rates of bait uptake by freshwater crocodiles (47% baits consumed), varanid lizards (19% baits consumed), and non-target taxa (34% baits consumed). Targeting specific predators can be achieved by manipulating bait location and time of deployment, as well as the force required to dislodge the bait. Crocodiles were best targeted with over-water baits, whereas varanid lizards preferred baits located at the edges of waterbodies. When testing bait longevity in ambient conditions, during the daytime baits desiccated fully within 12 h, and faster in the sun than in the shade. Based on studies using captive animals, the "pulling force" strength of reptilian predators scaled with body size and was greater in crocodiles than in varanid lizards. We present the first conservation baiting protocol designed specifically for reptiles. Our results demonstrate the feasibility of widespread and taxon-specific deployment of aversion-inducing baits to buffer the impacts of invasive cane toads, and our methods are applicable (with modification) to other research and management programs globally.}, } @article {pmid35762652, year = {2022}, author = {Sun, H and Li, J and Yan, J and Sun, B and Wei, X and Song, L and Yan, J}, title = {Decreased taste sensitivity to sucrose in dopamine D3 receptor mutant mice.}, journal = {Chemical senses}, volume = {47}, number = {}, pages = {}, doi = {10.1093/chemse/bjac014}, pmid = {35762652}, issn = {1464-3553}, mesh = {Animals ; *Dysgeusia/genetics ; Mice ; RNA, Messenger/genetics ; *Receptors, Dopamine D3/genetics ; Sucrose/pharmacology ; *Taste/physiology ; *Taste Buds/metabolism ; }, abstract = {Dopamine plays a key role in food rewards and sweet-taste stimulation. We examined the basis for behavioral responses to sweet taste in dopamine D3 receptor-deficient (D3-/-) mice by determining whether the absence of D3 receptors affects the sensitivity to dilute sucrose solutions. In experiment 1, we measured the intensity generalization threshold of conditioned taste aversion (CTA) to a 0.2 M sucrose solution. Results showed that the generalization thresholds were 0.025-0.05 M in D3-/- mice and 0.0025-0.005 M in wild-type (WT) mice. In experiment 2, we found that D3-/- and WT mice had similar capabilities to form and extinguish CTAs. Since the intensity generalization threshold is mainly due to a combination of sweet-taste sensitivity and the robust nature of CTA formation, the results showed that taste sensitivity to sucrose in D3-/- mice was lower than that in WT mice. In experiment 3, to test whether the peripheral sensory signaling may also be affected by the disruption of the dopamine D3 receptors, the mRNA expression levels of sweet-taste-related proteins in taste buds of D3-/- mice were determined. The T1R1 and BDNF mRNA expression levels in D3-/- mice were higher than the controls, whereas T1R2, T1R3, α-gustducin, and TRPM5 mRNA were similar. These findings suggest that disruption of dopamine D3 receptor-mediated signaling decreases the sweet-taste sensitivity and alters the mRNA expression levels of some taste-related molecules.}, } @article {pmid35697908, year = {2022}, author = {Lyu, H and Mizunami, M}, title = {Conditioned taste aversion in the cricket Gryllus bimaculatus.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9751}, pmid = {35697908}, issn = {2045-2322}, mesh = {Animals ; Avoidance Learning ; *Conditioning, Classical ; Lithium Chloride/pharmacology ; Mammals ; Sucrose/pharmacology ; *Taste ; }, abstract = {Conditioned taste aversion (CTA) is a form of classical conditioning in which animals associate the taste of a food with illness caused by toxin contained in the food. CTA in mammals is achieved with a long interval of up to several hours between food ingestion and illness induced by LiCl injection. Insects also exhibit CTA, but not much is known about its features. We investigated whether the cricket Gryllus bimaculatus exhibits CTA when ingestion of a sugar solution is followed by LiCl injection. Crickets that ingested sucrose solution 5-10 min before LiCl injection exhibited reduction of sucrose consumption tested 24 or 48 h after injection compared to that tested 24 h before injection. In contrast, crickets that ingested sucrose solution 5-10 min after LiCl injection or 1 h or 8 h before or after injection did not exhibit reduction of sucrose consumption, indicating that reduction of sucrose consumption by CTA training is pairing-specific. We conclude that CTA in crickets is similar to that in mammals in that one-trial pairing is sufficient to achieve memory retention for days, but it differs in that it is achieved with a relatively short interval (< 1 h) between food ingestion and toxin injection.}, } @article {pmid35679998, year = {2022}, author = {Reyes-García, SE and Gutiérrez-Vera, B and Escobar, ML}, title = {Calcineurin requirement for in vivo insular cortex LTD and CTA-extinction.}, journal = {Neurobiology of learning and memory}, volume = {193}, number = {}, pages = {107647}, doi = {10.1016/j.nlm.2022.107647}, pmid = {35679998}, issn = {1095-9564}, mesh = {Animals ; *Avoidance Learning/physiology ; *Calcineurin/metabolism ; Cerebral Cortex/physiology ; Insular Cortex ; Male ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {Currently, it is widely accepted that memory extinction involves the formation of a new associative memory rather than unlearning of the information previously acquired. Nonetheless, the cellular and molecular mechanisms underlying this process are still unclear. In this regard, it has been suggested that while kinases modulate conditioning and LTP, phosphatases are relevant for extinction and LTD. In particular, the protein phosphatase calcineurin (CaN) has been involved in the extinction of some behavioral tasks along with LTD. Indeed, studies of our research group have demonstrated that induction of LTD in the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) pathway facilitates the extinction of conditioned taste aversion (CTA), while the induction of LTP in this pathway slows it down. In addition, we have shown that the extinction of CTA elicits an increase of CaN. The aim of the present study was to evaluate the participation of calcineurin in the extinction of CTA and in the expression of in vivo LTD in the Bla-IC pathway. For this purpose, we chemically inhibited calcineurin in the IC of adult male Wistar rats, either during CTA-extinction or thirty minutes after LTD induction in the Bla-IC pathway. Our results show that calcineurin inhibition slows down the CTA-extinction and blocks the maintenance of LTD. Furthermore, we show that CaN levels increase after LTD induction. These findings support the idea that calcineurin is a key molecular actor for both CTA extinction and LTD expression in the IC, a highly relevant neocortical area for the processing of aversively motivated learning tasks, suggesting that both processes are associated at a molecular level.}, } @article {pmid35644274, year = {2022}, author = {Gutiérrez-Vera, B and Rivera-Olvera, A and Escobar, ML}, title = {Environmental enrichment attenuates conditioned taste aversion through the restoration of BDNF levels in the insular cortex.}, journal = {Behavioural brain research}, volume = {430}, number = {}, pages = {113947}, doi = {10.1016/j.bbr.2022.113947}, pmid = {35644274}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning ; Brain-Derived Neurotrophic Factor/*metabolism ; Cerebral Cortex/physiology ; Insular Cortex ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {It has been shown that exposure to an enriched environment (EE) can modulate the physiological impact of aversive stimuli in animals, promoting adaptive attitudes, as well as the development of resilience to stressful situations. These changes are known to be related to increased levels of some trophic factors, such as brain-derived neurotrophic factor (BDNF), which has been considered a regulatory protein for synaptic plasticity in the adult brain. Our previous studies have demonstrated that in the insular cortex (IC), a brain region of the temporal lobe implicated in the acquisition, consolidation, and retention of conditioned taste aversion (CTA) task, BDNF can reverse the CTA memory deficit caused by a protein synthesis inhibitor. Likewise, our research group have also shown that BDNF is required for the maintenance of CTA long-term memory. Here we evaluate the effects of the exposure to an enriched environment on the CTA memory strength, using a weak and strong version of this paradigm. The exposure to an EE for 21 days was able to attenuate the strong-CTA response through the restoration of BDNF levels in the IC of adult rats. These results provide evidence that environmental enrichment is capable of reducing the strength of an aversive memory trace, restoring the BDNF levels in a neocortical region of the adult brain.}, } @article {pmid35641228, year = {2022}, author = {Jung, AH and King, CT and Blonde, GD and King, M and Griggs, C and Hashimoto, K and Spector, AC and Schier, LA}, title = {A Subregion of Insular Cortex Is Required for Rapid Taste-Visceral Integration and Consequent Conditioned Taste Aversion and Avoidance Expression in Rats.}, journal = {eNeuro}, volume = {9}, number = {4}, pages = {}, pmid = {35641228}, issn = {2373-2822}, support = {R01 DC009821/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning/physiology ; Cerebral Cortex/physiology ; Conditioning, Classical/physiology ; Insular Cortex ; Lithium Chloride/pharmacology ; Rats ; Sucrose ; *Taste/physiology ; }, abstract = {Postingestive signals are important for shaping appetitive and consummatory responses, but the brain mechanisms required to assimilate interoceptive events with those at the frontlines of ingestion (taste-guided) are poorly understood. Here, we investigated whether an insular cortex (IC) region, which receives viscerosensory input, including gustatory, is required to modify taste-elicited consummatory reactions in response to a real-time interoceptive change using a serial taste reactivity (TR) test where the rats' oromotor and somatic reactions to intraoral (IO) infusions of sucrose were periodically assessed over 45 min following lithium chloride (LiCl) administration. Results showed that neurally-intact rats shifted from an ingestive repertoire to an aversive one as LiCl took effect. Overall, this hedonic shift was delayed in rats with bilateral neurotoxic IC lesions. Rats with greater neuronal loss in posterior gustatory IC displayed fewer aversive reactions to sucrose following this initial LiCl injection. We further assessed whether the failure to integrate interoceptive feedback with ongoing taste-guided behavior impaired acquisition and/or expression of conditioned aversion and/or avoidance in these same rats. Although, as a group, LiCl-injected rats with IC lesions subsequently avoided the sugar in a 48-h two-bottle test, their preference for sucrose was significantly greater than that of the LiCl-injected neurally-intact rats. Overall lesion size, as well as proportion of the posterior gustatory and/or anterior visceral IC were each associated with impaired avoidance. These findings reveal new roles for the posterior gustatory and anterior visceral ICs in multisensory integrative function.}, } @article {pmid35558436, year = {2022}, author = {Nakai, J and Chikamoto, N and Fujimoto, K and Totani, Y and Hatakeyama, D and Dyakonova, VE and Ito, E}, title = {Insulin and Memory in Invertebrates.}, journal = {Frontiers in behavioral neuroscience}, volume = {16}, number = {}, pages = {882932}, pmid = {35558436}, issn = {1662-5153}, abstract = {Insulin and insulin-like peptides (ILP) help to maintain glucose homeostasis, whereas insulin-like growth factor (IGF) promotes the growth and differentiation of cells in both vertebrates and invertebrates. It is sometimes difficult to distinguish between ILP and IGF in invertebrates, however, because in some cases ILP has the same function as IGF. In the present review, therefore, we refer to these peptides as ILP/IGF signaling (IIS) in invertebrates, and discuss the role of IIS in memory formation after classical conditioning in invertebrates. In the arthropod Drosophila melanogaster, IIS is involved in aversive olfactory memory, and in the nematode Caenorhabditis elegans, IIS controls appetitive/aversive response to NaCl depending on the duration of starvation. In the mollusk Lymnaea stagnalis, IIS has a critical role in conditioned taste aversion. Insulin in mammals is also known to play an important role in cognitive function, and many studies in humans have focused on insulin as a potential treatment for Alzheimer's disease. Although analyses of tissue and cellular levels have progressed in mammals, the molecular mechanisms, such as transcriptional and translational levels, of IIS function in cognition have been far advanced in studies using invertebrates. We anticipate that the present review will help to pave the way for studying the effects of insulin, ILPs, and IGFs in cognitive function across phyla.}, } @article {pmid35501556, year = {2022}, author = {Bouton, ME and Michaud, NL}, title = {Partial reinforcement effects on acquisition and extinction of a conditioned taste aversion.}, journal = {Learning & behavior}, volume = {50}, number = {3}, pages = {360-371}, pmid = {35501556}, issn = {1543-4508}, support = {R01 DA033123/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; *Extinction, Psychological ; Humans ; Hylobates ; Lithium Chloride/pharmacology ; Rats ; Reinforcement, Psychology ; }, abstract = {Four experiments with rat subjects asked whether a partial reinforcement extinction effect (PREE) occurs in taste aversion learning. The question has received little attention in the literature, and to our knowledge no taste aversion experiment has previously demonstrated a PREE. In each of the present experiments, experimental groups received a taste mixed in drinking water for 20 min; such taste exposures were sometimes paired with a lithium chloride (LiCl) injection and sometimes not. Control groups received only taste-LiCl pairings. There was evidence that each reinforced and non-reinforced trial produced increments and decrements in aversion strength (respectively), and trials mattered more than accumulated time during the conditioned stimulus and during the background (as emphasized in time-accumulation models like those of Gallistel and Gibbon, Psychological Review, 107, 289-344, 2000, and Gibbon and Balsam, Autoshaping and conditioning theory, Academic Press, New York, pp. 219-235, 1981). In addition, a partial reinforcement extinction effect was observed when there was a relatively large number of conditioning trials. The results extend our understanding of extinction in taste aversion learning and provide more evidence that aversion learning might follow rules that are qualitatively similar to those of other forms of learning.}, } @article {pmid35500755, year = {2022}, author = {Haines, KM and Czachowski, CL}, title = {Evaluating habit formation across pairs of female and male selectively bred alcohol-preferring and non-preferring rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {102}, number = {}, pages = {11-22}, doi = {10.1016/j.alcohol.2022.04.003}, pmid = {35500755}, issn = {1873-6823}, support = {P60 AA007611/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/genetics ; *Alcoholism/genetics ; Animals ; Conditioning, Classical ; *Ethanol ; Female ; Habits ; Male ; Rats ; }, abstract = {Some individuals with alcohol use disorder (AUD) continue to drink because they have developed a habit where they do not consider the consequences of their actions. Genetically selected lines of alcohol-preferring and non-preferring rats allow for exploration of how specific endophenotypes, such as tendency to form habits, may be risk factors that interact with a genetic predisposition of AUD. While high alcohol drinking (HAD) and alcohol-preferring (P) rats were selectively bred to consume high amounts of freely available ethanol, they exhibit differences in alcohol-seeking behaviors as well as impulsive behaviors, and may represent different behavioral models of AUD. The goal of the current study was to compare the tendency to develop habitual behaviors across female and male HAD1, HAD2, and P rats and their respective alcohol non-preferring counterparts. Alcohol-naïve rats were trained on a variable interval schedule using a non-ethanol reinforcer and were then tested in two extinction sessions, one prior to a reinforcer devaluation (conditioned taste aversion) procedure and one after. There were no differences in total lever presses between P and alcohol non-preferring (NP) rats, but there were differences between HAD and low-alcohol drinking (LAD) rats. All six strains decreased lever pressing after reinforcer devaluation. However, P and NP females did not increase latency to first lever press after devaluation, suggesting some inclination toward habitual behavior that was not apparent in either the HAD or LAD lines. Selective breeding for alcohol preference does not seem to influence the tendency to form habits, whereas background strain and sex may have an influence on this behavior.}, } @article {pmid35496768, year = {2022}, author = {Riley, AL and Manke, HN and Huang, S}, title = {Impact of the Aversive Effects of Drugs on Their Use and Abuse.}, journal = {Behavioural neurology}, volume = {2022}, number = {}, pages = {8634176}, pmid = {35496768}, issn = {1875-8584}, mesh = {Humans ; *Reward ; *Substance-Related Disorders/psychology ; Taste ; }, abstract = {Drug use and abuse are complex issues in that the basis of each may involve different determinants and consequences, and the transition from one to the other may be equally multifaceted. A recent model of the addiction cycle (as proposed by Koob and his colleagues) illustrates how drug-taking patterns transition from impulsive (acute use) to compulsive (chronic use) as a function of various neuroadaptations leading to the downregulation of DA systems, upregulation of stress systems, and the dysregulation of the prefrontal/orbitofrontal cortex. Although the nature of reinforcement in the initiation and mediation of these effects may differ (positive vs. negative), the role of reinforcement in drug intake (acute and chronic) is well characterized. However, drugs of abuse have other stimulus properties that may be important in their use and abuse. One such property is their aversive effects that limit drug intake instead of initiating and maintaining it. Evidence of such effects comes from both clinical and preclinical populations. In support of this position, the present review describes the aversive effects of drugs (assessed primarily in conditioned taste aversion learning), the fact that they occur concurrently with reward as assessed in combined taste aversion/place preference designs, the role of aversive effects in drug-taking (in balance with their rewarding effects), the dissociation of these affective properties in that they can be affected in different ways by the same manipulations, and the impact of various parametric, experiential, and subject factors on the aversive effects of drugs and the consequent impact of these factors on their use and abuse potential.}, } @article {pmid35456614, year = {2022}, author = {Lopalco, A and Manni, A and Keeley, A and Haider, S and Li, W and Lopedota, A and Altomare, CD and Denora, N and Tuleu, C}, title = {In Vivo Investigation of (2-Hydroxypropyl)-β-cyclodextrin-Based Formulation of Spironolactone in Aqueous Solution for Paediatric Use.}, journal = {Pharmaceutics}, volume = {14}, number = {4}, pages = {}, pmid = {35456614}, issn = {1999-4923}, abstract = {Spironolactone (SPL), a potent anti-aldosterone steroidal drug used to treat several diseases in paediatric patients (e.g., hypertension, primary aldosteronism, Bartter's syndrome, and congestive heart failure), is not available in child-friendly dosage forms, and spironolactone liquids have been reported to be unpalatable. Aiming to enhance SPL solubility in aqueous solution and overcome palatability, herein, the effects of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) were thoroughly investigated on solubilisation in water and on masking the unpleasant taste of SPL in vivo. Although the complexation of SPL with HP-β-CyD was demonstrated through phase solubility studies, Job's plot, NMR and computational docking studies, our in vivo tests did not show significant effects on taste aversion. Our findings, on the one hand, suggest that the formation of an inclusion complex of SPL with HP-β-CyD itself is not necessarily a good indicator for an acceptable degree of palatability, whereas, on the other hand, they constitute the basis for investigating other cyclodextrin-based formulations of the poorly water-soluble steroidal drug, including solid dosage forms, such as spray-dried powders and orodispersible tablets.}, } @article {pmid35409269, year = {2022}, author = {Berríos-Cárcamo, P and Quezada, M and Santapau, D and Morales, P and Olivares, B and Ponce, C and Ávila, A and De Gregorio, C and Ezquer, M and Quintanilla, ME and Herrera-Marschitz, M and Israel, Y and Ezquer, F}, title = {A Novel Morphine Drinking Model of Opioid Dependence in Rats.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409269}, issn = {1422-0067}, mesh = {Animals ; Disease Models, Animal ; Morphine/pharmacology ; *Morphine Dependence ; *Opioid-Related Disorders/drug therapy ; Quinine/pharmacology/therapeutic use ; Rats ; Taste ; Water ; }, abstract = {An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants' presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.}, } @article {pmid35360496, year = {2022}, author = {Gil-Lievana, E and Ramírez-Mejía, G and Urrego-Morales, O and Luis-Islas, J and Gutierrez, R and Bermúdez-Rattoni, F}, title = {Photostimulation of Ventral Tegmental Area-Insular Cortex Dopaminergic Inputs Enhances the Salience to Consolidate Aversive Taste Recognition Memory via D1-Like Receptors.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {823220}, pmid = {35360496}, issn = {1662-5102}, abstract = {Taste memory involves storing information through plasticity changes in the neural network of taste, including the insular cortex (IC) and ventral tegmental area (VTA), a critical provider of dopamine. Although a VTA-IC dopaminergic pathway has been demonstrated, its role to consolidate taste recognition memory remains poorly understood. We found that photostimulation of dopaminergic neurons in the VTA or VTA-IC dopaminergic terminals of TH-Cre mice improves the salience to consolidate a subthreshold novel taste stimulus regardless of its hedonic value, without altering their taste palatability. Importantly, the inhibition of the D1-like receptor into the IC impairs the salience to facilitate consolidation of an aversive taste recognition memory. Finally, our results showed that VTA photostimulation improves the salience to consolidate a conditioned taste aversion memory through the D1-like receptor into the IC. It is concluded that the dopamine activity from the VTA into IC is required to increase the salience enabling the consolidation of a taste recognition memory. Notably, the D1-like receptor activity into the IC is required to consolidate both innate and learned aversive taste memories but not appetitive taste memory.}, } @article {pmid35318075, year = {2022}, author = {Salguero, A and Marengo, L and Portillo-Salido, E and Ruiz-Leyva, L and Cendán, CM and Morón, I and Marcos Pautassi, R}, title = {Administration of the sigma-1 receptor agonist PRE-084 at emerging adulthood, but not at early adolescence, attenuated ethanol-induced conditioned taste aversion in female rats.}, journal = {Neuroscience letters}, volume = {778}, number = {}, pages = {136585}, doi = {10.1016/j.neulet.2022.136585}, pmid = {35318075}, issn = {1872-7972}, mesh = {Alcohol Drinking ; Animals ; Avoidance Learning ; *Ethanol/pharmacology ; Female ; Morpholines ; Rats ; Rats, Wistar ; Receptors, sigma ; *Taste ; }, abstract = {Ethanol-induced conditioned taste aversion (CTA) is greater in late adolescence or young adulthood than in early adolescence. The role of the sigma receptor system in this age-related difference has not been extensively explored, particularly in female rats. This study assessed the effects of the activation of sigma-1 receptors (S1-R), via the selective S1-R agonist PRE-084, on ethanol-induced CTA at early or at terminal adolescence/emerging adulthood (28 or 56 days-old at the beginning of the procedures, respectively) in female Wistar rats. The modulation of binge-like ethanol intake by PRE-084 was assessed at terminal adolescence. S1-R activation at the acquisition of ethanol-induced CTA attenuated such learning at terminal but not at early adolescence. PRE-084 did not significantly affect ethanol binge drinking in the terminal adolescents. These results highlight the role of S1-R in ethanol-induced CTA and suggest that differential functionality of this transmitter system may underlie age-specific sensitivities to the aversive effects of ethanol.}, } @article {pmid35295904, year = {2022}, author = {Ramos, R and Wu, CH and Turrigiano, GG}, title = {Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {854315}, pmid = {35295904}, issn = {1662-5102}, abstract = {Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least 2 weeks. Using brain slice electrophysiology and activity-dependent labeling of the conditioning-active neuronal ensemble within the gustatory cortex, we find that strong CTA conditioning induces a long-lasting increase in synaptic strengths that occurs uniformly across superficial and deep layers of GC. Repeated exposure to salt, the generalized tastant, causes a rapid attenuation of the generalized aversion that correlates with a reversal of the CTA-induced increases in synaptic strength. Unlike the uniform strengthening that happens across layers, reversal of the generalized aversion results in a more pronounced depression of synaptic strengths in superficial layers. Finally, the generalized aversion and its reversal do not impact the acquisition and maintenance of the aversion to the conditioned tastant (saccharin). The strong correlation between the generalized aversion and synaptic strengthening, and the reversal of both in superficial layers by repeated salt exposure, strongly suggests that the synaptic changes in superficial layers contribute to the formation and reversal of the generalized aversion. In contrast, the persistence of synaptic strengthening in deep layers correlates with the persistence of CTA. Taken together, our data suggest that layer-specific synaptic plasticity mechanisms separately govern the persistence and generalization of CTA memory.}, } @article {pmid35256559, year = {2022}, author = {Pham, H and Seeley, SL and D'Souza, MS}, title = {Pharmacological activation of kappa opioid receptors in the nucleus accumbens core and ventral tegmental area increases the aversive effects of nicotine.}, journal = {Behavioural pharmacology}, volume = {33}, number = {4}, pages = {266-281}, doi = {10.1097/FBP.0000000000000675}, pmid = {35256559}, issn = {1473-5849}, mesh = {3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology ; Animals ; Nicotine/pharmacology ; Nucleus Accumbens/metabolism ; Rats ; Rats, Wistar ; Receptors, Opioid, kappa/metabolism ; *Tobacco Use Disorder ; *Ventral Tegmental Area ; }, abstract = {Aversive effects of nicotine play an important role in the development of nicotine dependence. However, neural substrates and/or brain regions that play a role in the aversive effects of nicotine have not been fully identified. Previous work done in our laboratory showed that systemic administration of kappa opioid receptors (KORs) agonist ±U50488 increased the aversive effects of nicotine. In this study, we assessed the effects of KOR activation in specific brain regions, namely, the nucleus accumbens (NAcc) core and ventral tegmental area (VTA) on the aversive effects of nicotine using the conditioned taste aversion model. Separate groups of Wistar rats were implanted with cannulae above either the NAcc core or the VTA. KOR agonist (±U50488) was bilaterally infused in the NAcc core (0, 0.3, and 3 ug/0.5 ul/side) or VTA (0, 0.3, 1.5, and 3 ug/0.5 ul/side) prior to receiving nicotine (0.4 mg/kg, base; s.c.) during conditioning. Bilateral infusion of the KOR agonist (3 ug/0.5 ul/side) in the NAcc core or the VTA increased the aversive effects of nicotine compared with respective saline controls. Together, these results suggest that pharmacological activation of the KORs in the NAcc core and VTA dose dependently modulate the aversive effects of nicotine. Because aversive effects of nicotine determine susceptibility to development of nicotine dependence, we can conclude that KOR activity in the NAcc and VTA after administration of nicotine may determine susceptibility to the development of nicotine dependence.}, } @article {pmid35255434, year = {2022}, author = {Han, F and Xu, F and Zhu, Q and Sun, P and Zhou, Y and Yu, M}, title = {Virus-mediated GHS-R1a expression in the basolateral amygdala blocks extinction of conditioned taste aversion memory in rats.}, journal = {Biochemical and biophysical research communications}, volume = {602}, number = {}, pages = {57-62}, doi = {10.1016/j.bbrc.2022.02.105}, pmid = {35255434}, issn = {1090-2104}, mesh = {Animals ; *Avoidance Learning ; *Basolateral Nuclear Complex/metabolism ; Feeding Behavior ; Ghrelin/pharmacology ; Rats ; *Receptors, Ghrelin/metabolism ; Taste/physiology ; }, abstract = {Ghrelin is an orexigenic gastric hormone that promotes feeding behaviors and regulating energy homeostasis in both humans and rodents. Our previous studies have shown that ghrelin, when locally infused into the basolateral amygdala (BLA), blocks both acquisition and extinction of conditioned taste aversion (CTA) memory in rats. In this study, we further investigated the effect of virus-mediated overexpression of ghrelin receptor growth hormone secretagogue receptor 1a (GHS-R1a) in BLA pyramidal neurons on CTA memory processes. We found that upregulation of GHS-R1a expression in BLA pyramidal neurons repressed CTA extinction while it had no effect on CTA acquisition. In addition, we reported that local infusion of the endogenous GHS-R1a antagonist, liver-expressed antimicrobial peptide 2 (LEAP2), in the BLA abolished the inhibitory effect of increased GHS-R1a on CTA memory extinction. Those findings provide new supportive evidence that ghrelin/GHS-R1a signaling in the BLA circuit shapes emotional memory processes.}, } @article {pmid35169271, year = {2022}, author = {Yu, M and Zhu, QQ and Niu, ML and Li, N and Ren, BQ and Yu, TB and Zhou, ZS and Guo, JD and Zhou, Y}, title = {Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways.}, journal = {Acta pharmacologica Sinica}, volume = {43}, number = {9}, pages = {2242-2252}, pmid = {35169271}, issn = {1745-7254}, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning ; *Basolateral Nuclear Complex/physiology ; Feeding Behavior ; Ghrelin/pharmacology/physiology ; Glycogen Synthase Kinase 3/pharmacology ; Humans ; Mice ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction ; TOR Serine-Threonine Kinases ; Type C Phospholipases/metabolism ; }, abstract = {Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting Arc and zif268 mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin's effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin's repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.}, } @article {pmid35156560, year = {2022}, author = {Totani, Y and Nakai, J and Hatakeyama, D and Dyakonova, VE and Lukowiak, K and Ito, E}, title = {CNS serotonin content mediating food deprivation-enhanced learning is regulated by hemolymph tryptophan concentration and autophagic flux in the pond snail.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/1028415X.2022.2033045}, pmid = {35156560}, issn = {1476-8305}, abstract = {Nutritional status affects cognitive function in many types of organisms. In the pond snail Lymnaea stagnalis, 1 day of food deprivation enhances taste aversion learning ability by decreasing the serotonin (5-hydroxytryptamin; 5-HT) content in the central nervous system (CNS). On the other hand, after 5 days of food deprivation, learning ability and the CNS 5-HT concentration return to basal levels. How food deprivation leads to alterations of 5-HT levels in the CNS, however, is unknown. Here, we measured the concentration of the 5-HT precursor tryptophan in the hemolymph and CNS, and demonstrated that the CNS tryptophan concentration was higher in 5-day food-deprived snails than in non-food-deprived or 1-day food-deprived snails, whereas the hemolymph tryptophan concentration was not affected by the duration of food deprivation. This finding suggests the existence of a mediator of the CNS tryptophan concentration independent of food deprivation. To identify the mediator, we investigated autophagic flux in the CNS under different food deprivation conditions. We found that autophagic flux was significantly upregulated by inhibition of the tropomyosin receptor kinase (Trk)-Akt-mechanistic target of rapamycin complex 1 (MTORC1) pathway in the CNS of 5-day food-deprived snails. Moreover, when autophagy was inhibited, the CNS 5-HT content was significantly downregulated in 5-day food-deprived snails. Our results suggest that the hemolymph tryptophan concentration and autophagic flux in the CNS cooperatively regulate learning ability affected by different durations of food deprivation. This mechanism may underlie the selection of behaviors appropriate for animal survival depending on the degree of nutrition.}, } @article {pmid35091058, year = {2022}, author = {Boccia, L and Borner, T and Ghidewon, MY and Kulka, P and Piffaretti, C and Doebley, SA and De Jonghe, BC and Grill, HJ and Lutz, TA and Le Foll, C}, title = {Hypophagia induced by salmon calcitonin, but not by amylin, is partially driven by malaise and is mediated by CGRP neurons.}, journal = {Molecular metabolism}, volume = {58}, number = {}, pages = {101444}, pmid = {35091058}, issn = {2212-8778}, support = {R01 DK021397/DK/NIDDK NIH HHS/United States ; R01 DK112812/DK/NIDDK NIH HHS/United States ; R56 DK021397/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anorexia/chemically induced ; *Appetite Depressants/adverse effects/metabolism ; Calcitonin ; Calcitonin Gene-Related Peptide/metabolism ; *Islet Amyloid Polypeptide/metabolism ; Mice ; Nausea/metabolism ; Neurons/metabolism ; Rats ; Vomiting ; }, abstract = {OBJECTIVE: The behavioral mechanisms and the neuronal pathways mediated by amylin and its long-acting analog sCT (salmon calcitonin) are not fully understood and it is unclear to what extent sCT and amylin engage overlapping or distinct neuronal subpopulations to reduce food intake. We here hypothesize that amylin and sCT recruit different neuronal population to mediate their anorectic effects.

METHODS: Viral approaches were used to inhibit calcitonin gene-related peptide (CGRP) lateral parabrachial nucleus (LPBN) neurons and assess their role in amylin's and sCT's ability to decrease food intake in mice. In addition, to test the involvement of LPBN CGRP neuropeptidergic signaling in the mediation of amylin and sCT's effects, a LPBN site-specific knockdown was performed in rats. To deeper investigate whether the greater anorectic effect of sCT compared to amylin is due do the recruitment of additional neuronal pathways related to malaise multiple and distinct animal models tested whether amylin and sCT induce conditioned avoidance, nausea, emesis, and conditioned affective taste aversion.

RESULTS: Our results indicate that permanent or transient inhibition of CGRP neurons in LPBN blunts sCT-, but not amylin-induced anorexia and neuronal activation. Importantly, sCT but not amylin induces behaviors indicative of malaise including conditioned affective aversion, nausea, emesis, and conditioned avoidance; the latter mediated by CGRP[LPBN] neurons.

CONCLUSIONS: Together, the present study highlights that although amylin and sCT comparably decrease food intake, sCT is distinctive from amylin in the activation of anorectic neuronal pathways associated with malaise.}, } @article {pmid35049318, year = {2022}, author = {Flores, VL and Tanner, B and Katz, DB and Lin, JY}, title = {Cortical taste processing evolves through benign taste exposures.}, journal = {Behavioral neuroscience}, volume = {136}, number = {2}, pages = {182-194}, pmid = {35049318}, issn = {1939-0084}, support = {R21 DC016706/DC/NIDCD NIH HHS/United States ; F31 DC015931/DC/NIDCD NIH HHS/United States ; R01 DC006666/DC/NIDCD NIH HHS/United States ; R01 DC007703/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Learning/physiology ; Neurons/physiology ; Rats ; Rats, Long-Evans ; *Taste/physiology ; *Taste Perception/physiology ; }, abstract = {Experience impacts learning and perception. Familiarity with stimuli that later become the conditioned stimulus (CS) in a learning paradigm, for instance, reduces the strength of that learning-a fact well documented in studies of conditioned taste aversion (CTA; De la Casa & Lubow, 1995; Lubow, 1973; Lubow & Moore, 1959). Recently, we have demonstrated that even experience with "incidental" (i.e., non-CS) stimuli influences CTA learning: Long Evans rats pre-exposed to salty and/or sour tastes later learn unusually strong aversions to novel sucrose (Flores et al., 2016), and exhibit enhanced sucrose-responsiveness after learning in gustatory cortex (GC; Flores et al., 2018). These findings suggest that incidental taste exposure (TE) may change spiking responses that have been shown to underlie the processing of tastes in GC. Here, we test this hypothesis, evaluating whether GC neuron spiking responses change across 3 days of taste exposure. Our results demonstrate that the discriminability of GC ensemble taste responses increases with this familiarization. Analysis of single-neuron responses recorded across multiple sessions reveals that taste exposure not only enriches identity and palatability information in taste-evoked activity but also enhances the discriminability of even novel tastes. These findings demonstrate that "mere" familiarization with incidental episodes of tasting changes the neural spiking responses of taste processing and provides specific insight into how such TE may impact later learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35011797, year = {2021}, author = {Head, MA and McColl, LK and Klockars, A and Levine, AS and Olszewski, PK}, title = {Acute Hypophagia and Changes in c-Fos Immunoreactivity in Adolescent Rats Treated with Low Doses of Oxytocin and Naltrexone.}, journal = {Journal of clinical medicine}, volume = {11}, number = {1}, pages = {}, pmid = {35011797}, issn = {2077-0383}, abstract = {A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.}, } @article {pmid34916257, year = {2022}, author = {Arieli, E and Younis, N and Moran, A}, title = {Distinct Progressions of Neuronal Activity Changes Underlie the Formation and Consolidation of a Gustatory Associative Memory.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {42}, number = {5}, pages = {909-921}, pmid = {34916257}, issn = {1529-2401}, mesh = {Animals ; Association Learning ; Female ; Male ; *Memory Consolidation ; Neurons/*physiology ; Rats ; Rats, Long-Evans ; Sensorimotor Cortex/cytology/*physiology ; *Taste Perception ; }, abstract = {Acquiring new memories is a multistage process. Numerous studies have convincingly demonstrated that initially acquired memories are labile and are stabilized only by later consolidation processes. These multiple phases of memory formation are known to involve modification of both cellular excitability and synaptic connectivity, which in turn change neuronal activity at both the single neuron and ensemble levels. However, the specific mapping between the known phases of memory and the changes in neuronal activity at different organizational levels-the single-neuron, population representations, and ensemble-state dynamics-remains unknown. Here we address this issue in the context of conditioned taste aversion learning by continuously tracking gustatory cortex neuronal taste responses in alert male and female rats during the 24 h following a taste-malaise pairing. We found that the progression of activity changes depends on the neuronal organizational level: whereas the population response changed continuously, the population mean response amplitude and the number of taste-responsive neurons only increased during the acquisition and consolidation phases. In addition, the known quickening of the ensemble-state dynamics associated with the faster rejection of harmful foods appeared only after consolidation. Overall, these results demonstrate how complex dynamics in the different representational levels of cortical activity underlie the formation and stabilization of memory within the cortex.SIGNIFICANCE STATEMENT Memory formation is a multiphased process; early acquired memories are labile and consolidate to their stable forms over hours and days. The progression of memory is assumed to be supported by changes in neuronal activity, but the mapping between memory phases and neuronal activity changes remains elusive. Here we tracked cortical neuronal activity over 24 h as rats acquired and consolidated a taste-malaise association memory, and found specific differences between the progression at the single-neuron and populations levels. These results demonstrate how balanced changes on the single-neuron level lead to changes in the network-level representation and dynamics required for the stabilization of memories.}, } @article {pmid34907488, year = {2021}, author = {Boniatti, J and Tappin, MRR and da S Teixeira, RG and de A V Gandos, T and Rios, LPS and Ferreira, IAM and Oliveira, KC and Calil-Elias, S and Santana, AKM and da Fonseca, LB and Shimizu, FM and Carr, O and Oliveira, ON and Dantas, FML and Amendoeira, FC and Viçosa, AL}, title = {In Vivo and In Vitro Taste Assessment of Artesunate-Mefloquine, Praziquantel, and Benznidazole Drugs for Neglected Tropical Diseases and Pediatric Patients.}, journal = {AAPS PharmSciTech}, volume = {23}, number = {1}, pages = {22}, pmid = {34907488}, issn = {1530-9932}, mesh = {Animals ; Artesunate ; Child ; Humans ; *Mefloquine ; Nitroimidazoles ; *Praziquantel ; Rats ; Tablets ; Taste ; }, abstract = {The assessment of drug taste is crucial for pediatric treatments so that formulations can be developed to enhance their effectiveness. In this study, in vivo and in vitro methods were applied to evaluate the taste of tablets of three drugs administered to children without taste-masking excipients to treat tropical diseases, namely artesunate-mefloquine (ASMQ), praziquantel (PZQ), and benznidazole (BNZ). In the first method, a model of rat palatability was adapted with recirculation to ensure sample dispersion, and the data were analyzed using ANOVA (single factor, 95%). The taste assessment results (in vivo) indicated an aversion to the three medicines, denoted by the animals retracting themselves to the bottom of the box after the first contact with the drugs. For the placebo samples, the animals behaved normally, indicating that taste perception was acceptable. The second method was based on the in vitro analysis of capacitance data from a homemade impedimetric electronic tongue. Consistent with the in vivo taste assessment results, the data points obtained with PZQ, ASMQ, and BNZ were far away from those of their placebos in a map built with the multidimensional projection technique referred to as Interactive Document Mapping (IDMAP). A combined analysis of the results with the two methods allowed us to confirm the bitterness of the three drugs, also pointing to electronic tongues as a promising tool to replace in vivo palatability tests.}, } @article {pmid34898621, year = {2021}, author = {Bernanke, A and Burnette, E and Murphy, J and Hernandez, N and Zimmerman, S and Walker, QD and Wander, R and Sette, S and Reavis, Z and Francis, R and Armstrong, C and Risher, ML and Kuhn, C}, title = {Behavior and Fos activation reveal that male and female rats differentially assess affective valence during CTA learning and expression.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260577}, pmid = {34898621}, issn = {1932-6203}, mesh = {Acoustic Stimulation ; Amygdala/drug effects/metabolism ; Animals ; *Conditioning, Psychological/drug effects/radiation effects ; Female ; Lithium Chloride/pharmacology ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Sex Characteristics ; Ultrasonics ; }, abstract = {Females are more affected by psychiatric illnesses including eating disorders, depression, and post-traumatic stress disorder than males. However, the neural mechanisms mediating these sex differences are poorly understood. Animal models can be useful in exploring such neural mechanisms. Conditioned taste aversion (CTA) is a behavioral task that assesses how animals process the competition between associated reinforcing and aversive stimuli in subsequent task performance, a process critical to healthy behavior in many domains. The purpose of the present study was to identify sex differences in this behavior and associated neural responses. We hypothesized that females would value the rewarding stimulus (Boost®) relative to the aversive stimulus (LiCl) more than males in performing CTA. We evaluated behavior (Boost® intake, LiCl-induced behaviors, ultrasonic vocalizations (USVs), CTA performance) and Fos activation in relevant brain regions after the acute stimuli [acute Boost® (AB), acute LiCl (AL)] and the context-only task control (COT), Boost® only task (BOT) and Boost®-LiCl task (BLT). Acutely, females drank more Boost® than males but showed similar aversive behaviors after LiCl. Females and males performed CTA similarly. Both sexes produced 55 kHz USVs anticipating BOT and inhibited these calls in the BLT. However, more females emitted both 22 kHz and 55 kHz USVs in the BLT than males: the latter correlated with less CTA. Estrous cycle stage also influenced 55 kHz USVs. Fos responses were similar in males and females after AB or AL. Females engaged the gustatory cortex and ventral tegmental area (VTA) more than males during the BOT and males engaged the amygdala more than females in both the BOT and BLT. Network analysis of correlated Fos responses across brain regions identified two unique networks characterizing the BOT and BLT, in both of which the VTA played a central role. In situ hybridization with RNAscope identified a population of D1-receptor expressing cells in the CeA that responded to Boost® and D2 receptor-expressing cells that responded to LiCl. The present study suggests that males and females differentially process the affective valence of a stimulus to produce the same goal-directed behavior.}, } @article {pmid34856204, year = {2022}, author = {Shah, T and Dunning, JL and Contet, C}, title = {At the heart of the interoception network: Influence of the parasubthalamic nucleus on autonomic functions and motivated behaviors.}, journal = {Neuropharmacology}, volume = {204}, number = {}, pages = {108906}, pmid = {34856204}, issn = {1873-7064}, support = {P50 AA006420/AA/NIAAA NIH HHS/United States ; R01 AA026685/AA/NIAAA NIH HHS/United States ; R21 AA027372/AA/NIAAA NIH HHS/United States ; P60 AA006420/AA/NIAAA NIH HHS/United States ; R21 AA027636/AA/NIAAA NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Animals ; Anorexia/physiopathology ; Appetite ; Avoidance Learning ; Behavior/*physiology ; Behavior, Addictive ; Corticotropin-Releasing Hormone/metabolism ; Eating/physiology ; Emotions/physiology ; Humans ; Impulsive Behavior ; Interoception/*physiology ; Motivation/*physiology ; Neurons/metabolism/physiology ; Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism ; Posterior Thalamic Nuclei/metabolism/*physiology ; Substance P/metabolism ; }, abstract = {The parasubthalamic nucleus (PSTN), a small nucleus located on the lateral edge of the posterior hypothalamus, has emerged in recent years as a highly interconnected node within the network of brain regions sensing and regulating autonomic function and homeostatic needs. Furthermore, the strong integration of the PSTN with extended amygdala circuits makes it ideally positioned to serve as an interface between interoception and emotions. While PSTN neurons are mostly glutamatergic, some of them also express neuropeptides that have been associated with stress-related affective and motivational dysfunction, including substance P, corticotropin-releasing factor, and pituitary adenylate-cyclase activating polypeptide. PSTN neurons respond to food ingestion and anorectic signals, as well as to arousing and distressing stimuli. Functional manipulation of defined pathways demonstrated that the PSTN serves as a central hub in multiple physiologically relevant networks and is notably implicated in appetite suppression, conditioned taste aversion, place avoidance, impulsive action, and fear-induced thermoregulation. We also discuss the putative role of the PSTN in interoceptive dysfunction and negative urgency. This review aims to synthesize the burgeoning preclinical literature dedicated to the PSTN and to stimulate interest in further investigating its influence on physiology and behavior.}, } @article {pmid34782401, year = {2021}, author = {Garr, E and Padovan-Hernandez, Y and Janak, PH and Delamater, AR}, title = {Maintained goal-directed control with overtraining on ratio schedules.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {28}, number = {12}, pages = {435-439}, pmid = {34782401}, issn = {1549-5485}, support = {R01 DA035943/DA/NIDA NIH HHS/United States ; SC1 DA034995/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; *Conditioning, Operant ; *Goals ; Motivation ; Rats ; Reinforcement, Psychology ; }, abstract = {It is thought that goal-directed control of actions weakens or becomes masked by habits over time. We tested the opposing hypothesis that goal-directed control becomes stronger over time, and that this growth is modulated by the overall action-outcome contiguity. Despite group differences in action-outcome contiguity early in training, rats trained under random and fixed ratio schedules showed equivalent goal-directed control of lever pressing that appeared to grow over time. We confirmed that goal-directed control was maintained after extended training under another type of ratio schedule-continuous reinforcement-using specific satiety and taste aversion devaluation methods. These results add to the growing literature showing that extensive training does not reliably weaken goal-directed control and that it may strengthen it, or at least maintain it.}, } @article {pmid34768105, year = {2021}, author = {Smith, DW and Islam, M and Furst, KE and Mustaree, S and Crider, YS and Akter, N and Islam, SA and Sultana, S and Mahmud, ZH and Rahman, M and Mitch, WA and Davis, J}, title = {Chlorine taste can increase simulated exposure to both fecal contamination and disinfection byproducts in water supplies.}, journal = {Water research}, volume = {207}, number = {}, pages = {117806}, doi = {10.1016/j.watres.2021.117806}, pmid = {34768105}, issn = {1879-2448}, mesh = {Bangladesh ; Chlorine ; *Disinfectants ; Disinfection ; Escherichia coli ; Halogenation ; Humans ; Taste ; Trihalomethanes/analysis ; *Water Pollutants, Chemical/analysis ; *Water Purification ; Water Supply ; }, abstract = {Expanding drinking water chlorination could substantially reduce the burden of disease in low- and middle-income countries, but the taste of chlorinated water often impedes adoption. We developed a Monte Carlo simulation to estimate the effect of people's choice to accept or reject drinking water based on chlorine taste and their subsequent exposure to E. coli and trihalomethanes, a class of disinfection byproduct (DBP). The simulation used empirical data from Dhaka, Bangladesh, a megacity with endemic waterborne disease. We drew on published taste acceptability thresholds from Dhaka residents, measured residual chlorine and thermotolerant E. coli inactivation following the addition of six chlorine doses (0.25-3.0 mg/L as Cl2) to untreated piped water samples from 100 locations, and analyzed trihalomethane formation in 54 samples. A dose of 0.5 mg/L, 75% lower than the 2 mg/L dose typically recommended for household chlorination of low-turbidity waters, minimized overall exposure to E. coli. Doses of 1-2 mg/L maximized overall exposure to trihalomethanes. Accounting for chlorine taste aversion indicates that microbiological exposure increases and DBP exposure decreases above certain doses as a higher proportion of people reject chlorinated water in favor of untreated water. Taken together with findings from other modeling analyses, empirical studies, and field trials, our results suggest that taste acceptability should be a critical consideration in establishing chlorination dosing guidelines. Particularly when chlorination is first implemented in water supplies with low chlorine demand, lower doses than those generally recommended for household water treatment can help avoid taste-related objections while still meaningfully reducing contaminant exposure.}, } @article {pmid34744692, year = {2021}, author = {Shyu, BC and Gao, ZY and Wu, JJ and He, ABH and Cheng, CN and Huang, ACW}, title = {Methamphetamine and Modulation Functionality of the Prelimbic Cortex for Developing a Possible Treatment of Alzheimer's Disease in an Animal Model.}, journal = {Frontiers in aging neuroscience}, volume = {13}, number = {}, pages = {751913}, pmid = {34744692}, issn = {1663-4365}, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative condition that causes cognitive impairment and other neuropsychiatric symptoms. Previously, little research has thus far investigated whether methamphetamine (MAMPH) can enhance cognitive function or ameliorate AD symptoms. This study examined whether a low dose of MAMPH can induce conditioned taste aversion (CTA) learning, or can increase plasma corticosterone levels, neural activity, and neural plasticity in the medial prefrontal cortex (mPFC) (responsible for cognitive function), the nucleus accumbens (NAc) and the amygdala (related to rewarding and aversive emotion), and the hippocampus (responsible for spatial learning). Furthermore, the excitations or lesions of the prelimbic cortex (PrL) can affect MAMPH-induced CTA learning, plasma corticosterone levels, and neural activity or plasticity in the mPFC [i.e., PrL, infralimbic cortex (IL), cingulate cortex 1 (Cg1)], the NAc, the amygdala [i.e., basolateral amygdala (BLA) and central amygdala (CeA)], and the hippocampus [i.e., CA1, CA2, CA3, and dentate gyrus (DG)]. In the experimental procedure, the rats were administered either saline or NMDA solutions, which were injected into the PrL to excite or destroy PrL neurons. Additionally, rats received 0.1% saccharin solution for 15 min, followed by intraperitoneal injections of either normal saline or 1 mg/kg MAMPH to induce CTA. A one-way ANOVA was performed to analyze the effects of saccharin intake on CTA, plasma corticosterone levels, and the expression of c-Fos and p-ERK. The results showed that the MAMPH induced CTA learning and increased plasma corticosterone levels. The mPFC, and particularly the PrL and IL and the DG of the hippocampus, appeared to show increased neural activity in c-Fos expression or neural plasticity in p-ERK expression. The excitation of the PrL neurons upregulated neural activity in c-Fos expression and neural plasticity in p-ERK expression in the PrL and IL. In summary, MAMPH may be able to improve cognitive and executive function in the brain and reduce AD symptoms. Moreover, the excitatory modulation of the PrL with MAMPH administration can facilitate MAMPH-induced neural activity and plasticity in the PrL and IL of the mPFC. The present data provide clinical implications for developing a possible treatment for AD in an animal model.}, } @article {pmid34652631, year = {2021}, author = {Zheng, Y and Chen, ZY and Ma, WJ and Wang, QZ and Liang, H and Ma, AG}, title = {B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets.}, journal = {Current medical science}, volume = {41}, number = {5}, pages = {847-856}, pmid = {34652631}, issn = {2523-899X}, mesh = {Animals ; Cognitive Dysfunction/chemically induced/*drug therapy/enzymology ; Diet, High-Fat/*adverse effects ; Dietary Supplements ; Disease Models, Animal ; Folic Acid/administration & dosage/pharmacology ; Gene Expression Regulation, Enzymologic/drug effects ; Male ; Morris Water Maze Test/drug effects ; Niacin/administration & dosage/pharmacology ; Pyridoxine/administration & dosage/pharmacology ; Rats ; Riboflavin/administration & dosage/pharmacology ; Thiamine/administration & dosage/pharmacology ; Transketolase/*metabolism ; Vitamin B 12/administration & dosage/pharmacology ; Vitamin B Complex/*administration & dosage/pharmacology ; }, abstract = {OBJECTIVE: To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase (TK) expression and activity.

METHODS: To test this, we separated 50 rats into five groups that were either fed a standard chow diet (controls) or a high-fat diet (experimental groups H0, H1, H2, and H3). H0 group animals received no additional dietary supplementation, while H1 group animals were administered 100 mg/kg body weight (BW) thiamine, 100 mg/kg BW riboflavin, and 250 mg/kg BW niacin each day, and group H2 animals received daily doses of 100 mg/kg BW pyridoxine, 100 mg/kg BW cobalamin, and 5 mg/kg BW folate. Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day.

RESULTS: Over time, group H0 exhibited greater increases in BW and fat mass relative to other groups. When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion (CTA) and Morris Water Maze (MWM), we found B vitamin treatment was associated with significant improvements relative to untreated H0 controls. Similarly, B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in H0 (P<0.05).

CONCLUSION: Together, these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity. As such, B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.}, } @article {pmid34589798, year = {2021}, author = {Strekalova, T and Svirin, E and Veniaminova, E and Kopeikina, E and Veremeyko, T and Yung, AWY and Proshin, A and Walitza, S and Anthony, DC and Lim, LW and Lesch, KP and Ponomarev, ED}, title = {ASD-like behaviors, a dysregulated inflammatory response and decreased expression of PLP1 characterize mice deficient for sialyltransferase ST3GAL5.}, journal = {Brain, behavior, & immunity - health}, volume = {16}, number = {}, pages = {100306}, pmid = {34589798}, issn = {2666-3546}, abstract = {Gangliosides are glycosphingolipids, which are abundant in brain, are known to modulate ion channels and cell-to-cell communication. Deficiencies can result in aberrant myelination and altered immune responses, which can give rise to neurodevelopmental psychiatric disorders. However, to date, little mechanistic data is available on how ganglioside deficiencies contribute to the behavioural disorders. In humans, the loss of lactosylceramide-alpha-2,3-sialyltransferase (ST3Gal5) leads to a severe neuropathology, but in ST3Gal5 knock-out (St3gal5-/-) mice the absence of GM3 and associated a-, b- and c-series gangliosides is partially compensated by 0-series gangliosides and there is no overt behavioural phenotype. Here, we sought to examine the behavioural and molecular consequences of GM3 loss more closely. Mutants of both sexes exhibited impaired conditioned taste aversion in an inhibitory learning task and anxiety-like behaviours in the open field, moderate motor deficits, abnormal social interactions, excessive grooming and rearing behaviours. Taken together, the aberrant behaviours are suggestive of an autism spectrum disorder (ASD)-like syndrome. Molecular analysis showed decreased gene and protein expression of proteolipid protein-1 (Plp1) and over expression of proinflammatory cytokines, which has been associated with ASD-like syndromes. The inflammatory and behavioural responses to lipopolysaccharide (LPS) were also altered in the St3gal5-/- mice compared to wild-type, which is indicative of the importance of GM3 gangliosides in regulating immune responses. Together, the St3gal5-/- mice display ASD-like behavioural features, altered response to systemic inflammation, signs of hypomyelination and neuroinflammation, which suggests that deficiency in a- and b-series gangliosides could contribute to the development of an ASD-like pathology in humans.}, } @article {pmid34553981, year = {2021}, author = {Angulo, R and Arévalo-Romero, CA}, title = {Sexual dimorphism in classical conditioning? Sex differences in neophobia, latent inhibition, generalization, and extinction for rats (Rattus norvegicus) in a conditioned taste aversion preparation irrespective of housing conditions.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {135}, number = {3}, pages = {315-326}, doi = {10.1037/com0000275}, pmid = {34553981}, issn = {1939-2087}, mesh = {Animals ; Avoidance Learning ; *Conditioning, Classical ; Female ; Housing ; Male ; Rats ; *Sex Characteristics ; Taste ; }, abstract = {This study aimed to assess possible sex differences and a potential impact of social housing conditions for some Pavlovian conditioning effects in a conditioned taste aversion preparation with rats. The results of Experiment 1 suggest sex differences in neophobia, latent inhibition, and generalization. Specifically, for females, neophobia, and generalization appeared to be stronger while latent inhibition seemed to be attenuated. Experiment 2 confirmed these sex differences in neophobia and generalization, while also revealing slower extinction in males. Experiment 3 provided evidence for the same sex differences in neophobia and generalization, even when a perceptual learning effect was in operation following pre-exposures to the test stimulus. No effects of social housing conditions were found in either Experiment 1 or Experiment 2. In general, these findings appear to support the hypothesis of sexual dimorphism in Pavlovian conditioning, encouraging a systematic approach to the topic by means of further research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34547331, year = {2021}, author = {Dornellas, APS and Burnham, NW and Luhn, KL and Petruzzi, MV and Thiele, TE and Navarro, M}, title = {Activation of locus coeruleus to rostromedial tegmental nucleus (RMTg) noradrenergic pathway blunts binge-like ethanol drinking and induces aversive responses in mice.}, journal = {Neuropharmacology}, volume = {199}, number = {}, pages = {108797}, pmid = {34547331}, issn = {1873-7064}, support = {R01 AA022048/AA/NIAAA NIH HHS/United States ; R01 AA025809/AA/NIAAA NIH HHS/United States ; R37 AA013573/AA/NIAAA NIH HHS/United States ; T32 DA007244/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/*physiology ; Binge Drinking/*physiopathology/*therapy ; Disease Models, Animal ; Female ; Locus Coeruleus/*physiology ; Male ; Mice ; Mice, Transgenic ; Norepinephrine/*physiology ; Signal Transduction/physiology ; Ventral Tegmental Area/*physiology ; Vocalization, Animal/drug effects/physiology ; }, abstract = {There is strong evidence that ethanol entails aversive effects that can act as a deterrent to overconsumption. We have found that in doses that support the development of a conditioned taste aversion ethanol increases the activity of tyrosine hydroxylase (TH) positive neurons in the locus coeruleus (LC), a primary source of norepinephrine (NE). Using cre-inducible AAV8-ChR2 viruses in TH-ires-cre mice we found that the LC provides NE projections that innervate the rostromedial tegmental nucleus (RMTg), a brain region that has been implicated in the aversive properties of drugs. Because the neurocircuitry underlying the aversive effects of ethanol is poorly understood, we characterized the role of the LC to RMTg circuit in modulating aversive unconditioned responses and binge-like ethanol intake. Here, both male and female TH-ires-cre mice were cannulated in the RMTg and injected in the LC with rAVV viruses that encode for a Gq-expressing designer receptor exclusively activated by designer drugs (DREADDs) virus, or its control virus, to directly control the activity of NE neurons. A Latin Square paradigm was used to analyze both 20% ethanol and 3% sucrose consumption using the "drinking-in-the-dark" (DID) paradigm. Chemogenetic activation of the LC to RMTg pathway significantly blunted the binge-ethanol drinking, with no effect on the sucrose consumption, increased the emission of mid-frequency vocalizations and induced malaise-like behaviors in mice. The present findings indicate an important involvement of the LC to RMTg pathway in reducing ethanol consumption, and characterize unconditioned aversive reactions induced by activation of this noradrenergic pathway.}, } @article {pmid34545750, year = {2021}, author = {Simões, S and Almeida, AJ and Marto, J}, title = {Palatability of pediatric formulations: do rats predict aversiveness?.}, journal = {Drug development and industrial pharmacy}, volume = {47}, number = {7}, pages = {1121-1126}, doi = {10.1080/03639045.2021.1984519}, pmid = {34545750}, issn = {1520-5762}, mesh = {Animals ; Child ; Drug Compounding ; Flavoring Agents ; Humans ; Quinine ; Rats ; *Sweetening Agents ; *Taste ; }, abstract = {BACKGROUND: The brief-access taste aversion (BATA) model has been used as an alternative taste assessment tool to human taste panels and became an important element of pharmaceutical drug development, especially regarding pediatric patient's compliance. This model has been validated, demonstrating a concentration-dependent sensitivity to drug aversiveness, as well as the capacity to evaluate the taste-masking effects of cyclodextrins. In the BATA model, samples are presented randomly to rodents in numerous sipper tubes and a lickometer is used for the electronic record of licks in a sophisticated approach.

OBJECTIVES: The aim of this study was to test possible drug taste-masking strategies. Additionally, we have used an alternative approach to measure the animal lick number in the presence of different compounds, non-simultaneously.

RESULTS: In the present work we show for the first time the licking profile of different compounds during the time course of the experiment, with each animal being exposed to only one bottle of testing product. To validate the experiments, quinine hydrochloride dihydrate (QHD) was used as a bitter reference compound.

CONCLUSION: The results obtained using this simple approach showed that aversiveness is dependent on the assay duration, and that it is possible to predict the aversiveness just by measuring the mass of the tested substance consumption. Moreover, some taste-masking strategies, such as those used in pediatric formulations and corresponding to the addition of sweeteners or flavors, cannot be predicted from rodents BATA model.}, } @article {pmid34516195, year = {2021}, author = {Bouton, ME and Allan, SM and Tavakkoli, A and Steinfeld, MR and Thrailkill, EA}, title = {Effect of context on the instrumental reinforcer devaluation effect produced by taste-aversion learning.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {47}, number = {4}, pages = {476-489}, pmid = {34516195}, issn = {2329-8464}, support = {K01 DA044456/DA/NIDA NIH HHS/United States ; R01 DA033123/DA/NIDA NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Classical ; Conditioning, Operant ; *Extinction, Psychological ; Learning ; Rats ; *Taste ; }, abstract = {Four experiments manipulated the context in which taste-aversion conditioning occurred when the reinforcer was devalued after instrumental learning. In all experiments, rats learned to lever press in an operant conditioning chamber and then had an aversion to the food-pellet reinforcer conditioned by pairing it with lithium chloride (LiCl) in either that context or a different context. Lever pressing was then tested in extinction to assess its status as a goal-directed action. In Experiment 1, aversion conditioning in the operant conditioning chamber suppressed lever-pressing during the test, but aversion conditioning in the home cage did not. Exposure to the averted pellet in the operant conditioning chamber after conditioning in the home cage did not change this effect (Experiment 2). The same pattern was observed when the different context was a second operant-style chamber (counterbalanced), exposure to the contexts was controlled, and pellets were presented in them in the same manner (Experiment 3). The greater effect of aversion conditioning in the instrumental context was not merely due to potentiated contextual conditioning (Experiment 4). Importantly, consumption tests revealed that the aversion conditioned in the different context had transferred to the test context. Thus, when reinforcer devaluation occurred in a different context, the rats lever pressed in extinction for a reinforcer they would otherwise reject. The results suggest that animals encode contextual information about the reinforcer during instrumental learning and suggest caution in making inferences about action versus habit learning when the reinforcer is devalued in a different context. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34428526, year = {2021}, author = {Nakajima, S}, title = {Food avoidance learning based on entirely voluntary wheel running in laboratory mice (Mus musculus).}, journal = {Behavioural processes}, volume = {192}, number = {}, pages = {104484}, doi = {10.1016/j.beproc.2021.104484}, pmid = {34428526}, issn = {1872-8308}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; Food ; Mice ; *Motor Activity ; Taste ; }, abstract = {Previous studies (Nakajima, 2019a,b) demonstrated food avoidance learning based on wheel running in laboratory mice: Consumption of a target snack becomes suppressed if it is repeatedly paired with an opportunity to run in an activity wheel. This is a kind of Pavlovian conditioning, because the avoidance is specific to the paired snack. For example, in an experiment, mice were initially trained to run in closed wheels. Then, access to one of the two kinds of snacks (cheese or raisins, counterbalanced) was followed by confinement in a large pet cage with an open wheel, while access to the other snack was not. After several repetitions of these two types of trials, differentiation in consumption between the two snacks emerged: The intake of the unpaired snack increased gradually over days, while the increase was attenuated for the running-paired snack. The present study replicated this food avoidance learning without the pretraining of running in a closed wheel, emphasizing the intrinsic capacity of running to establish food avoidance. The results somewhat suggest that pretraining in open wheels facilitates running-based food avoidance, but this effect was too weak in the present study to draw a clear conclusion.}, } @article {pmid34376756, year = {2021}, author = {Zajdel, J and Sköld, J and Jaarola, M and Singh, AK and Engblom, D}, title = {Calcitonin gene related peptide α is dispensable for many danger-related motivational responses.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {16204}, pmid = {34376756}, issn = {2045-2322}, mesh = {Amygdala/metabolism/pathology ; Animals ; Anorexia/*physiopathology ; Avoidant Restrictive Food Intake Disorder ; *Behavior, Animal ; Calcitonin Gene-Related Peptide/*physiology ; Conditioning, Classical/*physiology ; Eating ; Fear/*psychology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motivation ; Neurons/metabolism/*pathology ; Nociception ; Pain/metabolism/*pathology ; Parabrachial Nucleus/metabolism/pathology ; }, abstract = {Calcitonin gene related peptide (CGRP) expressing neurons in the parabrachial nucleus have been shown to encode danger. Through projections to the amygdala and other forebrain structures, they regulate food intake and trigger adaptive behaviors in response to threats like inflammation, intoxication, tumors and pain. Despite the fact that this danger-encoding neuronal population has been defined based on its CGRP expression, it is not clear if CGRP is critical for its function. It is also not clear if CGRP in other neuronal structures is involved in danger-encoding. To examine the role of CGRP in danger-related motivational responses, we used male and female mice lacking αCGRP, which is the main form of CGRP in the brain. These mice had no, or only very weak, CGRP expression. Despite this, they did not behave differently compared to wildtype mice when they were tested for a battery of danger-related responses known to be mediated by CGRP neurons in the parabrachial nucleus. Mice lacking αCGRP and wildtype mice showed similar inflammation-induced anorexia, conditioned taste aversion, aversion to thermal pain and pain-induced escape behavior, although it should be pointed out that the study was not powered to detect any possible differences that were minor or sex-specific. Collectively, our findings suggest that αCGRP is not necessary for many threat-related responses, including some that are known to be mediated by CGRP neurons in the parabrachial nucleus.}, } @article {pmid34361981, year = {2021}, author = {Yu, Y and He, AB and Liou, M and Ou, C and Kozłowska, A and Chen, P and Huang, AC}, title = {The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration.}, journal = {Journal of clinical medicine}, volume = {10}, number = {15}, pages = {}, pmid = {34361981}, issn = {2077-0383}, abstract = {A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine's reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect-reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.}, } @article {pmid34327337, year = {2021}, author = {Dantzer, R}, title = {Love and fear in the times of sickness.}, journal = {Comprehensive psychoneuroendocrinology}, volume = {6}, number = {}, pages = {}, pmid = {34327337}, issn = {2666-4976}, support = {R01 CA193522/CA/NCI NIH HHS/United States ; R01 NS073939/NS/NINDS NIH HHS/United States ; }, abstract = {Sickness induced by gastrointestinal malaise or by microbial pathogens is more than a private experience. Sick individuals share their illness within their social environment by communicating their sickness to others. In turn, recipients of the communication respond with appropriate behavioral adaptations. Avoidance of sick individuals and the events associated with their sickness is advantageous for members of the group. However, these responses can conflict with the need for comfort or social support expressed by sick individuals. There is evidence that the relationship between the sick individual and its social environment involves neurobiological mechanisms that are similar to those that mediate social bonding. Despite their commonality the feelings of love and fear/disgust that are associated with the sociality of sickness have thus far been neglected by mainstream affective neuroscience.}, } @article {pmid34323519, year = {2021}, author = {Wu, CW and Ou, CY and Yu, YH and Yu, YC and Shyu, BC and Huang, ACW}, title = {Involvement of the ventral tegmental area but not periaqueductal gray matter in the paradoxical rewarding and aversive effects of morphine.}, journal = {Behavioral neuroscience}, volume = {135}, number = {6}, pages = {762-770}, doi = {10.1037/bne0000483}, pmid = {34323519}, issn = {1939-0084}, mesh = {Conditioning, Classical ; *Morphine/pharmacology ; Periaqueductal Gray ; Reward ; *Ventral Tegmental Area ; }, abstract = {The paradoxical effects of reward and aversion with abused drugs may interact to produce drug addiction, which is the so-called paradoxical effect hypothesis of abused drugs. However, there is no research examining how the ventral tegmental area (VTA) or periaqueductal gray matter (PAG) regulates morphine's paradoxical effect of reward and aversion. The present study addresses this issue, utilizing a high concentration of N-methyl-D-aspartic acid (NMDA) via injections to destroy the VTA or the PAG. Moreover, the study employed the new "pre- and postassociation" experimental paradigm (2010) to test whether the simultaneous rewarding and aversive effects of morphine can be affected by an NMDA lesion in the VTA or the PAG. The results indicated that the NMDA lesion of the VTA simultaneously reduced morphine-induced conditioned suppression of saccharin solution intake in conditioned taste aversion (CTA) and morphine-induced spent time in the preference compartment in conditioned place preference (CPP), whereas the PAG lesion did not change either measure. Thus, the VTA, but not the PAG, appears to contribute to the paradoxical effect reward in CPP and aversion in CTA induced by morphine. The VTA's involvement in morphine-induced CTA aversion and CPP reward supports the paradoxical effect hypothesis of abused drugs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34153368, year = {2021}, author = {Wang, YC and Chiu, WC and Cheng, CN and Lee, C and Chih Wei Huang, A}, title = {Examination of neuroinflammatory cytokine interleukin-1 beta expression in the medial prefrontal cortex, amygdala, and hippocampus for the paradoxical effects of reward and aversion induced by morphine.}, journal = {Neuroscience letters}, volume = {760}, number = {}, pages = {136076}, doi = {10.1016/j.neulet.2021.136076}, pmid = {34153368}, issn = {1872-7972}, mesh = {Amygdala/metabolism/pathology/physiopathology ; Animals ; Conditioning, Operant ; Disease Models, Animal ; Hippocampus/metabolism/pathology/physiopathology ; Humans ; Interleukin-1beta/*metabolism ; Male ; Morphine/administration & dosage/*adverse effects ; Morphine Dependence/*immunology/pathology/physiopathology ; Neuroinflammatory Diseases/*immunology/pathology/physiopathology ; Prefrontal Cortex/metabolism/pathology/physiopathology ; Rats ; *Reward ; Saccharin/administration & dosage ; Signal Transduction/immunology ; }, abstract = {A growing body of evidence has shown that abused drugs could simultaneously induce the paradoxical effect-reward and aversion. Moreover, the medial prefrontal cortex (mPFC), amygdala, and hippocampus were involved in this paradoxical effect by abused drugs. However, no research examined whether neuroinflammatory changes in the mPFC [including cingulate cortex area 1 (Cg1); prelimbic cortex (PrL); infralimbic cortex (IL)], basolateral amygdala, and hippocampus [e.g., CA1, CA2, CA3, and dentate gyrus (DG)] after morphine-induced reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA). The results showed that after morphine administration, the consumption of a 0.1% saccharin solution decreased; the mean time spent in the morphine-paired side compartment of the CPP box increased, indicating that morphine simultaneously induced the paradoxical effects of reward and aversion. The PrL and IL of the mPFC, the BLA of the amygdala, the CA1, CA2, CA3, and DG of the hippocampus but not the Cg1 presented hyperactive IL-1β expression in response to morphine's aversion and reward. The mPFC, amygdala, and hippocampus may appear neuroinflammation activity following morphine-induced paradoxical effect-reward in CPP and aversion in CTA. The present data may provide a better understanding of the relationship between neuroinflammation and morphine addiction.}, } @article {pmid34052874, year = {2021}, author = {Rivi, V and Batabyal, A and Juego, K and Kakadiya, M and Benatti, C and Blom, JMC and Lukowiak, K}, title = {To eat or not to eat: a Garcia effect in pond snails (Lymnaea stagnalis).}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {207}, number = {4}, pages = {479-495}, pmid = {34052874}, issn = {1432-1351}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical ; Feeding Behavior/*physiology ; HSP40 Heat-Shock Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Heat-Shock Response/physiology ; Lymnaea/*physiology ; Memory, Long-Term/*physiology ; Taste/*physiology ; }, abstract = {Taste aversion learning is universal. In animals, a single presentation of a novel food substance followed hours later by visceral illness causes animals to avoid that taste. This is known as bait-shyness or the Garcia effect. Humans demonstrate this by avoiding a certain food following the development of nausea after ingesting that food ('Sauce Bearnaise effect'). Here, we show that the pond snail Lymnaea stagnalis is capable of the Garcia effect. A single 'pairing' of a novel taste, a carrot slurry followed hours later by a heat shock stressor (HS) is sufficient to suppress feeding response elicited by carrot for at least 24 h. Other food tastes are not suppressed. If snails had previously been exposed to carrot as their food source, the Garcia-like effect does not occur when carrot is 'paired' with the HS. The HS up-regulates two heat shock proteins (HSPs), HSP70 and HSP40. Blocking the up-regulation of the HSPs by a flavonoid, quercetin, before the heat shock, prevented the Garcia effect in the snails. Finally, we found that snails exhibit Garcia effect following a period of food deprivation but the long-term memory (LTM) phenotype can be observed only if the animals are tested in a food satiated state.}, } @article {pmid33995059, year = {2021}, author = {Zhong, W and Darmani, NA}, title = {The HCN Channel Blocker ZD7288 Induces Emesis in the Least Shrew (Cryptotis parva).}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {647021}, pmid = {33995059}, issn = {1663-9812}, abstract = {Subtypes (1-4) of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in the central and peripheral nervous systems, as well as the cells of smooth muscles in many organs. They mainly serve to regulate cellular excitability in these tissues. The HCN channel blocker ZD7288 has been shown to reduce apomorphine-induced conditioned taste aversion on saccharin preference in rats suggesting potential antinausea/antiemetic effects. Currently, in the least shew model of emesis we find that ZD7288 induces vomiting in a dose-dependent manner, with maximal efficacies of 100% at 1 mg/kg (i.p.) and 83.3% at 10 µg (i.c.v.). HCN channel subtype (1-4) expression was assessed using immunohistochemistry in the least shrew brainstem dorsal vagal complex (DVC) containing the emetic nuclei (area postrema (AP), nucleus tractus solitarius and dorsal motor nucleus of the vagus). Highly enriched HCN1 and HCN4 subtypes are present in the AP. A 1 mg/kg (i.p.) dose of ZD7288 strongly evoked c-Fos expression and ERK1/2 phosphorylation in the shrew brainstem DVC, but not in the in the enteric nervous system in the jejunum, suggesting a central contribution to the evoked vomiting. The ZD7288-evoked c-Fos expression exclusively occurred in tryptophan hydroxylase 2-positive serotonin neurons of the dorsal vagal complex, indicating activation of serotonin neurons may contribute to ZD7288-induced vomiting. To reveal its mechanism(s) of emetic action, we evaluated the efficacy of diverse antiemetics against ZD7288-evoked vomiting including the antagonists/inhibitors of: ERK1/2 (U0126), L-type Ca[2+] channel (nifedipine); store-operated Ca[2+] entry (MRS 1845); T-type Ca[2+] channel (Z944), IP3R (2-APB), RyR receptor (dantrolene); the serotoninergic type 3 receptor (palonosetron); neurokinin 1 receptor (netupitant), dopamine type 2 receptor (sulpride), and the transient receptor potential vanilloid 1 receptor agonist, resiniferatoxin. All tested antiemetics except sulpride attenuated ZD7288-evoked vomiting to varying degrees. In sum, ZD7288 has emetic potential mainly via central mechanisms, a process which involves Ca[2+] signaling and several emetic receptors. HCN channel blockers have been reported to have emetic potential in the clinic since they are currently used/investigated as therapeutic candidates for cancer therapy related- or unrelated-heart failure, pain, and cognitive impairment.}, } @article {pmid33932558, year = {2021}, author = {Har-Paz, I and Arieli, E and Moran, A}, title = {ApoE4 attenuates cortical neuronal activity in young behaving apoE4 rats.}, journal = {Neurobiology of disease}, volume = {155}, number = {}, pages = {105373}, doi = {10.1016/j.nbd.2021.105373}, pmid = {33932558}, issn = {1095-953X}, mesh = {Action Potentials/*physiology ; Animals ; Apolipoprotein E4/*genetics ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Female ; Humans ; Neurons/*physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Transgenic ; }, abstract = {The E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD-related neuropathology. Understanding these primary dysfunctions is vital for the early detection of AD and the development of therapeutic strategies. Recently we reported impaired extra-hippocampal memory in young apoE4 mice, a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we tested the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 (hApoE4) and wildtype rats expressing rat apoE (rAE), before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young hApoE4 rats showed impaired CTA learning, consistent with our previous results in target-replacement apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Further taste coding analyses at the single neuron and ensemble levels revealed that GC neurons of the hApoE4 group correctly classified tastes, but were unable to undergo plasticity to support learning. These results suggest that apoE4 impacts brain excitability and plasticity early in life that may act as an initiator for later AD pathologies.}, } @article {pmid33930301, year = {2021}, author = {Yiannakas, A and Kolatt Chandran, S and Kayyal, H and Gould, N and Khamaisy, M and Rosenblum, K}, title = {Parvalbumin interneuron inhibition onto anterior insula neurons projecting to the basolateral amygdala drives aversive taste memory retrieval.}, journal = {Current biology : CB}, volume = {31}, number = {13}, pages = {2770-2784.e6}, doi = {10.1016/j.cub.2021.04.010}, pmid = {33930301}, issn = {1879-0445}, mesh = {Animals ; Avoidance Learning/physiology ; *Basolateral Nuclear Complex ; Interneurons ; Mammals ; Neurons/physiology ; Parvalbumins ; Taste/physiology ; }, abstract = {Memory retrieval refers to the fundamental ability of organisms to make use of acquired, sometimes inconsistent, information about the world. Although memory acquisition has been studied extensively, the neurobiological mechanisms underlying memory retrieval remain largely unknown. Conditioned taste aversion (CTA) is a robust associative paradigm, through which animals can be trained to express aversion toward innately appetitive tastants. The anterior insula (aIC) is indispensable in the ability of mammals to retrieve associative information regarding tastants that have been previously linked with gastric malaise. Here, we show that CTA memory retrieval promotes cell-type-specific activation in the aIC. Using chemogenetic tools in the aIC, we found that CTA memory acquisition requires activation of excitatory neurons and inhibition of inhibitory neurons, whereas retrieval necessitates activation of both excitatory and inhibitory aIC circuits. CTA memory retrieval at the aIC activates parvalbumin (PV) interneurons and increases synaptic inhibition onto activated pyramidal neurons projecting to the basolateral amygdala (aIC-BLA). Unlike innately appetitive taste memory retrieval, CTA retrieval increases synaptic inhibition onto aIC-BLA-projecting neurons that is dependent on activity in aIC PV interneurons. PV aIC interneurons coordinate CTA memory retrieval and are necessary for its dominance when conflicting internal representations are encountered over time. The reinstatement of CTA memories following extinction is also dependent on activation of aIC PV interneurons, which increase the frequency of inhibition onto aIC-BLA-projecting neurons. This newly described interaction of PV and a subset of excitatory neurons can explain the coherency of aversive memory retrieval, an evolutionary pre-requisite for animal survival.}, } @article {pmid33915300, year = {2021}, author = {Urrieta, E and Escobar, ML}, title = {Metaplastic regulation of neocortical long-term depression in vivo is sensitive to distinct phases of conditioned taste aversion.}, journal = {Neurobiology of learning and memory}, volume = {182}, number = {}, pages = {107449}, doi = {10.1016/j.nlm.2021.107449}, pmid = {33915300}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/*physiology ; Extinction, Psychological/physiology ; Insular Cortex/*physiology ; Long-Term Synaptic Depression/*physiology ; Neocortex/physiology ; Neural Pathways/physiology ; Neuronal Plasticity/physiology ; Rats ; *Taste ; }, abstract = {Metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Accumulated evidence has proposed that metaplasticity contributes to network function and cognitive processes such as learning and memory. In this regard, it has been observed that training in several behavioral tasks modifies the possibility to induce subsequent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). For instance, our previous studies have shown that conditioned taste aversion (CTA) training prevents the induction of in vivo LTP in the projection from the basolateral nucleus of the amygdala to the insular cortex (BLA-IC). Likewise, we reported that extinction of CTA allows induction but not maintenance of LTP in the same pathway. Besides, we showed that it is possible to express in vivo low-frequency stimulation LTD in the BLA-IC projection and that its induction prior to CTA training facilitates the extinction of this task. However, until now, little is known about the participation of LTD on metaplastic processes. The present study aimed to analyze whether CTA training modifies the expression of in vivo LTD in the BLA-IC projection. To do so, animals received low-frequency stimulation to induce IC-LTD 48 h after CTA training. Our results show that CTA training occludes the subsequent induction of LTD in the BLA-IC pathway in a retrieval-dependent manner. These findings reveal that CTA elicits a metaplastic regulation of long-lasting changes in the IC synaptic strength, as well as that specific phases of learning differentially take part in adjusting the expression of synaptic plasticity in neocortical regions.}, } @article {pmid33872755, year = {2021}, author = {de Brugada, I and González, F and Cándido, A and Hall, G}, title = {Contextual control of the retardation of flavour aversion learning by preexposure to the unconditioned stimulus: Acquisition or retrieval deficit?.}, journal = {Behavioural processes}, volume = {188}, number = {}, pages = {104394}, doi = {10.1016/j.beproc.2021.104394}, pmid = {33872755}, issn = {1872-8308}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; Conditioning, Operant ; Cues ; Lithium Chloride/pharmacology ; Rats ; Taste ; }, abstract = {Two experiments, using rats as the subjects, and flavour aversion learning with an injection of lithium chloride (LiCl) as the unconditioned stimulus (US), examined the effects of a context shift between phases of the procedure on the retardation of learning produced by preexposure to the US. Experiment 1 showed that the US-preexposure effect (the reduction in the size of the conditioned aversion) was not attenuated when the animals were given both preexposure to the US and the conditioning procedure in a novel context but received the test phase in a different context (the home cages). Experiment 2 showed that, after degrading the injection cues-illness association by interpolating saline injections between LiCl preexposures, the US-preexposure effect was attenuated when there was a context shift between preexposure and conditioning, but that the context shift was without effect when it occurred between conditioning and test. These results are consistent with the proposal that US preexposure obtained in this procedure has its effect by interfering with the formation of the target association; they provide no support for the suggestion that the effect depends on interference at the test stage.}, } @article {pmid33831511, year = {2021}, author = {Osorio-Gómez, D and Bermúdez-Rattoni, F and Guzmán-Ramos, KR}, title = {Cortical neurochemical signaling of gustatory stimuli and their visceral consequences during the acquisition and consolidation of taste aversion memory.}, journal = {Neurobiology of learning and memory}, volume = {181}, number = {}, pages = {107437}, doi = {10.1016/j.nlm.2021.107437}, pmid = {33831511}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/metabolism ; Cerebral Cortex/metabolism ; Dopamine/*metabolism ; Glutamic Acid/*metabolism ; Injections, Intraperitoneal ; Insular Cortex/*metabolism ; Interoception/physiology ; Lithium Chloride/adverse effects ; Norepinephrine/*metabolism ; Physical Stimulation ; Rats ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D5/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Recognition, Psychology/*physiology ; Taste ; }, abstract = {The insular cortex (IC) has a crucial role in taste recognition memory, including conditioned taste aversion (CTA). CTA is a learning paradigm in which a novel taste stimulus (CS) is associated with gastric malaise (US), inducing aversion to the CS in future encounters. The role of the IC in CTA memory formation has been extensively studied. However, the functional significance of neurotransmitter release during the presentation of taste stimuli and gastric malaise-inducing agents remains unclear. Using microdialysis in free-moving animals, we evaluated simultaneous changes in glutamate, norepinephrine and dopamine release in response to the presentation of an innate appetitive or aversive gustatory novel stimulus, as well as after i.p. administration of isotonic or hypertonic gastric malaise-inducing solutions. Our results demonstrate that the presentation of novel stimuli, regardless of their innate valence, induces an elevation of norepinephrine and dopamine. Administration of a gastric malaise inducing agent (LiCl) promotes an elevation of glutamate regardless of its concentration. In comparison, norepinephrine release is related to the LiCl concentration and its equimolar NaCl control. Additionally, we evaluated their functional role on short and long-term taste aversion memory. Results indicate that the blockade of noradrenergic β1,2 receptors in the IC spares CTA acquisition and memory consolidation. In contrast, blockade of dopamine D1/D5 receptors impaired CTA consolidation, whereas the NMDA receptor blockade impedes both acquisition and consolidation of CTA. These results suggest that dopaminergic and noradrenergic release are related to the salience of conditioned taste stimuli. However, only cortical D1/D5 dopaminergic activity, but not the noradrenergic β1,2 activity, is involved in the acquisition and consolidation of taste memory formation. Additionally, glutamatergic activity signals visceral distress caused by LiCl administration and activates NMDA receptors necessary for the acquisition and consolidation of long-lasting taste aversion memory.}, } @article {pmid33809564, year = {2021}, author = {Kotańska, M and Mika, K and Szafarz, M and Kubacka, M and Müller, CE and Sapa, J and Kieć-Kononowicz, K}, title = {Effects of GPR18 Ligands on Body Weight and Metabolic Parameters in a Female Rat Model of Excessive Eating.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {33809564}, issn = {1424-8247}, abstract = {GPR18 has been proposed to play a role in the progression of metabolic disease and obesity. Therefore, the aim of this study was to determine the effects of selective GRP18 ligands (the antagonists PSB-CB5 and PSB-CB27 and the agonist PSB-KK1415) on body mass and the development of metabolic disorders commonly accompanying obesity. Experiments were carried out on female Wistar rats. In order to determine the anorectic activity of the investigated ligands, their effect on food and water intake in a model of excessive eating was assessed. Lipid profile, glucose and insulin levels as well as alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase activity in plasma were also evaluated. Potential side effects were examined in rat models of pica behavior and conditioned taste aversion. Animals treated with different ligands gained significantly less weight than rats from the obese control group. Effects of GPR18 antagonists on food intake and body weight were specific and unrelated to visceral illness, stress or changes in spontaneous activity. However, the GPR18 agonist is likely to affect body weight by inducing gastrointestinal disorders such as nausea. The presented preliminary data support the idea that the search for selective GPR18 antagonists for the treatment of obesity might be promising.}, } @article {pmid33804920, year = {2021}, author = {Calder, AN and Yu, T and Dahir, NS and Sun, Y and Gilbertson, TA}, title = {Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33804920}, issn = {2072-6643}, support = {R01 DC013318/DC/NIDCD NIH HHS/United States ; R21 DC013194/DC/NIDCD NIH HHS/United States ; R01DC013318, R21DC013194/NH/NIH HHS/United States ; }, mesh = {Animal Feed ; Animals ; Appetite/*physiology ; Fats/*administration & dosage ; Feeding Behavior/*physiology ; Female ; Mice ; Mice, Transgenic ; Models, Animal ; Receptors, Ghrelin/*metabolism ; Taste/*physiology ; }, abstract = {Ghrelin is a major appetite-stimulating neuropeptide found in circulation. While its role in increasing food intake is well known, its role in affecting taste perception, if any, remains unclear. In this study, we investigated the role of the growth hormone secretagogue receptor's (GHS-R; a ghrelin receptor) activity in the peripheral taste system using feeding studies and conditioned taste aversion assays by comparing wild-type and GHS-R-knockout models. Using transgenic mice expressing enhanced green fluorescent protein (GFP), we demonstrated GHS-R expression in the taste system in relation phospholipase C ß2 isotype (PLCβ2; type II taste cell marker)- and glutamate decarboxylase type 67 (GAD67; type III taste cell marker)-expressing cells using immunohistochemistry. We observed high levels of co-localization between PLCβ2 and GHS-R within the taste system, while GHS-R rarely co-localized in GAD67-expressing cells. Additionally, following 6 weeks of 60% high-fat diet, female Ghsr[-/-] mice exhibited reduced responsiveness to linoleic acid (LA) compared to their wild-type (WT) counterparts, while no such differences were observed in male Ghsr[-/-] and WT mice. Overall, our results are consistent with the interpretation that ghrelin in the taste system is involved in the complex sensing and recognition of fat compounds. Ghrelin-GHS-R signaling may play a critical role in the recognition of fatty acids in female mice, and this differential regulation may contribute to their distinct ingestive behaviors.}, } @article {pmid33798429, year = {2021}, author = {Wu, CH and Ramos, R and Katz, DB and Turrigiano, GG}, title = {Homeostatic synaptic scaling establishes the specificity of an associative memory.}, journal = {Current biology : CB}, volume = {31}, number = {11}, pages = {2274-2285.e5}, pmid = {33798429}, issn = {1879-0445}, support = {R01 EY025613/EY/NEI NIH HHS/United States ; T32 MH019929/MH/NIMH NIH HHS/United States ; F31 NS108506/NS/NINDS NIH HHS/United States ; R01 DC006666/DC/NIDCD NIH HHS/United States ; R35 NS111562/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; *Conditioning, Classical/drug effects ; Female ; *Homeostasis/drug effects ; Insular Cortex/*physiology ; Male ; *Memory/drug effects ; *Neuronal Plasticity/drug effects ; Rats ; Saccharin/*administration & dosage ; Synapses/drug effects/*metabolism ; }, abstract = {Correlation-based (Hebbian) forms of synaptic plasticity are crucial for the initial encoding of associative memories but likely insufficient to enable the stable storage of multiple specific memories within neural circuits. Theoretical studies have suggested that homeostatic synaptic normalization rules provide an essential countervailing force that can stabilize and expand memory storage capacity. Although such homeostatic mechanisms have been identified and studied for decades, experimental evidence that they play an important role in associative memory is lacking. Here, we show that synaptic scaling, a widely studied form of homeostatic synaptic plasticity that globally renormalizes synaptic strengths, is dispensable for initial associative memory formation but crucial for the establishment of memory specificity. We used conditioned taste aversion (CTA) learning, a form of associative learning that relies on Hebbian mechanisms within gustatory cortex (GC), to show that animals conditioned to avoid saccharin initially generalized this aversion to other novel tastants. Specificity of the aversion to saccharin emerged slowly over a time course of many hours and was associated with synaptic scaling down of excitatory synapses onto conditioning-active neuronal ensembles within gustatory cortex. Blocking synaptic scaling down in the gustatory cortex enhanced the persistence of synaptic strength increases induced by conditioning and prolonged the duration of memory generalization. Taken together, these findings demonstrate that synaptic scaling is crucial for sculpting the specificity of an associative memory and suggest that the relative strengths of Hebbian and homeostatic plasticity can modulate the balance between stable memory formation and memory generalization.}, } @article {pmid33693689, year = {2021}, author = {Igarashi, A and Ogasawara, S and Takagi, R and Okada, K and Ito, YM and Hara, H and Hira, T}, title = {Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.}, journal = {The Journal of nutrition}, volume = {151}, number = {5}, pages = {1320-1328}, doi = {10.1093/jn/nxab013}, pmid = {33693689}, issn = {1541-6100}, mesh = {Administration, Oral ; Animals ; *Appetite Regulation ; Calcium/administration & dosage/*pharmacology ; Calcium Chloride/pharmacology ; Calcium, Dietary/administration & dosage/*pharmacology ; Eating/*drug effects ; Energy Intake/drug effects ; Fasting ; Male ; Peptide YY/*blood ; Postprandial Period ; Rats, Sprague-Dawley ; Receptors, Calcium-Sensing/*blood ; Receptors, Gastrointestinal Hormone/metabolism ; Satiation ; Satiety Response/*drug effects ; }, abstract = {BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear.

OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism.

METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium.

RESULTS: Oral CaCl2 reduced food intake acutely (30 min, ∼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (∼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake.

CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium.}, } @article {pmid33605825, year = {2021}, author = {Karavasili, C and Gkaragkounis, A and Fatouros, DG}, title = {Patent landscape of pediatric-friendly oral dosage forms and administration devices.}, journal = {Expert opinion on therapeutic patents}, volume = {31}, number = {7}, pages = {663-686}, doi = {10.1080/13543776.2021.1893691}, pmid = {33605825}, issn = {1744-7674}, mesh = {Administration, Oral ; Chemistry, Pharmaceutical/*methods ; Child ; *Dosage Forms ; Drug Industry/methods ; Excipients/chemistry ; Humans ; Patents as Topic ; Pharmaceutical Preparations/administration & dosage/chemistry ; Taste ; Technology, Pharmaceutical/*methods ; }, abstract = {INTRODUCTION: The current availability of dosage forms designed specifically for children is limited, constituting common practice the use of unlicensed or off-labeled medicines and extemporaneous preparations. Swallowing difficulties and taste aversion are the primary reasons for medicine rejection; therefore, enhancing palatability and ease of administration are the most common approaches adopted to overcome these issues.

AREAS COVERED: A search of patents was performed for pediatric dosage forms and devices. The review aims to provide an overview on new formulation approaches and technologies adopted to develop pediatric-friendly dosage forms and devices, as well as on the regulatory efforts aiming to support the pediatrics market.

EXPERT OPINION: Children deserve medicines of the same efficacy, quality and safety as adults. The present review highlights the momentum developed by pharmaceutical industries in the field of pediatrics, since more than 60 patents have been published in the last 5 years. An increasing interest, especially in mini-tablets, orodispersible, and chewable dosage forms, as well as on excipients and methods, to achieve sufficient taste-masking was identified, recognizing also the need for coordinated research networks and sustainable collaborations across the public and private sectors to provide better medicines for children.}, } @article {pmid33593916, year = {2021}, author = {Sabatini, PV and Frikke-Schmidt, H and Arthurs, J and Gordian, D and Patel, A and Rupp, AC and Adams, JM and Wang, J and Beck Jørgensen, S and Olson, DP and Palmiter, RD and Myers, MG and Seeley, RJ}, title = {GFRAL-expressing neurons suppress food intake via aversive pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {8}, pages = {}, pmid = {33593916}, issn = {1091-6490}, support = {T32 DK071212/DK/NIDDK NIH HHS/United States ; T32 DK101357/DK/NIDDK NIH HHS/United States ; P30 DK089503/DK/NIDDK NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; R01 DA024908/DA/NIDA NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 DK119188/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight ; Eating/*drug effects ; Feeding Behavior/*drug effects ; Female ; Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics/*metabolism ; Growth Differentiation Factor 15/*pharmacology ; Male ; Mice ; Neurons/drug effects/*physiology ; Parabrachial Nucleus/drug effects/*physiology ; Rats ; Rats, Long-Evans ; }, abstract = {The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α-like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated Gfral[Cre] and conditional Gfral[CreERT] mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating Gfral[Cre] -expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRP[PBN]) neurons. Silencing CGRP[PBN] neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated pathophysiologic signals to suppress nutrient uptake and absorption.}, } @article {pmid33511630, year = {2021}, author = {Dannenhoffer, CA and Werner, DF and Varlinskaya, EI and Spear, LP}, title = {Adolescent intermittent ethanol exposure does not alter responsiveness to ifenprodil or expression of vesicular GABA and glutamate transporters.}, journal = {Developmental psychobiology}, volume = {63}, number = {5}, pages = {903-914}, pmid = {33511630}, issn = {1098-2302}, support = {T32 AA025606/AA/NIAAA NIH HHS/United States ; U01 AA019972/AA/NIAAA NIH HHS/United States ; }, mesh = {*Amino Acid Transport System X-AG ; Animals ; *Ethanol/pharmacology ; Female ; Glutamates ; Male ; Piperidines ; Rats ; gamma-Aminobutyric Acid ; }, abstract = {Adolescent intermittent ethanol (AIE) exposure in the rat results in a retention of adolescent-like responsiveness to ethanol into adulthood characterized by enhanced sensitivity to socially facilitating and decreased sensitivity to socially suppressing and aversive effects. Similar pattern of responsiveness to social and aversive effects of the selective glutamate NMDA NR2B receptor antagonist ifenprodil is evident in adolescent rats, suggesting that AIE would also retain this pattern of ifenprodil sensitivity into adulthood. Social (Experiment 1) and aversive (measured via conditioned taste aversion; Experiment 2) effects of ifenprodil were assessed in adult male and female rats following AIE exposure. Sensitivity to the social and aversive effects of ifenprodil was not affected by AIE exposure. Experiment 3 assessed protein expression of vesicular transporters of GABA (vGAT) and glutamate (vGlut2) within the prelimbic cortex and nucleus accumbens in adolescents versus adults and in AIE adults versus controls. vGlut2 expression was higher in adolescents relative to adults within the PrL, but lower in the NAc. AIE adults did not retain these adolescent-typical ratios. These findings suggest that AIE is not associated with the retention of adolescent-typical sensitivity to NR2B receptor antagonism, along with no AIE-induced shift in vGlut2 to vGAT ratios.}, } @article {pmid33502048, year = {2021}, author = {Indigo, NL and Jolly, CJ and Kelly, E and Smith, J and Webb, JK and Phillips, BL}, title = {Effects of learning and adaptation on population viability.}, journal = {Conservation biology : the journal of the Society for Conservation Biology}, volume = {35}, number = {4}, pages = {1245-1255}, doi = {10.1111/cobi.13691}, pmid = {33502048}, issn = {1523-1739}, mesh = {Animals ; Biological Evolution ; Bufo marinus ; *Conservation of Natural Resources ; Humans ; *Marsupialia ; Phenotype ; }, abstract = {Cultural adaptation is one means by which conservationists may help populations adapt to threats. A learned behavior may protect an individual from a threat, and the behavior can be transmitted horizontally (within generations) and vertically (between generations), rapidly conferring population-level protection. Although possible in theory, it remains unclear whether such manipulations work in a conservation setting; what conditions are required for them to work; and how they might affect the evolutionary process. We examined models in which a population can adapt through both genetic and cultural mechanisms. Our work was motivated by the invasion of highly toxic cane toads (Rhinella marina) across northern Australia and the resultant declines of endangered northern quolls (Dasyurus hallucatus), which attack and are fatally poisoned by the toxic toads. We examined whether a novel management strategy in which wild quolls are trained to avoid toads can reduce extinction probability. We used a simulation model tailored to quoll life history. Within simulations, individuals were trained and a continuous evolving trait determined innate tendency to attack toads. We applied this model in a population viability setting. The strategy reduced extinction probability only when heritability of innate aversion was low (<20%) and when trained mothers trained >70% of their young to avoid toads. When these conditions were met, genetic adaptation was slower, but rapid cultural adaptation kept the population extant while genetic adaptation was completed. To gain insight into the evolutionary dynamics (in which we saw a transitory peak in cultural adaptation over time), we also developed a simple analytical model of evolutionary dynamics. This model showed that the strength of natural selection declined as the cultural transmission rate increased and that adaptation proceeded only when the rate of cultural transmission was below a critical value determined by the relative levels of protection conferred by genetic versus cultural mechanisms. Together, our models showed that cultural adaptation can play a powerful role in preventing extinction, but that rates of cultural transmission need to be high for this to occur.}, } @article {pmid33443041, year = {2021}, author = {Itoh, A and Komatsuzaki, Y and Lukowiak, K and Saito, M}, title = {Epicatechin increases the persistence of long-term memory formed by conditioned taste aversion in Lymnaea.}, journal = {The Journal of experimental biology}, volume = {224}, number = {Pt 3}, pages = {}, doi = {10.1242/jeb.238055}, pmid = {33443041}, issn = {1477-9145}, mesh = {Animals ; *Catechin ; Conditioning, Operant ; Feeding Behavior ; *Lymnaea ; Memory, Long-Term ; Taste ; }, abstract = {We examined the effects of epicatechin (Epi), a flavonoid abundant in green tea and cocoa, on long-term memory (LTM) formed following conditioned taste aversion (CTA) training in Lymnaeastagnalis In CTA training, the snails learnt to avoid a food that initially they liked (i.e. sucrose). Twenty-four hours after CTA training, 67% of the trained snails showed a significant decrease in the feeding behaviour elicited by sucrose. Placing snails in the Epi solution in CTA training did not alter the percentage of snails exhibiting LTM, but it significantly increased LTM persistence. We also examined changes following Epi exposure in spontaneous activity of the cerebral giant cells (CGCs) that modulate feeding behaviour and are necessary for CTA-LTM. Our data suggest that Epi causes a decrease in CGC activity and increases LTM persistence, possibly via a GABAergic mechanism.}, } @article {pmid33383859, year = {2020}, author = {Toyoda, H and Katagiri, A and Kato, T and Sato, H}, title = {Intranasal Administration of Rotenone Reduces GABAergic Inhibition in the Mouse Insular Cortex Leading to Impairment of LTD and Conditioned Taste Aversion Memory.}, journal = {International journal of molecular sciences}, volume = {22}, number = {1}, pages = {}, pmid = {33383859}, issn = {1422-0067}, mesh = {Administration, Intranasal ; Animals ; Cerebral Cortex/cytology/*drug effects/*metabolism ; GABAergic Neurons/*drug effects/*metabolism ; Long-Term Potentiation/*drug effects ; *Memory ; Mice ; Pyramidal Cells/drug effects/metabolism ; Receptors, GABA-A/metabolism ; Rotenone/*administration & dosage ; Taste Perception/*drug effects/genetics ; }, abstract = {The pesticide rotenone inhibits mitochondrial complex I and is thought to cause neurological disorders such as Parkinson's disease and cognitive disorders. However, little is known about the effects of rotenone on conditioned taste aversion memory. In the present study, we investigated whether intranasal administration of rotenone affects conditioned taste aversion memory in mice. We also examined how the intranasal administration of rotenone modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex that is critical for conditioned taste aversion memory. We found that the intranasal administration of rotenone impaired conditioned taste aversion memory to bitter taste. Regarding its cellular mechanisms, long-term depression (LTD) but not long-term potentiation (LTP) was impaired in rotenone-treated mice. Furthermore, spontaneous inhibitory synaptic currents and tonic GABA currents were decreased in layer V pyramidal neurons of rotenone-treated mice compared to the control mice. The impaired LTD observed in pyramidal neurons of rotenone-treated mice was restored by a GABAA receptor agonist muscimol. These results suggest that intranasal administration of rotenone decreases GABAergic synaptic transmission in layer V pyramidal neurons of the mouse insular cortex, the result of which leads to impairment of LTD and conditioned taste aversion memory.}, } @article {pmid33357702, year = {2021}, author = {Kawabata, F and Yoshida, Y and Inoue, Y and Kawabata, Y and Nishimura, S and Tabata, S}, title = {Research Note: Behavioral preference and conditioned taste aversion to oleic acid solution in chickens.}, journal = {Poultry science}, volume = {100}, number = {1}, pages = {372-376}, pmid = {33357702}, issn = {1525-3171}, mesh = {Animals ; *Avoidance Learning/drug effects ; *Chickens ; *Feeding Behavior/drug effects ; Female ; Oleic Acid/pharmacology ; *Taste ; }, abstract = {A functional fatty acid taste receptor, GPR120, is present in chicken oral tissues, and chickens show a preference for lipid in feed. However, it remains unclear whether chickens can detect fatty acids. To address this issue, we adopted 2 behavioral paradigms: a one-bowl drinking test to evaluate the preference for oleic acid solution and a conditioned taste aversion test to investigate the role of gustation in chickens' ability to detect oleic acid. In the one-bowl drinking test, chickens did not show any preference for solution containing 0.001, 0.01, 0.03, 0.1, or 30 mmol/L oleic acid although 30 mmol/L oleic acid was enough to fully activate GPR120, confirmed by Ca[2+] imaging. On the other hand, chickens conditioned to avoid 30 mmol/L oleic acid solution also learned to avoid the solution. These results suggested that chickens have a gustatory perception of oleic acid solution but do not have a preference for it. The present results support the idea that chickens prefer lipid in feed, not only by a postingestive effect but also by sensing the taste of fatty acid.}, } @article {pmid33352200, year = {2021}, author = {Wyszogrodzka, E and Dyr, W and Siwińska-Ziółkowska, A and Mierzejewski, P}, title = {Higher sensitivity to ethanol's aversive properties in WLP (Warsaw Low Preferring) vs. WHP (Warsaw High Preferring) rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {90}, number = {}, pages = {67-73}, doi = {10.1016/j.alcohol.2020.12.002}, pmid = {33352200}, issn = {1873-6823}, mesh = {*Alcohol Drinking ; Animals ; Anxiety ; *Avoidance Learning ; *Conditioning, Classical ; Ethanol/administration & dosage ; Rats ; }, abstract = {Ethanol can have both an aversive and rewarding effect, which may have a significant relationship to its individual preference. So far, the reasons for the high and low ethanol preference in the WHP (Warsaw High Preferring) and WLP (Warsaw Low Preferring) lines have not been found. WHP rats spontaneously drink over 5 g/kg/day of ethanol, while WLP rats drink under 2 g/kg/day. The purpose of the work was to study the sensitivity of WHP and WLP rats to the aversive effects of ethanol at doses of 1.5 g/kg and 2.0 g/kg in the conditioned taste aversion (CTA) procedure. Lower doses (0.5 and 1.0 g/kg, i.p. [intraperitoneally]) were tested earlier and only 1.0 g/kg produced a slight aversion in WLP rats. The secondary aim was to check the additional potential factors (blood ethanol concentration, pain sensitivity, anxiety-related behavior, learning, and memory) that may constitute an important differentiating feature of the WHP and WLP lines. For this purpose, the following tests were conducted: blood ethanol concentration, novel object recognition (NOR), flinch-jump, hot-plate, and elevated plus maze (EPM). The 1.5 g/kg i.p. dose of ethanol caused the development of an aversion only in WLP rats and the aversion extinguished in the post-conditioning phase. The 2.0 g/kg i.p. dose of ethanol resulted in the development of an aversion in both the tested groups, with the aversion being maintained throughout the whole post-conditioning period only in the WLP rats. There were no differences between the lines in terms of the blood ethanol concentration and the EPM tests. WHP rats had a higher pain sensitivity compared to WLP rats in flinch-jump and hot-plate tests. WLP rats showed a shorter exploration time for both objects compared to WHP in the NOR test. In conclusion, WHP and WLP rats differ in sensitivity to the aversive effects of ethanol. This difference may partially explain their opposite ethanol preference.}, } @article {pmid33333877, year = {2020}, author = {Robinson, SL and Dornellas, APS and Burnham, NW and Houck, CA and Luhn, KL and Bendrath, SC and Companion, MA and Brewton, HW and Thomas, RD and Navarro, M and Thiele, TE}, title = {Distinct and Overlapping Patterns of Acute Ethanol-Induced C-Fos Activation in Two Inbred Replicate Lines of Mice Selected for Drinking to High Blood Ethanol Concentrations.}, journal = {Brain sciences}, volume = {10}, number = {12}, pages = {}, pmid = {33333877}, issn = {2076-3425}, support = {AA022048/AA/NIAAA NIH HHS/United States ; R37 AA013573/AA/NIAAA NIH HHS/United States ; T32 DA007244/DA/NIDA NIH HHS/United States ; AA013573/AA/NIAAA NIH HHS/United States ; AA025811/AA/NIAAA NIH HHS/United States ; R01 AA025809/AA/NIAAA NIH HHS/United States ; AA025809/AA/NIAAA NIH HHS/United States ; }, abstract = {UNLABELLED: The inbred high drinking in the dark (iHDID1 and iHDID2) strains are two replicate lines bred from the parent HS/Npt (HS) line for achieving binge levels of blood ethanol concentration (≥80 mg/dL BEC) in a four-hour period. In this work, we sought to evaluate differences in baseline and ethanol-induced c-Fos activation between the HS, iHDID1, and iHDID2 genetic lines in brain regions known to process the aversive properties of ethanol.

METHODS: Male and female HS, iHDID1, and iHDID2 mice underwent an IP saline 2 3 g/kg ethanol injection. Brain sections were then stained for c-Fos expression in the basolateral/central amygdala (BLA/CeA), bed nucleus of the stria terminals (BNST), A2, locus coeruleus (LC), parabrachial nucleus (PBN), lateral/medial habenula (LHb/MHb), paraventricular nucleus of the thalamus (PVT), periaqueductal gray (PAG), Edinger-Westphal nuclei (EW), and rostromedial tegmental nucleus (RMTg).

RESULTS: The iHDID1 and iHDID2 lines showed similar and distinct patterns of regional c-Fos; however, in no region did the two both significantly differ from the HS line together.

CONCLUSIONS: These data lend further support to altered baseline or ethanol-induced activation in brain regions associated with processing the aversive properties of ethanol in the iHDID1 and iHDID2 genetic lines.}, } @article {pmid33290705, year = {2020}, author = {Stensmyr, MC and Caron, SJC}, title = {Neuroscience: The Secret of Sauce Béarnaise Syndrome Is in the Circuit.}, journal = {Current biology : CB}, volume = {30}, number = {23}, pages = {R1413-R1415}, doi = {10.1016/j.cub.2020.09.085}, pmid = {33290705}, issn = {1879-0445}, mesh = {Animals ; *Avoidance Learning ; Cues ; Eating ; *Mushroom Bodies ; Taste ; }, abstract = {During conditioned food aversion - a.k.a. sauce béarnaise syndrome - the ingestion of a spoiled food item leads to a lasting aversion towards cues reminiscent of the item. A new study finds that, in Drosophila, taste aversion depends on the immune system and the mushroom body.}, } @article {pmid33256267, year = {2020}, author = {Nakai, J and Totani, Y and Hatakeyama, D and Dyakonova, VE and Ito, E}, title = {Another Example of Conditioned Taste Aversion: Case of Snails.}, journal = {Biology}, volume = {9}, number = {12}, pages = {}, pmid = {33256267}, issn = {2079-7737}, abstract = {Conditioned taste aversion (CTA) in mammals has several specific characteristics: (1) emergence of a negative symptom in subjects due to selective association with a taste-related stimulus, (2) robust long-term memory that is resistant to extinction induced by repeated presentation of the conditioned stimulus (CS), (3) a very-long-delay presentation of the unconditioned stimulus (US), and (4) single-trial learning. The pond snail, Lymnaea stagnalis, can also form a CTA. Although the negative symptoms, like nausea, in humans cannot be easily observed in invertebrate animal models of CTA, all the other characteristics of CTA seem to be present in snails. Selective associability was confirmed using a sweet sucrose solution and a bitter KCl solution. Once snails form a CTA, repeated presentation of the CS does not extinguish the CTA. A long interstimulus interval between the CS and US, like in trace conditioning, still results in the formation of a CTA in snails. Lastly, even single-trial learning has been demonstrated with a certain probability. In the present review, we compare, in detail, CTA in mammals and snails, and discuss the possible molecular events in CTA.}, } @article {pmid33169666, year = {2020}, author = {Haley, MS and Bruno, S and Fontanini, A and Maffei, A}, title = {LTD at amygdalocortical synapses as a novel mechanism for hedonic learning.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33169666}, issn = {2050-084X}, support = {NS115779//NIH Blueprint for Neuroscience Research/International ; DC013770//NIH Blueprint for Neuroscience Research/International ; R01 DC015234/DC/NIDCD NIH HHS/United States ; R01 DC013770/DC/NIDCD NIH HHS/United States ; DC015234//NIH Blueprint for Neuroscience Research/International ; UF1 NS115779/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/*physiology ; Cerebral Cortex/*physiology ; Conditioning, Classical/*physiology ; Female ; Male ; *Models, Neurological ; Neuronal Plasticity/physiology ; Optogenetics ; Rats ; Synapses/*physiology ; Taste Perception ; }, abstract = {A novel, pleasant taste stimulus becomes aversive if associated with gastric malaise, a form of learning known as conditioned taste aversion (CTA). CTA is common to vertebrates and invertebrates and is an important survival response: eating the wrong food may be deadly. CTA depends on the gustatory portion of the insular cortex (GC) and the basolateral nucleus of the amygdala (BLA) however, its synaptic underpinnings are unknown. Here we report that CTA was associated with decreased expression of immediate early genes in rat GC of both sexes, and with reduced amplitude of BLA-GC synaptic responses, pointing to long-term depression (LTD) as a mechanism for learning. Indeed, association of a novel tastant with induction of LTD at the BLA-GC input in vivo was sufficient to change the hedonic value of a taste stimulus. Our results demonstrate a direct role for amygdalocortical LTD in taste aversion learning.}, } @article {pmid33152457, year = {2021}, author = {Morin, JP and Rodríguez-Nava, E and Torres-García, VM and Contreras-Vázquez, OA and Castellanos-Pérez, CA and Tovar-Díaz, J and Roldán-Roldán, G}, title = {Muscarinic receptor signaling in the amygdala is required for conditioned taste aversion.}, journal = {Neuroscience letters}, volume = {740}, number = {}, pages = {135466}, doi = {10.1016/j.neulet.2020.135466}, pmid = {33152457}, issn = {1872-7972}, mesh = {Amygdala/drug effects/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Emotions ; Male ; Memory Consolidation/drug effects ; Mental Recall/drug effects ; Microinjections ; Muscarinic Antagonists/administration & dosage/pharmacology ; Parasympathetic Nervous System/drug effects/physiology ; Rats ; Rats, Wistar ; Receptors, Muscarinic/drug effects/*physiology ; Scopolamine/administration & dosage/pharmacology ; Signal Transduction/drug effects/*physiology ; Taste/drug effects/*physiology ; }, abstract = {The sense of taste provides information regarding the nutrient content, safety or potential toxicity of an edible. This is accomplished via a combination of innate and learned taste preferences. In conditioned taste aversion (CTA), rats learn to avoid ingesting a taste that has previously been paired with gastric malaise. Recent evidence points to a role of cholinergic muscarinic signaling in the amygdala for the learning and storage of emotional memories. The present study tested the participation of muscarinic receptors in the amygdala during the formation of CTA by infusing the non-specific antagonist scopolamine into the basolateral or central subnuclei before or after conditioning, as well as before retrieval. Our data show that regardless of the site of infusion, pre-conditioning administration of scopolamine impaired CTA acquisition whereas post-conditioning infusion did not affect its storage. Also, infusions into the basolateral but not in the central amygdala before retrieval test partially reduced the expression of CTA. Our results indicate that muscarinic receptors activity is required for acquisition but not consolidation of CTA. In addition, our data add to recent evidence pointing to a role of cholinergic signaling in peri-hippocampal structures in the process of memory retrieval.}, } @article {pmid33119327, year = {2021}, author = {Steinfeld, MR and Bouton, ME}, title = {Renewal of goal direction with a context change after habit learning.}, journal = {Behavioral neuroscience}, volume = {135}, number = {1}, pages = {79-87}, pmid = {33119327}, issn = {1939-0084}, support = {R01 DA033123/DA/NIDA NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Animals ; Extinction, Psychological ; Female ; *Goals ; *Habits ; *Learning ; Motivation ; Rats ; }, abstract = {An instrumental action can be goal-directed after a moderate amount of practice and then convert to habit after more extensive practice. Recent evidence suggests, however, that habits can return to action status after different environmental manipulations. The present experiments therefore asked whether habit learning interferes with goal direction in a context-dependent manner like other types of retroactive interference (e.g., extinction, punishment, counterconditioning). In Experiment 1, rats were given a moderate amount of instrumental training to form an action in one context (Context A) and then more extended training of the same response to form a habit in another context (Context B). We then performed reinforcer devaluation with taste aversion conditioning in both contexts, and tested the response in both contexts. The response remained habitual in Context B, but was goal-directed in Context A, indicating renewal of goal direction after habit learning. Experiment 2 expanded on Experiment 1 by testing the response in a third context (Context C). It found that the habitual response also renewed as action in this context. Together, the results establish a parallel between habit and extinction learning: Conversion to habit does not destroy action knowledge, but interferes with it in a context-specific way. They are also consistent with other results suggesting that habit is specific to the context in which it is learned, whereas goal-direction can transfer between contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33077494, year = {2020}, author = {Fonseca, E and Sandoval-Herrera, V and Simon, SA and Gutierrez, R}, title = {Behavioral Disassociation of Perceived Sweet Taste Intensity and Hedonically Positive Palatability.}, journal = {eNeuro}, volume = {7}, number = {5}, pages = {}, pmid = {33077494}, issn = {2373-2822}, mesh = {Animals ; Conditioning, Classical ; Food Preferences ; Rats ; Sucrose ; *Taste ; *Taste Perception ; }, abstract = {The intensity of sucrose (its perceived concentration) and its palatability (positive hedonic valence associated with ingestion) are two taste attributes that increase its attractiveness and overconsumption. Although both sensory attributes covary, in that increases in sucrose concentration leads to similar increases in its palatability, this covariation does not imply that they are part of the same process or whether they represent separate processes. Both these possibilities are considered in the literature. For this reason, we tested whether sucrose's perceived intensity could be separated from its hedonically positive palatability. To address this issue, rats were trained in a sucrose intensity task to report the perceived intensity of a range of sucrose concentrations before and after its palatability was changed using a conditioned taste aversion (CTA) protocol. We found that the subjects' performance remained essentially unchanged, although its palatability was changed from hedonically positive to negative. Overall, these data demonstrate that sucrose's perceived intensity and its positive palatability can be dissociated, meaning that changes of one taste attribute render the other mostly unaffected. Thus, the intensity attribute is sufficient to inform the perceptual judgments of sucrose's concentrations.}, } @article {pmid33065316, year = {2020}, author = {Sato, T and Hirai, Y and Su, S and Zimo, W and Yasuura, N and Inui, T and Funahashi, M}, title = {Involvement of the area postrema and the nucleus tractus solitarius in the emetogenic action of emetine in rats.}, journal = {Journal of oral biosciences}, volume = {62}, number = {4}, pages = {310-314}, doi = {10.1016/j.job.2020.10.001}, pmid = {33065316}, issn = {1880-3865}, mesh = {Animals ; *Area Postrema ; Emetics ; Emetine ; Nausea ; Rats ; *Solitary Nucleus ; }, abstract = {OBJECTIVES: The aim of the present study was to demonstrate the effective dose of emetine for inducing nausea and/or emesis, and the effects of emetine on the excitability of central neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS).

METHODS: Rats were used as experimental animals. We measured the conditioned taste aversion (CTA) induced by the intraperitoneal administration of emetine solution (0.03, 0.1, 0.3, 0.5, and 1.0 mM in saline) and that of only saline. We also performed immunohistochemical analyses of c-Fos expression in the area postrema and the NTS, to examine changes in the excitability of brainstem neurons that may be responsible for emetine-induced nausea and/or emesis.

RESULTS: The emetine-induced CTA occurred in a dose-dependent manner. The half maximal inhibitory concentration (IC50) of emetine on the saccharin preference was calculated to be 0.348 mM using the Hill equation. In the animals injected with emetine (0.5 and 1.0 mM), many c-Fos-like immunoreactive (Fos-ir) cells were observed in the area postrema and the NTS, while few Fos-ir cells were identified in the animals injected with saline. The average number of Fos-ir cells in the area postrema and the NTS was significantly larger in animals injected with emetine than in animals injected with saline.

CONCLUSIONS: The present study demonstrated a dose-responsive manner of emetine effects and emetine-induced upregulation of neuronal excitability in the area postrema and the NTS that form a part of the induction mechanisms of emetine-induced nausea and/or emesis.}, } @article {pmid33011270, year = {2020}, author = {Tobajas, J and Ruiz-Aguilera, MJ and López-Bao, JV and Ferreras, P and Mateo, R}, title = {The effectiveness of conditioned aversion in wolves: Insights from experimental tests.}, journal = {Behavioural processes}, volume = {181}, number = {}, pages = {104259}, doi = {10.1016/j.beproc.2020.104259}, pmid = {33011270}, issn = {1872-8308}, mesh = {Animals ; Livestock ; Odorants ; Predatory Behavior ; Taste ; *Wolves ; }, abstract = {It has been suggested that conditioned food aversion (CFA) could be a potential non-lethal intervention by which to deter attacks on livestock by large carnivores. CFA occurs when an animal associates the characteristics of a food with an illness, thus rejecting that food in subsequent encounters. CFA can be associated with an artificial odour during conditioning. Despite the debate surrounding the use of this intervention, more studies evaluating the effectiveness of CFA are necessary. We experimentally evaluated the potential of microgranulated levamisole + a vanilla odour cue to induce CFA in captive Iberian wolves (Canis lupus signatus). Four out of the five wolves treated showed an aversion to the meat for a minimum of one month after conditioning. The microgranulated presentation masked the flavour and smell of the levamisole but increased its volume, which may have facilitated its detection by the wolves. We also observed that the strength of the odour played an important role in the aversion extinction. The use of microgranulated levamisole + an odour cue has the potential to be used as an intervention by which to induce aversive conditioning in wolves in the wild, although rigorous field tests are required. We discuss the potential of CFA to deter attacks on livestock by large carnivores.}, } @article {pmid32994339, year = {2020}, author = {Fukabori, R and Iguchi, Y and Kato, S and Takahashi, K and Eifuku, S and Tsuji, S and Hazama, A and Uchigashima, M and Watanabe, M and Mizuma, H and Cui, Y and Onoe, H and Hikishima, K and Yasoshima, Y and Osanai, M and Inagaki, R and Fukunaga, K and Nishijo, T and Momiyama, T and Benton, R and Kobayashi, K}, title = {Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {40}, number = {43}, pages = {8367-8385}, pmid = {32994339}, issn = {1529-2401}, mesh = {Animals ; Arousal/physiology ; Drosophila melanogaster ; Electrophysiological Phenomena ; Humans ; Locus Coeruleus/cytology/*drug effects ; Memory/drug effects/*physiology ; Mental Recall/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Activity/physiology ; Norepinephrine/*physiology ; Phenylacetates/pharmacology ; Receptors, Adrenergic/drug effects/*physiology ; Receptors, Odorant/physiology ; Sensory Receptor Cells/drug effects/*physiology ; Taste/drug effects/genetics/*physiology ; }, abstract = {The ability of animals to retrieve memories stored in response to the environment is essential for behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear. Here, we developed a novel chemogenetic activation strategy exploiting insect olfactory ionotropic receptors (IRs), termed "IR-mediated neuronal activation," and used it for selective stimulation of NE neurons in the locus coeruleus (LC). Drosophila melanogaster IR84a and IR8a subunits were expressed in LC NE neurons in transgenic mice. Application of phenylacetic acid (a specific ligand for the IR84a/IR8a complex) at appropriate doses induced excitatory responses of NE neurons expressing the receptors in both slice preparations and in vivo electrophysiological conditions, resulting in a marked increase of NE release in the LC nerve terminal regions (male and female). Ligand-induced activation of LC NE neurons enhanced the retrieval process of conditioned taste aversion without affecting taste sensitivity, general arousal state, and locomotor activity. This enhancing effect on taste memory retrieval was mediated, in part, through α1- and β-adrenergic receptors in the basolateral nucleus of the amygdala (BLA; male). Pharmacological inhibition of LC NE neurons confirmed the facilitative role of these neurons in memory retrieval via adrenergic receptors in the BLA (male). Our findings indicate that the LC NE system, through projections to the BLA, controls the retrieval process of taste associative memory.SIGNIFICANCE STATEMENT Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation, but the role of the NE system in memory retrieval remains unclear. We developed a chemogenetic activation system based on insect olfactory ionotropic receptors and used it for selective stimulation of NE neurons in the locus coeruleus (LC) in transgenic mice. Ligand-induced activation of LC NE neurons enhanced the retrieval of conditioned taste aversion, which was mediated, in part, through adrenoceptors in the basolateral amygdala. Pharmacological blockade of LC activity confirmed the facilitative role of these neurons in memory retrieval. Our findings indicate that the LC-amygdala pathway plays an important role in the recall of taste associative memory.}, } @article {pmid32991926, year = {2021}, author = {Grijalva, LE and Miranda, MI and Paredes, RG}, title = {Differential changes in GAP-43 or synaptophysin during appetitive and aversive taste memory formation.}, journal = {Behavioural brain research}, volume = {397}, number = {}, pages = {112937}, doi = {10.1016/j.bbr.2020.112937}, pmid = {32991926}, issn = {1872-7549}, mesh = {Animals ; Appetitive Behavior/*physiology ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/*metabolism ; Central Amygdaloid Nucleus/*metabolism ; Cerebral Cortex/*metabolism ; Frontal Lobe/metabolism ; GAP-43 Protein/*metabolism ; Male ; Neuronal Plasticity/*physiology ; Rats ; Rats, Wistar ; Synaptophysin/*metabolism ; Taste Perception/*physiology ; }, abstract = {Association between events in time and space is a major mechanism for all animals, including humans, which allows them to learn about the world and potentially change their behavior in the future to adapt to different environments. Conditioning taste aversion (CTA) is a single-trial learning paradigm where animals are trained to avoid a novel flavor which is associated with malaise. Many variables can be analyzed with this model and the circuits involved are well described. Thus, the amygdala and the gustatory cortex (GC) are some of the most relevant structures involved in CTA. In the present study we focused in plastic changes that occur during appetitive and/or aversive taste memory formation. Previous studies have demonstrated that memory consolidation, in hippocampal dependent paradigms, induces plastic changes like increase in the concentration of proteins considered as markers of neuronal plasticity, such as the growth associated protein 43 (GAP-43) and synaptophysin (SYN). In the present experiment in male rats we evaluated changes in GAP-43 and SYN expression, using immunofluorescence, induce by the formation of aversive and appetitive taste memory. We found that taste aversive memory formation can induce an increase in GAP-43 in the granular layer of the GC. Furthermore, we also found an increase in SYN expression in both layers of the GC, the basolateral amygdala (BLA) and the central amygdala (CeA). These results suggest that aversive memory representation induces a new circuitry (inferred from an increase in GAP 43). On the other hand, an appetitive taste learning increased SYN expression in the GC (both layers), the BLA and the CeA without any changes in GAP 43. Together these results indicate that aversive memory formation induces structural and synaptic changes, while appetitive memory formation induces synaptic changes; suggesting that aversive and appetitive memories require a different set of cortical and amygdala plastic changes.}, } @article {pmid32981845, year = {2020}, author = {Heyes, C and Chater, N and Dwyer, DM}, title = {Sinking In: The Peripheral Baldwinisation of Human Cognition.}, journal = {Trends in cognitive sciences}, volume = {24}, number = {11}, pages = {884-899}, doi = {10.1016/j.tics.2020.08.006}, pmid = {32981845}, issn = {1879-307X}, mesh = {Adaptation, Biological ; *Cognition ; Fear ; Humans ; Language ; *Learning ; }, abstract = {The Baldwin effect is a hypothetical process in which a learned response to environmental change evolves a genetic basis. Modelling has shown that the Baldwin effect offers a plausible and elegant explanation for the emergence of complex behavioural traits, but there is little direct empirical evidence for its occurrence. We highlight experimental evidence of the Baldwin effect and argue that it acts preferentially on peripheral rather than on central cognitive processes. Careful scrutiny of research on taste-aversion and fear learning, language, and imitation indicates that their efficiency depends on adaptively specialised input and output processes: analogues of scanner and printer interfaces that feed information to core inference processes and structure their behavioural expression.}, } @article {pmid32936829, year = {2020}, author = {Galistu, A and D'Aquila, PS}, title = {Memantine effects on ingestion microstructure and the effect of administration time: A within-subject study.}, journal = {PloS one}, volume = {15}, number = {9}, pages = {e0239270}, pmid = {32936829}, issn = {1932-6203}, mesh = {Animals ; Conditioning, Classical/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Eating ; Feeding Behavior/*drug effects ; Humans ; Memantine/adverse effects/*pharmacology ; Memory/*drug effects/physiology ; Rats ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/genetics ; }, abstract = {In a between-subject comparison of two memantine administration schedules we observed that treatment with the NMDA receptor antagonist memantine before testing sessions reduced ingestion of a 10% sucrose solution in rats, due to reduced licking burst size, thus suggesting a blunted hedonic response. Conversely, daily post-session administration reduced burst number, indicating a reduced level of behavioural activation, likely due to the development of conditioned taste aversion (CTA). In this study, the effect of pre-session and post-session memantine administration was investigated within-subjects. Memantine was administered in daily intraperitoneal injections for 13 days, on alternate days, either 1-h before-"before testing" sessions-or immediately after a 30-min session-"after testing" sessions. The effects on the microstructure of licking for a 10% sucrose solution were examined in the course of treatment and for 21 days after treatment discontinuation. The results show reduced burst size in the "before testing" sessions, without effects on the intra-burst lick rate, an index of motoric effects. Moreover, burst number was reduced since the third session of both administration conditions until the end of treatment. Interestingly, the effect of memantine of reducing the activation of ingestive behaviour was less pronounced in this study with respect to that observed with the previous study post-session administration schedule, in spite of the longer treatment. This apparent paradox might be explained if one considers these effects as instances of a memory-related effect, such as the development of CTA. In the framework of this hypothesis, the "before testing" sessions, not being followed by memantine administration, can be considered as extinction sessions performed every other day. Moreover, the animals treated with memantine at the highest dose failed to recover to pre-treatment ingestion levels 21 days after treatment discontinuation, while the animals treated after testing sessions in the previously published study showed a complete recovery well before the 15th day test. Within the same interpretative framework, this might depend by the reduced number and frequency of the extinction trials-i.e. the number of the sessions run after treatment discontinuation-in the present study. These results provide further support to the conclusion that memantine administration before sessions reduce burst size, an effect which is likely due to blockade of NMDA receptors occurring during behavioural testing. The observation that this effect can be obtained even in absence of a reduced intra-burst lick rate, which rules out the involvement of motor impairment, provides an important piece of evidence in support to the interpretation of this effect as a blunted hedonic response. Moreover, these results provide further evidence that burst number reduction is due to a memory-related effect induced by memantine administration after sessions.}, } @article {pmid32857870, year = {2020}, author = {Arieli, E and Gerbi, R and Shein-Idelson, M and Moran, A}, title = {Temporally-precise basolateral amygdala activation is required for the formation of taste memories in gustatory cortex.}, journal = {The Journal of physiology}, volume = {598}, number = {23}, pages = {5505-5522}, doi = {10.1113/JP280213}, pmid = {32857870}, issn = {1469-7793}, mesh = {Amygdala ; Animals ; Avoidance Learning ; *Basolateral Nuclear Complex ; Cerebral Cortex ; Memory ; Rats ; Taste ; }, abstract = {KEY POINTS: The basolateral amygdala (BLA), the nucleus basalis magnocellularis (NBM), and the gustatory cortex (GC) are involved in taste processing, taste memory formation and conditioned taste aversion (CTA) learning, but their fine-temporal interactions that support these cognitive functions are not well understood. We found that the formation of novel-taste and CTA memories in the GC depend on a distinct late response (700-3000 ms) of BLA projection neurons. In contrast, BLA activity was not essential for palatability-related behaviour and coding in the GC prior to CTA. We identified the BLA→NBM pathway as a potential pathway for the transmission of taste novelty information, required for the formation of taste and CTA memories in the GC. Our results demonstrate how neuronal dynamics across multiple brain regions support long-term memory formation.

ABSTRACT: Learning to associate malaise with the intake of novel food is critical for survival. Since food poisoning may take hours to take effect, animals developed brain circuits to transform the current novel taste experience into a taste memory trace (TMT) and bridge this time lag. Ample studies showed that the basolateral amygdala (BLA), the nucleus basalis magnocellularis (NBM) and the gustatory cortex (GC) are involved in TMT formation and taste-malaise association. However, how dynamic activity across these brain regions during novel taste experience promotes the formation of these memories is currently unknown. We used the conditioned taste aversion (CTA) learning paradigm in combination with short-term optogenetics and electrophysiological recording in rats to test the hypothesis that temporally specific activation of BLA projection neurons is essential for TMT formation in the GC, and consequently CTA. We found that a short late epoch (LE, 700-3000 ms), but not the early epoch (EE, 0-500 ms), of BLA activation during novel taste experience is essential for normal CTA, for early c-Fos expression in the GC (a marker of TMT formation) and for the post-CTA changes in GC ensemble palatability coding. Interestingly, BLA activity was not required for intact taste identity or palatability perceptions before CTA. We further show that BLA-LE information is transmitted to GC through the BLA→NBM pathway where it affects the formation of taste memories. These results expose the dependence of long-term memory formation on specific temporal windows during sensory responses and the distributed circuits supporting this dependence.}, } @article {pmid32779566, year = {2020}, author = {Levitan, D and Liu, C and Yang, T and Shima, Y and Lin, JY and Wachutka, J and Marrero, Y and Ali Marandi Ghoddousi, R and Veiga Beltrame, ED and Richter, TA and Katz, DB and Nelson, SB}, title = {Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32779566}, issn = {2050-084X}, support = {R21 DC016706/DC/NIDCD NIH HHS/United States ; R01 NS109916/NS/NINDS NIH HHS/United States ; T90 DA032435/DA/NIDA NIH HHS/United States ; DC006666/DC/NIDCD NIH HHS/United States ; NS109916/NS/NINDS NIH HHS/United States ; R90 DA033463/DA/NIDA NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases ; Animals ; *Basolateral Nuclear Complex/chemistry/cytology/metabolism ; Conditioning, Classical/*physiology ; Female ; Gene Knockout Techniques ; Male ; Memory, Long-Term/*physiology ; Mice ; Neurons/chemistry/metabolism ; *Protein Serine-Threonine Kinases/genetics/metabolism ; *Proto-Oncogene Proteins c-fos/genetics/metabolism ; Taste/physiology ; }, abstract = {Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms remain poorly understood. RNAseq from BLApn identified changes in multiple candidate learning-related transcripts including the expected immediate early gene Fos and Stk11, a master kinase of the AMP-related kinase pathway with important roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 in BLApn blocked memory prior to training, but not following it and increased neuronal excitability. Conversely, BLApn had reduced excitability following CTA. BLApn knockout of a second learning-related gene, Fos, also increased excitability and impaired learning. Independently increasing BLApn excitability chemogenetically during CTA also impaired memory. STK11 and C-FOS activation were independent of one another. These data suggest key roles for Stk11 and Fos in CTA long-term memory formation, dependent at least partly through convergent action on BLApn intrinsic excitability.}, } @article {pmid32727819, year = {2020}, author = {Hurley, SW and Carelli, RM}, title = {Activation of Infralimbic to Nucleus Accumbens Shell Pathway Suppresses Conditioned Aversion in Male But Not Female Rats.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {40}, number = {36}, pages = {6888-6895}, pmid = {32727819}, issn = {1529-2401}, support = {F32 MH115653/MH/NIMH NIH HHS/United States ; R01 DA014339/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Aversive Agents ; *Conditioning, Classical ; Female ; Limbic System/*physiology ; Male ; Neural Pathways/physiology ; Nucleus Accumbens/*physiology ; Quinine ; Rats ; Rats, Sprague-Dawley ; Sex Factors ; *Taste Perception ; }, abstract = {Hedonic processing plays an integral role in directing appropriate behavior, but disrupted hedonic processing is associated with psychiatric disorders such as depression. The infralimbic cortex (IL) is a key structure in affective processing in rodents and activation of its human homolog, the ventromedial prefrontal cortex, has been implicated in suppressing aversive states. Here, we tested whether optogenetic activation of glutamatergic projections from the IL to the nucleus accumbens shell (NAcSh) suppresses the aversive impact of sucrose devalued using the conditioned taste aversion paradigm in males and female rats. In naive rats, no significant differences in appetitive or aversive taste reactivity (TR) to sucrose was observed indicating that initial sucrose palatability was equivalent across sex. However, we found that optical activation of the IL-NAcSh pathway during intraoral infusion of devalued sucrose inhibited aversive TR in male but not female rats. Interestingly, when allowed to freely ingest water and sucrose in a two-bottle test both males and females with a history of IL-NAcSh stimulation exhibited greater preference for sucrose. Optical pathway activation failed to alter TR to innately bitter quinine in either sex. Finally, both sexes lever pressed to self-stimulate the IL-NAcSh pathway. These results indicate that the IL-NAcSh pathway plays an important role in suppressing learned aversive states selectively in males but spares hedonic processing of innately aversive tastants. Further, pathway activation is reinforcing in both sexes, indicating that suppression of conditioned aversive TR can be dissociable from the effects of unconditioned rewarding properties of IL-NAcSh pathway activation.SIGNIFICANCE STATEMENT Negative emotional states contribute to psychiatric disorders including depression and substance use disorders. In this study, we examined whether brain circuitry previously implicated in suppressing negative emotional states in humans can inhibit learned aversion in male and female rats. We found that optical activation of the infralimbic to nucleus accumbens shell pathway attenuates learned aversive responses in male but not female rats, indicating an important sex difference in the function of this brain pathway. Furthermore, we found that pathway stimulation was reinforcing in both sexes. Collectively, these findings support the role of the infralimbic cortex and its projection to the nucleus accumbens shell in suppressing learned negative emotional states and highlight an important sex-specific function of this pathway.}, } @article {pmid32723372, year = {2020}, author = {Abe, K and Kuroda, M and Narumi, Y and Kobayashi, Y and Itohara, S and Furuichi, T and Sano, Y}, title = {Cortico-amygdala interaction determines the insular cortical neurons involved in taste memory retrieval.}, journal = {Molecular brain}, volume = {13}, number = {1}, pages = {107}, pmid = {32723372}, issn = {1756-6606}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/physiology ; Cerebral Cortex/*physiology ; Conditioning, Classical ; Learning ; Male ; Mental Recall/*physiology ; Mice, Inbred C57BL ; Nerve Net ; Neurons/*physiology ; Taste/*physiology ; }, abstract = {The insular cortex (IC) is the primary gustatory cortex, and it is a critical structure for encoding and retrieving the conditioned taste aversion (CTA) memory. In the CTA, consumption of an appetitive tastant is associated with aversive experience such as visceral malaise, which results in avoidance of consuming a learned tastant. Previously, we showed that levels of the cyclic-AMP-response-element-binding protein (CREB) determine the insular cortical neurons that proceed to encode a conditioned taste memory. In the amygdala and hippocampus, it is shown that CREB and neuronal activity regulate memory allocation and the neuronal mechanism that determines the specific neurons in a neural network that will store a given memory. However, cellular mechanism of memory allocation in the insular cortex is not fully understood. In the current study, we manipulated the neuronal activity in a subset of insular cortical and/or basolateral amygdala (BLA) neurons in mice, at the time of learning; for this purpose, we used an hM3Dq designer receptor exclusively activated by a designer drug system (DREADD). Subsequently, we examined whether the neuronal population whose activity is increased during learning, is reactivated by memory retrieval, using the expression of immediate early gene c-fos. When an hM3Dq receptor was activated only in a subset of IC neurons, c-fos expression following memory retrieval was not significantly observed in hM3Dq-positive neurons. Interestingly, the probability of c-fos expression in hM3Dq-positive IC neurons after retrieval was significantly increased when the IC and BLA were co-activated during conditioning. Our findings suggest that functional interactions between the IC and BLA regulates CTA memory allocation in the insular cortex, which shed light on understanding the mechanism of memory allocation regulated by interaction between relevant brain areas.}, } @article {pmid32712137, year = {2020}, author = {Angulo, R and Bustamante, J and Arévalo-Romero, CA}, title = {Age, sex and pre-exposure effects on acquisition and generalization of conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {394}, number = {}, pages = {112813}, doi = {10.1016/j.bbr.2020.112813}, pmid = {32712137}, issn = {1872-7549}, mesh = {Aging/*psychology ; Animals ; *Avoidance Learning ; Female ; *Generalization, Psychological ; Male ; Rats, Sprague-Dawley ; *Sex Characteristics ; Sex Factors ; *Taste ; }, abstract = {The main aim of the present study was to assess the effect of sex and aging in two pre-exposure learning effects, latent inhibition (LI) and perceptual learning (PL), with a conditioned taste aversion paradigm. Young adult (90 days) and aged (more than 18 months) males and females received 8 pre-exposure trials either with stimulus AX (LI conditions) or BX (PL conditions). Then, all animals received a conditioning trial with AX and two test trials, one with AX and other with BX. The level of generalization between AX and BX was assessed by means of the absolute level of consumption of BX and by the difference in consumption between both stimuli. The results showed an attenuation of latent inhibition as well a stronger generalization of conditioned taste aversion in females when generalization is inferred from the BX consumption. A facilitation of conditioning for the aged animals was also found regardless of the pre-exposed stimulus. Pre-exposures to BX resulted in little generalization, but pre-exposures to AX resulted in a very similar consumption of both compounds, indicating a strong generalization between them. Overall, the study provided novel evidence about the effect of sex and aging on taste aversion, raising at the same time some relevant questions about perceptual learning and how such pre-exposure effect has been typically assessed.}, } @article {pmid32681199, year = {2021}, author = {Miranda, MI and Rangel-Hernández, A and Vera-Rivera, G and Cortes, C and Eguibar, JR}, title = {Taste association capabilities differ in high- and low-yawning rats versus outbred Sprague-Dawley rats after prolonged sugar consumption.}, journal = {Animal cognition}, volume = {24}, number = {1}, pages = {41-52}, pmid = {32681199}, issn = {1435-9456}, mesh = {Animals ; Avoidance Learning ; Dietary Sugars ; Rats ; Rats, Sprague-Dawley ; Sugars ; *Taste ; *Yawning ; }, abstract = {Yawning is a stereotypical behavior pattern commonly associated with other behaviors such as grooming, sleepiness, and arousal. Several differences in behavioral and neurochemical characteristics have been described in high-yawning (HY) and low-yawning (LY) sublines from Sprague-Dawley (SD) rats that support they had changes in the neural mechanism between sublines. Differences in behavior and neurochemistry observed in yawning sublines could also overlap in processes needed during taste learning, particularly during conditioned taste aversion (CTA) and its latent inhibition. Therefore, the aim of this study was to analyze taste memory differences, after familiarization to novel or highly sweet stimuli, between yawning sublines and compare them with outbred SD rats. First, we evaluated changes in appetitive response during long-term sugar consumption for 14 days. Then, we evaluated the latent inhibition of CTA strength induced by this long pre-exposure, and we also measured aversive memory extinction rate. The results showed that SD rats and the two sublines developed similar CTA for novel sugar and significantly stronger appetitive memory after long-term sugar exposure. However, after 14 days of sugar exposure, HY and LY sublines were unable to develop latent inhibition of CTA after two acquisition trials and had a slower aversive memory extinction rate than outbreed rats. Thus, the inability of the HY and LY sublines to develop latent inhibition of CTA after long-term sugar exposure could be related to the time/context processes involved in long-term appetitive re-learning, and in the strong inbreeding that characterizes the behavioral traits of these sublines, suggesting that inbreeding affects associative learning, particularly after long-term exposure to sweet stimuli which reflects high familiarization.}, } @article {pmid32655385, year = {2020}, author = {Angulo, R and Bustamante, J and Estades, V and Ramírez, V and Jorquera, B}, title = {Sex Differences in Cue Competition Effects With a Conditioned Taste Aversion Preparation.}, journal = {Frontiers in behavioral neuroscience}, volume = {14}, number = {}, pages = {107}, pmid = {32655385}, issn = {1662-5153}, abstract = {This study aimed to test whether male and female rats might show differences in cue competition effects in a conditioned taste aversion (CTA) model. Experiment 1 tested for sex differences in overshadowing. After conditioning of a flavored compound AB or only one simple flavor A (being A and B a solution of sugar 10% and salt 1%, counterbalanced), consumption of the A solution at test was larger in the former than in the latter case only in males. Thus, the usual effect of overshadowing was observed in males but not in females. Experiment 2 examined sex differences in blocking with the same stimuli used in Experiment 1. After conditioning of AB, the consumption of B was larger for the animals that previously received a single conditioning trial with A than for those that received unpaired presentations of A and the illness. As observed in Experiment 1, the typical blocking effect appeared only in males but not in females. The present findings thus support the hypothesis that sex dimorphism might be expressed in classical conditioning, or at least, in cue competition effects such as overshadowing and blocking with a taste aversion model.}, } @article {pmid32652234, year = {2020}, author = {Lai, Y and Despouy, E and Sandoz, JC and Su, S and de Brito Sanchez, MG and Giurfa, M}, title = {Degradation of an appetitive olfactory memory via devaluation of sugar reward is mediated by 5-HT signaling in the honey bee.}, journal = {Neurobiology of learning and memory}, volume = {173}, number = {}, pages = {107278}, doi = {10.1016/j.nlm.2020.107278}, pmid = {32652234}, issn = {1095-9564}, mesh = {Animals ; Bees ; Memory/*drug effects/physiology ; *Odorants ; *Reward ; Serotonin/*metabolism ; Signal Transduction/*drug effects/physiology ; Sugars/pharmacology ; }, abstract = {Conditioned taste aversion (CTA) learning induces the devaluation of a preferred food through its pairing with a stimulus inducing internal illness. In invertebrates, it is still unclear how this aversive learning impairs the memories of stimuli that had been associated with the appetitive food prior to its devaluation. Here we studied this phenomenon in the honey bee and characterized its neural underpinnings. We first trained bees to associate an odorant (conditioned stimulus, CS) with appetitive fructose solution (unconditioned stimulus, US) using a Pavlovian olfactory conditioning. We then subjected the bees that learned the association to a CTA training during which the antennal taste of fructose solution was contingent or not to the ingestion of quinine solution, which induces malaise a few hours after ingestion. Only the group experiencing contingent fructose stimulation and quinine-based malaise exhibited a decrease in responses to the fructose and a concomitant decrease in odor-specific retention in tests performed 23 h after the original odor conditioning. Furthermore, injection of dopamine- and serotonin-receptor antagonists after CTA learning revealed that this long-term decrease was mediated by serotonergic signaling as its blockade rescued both the responses to fructose and the odor-specific memory 23 h after conditioning. The impairment of a prior CS memory by subsequent CTA conditioning confirms that bees retrieve a devaluated US representation when presented with the CS. Our findings further highlight the importance of serotonergic signaling in aversive learning in the bee and uncover mechanisms underlying aversive memories induced by internal illness in invertebrates.}, } @article {pmid32650432, year = {2020}, author = {Molero-Chamizo, A and Rivera-Urbina, GN}, title = {Taste Processing: Insights from Animal Models.}, journal = {Molecules (Basel, Switzerland)}, volume = {25}, number = {14}, pages = {}, pmid = {32650432}, issn = {1420-3049}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Psychological/*physiology ; Humans ; *Models, Neurological ; Olfactory Perception/*physiology ; Taste Perception/*physiology ; }, abstract = {Taste processing is an adaptive mechanism involving complex physiological, motivational and cognitive processes. Animal models have provided relevant data about the neuroanatomical and neurobiological components of taste processing. From these models, two important domains of taste responses are described in this review. The first part focuses on the neuroanatomical and neurophysiological bases of olfactory and taste processing. The second part describes the biological and behavioral characteristics of taste learning, with an emphasis on conditioned taste aversion as a key process for the survival and health of many species, including humans.}, } @article {pmid32604471, year = {2021}, author = {Blednov, YA and Da Costa, A and Mayfield, J and Harris, RA and Messing, RO}, title = {Deletion of Tlr3 reduces acute tolerance to alcohol and alcohol consumption in the intermittent access procedure in male mice.}, journal = {Addiction biology}, volume = {26}, number = {2}, pages = {e12932}, pmid = {32604471}, issn = {1369-1600}, support = {U24 AA025479/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Diazepam/pharmacology ; Drug Tolerance/*genetics ; Ethanol/*pharmacology ; Isoxazoles/pharmacology ; Male ; Mice ; Mice, Knockout ; Myeloid Differentiation Factor 88/*genetics ; Sex Factors ; Substance Withdrawal Syndrome ; Toll-Like Receptor 3/*genetics ; gamma-Aminobutyric Acid/drug effects ; }, abstract = {Pharmacological studies implicate toll-like receptor 3 (TLR3) signaling in alcohol drinking. We examined the role of TLR3 in behavioral responses to alcohol and GABAergic drugs by studying Tlr3 [-/-] mice. Because of opposing signaling between TLR3 and MyD88 pathways, we also evaluated Myd88 [-/-] mice. Ethanol consumption and preference decreased in male but not in female Tlr3 [-/-] mice during two-bottle choice every-other-day (2BC-EOD) drinking. There were no genotype differences in either sex during continuous or limited-access drinking. Null mutations in Tlr3 or Myd88 did not alter conditioned taste aversion to alcohol and had small or no effects on conditioned place preference. The Tlr3 null mutation did not alter acute alcohol withdrawal. Male, but not female, Tlr3 [-/-] mice took longer than wild-type littermates to recover from ataxia by ethanol or diazepam and longer to recover from sedative-hypnotic effects of ethanol or gaboxadol, indicating regulation of GABAergic signaling by TLR3. Acute functional tolerance (AFT) to alcohol-induced ataxia was decreased in Tlr3 [-/-] mice but was increased in Myd88 [-/-] mice. Thus, MyD88 and TLR3 pathways coordinately regulate alcohol consumption and tolerance to intoxicating doses of alcohol and GABAergic drugs. Despite similar alcohol metabolism and similar amounts of total alcohol consumed during 2BC and 2BC-EOD procedures in C57BL/6J mice, only 2BC-EOD drinking induced tolerance to alcohol-induced ataxia. Ataxia recovery was inversely correlated with level of drinking in wild-type and Tlr3 [-/-] littermates. Thus, deleting Tlr3 reduces alcohol consumption by reducing AFT to alcohol and not by altering tolerance induced by 2BC-EOD drinking.}, } @article {pmid32603778, year = {2020}, author = {Yamamura, T and Nakamura, F and Yasuo, T and Suwabe, T and Sako, N}, title = {Effect of the duration of a conditioned stimulus on component recognition in binary taste mixtures in rats.}, journal = {Journal of oral biosciences}, volume = {62}, number = {3}, pages = {267-271}, doi = {10.1016/j.job.2020.06.001}, pmid = {32603778}, issn = {1880-3865}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; Conditioning, Operant ; Conditioning, Psychological ; Rats ; *Taste ; }, abstract = {OBJECTIVES: The aim of this behavioral study was to investigate the duration of a conditioned stimulus (CS-duration) necessary for rats to recognize the components of a binary taste mixture in a conditioned taste aversion (CTA) paradigm as well as the relationship between CS-duration and their spontaneous recovery.

METHODS: The experimental rats were categorized under conditioned and control groups and further divided into three groups according to the CS-duration: 10, 30, and 60 s. As the test stimuli, a mixture of 100 mM sucrose (S) + 30 μM quinine hydrochloride (Q) and its components were used.

RESULTS: On day 1 of the CTA test, the number of licks (NL) for S + Q and S in all conditioned groups was significantly lower than that of the control group presented with CS for 60 s (CON-60), which was the representative control group determined by the initial CTA test. For Q, there was no significant difference between NL of the CTA group presented with CS for 10 s and that of CON-60; however, NL in the other two CTA groups, i.e., CTA-30 and CTA-60, was significantly lower than that of CON-60. When the rats were presented with a shorter CS-duration, they showed spontaneous recovery earlier depending on the CS-duration.

CONCLUSIONS: These results suggest that rats can recognize a binary taste mixture and its components using a CS-duration of more than 30 s and that spontaneous recovery from CTA learning depends on the CS- duration.}, } @article {pmid32602851, year = {2020}, author = {Molero-Chamizo, A and Rivera-Urbina, GN}, title = {Temporal specificity of latent inhibition in rats with daily water restriction prior to taste conditioning.}, journal = {Acta neurobiologiae experimentalis}, volume = {80}, number = {2}, pages = {99-107}, pmid = {32602851}, issn = {1689-0035}, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Psychological/*physiology ; *Inhibition, Psychological ; Male ; Memory/physiology ; Rats, Wistar ; Taste/*physiology ; *Water ; }, abstract = {Temporal specificity of latent inhibition of conditioned taste aversion (CTA) has been demonstrated after prolonged habituation to temporal contexts in the stages preceding conditioning, and it has been eliminated by restricting consumption during conditioning. However, it is not known if latent inhibition of CTA is still dependent on the temporal context when fluid consumption is limited in the stages prior to conditioning. We tested temporal specificity of latent inhibition in rats with (different time of day for the conditioning stage) and without (same time of day for pre-exposure and conditioning stages) temporal changes on the conditioning day. All animals had limited access to water in the morning sessions of the stages prior to the conditioning day and 15 min of free access to fluid in the evening sessions of these stages. Compared to animals without temporal changes between stages, animals with a different temporal context during conditioning did not show evidence of latent inhibition. Unlike the effects observed after taste stimulus restrictions during conditioning, these results suggest that the temporal specificity of latent inhibition of CTA is not abolished when access to water is limited in the stages preceding conditioning.}, } @article {pmid32565406, year = {2020}, author = {Hao, L and Kshatriya, D and Li, X and Badrinath, A and Szmacinski, Z and Goedken, MJ and Polunas, M and Bello, NT}, title = {Acute feeding suppression and toxicity of raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] in mice.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {143}, number = {}, pages = {111512}, pmid = {32565406}, issn = {1873-6351}, support = {R01 AT008933/AT/NCCIH NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Butanones/administration & dosage/*toxicity ; Feeding Behavior/*drug effects ; Female ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is used by the food and cosmetic industry as a flavoring agent. RK is also marketed as a dietary supplement for weight maintenance and appetite control. The purpose of the study was to characterize the acute feeding suppression with RK (64-640 mg/kg) by oral gavage in male and female C57BL/6J mice. Cumulative 24 h food intake was reduced at 200 mg/kg (24% feeding suppression) in males and reliably reduced at 640 mg/kg (49-77% feeding suppression). Feeding suppression was not associated with pica behavior over the range of doses or conditioned taste aversion. In a separate experiment, a single oral gavage of RK (640 mg/kg) resulted in approximate 43% mortality rate (6 out 14 male mice) within 2 days. Atrophy of white adipose tissue, splenic abnormalities, and thymus involution were noted after 2-4 days after oral gavage RK. Total white blood cell count, lymphocytes, monocytes, eosinophils were significantly lower, while mean red blood cells, hemoglobin, and hematocrit were significantly higher with RK treatment. Our findings indicated a dose-dependent feeding suppression with acute RK, but doses that reliable suppress food intake are associated with pathological changes.}, } @article {pmid32472169, year = {2020}, author = {Csikós, V and Varró, P and Bódi, V and Oláh, S and Világi, I and Dobolyi, A}, title = {The mycotoxin deoxynivalenol activates GABAergic neurons in the reward system and inhibits feeding and maternal behaviours.}, journal = {Archives of toxicology}, volume = {94}, number = {9}, pages = {3297-3313}, pmid = {32472169}, issn = {1432-0738}, mesh = {Animal Feed/microbiology ; Animals ; Feeding Behavior/*drug effects ; Food Contamination ; GABAergic Neurons/drug effects/*physiology ; Maternal Behavior/*drug effects ; Mice ; Mycotoxins/*toxicity ; Rats ; Trichothecenes/*toxicity ; }, abstract = {Deoxynivalenol (DON) or vomitoxin, is a trichothecene mycotoxin produced mainly by Fusarium graminearum and culmorum. Mycotoxins or secondary metabolic products of mold fungi are micro-pollutants, which may affect human and animal health. The neuronal and behavioural actions of DON were analysed in the present study. To address, which neurons can be affected by DON, the neuronal activation pattern following intraperitoneal injection of DON (1 mg/kg) was investigated in adult male rats and the results were confirmed in mice, too. DON-induced neuronal activation was assessed by c-Fos immunohistochemistry. DON injection resulted in profound c-Fos activation in only the elements of the reward system, such as the accumbens nucleus, the medial prefrontal cortex, and the ventral tegmental area. Further double labelling studies suggested that GABAergic neurons were activated by DON treatment. To study the behavioural relevance of this activation, we examined the effect of DON on feed intake as an example of reward-driven behaviours. Following DON injection, feed consumption was markedly reduced but returned to normal the following day suggesting an inhibitory action of DON on feed intake without forming taste-aversion. To further test how general the effect of DON on goal-directed behaviours is, its actions on maternal behaviour was also examined. Pup retrieval latencies were markedly increased by DON administration, and DON-treated mother rats spent less time with nursing suggesting reduced maternal motivation. In a supplementary control experiment, DON did not induce conditioned place preference arguing against its addictive or aversive actions. The results imply that acute uptake of the mycotoxin DON can influence the reward circuit of the brain and exert inhibitory actions on goal-directed, reward-driven behaviours. In addition, the results also suggest that DON exposure of mothers may have specific implications.}, } @article {pmid32407964, year = {2020}, author = {Huang, ACW and Yu, YH and He, ABH and Ou, CY}, title = {Interactions between prelimbic cortex and basolateral amygdala contribute to morphine-induced conditioned taste aversion in conditioning and extinction.}, journal = {Neurobiology of learning and memory}, volume = {172}, number = {}, pages = {107248}, doi = {10.1016/j.nlm.2020.107248}, pmid = {32407964}, issn = {1095-9564}, mesh = {Analgesics, Opioid/*administration & dosage ; Animals ; Basolateral Nuclear Complex/drug effects/*physiology ; Conditioning, Classical/*drug effects/*physiology ; Corticosterone/blood ; Extinction, Psychological/*drug effects/*physiology ; Male ; Morphine/*administration & dosage ; Neurons/drug effects/physiology ; Prefrontal Cortex/drug effects/*physiology ; Rats, Wistar ; Signal Transduction ; }, abstract = {The consequences of exciting or destroying the prelimbic cortex (PrL) or the basolateral amygdala (BLA) remain unclear, including the effects on morphine-induced conditioned taste aversion (CTA) in the conditioning and extinction phases, plasma corticosterone (CORT) levels, and c-Fos/p-ERK expressions in the subareas of the medial prefrontal cortex (i.e., PrL, infralimbic cortex [IL], cingulate cortex 1 [Cg1]), basolateral amygdala (BLA), central amygdala (CeA), hippocampus (i.e., CA1, CA2, CA3, and dentate gyrus [DG]), nucleus accumbens (NAc), lateral hypothalamus (LH), and piriform cortex (PC). During conditioning, excitation of the PrL glutamate neurons via NMDA injections disrupted morphine-induced CTA and decreased plasma CORT levels; moreover, c-Fos and p-ERK expression was hyperactive in the PrL and IL but hypoactive in the Cg1 and BLA. In conditioning, excitation of the BLA glutamate neurons via NMDA injections facilitated morphine-induced CTA and increased plasma CORT levels. The expression of c-Fos and p-ERK was hypoactive in the PrL and IL but hyperactive in the BLA. During extinction, lesion of the PrL glutamate neurons via NMDA injections impaired morphine-induced CTA extinction and enhanced plasma CORT levels. The expression of c-Fos and p-ERK was hypoactive in the PrL and IL but hyperactive in the BLA. In extinction, excitation of the PrL glutamatergic neurons via NMDA injections facilitated morphine-induced CTA extinction and did not affect plasma CORT levels; moreover, the expression of c-Fos and p-ERK was hypoactive in the Cg1, PrL, and IL but hyperactive in the BLA. Altogether, the interaction between the PrL and BLA plays a balancing role in morphine-induced CTA conditioning and extinction. During conditioning, the activity of the PrL correlated negatively with plasma CORT secretions, whereas the activity of the BLA correlated positively with the plasma CORT levels. During extinction, the activity of the PrL correlated negatively with plasma CORT secretions; however, the activity of the BLA may be negatively associated with the plasma CORT levels. The data presented here provide some implications for morphine addiction and dependence.}, } @article {pmid32385589, year = {2020}, author = {Nakai, J and Totani, Y and Kojima, S and Sakakibara, M and Ito, E}, title = {Features of behavioral changes underlying conditioned taste aversion in the pond snail Lymnaea stagnalis.}, journal = {Invertebrate neuroscience : IN}, volume = {20}, number = {2}, pages = {8}, doi = {10.1007/s10158-020-00241-7}, pmid = {32385589}, issn = {1439-1104}, mesh = {Animals ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Lymnaea/*physiology ; Memory Consolidation/*physiology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) in the freshwater pulmonate Lymnaea stagnalis can be formed by presenting ten pairings of sucrose as the conditioned stimulus (CS) and KCl as the unconditioned stimulus (US). The CTA is consolidated to long-term memory (LTM) lasting longer than a month. In the present study, we examined the time course of protein synthesis-dependent period during the consolidation of Lymnaea CTA to LTM by pharmacological inhibition of transcription or translation. The robustness for CTA-LTM was then examined by extinction trials, i.e., repeated presentations of the CS alone. Furthermore, we evaluated the effects of the interstimulus interval (ISI) between the presentation of the CS and US. Our findings indicated that the protein synthesis-dependent period coincides with the CTA training. Repeated presentations of the CS alone after establishment of CTA did not extinguish the CTA, demonstrating the robustness of the CTA-LTM. The ISI ranged from 10 s to a few minutes, and there was no inverted U-shaped function between the ISI and the conditioned response (i.e., suppression of feeding). Thus, CTA still formed even when the presentation of the US was delayed. These features of Lymnaea CTA complement the knowledge for mammalian CTA.}, } @article {pmid32378909, year = {2020}, author = {Steinfeld, MR and Bouton, ME}, title = {Context and renewal of habits and goal-directed actions after extinction.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {46}, number = {4}, pages = {408-421}, pmid = {32378909}, issn = {2329-8464}, support = {R01 DA033123/DA/NIDA NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Conditioning, Operant/*physiology ; Extinction, Psychological/*physiology ; Female ; *Goals ; *Habits ; Motor Activity/*physiology ; Psychomotor Performance/*physiology ; Rats, Wistar ; }, abstract = {Instrumental behaviors that are goal-directed actions after moderate amounts of training can become habits after more extended training. Little research has asked how actions and habits are affected by retroactive interference treatments like extinction. The present experiments begin to fill this gap in the literature. In Experiments 1a and 1b, lever pressing in rats was minimally trained (1a) or extensively trained (1b) in one context (Context A), extinguished in a second context (Context B), and then tested in the acquisition context (Context A). Exposure to both contexts was equated and controlled throughout, and the status of the behavior as action or habit was determined by reinforcer devaluation methods (taste aversion conditioning). Results confirmed that action (1a) and habit (1b) renewed with action or habit status, respectively, when they were returned to Context A. Experiments 2a and 2b then similarly tested action and habit after extinction in an ABC renewal paradigm. Here, lever pressing that was trained in Context A and extinguished in Context B renewed as action in Context C regardless of whether it had been an action or habit before extinction. The apparent conversion of habit to action during renewal testing in Context C was consistent with other results suggesting that habits converted to action when the context was changed at the start of extinction. Together, the results suggest that extinction in a second context inhibits instrumental behaviors trained as either actions or habits in a context-specific manner. They also expand on prior findings suggesting that actions transfer across contexts, and that habits do not. A change of context may be sufficient to convert a habit to goal-directed action. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32316692, year = {2020}, author = {Keating, AV and Soto, J and Forbes, C and Zhao, M and Craig, DQM and Tuleu, C}, title = {Multi-Methodological Quantitative Taste Assessment of Anti-Tuberculosis Drugs to Support the Development of Palatable Paediatric Dosage Forms.}, journal = {Pharmaceutics}, volume = {12}, number = {4}, pages = {}, pmid = {32316692}, issn = {1999-4923}, abstract = {The unpalatability of antituberculosis drugs is often cited as a major cause of non-adherence in children, yet limited quantitative taste assessment data are available. The aim of this research was to quantify the bitterness of isoniazid, rifampicin, pyrazinamide, and ethambutol dihydrochloride using two in vivo (a human taste panel and a rat brief-access taste aversion (BATA) model) and one in vitro (sensor) method. The response of the Insent TS-5000Z electronic tongue was compared to the in vivo drug concentration found to elicit and suppress half the maximum taste response (EC50 in human and IC50 in rats). Using dose-relevant concentrations, an overarching rank order of bitterness was derived (rifampicin > ethambutol > pyrazinamid~isoniazid). In vitro, only ethambutol exhibited a linear response for all sensors/concentrations. Based on the EC50/IC50 generated, a 'taste index' was proposed to allow for anticipation of the likelihood of taste issues in practice, taking in account the saturability in the saliva and therapeutic doses; ethambutol and isoniazid were found to be the worst tasting using this measure. The study presents the first quantitative taste analysis of these life-saving drugs and has allowed for a comparison of three methods of obtaining such data. Such information allows the operator to identify and prioritise the drugs requiring taste masking to produce palatable formulations.}, } @article {pmid32315693, year = {2020}, author = {Sandoval-Sánchez, AR and Cedillo Zavaleta, LN and Jiménez, JC and Ruíz-García, I and Miranda, F}, title = {Administration of low doses of the 5-HT1A receptor agonist 8-OH-DPAT attenuates the discriminative signal of amphetamine in the conditioned taste aversion procedure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {193}, number = {}, pages = {172932}, doi = {10.1016/j.pbb.2020.172932}, pmid = {32315693}, issn = {1873-5177}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/*administration & dosage ; Amphetamine/*administration & dosage ; Animals ; Aversive Agents/*administration & dosage ; Central Nervous System Stimulants/*administration & dosage ; Dopamine/metabolism ; Extracellular Space/metabolism ; Male ; Microdialysis ; Nucleus Accumbens/metabolism ; Raphe Nuclei/metabolism ; Rats ; Rats, Wistar ; Receptor, Serotonin, 5-HT1A ; Receptors, Presynaptic/metabolism ; Serotonin 5-HT1 Receptor Agonists/*administration & dosage ; Serotonin 5-HT1 Receptor Antagonists/administration & dosage ; Signal Transduction/drug effects ; Taste/*drug effects ; Ventral Tegmental Area/metabolism ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {Several studies have reported that low doses of the 5-HT1A receptor agonist 8-OH-DPAT reduce cocaine-induced locomotor activity. However, it has also been reported that high doses of 8-OH-DPAT do not substitute for or alter the discriminative signal of cocaine (COC) or amphetamine (AMPH). This study aimed to evaluate the effects of low and high doses of the 5-HT1A agonist 8-OH-DPAT on the discriminative signal of AMPH using conditioned taste aversion as a drug discrimination procedure. Additionally, to establish a correlation between the behavioral effects in drug discrimination and changes in dopamine (DA) and gamma-aminobutyric acid (GABA) concentrations, we evaluated the effect of systemic administration of low or high doses of the 5-HT1A receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist WAY100135 on DA and GABA extracellular concentrations in the nucleus accumbens (nAcc) and ventral tegmental area (VTA), respectively, using cerebral microdialysis. The behavioral results showed that low but not high doses of 8-OH-DPAT produced a reduction in the AMPH-induced discriminative signal, while WAY100135 administration prevented such effects. The microdialysis results showed that a low dose of 8-OH-DPAT decreased extracellular DA concentrations in the nAcc and increased GABA concentrations in the VTA. Pretreatment with WAY100135 prevented these effects. These data support the hypothesis that 5-HT1A receptors modulate the behavioral effects of psychostimulant drugs, such as AMPH, through somatodendritic 5-HT1A autoreceptors in the raphe nucleus indicating that 5-HT1A receptors may be an important target for the development of pharmacological treatments for psychostimulant addiction.}, } @article {pmid32297780, year = {2020}, author = {Nakajima, S}, title = {Effect of pretrial running on running-based taste aversion learning in rats.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {46}, number = {3}, pages = {273-285}, doi = {10.1037/xan0000243}, pmid = {32297780}, issn = {2329-8464}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Male ; Rats ; Rats, Wistar ; Running/*physiology ; Taste Perception/*physiology ; }, abstract = {Voluntary wheel running works as an effective unconditioned stimulus (US) to establish conditioned taste aversion (CTA) in rats with a preceding taste solution as a conditioned stimulus (CS): repeated CS-US pairings evoke avoidance of the CS in the two-choice (CS vs. tap water) test administered at the end of the training. Experiment 1 demonstrated that exposure to running immediately before each CS-US trial alleviates CTA. Subsequent two experiments explored the characteristics of the proximal US-preexposure effect: the alleviation of CTA by the pretrial running was not affected by changing the background contexts between the pretrial and the trial running (Experiment 2) or by signaling the pretrial running via another taste cue (Experiment 3). These results indicate the robustness of the proximal US-preexposure effect and fit well with the predictions of Wagner's (1976, 1978) priming theory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32291265, year = {2020}, author = {Totani, Y and Nakai, J and Dyakonova, VE and Lukowiak, K and Sakakibara, M and Ito, E}, title = {Induction of LTM following an Insulin Injection.}, journal = {eNeuro}, volume = {7}, number = {2}, pages = {}, pmid = {32291265}, issn = {2373-2822}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Operant ; *Insulin ; Lymnaea ; Memory, Long-Term ; Taste ; }, abstract = {The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). One-day food-deprived snails (day 1 snails) show the best CTA learning and memory, whereas more severely food-deprived snails (5 d) do not express good memory. However, previous studies showed that CTA-LTM was indeed formed in 5-d food-deprived snails (day 5 snails), but its recall was prevented by the effects of food deprivation. CTA-LTM recall in day 5 snails was expressed following 7 d of feeding and then 1 d of food deprivation (day 13 snails). In the present study, we thus hypothesized that memory recall occurs because day 13 snails are in an optimal internal state. One day of food deprivation before the memory test in day 13 snails increased the mRNA level of molluscan insulin-related peptide (MIP) in the CNS. Thus, we further hypothesized that an injection of insulin into day 5 snails following seven additional days with access to food (day 12 snails) activates CTA neurons and mimics the food deprivation state before the memory test in day 13 snails. Day 12 snails injected with insulin could recall the memory. In addition, the simultaneous injection of an anti-insulin receptor antibody and insulin into day 12 snails did not allow memory recall. Insulin injection also decreased the hemolymph glucose concentration. Together, the results suggest that an optimal internal state (i.e., a spike in insulin release and specific glucose levels) are necessary for LTM recall following CTA training in snails.}, } @article {pmid32179656, year = {2020}, author = {Amaya, KA and Stott, JJ and Smith, KS}, title = {Sign-tracking behavior is sensitive to outcome devaluation in a devaluation context-dependent manner: implications for analyzing habitual behavior.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {27}, number = {4}, pages = {136-149}, pmid = {32179656}, issn = {1549-5485}, support = {F99 NS115270/NS/NINDS NIH HHS/United States ; R01 DA044199/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Conditioning, Operant/physiology ; Cues ; *Habits ; Male ; Motivation/*physiology ; Rats ; Rats, Long-Evans ; Reinforcement, Psychology ; *Reward ; Taste Perception/physiology ; }, abstract = {Motivationally attractive cues can draw in behavior in a phenomenon termed incentive salience. Incentive cue attraction is an important model for animal models of drug seeking and relapse. One question of interest is the extent to which the pursuit of motivationally attractive cues is related to the value of the paired outcome or can become unrelated and habitual. We studied this question using a sign-tracking (ST) paradigm in rats, in which a lever stimulus preceding food reward comes to elicit conditioned lever-interaction behavior. We asked whether reinforcer devaluation by means of conditioned taste aversion, a classic test of habitual behavior, can modify ST to incentive cues, and whether this depends upon the manner in which reinforcer devaluation takes place. In contrast to several recent reports, we conclude that ST is indeed sensitive to reinforcer devaluation. However, this effect depends critically upon the congruence between the context in which taste aversion is learned and the context in which it is tested. When the taste aversion successfully transfers to the testing context, outcome value strongly influences ST behavior, both when the outcome is withheld (in extinction) and when animals can learn from outcome feedback (reacquisition). When taste aversion does not transfer to the testing context, ST remains high. In total, the extent to which ST persists after outcome devaluation is closely related to the extent to which that outcome is truly devalued in the task context. We believe this effect of context on devaluation can reconcile contradictory findings about the flexibility/inflexibility of ST. We discuss this literature and relate our findings to the study of habits generally.}, } @article {pmid32165443, year = {2020}, author = {Xu, LH and Yang, Y and Liu, HX and Xiao, SF and Qiu, WX and Wang, JX and Zhao, CC and Gui, YH and Liu, GZ and Peng, B and Li, X and Wang, GH and Zhou, X and Jiang, ZL}, title = {Inner Ear Arginine Vasopressin-Vasopressin Receptor 2-Aquaporin 2 Signaling Pathway Is Involved in the Induction of Motion Sickness.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {373}, number = {2}, pages = {248-260}, doi = {10.1124/jpet.119.264390}, pmid = {32165443}, issn = {1521-0103}, mesh = {Animals ; Antidiuretic Hormone Receptor Antagonists/therapeutic use ; Aquaporin 2/*physiology ; Arginine Vasopressin/blood/*physiology ; Benzazepines/therapeutic use ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Dogs ; Ear, Inner/*physiology ; Female ; Male ; Motion Sickness/drug therapy/*etiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Vasopressin/*physiology ; Signal Transduction/physiology ; }, abstract = {It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.}, } @article {pmid32032742, year = {2020}, author = {László, BR and Hormay, E and Szabó, I and Mintál, K and Nagy, B and László, K and Péczely, L and Ollmann, T and Lénárd, L and Karádi, Z}, title = {Disturbance of taste reactivity and other behavioral alterations after bilateral interleukin-1β microinjection into the cingulate cortex of the rat.}, journal = {Behavioural brain research}, volume = {383}, number = {}, pages = {112537}, doi = {10.1016/j.bbr.2020.112537}, pmid = {32032742}, issn = {1872-7549}, mesh = {Animals ; Behavior, Animal/*drug effects ; Conditioning, Psychological ; Drinking/drug effects ; Drinking Behavior/*drug effects ; Eating/drug effects ; Exploratory Behavior/drug effects ; Feeding Behavior/*drug effects ; *Gyrus Cinguli ; Interleukin-1beta/*pharmacology ; Locomotion/drug effects ; Microinjections ; Motivation ; Rats ; Taste Perception/*drug effects ; }, abstract = {The anterior cingulate cortex (ACC), is known to be intimately involved in food-related motivational processes and their behavioral organization, primarily by evaluating hedonic properties of the relevant stimuli. In the present study, the involvement of cingulate cortical interleukin-1β (IL-1β) mediated mechanisms in a) gustation associated facial and somato-motor behavioral patterns of Wistar rats were examined in taste reactivity test (TR). In addition, b) conditioned taste aversion (CTA) paradigm was performed to investigate the role of these cytokine mechanisms in taste sensation associated learning processes, c) the general locomotor activity of the animals was observed in open field test (OPF), and d) the potentially negative reinforcing effect of IL-1β was examined in conditioned place preference test (CPP). During the TR test, species specific behavioral patterns in response to the five basic tastes were analyzed. Response rates of ingestive and aversive patterns of the cytokine treated and the control groups differed significantly in case of the weaker bitter (QHCl, 0.03 mM), and the stronger umami (MSG, 0.5 M) tastes. IL-1β itself did not elicit CTA, it did not interfere with the acquisition of LiCl induced CTA, and it also failed to cause place preference or aversion in the CPP test. In the OPF paradigm, however, significant differences were found between the cytokine treated and the control groups in the rearing and grooming, the number of crossings, and in the distance moved. Our results indicate the involvement of cingulate cortical IL-1β mechanisms in the control of taste perception and other relevant behavioral processes.}, } @article {pmid31990947, year = {2020}, author = {Chia, J and Scott, K}, title = {Activation of specific mushroom body output neurons inhibits proboscis extension and sucrose consumption.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0223034}, pmid = {31990947}, issn = {1932-6203}, support = {R01 DC013280/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/physiology ; Avoidance Learning/*physiology ; Dendrites/physiology ; Drosophila/physiology ; Light ; Mushroom Bodies/*physiology ; Neurons/drug effects/*metabolism/physiology ; Odorants/analysis ; Smell/physiology ; Sucrose/*metabolism ; Taste/physiology ; }, abstract = {The ability to modify behavior based on prior experience is essential to an animal's survival. For example, animals may become attracted to a previously neutral odor or reject a previously appetitive food source based on previous encounters. In Drosophila, the mushroom bodies (MBs) are critical for olfactory associative learning and conditioned taste aversion, but how the output of the MBs affects specific behavioral responses is unresolved. In conditioned taste aversion, Drosophila shows a specific behavioral change upon learning: proboscis extension to sugar is reduced after a sugar stimulus is paired with an aversive stimulus. While studies have identified MB output neurons (MBONs) that drive approach or avoidance behavior, whether the same MBONs impact innate proboscis extension behavior is unknown. Here, we tested the role of MB pathways in altering proboscis extension and identified MBONs that synapse onto multiple MB compartments that upon activation significantly decreased proboscis extension to sugar. Activating several of these lines also decreased sugar consumption, revealing that these MBONs have a general role in modifying feeding behavior beyond proboscis extension. The MBONs that decreased proboscis extension and ingestion are different from those that drive avoidance behavior in another context. These studies provide insight into how activation of MB output neurons decreases proboscis extension to taste compounds.}, } @article {pmid31980843, year = {2020}, author = {Derman, RC and Bass, CE and Ferrario, CR}, title = {Effects of hM4Di activation in CamKII basolateral amygdala neurons and CNO treatment on sensory-specific vs. general PIT: refining PIT circuits and considerations for using CNO.}, journal = {Psychopharmacology}, volume = {237}, number = {5}, pages = {1249-1266}, pmid = {31980843}, issn = {1432-2072}, support = {R21DA043190/DA/NIDA NIH HHS/United States ; R01DK115526/DK/NIDDK NIH HHS/United States ; R01 DK115526/DK/NIDDK NIH HHS/United States ; F31 DK111194/DK/NIDDK NIH HHS/United States ; R01DK106188/DK/NIDDK NIH HHS/United States ; R01 DK106188/DK/NIDDK NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; R21 DA043190/DA/NIDA NIH HHS/United States ; 1F31-DK111194-01/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basolateral Nuclear Complex/drug effects/*metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism ; Clozapine/administration & dosage/*analogs & derivatives ; Conditioning, Classical/drug effects/*physiology ; Feeding Behavior/drug effects/physiology/psychology ; Female ; Male ; Motivation/drug effects/physiology ; Neurons/drug effects/*metabolism ; Piperazines/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Pavlovian stimuli can influence instrumental behaviors via phenomena such as Pavlovian-to-instrumental transfer (PIT). PIT arises via dissociable processes as sensory-specific PIT (SS-PIT) and general PIT. The basolateral amygdala (BLA) mediates SS-PIT, but not general PIT. However, the specific BLA neuronal populations involved are unknown.

AIMS: To determine the contribution of glutamatergic BLA neurons to the expression of SS-PIT and to the recall of sensory-specific properties of stimulus-outcome associations.

METHODS: BLA neurons were transduced with virus containing either GFP or hM4Di, driven by the CamKII promoter. Rats were then tested for SS and general PIT and subsequently for expression of Pavlovian outcome devaluation effects and conditioned taste aversion following injections of vehicle or clozapine-N-oxide (CNO, the hM4Di agonist).

RESULTS: CNO selectively blocked SS-PIT in the hM4Di-expressing group, but not controls, without altering expression of Pavlovian outcome devaluation or sensory-specific taste aversion in either group. Unexpectedly, CNO disrupted general PIT in both groups.

CONCLUSIONS: CamKII BLA neurons mediate the expression of SS-PIT by enabling Pavlovian stimuli to trigger recall of the correct action-outcome associations rather than by mediating recall of the sensory-specific properties of the stimulus-outcome association. Separately, our data demonstrate that CNO alone is sufficient to disrupt affective, but not sensory-specific processes, an effect that was not due to generalized motor disruption. This non-specific effect on general PIT may be related to CNO-induced shifts in internal state. Together, these data identify BLA CamKII neurons as critical for the expression of SS-PIT and reveal important considerations for using CNO to study general affective motivation.}, } @article {pmid31933521, year = {2019}, author = {Liu, DW and Ma, L and Zhang, XH and Wang, YY}, title = {Conditioned taste aversion memory extinction temporally induces insular cortical BDNF release and inhibits neuronal apoptosis.}, journal = {Neuropsychiatric disease and treatment}, volume = {15}, number = {}, pages = {2403-2414}, pmid = {31933521}, issn = {1176-6328}, abstract = {BACKGROUND: Memory extinction has been reported to be related to psychiatric disorders, such as post-traumatic stress disorder (PTSD). Secretion and synthesis of brain-derived neurotrophic factor (BDNF) have been shown to temporally regulate various memory processes via activation of tropomyosin-related kinase B (TrkB) receptors. However, whether memory extinction induces the synthesis and secretion of BDNF on the basis of its localization is not understood. In this study, we aim to investigate activity-dependent BDNF secretion and synthesis in the insular cortex (IC) in the setting of conditioned taste aversion (CTA) memory extinction.

MATERIALS AND METHODS: Rats were subjected to CTA memory extinction and BDNF antibody (or the equal volume of vehicle) was microinjected into the IC immediately after the extinction testing. Real-time polymerase chain reaction and in situ hybridization were used to detect the gene expression of BDNF, NGF and NT4. The protein levels of BDNF were determined through the enzyme-linked immunosorbent assay. In addition, the levels of phosphorylated TrkB normalized to total TrkB were evaluated using immunoprecipitation and immunoblotting. c-Fos, total extracellular signal-regulated kinase (Erk), phosphorylated Erk, and apoptosis-related protein (caspase-3), were detected by Western blotting.

RESULTS: We found that blocking BDNF signaling within the IC disrupts CTA extinction, suggesting that BDNF signaling in the IC is necessary for CTA extinction. Increased expression levels of c-Fos indicate the induced neuronal activity in the IC during CTA extinction. In addition, temporal changes in the gene expression and protein levels of BDNF in the IC were noted during extinction. Moreover, we found that phosphorylation of TrkB increased prior to the enhanced BDNF expression, suggesting that CTA extinction induces rapid activity-dependent BDNF secretion in the IC. Finally, we found decreased expression of caspase-3 in the IC after CTA extinction.

CONCLUSION: These results demonstrate that CTA memory extinction temporally induces the release and synthesis of BDNF in the IC and inhibits neuronal apoptosis.}, } @article {pmid31927082, year = {2020}, author = {Bouton, ME and Broomer, MC and Rey, CN and Thrailkill, EA}, title = {Unexpected food outcomes can return a habit to goal-directed action.}, journal = {Neurobiology of learning and memory}, volume = {169}, number = {}, pages = {107163}, pmid = {31927082}, issn = {1095-9564}, support = {R01 DA033123/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; *Conditioning, Operant ; Extinction, Psychological ; Female ; *Goals ; *Habits ; Rats, Wistar ; *Reinforcement, Psychology ; }, abstract = {Three experiments examined the return of a habitual instrumental response to the status of goal-directed action. In all experiments, rats received extensive training in which lever pressing was reinforced with food pellets on a random-interval schedule of reinforcement. In Experiment 1, the extensively-trained response was not affected by conditioning a taste aversion to the reinforcer, and was therefore considered a habit. However, if the response had earned a new and unexpected food pellet during the final training session, the response was affected by taste aversion conditioning to the (first) reinforcer, and had thus been converted to a goal-directed action. In Experiment 3, 30 min of prefeeding with an irrelevant food pellet immediately before the test also converted a habit back to action, as judged by the taste-aversion devaluation method. That result was consistent with difficulty in finding evidence of habit with the sensory-specific satiety method after extensive instrumental training (Experiment 2). The results suggest that an instrumental behavior's status as a habit is not permanent, and that a habit can be returned to action status by associating it with a surprising reinforcer (Experiment 1) or by giving the animal an unexpected prefeeding immediately prior to the action/habit test (Experiment 3).}, } @article {pmid31927081, year = {2020}, author = {Trask, S and Shipman, ML and Green, JT and Bouton, ME}, title = {Some factors that restore goal-direction to a habitual behavior.}, journal = {Neurobiology of learning and memory}, volume = {169}, number = {}, pages = {107161}, pmid = {31927081}, issn = {1095-9564}, support = {R01 DA033123/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; *Conditioning, Operant ; *Goals ; *Habits ; Male ; Rats, Wistar ; *Reinforcement, Psychology ; }, abstract = {Recent findings from our laboratory suggest that an extensively-practiced instrumental behavior can appear to be a goal-directed action (rather than a habit) when a second behavior is added and reinforced during intermixed final sessions (Shipman et al., 2018). The present experiments were designed to explore and understand this finding. All used the taste aversion method of devaluing the reinforcer to distinguish between goal-directed actions and habits. Experiment 1 confirmed that reinforcing a second response in a separate context (but not mere exposure to that context) can return an extensively-trained habit to the status of goal-directed action. Experiment 2 showed that training of the second response needs to be intermixed with training of the first response to produce this effect; training the second response after the first-response training was complete preserved the first response as a habit. Experiment 3 demonstrated that reinforcing the second response with a different reinforcer breaks the habit status of the first response. Experiment 4 found that free reinforcers (that were not response-contingent) were sufficient to restore goal-directed performance. Together, the results suggest that unexpected reinforcer delivery can render a habitual response goal-directed again.}, } @article {pmid31882185, year = {2020}, author = {Alapin, JM and Dines, M and Lamprecht, R}, title = {EphB2 receptor forward signaling is needed for normal long-term memory formation in aged mice.}, journal = {Neurobiology of aging}, volume = {86}, number = {}, pages = {11-15}, doi = {10.1016/j.neurobiolaging.2019.10.019}, pmid = {31882185}, issn = {1558-1497}, mesh = {Animals ; Healthy Aging/*psychology ; Male ; Memory, Long-Term/*physiology ; Mice, Inbred C57BL ; Receptor, EphB2/*metabolism/*physiology ; Signal Transduction/*physiology ; Taste Perception/physiology ; }, abstract = {The molecular mechanisms underpinning age-related changes in the ability to form long-term memory need to be clarified. EphB2 receptors and their ephrin ligands are involved in key cellular functions such as neuronal morphogenesis and synaptic transmission believed to be involved in long-term memory formation. We were therefore interested to explore whether EphB2 is involved in the alterations in memory formation abilities observed in old age. Toward that end, we examined the ability to form long-term memory in mice that lack EphB2 (EphB2[-/-]). A previous study has shown that the ability to form long-term conditioned taste aversion (CTA) memory in young EphB2[-/-] mice remains intact. In the present study, we report that long-term CTA memory formation is improved in old wild-type mice but not in age-matched old EphB2[-/-] mice. To further explore EphB2 mechanisms responsible for this difference in memory formation ability, we examined CTA memory in EphB2[lacZ/lacZ] mice devoid of EphB2 forward signaling. We found that the ability to create CTA long-term memory is unaffected in young EphB2[lacZ/lacZ] mice. However, the ability to form an increased long-term CTA memory shown in old wild-type mice is impaired in old EphB2[lacZ/lacZ] mice. The inability to form enhanced CTA long-term memory in EphB2[-/-] and EphB2[lacZ/lacZ] old mice was not caused by differences in taste perception or ability to consume fluids. Thus, our observations show that the absence of EphB2 forward signaling in old mice impairs the ability to form enhanced long-term CTA memory and indicate that EphB2 forward signaling is needed for normal memory formation in aged mice.}, } @article {pmid31829643, year = {2020}, author = {Keefer, SE and Petrovich, GD}, title = {The basolateral amygdala-medial prefrontal cortex circuitry regulates behavioral flexibility during appetitive reversal learning.}, journal = {Behavioral neuroscience}, volume = {134}, number = {1}, pages = {34-44}, pmid = {31829643}, issn = {1939-0084}, support = {R01 DK085721/DK/NIDDK NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Animals ; Basolateral Nuclear Complex/metabolism/*physiology ; Behavior, Animal/physiology ; Brain/physiology ; Conditioning, Classical/physiology ; Cues ; Extinction, Psychological/physiology ; Male ; Memory/physiology ; Neural Pathways/physiology ; Prefrontal Cortex/metabolism/*physiology ; Rats ; Rats, Long-Evans ; Reinforcement, Psychology ; Reversal Learning/*physiology ; }, abstract = {Environmental cues can become predictors of food availability through Pavlovian conditioning. Two forebrain regions important in this associative learning are the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). Recent work showed the BLA-mPFC pathway is activated when a cue reliably signals food, suggesting the BLA informs the mPFC of the cue's value. The current study tested this hypothesis by altering the value of 2 food cues using reversal learning and illness-induced devaluation paradigms. Rats that received unilateral excitotoxic lesions of the BLA and mPFC contralaterally placed, along with ipsilateral and sham controls, underwent discriminative conditioning, followed by reversal learning and then devaluation. All groups successfully discriminated between 2 auditory stimuli that were followed by food delivery (conditional stimulus [CS] +) or not rewarded (CS-), demonstrating this learning does not require BLA-mPFC communication. When the outcomes of the stimuli were reversed, the rats with disconnected BLA-mPFC (contralateral condition) showed increased responding to the CSs, especially to the rCS + (original CS-) during the first session, suggesting impaired cue memory recall and behavioral inhibition compared to the other groups. For devaluation, all groups successfully learned conditioned taste aversion; however, there was no evidence of cue devaluation or differences between groups. Interestingly, at the end of testing, the nondevalued contralateral group was still responding more to the original CS + (rCS-) compared to the devalued contralateral group. These results suggest a potential role for BLA-mPFC communication in guiding appropriate responding during periods of behavioral flexibility when the outcomes, and thus the values, of learned cues are altered. (PsycINFO Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid31744862, year = {2020}, author = {Torruella-Suárez, ML and Vandenberg, JR and Cogan, ES and Tipton, GJ and Teklezghi, A and Dange, K and Patel, GK and McHenry, JA and Hardaway, JA and Kantak, PA and Crowley, NA and DiBerto, JF and Faccidomo, SP and Hodge, CW and Stuber, GD and McElligott, ZA}, title = {Manipulations of Central Amygdala Neurotensin Neurons Alter the Consumption of Ethanol and Sweet Fluids in Mice.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {40}, number = {3}, pages = {632-647}, pmid = {31744862}, issn = {1529-2401}, support = {K01 AA023555/AA/NIAAA NIH HHS/United States ; U01 AA020911/AA/NIAAA NIH HHS/United States ; K01 DK115902/DK/NIDDK NIH HHS/United States ; P60 AA011605/AA/NIAAA NIH HHS/United States ; U24 AA025475/AA/NIAAA NIH HHS/United States ; F31 AA026183/AA/NIAAA NIH HHS/United States ; R00 MH115165/MH/NIMH NIH HHS/United States ; T32 NS007431/NS/NINDS NIH HHS/United States ; T32 MH093315/MH/NIMH NIH HHS/United States ; K99 MH115165/MH/NIMH NIH HHS/United States ; R37 AA014983/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*psychology ; Animals ; Anxiety/psychology ; Central Amygdaloid Nucleus/cytology/*physiology ; Food Preferences/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/physiology ; Neural Pathways/cytology/physiology ; Neurons/*physiology ; Neurotensin/*physiology ; Optogenetics ; Parabrachial Nucleus/cytology/physiology ; Patch-Clamp Techniques ; Reward ; Sweetening Agents ; Taste/physiology ; }, abstract = {The central nucleus of the amygdala plays a significant role in alcohol use and other affective disorders; however, the genetically-defined neuronal subtypes and projections that govern these behaviors are not well known. Here we show that neurotensin neurons in the central nucleus of the amygdala of male mice are activated by in vivo ethanol consumption and that genetic ablation of these neurons decreases ethanol consumption and preference in non-ethanol-dependent animals. This ablation did not impact preference for sucrose, saccharin, or quinine. We found that the most robust projection of the central amygdala neurotensin neurons was to the parabrachial nucleus, a brain region known to be important in feeding behaviors, conditioned taste aversion, and alarm. Optogenetic stimulation of projections from these neurons to the parabrachial nucleus is reinforcing, and increases ethanol drinking as well as consumption of sucrose and saccharin solutions. These data suggest that this central amygdala to parabrachial nucleus projection influences the expression of reward-related phenotypes and is a novel circuit promoting consumption of ethanol and palatable fluids.SIGNIFICANCE STATEMENT Alcohol use disorder (AUD) is a major health burden worldwide. Although ethanol consumption is required for the development of AUD, much remains unknown regarding the underlying neural circuits that govern initial ethanol intake. Here we show that ablation of a population of neurotensin-expressing neurons in the central amygdala decreases intake of and preference for ethanol in non-dependent animals, whereas the projection of these neurons to the parabrachial nucleus promotes consumption of ethanol as well as other palatable fluids.}, } @article {pmid31733301, year = {2020}, author = {Basu, S and Alapin, JM and Dines, M and Lamprecht, R}, title = {Long-term memory is maintained by continuous activity of Arp2/3 in lateral amygdala.}, journal = {Neurobiology of learning and memory}, volume = {167}, number = {}, pages = {107115}, doi = {10.1016/j.nlm.2019.107115}, pmid = {31733301}, issn = {1095-9564}, mesh = {Actin-Related Protein 2-3 Complex/antagonists & inhibitors/*physiology ; Animals ; Basolateral Nuclear Complex/drug effects/*physiology ; Conditioning, Classical/drug effects/physiology ; Fear ; Indoles/administration & dosage ; Male ; Memory, Long-Term/drug effects/*physiology ; Rats, Sprague-Dawley ; }, abstract = {Evidence indicates that long-term memory formation involves alterations in synaptic efficacy produced by modifications in neural transmission and morphology. However, it is not clear how such changes induced by learning, that encode memory, are maintained over long period of time to preserve long-term memory. It has been shown that the actin nucleating protein Arp2/3 is essential for supporting neuronal morphology and synaptic transmission. We therefore hypothesized that continuous Arp2/3 activity is needed to maintain long-term memory over time. To test this hypothesis we microinjected into lateral amygdala (LA) of rats CK-666, a specific inhibitor of Arp2/3, two days after fear conditioning and tested the effect on long-term fear memory maintenance a day afterward. We found that injection of CK-666 two days after training abolished fear conditioning memory. Fear conditioning could be formed when a control compound CK-689 was applied two days after training. Microinjection of CK-666 a day before fear conditioning training had no effect on fear conditioning learning and long-term memory formation. We revealed that Arp2/3 is also needed to maintain long-term conditioned taste aversion (CTA) memory in LA. Microinjection of CK-666 two days after CTA training impaired long-term memory tested a day afterwards. We conclude that continuous activity of Arp2/3 in LA is essential for the maintenance of long-term memory.}, } @article {pmid31726218, year = {2020}, author = {Ali, J and Chiang, M and Lee, JB and Voronin, GO and Bennett, J and Cram, A and Kagan, L and Garnett, MC and Roberts, CJ and Gershkovich, P}, title = {Is rat a good model for assessment of particulate-based taste-masked formulations?.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {146}, number = {}, pages = {1-9}, doi = {10.1016/j.ejpb.2019.11.001}, pmid = {31726218}, issn = {1873-3441}, mesh = {Administration, Oral ; Animals ; Aversive Agents/administration & dosage ; Chemistry, Pharmaceutical ; Child ; Drug Compounding/*methods ; Drug Evaluation, Preclinical/*standards ; Drug Liberation ; Excipients/*chemistry ; Flavoring Agents/administration & dosage ; Humans ; Models, Animal ; Mouth Mucosa/metabolism/physiology ; Rats/*physiology ; Saliva/chemistry/physiology ; Species Specificity ; Taste/*drug effects/physiology ; }, abstract = {Recently there has been an increased interest to develop specialised dosage forms that are better suited to specific patient populations, such as paediatrics and geriatrics. In these patient populations the acceptability of the oral dosage form can be paramount to the products success. However, many Active Pharmaceutical Ingredients (APIs) are known to cause an aversive taste response. One way to increase the acceptability and to enhance the palatability of the formulation is to design coated taste-masked particulate-based dosage forms. The masking of poorly tasting drugs with physical barriers such as polymer coatings can be utilised to prevent the release of drug within the oral cavity, thus preventing a taste response. However, currently, there are few assessment tools and models available to test the efficiency of these particulate-based taste-masked formulations. The rat brief access taste aversion model has been shown to be useful in assessment of taste for liquid dosage forms. However, the applicability of the rat model for particulate-based taste masked formulations is yet to be assessed. It is not understood whether dissolution, solubility and thus exposure of the drug to taste receptors would be the same in rat and human. Therefore, rat saliva must be compared to human saliva to determine the likelihood that drug release would be similar within the oral cavity for both species. In this study rat saliva was characterised for parameters known to be important for drug dissolution, such as pH, buffer capacity, surface tension, and viscosity. Subsequently dissolution of model bitter tasting compounds, sildenafil citrate and efavirenz, in rat saliva was compared to dissolution in human saliva. For all parameters characterised and for the dissolution of both drugs in rat saliva, a substantial difference was observed when compared to human saliva. This discrepancy in saliva parameters and dissolution of model drugs suggests that preclinical taste evaluation of particulate-based taste-masked formulations suggests rat is not a good model for predicting taste of solid dosage forms or undissolved drug where dissolution is required. Alternative preclinical in vivo models in other species, or improved biorelevant in vitro models should be considered instead.}, } @article {pmid31655082, year = {2019}, author = {Song, L and Chen, K and Yan, J and Zhang, Y and Mao, X and Lu, B and Sun, B}, title = {Maternal high-fat diet during gestation and lactation increases conditioned aversion threshold for sucrose and alters sweet taste receptors expression in taste buds in rat offspring.}, journal = {Physiology & behavior}, volume = {212}, number = {}, pages = {112709}, doi = {10.1016/j.physbeh.2019.112709}, pmid = {31655082}, issn = {1873-507X}, mesh = {Animals ; Avoidance Learning/*physiology ; Choice Behavior/drug effects ; *Diet, High-Fat ; Female ; Lactation ; Male ; Maternal Nutritional Physiological Phenomena/*physiology ; Pregnancy ; Rats ; Receptors, G-Protein-Coupled/biosynthesis/*physiology ; Sex Factors ; Sucrose/pharmacology ; Taste/drug effects/*physiology ; Taste Buds/metabolism/physiology ; Taste Threshold/*physiology ; Transducin/biosynthesis ; }, abstract = {Maternal high-fat (HF) diet affects offspring's metabolic phenotype. Sweet taste is an important factor in promoting appetite. In order to determine the effects of maternal HF diet throughout gestation and lactation on taste sensitivity to sucrose in rat offspring, we measured conditioned aversion threshold for sucrose by conditioned taste aversion (CTA) associated with two-bottle choice tests, and measured mRNA expression of sweet taste receptors in taste buds. In male offspring, conditioned aversion threshold for sucrose lay between 0.007 M and 0.009 M in control group, while in those with HF dams, the threshold significantly increased to be between 0.011 M and 0.02 M. In female offspring, conditioned aversion threshold for sucrose lay between 0.003 M and 0.005 M in control group, whereas maternal HF diet increased it to be between 0.007 M and 0.009 M. Maternal HF diet increased T1R2 and T1R3 mRNA expression in taste buds of male offspring, while only increased T1R2 mRNA expression in female offspring. Both male and female offspring with HF dams had lower α-gustducin mRNA expression, whereas only male offspring with HF dams had lower OB-Rb mRNA expression in taste buds. Our data suggest that maternal HF diet decreased taste sensitivity to sucrose in both male and female offspring, which may be partly due to altered expression of sweet taste receptors and related downstream pathways in taste buds.}, } @article {pmid31597726, year = {2019}, author = {Kayyal, H and Yiannakas, A and Kolatt Chandran, S and Khamaisy, M and Sharma, V and Rosenblum, K}, title = {Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {39}, number = {47}, pages = {9369-9382}, pmid = {31597726}, issn = {1529-2401}, support = {//CIHR/Canada ; }, mesh = {Amygdala/chemistry/*physiology ; Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/chemistry/*physiology ; Male ; Mice ; Neural Pathways/chemistry/physiology ; Neurons/chemistry/*physiology ; Organ Culture Techniques ; Random Allocation ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is an associative learning paradigm, wherein consumption of an appetitive tastant (e.g., saccharin) is paired to the administration of a malaise-inducing agent, such as intraperitoneal injection of LiCl. Aversive taste learning and retrieval require neuronal activity within the anterior insula (aIC) and the basolateral amygdala (BLA). Here, we labeled neurons of the aIC projecting to the BLA in adult male mice using a retro-AAV construct and assessed their necessity in aversive and appetitive taste learning. By restricting the expression of chemogenetic receptors in aIC-to-BLA neurons, we demonstrate that activity within the aIC-to-BLA projection is necessary for both aversive taste memory acquisition and retrieval, but not for its maintenance, nor its extinction. Moreover, inhibition of the projection did not affect incidental taste learning per se, but effectively suppressed aversive taste memory retrieval when applied either during or before the encoding of the unconditioned stimulus for CTA (i.e., malaise). Remarkably, activation of the projection after novel taste consumption, without experiencing any internal discomfort, was sufficient to form an artificial aversive taste memory, resulting in strong aversive behavior upon retrieval. Our results indicate that aIC-to-BLA projecting neurons are an essential component in the ability of the brain to associate taste sensory stimuli with body states of negative valence and guide the expression of valence-specific behavior upon taste memory retrieval.SIGNIFICANCE STATEMENT In the present study we subjected mice to the conditioned taste aversion paradigm, where animals learn to associate novel taste with malaise (i.e., assign it negative valence). We show that activation of neurons in the anterior insular cortex (aIC) that project into the basolateral amygdala (BLA) in response to conditioned taste aversion is necessary to form a memory for a taste of negative valence. Moreover, artificial activation of this pathway (without any feeling of pain) after the sampling of a taste can also lead to such associative memory. Thus, activation of aIC-to-BLA projecting neurons is necessary and sufficient to form and retrieve aversive taste memory.}, } @article {pmid31561365, year = {2019}, author = {Har-Paz, I and Roisman, N and Michaelson, DM and Moran, A}, title = {Extra-Hippocampal Learning Deficits in Young Apolipoprotein E4 Mice and Their Synaptic Underpinning.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {72}, number = {1}, pages = {71-82}, doi = {10.3233/JAD-190564}, pmid = {31561365}, issn = {1875-8908}, mesh = {Animals ; Apolipoprotein E4/genetics/*metabolism ; Avoidance Learning/*physiology ; Extinction, Psychological/physiology ; Female ; Hippocampus/*metabolism ; Male ; Memory Disorders/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Synapses/genetics/*metabolism ; }, abstract = {The E4 allele of apolipoprotein (apoE4) is the primary genetic risk factor for late onset Alzheimer's disease (AD), yet the exact manner in which apoE4 leads to the development of AD is undetermined. Human and animal studies report that apoE4-related memory deficits appear earlier than the AD clinical manifestation, thus suggesting the existence of early, pre-pathological, apoE4 impairments that may later lead to AD onset. While current research regards the hippocampus as the initial and primary effected locus by apoE4, we presently investigate the possibility that apoE4 innately impairs any brain area that requires synaptic plasticity. To test this hypothesis, we trained young (3-4-month-old) target-replacement apoE3 and apoE4 mice in conditioned taste aversion (CTA) acquisition and extinction learnings- hippocampus-independent learnings that are easily performed at a young age. Synaptic vesicular markers analysis was conducted in the gustatory cortex (GC), basolateral amygdala (BLA), medial prefrontal cortex (mPFC), and hippocampal CA3 to reveal underlying apoE4-related impairments. We have found that young apoE4 mice are severely impaired in CTA acquisition and extinction learning. CTA acquisition impairments were correlated with reduced vGat and vGlut levels in the BLA and GC, but not in the CA3. CTA extinction was correlated with lower synaptophysin and vGlut levels in the mPFC, a central region in CTA extinction. Our results support apoE4-related early-life plasticity impairments that precede the AD clinical manifestations and affect any brain area that depends on extensive plasticity; early impairments that may promote the development of AD pathologies later in life.}, } @article {pmid31521799, year = {2019}, author = {He, ABH and Huang, CL and Kozłowska, A and Chen, JC and Wu, CW and Huang, ACW and Liu, YQ}, title = {Involvement of neural substrates in reward and aversion to methamphetamine addiction: Testing the reward comparison hypothesis and the paradoxical effect hypothesis of abused drugs.}, journal = {Neurobiology of learning and memory}, volume = {166}, number = {}, pages = {107090}, doi = {10.1016/j.nlm.2019.107090}, pmid = {31521799}, issn = {1095-9564}, mesh = {Amphetamine-Related Disorders/*metabolism ; Animals ; Basolateral Nuclear Complex/*drug effects/metabolism ; Central Nervous System Stimulants/*administration & dosage ; Cerebral Cortex/drug effects ; Conditioning, Operant/drug effects ; Drug-Seeking Behavior/drug effects ; Extinction, Psychological/drug effects ; Immunohistochemistry ; MAP Kinase Signaling System/physiology ; Male ; Methamphetamine/administration & dosage ; Nucleus Accumbens/*drug effects/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Wistar ; Reward ; }, abstract = {Clinical studies of drug addiction focus on the reward impact of abused drugs that produces compulsive drug-seeking behavior and drug dependence. However, a small amount of research has examined the opposite effect of aversion to abused drugs to balance the reward effect for drug taking. An aversive behavioral model of abused drugs in terms of conditioned taste aversion (CTA) was challenged by the reward comparison hypothesis (Grigson, 1997). To test the reward comparison hypothesis, the present study examined the rewarding or aversive neural substrates involved in methamphetamine-induced conditioned suppression. The behavioral data showed that methamphetamine induced conditioned suppression on conditioning and reacquisition but extinguished it on extinction. A higher level of stressful aversive corticosterone occurred on conditioning and reacquisition but not extinction. The c-Fos or p-ERK immunohistochemical activity showed that the cingulated cortex area 1 (Cg1), infralimbic cortex (IL), prelimbic cortex (PrL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) of the hippocampus were overexpressed in aversive CTA induced by methamphetamine. These data may indicate that the Cg1, IL, PrL, BLA, NAc, and DG probably mediated the paradoxical effect-reward and aversion. Altogether, our data conflicted with the reward comparison hypothesis, and methamphetamine may simultaneously induce the paradoxical effect of reward and aversion in the brain to support the paradoxical effect hypothesis of abused drugs. The present data implicate some insights for drug addiction in clinical aspects.}, } @article {pmid31520676, year = {2019}, author = {Nakajima, S}, title = {Further demonstration of running-based food avoidance learning in laboratory mice (Mus musculus).}, journal = {Behavioural processes}, volume = {168}, number = {}, pages = {103962}, doi = {10.1016/j.beproc.2019.103962}, pmid = {31520676}, issn = {1872-8308}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; Conditioning, Classical ; *Feeding Behavior ; Habituation, Psychophysiologic ; Male ; Mice ; *Running ; Taste ; }, abstract = {Voluntary wheel running has hedonically bivalent properties in laboratory rats and mice. While it works as a reward for instrumental performance such as bar pressing, it also functions as an aversive stimulus to establish Pavlovian conditioned avoidance of the paired stimulus. The present study focused on the latter case. Running in closed wheels hampered habituation of a reluctance to eat a target snack in rats (Experiment 1A) and mice (Experiment 1B) trained by pairing access to a target snack with confinement to a wheel attached to the cage. Experiment 2 successfully confirmed and extended this finding with mice running in both open and closed wheels. A differential conditioning procedure employed in Experiment 3 ensured that this phenomenon is specific to the snack paired with running, implying that it reflects Pavlovian conditioned flavor avoidance (CFA). Free exploration in cages without wheels, however, did not results in a CFA.}, } @article {pmid31473281, year = {2019}, author = {Osorio-Gómez, D and Bermúdez-Rattoni, F and Guzmán-Ramos, K}, title = {Artificial taste avoidance memory induced by coactivation of NMDA and β-adrenergic receptors in the amygdala.}, journal = {Behavioural brain research}, volume = {376}, number = {}, pages = {112193}, doi = {10.1016/j.bbr.2019.112193}, pmid = {31473281}, issn = {1872-7549}, mesh = {Amygdala/drug effects/physiology ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/drug effects/physiology ; Conditioning, Classical/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/pharmacology ; Male ; Memory/physiology ; N-Methylaspartate/pharmacology ; Norepinephrine/pharmacology ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Saccharin/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {The association between a taste and gastric malaise allows animals to avoid the ingestion of potentially toxic food. This association has been termed conditioned taste aversion (CTA) and relies on the activity of key brain structures such as the amygdala and the insular cortex. The establishment of this gustatory-avoidance memory is related to glutamatergic and noradrenergic activity within the amygdala during two crucial events: gastric malaise (unconditioned stimulus, US) and the post-acquisition spontaneous activity related to the association of both stimuli. To understand the functional implications of these neurochemical changes on avoidance memory formation, we assessed the effects of pharmacological stimulation of β-adrenergic and glutamatergic NMDA receptors through the administration of a mixture of L-homocysteic acid and isoproterenol into the amygdala after saccharin exposure on specific times to emulate the US and post-acquisition local signals that would be occurring naturally under CTA training. Our results show that activation of NMDA and β-adrenergic receptors generated a long-term avoidance response to saccharin, like a naturally induced rejection with LiCl. Moreover, the behavioral outcome was accompanied by changes in glutamate, norepinephrine and dopamine levels within the insular cortex, analogous to those displayed during memory retrieval of taste aversion memory. Therefore, we suggest that taste avoidance memory can be induced artificially through the emulation of specific amygdalar neurochemical signals, promoting changes in the amygdala-insular cortex circuit enabling memory establishment.}, } @article {pmid31434277, year = {2019}, author = {Cunningham, CL}, title = {Genetic Relationships Between Ethanol-Induced Conditioned Place Aversion and Other Ethanol Phenotypes in 15 Inbred Mouse Strains.}, journal = {Brain sciences}, volume = {9}, number = {8}, pages = {}, pmid = {31434277}, issn = {2076-3425}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; R01AA007702/AA/NIAAA NIH HHS/United States ; }, abstract = {The genetic relationships between different behaviors used to index the aversive effects of ethanol are unknown. To address this issue, ethanol-induced conditioned place aversion (CPA) was tested in a genetically diverse panel of 15 inbred mouse strains. Mice were exposed to an unbiased place conditioning procedure using ethanol doses of 0, 2, or 4 g/kg; all injections were given immediately after 5-min exposure to distinctive tactile cues. There were dose-dependent effects of ethanol on CPA and on the change in pre-injection activity rates between the first and last conditioning trials. Most strains (80%) developed CPA, demonstrating the generalizability of this behavior. Moreover, genotype had significant effects on CPA magnitude and locomotor activity rates. Strain means from this study and previously published studies were then used to examine genetic correlations. These analyses showed significant genetic correlations between CPA and ethanol intake/preference, conditioned taste aversion, and drug withdrawal (but not blood ethanol concentration or conditioned place preference), supporting the idea of commonality in the genes underlying CPA and each of these behaviors. The overall pattern of findings is consistent with previous data suggesting that genetic differences in sensitivity to ethanol's aversive effects play a role in determining strain differences in ethanol drinking. The broader implication is that individuals who are more sensitive to the aversive effects of ethanol may be protected from developing the excessive drinking behaviors characteristic of alcohol use disorders.}, } @article {pmid31414153, year = {2020}, author = {Galistu, A and D'Aquila, PS}, title = {Daily memantine treatment blunts hedonic response to sucrose in rats.}, journal = {Psychopharmacology}, volume = {237}, number = {1}, pages = {103-114}, pmid = {31414153}, issn = {1432-2072}, mesh = {Analysis of Variance ; Animals ; Behavior, Animal/drug effects ; Binge-Eating Disorder/*drug therapy ; Conditioning, Classical/drug effects ; Dopamine Agents/*pharmacology ; Eating/drug effects ; Feeding Behavior/*drug effects ; Male ; Memantine/*pharmacology ; Motivation/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Reward ; Sucrose/administration & dosage ; Taste/drug effects ; }, abstract = {RATIONALE: Preclinical and clinical studies suggest the potential use of memantine in the treatment of binge eating disorder. The aim of this study was to further investigate the mechanisms by which memantine influences the motivational aspects of ingestion through the analysis of licking microstructure. To interpret treatment effects in relation to drug action at specific functionally relevant times, we compared the effect of two different administration schedules.

METHODS: Memantine was administered daily for a week, either 1 h before or immediately after a 30-min daily session. The effects on the microstructure of licking for a 10% sucrose solution in rats were examined in the course of treatment and for 15 days after treatment discontinuation.

RESULTS: Treatment before testing reduced ingestion due to reduced burst size and increased latency in the first session. However, a progressive increase in burst number across sessions led to a full recovery of ingestion levels by the end of treatment. Daily post-session administration induced a dramatic decrease of activation of licking behaviour, indicated by reduced burst number, accompanied to reduced burst size. A slow recovery of ingestion took place after treatment discontinuation.

CONCLUSION: These results suggest a reduced hedonic/reward evaluation response, an effect likely due to NMDA receptor blockade occurring during the testing time and support the hypothesis that memantine interferes with the hedonic/non-homeostatic mechanisms regulating food intake and food-seeking. The effect of post-session administration might be explained by the development of conditioned taste aversion.}, } @article {pmid31410739, year = {2019}, author = {Wills, AJ and Edmunds, CER and Le Pelley, ME and Milton, F and Newell, BR and Dwyer, DM and Shanks, DR}, title = {Dissociable learning processes, associative theory, and testimonial reviews: A comment on Smith and Church (2018).}, journal = {Psychonomic bulletin & review}, volume = {26}, number = {6}, pages = {1988-1993}, pmid = {31410739}, issn = {1531-5320}, mesh = {Conditioning, Classical ; Feedback ; Humans ; Learning ; *Psychology, Comparative ; }, abstract = {Smith and Church (Psychonomic Bulletin & Review, 25, 1565-1584 2018) present a "testimonial" review of dissociable learning processes in comparative and cognitive psychology, by which we mean they include only the portion of the available evidence that is consistent with their conclusions. For example, they conclude that learning the information-integration category-learning task with immediate feedback is implicit, but do not consider the evidence that people readily report explicit strategies in this task, nor that this task can be accommodated by accounts that make no distinction between implicit and explicit processes. They also consider some of the neuroscience relating to information-integration category learning, but do not report those aspects that are more consistent with an explicit than an implicit account. They further conclude that delay conditioning in humans is implicit, but do not report evidence that delay conditioning requires awareness; nor do they present the evidence that conditioned taste aversion, which should be explicit under their account, can be implicit. We agree with Smith and Church that it is helpful to have a clear definition of associative theory, but suggest that their definition may be unnecessarily restrictive. We propose an alternative definition of associative theory and briefly describe an experimental procedure that we think may better distinguish between associative and non-associative processes.}, } @article {pmid31404849, year = {2019}, author = {Harris, AC and Muelken, P and Swain, Y and Palumbo, M and Jain, V and Goniewicz, ML and Stepanov, I and LeSage, MG}, title = {Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats.}, journal = {Drug and alcohol dependence}, volume = {203}, number = {}, pages = {51-60}, pmid = {31404849}, issn = {1879-0046}, support = {R03 DA042009/DA/NIDA NIH HHS/United States ; T32 DA007097/DA/NIDA NIH HHS/United States ; }, mesh = {Aerosols ; Age Factors ; Alkaloids/administration & dosage ; Animals ; Aversive Agents/*administration & dosage ; Avoidance Learning/drug effects/physiology ; E-Cigarette Vapor/*administration & dosage ; *Electronic Nicotine Delivery Systems ; Female ; Male ; Menthol/*administration & dosage ; Nicotine/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Self Stimulation/drug effects ; }, abstract = {BACKGROUND: Development of preclinical methodology for evaluating the abuse liability of electronic cigarettes (ECs) in adolescents is urgently needed to inform FDA regulation of these products. We previously reported reduced aversive effects of EC liquids containing nicotine and a range of non-nicotine constituents (e.g., propylene glycol, minor tobacco alkaloids) compared to nicotine alone in adult rats as measured using intracranial self-stimulation. The goal of this study was to compare the aversive effects of nicotine alone and EC aerosol extracts in adolescent rats as measured using conditioned taste aversion (CTA), which can be conducted during the brief adolescent period.

METHODS AND RESULTS: In Experiment 1, nicotine alone (1.0 or 1.5 mg/kg, s.c.) produced significant CTA in adolescent rats in a two-bottle procedure, thereby establishing a model to study the effects of EC extracts. At a nicotine dose of 1.0 mg/kg, CTA to Vuse Menthol EC extract, but not Aroma E-Juice EC extract, was attenuated compared to nicotine alone during repeated two-bottle CTA tests (Experiment 2a). At a nicotine dose of 0.5 mg/kg, CTA to Vuse Menthol EC extract did not differ from nicotine alone during the first two-bottle CTA test but extinguished more rapidly across repeated two-bottle tests (Experiment 2b).

CONCLUSIONS: Non-nicotine constituents in Vuse Menthol EC extracts attenuated CTA in a two-bottle procedure in adolescents. This model may be useful for anticipating the abuse liability of ECs in adolescents and for modeling FDA-mandated changes in product standards for nicotine or other constituents in ECs.}, } @article {pmid31401881, year = {2019}, author = {Cui, Y and Wu, H and Li, Q and Liao, J and Gao, P and Sun, F and Zhang, H and Lu, Z and Wei, X and He, C and Ma, T and Wei, X and Chen, X and Zheng, H and Yang, G and Liu, D and Zhu, Z}, title = {Impairment of Bitter Taste Sensor Transient Receptor Potential Channel M5-Mediated Aversion Aggravates High-Salt Intake and Hypertension.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {74}, number = {4}, pages = {1021-1032}, doi = {10.1161/HYPERTENSIONAHA.119.13358}, pmid = {31401881}, issn = {1524-4563}, mesh = {Animals ; Feeding Behavior/*physiology ; Humans ; Hypertension/genetics/*metabolism/physiopathology ; Mice ; Mice, Knockout ; Sodium Chloride, Dietary ; TRPM Cation Channels/genetics/*metabolism ; Taste/genetics/*physiology ; Taste Perception/genetics/*physiology ; Tongue/metabolism ; }, abstract = {Excessive salt consumption leads to cardiovascular diseases. Despite various measures designed to reduce salt intake, daily salt intake remains at a high level. Appropriate salt intake is balanced by salt taste preference triggered by epithelium sodium channel and salt taste aversion evoked by bitter taste sensor, transient receptor potential channel M5 (TRPM5). However, the behavioral mechanism of excessive salt intake remains largely elusive. In this study, wild type and TRPM5[-/-] mice were applied to study the influence of high-salt administration on epithelium sodium channel/TRPM5 and the associated behavior to salt consumption. We found that long-term high-salt intake impaired the aversive behavior to high-salt stimulation but did not alter the preference to low salt in mice. The mechanistic evidence demonstrated that high-salt intake blunted the TRPM5-mediated aversive behavior to noxious salt stimulation through inhibiting PKC (protein kinase C) activity and PKC-dependent threonine phosphorylation in the tongue epithelium but did not affect the epithelium sodium channel-dependent salt taste preference. Inhibition of TRPM5 also resulted in an impaired aversive response to high salt, with reduced taste perception in bitter cortical field of mice. TRPM5[-/-] mice showed a lowered aversion to high-salt diet and developed salt-induced hypertension. The impaired perception to bitter taste evoked by high-salt intake also existed in hypertensive patients with high-salt consumption. We demonstrate that long-term high-salt consumption impairs aversive response to concentrated salt by downregulating bitter taste sensor TRPM5. It suggests that enhancing TRPM5 function might antagonize excessive salt intake and high salt-induced hypertension.}, } @article {pmid31374869, year = {2019}, author = {Ruiz, F and Keeley, A and Léglise, P and Tuleu, C and Lachuer, C and Rwabihama, JP and Bachalat, N and Boulaich, I and Abdallah, F and Rabus, M and Ribemont, AC and Michelon, H and Wojcicki, AD and Orlu, M and Vallet, T and Boudy, V}, title = {Sex Differences in Medicine Acceptability: A New Factor to Be Considered in Medicine Formulation.}, journal = {Pharmaceutics}, volume = {11}, number = {8}, pages = {}, pmid = {31374869}, issn = {1999-4923}, abstract = {Palatability is a recognized driver of medicine acceptability in pediatrics but deemed less relevant in older populations due to sensory decline. Preliminary findings from an observational study implicated palatability problems with one Alzheimer's medicine. Among 1517 observer reports combining multiple measures on medicines uses in patients aged over 64, we focused on two original formulations of memantine (Ebixa[®], tablets (n = 25) and oral solution (n = 60)). Evaluations were scored with an acceptability reference framework (CAST), the rodent Brief Access Taste Aversion (BATA) model tested aversiveness. Focusing on women treated with Ebixa[®] (n = 54), the oral formulation sub-group was classified as "negatively accepted", while the coated tablet was associated with the "positively accepted" cluster. In men, both formulations belonged to the "positively accepted" profile. Using BATA, the original oral solution was categorized as highly aversive/untolerated while solutions of excipients only were well tolerated. Furthermore, the number of licks was significantly lower in female than in male rats. These results revealed that medicine palatability remains important for acceptability in older populations. Moreover, converging results from humans and animal models highlighted that palatability profiles can significantly vary between the sexes. These drivers should be closely considered during drug development to enhance acceptability in this population.}, } @article {pmid31325496, year = {2019}, author = {Olvera, MJ and Miranda, MI}, title = {Specific inter-stimulus interval effect of NMDA receptor activation in the insular cortex during conditioned taste aversion.}, journal = {Neurobiology of learning and memory}, volume = {164}, number = {}, pages = {107043}, doi = {10.1016/j.nlm.2019.107043}, pmid = {31325496}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Excitatory Amino Acid Agonists/administration & dosage ; Extinction, Psychological/drug effects/physiology ; Male ; N-Methylaspartate/administration & dosage ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/agonists/*physiology ; Taste Perception/*physiology ; Time Factors ; }, abstract = {Taste memory recognition is crucial for species survival; thus, the acquisition of conditioned taste aversion (CTA) protects animals against consuming poisons or toxins. In nature, food and poison are confined in the same edible item; however, in the laboratory these food constituents are usually presented separately for experimental analysis. The taste, or conditioned stimulus (CS), can be hours apart from the gastric malaise, or unconditioned stimulus (US); this extended inter-stimulus interval (ISI) allows the analysis of a particular learning phase. Evidence indicates a relevant function of glutamatergic activity in the insular cortex (IC) throughout the ISI. N-methyl-D-aspartate receptors (NMDAR) are crucial during CTA acquisition and retrieval. However, the exact participation of NMDAR in the IC during the ISI has not been demonstrated. Thus, the aim of this work was to evaluate the effects of temporal NMDAR activation during four time frames throughout the ISI of conditioned sugar aversion with bilateral injections of NMDA at a physiological dose (1 µg/µl) in the IC, given (1) immediately before or (2) immediately after sugar presentation, or (3) immediately before or (4) immediately after LiCl i.p. injection. The results showed that NMDAR activation in the IC had a specific ISI effect during CTA acquisition, increasing aversive memory formation and delaying extinction only after CS presentation. Overall, these results demonstrate that NMDAR in the IC have a particular enhancing associative effect after CS and suggest that there is a precise coincidence in neurochemical events in the IC that correlates with the stimulus to be associated and the glutamate NMDAR activity that must be finely tuned in the ISI during CTA acquisition.}, } @article {pmid31310793, year = {2019}, author = {Tobajas, J and Gómez-Ramírez, P and María-Mojica, P and Navas, I and García-Fernández, AJ and Ferreras, P and Mateo, R}, title = {Selection of new chemicals to be used in conditioned aversion for non-lethal predation control.}, journal = {Behavioural processes}, volume = {166}, number = {}, pages = {103905}, doi = {10.1016/j.beproc.2019.103905}, pmid = {31310793}, issn = {1872-8308}, mesh = {Animals ; Animals, Wild ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Dogs ; Fluconazole/pharmacology ; Isoxazoles/pharmacology ; Levamisole/pharmacology ; Male ; Predatory Behavior/*drug effects ; *Taste ; Thiabendazole/pharmacology ; Thiram/pharmacology ; }, abstract = {Globally, native predators and scavengers are threatened through the incidence of illegal poisoning due to increasing human-wildlife conflicts. The use of conditioned taste aversion (CTA) may mitigate such conflicts. CTA is a robust learning paradigm that occurs when animals associate a food with a discomfort induced by a chemical, thereby avoiding that food in subsequent encounters. We reviewed the potential of 167 chemical compounds to be used in CTA, considering effects, margin of safety, accessibility, and detectability. After the review, 15 compounds fulfilled the required characteristics, but only five (thiabendazole, thiram, levamisole, fluconazole and fluralaner) were finally selected to be tested in CTA assays with dogs. Of the tested compounds, thiabendazole, thiram and levamisole caused target food rejection by dogs and reduced the time spent eating during post-conditioning. However, despite being microencapsulated, levamisole appeared to be detectable by dogs, whereas thiram and thiabendazole were not. Fluconazole and fluralaner did not produce any CTA effect. Thiabendazole, thiram and levamisole can therefore induce CTA, and thus are potential candidates as aversive compounds for wildlife management. Thiram is an undetectable, relatively safe and accessible compound that can induce CTA in canids, and opens new possibilities to develop methods of non-lethal predation control.}, } @article {pmid31287232, year = {2020}, author = {Tobajas, J and Gómez-Ramírez, P and Ferreras, P and García-Fernández, AJ and Mateo, R}, title = {Conditioned food aversion in domestic dogs induced by thiram.}, journal = {Pest management science}, volume = {76}, number = {2}, pages = {568-574}, doi = {10.1002/ps.5548}, pmid = {31287232}, issn = {1526-4998}, mesh = {Animals ; Animals, Wild ; Dogs ; Odorants ; Predatory Behavior ; *Thiram ; }, abstract = {BACKGROUND: The conflict between predators and humans for resources such as game species or livestock is an ancient issue, and it is especially sharp in the case of medium-large wild canids. In order to manage this conflict, lethal control methods are often used, which can sometimes be illegal, such as poisoning. As an alternative, conditioned food aversion (CFA) is a non-lethal method to reduce predation in which animals learn to avoid a given food due to the adverse effects caused by the ingestion of an undetectable chemical compound added to this food. The present study aimed to test thiram as a CFA agent in penned dogs as a first approach to use this substance for reducing the predation conflict associated with wild canids.

RESULTS: Thiram, with or without an additional odor cue, produced CFA in penned dogs for more than 2 months. Moreover, thiram seemed to be undetectable and safe after the third ingestion of a 40-60 mg kg[-1] dose. Desirable adverse effects, such as vomits, appeared around 1 h after exposure. These characteristics make thiram optimal for its use in predation reduction through CFA. However, individual variability could prevent CFA acquisition by some animals.

CONCLUSIONS: Thiram has the potential to be used as a CFA agent in wildlife management and conservation to reduce predation by wild canids. Since thiram produced CFA without the problems of detectability and toxicity caused by other substances, it may be an alternative to lethal control methods used to reduce predation on game, livestock and endangered species. © 2019 Society of Chemical Industry.}, } @article {pmid31257806, year = {2019}, author = {Li, LM and Liao, YY and Jiang, ES}, title = {[The electrophysiological response of chorda tympani nerve to taste stimuli in rats with conditioned taste aversion to saltiness].}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {35}, number = {3}, pages = {239-244}, doi = {10.12047/j.cjap.5768.2019.051}, pmid = {31257806}, issn = {1000-6834}, mesh = {Amiloride/pharmacology ; Animals ; Chorda Tympani Nerve/*physiology ; *Conditioning, Classical ; *Electrophysiological Phenomena ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; Taste/*physiology ; }, abstract = {OBJECTIVE: To explore the characteristic changes of the peripheral chorda tympanic nerve (CT) electrophysiological responses to salty stimulus and other taste stimuli in rats with the conditioned taste aversion to saltiness.

METHODS: Fourteen adult SD male rats were divided into a conditioned taste aversion to salty group (CTA) and a control group (Ctrl) (n=7/group). On the first day of the experiment, rats were given a 0.1 mol/L NaCl intake for 30 min, then, the rats in CTA and Ctrl groups were injected intraperitoneally with 2 ml of 0.15 mol/L LiCl and the same amount of saline respectively. On day 2, 3 and 4, the 30 min consumption of NaCl and distilled water was measured for both groups of rats. On the 4th day after the behavioral test of that day, CT electrophysiological recording experiments were performed on CTA rats and control rats.

RESULTS: Compared with the rats in Ctrl group, the electrophysiological characteristics of CT in CTA group rats did not change significantly the responses to the series of NaCl and other four basic taste stimuli (P>0.05). The amiloride, the epithelial sodium channel blocker, strongly inhibited the response of CT to NaCl in CTA and Ctrl group rats (P<0.01).

CONCLUSION: The electrophysiological responses of CT to various gustatory stimuli do not significantly change in rats after the establishment of conditional taste aversion to the saltiness.}, } @article {pmid31235467, year = {2019}, author = {Inui, T and Sugishita, T and Inui-Yamamoto, C and Yasoshima, Y and Shimura, T}, title = {The Basolateral Nucleus of the Amygdala Executes the Parallel Processes of Avoidance and Palatability in the Retrieval of Conditioned Taste Aversion in Male Rats.}, journal = {eNeuro}, volume = {6}, number = {4}, pages = {}, pmid = {31235467}, issn = {2373-2822}, mesh = {Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/*physiology ; Behavior, Animal ; Conditioning, Classical ; Male ; Mental Recall/*physiology ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is an essential behavior for animal survival. Conditioned animals show avoidance and decreased palatability to a conditioned stimulus (CS) on CTA retrieval. In this study, we aimed to determine whether the basolateral nucleus of the amygdala (BLA) is involved in CTA retrieval and whether avoidance and palatability in CTA retrieval are processed in the BLA. We developed an experimental chamber for time-course analysis of the behavior to approach a spout and lick a CS. In this experimental chamber, we analyzed the behavior of male rats following microinjections of GABAA receptor agonist muscimol or saline into the BLA. The rats showed two types of approach behavior: they either (1) approached and licked the spout or (2) approached but did not lick the spout. Muscimol injection into the BLA decreased the frequency of the latter type of approach behavior, indicating that BLA inactivation reduced avoidance to the CS. The muscimol injection into the BLA also significantly increased the consumption of the CS. Lick microstructure analysis demonstrated that intra-BLA muscimol significantly increased licking burst number and size, indicating that BLA inactivation attenuated aversion to the CS as large burst licking is an indicator of high palatability. These results suggest that the increase in CS consumption with intra-BLA muscimol injection was due to alterations in approach and aversive responses to the CS. Therefore, we conclude that the BLA plays an essential role in CTA retrieval by parallel processing of avoidance and palatability.}, } @article {pmid31229633, year = {2019}, author = {Tanaka, DH and Li, S and Mukae, S and Tanabe, T}, title = {Genetic Access to Gustatory Disgust-Associated Neurons in the Interstitial Nucleus of the Posterior Limb of the Anterior Commissure in Male Mice.}, journal = {Neuroscience}, volume = {413}, number = {}, pages = {45-63}, doi = {10.1016/j.neuroscience.2019.06.021}, pmid = {31229633}, issn = {1873-7544}, mesh = {Animals ; Anterior Commissure, Brain/*metabolism ; Avoidance Learning/physiology ; Conditioning, Classical/physiology ; Cytoskeletal Proteins/genetics/metabolism ; *Disgust ; Lithium Chloride ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/*metabolism ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Quinine ; Saccharin ; Taste/physiology ; Taste Perception/*physiology ; }, abstract = {Orofacial and somatic disgust reactions are observed in rats following intraoral infusion of not only bitter quinine (innate disgust) but also sweet saccharin previously paired with illness (learned disgust). It remains unclear, however, whether these innate and learned disgust reactions share a common neural basis and which brain regions, if any, host it. In addition, there is no established method to genetically access neurons whose firing is associated with disgust (disgust-associated neurons). Here, we examined the expression of cFos and Arc, two markers of neuronal activity, in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) of male mice that showed innate disgust and mice that showed learned disgust. Furthermore, we used a targeted recombination in active populations (TRAP) method to genetically label the disgust-associated neurons in the IPAC with YFP. We found a significant increase of both cFos-positive neurons and Arc-positive neurons in the IPAC of mice that showed innate disgust and mice that showed learned disgust. In addition, TRAP following quinine infusion (Quinine-TRAP) resulted in significantly more YFP-positive neurons in the IPAC, compared to TRAP following water infusion. A significant number of the YFP-positive neurons following Quinine-TRAP were co-labeled with Arc following the second quinine infusion, confirming that Quinine-TRAP preferentially labeled quinine-activated neurons in the IPAC. Our results suggest that the IPAC activity is associated with both innate and learned disgust and that disgust-associated neurons in the IPAC are genetically accessible by TRAP.}, } @article {pmid31216290, year = {2019}, author = {Schier, LA and Hyde, KM and Spector, AC}, title = {Conditioned taste aversion versus avoidance: A re-examination of the separate processes hypothesis.}, journal = {PloS one}, volume = {14}, number = {6}, pages = {e0217458}, pmid = {31216290}, issn = {1932-6203}, support = {R01 DK106112/DK/NIDDK NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Aversive Agents/pharmacology ; Avoidance Learning/drug effects/*physiology ; Lithium Chloride/pharmacology ; Male ; *Models, Biological ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Taste/*physiology ; Taste Perception/drug effects/*physiology ; }, abstract = {Rats not only avoid ingesting a substance associated with LiCl toxicosis, but they display rejection reflexes (e.g., gapes) to its taste; this latter response is thought to reflect disgust or taste aversion. Prior work has shown that rats also avoid consuming foods/fluids associated with other adverse gastrointestinal (GI) effects like lactose indigestion but without the concomitant change in oromotor responses (taste reactivity; TR) indicative of aversion. Because of interpretive limitations of the methods used in those studies, we revisited the taste aversion-avoidance distinction with a design that minimized non-treatment differences among groups. Effects on intake and preference (Experiments 1a, 1b, and 2), as well as consummatory (TR, Experiment 1a and 1b) and appetitive (Progressive Ratio, Experiment 2) behaviors to the taste stimulus were assessed after training. In both experiments, rats were trained to associate 0.2% saccharin (CS) with intraduodenal infusions of LiCl, Lactose, or NaCl control. Rats trained with 18% lactose, 0.3 and 1.5 mEq/kg dose of LiCl subsequently avoided the taste CS in post-training single-bottle intake tests and two-bottle choice tests. However, only those trained with 1.5 mEq/kg LiCl displayed post-conditioning increases in taste CS-elicited aversive TR (Experiment 1a and 1b). This dose of LiCl also led to reductions in breakpoint for saccharin. The fact that conditioned avoidance is not always accompanied by changes in other common appetitive and/or consummatory indices of ingestive motivation further supports a functional dissociation between these processes, and highlights the intricacies of visceral influences on taste-guided ingestive motivation.}, } @article {pmid31205005, year = {2019}, author = {Devineni, AV and Sun, B and Zhukovskaya, A and Axel, R}, title = {Acetic acid activates distinct taste pathways in Drosophila to elicit opposing, state-dependent feeding responses.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31205005}, issn = {2050-084X}, support = {54951//Simons Foundation/International ; }, mesh = {Acetic Acid/*pharmacology ; Animals ; Appetite/drug effects/physiology ; Drosophila melanogaster/*drug effects/physiology ; Feeding Behavior/*drug effects/physiology ; Hunger/physiology ; Neural Pathways/drug effects/physiology ; Sensory Receptor Cells/*drug effects/physiology ; Taste/*drug effects/physiology ; }, abstract = {Taste circuits are genetically determined to elicit an innate appetitive or aversive response, ensuring that animals consume nutritious foods and avoid the ingestion of toxins. We have examined the response of Drosophila melanogaster to acetic acid, a tastant that can be a metabolic resource but can also be toxic to the fly. Our data reveal that flies accommodate these conflicting attributes of acetic acid by virtue of a hunger-dependent switch in their behavioral response to this stimulus. Fed flies show taste aversion to acetic acid, whereas starved flies show a robust appetitive response. These opposing responses are mediated by two different classes of taste neurons, the sugar- and bitter-sensing neurons. Hunger shifts the behavioral response from aversion to attraction by enhancing the appetitive sugar pathway as well as suppressing the aversive bitter pathway. Thus a single tastant can drive opposing behaviors by activating distinct taste pathways modulated by internal state.}, } @article {pmid31200091, year = {2019}, author = {González-Sánchez, H and Tovar-Díaz, J and Morin, JP and Roldán-Roldán, G}, title = {NMDA receptor and nitric oxide synthase activity in the central amygdala is involved in the acquisition and consolidation of conditioned odor aversion.}, journal = {Neuroscience letters}, volume = {707}, number = {}, pages = {134327}, doi = {10.1016/j.neulet.2019.134327}, pmid = {31200091}, issn = {1872-7972}, mesh = {Animals ; *Avoidance Learning ; *Behavior, Animal ; Central Amygdaloid Nucleus/*metabolism ; Conditioning, Psychological ; Male ; Nitric Oxide Synthase Type I/*metabolism ; Odorants ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*metabolism ; *Smell ; }, abstract = {Rats readily learn to avoid a tasteless odorized solution if they experience visceral malaise after consuming it. This phenomenon is referred to as conditioned odor aversion (COA). Several studies have shown that COA depends on the functional integrity of the amygdala, with most studies focusing on the basolateral nucleus. On the other hand, the role of the central amygdala (CeA) which is known to be involved in the consolidation of conditioned taste aversion (CTA) remains to be established. To address this issue, we evaluated the effect of inhibiting NMDA receptor activity in this structure on COA memory formation. Intra-CeA infusions of non-competitive NMDA receptor inhibitor MK-801 prevented memory formation both when administered before and up to 15 min after COA conditioning, while no effect of this drug was observed when given before long-term memory test. We next evaluated the role of one of the main downstream effectors of brain NMDA receptor signaling, nitric oxide synthase (NOS), known to play a key role in a wide variety learning tasks including some types of olfactory conditioning. Similar results were obtained with inhibition of either NOS or neuron-specific NOS; which proved to be required both during and after COA training, though for a shorter time span than NMDA receptors. Also, neither isoform showed to be required to memory retrieval. These results suggest that the US signaling during acquisition and the initial consolidation step of COA depends on glutamate-NO system activation in the CeA.}, } @article {pmid31087376, year = {2019}, author = {Dannenhoffer, CA and Spear, LP}, title = {Excitatory/inhibitory balance across ontogeny contributes to age-specific behavioral outcomes of ethanol-like challenge in conditioned taste aversion.}, journal = {Developmental psychobiology}, volume = {61}, number = {8}, pages = {1157-1167}, pmid = {31087376}, issn = {1098-2302}, support = {T32 AA025606/AA/NIAAA NIH HHS/United States ; U01 AA019972/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Central Nervous System Depressants/administration & dosage/*pharmacology ; Conditioning, Classical/*drug effects ; Ethanol/administration & dosage/*pharmacology ; Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology ; Female ; GABA-A Receptor Agonists/administration & dosage/*pharmacology ; Isoxazoles/pharmacology ; Male ; Piperidines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/*antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Taste Perception/*drug effects ; }, abstract = {Adolescent-typical sensitivities to ethanol (EtOH) are characterized in part by reduced sensitivity to EtOH's aversive effects. Rodent studies have shown that adolescents are less sensitive than adults to aversive properties of EtOH in a conditioned taste aversion (CTA) paradigm. To the extent that EtOH exerts antagonist-like actions upon glutamate receptors and/or agonist-like actions upon γ-aminobutyric acid (GABA) receptors, age differences in excitatory/inhibitory balance may regulate age-specific EtOH sensitivities, such as attenuated sensitivity of adolescents to EtOH aversion. In our experiments, adolescent and adult Sprague-Dawley rats were tested for CTA following challenge with one of the following pharmacological agents: glutamatergic AMPA1 receptor antagonist NBQX, glutamatergic N-methyl-d-aspartate NR2B receptor antagonist ifenprodil, and extrasynaptic GABAA receptor agonist THIP to determine whether these induced age-specific aversive sensitivities like those seen with EtOH. NBQX administration did not induce CTA. The highest dose of extrasynaptic GABAA agonist THIP induced CTA in adolescents but not adults, an opposite ontogenetic profile as seen following EtOH. Ifenprodil exerted an age-specific pattern of CTA similar to that seen with EtOH in males, with adolescents being insensitive to ifenprodil's aversive effects relative to adults. Thus, only antagonism of NR2B receptors in male rats mimicked age-specific sensitivities to the aversive effects of EtOH.}, } @article {pmid31082409, year = {2019}, author = {Grau-Perales, AB and Gómez-Chacón, B and Gallo, M}, title = {Differential activity pattern of c-Fos in the nucleus accumbens between adult and aged rats during flavor recognition memory.}, journal = {Behavioural brain research}, volume = {371}, number = {}, pages = {111935}, doi = {10.1016/j.bbr.2019.111935}, pmid = {31082409}, issn = {1872-7549}, mesh = {*Age Factors ; Animals ; Avoidance Learning/physiology ; Conditioning, Classical/physiology ; Female ; Male ; Memory/physiology ; Nucleus Accumbens/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Wistar ; Recognition, Psychology/physiology ; Taste/*physiology ; }, abstract = {Previous studies have addressed the role of the nucleus accumbens core (NAcbC) and shell (NAcbSh) in taste aversion learning and in the processing of taste palatability which is affected by aging. However, little is known about its implication in safe taste memory and the aging impact. To explore the role of the NAcb in flavor neophobia and its attenuation during aging, we applied c-Fos immunohistochemistry as an index of neural activity of the NAcbC and NAcbSh. Twenty one adult (5-month-old) and 24 aged (24-month-old) male Wistar rats were exposed to a 3% cider vinegar solution for 1, 2 or 6 consecutive days (n = 7 adult and n = 8 aged rats per group). Aged rats exhibited slower attenuation of flavor neophobia than adult rats. Adult rats showed increased NAcbSh c-Fos activity on day 2 compared to days 1 and 6, while this increase was delayed to day 6 in aged rats. There were no differences in the number of NAcbC c-Fos positive cells. This suggests that changes in the activity of neural circuits of palatability processing during normal aging could contribute to the slower attenuation of flavor neophobia in aged rats.}, } @article {pmid31001093, year = {2019}, author = {Totani, Y and Aonuma, H and Oike, A and Watanabe, T and Hatakeyama, D and Sakakibara, M and Lukowiak, K and Ito, E}, title = {Monoamines, Insulin and the Roles They Play in Associative Learning in Pond Snails.}, journal = {Frontiers in behavioral neuroscience}, volume = {13}, number = {}, pages = {65}, pmid = {31001093}, issn = {1662-5153}, abstract = {Molluscan gastropods have long been used for studying the cellular and molecular mechanisms underlying learning and memory. One such gastropod, the pond snail Lymnaea stagnalis, exhibits long-term memory (LTM) following both classical and operant conditioning. Using Lymnaea, we have successfully elucidated cellular mechanisms of learning and memory utilizing an aversive classical conditioning procedure, conditioned taste aversion (CTA). Here, we present the behavioral changes following CTA training and show that the memory score depends on the duration of food deprivation. Then, we describe the relationship between the memory scores and the monoamine contents of the central nervous system (CNS). A comparison of learning capability in two different strains of Lymnaea, as well as the filial 1 (F1) cross from the two strains, presents how the memory scores are correlated in these populations with monoamine contents. Overall, when the memory scores are better, the monoamine contents of the CNS are lower. We also found that as the insulin content of the CNS decreases so does the monoamine contents which are correlated with higher memory scores. The present review deepens the relationship between monoamine and insulin contents with the memory score.}, } @article {pmid30964149, year = {2019}, author = {Williams, RSB and Andrews, PLR}, title = {Advice on avoiding the Valley of Death: insights from a 3Rs model of aversive and emetic compound identification.}, journal = {ALTEX}, volume = {36}, number = {3}, pages = {466-469}, doi = {10.14573/altex.1810182}, pmid = {30964149}, issn = {1868-8551}, support = {NC/M001504/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; NC/S01201/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; }, mesh = {*Animal Testing Alternatives ; Animals ; Dictyostelium/drug effects ; Emetics/*adverse effects ; Humans ; Pharmaceutical Preparations/*chemistry ; Taste/*drug effects ; }, } @article {pmid30936142, year = {2019}, author = {Ratner, C and He, Z and Grunddal, KV and Skov, LJ and Hartmann, B and Zhang, F and Feuchtinger, A and Bjerregaard, A and Christoffersen, C and Tschöp, MH and Finan, B and DiMarchi, RD and Leinninger, GM and Williams, KW and Clemmensen, C and Holst, B}, title = {Long-Acting Neurotensin Synergizes With Liraglutide to Reverse Obesity Through a Melanocortin-Dependent Pathway.}, journal = {Diabetes}, volume = {68}, number = {6}, pages = {1329-1340}, pmid = {30936142}, issn = {1939-327X}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 DK100699/DK/NIDDK NIH HHS/United States ; R01 DK119169/DK/NIDDK NIH HHS/United States ; }, mesh = {Adiposity/*drug effects ; Animals ; Blood Glucose/*drug effects/metabolism ; Body Weight/*drug effects ; Delayed-Action Preparations ; Drug Synergism ; Eating/*drug effects ; Fatty Liver/metabolism/pathology ; Hypoglycemic Agents/*pharmacology ; Liraglutide/*pharmacology ; Liver/drug effects/metabolism/pathology ; Melanocortins/metabolism ; Mice ; Mice, Knockout ; Neurotensin/*pharmacology ; Obesity/*metabolism ; Polyethylene Glycols ; }, abstract = {Neurotensin (NT), a gut hormone and neuropeptide, increases in circulation after bariatric surgery in rodents and humans and inhibits food intake in mice. However, its potential to treat obesity and the subsequent metabolic dysfunctions have been difficult to assess owing to its short half-life in vivo. Here, we demonstrate that a long-acting, pegylated analog of the NT peptide (P-NT) reduces food intake, body weight, and adiposity in diet-induced obese mice when administered once daily for 6 days. Strikingly, when P-NT was combined with the glucagon-like peptide 1 mimetic liraglutide, the two peptides synergized to reduce food intake and body weight relative to each monotherapy, without inducing a taste aversion. Further, P-NT and liraglutide coadministration improved glycemia and reduced steatohepatitis. Finally, we show that the melanocortin pathway is central for P-NT-induced anorexia and necessary for the full synergistic effect of P-NT and liraglutide combination therapy. Overall, our data suggest that P-NT and liraglutide combination therapy could be an enhanced treatment for obesity with improved tolerability compared with liraglutide monotherapy.}, } @article {pmid30900905, year = {2019}, author = {Keeley, A and Teo, M and Ali, Z and Frost, J and Ghimire, M and Rajabi-Siahboomi, A and Orlu, M and Tuleu, C}, title = {In Vitro Dissolution Model Can Predict the in Vivo Taste Masking Performance of Coated Multiparticulates.}, journal = {Molecular pharmaceutics}, volume = {16}, number = {5}, pages = {2095-2105}, doi = {10.1021/acs.molpharmaceut.9b00060}, pmid = {30900905}, issn = {1543-8392}, mesh = {Administration, Oral ; Adolescent ; Adult ; Animals ; Cellulose/analogs & derivatives/chemistry ; Chlorpheniramine/administration & dosage/pharmacology ; Drug Compounding/*methods ; Drug Development/*methods ; *Drug Liberation ; Female ; Healthy Volunteers ; Humans ; Hydrogen-Ion Concentration ; Inhibitory Concentration 50 ; Male ; Middle Aged ; Rats ; Single-Blind Method ; Solubility ; Sugars/chemistry ; Taste/*physiology ; Young Adult ; }, abstract = {The majority of active pharmaceutical ingredients (APIs) are bitter. Therefore, compliance can be a problem where adequate taste masking has not been achieved; this is most problematic in pediatrics. Taste masking is thus a key stage during pharmaceutical development with an array of strategies available to the formulation scientist. Solid oral dosage forms can be taste-masked quite simply by polymer coating, which prevents drug release in the mouth, without unwantedly impairing drug release further down the gastrointestinal tract. At the early stages of pharmaceutical development, an in vitro method for the assessment of taste masking is necessary given the lack of toxicological data preventing the use of human taste panels. Currently, there is no such tool allowing prediction of taste masking efficiency. In this study, drug dissolution in the context of aversive taste thresholds was proposed as a means to bridge this knowledge gap. Thus, a biorelevant buccal dissolution test was developed in which previously determined taste thresholds in vivo were used to evaluate taste masking efficiency: if drug release exceeded said thresholds, the formulation was deemed to be poorly taste-masked, and vice versa. This novel dissolution test was compared to the USP I (basket) dissolution test, and the biopharmaceutical implications of taste masking were also assessed by performing USP I (basket) dissolution testing in simulated gastric fluid (SGF). Chlorphenamine maleate, a model bitter BCS class 1 API, was layered onto sugar spheres and taste-masked using polymer coatings. An array of coating technologies were employed and assessed single blinded: two pH-independent water-insoluble coatings (Surelease:Opadry at 8, 12, and 16% weight gain and Opadry EC at 4, 6, and 8% weight gain) and a pH-dependent water-insoluble reverse-enteric coating (developmental fully formulated system based on Kollicoat Smartseal 100P at 10% weight gain). Both the biorelevant buccal and the USP I dissolution tests were capable of discriminating between both type and level of coating used. However, only the buccal dissolution test was able to provide absolute quantification of the level of taste masking achieved in the context of previously determined taste thresholds, while the USP I test merely provided a relative comparison between the different technologies assessed. When the release data from the buccal test were assessed in parallel to that in SGF, it was possible to predict in vitro optimized taste masking without compromising bioavailability. The fully formulated system based on Smartseal 100P was identified as the most effective coating and Surelease:Opadry the least effective. The developed methodology provides true insight for the formulator, enabling more informed patient-centric formulation decisions, better taste masking, and ultimately more effective medicines.}, } @article {pmid30797833, year = {2019}, author = {Saalfield, J and Spear, L}, title = {Fos activation patterns related to acute ethanol and conditioned taste aversion in adolescent and adult rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {78}, number = {}, pages = {57-68}, pmid = {30797833}, issn = {1873-6823}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects ; Brain/*metabolism ; Conditioning, Psychological/*drug effects ; Edinger-Westphal Nucleus ; Ethanol/*pharmacology ; Immunohistochemistry ; Male ; Nucleus Accumbens/metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Reward ; *Taste Perception ; }, abstract = {Studies in rats have revealed marked age differences in sensitivity to the aversive properties of ethanol, with a developmental insensitivity to ethanol aversion that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion; however, it is unknown how ontogenetic changes within this reward/aversion circuitry contribute to developmental differences in aversive sensitivity. The current study examined early adolescent (postnatal day [P]28-30) and adult (P72-74) Sprague-Dawley male rats for conditioned taste aversion (CTA) after doses of 0, 1.0, or 2.5 g/kg ethanol, and patterns of neuronal activation in response to ethanol using Fos-like immunohistochemistry (Fos+) to uncover regions where age differences in activation are associated with ethanol aversion. An adolescent-specific ethanol-induced increase in Fos+ staining was seen within the nucleus accumbens shell and core. An age difference was also noted within the Edinger-Westphal nucleus (EW) following administration of the lower dose of ethanol, with 1 g/kg ethanol producing CTA in adults but not in adolescents and inducing a greater EW Fos response in adults than adolescents. Regression analysis revealed that greater numbers of Fos+ neurons within the EW and insula (Ins) were related to lower consumption of the conditioned stimulus (CS) on test day (reflecting greater CTA). Some regionally specific age differences in Fos+ were noted under baseline conditions, with adolescents displaying fewer Fos+ neurons than adults within the prelimbic (PrL) cortex, but more than adults in the bed nucleus of the stria terminalis (BNST). In the BNST (but not PrL), ethanol-induced increases in Fos-immunoreactivity (IR) were evident at both ages. Increased ethanol-induced activity within critical appetitive brain regions (NAc core and shell) supports a role for greater reward-related activation during adolescence, possibly along with attenuated responsiveness to ethanol in EW and Ins in the age-typical resistance of adolescents to the aversive properties of ethanol.}, } @article {pmid30769105, year = {2019}, author = {Pohjanvirta, R and Mahiout, S}, title = {Aryl hydrocarbon receptor is indispensable for β-naphthoflavone-induced novel food avoidance and may be involved in LiCl-triggered conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {204}, number = {}, pages = {58-64}, doi = {10.1016/j.physbeh.2019.02.014}, pmid = {30769105}, issn = {1873-507X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Basic Helix-Loop-Helix Transcription Factors/drug effects/genetics/*physiology ; Cytochrome P-450 CYP1A1/biosynthesis/genetics ; Enzyme Induction/drug effects ; Feeding Behavior/*drug effects ; Gene Knockout Techniques ; Lithium Chloride/*pharmacology ; Neurons, Afferent/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Aryl Hydrocarbon/drug effects/genetics/*physiology ; Taste/*drug effects ; Vagotomy ; beta-Naphthoflavone/*pharmacology ; }, abstract = {Previous studies have shown that several aryl hydrocarbon receptor (AHR) agonists, including β-naphthoflavone (BNF), elicit avoidance of novel food items in rodents, with this behavioral response displaying a similar dose-response to hepatic induction of CYP1A1. The avoidance has been found to bear substantial similarity to conditioned taste avoidance/aversion (CTA). The present study set out to confirm the indispensability of AHR in the avoidance response, to verify whether vagal afferent fibers are involved in it, and to see if AHR signaling might interfere with the effect of the classic trigger of CTA, LiCl. To this end, globally AHR deficient (AHRKO) or vagotomized wildtype rats were treated by gavage with 60 mg/kg BNF or ip with 0.15 M LiCl (4 ml/kg), and presented with chocolate which was either novel or familiar to them. Both the avoidance response and Cyp1a1 induction were missing in AHRKO rats. In contrast, Ahr[+/-] rats exhibited them in full, save for a single outlier. Total subdiaphragmatic vagotomy failed to interfere with the avoidance of novel or familiar chocolate or induction of Cyp1a1. After LiCl administration, male AHRKO rats showed a significantly mitigated suppression of chocolate consumption compared with wildtype animals (~60% vs. ~10% of control chocolate intake, respectively). A similar tendency was seen in females, but they were less responsive to LiCl. These findings corroborate AHR as a prerequisite of the BNF-induced novel food avoidance, prove vagal afferents unlikely mediators of this response, and imply an unforeseen involvement of AHR signaling in the thoroughly-characterized CTA instigated by LiCl.}, } @article {pmid30676659, year = {2019}, author = {Katzman, DK and Norris, ML and Zucker, N}, title = {Avoidant restrictive food intake disorder: First do no harm.}, journal = {The International journal of eating disorders}, volume = {52}, number = {4}, pages = {459-461}, doi = {10.1002/eat.23021}, pmid = {30676659}, issn = {1098-108X}, support = {R33-MH-097959/MH/NIMH NIH HHS/United States ; }, mesh = {Anorexia Nervosa/*psychology/therapy ; Feeding and Eating Disorders/*psychology/therapy ; Humans ; Retrospective Studies ; }, abstract = {OBJECTIVE: This opinion piece offers some considerations, both medical and psychological, for the use of nasogastric tube (NGT) feedings in the treatment of avoidant restrictive food intake disorder (ARFID) in children and adolescents.

METHOD: Although there is empirical support for the use of NGT feedings in the treatment of anorexia nervosa, this evidence base does not exist for the treatment of ARFID. As such, there is need to delineate pragmatic considerations in the use of this procedure.

RESULTS: Issues of medical necessity notwithstanding, we advise that the use of this procedure be considered more cautiously due to the oral sensitivities inherent in many individuals with ARFID and the potential psychological consequences. These sensitivities may make the experience of NGT feedings particularly aversive, with the potential of creating iatrogenic conditioned food aversions.

DISCUSSION: This article encourages clinicians to give careful thought and attention when considering NGT feedings in children and adolescents with ARFID.}, } @article {pmid30639358, year = {2019}, author = {Patel, S and Alvarez-Guaita, A and Melvin, A and Rimmington, D and Dattilo, A and Miedzybrodzka, EL and Cimino, I and Maurin, AC and Roberts, GP and Meek, CL and Virtue, S and Sparks, LM and Parsons, SA and Redman, LM and Bray, GA and Liou, AP and Woods, RM and Parry, SA and Jeppesen, PB and Kolnes, AJ and Harding, HP and Ron, D and Vidal-Puig, A and Reimann, F and Gribble, FM and Hulston, CJ and Farooqi, IS and Fafournoux, P and Smith, SR and Jensen, J and Breen, D and Wu, Z and Zhang, BB and Coll, AP and Savage, DB and O'Rahilly, S}, title = {GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.}, journal = {Cell metabolism}, volume = {29}, number = {3}, pages = {707-718.e8}, pmid = {30639358}, issn = {1932-7420}, support = {200848/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; U54 GM104940/GM/NIGMS NIH HHS/United States ; 106263/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 095515/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_00014/5/MRC_/Medical Research Council/United Kingdom ; MC_UU_12012/1/MRC_/Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; G0600717/MRC_/Medical Research Council/United Kingdom ; MC_UU_00014/2/MRC_/Medical Research Council/United Kingdom ; MC_UU_12012/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_00014/3/MRC_/Medical Research Council/United Kingdom ; 107064//Wellcome Trust/United Kingdom ; MC_UU_12012/2/MRC_/Medical Research Council/United Kingdom ; 106262/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 098497/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; G0802051/MRC_/Medical Research Council/United Kingdom ; G9824984/MRC_/Medical Research Council/United Kingdom ; 100574/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; G0900554/MRC_/Medical Research Council/United Kingdom ; G0400192/MRC_/Medical Research Council/United Kingdom ; WT 107064/WT_/Wellcome Trust/United Kingdom ; MC_UU_00014/1/MRC_/Medical Research Council/United Kingdom ; 100140//Wellcome Trust/United Kingdom ; MC_UU_12012/5/MRC_/Medical Research Council/United Kingdom ; RG/12/13/29853/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adult ; Animals ; Cell Line ; Diet, High-Fat/methods ; Energy Intake/*physiology ; Growth Differentiation Factor 15/*metabolism/pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Young Adult ; }, abstract = {GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.}, } @article {pmid30609665, year = {2019}, author = {Crabbe, JC and Metten, P and Savarese, AM and Ozburn, AR and Schlumbohm, JP and Spence, SE and Hack, WR}, title = {Ethanol Conditioned Taste Aversion in High Drinking in the Dark Mice.}, journal = {Brain sciences}, volume = {9}, number = {1}, pages = {}, pmid = {30609665}, issn = {2076-3425}, support = {IK2 BX002488/BX/BLRD VA/United States ; AA013519/AA/NIAAA NIH HHS/United States ; T32 AA007468/AA/NIAAA NIH HHS/United States ; U01 AA013519/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; I01 BX000313/BX/BLRD VA/United States ; AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; R24 AA020245/AA/NIAAA NIH HHS/United States ; AA020245/AA/NIAAA NIH HHS/United States ; }, abstract = {Two independent lines of High Drinking in the Dark (HDID-1, HDID-2) mice have been bred to reach high blood alcohol levels after a short period of binge-like ethanol drinking. Male mice of both lines were shown to have reduced sensitivity to develop a taste aversion to a novel flavor conditioned by ethanol injections as compared with their unselected HS/NPT founder stock. We have subsequently developed inbred variants of each line. The current experiments established that reduced ethanol-conditioned taste aversion is also seen in the inbred variants, in both males and females. In other experiments, we asked whether HDID mice would ingest sufficient doses of ethanol to lead to a conditioned taste aversion upon retest. Different manipulations were used to elevate consumption of ethanol on initial exposure. Access to increased ethanol concentrations, to multiple tubes of ethanol, and fluid restriction to increase thirst motivation all enhanced initial drinking of ethanol. Each condition led to reduced intake the next day, consistent with a mild conditioned taste aversion. These experiments support the conclusion that one reason contributing to the willingness of HDID mice to drink to the point of intoxication is a genetic insensitivity to the aversive effects of ethanol.}, } @article {pmid30597200, year = {2019}, author = {Gore-Langton, JK and Spear, LP}, title = {Prenatal ethanol exposure attenuates sensitivity to the aversive effects of ethanol in adolescence and increases adult preference for a 5% ethanol solution in males, but not females.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {79}, number = {}, pages = {59-69}, pmid = {30597200}, issn = {1873-6823}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; *Alcohol Drinking ; Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/*pharmacology ; Conditioning, Classical/*drug effects ; Ethanol/*pharmacology ; Female ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Sex Factors ; Sodium Chloride/administration & dosage ; Taste/*drug effects ; }, abstract = {The present set of experiments investigated the effects of a moderate dose of ethanol (2 g/kg; 20% v/v intragastrically) during late gestation (G17-20 [gestational day]) on ethanol-induced conditioned taste aversion (CTA) in adolescence, and on ethanol consumption during adolescence and early adulthood. In experiment 1, male and female Sprague-Dawley rats were given 30-min access to a sweetened "supersaccharin" (SS) solution or sodium chloride (NaCl), followed by an intraperitoneal injection of 20% ethanol (0, 1, 1.25, or 1.5 g/kg) for three conditioning/test sessions. Among animals conditioned with SS, prenatally ethanol-exposed males exhibited attenuated ethanol-induced CTA relative to males prenatally gavaged with water or non-manipulated, whereas prenatal treatment had no effect on CTA in females. Among animals conditioned with NaCl, there were no exposure group differences in males, with modest evidence for attenuated CTA in prenatally ethanol-exposed females. In experiment 2, the effects of prenatal ethanol exposure on ethanol consumption in adolescents (P35 ± 1 day [postnatal day]) and adults (P56-60) were explored. At the beginning of the dark cycle, pair-housed rats were given three bottles containing 0, 5, and 10% ethanol for 18 h every other day (i.e., Monday, Wednesday, Friday) for 3 weeks. Relative to water controls, adult males prenatally exposed to ethanol showed greater preference and more intake (g/kg) of 5% ethanol, while showing lower intake of 10% ethanol. These intake and preference differences were not evident in adolescent males. Among females at both ages, ethanol-exposed animals showed lower preference and intake (g/kg) of 5% ethanol than their water-exposed controls. Thus, moderate ethanol exposure during late gestation produced a largely male-specific attenuation in the aversive effects of ethanol during adolescence that could contribute to later increases in preference and intake of a 5% ethanol solution, although this emergent effect was not evident in adolescence (or in females), but only manifested in adulthood.}, } @article {pmid30596779, year = {2018}, author = {Mura, E and Taruno, A and Yagi, M and Yokota, K and Hayashi, Y}, title = {Innate and acquired tolerance to bitter stimuli in mice.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0210032}, pmid = {30596779}, issn = {1932-6203}, mesh = {Adaptation, Physiological/*drug effects ; Animals ; Behavior, Animal/*drug effects ; Female ; Isoleucine/*pharmacology ; Mice ; Taste Perception/*drug effects ; Tryptophan/*pharmacology ; }, abstract = {Tolerance to bitter foods and its potentiation by repetitive exposure are commonly experienced and potentially underlie the consumption of bitter foods, but it remains unknown whether permissive and adaptive responses are general phenomena for bitter-tasting substances or specific to certain substances, and they have not been rigorously studied in mice. Here, we investigated the effects of prolonged exposure to a bitter compound on both recognition and rejection behaviors to the same compound in mice. Paired measurements of rejection (RjT) and apparent recognition (aRcT) thresholds were conducted using brief-access two-bottle choice tests before and after taste aversion conditioning, respectively. First, RjT was much higher than aRcT for the bitter amino acids L-tryptophan and L-isoleucine, which mice taste daily in their food, indicating strong acceptance of those familiar stimuli within the concentration range between RjT and aRcT. Next, we tested five other structurally dissimilar bitter compounds, to which mice were naive at the beginning of experiments: denatonium benzoate, quinine-HCl, caffeine, salicin, and epigallocatechin gallate. RjT was moderately higher than aRcT for all the compounds tested, indicating the presence of innate acceptance to these various, unfamiliar bitter stimuli in mice. Lastly, a 3-week forced exposure increased RjT for all the bitter compounds except salicin, demonstrating that mice acquire tolerance to a broad array of bitter compounds after long-term exposure to them. Although the underlying mechanisms remain to be determined, our studies provide behavioral evidence of innate and acquired tolerance to various bitter stimuli in mice, suggesting its generality among bitterants.}, } @article {pmid30564271, year = {2018}, author = {Zhou, D and Zhao, Y and Hook, M and Zhao, W and Starlard-Davenport, A and Cook, MN and Jones, BC and Hamre, KM and Lu, L}, title = {Ethanol's Effect on Coq7 Expression in the Hippocampus of Mice.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {602}, pmid = {30564271}, issn = {1664-8021}, support = {R01 AA021951/AA/NIAAA NIH HHS/United States ; U01 AA014425/AA/NIAAA NIH HHS/United States ; }, abstract = {Coenzyme Q (CoQ) is a well-studied molecule, present in every cell membrane in the body, best known for its roles as a mitochondrial electron transporter and a potent membrane anti-oxidant. Much of the previous work was done in vitro in yeast and more recent work has suggested that CoQ may have additional roles prompting calls for a re-assessment of its role using in vivo systems in mammals. Here we investigated the putative role of Coenzyme Q in ethanol-induced effects in vivo using BXD RI mice. We examined hippocampal expression of Coq7 in saline controls and after an acute ethanol treatment, noting enriched biologic processes and pathways following ethanol administration. We also identified 45 ethanol-related phenotypes that were significantly correlated with Coq7 expression, including six phenotypes related to conditioned taste aversion and ethanol preference. This analysis highlights the need for further investigation of Coq7 and related genes in vivo as well as previously unrecognized roles that it may play in the hippocampus.}, } @article {pmid30557602, year = {2019}, author = {Nakajima, S}, title = {Food avoidance learning based on voluntary wheel running in laboratory mice (Mus musculus).}, journal = {Behavioural processes}, volume = {159}, number = {}, pages = {31-36}, doi = {10.1016/j.beproc.2018.12.010}, pmid = {30557602}, issn = {1872-8308}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; *Food ; Food Deprivation ; Male ; Mice/*psychology ; *Motor Activity ; Taste ; }, abstract = {Mice show a reluctance to eat unfamiliar food, when they first encounter it. This neophobic reaction is conventionally habituated by repeated trials: the mice gradually increase their consumption of the novel food. The new finding reported here is that the consumption remains low in mice that voluntarily run in activity wheels after the novel food access. This effect implies that running yields Pavlovian conditioned flavor aversion, which suppresses, otherwise increasing, consumption of the novel food. In the present research, the effect was demonstrated with a between-group design by pitting experimental mice receiving cheese-running paired treatment against cheese/running unpaired control mice (Experiment 1). The running-based food avoidance in mice was also shown in a differential conditioning paradigm, where one of two novel snacks (chocolate and marshmallow) was paired with running while the other was not, in non-deprived animals (Experiment 2 A) and food-deprived animals (Experiment 2B). These results concord with those previously reported in rats, indicating the generality of the phenomenon.}, } @article {pmid30500564, year = {2019}, author = {Serita, T and Miyahara, M and Tanimizu, T and Takahashi, S and Oishi, S and Nagayoshi, T and Tsuji, R and Inoue, H and Uehara, M and Kida, S}, title = {Dietary magnesium deficiency impairs hippocampus-dependent memories without changes in the spine density and morphology of hippocampal neurons in mice.}, journal = {Brain research bulletin}, volume = {144}, number = {}, pages = {149-157}, doi = {10.1016/j.brainresbull.2018.11.019}, pmid = {30500564}, issn = {1873-2747}, mesh = {Animals ; Anxiety/physiopathology ; Conditioning, Classical/physiology ; Dendritic Spines ; Dietary Supplements ; Fear/physiology ; Glutamic Acid/pharmacology ; Hippocampus/drug effects ; Learning/physiology ; Magnesium/metabolism ; Magnesium Deficiency/*metabolism/physiopathology ; Male ; Memory/*drug effects/*physiology ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity/physiology ; Neurons/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Recognition, Psychology ; Synaptic Transmission/physiology ; }, abstract = {Magnesium (Mg[2+]) is an essential mineral for maintaining biological functions. One major action of Mg[2+] in the brain is modulating the voltage-dependent blockade of N-methyl-d-aspartate type glutamate receptors, thereby controlling their opening, which is crucial for synaptic plasticity. Therefore, Mg[2+] has been shown to play critical roles in learning and memory, and synaptic plasticity. However, the effects of dietary Mg[2+] deficiency (MgD) on learning and memory and the morphology of neurons contributing to memory performance have not been examined in depth. Here, we show that MgD impairs hippocampus-dependent memories in mice. Mice fed an MgD diet showed deficits in hippocampus-dependent contextual fear, spatial and social recognition memories, although they showed normal amygdala- and insular cortex-dependent conditioned taste aversion memory, locomotor activity, and emotional behaviors such as anxiety-related and social behaviors. However, MgD mice showed normal spine density and morphology of hippocampal neurons. These findings suggest that MgD impairs hippocampus-dependent memory without affecting the morphology of hippocampal neurons.}, } @article {pmid30472309, year = {2019}, author = {Barney, TM and Vore, AS and Gano, A and Mondello, JE and Deak, T}, title = {The influence of central interleukin-6 on behavioral changes associated with acute alcohol intoxication in adult male rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {79}, number = {}, pages = {37-45}, pmid = {30472309}, issn = {1873-6823}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; T32 AA025606/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholic Intoxication/*metabolism ; Animals ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/*pharmacology ; Ethanol/administration & dosage ; Interleukin-6/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Reflex, Righting/*drug effects ; Signal Transduction/drug effects ; Sucrose/administration & dosage ; Taste/drug effects ; Tyrphostins/*pharmacology ; }, abstract = {Recent studies have demonstrated brain cytokine fluctuations associated with acute ethanol intoxication (increased IL-6) and withdrawal (increased IL-1β and TNFα). The purpose of the present studies was to examine the potential functional role of increased central interleukin-6 (IL-6). We utilized two tests of ethanol sensitivity to establish a potential role for IL-6 after high (3.5-4.0 g/kg, intraperitoneally [i.p.]) or moderate (2.0 g/kg, i.p.) doses of ethanol: loss of righting reflex (LORR) and conditioned taste aversion (CTA), respectively. Briefly, guide cannulae were implanted into the third ventricle of adult male Sprague-Dawley rats. In the first experiments, rats were infused with 25, 50, 100, or 200 ng of IL-6; or 0.3, 3.0, or 9.0 μg of the JAK/STAT inhibitor AG490 30 min prior to a high-dose ethanol challenge. Although sleep time was not affected by exogenous IL-6, infusion of AG490 increased latency to lose the righting reflex relative to vehicle-infused rats. Next, we assessed whether IL-6 was sufficient to produce a CTA. Moderately water-deprived rats received intracerebroventricular (i.c.v.) infusions of 25, 50, or 100 ng IL-6 immediately after 60-min access to 5% sucrose solution. Forty-eight hours later, rats were returned to the context and given 60-min access to sucrose solution. IL-6 infusion had no significant effect on sucrose intake when all rats were considered together. However, a median split revealed that low sucrose-consuming rats significantly increased their drinking on test day, an effect that was not seen in rats that received 50 or 100 ng of IL-6. In the last study, AG490 had no effect on ethanol-induced CTA (2 g/kg). Overall, these studies suggest that IL-6 had only a minor influence on ethanol-induced behavioral changes, yet phenotypic differences in sensitivity to IL-6 were apparent. These studies are among the first to examine a potential functional role for IL-6 in ethanol-related behaviors, and may have important implications for understanding the relationship between acute ethanol intoxication and its associated behavioral alterations.}, } @article {pmid30465759, year = {2018}, author = {Barik, A and Krashes, MJ}, title = {Remembering a Bad Taste.}, journal = {Neuron}, volume = {100}, number = {4}, pages = {765-767}, doi = {10.1016/j.neuron.2018.11.012}, pmid = {30465759}, issn = {1097-4199}, mesh = {*Avoidance Learning ; Conditioning, Classical ; Memory ; Neurons ; *Taste ; }, abstract = {The phenomenon of conditioned taste aversion (CTA) is generated after ingestion of a specific food is associated with an adverse outcome, i.e., sickness. In this issue of Neuron, Chen et al. (2018) interrogate the pivotal role of PBN[CGRP] neurons in both the acquisition and the expression of CTA.}, } @article {pmid30447220, year = {2019}, author = {Delay, ER and Weaver, B and Lane, DR and Kondoh, T}, title = {Dried bonito dashi: Contributions of mineral salts and organic acids to the taste of dashi.}, journal = {Physiology & behavior}, volume = {199}, number = {}, pages = {127-136}, doi = {10.1016/j.physbeh.2018.11.016}, pmid = {30447220}, issn = {1873-507X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Flavoring Agents/*pharmacology ; Generalization, Psychological/*drug effects ; Male ; Mice ; Salts/*pharmacology ; Smell/*drug effects ; }, abstract = {Dried bonito dashi is often used in Japanese cuisine with a number of documented positive health effects. Its major taste is thought to be umami, elicited by inosine 5'-monophosphate (IMP) and L-amino acids. Previously we found that lactic acid, a major component of dried bonito dashi, enhanced the contribution of many of these amino acids to the taste of dried bonito dashi, and reduced the contribution of other amino acids. In addition to amino acids, dried bonito dashi also has a significant mineral salt component. The present study used conditioned taste aversion methods with mice (all had compromised olfactory systems) to compare the taste qualities of dried bonito dashi with four salts (NaCl, KCl, CaCl2 and MgCl2), with and without lactic acid or citric acid. A conditioned taste aversion to 25% dried bonitio dashi generalized significantly to NaCl and KCl, with or without 0.9% lactic acid added but not when citric acid was added. Generalization of the CTA to dried bonito dashi was much stronger to the divalent salts, but when either lactic acid or citric acid was added, this aversion was eliminated. These results suggest that these salts contribute to the complex taste of dried bonito dashi and that both organic acids appear able to modify the tastes of divalent salts.}, } @article {pmid30407064, year = {2018}, author = {Bernal-Gamboa, R and Rosas, JM and Nieto, J}, title = {Extinction makes acquisition context-specific in conditioned taste aversion regardless of the context where acquisition and testing take place.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {44}, number = {4}, pages = {385-395}, doi = {10.1037/xan0000183}, pmid = {30407064}, issn = {2329-8464}, mesh = {Analysis of Variance ; Animals ; *Association ; Attention/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Cues ; Extinction, Psychological/*physiology ; Feeding Behavior ; Female ; Mental Recall ; Rats ; Rats, Wistar ; Taste/*physiology ; Time Factors ; }, abstract = {Retrieval of a flavor-illness association has been found to show contextual dependence when the association is learned after a nontarget flavor-illness association has been extinguished in what has been named as the extinction makes acquisition context-specific (EMACS) effect. Four experiments were designed to further explore the EMACS effect in conditioned taste aversion. Experiments 1 and 2 replicated the EMACS effect using rats that did not experience extinction, and rats that underwent extinction of a different flavor as controls. Experiments 3 and 4 found that the experience of extinction with the nontarget Flavor X in a given context (A) led to context-specificity of performance to the target Flavor Y both, when Y was trained in a highly familiar context (B) and tested in the context where X had been trained (Context A, Experiment 3), and when the test was conducted in a less familiar context (C) where no cues or outcomes were presented before (Experiment 4). These results are consistent with the idea that the experience of extinction encourages organism's attention to the contexts, making retrieval of new learning context-specific. (PsycINFO Database Record (c) 2018 APA, all rights reserved).}, } @article {pmid30407063, year = {2018}, author = {Thrailkill, EA and Trask, S and Vidal, P and Alcalá, JA and Bouton, ME}, title = {Stimulus control of actions and habits: A role for reinforcer predictability and attention in the development of habitual behavior.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {44}, number = {4}, pages = {370-384}, pmid = {30407063}, issn = {2329-8464}, support = {R01 DA033123/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Attention/*physiology ; Avoidance Learning/physiology ; Conditioning, Operant/*physiology ; Discrimination, Psychological/*physiology ; Fasting ; Female ; *Habits ; Rats ; Rats, Wistar ; Reaction Time/physiology ; *Reinforcement, Psychology ; Time Factors ; }, abstract = {Goal-directed actions are instrumental behaviors whose performance depends on the organism's knowledge of the reinforcing outcome's value. In contrast, habits are instrumental behaviors that are insensitive to the outcome's current value. Although habits in everyday life are typically controlled by stimuli that occasion them, most research has studied habits using free-operant procedures in which no discrete stimuli are present to occasion the response. We therefore studied habit learning when rats were reinforced for lever pressing on a random-interval 30-s schedule in the presence of a discriminative stimulus (S) but not in its absence. In Experiment 1, devaluing the reinforcer with taste aversion conditioning weakened instrumental responding in a 30-s S after 4, 22, and 66 sessions of instrumental training. Even extensive practice thus produced goal-directed action, not habit. Experiments 2 and 3 contrastingly found habit when the duration of S was increased from 30 s to 8 min. Experiment 4 then found habit with the 30-s S when it always contained a reinforcer; goal-directed action was maintained when reinforcers were earned at the same rate but occurred in only 50% of Ss (as in the previous experiments). The results challenge the view that habits are an inevitable consequence of repeated reinforcement (as in the law of effect) and instead suggest that discriminated habits develop when the reinforcer becomes predictable. Under those conditions, organisms may pay less attention to their behavior, much as they pay less attention to signals associated with predicted reinforcers in Pavlovian conditioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).}, } @article {pmid30375738, year = {2019}, author = {Yasumatsu, K and Iwata, S and Inoue, M and Ninomiya, Y}, title = {Fatty acid taste quality information via GPR120 in the anterior tongue of mice.}, journal = {Acta physiologica (Oxford, England)}, volume = {226}, number = {1}, pages = {e13215}, doi = {10.1111/apha.13215}, pmid = {30375738}, issn = {1748-1716}, support = {JP 26670810//JSPS KAKENHI/International ; JP 15H02571//JSPS KAKENHI/International ; JP 18H02968//JSPS KAKENHI/International ; JP 18K19653//JSPS KAKENHI/International ; //Japan Society for the Promotion of Science/International ; }, mesh = {Animals ; Behavior, Animal ; Benzoates/pharmacology ; Chorda Tympani Nerve/drug effects/physiology ; Fatty Acids/*pharmacology ; Gene Expression Regulation/drug effects ; Mice ; Pyrimidines/pharmacology ; Receptors, G-Protein-Coupled/antagonists & inhibitors/genetics/*metabolism ; Sulfonamides/pharmacology ; Taste/*physiology ; Tongue/*physiology ; Xanthenes/pharmacology ; }, abstract = {AIM: To elucidate whether fatty acid taste has a quality that does not overlap with other primary qualities, we investigated potential neuron types coding fatty acid information and how GPR120 is involved.

METHODS: Single fibre recordings in the chorda tympani (CT) nerve and behavioural response measurements using a conditioned taste aversion paradigm were performed in GPR120-knockout (KO) and wild-type (WT) mice.

RESULTS: Single fibres can be classified into fatty acid (F)-, S-, M-, electrolyte (E)-, Q-, and N-type groups according to the maximal response among oleic acid, sucrose, monopotassium glutamate (MPG), HCl, quinine hydrochloride, and NaCl respectively. Among fibres, 4.0% in GPR120-KO and 17.9% in WT mice showed a maximal response to oleic acid (F-type). Furthermore, half or more of S- and M-type fibres showed responses to fatty acids in both mouse strains, although the thresholds in KO mice were significantly higher and impulse frequencies lower than those in WT mice. GPR120-KO mice conditioned to avoid linoleic acid showed generalized stimulus avoidances for MPG, indicating qualitative similarity between linoleic acid and MPG. The KO mice showed a higher generalization threshold for linoleic acid than that of WT mice.

CONCLUSION: Fatty acid taste is suggested to have a unique quality owing to the discovery of F-type fibres, with GPR120 involved in neural information pathways for a unique quality and palatable taste qualities in the mouse CT nerve. GPR120 plays roles in distinguishing fatty acid taste from other primary tastes and the detection of low linoleic acid concentrations.}, } @article {pmid30359063, year = {2019}, author = {Schoenberg, HL and Sola, EX and Seyller, E and Kelberman, M and Toufexis, DJ}, title = {Female rats express habitual behavior earlier in operant training than males.}, journal = {Behavioral neuroscience}, volume = {133}, number = {1}, pages = {110-120}, doi = {10.1037/bne0000282}, pmid = {30359063}, issn = {1939-0084}, mesh = {Animals ; *Conditioning, Operant ; Extinction, Psychological ; Female ; *Habits ; Male ; Rats, Long-Evans ; *Reinforcement, Psychology ; }, abstract = {Habitual behavior can be advantageous by increasing the availability of cognitive resources for use in other tasks. However, habitual behaviors are problematic when they are coopted to prolong the maladaptive responding present in several psychopathologies such as substance abuse, dysregulated fear responding in posttraumatic stress disorder, and obsessive-compulsive disorder. Although sex differences exist in the occurrence or progression of these psychopathologies, there are no studies that compare the development of habitual behavior systematically in male and female animals. In the present study, male and female rats were identically trained on a variable interval 30-s (VI 30-s) schedule of reinforcement to nose-poke for sucrose pellet reinforcers. Subsequently, the sucrose was devalued in one half of the animals by pairing its presentation with injections of lithium chloride (LiCl) to induce nausea, thus conditioning a taste aversion. Habitual behavior was operationalized as continued operant responding in an extinction test following devaluation of the sucrose reinforcer. Successful devaluation was confirmed with both a consumption and reacquisition test. Given identical training to 240 sucrose pellets, female rats demonstrate habitual behavior whereas male rats remain goal-directed. Additionally, females are habitual after 200 or 160 reinforcers earned on a VI 30-s schedule, but remain goal-directed at 120 and 80 reinforcers on this schedule. These data suggest that behavioral flexibility may be compromised in female rats compared to males due to accelerated habit formation in females. These results are important because sex differences are present in several psychopathologies, which may be related to differences in the development of habitual behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, } @article {pmid30344042, year = {2018}, author = {Chen, JY and Campos, CA and Jarvie, BC and Palmiter, RD}, title = {Parabrachial CGRP Neurons Establish and Sustain Aversive Taste Memories.}, journal = {Neuron}, volume = {100}, number = {4}, pages = {891-899.e5}, pmid = {30344042}, issn = {1097-4199}, support = {/HHMI_/Howard Hughes Medical Institute/United States ; R01 DA024908/DA/NIDA NIH HHS/United States ; T32 DA007278/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Calcitonin Gene-Related Peptide/genetics/*metabolism ; Female ; Male ; Memory/*physiology ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Neurons/chemistry/*metabolism ; Parabrachial Nucleus/chemistry/*metabolism ; Photic Stimulation/methods ; Taste/*physiology ; }, abstract = {Food aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. We identified calcitonin-gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) as sufficient and necessary for establishing a conditioned taste aversion (CTA). Photoactivating projections from CGRP[PBN] neurons to either the central nucleus of the amygdala or the bed nucleus of the stria terminalis can also induce robust CTA. CGRP[PBN] neurons undergo plasticity following CTA, and inactivation of either Arc or Grin1 (genes involved in memory consolidation) prevents establishment of a strong CTA. Calcium imaging reveals that the novel food re-activates CGRP[PBN] neurons after conditioning. Inhibition of these neurons or inactivation of the Grin1 gene after conditioning attenuates CTA expression. Our results indicate that CGRP[PBN] neurons not only play a key role for learning food aversions but also contribute to the maintenance and expression of those memories.}, } @article {pmid30336209, year = {2018}, author = {Arthurs, J and Lin, JY and Reilly, S}, title = {Inhibiting gustatory thalamus or medial amygdala has opposing effects on taste neophobia.}, journal = {Neurobiology of learning and memory}, volume = {156}, number = {}, pages = {24-32}, pmid = {30336209}, issn = {1095-9564}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Conditioning, Classical/*drug effects ; Corticomedial Nuclear Complex/*drug effects ; GABA Agonists/*pharmacology ; Genetic Techniques ; Male ; Rats ; Rats, Sprague-Dawley ; Taste Perception/*drug effects ; Ventral Thalamic Nuclei/*drug effects ; }, abstract = {Taste neophobia is a feeding system defense mechanism that limits consumption of an unknown, and therefore potentially dangerous, edible until the post-ingestive consequences are experienced. We found that transient pharmacological inhibition (induced with the GABA agonists baclofen and muscimol) of the gustatory thalamus (GT; Experiment 1), but not medial amygdala (MeA; Experiment 2), during exposure to a novel saccharin solution attenuated taste neophobia. In Experiment 3 we found that inhibition of MeA neurons (induced with the chemogenetic receptor hM4DGi) enhanced the expression of taste neophobia whereas excitation of MeA neurons (with hM3DGq) had no influence of taste neophobia. Overall, these results refine the temporal involvement of the GT in the occurrence of taste neophobia and support the hypothesis that neuronal excitation in the GT is necessary for taste neophobia. Conversely, we show that chemogenetically, but not pharmacologically, inhibiting MeA neurons is sufficient to exaggerate the expression of taste neophobia.}, } @article {pmid30322892, year = {2018}, author = {Flores, VL and Parmet, T and Mukherjee, N and Nelson, S and Katz, DB and Levitan, D}, title = {The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {25}, number = {11}, pages = {587-600}, pmid = {30322892}, issn = {1549-5485}, support = {F31 DC015931/DC/NIDCD NIH HHS/United States ; R01 DC006666/DC/NIDCD NIH HHS/United States ; R01 DC007703/DC/NIDCD NIH HHS/United States ; T32 GM084907/GM/NIGMS NIH HHS/United States ; R90 DA033463/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Cerebral Cortex/cytology/*physiology ; Citric Acid ; Dietary Sucrose ; Female ; Gene Expression ; Immunohistochemistry ; Learning/*physiology ; Optogenetics ; Proto-Oncogene Proteins c-fos/metabolism ; Random Allocation ; Rats, Long-Evans ; Sodium Chloride ; Taste Perception/*physiology ; }, abstract = {The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with "incidental" stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste preexposure-TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (c-Fos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change c-Fos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA-related c-Fos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.}, } @article {pmid30314288, year = {2018}, author = {Kivell, BM and Paton, KF and Kumar, N and Morani, AS and Culverhouse, A and Shepherd, A and Welsh, SA and Biggerstaff, A and Crowley, RS and Prisinzano, TE}, title = {Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {10}, pages = {}, pmid = {30314288}, issn = {1420-3049}, support = {P20 GM113117/GM/NIGMS NIH HHS/United States ; T32 GM008545/GM/NIGMS NIH HHS/United States ; R01 DA018151/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Anxiety/drug therapy/metabolism ; Behavior, Animal/*drug effects ; Cocaine/*adverse effects ; Cocaine-Related Disorders/drug therapy/*metabolism/*psychology ; Diterpenes/adverse effects/chemistry/*pharmacology ; Diterpenes, Clerodane/adverse effects/chemistry/*pharmacology ; Learning/drug effects ; Male ; Mesylates/adverse effects/chemistry/*pharmacology ; Mice ; Motor Activity/drug effects ; Nociception/drug effects ; Pain/drug therapy/etiology/metabolism ; Rats ; Receptors, Opioid, kappa/*agonists ; Recognition, Psychology/drug effects ; }, abstract = {The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant Salvia divinorum. We assessed the antinociceptive, anti-cocaine, and side-effects of Mesyl Sal B. The anti-cocaine effects are evaluated in cocaine-induced hyperactivity and behavioral sensitization to cocaine in male Sprague Dawley rats. Mesyl Sal B was assessed for anhedonia (conditioned taste aversion), aversion (conditioned place aversion), pro-depressive effects (forced swim test), anxiety (elevated plus maze) and learning and memory deficits (novel object recognition). In male B6.SJL mice, the antinociceptive effects were evaluated in warm-water (50 °C) tail withdrawal and intraplantar formaldehyde (2%) assays and the sedative effects measured with the rotarod performance task. Mesyl Sal B (0.3 mg/kg) attenuated cocaine-induced hyperactivity and behavioral sensitization to cocaine without modulating sucrose self-administration and without producing aversion, sedation, anxiety, or learning and memory impairment in rats. However, increased immobility was observed in the forced swim test indicating pro-depressive effects. Mesyl Sal B was not as potent as Sal A at reducing pain in the antinociceptive assays. In conclusion, Mesyl Sal B possesses anti-cocaine effects, is longer acting in vivo and has fewer side-effects when compared to Sal A, however, the antinociceptive effects are limited.}, } @article {pmid30300803, year = {2018}, author = {Tai, S and Vasiljevik, T and Sherwood, AM and Eddington, S and Wilson, CD and Prisinzano, TE and Fantegrossi, WE}, title = {Assessment of rimonabant-like adverse effects of purported CB1R neutral antagonist / CB2R agonist aminoalkylindole derivatives in mice.}, journal = {Drug and alcohol dependence}, volume = {192}, number = {}, pages = {285-293}, pmid = {30300803}, issn = {1879-0046}, support = {P20 GM113117/GM/NIGMS NIH HHS/United States ; R01 DA018151/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Cannabinoid Receptor Agonists/adverse effects/*pharmacology ; Cannabinoid Receptor Antagonists/adverse effects/*pharmacology ; Cannabinoids/pharmacology ; Dose-Response Relationship, Drug ; Male ; Mice ; Reaction Time ; Receptor, Cannabinoid, CB1/*antagonists & inhibitors/physiology ; Receptor, Cannabinoid, CB2/*agonists/physiology ; Rimonabant/adverse effects/*pharmacology ; Taste/drug effects/physiology ; }, abstract = {BACKGROUND: Cannabinoids may be useful in the treatment of CNS disorders including drug abuse and addiction, where both CB1R antagonists / inverse agonists and CB2R agonists have shown preclinical efficacy. TV-5-249 and TV-6-41, two novel aminoalkylindoles with dual action as neutral CB1R antagonists and CB2R agonists, previously attenuated abuse-related effects of ethanol in mice.

PURPOSE: To further characterize these drugs, TV-5-249 and TV-6-41 were compared with the CB1R antagonist / inverse agonist rimonabant in assays relevant to adverse effects and cannabinoid withdrawal.

PROCEDURES AND FINDINGS: The cannabinoid tetrad confirmed that TV-5-249 and TV-6-41 were devoid of CB1R agonist effects at behaviorally-relevant doses, and neither of the novel drugs induced rimonabant-like scratching. Generalized aversive effects were assessed, and rimonabant and TV-5-249 induced taste aversion, but TV-6-41 did not. Schedule-controlled responding and observation of somatic signs were used to assess withdrawal-like effects precipitated by rimonabant or TV-6-41 in mice previously treated with the high-efficacy CB1R agonist JWH-018 or vehicle. Rimonabant and TV-6-41 dose-dependently suppressed response rates in all subjects, but TV-6-41 did so more potently in JWH-018-treated mice than in vehicle-treated mice, while rimonabant equally suppressed responding in both groups. Importantly, rimonabant elicited dramatic withdrawal signs, but TV-6-41 did not.

CONCLUSIONS: These findings suggest differences in both direct adverse effects and withdrawal-related effects elicited by rimonabant, TV-5-249, and TV-6-41, which could relate to neutral CB1R antagonism, CB2R agonism, or a combination of both. Both mechanisms should be explored and exploited in future drug design efforts to develop pharmacotherapies for drug dependence.}, } @article {pmid30295681, year = {2018}, author = {Molero-Chamizo, A}, title = {Effects of extensive amygdaloid lesions on conditioned taste aversion in rats.}, journal = {Acta neurobiologiae experimentalis}, volume = {78}, number = {3}, pages = {242-250}, pmid = {30295681}, issn = {1689-0035}, mesh = {Amygdala/*drug effects ; Animals ; Avoidance Learning/drug effects ; Brain Mapping/methods ; Conditioning, Classical/*physiology ; Lithium Chloride/*pharmacology ; Male ; Rats, Wistar ; Taste/*physiology ; }, abstract = {The role of the amygdala in the acquisition of conditioned taste aversion (CTA) is unclear. The lesion studies that have explored specific nuclei of the amygdala point to a probable involvement of the basolateral amygdala, but it remains unclear whether the function of the amygdala in CTA is limited to the activity of the basolateral amygdala. In the current study, extensive bilateral lesions of the amygdala were performed in Wistar rats to explore if the destruction of the amygdala affects the acquisition of CTA, as has been reported with selective lesions of the basolateral amygdala. The magnitude of the taste aversion of animals with extensive lesions of the amygdala was compared with those of animals with similar lesions of the striatum (a structure apparently unrelated to CTA) and animals without lesions. Taste aversion was analyzed by the one‑bottle test and two‑bottle choice test. The results of the one‑bottle test indicated that amygdaloid lesions significantly reduced the magnitude of taste aversion compared with that of animals without lesions. Animals with lesions of the amygdala also showed a greater preference for the conditioned taste stimulus, but this preference did not reach statistical significance. Besides the effect on CTA, animals with amygdaloid lesions showed no evidence of taste neophobia on the day of conditioning. These findings suggest that amygdaloid lesions may affect CTA by disrupting the perception of novelty during conditioning in a manner similar to the effect reported with basolateral lesions.}, } @article {pmid30282846, year = {2019}, author = {Nakajima, S}, title = {Food aversion learning based on voluntary running in non-deprived rats: a technique for establishing aversive conditioning with minimized discomfort.}, journal = {Experimental animals}, volume = {68}, number = {1}, pages = {71-79}, pmid = {30282846}, issn = {1881-7122}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/*physiology ; Eating/*psychology ; *Food ; Kaolin/administration & dosage ; Male ; Memory/physiology ; Nausea/physiopathology/psychology ; Rats, Wistar ; Running/*psychology ; }, abstract = {This article presents an experimental preparation for establishing conditioned food aversion (CFA) by voluntary wheel running in rats with laboratory chow and water freely available. In Experiment 1, unfamiliar food (raisins) was avoided by rats when they first encountered it. This neophobic food avoidance was habituated by repeated tests; the rats gradually increased their raisin consumption. However, the consumption remained suppressed in rats that accessed the raisins after wheel running. This finding implies that running yielded CFA, which suppressed consumption of the unfamiliar food rather than increasing it. Because running generated kaolin clay ingestion, which is a behavioral marker of nausea, it is suggested that the running-based CFA was mediated by weak gastrointestinal discomfort. Experiment 2 supported the claim that the suppressed consumption is due to running-based CFA by showing the specificity of food suppression. Demonstration of CFA based on voluntary activity in non-deprived rats will contribute to basic research on learning and memory as an alternative technique for studying aversive conditioning with minimized discomfort in animals.}, } @article {pmid30267837, year = {2018}, author = {Soto, J and Keeley, A and Keating, AV and Mohamed-Ahmed, AHA and Sheng, Y and Winzenburg, G and Turner, R and Desset-Brèthes, S and Orlu, M and Tuleu, C}, title = {Rats can predict aversiveness of Active Pharmaceutical Ingredients.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {133}, number = {}, pages = {77-84}, doi = {10.1016/j.ejpb.2018.09.027}, pmid = {30267837}, issn = {1873-3441}, mesh = {Adult ; Animals ; Chemistry, Pharmaceutical/methods ; Female ; Humans ; Male ; Pharmaceutical Preparations/*chemistry ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; Young Adult ; }, abstract = {Taste is crucial for patient acceptability and compliance with prescribed medicines, in particular with pediatric patients. Evaluating the taste of new active pharmaceutical ingredients (APIs) is therefore essential to put in place adequate taste-masking techniques, if needed, which will lead to acceptable palatable formulations. Thus, there is an urgent need to develop and optimize taste assessment methods that could be used at different stages of the drug development process. The aim of this study was to investigate the suitability of the rat brief-access taste aversion (BATA) model as a screening tool for assessment of APIs aversiveness that could predict human taste responses. Presently, the taste intensity of nine marketed APIs known to have different levels of bitter intensity (quinine hydrochloride dihydrate, 6-n-propylthiouracil, sildenafil citrate, diclofenac sodium, ranitidine hydrochloride, caffeine citrate, isoniazid, telbivudine and paracetamol) was investigated at different overlapping concentrations with two in vivo taste assessment methods: the rat BATA model and human taste panels with the intention of determining the drugs' concentrations to produce half of the maximal rating. Overall there was a strong correlation (R[2] = 0.896) between rats IC50 and humans EC50 values. This correlation verifies the BATA model as a rapid and reliable tool for quantitative assessment of API aversiveness. A comparable ranking order was obtained mainly for high and medium aversive compounds, whereas it was less aligned for weakly aversive compounds. It was nonetheless possible to propose a classification of poor taste intensity determined in rats that would predict human taste tolerability.}, } @article {pmid30219263, year = {2019}, author = {Rodríguez-Blanco, LA and Rivera-Olvera, A and Escobar, ML}, title = {Consolidation of an aversive taste memory requires two rounds of transcriptional and epigenetic regulation in the insular cortex.}, journal = {Behavioural brain research}, volume = {356}, number = {}, pages = {371-374}, doi = {10.1016/j.bbr.2018.09.009}, pmid = {30219263}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/drug effects ; Cerebral Cortex/*drug effects/physiology ; Conditioning, Classical/drug effects/physiology ; Epigenesis, Genetic/*drug effects ; Male ; Memory/*drug effects/physiology ; Memory, Long-Term/drug effects ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {The current view of the neurobiology of learning and memory suggests that long-term memory (LTM) depends not only on the de novo protein synthesis but also on the synthesis of mRNA even hours after the acquisition of memory, as well as that the regulation of transcription through the histone acetylation is essential for the memory establishment. Our previous studies showed that protein synthesis inhibition around the time of training and 5-7 hours after acquisition in the insular cortex (IC) prevents the consolidation of conditioned taste aversion (CTA), a well-established learning and memory paradigm in which an animal learns to associate a novel taste with nausea. However, the participation of mRNA synthesis and the epigenetic regulation through histone acetylation in this process remains unexplored. In the present study we evaluated the effect of the inhibition of transcription as well as deacetylation of histones at two temporal windows on the consolidation of CTA. Thus, immediately or seven hours after CTA acquisition animals received a microinfusion of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) or MS-275 in the IC, respectively. The present results show that transcription inhibition immediately and 7 h after acquisition impairs the CTA memory consolidation, whereas the inhibition of histone deacetylation strengths this memory at those temporal windows. These findings reveal that CTA memory requires recurrent rounds of transcriptional modulation events in the IC in order to consolidate this memory trace, demonstrating that transcriptional and epigenetic modulation substantially contribute to memory-consolidation-related functions performed by a neocortical area even several hours after memory acquisition.}, } @article {pmid30172953, year = {2018}, author = {Lin, JY and Arthurs, J and Reilly, S}, title = {The effects of amygdala and cortical inactivation on taste neophobia.}, journal = {Neurobiology of learning and memory}, volume = {155}, number = {}, pages = {322-329}, pmid = {30172953}, issn = {1095-9564}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Baclofen/administration & dosage ; Basolateral Nuclear Complex/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Eating ; GABA-A Receptor Agonists/administration & dosage ; Male ; Muscimol/administration & dosage ; Rats, Sprague-Dawley ; Taste Perception/drug effects/*physiology ; }, abstract = {The current study examined the effects of transient inactivation of the basolateral amygdala (BLA; Experiment 1) and gustatory cortex (GC; Experiment 2) on the expression of taste neophobia and its recovery. We found that inactivation (induced by infusions of baclofen/muscimol) of each structure before exposure to a novel saccharin (0.5%) solution elevated intake on Trial 1 (i.e., taste neophobia was attenuated) and, surprisingly, decreased intake on Trial 2. It seems unlikely that this intake reduction on Trial 2 can be attributed to taste aversion learning caused by drug infusions because in the subsequent experiments with the same set of the implanted animals, the rats did not decrease intake when baclofen/muscimol was infused after taste presentation on Trial 1. The latter result suggests that BLA or GC inactivation that attenuates taste neophobia may also impair memory consolidation of a safe taste experience.}, } @article {pmid30129253, year = {2019}, author = {Weera, MM and Agim, ZS and Cannon, JR and Chester, JA}, title = {Genetic correlations between nicotine reinforcement-related behaviors and propensity toward high or low alcohol preference in two replicate mouse lines.}, journal = {Genes, brain, and behavior}, volume = {18}, number = {3}, pages = {e12515}, pmid = {30129253}, issn = {1601-183X}, support = {R01ES025750/ES/NIEHS NIH HHS/United States ; P60 AA007611/AA/NIAAA NIH HHS/United States ; P50 AA007611/AA/NIAAA NIH HHS/United States ; AA013522, AA07611/AA/NIAAA NIH HHS/United States ; U24 AA015512/AA/NIAAA NIH HHS/United States ; R01 ES025750/ES/NIEHS NIH HHS/United States ; U01 AA013522/AA/NIAAA NIH HHS/United States ; U24 AA013522/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholism/*genetics ; Animals ; Biogenic Monoamines/metabolism ; Female ; *Genotype ; Male ; Mecamylamine/pharmacology ; Mice ; Nicotine/*pharmacology ; Nicotinic Agonists/pharmacology ; Nicotinic Antagonists/pharmacology ; Nucleus Accumbens/drug effects/metabolism ; *Reinforcement, Psychology ; Tobacco Smoking/*genetics ; }, abstract = {Common genetic factors may contribute to the high comorbidity between tobacco smoking and alcohol use disorder. Here, we assessed behavioral and biological effects of nicotine in replicate mouse lines selectively bred for high (HAP2/3) or low alcohol preference (LAP2/3). In Experiment 1, free-choice (FC) oral nicotine and quinine intake were assessed in HAP2/3 and LAP2/3 mice. Effects of nicotinic acetylcholine receptor blockade by mecamylamine on nicotine intake in HAP2 mice were also examined. In Experiment 2, HAP2/3 and LAP2/3 mice were tested for differences in sensitivity to nicotine-induced taste conditioning. In Experiment 3, the effects of a single nicotine injection on nucleus accumbens (NAc) and dorsal striatum monoamine levels in HAP2/3 and LAP2/3 mice were tested. In Experiment 1, HAP2/3 mice showed greater nicotine intake and intake ratio than LAP2/3 mice. There were no line differences in quinine intake. Mecamylamine reduced nicotine intake and intake ratio in HAP2 mice. In Experiment 2, HAP2/3 mice showed weaker nicotine-induced conditioned taste aversion (CTA) compared with LAP2/3 mice. In Experiment 3, nicotine treatment increased NAc dopamine turnover across both HAP2/3 and LAP2/3 mouse lines. These results show that there is a positive genetic correlation between oral alcohol intake (high alcohol intake/preference selection phenotype) and oral nicotine intake and a negative genetic correlation between oral alcohol intake and sensitivity to nicotine-induced CTA.}, } @article {pmid30126972, year = {2018}, author = {Moschak, TM and Wang, X and Carelli, RM}, title = {A Neuronal Ensemble in the Rostral Agranular Insula Tracks Cocaine-Induced Devaluation of Natural Reward and Predicts Cocaine Seeking.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {38}, number = {39}, pages = {8463-8472}, pmid = {30126972}, issn = {1529-2401}, support = {R01 DA014339/DA/NIDA NIH HHS/United States ; }, mesh = {Affect/drug effects/*physiology ; Animals ; Cerebral Cortex/drug effects/*physiology ; Cocaine/*administration & dosage ; Conditioning, Operant ; Drug-Seeking Behavior/drug effects/*physiology ; Lithium Chloride/administration & dosage ; Male ; Neurons/drug effects/*physiology ; Quinine/administration & dosage ; Rats, Sprague-Dawley ; *Reward ; Saccharin/administration & dosage ; Taste/drug effects/physiology ; Taste Perception/drug effects/physiology ; }, abstract = {In substance use disorders, negative affect associated with drug withdrawal can elicit strong drug craving and promote relapse. One brain region implicated in those processes is the rostral agranular insular cortex (RAIC), although precisely how this region encodes negative affect associated with drug seeking is unknown. Here, a preclinical model was used where RAIC activity was examined in male Sprague Dawley rats during intraoral infusions of a sweet (saccharin) paired with impending but delayed access to cocaine self-administration, and for comparative purposes, during the sweet predicting saline self-administration or injection of lithium chloride (LiCl), or during intraoral infusions of a bitter taste (quinine). Consistent with previous work, cocaine-paired saccharin, LiCl-paired saccharin, and quinine all elicited aversive taste reactivity. However, the aversive taste reactivity elicited by the cocaine-paired tastant was qualitatively different from that evoked by the other two agents. Furthermore, differences in taste reactivity were reflected in RAIC cell firing, where distinct shifts in neural signaling were observed specifically after cocaine but not LiCl conditioning. Notably, low motivation for cocaine (indicated by low loading and slower latencies to lever press) was correlated with this shift in RAIC signaling, but aversive (gaping) responses were not. Collectively, these findings indicate that cocaine-paired tastants elicit unique aspects of aversive behaviors that differ from traditional conditioned taste aversion (LiCl) or quinine and that the RAIC plays a role in modulating drug-seeking behaviors driven by drug-induced dysphoria (craving), but not negative affect per se.SIGNIFICANCE STATEMENT In substance use disorders, negative affect associated with drug cues can elicit craving and promote relapse; however, the underlying neurocircuitry of this phenomenon is unknown. Here, we investigated the role of the rostral agranular insula cortex (RAIC) in these processes using a preclinical model wherein intraoral delivery of a sweet is paired with delayed access to cocaine self-administration. The taste comes to elicit negative affect that predicts heightened drug seeking. Here, we found that a population of RAIC neurons became inhibited during presentation of the cocaine-paired tastant (when negative affect is high) and that this inhibitory neural profile predicted lower drug seeking. These findings suggest that the RAIC may function to oppose cue-induced cocaine craving and help reduce motivation for the drug.}, } @article {pmid30115766, year = {2018}, author = {Kubilius, RA and Kaplick, PM and Wotjak, CT}, title = {Highway to hell or magic smoke? The dose-dependence of Δ[9]-THC in place conditioning paradigms.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {25}, number = {9}, pages = {446-454}, pmid = {30115766}, issn = {1549-5485}, mesh = {Animals ; Behavior, Animal/*drug effects ; Cannabinoid Receptor Agonists/*pharmacology ; Conditioning, Classical/*drug effects ; Dronabinol/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {The prerequisites for responsible cannabis use are at the heart of current inquiries into cannabis decriminalization by policy makers as well as academic and nonacademic stakeholders at a global scale. Δ[9]-tetrahydrocannabinol (Δ[9]-THC), the prime psychoactive compound of the cannabis sativa, as well as cannabimimetics that resemble the pharmacological properties and psychological effects of Δ[9]-THC, lend themselves handsomely to the preclinical scrutiny of reward-related behavior because they carry marked translational value. Although a functional dichotomy of the psychological effects of Δ[9]-THC (rewarding versus aversive) has been abundantly reported in place conditioning (PC) paradigms, and might be best attributed to a dose-dependence of Δ[9]-THC, most PC studies with Δ[9]-THC feature no significant effects at all. Therefore, after decades of rigorous research, it still remains undetermined whether Δ[9]-THC generally exerts rewarding or aversive effects in rodents. Here, we set out to extrapolate the commonly alleged dose-dependence of the rewarding and aversive effects of Δ[9]-THC from the existing literature, at the behavioral pharmacological level of analysis. Specifically, our meta-analysis investigated: (i) the alleged bidirectional effects and dose-dependence of Δ[9]-THC in the PC test; (ii) methodological inconsistencies between PC studies; and (iii) other pharmacological studies on cannabinoids (i.e., dopamine release, anxiety, stress, conditioned taste aversion, catalepsy) to substantiate the validity of PC findings. Our findings suggest that: (i) Δ[9]-THC dose-dependently generates rewarding (1 mg/kg) and aversive (5 mg/kg) effects in PC; (ii) an inconsistent use of priming injections hampers a clear establishment of the rewarding effects of Δ[9]-THC in PC tests and might explain the seemingly contradictory plethora of nonsignificant THC studies in the PC test; and (iii) other pharmacological studies on Δ[9]-THC substantiate the dose-dependent biphasic effects of Δ[9]-THC in PC. A standardized experimental design would advance evidence-based practice in future PC studies with Δ[9]-THC and facilitate the pointed establishment of rewarding and aversive effects of the substance.}, } @article {pmid30110433, year = {2018}, author = {Agee, LA and Monfils, MH}, title = {Effect of demonstrator reliability and recency of last demonstration on acquisition of a socially transmitted food preference.}, journal = {Royal Society open science}, volume = {5}, number = {6}, pages = {172391}, pmid = {30110433}, issn = {2054-5703}, abstract = {In the social transmission of food preference paradigm, naive observer rats acquire safety information about novel food sources in the environment through social interaction with a demonstrator rat that has recently eaten said food. Research into the behavioural mechanisms governing this form of learning has found that observers show increased reliance on socially acquired information when the state of the environment makes personal examination of their surroundings risky. We aimed to (1) determine whether reliance on social information would decrease if previous reliance on social learning was unsuccessful, and (2) whether reliance on the specific demonstrator that had transmitted poor information would similarly decrease. By inducing illness in observers following consumption of a socially demonstrated food, we created an environmental situation in which reliance on socially acquired information was maladaptive. We found that under these conditions, observers showed no change in their reliance on a specific demonstrator or socially learned information in general. Our experiment also unexpectedly produced results showing that recent demonstrators were more influential in later transmissions than demonstrators that had been learned from less recently. Notably, this effect only emerged when the observer simultaneously interacted with both demonstrators, indicating that demonstrators must be in direct competition for this effect to manifest.}, } @article {pmid30085976, year = {2018}, author = {Gartner, SN and Klockars, A and Prosser, C and Carpenter, EA and Levine, AS and Olszewski, PK}, title = {Identification of central mechanisms underlying anorexigenic effects of intraperitoneal L-tryptophan.}, journal = {Neuroreport}, volume = {29}, number = {15}, pages = {1293-1300}, doi = {10.1097/WNR.0000000000001110}, pmid = {30085976}, issn = {1473-558X}, mesh = {Animals ; Anti-Obesity Agents/*administration & dosage ; Brain/*drug effects/metabolism ; Camphanes/pharmacology ; Central Nervous System Agents/pharmacology ; Eating/*drug effects/physiology ; Food Deprivation ; Injections, Intraperitoneal ; Male ; Motivation/drug effects/physiology ; Neurons/drug effects/metabolism ; Piperazines/pharmacology ; Rats, Sprague-Dawley ; Receptors, Oxytocin/antagonists & inhibitors/metabolism ; Taste Perception ; Tryptophan/*administration & dosage ; }, abstract = {A free essential amino acid, L-tryptophan (TRP), administered through a diet or directly into the gut, decreases food intake by engaging neural mechanisms. The ability of intragastric TRP to cross into the general circulation and through the blood-brain barrier, at least partly underlies hypophagia. It is unclear although, whether TRP's anorexigenic effects and accompanying neural processes occur in the absence of the initial action of TRP on the gut mucosa. Here, we addressed this issue by using a fundamental approach of examining effects of intraperitoneally administered TRP on feeding and neuronal activation in rats. We found that 30 mg/kg, intraperitoneal, TRP decreases deprivation-induced intake of standard chow and thirst-driven water intake. A 100 mg/kg dose was necessary to suppress consumption of palatable chow and of sucrose and saccharin solutions in nondeprived animals. Intraperitoneally TRP did not induce a conditioned taste aversion; thus, its anorexigenic effects were unrelated to sickness/malaise. c-Fos mapping in feeding-related brain sites revealed TRP-induced changes in the dorsal vagal complex, hypothalamic paraventricular and supraoptic nuclei and in the basolateral amygdala. TRP enhanced activation of hypothalamic neurons synthesizing an anorexigen, oxytocin (OT). Pharmacological blockade of the OT receptor with a blood-brain barrier -penetrant antagonist, L-368,899, attenuated TRP-induced decrease in deprivation-induced chow intake, but not in thirst-driven water consumption. We conclude that TRP triggers anorexigenic action and underlying neural responses even when it does not directly contact the gut mucosa. TRP requires OT to decrease energy intake, whereas OT is nonobligatory in TRP's effects on drinking behavior.}, } @article {pmid30035267, year = {2018}, author = {Chambers, KC}, title = {Conditioned taste aversions.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {4}, number = {1}, pages = {92-100}, pmid = {30035267}, issn = {2589-1081}, abstract = {When one becomes ill after consuming a meal, there is a propensity to target a particular taste as the cause of the illness. The qualities of the taste most likely targeted include more novel, less preferred, and higher protein content. This association between a particular taste and illness is a form of learning that is termed conditioned taste aversion (CTA). A consequence of the learned association is that the taste will become aversive. When experiencing the taste again, individuals will show aversive reactions such as expressions of loathing, will experience mimicked illness sensations such as nausea, and subsequently, will avoid further exposure to the taste. The ability to acquire CTA occurs across species and across ages within a species. In the rat animal model, however, age differences exist in the capability of acquiring CTAs when increasingly longer intervals are imposed between consumption of a novel sweet solution and onset of illness. Pups have a decreased ability compared to young adults while aged rats have an increased ability. Evidence suggests that the failure of pups to acquire CTA at longer intervals is due to an immature retrieval mechanism and the facilitated ability of aged rats is due to a compromised clock mechanism that tracks the passage of time. Learned taste-illness association serves the critical function of informing individuals of the toxic nature of certain foods, thus preventing further illness and potentially death. Additionally, it contributes to the hypophagia observed during cancer chemotherapy and may contribute to the hypophagia found while suffering from bacterial infection, chronic medical conditions such as cancer, and restrictive food intake disorders such as anorexia nervosa.}, } @article {pmid30029019, year = {2018}, author = {Loney, GC and Pautassi, RM and Kapadia, D and Meyer, PJ}, title = {Nicotine affects ethanol-conditioned taste, but not place, aversion in a simultaneous conditioning procedure.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {71}, number = {}, pages = {47-55}, pmid = {30029019}, issn = {1873-6823}, support = {R01 AA024112/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Classical/*drug effects ; Cues ; Drug Interactions ; Ethanol/*pharmacology ; Male ; Motor Activity/drug effects ; Nicotine/*pharmacology ; Rats ; Taste Perception/*drug effects ; }, abstract = {The conditioned taste aversion (CTA) induced by ethanol is a key factor limiting ethanol intake. Nicotine, a drug co-consumed with ethanol, may decrease this aversion by modulating the unconditioned effects of ethanol or by disrupting the association between ethanol and its associated cues. This study analyzed ethanol-induced CTA and conditioned place aversion (CPA) in Long-Evans rats with subchronic exposure to nicotine. The rats were treated with nicotine (0.0 or 0.4 mg/kg) three times before conditioning (on lickometer training sessions 3, 4, and 5) and across conditioning days. During the conditioning the rats were given ethanol (1.3 g/kg) preceded and followed by presentation of a taste (NaCl) and tactile (rod or hole floors) conditioned stimulus (CS+), respectively. On CS- conditioning days, the rats were given vehicle and exposed to alternative stimuli. Three CTA and CPA testing sessions were then conducted. It was found that nicotine reduced ethanol-induced CTA and enhanced locomotor activity, but did not significantly modify the magnitude of ethanol-induced CPA. The effects of nicotine on CTA were observed during both conditioning and testing sessions, and were specific to the NaCl CS+, having no effect on reactivity to water. The dissociation between the effect of nicotine on ethanol-induced CTA and CPA suggests that nicotine does not alter ethanol's motivational properties by generally increasing its positive rewarding effects, nor does it blunt all aversive-like responses to this drug. Instead, nicotine may impede ethanol-induced CTA induced by ethanol by disrupting the neural underpinnings of this specific form of associative learning.}, } @article {pmid29996089, year = {2018}, author = {Lavi, K and Jacobson, GA and Rosenblum, K and Lüthi, A}, title = {Encoding of Conditioned Taste Aversion in Cortico-Amygdala Circuits.}, journal = {Cell reports}, volume = {24}, number = {2}, pages = {278-283}, doi = {10.1016/j.celrep.2018.06.053}, pmid = {29996089}, issn = {2211-1247}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; *Conditioning, Classical ; Imaging, Three-Dimensional ; Male ; Mice, Inbred C57BL ; Nerve Net/*physiology ; Taste/*physiology ; }, abstract = {Avoidance of potentially toxic food by means of conditioned taste aversion is critical for survival of many animals. However, the underlying neuronal mechanisms are poorly understood. Here, using two-photon calcium imaging of defined gustatory cortex neurons in vivo, we show that conditioned taste aversion dynamically shifts neuronal population coding by stimulus-specific recruitment of neurons that project to the basolateral amygdala.}, } @article {pmid29955564, year = {2018}, author = {Aonuma, H and Totani, Y and Sakakibara, M and Lukowiak, K and Ito, E}, title = {Comparison of brain monoamine content in three populations of Lymnaea that correlates with taste-aversive learning ability.}, journal = {Biophysics and physicobiology}, volume = {15}, number = {}, pages = {129-135}, pmid = {29955564}, issn = {2189-4779}, abstract = {To find a causal mechanism of learning and memory is a heuristically important topic in neuroscience. In the pond snail Lymnaea stagnalis, the following experimental facts have accrued regarding a classical conditioning procedure known as conditioned taste aversion (CTA): (1) one-day food-deprived Dutch snails have superior CTA memory formation; (2) the one-day food-deprived snails have a low monoamine content (e.g., serotonin, dopamine, octopamine) in their central nervous system (CNS); (3) fed or five-day food-deprived snails have poorer CTA memory and a higher monoamine content; (4) the Dutch snails form better CTA memory than the Canadian TC1 strain; and, (5) the F1 cross snails between the Dutch and Canadian TC1 strains also form poor CTA memory. Here, in one-day food-deprived snails, we measured the monoamine content in the CNSs of the 3 populations. In most instances, the monoamine content of the Dutch strain was lower than in the other two populations. The F1 cross snails had the highest monoamine content. A lower monoamine content is correlated with the better CTA memory formation.}, } @article {pmid29922201, year = {2018}, author = {Angulo, R}, title = {Pre-exposure Schedule Effects on Generalization of Taste Aversion and Palatability for Thirsty and Not Thirsty Rats.}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {878}, pmid = {29922201}, issn = {1664-1078}, abstract = {The study reported four experiments aiming to test the effects of the pre-exposure schedule and water deprivation on the generalization of a conditioned taste aversion in rats, with a particular focus on testing whether or not the concurrent schedule might enhance generalization. In two experiments, non-water-deprived rats received concurrent, intermixed, or blocked exposure to a sweet-acid solution and a salty-acid solution before conditioning of one of these compounds and testing of both flavors. During pre-exposure, the rats consumed a greater amount of the sweet-acid solution than the salty-acid solution (Experiments 1 and 2), consumption of the former increasing during pre-exposure while consumption of the latter decreased (Experiment 1). Furthermore, consumption of the salty-acid solution was lower during concurrent than intermixed or blocked pre-exposure (Experiment 1 and 2) while consumption of the sweet-acid solution was greater during intermixed than concurrent or blocked pre-exposure (Experiment 1). It is discussed whether the pre-exposure schedule might modify stimulus perception beyond the mere enhancement of stimulus differentiation, by, for instance, affecting the palatability of gustatory stimuli. Evidence for enhanced generalization after concurrent pre-exposure was not found for either deprived (Experiments 1, 2, and 3) or non-deprived rats (Experiments 3 and 4), with deprivation leading to a general increase in consumption of both the conditioned and test flavors. This then raised the question of whether or not concurrent pre-exposure to flavors always increases generalization between them. The present study highlights the importance of this issue for various accounts of perceptual learning.}, } @article {pmid29920309, year = {2019}, author = {Caynas-Rojas, S and Rodríguez-García, G and Delint-Ramírez, I and Miranda, MI}, title = {Differential function of medial prefrontal cortex catecholaminergic receptors after long-term sugar consumption.}, journal = {Behavioural brain research}, volume = {356}, number = {}, pages = {495-503}, doi = {10.1016/j.bbr.2018.06.009}, pmid = {29920309}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cerebral Cortex/physiology ; Conditioning, Classical/physiology ; Extinction, Psychological/drug effects ; Male ; Memory/*drug effects/physiology ; Prefrontal Cortex/*drug effects/physiology ; Propranolol/pharmacology ; Rats, Wistar ; Sugars/*adverse effects ; Taste/drug effects ; Time ; }, abstract = {The medial prefrontal cortex (mPFC) has reciprocal projections with many cerebral structures that are crucial in the control of food ingestion behavior and reward processing; Thus the mPFC has an important function in taste memory recognition. Previous results indicate that long-term consumption of sugar produces changes in appetitive re-learning and suggest that this could trigger an escalating consumption due to the inability to learn new negative consequences related to the same taste. Further evidence suggests that general identity reward value could be encoded in the mPFC. Therefore, the purpose of this study was to evaluate in rats whether after 21 days of sugar consumption the increase in sweet taste preference and latent inhibition of conditioned taste aversion (CTA) were affected differentially by pharmacological activation or blockage of dopaminergic and β-adrenergic receptors, in the mPFC, during CTA acquisition. Results showed that after long-term sugar exposure, mPFC activation of β-adrenergic receptors with clenbuterol delayed aversive memory extinction, but the blockade with propranolol or activation of dopaminergic receptors with apomorphine increased CTA latent inhibition and accelerated aversive memory extinction only after acute sugar exposure. Only dopaminergic blockade with haloperidol prevented sweet taste preference expression after long-term sugar consumption, increased CTA latent inhibition and accelerated extinction after acute sugar exposure. Taken together, the present data provide evidence that catecholaminergic receptors in the mPFC after prolonged sugar consumption underwent functional changes related to re-learning and new aversive taste learning.}, } @article {pmid29862893, year = {2020}, author = {Vera-Rivera, G and Miranda, MI and Rangel-Hernández, JA and Badillo-Juárez, D and Fregoso-Urrutia, D and Caynas-Rojas, S}, title = {Effects of caloric or non-caloric sweetener long-term consumption on taste preferences and new aversive learning.}, journal = {Nutritional neuroscience}, volume = {23}, number = {2}, pages = {128-138}, doi = {10.1080/1028415X.2018.1478654}, pmid = {29862893}, issn = {1476-8305}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects/physiology ; Dietary Sugars/*administration & dosage ; *Energy Intake ; Extinction, Psychological/drug effects ; Food Preferences/drug effects/*physiology ; Male ; Rats ; Rats, Wistar ; Saccharin/*administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {Food palatability and caloric content are crucial factors in guiding diet choice and amount consumed; as a result, sweet caloric tastes are associated with a positive hedonic value. Recent evidence in rodents indicates that consumption of artificial (non-caloric) sweeteners, in which sweet taste is dissociated from normal caloric consequences, could induce changes in energy and body weight regulation, suggesting that sweeteners not only modify intake and appetitive behavior, but could also change taste-learning processes. Particularly, there are different properties in some artificial sweeteners, like saccharin, that might differ from sugar in the reward responses that, after long-term consumption, could also be associated with the inability to learn new negative consequences related to the same taste. Thus, the main goal of this study was to determine, in adult rats, the effects of long-term consumption (14 days) of sugar or saccharin, on taste preference, on new aversive learning, i.e. latent inhibition (LI) of conditioned taste aversion (CTA), and appetitive taste re-learning after aversive taste associations. The results showed that 14 days' exposure to sugar, but not to saccharin, induced a significant increment in the LI of CTA and that taste preference is rapidly recovered during the next 3 days (e.g. CTA extinctions), indicating that long-term sugar consumption significantly accelerates aversive memory extinction during appetitive re-learning of a specific sweet taste; furthermore, high familiarization to sugar, but not to saccharin, promotes appetitive learning for the same taste. Overall, the results indicate that long-term consumption of sugar, but not saccharin, produces changes in appetitive re-learning and suggests that long-term sugar consumption could trigger escalating consumption due to the inability to learn new negative consequences associated with the same taste.}, } @article {pmid29687910, year = {2018}, author = {Varnon, CA and Dinges, CW and Black, TE and Wells, H and Abramson, CI}, title = {Failure to Find Ethanol-Induced Conditioned Taste Aversion in Honey Bees (Apis mellifera L.).}, journal = {Alcoholism, clinical and experimental research}, volume = {42}, number = {7}, pages = {1260-1270}, pmid = {29687910}, issn = {1530-0277}, support = {P20 GM103499/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Bees ; Conditioning, Classical/*drug effects/physiology ; Ethanol/*administration & dosage ; Odorants ; Smell/drug effects/physiology ; Sucrose/administration & dosage ; Taste/*drug effects/physiology ; }, abstract = {BACKGROUND: Conditioned taste aversion (CTA) learning is a highly specialized form of conditioning found across taxa that leads to avoidance of an initially neutral stimulus, such as taste or odor, that is associated with, but is not the cause of, a detrimental health condition. This study examines if honey bees (Apis mellifera L.) develop ethanol (EtOH)-induced CTA.

METHODS: Restrained bees were first administered a sucrose solution that was cinnamon scented, lavender scented, or unscented, and contained either 0, 2.5, 5, 10, or 20% EtOH. Then, 30 minutes later, we used a proboscis extension response (PER) conditioning procedure where the bees were taught to associate either cinnamon odor, lavender odor, or an air-puff with repeated sucrose feedings. For some bees, the odor of the previously consumed EtOH solution was the same as the odor associated with sucrose in the conditioning procedure. If bees are able to learn EtOH-induced CTA, they should show an immediate low level of response to odors previously associated with EtOH.

RESULTS: We found that bees did not develop CTA despite the substantial inhibitory and aversive effects EtOH has on behavior. Instead, bees receiving a conditioning odor that was previously associated with EtOH showed an immediate high level of response. While this demonstrates bees are capable of one-trial learning common to CTA experiments, this high level of response is the opposite of what would occur if the bees developed a CTA. Responding on subsequent trials also showed a general inhibitory effect of EtOH. Finally, we found that consumption of cinnamon extract reduced the effects of EtOH.

CONCLUSIONS: The honey bees' lack of learned avoidance to EtOH mirrors that seen in human alcoholism. These findings demonstrate the usefulness of honey bees as an insect model for EtOH consumption.}, } @article {pmid29684475, year = {2018}, author = {Risco, S and Mediavilla, C}, title = {Orexin A in the ventral tegmental area enhances saccharin-induced conditioned flavor preference: The role of D1 receptors in central nucleus of amygdala.}, journal = {Behavioural brain research}, volume = {348}, number = {}, pages = {192-200}, doi = {10.1016/j.bbr.2018.04.010}, pmid = {29684475}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/drug effects ; Central Amygdaloid Nucleus/metabolism ; Cerebellar Nuclei/metabolism ; Conditioning, Psychological/drug effects ; Dopamine Antagonists/pharmacology ; Dopamine D2 Receptor Antagonists/pharmacology ; Male ; Orexins/*metabolism/*physiology ; Rats ; Rats, Wistar ; Receptors, Dopamine D1 ; Receptors, Dopamine D2/metabolism ; Saccharin/pharmacology ; Taste/drug effects ; Ventral Tegmental Area/*drug effects ; }, abstract = {In industrialized societies, food intake is largely determined by its hedonic characteristics, which can be modified by our experience via taste learning. In this learning, the hedonic value of a neutral flavor changes after its association with a motivationally significant stimulus. Experiment 1 analyzes the effect of orexin administration (53 and 107 ng) in the ventral tegmental area (VTA) on hedonic intake through acquisition of a flavor-taste preference and a flavor-taste aversion. Accordingly, animals underwent four one-bottle acquisition sessions with unilateral application of orexin-A or saline in the VTA at 10 min before a 15-min flavor intake period. Preference and aversion were tested by a two-bottle test containing the flavors used for CS+ and CS-. Results indicate that intra-VTA orexin strengthens flavor-taste conditioned flavor preference (CFP) by saccharin but does not facilitate flavor-taste aversion induced by association of a neutral flavor with the unpalatable taste of quinine. Experiment 2 examines the acquisition of a flavor-taste preference after co-administration of an effective dose of orexin-A in the VTA and of D1-like dopamine receptor antagonist SCH23390 (6 and 12 nmol) in the central nucleus of the amygdala (CeA). SCH23390 impedes the CFP strengthening observed after intra-VTA orexin administration, indicating that this effect may be mediated by dopaminergic receptors in the CeA. These data suggest that the simultaneous presentation of a flavor and a hedonically positive taste may be detected by orexinergic neurons that activate dopamine-releasing neurons of the VTA, thereby reinforcing the positive signals required to develop a taste preference.}, } @article {pmid29672108, year = {2018}, author = {Koh, MT and Ahrens, PS and Gallagher, M}, title = {A greater tendency for representation mediated learning in a ketamine mouse model of schizophrenia.}, journal = {Behavioral neuroscience}, volume = {132}, number = {2}, pages = {106-113}, pmid = {29672108}, issn = {1939-0084}, support = {P50 MH094268/MH/NIMH NIH HHS/United States ; }, mesh = {Amphetamine/pharmacology ; Animals ; Antipsychotic Agents/pharmacology ; Central Nervous System Stimulants/pharmacology ; Delusions/drug therapy ; Disease Models, Animal ; Feeding Behavior/drug effects ; Hallucinations/drug therapy ; Ketamine ; *Learning ; Male ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Olfactory Perception/drug effects ; Risperidone/pharmacology ; Schizophrenia/drug therapy ; *Schizophrenic Psychology ; }, abstract = {Representation mediated learning is a behavioral paradigm that could be used to potentially capture psychotic symptoms including hallucinations and delusions in schizophrenia. In studies of mediated learning, representations of prior experience can enter into current associations. Using a ketamine model of schizophrenia, we investigated whether mice exposed to ketamine during late adolescence subsequently showed an increased tendency to use a representation of a prior gustatory experience to form associations in learning. Mice were given prior experience of an odor and a taste presented together. The odor was subsequently presented alone with gastrointestinal illness induced by a lithium chloride injection. A consumption test was then given to assess whether the taste, despite its absence during conditioning, entered into an association with the induced illness. Such learning would be mediated via a representation of the taste activated by the odor. Our results showed that control mice displayed no aversion to the taste following the procedures just described, but mice that had been treated developmentally with ketamine exhibited a significant taste aversion, suggesting a greater propensity for mediated learning. Complementary to that finding, ketamine-exposed mice also showed a greater susceptibility to mediated extinction. Chronic treatment with the antipsychotic drug, risperidone, in ketamine-exposed mice attenuated mediated learning, a finding that may be related to its known efficacy in reducing the positive symptoms of schizophrenia. These data provide a setting with potential relevance to preclinical research on schizophrenia, to study the neural mechanisms underlying a propensity for aberrant associations and assessment of therapeutics. (PsycINFO Database Record}, } @article {pmid29631000, year = {2018}, author = {Rivera-Olvera, A and Nelson-Mora, J and Gonsebatt, ME and Escobar, ML}, title = {Extinction of aversive taste memory homeostatically prevents the maintenance of in vivo insular cortex LTP: Calcineurin participation.}, journal = {Neurobiology of learning and memory}, volume = {154}, number = {}, pages = {54-61}, doi = {10.1016/j.nlm.2018.04.005}, pmid = {29631000}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/physiology ; Calcineurin/*physiology ; Cerebral Cortex/*physiology ; Extinction, Psychological/*physiology ; *Long-Term Potentiation ; Male ; Memory/*physiology ; Neural Pathways/physiology ; Rats, Wistar ; Taste ; Taste Perception ; }, abstract = {Accumulating evidence indicates that homeostatic plasticity mechanisms dynamically adjust synaptic strength to promote stability that is crucial for memory storage. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. We have also reported that induction of LTP in the Bla-IC pathway modifies the CTA extinction. Memoryextinction involves the formation of a new associativememorythat inhibits a previously conditioned association. The aim of the present study was to analyze the effect of CTA extinction on the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, 48 h after CTA extinction animals received high frequency stimulation in order to induce IC-LTP. Our results show that extinction training allows the induction but not the maintenance of IC-LTP. In addition, with the purpose of exploring part of the mechanisms involved in this process and since a body of evidence suggests that protein phosphatase calcineurin (CaN) is involved in the extinction of some behavioral tasks, we analyzed the participation of this phosphatase. The present results show that extinction training increases the CaN expression in the IC, as well as that the inhibition of this phosphatase reverts the effects of the CTA-extinction on the IC-LTP. These findings reveal that CTA extinction promotes a homeostatic regulation of subsequent IC synaptic plasticity maintenance through increases in CaN levels.}, } @article {pmid29593595, year = {2018}, author = {Garcia-Burgos, D and Maglieri, S and Vögele, C and Munsch, S}, title = {How Does Food Taste in Anorexia and Bulimia Nervosa? A Protocol for a Quasi-Experimental, Cross-Sectional Design to Investigate Taste Aversion or Increased Hedonic Valence of Food in Eating Disorders.}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {264}, pmid = {29593595}, issn = {1664-1078}, abstract = {Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED), and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology. Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated with binge-eating episodes. No trial registration was required for this protocol, which was approved by the Swiss ethics committee (CER-VD, n° 2016-02150) and the Ethics Review Panel of the University of Luxembourg.}, } @article {pmid29588172, year = {2018}, author = {Yoshida, Y and Kawabata, F and Kawabata, Y and Nishimura, S and Tabata, S}, title = {Short-term perception of and conditioned taste aversion to umami taste, and oral expression patterns of umami taste receptors in chickens.}, journal = {Physiology & behavior}, volume = {191}, number = {}, pages = {29-36}, doi = {10.1016/j.physbeh.2018.03.020}, pmid = {29588172}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Animals, Newborn ; Avoidance Learning/drug effects/*physiology ; Chickens ; Dose-Response Relationship, Drug ; Gene Expression Regulation/*drug effects ; Glutamic Acid/pharmacology ; Inosine Monophosphate/*pharmacology ; Piperidines/pharmacology ; RNA, Messenger/metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Taste/drug effects/*physiology ; Taste Perception/drug effects/*physiology ; Time Factors ; }, abstract = {Umami taste is one of the five basic tastes (sweet, umami, bitter, sour, and salty), and is elicited by l-glutamate salts and 5'-ribonucleotides. In chickens, the elucidation of the umami taste sense is an important step in the production of new feedstuff for the animal industry. Although previous studies found that chickens show a preference for umami compounds in long-term behavioral tests, there are limitations to our understanding of the role of the umami taste sense in chicken oral tissues because the long-term tests partly reflected post-ingestive effects. Here, we performed a short-term test and observed agonists of chicken umami taste receptor, l-alanine and l-serine, affected the solution intakes of chickens. Using this method, we found that chickens could respond to umami solutions containing monosodium l-glutamate (MSG) + inosine 5'-monophosphate (IMP) within 5 min. We also demonstrated that chickens were successfully conditioned to avoid umami solution by the conditioned taste aversion test. It is noted that conditioning to umami solution was generalized to salty and sweet solutions. Thus, chickens may perceive umami taste as a salty- and sweet-like taste. In addition, we found that umami taste receptor candidates were differentially expressed in different regions of the chicken oral tissues. Taken together, the present results strongly suggest that chickens have a sense of umami taste and have umami taste receptors in their oral tissue.}, } @article {pmid29562120, year = {2017}, author = {Tingley, R and Ward-Fear, G and Schwarzkopf, L and Greenlees, MJ and Phillips, BL and Brown, G and Clulow, S and Webb, J and Capon, R and Sheppard, A and Strive, T and Tizard, M and Shine, R}, title = {New Weapons in the Toad Toolkit: A Review of Methods to Control and Mitigate the Biodiversity Impacts of Invasive Cane Toads (Rhinella Marina).}, journal = {The Quarterly review of biology}, volume = {92}, number = {2}, pages = {123-149}, doi = {10.1086/692167}, pmid = {29562120}, issn = {0033-5770}, mesh = {*Adaptation, Physiological ; Animals ; Australia ; *Biodiversity ; Bufo marinus/*physiology ; *Ecosystem ; *Introduced Species ; Pest Control/*methods ; Population Dynamics ; }, abstract = {Our best hope of developing innovative methods to combat invasive species is likely to come from the study of high-profile invaders that have attracted intensive research not only into control, but also basic biology. Here we illustrate that point by reviewing current thinking about novel ways to control one of the world’s most well-studied invasions: that of the cane toad in Australia. Recently developed methods for population suppression include more effective traps based on the toad’s acoustic and pheromonal biology. New tools for containing spread include surveillance technologies (e.g., eDNA sampling and automated call detectors), as well as landscape-level barriers that exploit the toad’s vulnerability to desiccation—a strategy that could be significantly enhanced through the introduction of sedentary, range-core genotypes ahead of the invasion front. New methods to reduce the ecological impacts of toads include conditioned taste aversion in free-ranging predators, gene banking, and targeted gene flow. Lastly, recent advances in gene editing and gene drive technology hold the promise of modifying toad phenotypes in ways that may facilitate control or buffer impact. Synergies between these approaches hold great promise for novel and more effective means to combat the toad invasion and its consequent impacts on biodiversity.}, } @article {pmid29560525, year = {2018}, author = {Brox, BW and Ellenbroek, BA}, title = {A genetic reduction in the serotonin transporter differentially influences MDMA and heroin induced behaviours.}, journal = {Psychopharmacology}, volume = {235}, number = {7}, pages = {1907-1914}, pmid = {29560525}, issn = {1432-2072}, mesh = {Analgesics, Opioid/administration & dosage ; Animals ; Avoidance Learning/*drug effects/physiology ; Behavior, Addictive/chemically induced/*genetics/metabolism ; Central Nervous System Stimulants/administration & dosage ; Dose-Response Relationship, Drug ; Heroin/*administration & dosage ; Locomotion/*drug effects/physiology ; Male ; N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage ; RNA-Binding Proteins/*genetics/metabolism ; Rats ; Rats, Transgenic ; Rats, Wistar ; Reinforcement, Psychology ; Self Administration ; Serotonin Agents/administration & dosage ; Taste/drug effects/physiology ; }, abstract = {BACKGROUND: Despite ongoing study and research to better understand drug addiction, it continues to be a heavy burden. Only a small percentage of individuals who take drugs of abuse go on to develop addiction. However, there is growing evidence to suggest that a reduction in the serotonin transporter may play an important role for those that transition to compulsive drug taking. Studies have demonstrated that reduced serotonin transporter function potentiates self-administration of psychostimulant drugs ("ecstasy," MDMA; cocaine); however, additional research revealed no differences between genotypes when the opioid heroin was self-administered. These results suggest that a reduction in the serotonin transporter may confer susceptibility to the development of addiction to some classes of drugs but not others. Importantly, the mechanism underlying facilitated psychostimulant self-administration is currently unknown.

METHODS: Therefore, to continue investigating the relationship between compromised serotonergic function and different classes of drugs, a series of experiments was conducted investigating locomotor activity (LMA) and conditioned taste aversion (CTA) in the serotonin transporter knockout (SERT KO) rat model.

RESULTS: MDMA-induced hyperactivity was reduced, while MDMA-induced CTA was enhanced, in SERT KO rats. However, there were no genotype differences in heroin-induced behaviours.

CONCLUSIONS: These results reinforce the idea that a reduction in the serotonin transporter drives differential effects between disparate classes of drugs of abuse.}, } @article {pmid29538098, year = {2018}, author = {Klockars, OA and Klockars, A and Levine, AS and Olszewski, PK}, title = {Oxytocin administration in the basolateral and central nuclei of amygdala moderately suppresses food intake.}, journal = {Neuroreport}, volume = {29}, number = {6}, pages = {504-510}, doi = {10.1097/WNR.0000000000001005}, pmid = {29538098}, issn = {1473-558X}, mesh = {Animals ; Avoidance Learning/drug effects ; Basolateral Nuclear Complex/*drug effects/metabolism ; Camphanes/pharmacology ; Central Amygdaloid Nucleus/*drug effects/metabolism ; Drinking/drug effects ; Eating/*drug effects ; Food Deprivation ; Male ; Oxytocics/*administration & dosage ; Oxytocin/*administration & dosage/antagonists & inhibitors ; Piperazines/pharmacology ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Oxytocin/genetics/metabolism ; Taste/drug effects ; }, abstract = {Oxytocin (OT) at acting central nuclei decreases meal size and reduces intake of palatable sweet solutions. It remains largely unclear as to which brain sites mediate OT's effect on palatability versus energy or the combination of those aspects of consumption. Here, we expanded the search for sites that mediate anorexigenic properties of OT by focusing on two subdivisions of the amygdala, its central (CNA) and basolateral (BLA) nuclei. We injected OT directly into the BLA or CNA in rats and assessed intake of standard chow induced by energy deprivation and intake of sweet solutions in nondeprived animals. We examined whether these effects are reversible by OT receptor (OTr) antagonism and whether OT presence in BLA or CNA induces taste aversion. We also determined the effect of energy deprivation and exposure to sweet saccharin on BLA and CNA expression of OTr mRNA. OT administration in BLA at 0.3 μg and in CNA at 1 μg reduced standard chow intake after deprivation by ~25%. Only administration of OT in BLA was effective in suppressing consumption of sucrose and saccharin solutions. The anorexigenic effects of OT in BLA and CNA were attenuated by OTr antagonist, L-368,899, pretreatment. OT at anorexigenic doses did not promote acquisition of taste aversion. BLA OTr mRNA expression was affected by exposure to palatable saccharin, whereas that of CNA OTr, by energy deprivation. OT in the amygdala moderately decreases food intake. The functional relationship between amygdalar OT and energy intake versus palatability-driven intake depends on the discrete localization of the OTr within this complex structure.}, } @article {pmid29499345, year = {2018}, author = {Richardson, RA and Michener, PN and Schachtman, TR}, title = {Effects of extinction of a nontarget CS on performance to a target CS.}, journal = {Behavioural processes}, volume = {154}, number = {}, pages = {13-20}, doi = {10.1016/j.beproc.2018.02.017}, pmid = {29499345}, issn = {1872-8308}, mesh = {Animals ; *Conditioning, Classical ; *Extinction, Psychological ; Male ; Rats ; Retrospective Studies ; }, abstract = {When a target conditioned stimulus (CS A) is paired with an unconditioned stimulus in the presence of a second, conditioned stimulus (CS B) during compound conditioning trials, the associative strength of CS B can influence the magnitude of the conditioned response (CR) to CS A. For example, extinction of the competing, nontarget CS B can influence the CR to CS A. An enhancement of the CR to the target CS A due to extinction of the nontarget CS B after compound conditioning is sometimes referred to as "recovery from overshadowing" - a type of retrospective revaluation. The present experiments examined retrospective revaluation effects using a conditioned taste aversion procedure. The experiments obtained an effect on the CR to CS A following extinction of CS B. The results are discussed with respect to the comparator hypothesis, within-compound associations, and retrieval as well as other relationships between the target CS and nontarget CS.}, } @article {pmid29486102, year = {2018}, author = {Dadam, F and Zádor, F and Caeiro, X and Szűcs, E and Erdei, AI and Samavati, R and Gáspár, R and Borsodi, A and Vivas, L}, title = {The effect of increased NaCl intake on rat brain endogenous μ-opioid receptor signalling.}, journal = {Journal of neuroendocrinology}, volume = {30}, number = {4}, pages = {e12585}, doi = {10.1111/jne.12585}, pmid = {29486102}, issn = {1365-2826}, mesh = {Animals ; Brain/*drug effects/metabolism ; Preoptic Area/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu/*metabolism ; Signal Transduction/*drug effects ; Sodium Chloride/*administration & dosage ; }, abstract = {Numerous studies demonstrate the significant role of central β-endorphin and its receptor, the μ-opioid receptor (MOR), in sodium intake regulation. The present study aimed to investigate the possible relationship between chronic high-NaCl intake and brain endogenous MOR functioning. We examined whether short-term (4 days) obligatory salt intake (2% NaCl solution) in rats induces changes in MOR mRNA expression, G-protein activity and MOR binding capacity in brain regions involved in salt intake regulation. Plasma osmolality and electrolyte concentrations after sodium overload and the initial and final body weight of the animals were also examined. After 4 days of obligatory hypertonic sodium chloride intake, there was clearly no difference in MOR mRNA expression and G-protein activity in the median preoptic nucleus (MnPO). In the brainstem, MOR binding capacity also remained unaltered, although the maximal efficacy of MOR G-protein significantly increased. Finally, no significant alterations were observed in plasma osmolality and electrolyte concentrations. Interestingly, animals that received sodium gained significantly less weight than control animals. In conclusion, we found no significant alterations in the MnPO and brainstem in the number of available cell surface MORs or de novo syntheses of MOR after hypertonic sodium intake. The increased MOR G-protein activity following acute sodium overconsumption may participate in the maintenance of normal blood pressure levels and/or in enhancing sodium taste aversion and sodium overload-induced anorexia.}, } @article {pmid29471071, year = {2018}, author = {Gartner, SN and Aidney, F and Klockars, A and Prosser, C and Carpenter, EA and Isgrove, K and Levine, AS and Olszewski, PK}, title = {Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice.}, journal = {Appetite}, volume = {125}, number = {}, pages = {278-286}, doi = {10.1016/j.appet.2018.02.015}, pmid = {29471071}, issn = {1095-8304}, mesh = {Animals ; Appetite/*drug effects ; Brain/cytology/*drug effects ; Dietary Fats/administration & dosage ; Dietary Sucrose/administration & dosage ; Dietary Supplements ; Drinking/drug effects ; Eating/*drug effects ; Energy Intake/*drug effects ; Feeding Behavior/*drug effects ; Food Deprivation ; Lipids/administration & dosage ; Male ; Mice, Inbred C57BL ; Oxytocin/*agonists ; Receptors, Oxytocin/metabolism ; Saccharin/administration & dosage ; Satiety Response/drug effects ; Sweetening Agents/administration & dosage ; Taste ; Thirst ; Tryptophan/*pharmacology ; Water ; }, abstract = {Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT.}, } @article {pmid29469954, year = {2018}, author = {Blednov, YA and Da Costa, AJ and Harris, RA and Messing, RO}, title = {Apremilast Alters Behavioral Responses to Ethanol in Mice: II. Increased Sedation, Intoxication, and Reduced Acute Functional Tolerance.}, journal = {Alcoholism, clinical and experimental research}, volume = {42}, number = {5}, pages = {939-951}, pmid = {29469954}, issn = {1530-0277}, support = {R01 AA006399/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {*Alcoholic Intoxication ; Animals ; Behavior, Animal/*drug effects ; Drug Interactions ; Drug Tolerance ; Ethanol/antagonists & inhibitors/pharmacology ; Female ; Hypnotics and Sedatives/pharmacology ; Male ; Mice ; Thalidomide/*analogs & derivatives/pharmacology ; }, abstract = {BACKGROUND: In our companion paper, we reported that the phosphodiesterase type 4 inhibitor apremilast reduced ethanol (EtOH) intake and preference in different drinking models in male and female C57BL/6J mice. In this study, we measured the effects of apremilast on other behaviors that are correlated with EtOH consumption.

METHODS: The effects of apremilast (20 mg/kg) on the following behaviors were studied in male and female C57BL/6J mice: locomotor response to a novel situation; EtOH- and lithium chloride (LiCl)-induced conditioned taste aversion (CTA) to saccharin; conditioned place preference (CPP) and conditioned place avoidance (CPA) to EtOH; severity of handling-induced convulsions after EtOH administration; EtOH-induced anxiolytic-like behavior in the elevated plus maze; duration of EtOH-induced loss of righting reflex (LORR); recovery from EtOH-induced motor impairment on the rotarod; and acute functional tolerance (AFT) to EtOH's ataxic effects.

RESULTS: Apremilast did not change the acquisition of EtOH-induced CPP, severity of acute withdrawal from EtOH, or EtOH's anxiolytic-like effect. Apremilast did not alter the extinction of EtOH- or LiCl-induced CTA, but may interfere with acquisition of CTA to EtOH. Apremilast increased the acquisition of CPA to EtOH, reduced locomotor responses to a novel situation, and prolonged the duration of LORR and the recovery from acute motor incoordination induced by EtOH. The longer recovery from the ataxic effect may be attributed to reduced development of AFT to EtOH.

CONCLUSIONS: Our results suggest that apremilast increases the duration of EtOH intoxication by reducing AFT. Apremilast also reduces some aspects of general reward and increases EtOH's aversive properties, which might also contribute to its ability to reduce EtOH drinking.}, } @article {pmid29452828, year = {2018}, author = {Tooley, J and Marconi, L and Alipio, JB and Matikainen-Ankney, B and Georgiou, P and Kravitz, AV and Creed, MC}, title = {Glutamatergic Ventral Pallidal Neurons Modulate Activity of the Habenula-Tegmental Circuitry and Constrain Reward Seeking.}, journal = {Biological psychiatry}, volume = {83}, number = {12}, pages = {1012-1023}, pmid = {29452828}, issn = {1873-2402}, support = {R25 GM055036/GM/NIGMS NIH HHS/United States ; Z99 DK999999//Intramural NIH HHS/United States ; }, mesh = {Action Potentials/drug effects/genetics ; Animals ; Avoidance Learning/physiology ; Bacterial Proteins/genetics/metabolism ; Basal Forebrain/*cytology ; Channelrhodopsins/genetics/metabolism ; Choline O-Acetyltransferase/genetics/metabolism ; Conditioning, Operant/physiology ; Dopamine/metabolism ; Excitatory Amino Acid Agents/pharmacology ; Excitatory Postsynaptic Potentials/drug effects/genetics ; Female ; Glutamic Acid/*metabolism/pharmacology ; Habenula/*physiology ; Luminescent Proteins/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/*physiology ; Optogenetics ; Parvalbumins/genetics/metabolism ; Patch-Clamp Techniques ; *Reward ; Taste ; Transduction, Genetic ; Ventral Tegmental Area/*physiology ; Vesicular Glutamate Transport Protein 2/genetics/metabolism ; Vesicular Inhibitory Amino Acid Transport Proteins/genetics/metabolism ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {BACKGROUND: The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modulate these behaviors is not known. We identify a noncanonical population of glutamatergic VP neurons that play a unique role in responding to aversive stimuli and constraining inappropriate reward seeking.

METHODS: Using neurochemical, genetic, and electrophysiological approaches, we characterized glutamatergic VP neurons (n = 4-8 mice/group). We performed patch clamp and in vivo electrophysiology recordings in the lateral habenula, rostromedial tegmental nucleus, and ventral tegmental area to determine the effect of glutamatergic VP neuron activation in these target regions (n = 6-10 mice/group). Finally, we selectively optogenetically stimulated glutamatergic VP neurons in a real-time place preference task and ablated these neurons using a virally expressed caspase to determine their necessity for reward seeking.

RESULTS: Glutamatergic VP neurons exhibit little overlap with cholinergic or gamma-aminobutyric acidergic markers, the canonical VP subtypes, and exhibit distinct membrane properties. Glutamatergic VP neurons innervate and increase firing activity of the lateral habenula, rostromedial tegmental nucleus, and gamma-aminobutyric acidergic ventral tegmental area neurons. While nonselective optogenetic stimulation of the VP induced a robust place preference, selective activation of glutamatergic VP neurons induced a place avoidance. Viral ablation of glutamatergic VP neurons increased reward responding and abolished taste aversion to sucrose.

CONCLUSIONS: Glutamatergic VP neurons constitute a noncanonical subpopulation of VP neurons. These glutamatergic VP neurons increase activity of the lateral habenula, rostromedial tegmental nucleus, and gamma-aminobutyric acidergic ventral tegmental area neurons and adaptively constrain reward seeking.}, } @article {pmid29447835, year = {2018}, author = {Nakajima, S}, title = {Clay eating attenuates lithium-based taste aversion learning in rats: A remedial effect of kaolin on nausea.}, journal = {Physiology & behavior}, volume = {188}, number = {}, pages = {199-204}, doi = {10.1016/j.physbeh.2018.02.020}, pmid = {29447835}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Antidiarrheals/*therapeutic use ; Antimanic Agents/toxicity ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Eating/drug effects ; Kaolin/*therapeutic use ; Lithium Chloride/toxicity ; Male ; Nausea/chemically induced/*drug therapy ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Kaolin clay eating has been considered as a marker of nausea in rats, because a variety of treatments, which evoke nausea in humans, generate consumption of kaolin clay in rats. The present study with two experiments replicated kaolin clay ingestion induced by an injection of emetic lithium chloride (LiCl). The LiCl injection, however, did not generate eating of wooden objects in rats. The present study also provides a new finding that consumption of kaolin clay alleviates rats' taste aversion learning caused by an LiCl injection. This finding is congruent with the contention that consumption of kaolin clay is not only a useful index of, but also an effective remedy for, drug-induced nausea in rats.}, } @article {pmid29403379, year = {2017}, author = {Reed, C and Baba, H and Zhu, Z and Erk, J and Mootz, JR and Varra, NM and Williams, RW and Phillips, TJ}, title = {A Spontaneous Mutation in Taar1 Impacts Methamphetamine-Related Traits Exclusively in DBA/2 Mice from a Single Vendor.}, journal = {Frontiers in pharmacology}, volume = {8}, number = {}, pages = {993}, pmid = {29403379}, issn = {1663-9812}, support = {T32 DA007262/DA/NIDA NIH HHS/United States ; R01 DA034388/DA/NIDA NIH HHS/United States ; U01 DA041579/DA/NIDA NIH HHS/United States ; P50 DA018165/DA/NIDA NIH HHS/United States ; R24 AA020245/AA/NIAAA NIH HHS/United States ; I01 BX002106/BX/BLRD VA/United States ; }, abstract = {Major gene effects on traits associated with substance use disorders are rare. Previous findings in methamphetamine drinking (MADR) lines of mice, bred for high or low voluntary MA intake, and in null mutants demonstrate a major impact of the trace amine-associated receptor 1 (Taar1) gene on a triad of MA-related traits: MA consumption, MA-induced conditioned taste aversion and MA-induced hypothermia. While inbred strains are fundamentally genetically stable, rare spontaneous mutations can become fixed and result in new or aberrant phenotypes. A single nucleotide polymorphism in Taar1 that encodes a missense proline to threonine mutation in the second transmembrane domain (Taar1[m1J]) has been identified in the DBA/2J strain. MA is an agonist at this receptor, but the receptor produced by Taar1[m1J] does not respond to MA or endogenous ligands. In the present study, we used progeny of the C57BL/6J × DBA/2J F2 cross, the MADR lines, C57BL/6J × DBA/2J recombinant inbred strains, and DBA/2 mice sourced from four vendors to further examine Taar1-MA phenotype relations and to define the chronology of the fixation of the Taar1[m1J] mutation. Mice homozygous for Taar1[m1J] were found at high frequency early in selection for high MA intake in multiple replicates of the high MADR line, whereas Taar1[m1J] homozygotes were absent in the low MADR line. The homozygous Taar1[m1J] genotype is causally linked to increased MA intake, reduced MA-induced conditioned taste aversion, and reduced MA-induced hypothermia across models. Genotype-phenotype correlations range from 0.68 to 0.96. This Taar1 polymorphism exists in DBA/2J mice sourced directly from The Jackson Laboratory, but not DBA/2 mice sourced from Charles River (DBA/2NCrl), Envigo (formerly Harlan Sprague Dawley; DBA/2NHsd) or Taconic (DBA/2NTac). By genotyping archived samples from The Jackson Laboratory, we have determined that this mutation arose in 2001-2003. Our data strengthen the conclusion that the mutant Taar1[m1J] allele, which codes for a non-functional receptor protein, increases risk for multiple MA-related traits, including MA intake, in homozygous Taar1[m1J] individuals.}, } @article {pmid29326059, year = {2018}, author = {Guzmán-Ramos, K and Venkataraman, A and Morin, JP and Osorio-Gómez, D and Bermúdez-Rattoni, F}, title = {Differential requirement of de novo Arc protein synthesis in the insular cortex and the amygdala for safe and aversive taste long-term memory formation.}, journal = {Behavioural brain research}, volume = {342}, number = {}, pages = {89-93}, doi = {10.1016/j.bbr.2018.01.006}, pmid = {29326059}, issn = {1872-7549}, mesh = {Amygdala/drug effects/physiology ; Animals ; Avoidance Learning/drug effects ; Cerebral Cortex/drug effects/physiology ; Conditioning, Classical/physiology ; Cytoskeletal Proteins/biosynthesis/*metabolism ; Male ; Memory/physiology ; Memory, Long-Term/*physiology ; Nerve Tissue Proteins/biosynthesis/*metabolism ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Taste/*drug effects/physiology ; }, abstract = {Several immediate early genes products are known to be involved in the facilitation of structural and functional modifications at distinct synapses activated through experience. The IEG-encoded protein Arc (activity regulated cytoskeletal-associated protein) has been widely implicated in long-term memory formation and stabilization. In this study, we sought to evaluate a possible role for de novo Arc protein synthesis in the insular cortex (IC) and in the amygdala (AMY) during long-term taste memory formation. We found that acute inhibition of Arc protein synthesis through the infusion of antisense oligonucleotides administered in the IC before a novel taste presentation, affected consolidation of a safe taste memory trace (ST) but spared consolidation of conditioned taste aversion (CTA). Conversely, blocking Arc synthesis within the AMY impaired CTA consolidation but had no effect on ST long-term memory formation. Our results suggest that Arc-dependent plasticity during taste learning is required within distinct structures of the medial temporal lobe, depending on the emotional valence of the memory trace.}, } @article {pmid29294381, year = {2018}, author = {Aonuma, H and Totani, Y and Kaneda, M and Nakamura, R and Watanabe, T and Hatakeyama, D and Dyakonova, VE and Lukowiak, K and Ito, E}, title = {Effects of 5-HT and insulin on learning and memory formation in food-deprived snails.}, journal = {Neurobiology of learning and memory}, volume = {148}, number = {}, pages = {20-29}, doi = {10.1016/j.nlm.2017.12.010}, pmid = {29294381}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/*physiology ; Central Nervous System/drug effects/*metabolism ; *Cognitive Dysfunction/drug therapy/etiology/metabolism/physiopathology ; Conditioning, Psychological/drug effects/*physiology ; Food Deprivation/*physiology ; Hypoglycemic Agents/administration & dosage/*pharmacology ; Insulin/administration & dosage/*pharmacology ; Lymnaea/drug effects/metabolism/*physiology ; Memory, Long-Term/drug effects/*physiology ; Serotonin/*metabolism ; Taste Perception/drug effects/*physiology ; Time Factors ; }, abstract = {The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). How well they learn and form memory depends on the degree of food deprivation. Serotonin (5-HT) plays an important role in mediating feeding, and insulin enhances the memory consolidation process following CTA training. However, the relationship between these two signaling pathways has not been addressed. We measured the 5-HT content in the central nervous system (CNS) of snails subjected to different durations of food deprivation. One-day food-deprived snails, which exhibit the best learning and memory, had the lowest 5-HT content in the CNS, whereas 5-day food-deprived snails, which do not learn, had a high 5-HT content. Immersing 1-day food-deprived snails in 5-HT impaired learning and memory by causing an increase in 5-HT content, and that the injection of insulin into these snails reversed this impairment. We conclude that insulin rescues the CTA deficit and this may be due to a decrease in the 5-HT content in the CNS of Lymnaea.}, } @article {pmid29254662, year = {2018}, author = {Li, N and Song, G and Wang, Y and Zhu, Q and Han, F and Zhang, C and Zhou, Y}, title = {Blocking constitutive activity of GHSR1a in the lateral amygdala facilitates acquisition of conditioned taste aversion.}, journal = {Neuropeptides}, volume = {68}, number = {}, pages = {22-27}, doi = {10.1016/j.npep.2017.12.001}, pmid = {29254662}, issn = {1532-2785}, mesh = {Animals ; *Avoidance Learning ; Basolateral Nuclear Complex/*physiology ; *Conditioning, Classical ; Ghrelin/administration & dosage/physiology ; Male ; Mental Recall/drug effects ; Rats, Wistar ; Receptors, Ghrelin/antagonists & inhibitors/*physiology ; }, abstract = {Ghrelin is a circulating peptide hormone promoting feeding and regulating energy metabolism in human and rodents. Ghrelin functions by binding to its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), which are widely distributed throughout the brain including the amygdala, a brain region important for regulating valenced behavior, such as aversion. Interestingly, GHSR1a was once characterized by highly constitutive, ligand-independent activity. However, the physiological importance of such ligand-independent signaling on aversive memory processing has not been tested yet. Here, we applied [D-Arg[1], D-Phe[5], D-Trp[7,9], Leu[11]]-Substance P (D-SP), a full inverse agonist for GHSR1a, into the lateral amygdala (LA) and investigated the effect of blocking GHSR1a constitutive activity on conditioned taste aversion (CTA) in rats. We found that intra-LA infusion of a single low dose of D-SP (8ng/0.5μl/side) facilitates CTA acquisition. Moreover, pre-administration of a high dose of D-SP into the LA abolishes the suppressive effect of exogenous ghrelin on CTA acquisition. In contrast, pre-administration of the same dose of D-SP does not affect the suppression of substance P, a potent neurokinin-1 (NK1) receptor ligand, on CTA. Therefore, our data indicated that the spontaneous or basal activity of GHSR1a signaling in the LA might interfere with CTA memory formation. D-SP decreases the constitutive activity of GHSR1a and thus facilitates CTA. Altogether, our present findings along with previous results support the idea that ghrelin/GHSR1a signaling in the LA circuit blocks conditioned taste aversion.}, } @article {pmid29184500, year = {2017}, author = {Juárez-Muñoz, Y and Ramos-Languren, LE and Escobar, ML}, title = {CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory Persistence.}, journal = {Frontiers in pharmacology}, volume = {8}, number = {}, pages = {822}, pmid = {29184500}, issn = {1663-9812}, abstract = {Calcium-calmodulin/dependent protein kinase II (CaMKII) plays an essential role in LTP induction, but since it has the capacity to remain persistently activated even after the decay of external stimuli it has been proposed that it can also be necessary for LTP maintenance and therefore for memory persistence. It has been shown that basolateral amygdaloid nucleus (Bla) stimulation induces long-term potentiation (LTP) in the insular cortex (IC), a neocortical region implicated in the acquisition and retention of conditioned taste aversion (CTA). Our previous studies have demonstrated that induction of LTP in the Bla-IC pathway before CTA training increased the retention of this task. Although it is known that IC-LTP induction and CTA consolidation share similar molecular mechanisms, little is known about the molecular actors that underlie their maintenance. The purpose of the present study was to evaluate the role of CaMKII in the maintenance of in vivo Bla-IC LTP as well as in the persistence of CTA long-term memory (LTM). Our results show that acute microinfusion of myr-CaMKIINtide, a selective inhibitor of CaMKII, in the IC of adult rats during the late-phase of in vivo Bla-IC LTP blocked its maintenance. Moreover, the intracortical inhibition of CaMKII 24 h after CTA acquisition impairs CTA-LTM persistence. Together these results indicate that CaMKII is a central key component for the maintenance of neocortical synaptic plasticity as well as for persistence of CTA-LTM.}, } @article {pmid29182614, year = {2017}, author = {Hurtado, MM and García, R and Puerto, A}, title = {Tiapride prevents the aversive but not the rewarding effect induced by parabrachial electrical stimulation in a place preference task.}, journal = {Acta neurobiologiae experimentalis}, volume = {77}, number = {3}, pages = {236-243}, pmid = {29182614}, issn = {1689-0035}, mesh = {Analysis of Variance ; Animals ; Antipsychotic Agents/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Electric Stimulation/methods ; Male ; Maze Learning/drug effects ; Parabrachial Nucleus/*physiology ; Random Allocation ; Rats ; Rats, Wistar ; *Reward ; Tiapride Hydrochloride/*pharmacology ; }, abstract = {The parabrachial complex has been related to the processing of both rewarding and aversive signals. This pontine area is activated after the gastrointestinal administration of rewarding nutrients, in taste aversion learning, and in response to the reinforcing and aversive effects of some drugs of abuse. Electrical stimulation of this region can induce, in different animals, preference or aversion behaviors towards a place in a rectangular three-chamber maze task. This study examined the effect of tiapride, a D2/D3 receptor antagonist, on the aversive or rewarding effects induced by electrical stimulation of the external lateral parabrachial subnucleus (NLPBe). As previously observed, administration of tiapride interrupted the aversive effect induced by NLPBe electrical stimulation. However, in contrast to the effects of dopamine antagonists on other rewarding systems, tiapride did not impair the place preference induced by NLPBe stimulation, an activation effect that is subject to tolerance. Tiapride administration also appeared to have no effect on the horizontal motor activity (crossings) of the electrically stimulated animals. We discuss the specific relevance of parabrachial reward with respect to other reinforcing brain components or systems, especially in relation to the preference effect of drugs of abuse, such as opiates, after dopamine antagonist administration.}, } @article {pmid29176267, year = {2018}, author = {Hojo, R and Takaya, M and Yasuda, A and Tsuchiya, M and Ogawa, Y}, title = {Examination of validity of a conditioned odor aversion (COA) procedure using low-dose of organic solvent as an applied procedure of the conditioned taste aversion.}, journal = {Industrial health}, volume = {56}, number = {2}, pages = {141-149}, pmid = {29176267}, issn = {1880-8026}, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Classical/physiology ; Lithium Chloride/administration & dosage ; Male ; Rats, Sprague-Dawley ; Smell/*physiology ; Taste/*physiology ; *Xylenes ; }, abstract = {Smell of very low dose of chemical might evoke subjective physical symptoms in human by some process of learning named the aversion conditioning. But few scientific evidences of the hypothesis have been reported so far. Validity of conditioned odor aversion (COA) using low-doses of organic solvent as odor conditioned stimulus (CS) was examined. In conditioning phase, water-deprived male Sprague-Dawley rats were presented low, medium or high dose solution for 30 min followed by 0.3 M Lithium Chloride (LiCl) solution or saline injection. The xylene solution and drink water were simultaneously provided on the next day as two-bottle test. Consumption of medium dose of xylene solution was significantly decreased in LiCl injection group as compared with saline group. There was no difference between LiCl and saline injected animals in low group. Animals in high dose did not access to xylene even on the conditioning. These results indicate that animals showed high sensitivity for discrimination against concentration of xylene and that the medium dose of xylene functioned as the CS. We concluded that the COA used in the present study may be one of useful procedures to investigate olfaction of animal.}, } @article {pmid29126997, year = {2018}, author = {Molero-Chamizo, A}, title = {Changes in the time of day of conditioning with respect to the pre-exposure interfere with the latent inhibition of conditioned taste aversion in rats.}, journal = {Behavioural processes}, volume = {146}, number = {}, pages = {22-26}, doi = {10.1016/j.beproc.2017.11.003}, pmid = {29126997}, issn = {1872-8308}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Cues ; Male ; Memory/physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; Time Factors ; }, abstract = {In rats, the reduction of the magnitude of a conditioned taste aversion (CTA) that occurs after taste pre-exposures (that is, the latent inhibition of CTA) can be attenuated by contextual changes of the external cues in the conditioning stage. Similarly, circadian internal cues such as those induced by the time of day may also modulate the magnitude of the taste aversion. Under a long period of temporal-contextual habituation, the latent inhibition of CTA is reduced if the pre-exposure and conditioning stages occur at different times of day. However, it is unknown if this effect is consistent when different changes in the time of day of conditioning with respect to the pre-exposure are compared. In this study, the effect of two different changes in the time of day of conditioning (one from morning to evening, and one from evening to morning) on the latent inhibition of CTA was compared with the response of a typical latent inhibition group without temporal change between stages, and with control groups without pre-exposures. The results indicate that the latent inhibition of CTA of both groups with temporal change between pre-exposure and conditioning is significantly reduced when compared with the latent inhibition of the group without temporal change. These findings suggest that the temporal context may be a critical cue for the latent inhibition of CTA, and they show that different changes in the time of day of conditioning interfere similarly with this learning.}, } @article {pmid29124570, year = {2018}, author = {Kislal, S and Blizard, DA}, title = {Acquisition and retention of conditioned aversions to context and taste in laboratory mice.}, journal = {Learning & behavior}, volume = {46}, number = {2}, pages = {198-212}, pmid = {29124570}, issn = {1543-4508}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Extinction, Psychological/*physiology ; Lithium Chloride/pharmacology ; Male ; Mice ; Retention, Psychology/drug effects/*physiology ; Taste/drug effects/*physiology ; }, abstract = {We compared the rate of acquisition and strength of retention of conditioned context aversion (CCA) with conditioned taste aversion (CTA) using pigmented, genetically heterogeneous mice (derived from Large and Small strains). Extending previous findings, in Experiment 1, mice accustomed to drinking from large glass bottles in the colony room learned to avoid graduated tubes after a single conditioning trial when drinking from these novel tubes was paired with injections of LiCl. The results also showed that CCA could be developed even when there was a 30-minute delay between conditioned stimulus and unconditioned stimulus. Retention of the aversion lasted for 4 weeks in both Immediate and Delay groups. Studies of conditioned saccharin aversion were conducted in Experiment 2. CTA acquisition was very similar to that observed in CCA and duration of aversion retention was similar in the CCA and CTA Delay groups, although at least 2 weeks longer in the Immediate group. Thus, CCA acquisition and retention characteristics are closer to those seen for CTA than has previously been reported. In Experiment 3, we examined whether albino mice (which are known to have weaker visual abilities compared to pigmented mice) would develop CCA comparable to those of pigmented mice. The development of conditioned aversion and its duration of retention was similar in albinos and pigmented mice. Nonspecific aversion emerged as an important contributor to strength of aversion during retention trials in both CCA and CTA paradigms with pigmented (but not albino) mice and deserves additional scrutiny in this field of inquiry.}, } @article {pmid29124569, year = {2018}, author = {Nakajima, S}, title = {Running-based pica and taste avoidance in rats.}, journal = {Learning & behavior}, volume = {46}, number = {2}, pages = {182-197}, pmid = {29124569}, issn = {1543-4508}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/*physiology ; Feeding Behavior/*physiology ; Male ; Motor Activity/*physiology ; *Pica ; Rats ; Taste/*physiology ; }, abstract = {Running in an activity wheel generates pica behavior (kaolin clay intake) in rats. Wheel running also results in Pavlovian conditioned avoidance of the taste solution consumed immediately before the running. Since pica has been considered a behavioral marker of nausea in rats, these findings suggest that wheel running induces nausea, which is the underlying physiological state for establishing taste avoidance. This article reports a replication of running-based pica in rats (Experiment 1) and concurrent demonstrations of running-based pica and taste avoidance in the same animals (Experiments 2 and 3). Also shown is that pica does not alleviate running-based taste avoidance (Experiment 3). Another finding is that pica is generated by a nausea-inducing lithium chloride injection but not by a pain-inducing hypertonic saline injection (Experiment 4). These results, when taken together, support the hypothesis that pica behavior generated by wheel running reflects nausea in rats.}, } @article {pmid29104056, year = {2018}, author = {Cheung, LC and Nguyen, M and Tang, E and von Ungern Sternberg, BS and Salman, S and Tuleu, C and Mohamed Ahmed, AHA and Soto, J and Lim, LY}, title = {Taste evaluation of a novel midazolam tablet for pediatric patients: In vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles.}, journal = {International journal of pharmaceutics}, volume = {535}, number = {1-2}, pages = {194-200}, doi = {10.1016/j.ijpharm.2017.10.060}, pmid = {29104056}, issn = {1873-3476}, mesh = {Administration, Oral ; Adolescent ; Animals ; Child ; Child, Preschool ; *Chocolate ; Drug Compounding ; Drug Liberation ; Facial Expression ; Feeding Behavior/*drug effects ; Flavoring Agents/*chemistry ; Humans ; Hypnotics and Sedatives/*administration & dosage/chemistry ; Injections, Intravenous ; Male ; Midazolam/*administration & dosage/chemistry ; Prospective Studies ; Rats, Sprague-Dawley ; Tablets ; Taste Perception/*drug effects ; }, abstract = {Harmonized methodologies are urgently required for the taste evaluation of novel pediatric medicines. This study utilized in vitro, in vivo and clinical data to evaluate the palatability of a novel midazolam chocolate tablet. In vitro dissolution experiments showed the crushed tablet to release within 5 min 1.68 mg of midazolam into simulated saliva. This translated to a drug level of 0.84 mg/ml in the oral cavity, which would be higher than the midazolam bitterness detection threshold concentration of 0.03 mg/ml determined in a rat 'brief access taste aversion' (BATA) model. The visual analogue scale scores of patients aged 4-16 years prescribed with midazolam pre-surgery showed a clear preference for the midazolam chocolate tablets (3.35 ± 1.04, n = 20) compared to the control midazolam solution (1.47 ± 0.62, n = 17). The clinical data was in agreement with the in vivo rodent data in showing the novel chocolate tablet matrix to be effective at taste-masking the bitter midazolam.}, } @article {pmid29081083, year = {2017}, author = {Lee, MJ and Sung, HY and Jo, H and Kim, HW and Choi, MS and Kwon, JY and Kang, K}, title = {Ionotropic Receptor 76b Is Required for Gustatory Aversion to Excessive Na+ in Drosophila.}, journal = {Molecules and cells}, volume = {40}, number = {10}, pages = {787-795}, pmid = {29081083}, issn = {0219-1032}, mesh = {Animals ; Behavior, Animal/drug effects ; Caffeine/administration & dosage ; Drosophila Proteins/*genetics ; Drosophila melanogaster/genetics/physiology ; Neurons/*drug effects/physiology ; Receptors, Cell Surface/*genetics ; Receptors, Ionotropic Glutamate/*genetics ; Salts/administration & dosage ; Sodium Channels/*genetics ; Taste/*genetics ; }, abstract = {Avoiding ingestion of excessively salty food is essential for cation homeostasis that underlies various physiological processes in organisms. The molecular and cellular basis of the aversive salt taste, however, remains elusive. Through a behavioral reverse genetic screening, we discover that feeding suppression by Na[+]-rich food requires Ionotropic Receptor 76b (Ir76b) in Drosophila labellar gustatory receptor neurons (GRNs). Concentrated sodium solutions with various anions caused feeding suppression dependent on Ir76b. Feeding aversion to caffeine and high concentrations of divalent cations and sorbitol was unimpaired in Ir76b-deficient animals, indicating sensory specificity of Ir76b-dependent Na[+] detection and the irrelevance of hyperosmolarity-driven mechanosensation to Ir76b-mediated feeding aversion. Ir76b-dependent Na[+]-sensing GRNs in both L- and s-bristles are required for repulsion as opposed to the previous report where the L-bristle GRNs direct only low-Na[+] attraction. Our work extends the physiological implications of Ir76b from low-Na[+] attraction to high-Na[+] aversion, prompting further investigation of the physiological mechanisms that modulate two competing components of Na[+]-evoked gustation coded in heterogeneous Ir76b-positive GRNs.}, } @article {pmid29080021, year = {2017}, author = {Torrealba, F and Madrid, C and Contreras, M and Gómez, K}, title = {Plasticity in the Interoceptive System.}, journal = {Advances in experimental medicine and biology}, volume = {1015}, number = {}, pages = {59-74}, doi = {10.1007/978-3-319-62817-2_4}, pmid = {29080021}, issn = {0065-2598}, mesh = {Animals ; Avoidance Learning/physiology ; Cerebral Cortex/*physiology ; Interoception/*physiology ; Learning/*physiology ; Neuronal Plasticity/*physiology ; Rats ; }, abstract = {The most outstanding manifestations of the plastic capacities of brain circuits and their neuronal and synaptic components in the adult CNS are learning and memory. A reduced number of basic plastic mechanisms underlie learning capacities at many levels and regions of the brain. The interoceptive system is no exception, and some of the most studied behavioral changes that involve learning and memory engage the interoceptive pathways at many levels of their anatomical and functional organization.In this chapter, we will review four examples of learning, mostly in rats, where the interoceptive system has a role. In the case of conditioned taste aversion, the interoceptive system is of outstanding importance. In drug addiction, the role of the insular cortex - the highest level of the interoceptive system- is unusual and complex, as many forebrain regions are engaged by the process of addiction. In the third example, neophobia, the gustatory region of the insular cortex plays a major role. Finally, the role of different areas of the insular cortex in different processes of aversive memory, particularly fear conditioning, will be reviewed.}, } @article {pmid29056353, year = {2018}, author = {Rodriguez, JA and Fehrentz, JA and Martinez, J and Ben Haj Salah, K and Wellman, PJ}, title = {The GHR-R antagonist JMV 2959 neither induces malaise nor alters the malaise property of LiCl in the adult male rat.}, journal = {Physiology & behavior}, volume = {183}, number = {}, pages = {46-48}, doi = {10.1016/j.physbeh.2017.10.017}, pmid = {29056353}, issn = {1873-507X}, mesh = {Animals ; Appetite/drug effects ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Feeding Behavior/*drug effects/psychology ; Glycine/*analogs & derivatives/pharmacology ; Lithium Chloride/*pharmacology ; Male ; Nicotine/pharmacology ; Psychotropic Drugs/*pharmacology ; Random Allocation ; Rats, Sprague-Dawley ; Receptors, Ghrelin/*antagonists & inhibitors ; *Reinforcement, Psychology ; Saccharin ; Sodium, Dietary ; Taste Perception/drug effects ; Triazoles/*pharmacology ; }, abstract = {The orexigenic peptide ghrelin (GHR) interacts with ghrelin receptors (GHR-Rs) to modulate brain reinforcement and feeding circuits. Pharmacological inactivation of GHR-Rs via administration of the drug JMV 2959 attenuates the rewarding/reinforcing effects of several drugs of abuse including alcohol, morphine, amphetamine and nicotine. One view of these results is that inactivation of GHR-Rs taps into brain reinforcement/feeding circuits acted upon by drugs of abuse. An alternate explanation is that JMV 2959 may induce malaise, which in turn may limit reinforcement as well as food ingestion. This is a variable of interest given that nicotine alone can induce malaise which may be enhanced by JMV 2959. In the present study, we assessed the capacity of JMV 2959 to produce malaise using a conditioned taste aversion (CTA) task. Adult male rats were allowed to consume a 0.1% sodium saccharin solution and then injected IP with either vehicle, 0.4mg/kg nicotine, 3mg/kg JMV 2959, a combination of 0.4mg/kg nicotine and 3mg/kg JMV 2959, or 32mg/kg lithium chloride (a positive control known to support induction of CTA). Lithium chloride produced a robust avoidance of the saccharin solution in subsequent 2 bottle (water and saccharin) tests, whereas JMV 2959 alone did not induce CTA. The combination of JMV 2959 and nicotine induced a moderate degree of CTA that was similar to that produced by nicotine alone. These results suggest that JMV 2959 is unlikely to limit either reinforcement or food ingestion via induction of malaise.}, } @article {pmid29037662, year = {2018}, author = {Ward, M and Norman, H and D'Souza, MS}, title = {Effects of pharmacological manipulation of the kappa opioid receptors on the aversive effects of nicotine.}, journal = {Behavioural brain research}, volume = {338}, number = {}, pages = {56-65}, doi = {10.1016/j.bbr.2017.10.011}, pmid = {29037662}, issn = {1872-7549}, mesh = {3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Male ; Naltrexone/*analogs & derivatives/pharmacology ; Narcotic Antagonists/*pharmacology ; Nicotine/*pharmacology ; Rats ; Rats, Wistar ; Receptors, Opioid, kappa/*antagonists & inhibitors ; Taste ; }, abstract = {Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified. In this study, we evaluated the role of kappa opioid receptors (KORs) in the aversive effects of nicotine (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion (CTA) model in Wistar rats. The KORs were activated using the selective KOR agonist (±)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate groups of rats using a between-subjects design. Pretreatment with the KOR agonist (±)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine-associated solution. Additionally, (±)U-50,488H (0.3mg/kg) on its own induced aversion to the flavored solution associated with it even in the absence of nicotine, suggesting that the KOR agonist induced increase in nicotine-induced aversion was an additive effect. Interestingly, administration of the KOR antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not after conditioning with nicotine/saline, attenuated nicotine-induced aversive effects compared to saline controls. Taken together, these data suggest a role for KORs in the aversive effects of nicotine.}, } @article {pmid29030219, year = {2018}, author = {Song, G and Zhu, Q and Han, F and Liu, S and Zhao, C and Zhou, Y}, title = {Local infusion of ghrelin into the lateral amygdala blocks extinction of conditioned taste aversion in rats.}, journal = {Neuroscience letters}, volume = {662}, number = {}, pages = {71-76}, doi = {10.1016/j.neulet.2017.10.012}, pmid = {29030219}, issn = {1872-7972}, mesh = {Amygdala/drug effects/*physiology ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; *Extinction, Psychological ; Ghrelin/pharmacology/*physiology ; Male ; Microinjections ; Phosphatidylinositol 3-Kinase/metabolism ; Rats, Wistar ; Taste/drug effects/*physiology ; }, abstract = {Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. Our previous study showed that ghrelin locally infused into the lateral amygdala (LA) activates its receptor GHS-R1a and blocks acquisition of conditioned taste aversion (CTA) in rats. In this study, we further investigated the effect of ghrelin/GHS-R1a signaling on extinction of CTA. We found that local infusion of ghrelin (5μM, 0.5μl/side) into the LA not only interfered with CTA memory formation, but also the extinction of CTA memory. Pre-administration of GHS-R1a antagonist blocked ghrelin's effect on both CTA acquisition and extinction. However, pre-treatment with PI3K inhibitor only abolished the inhibitory effect of ghrelin on acquisition, but not on extinction. Altogether, our data indicated that ghrelin/GHS-R1a signaling in the LA circuit modulates both acquisition and extinction of CTA, the two forms of taste aversion processes with distinct mechanisms may also share certain molecular and circuit components in common.}, } @article {pmid29021746, year = {2017}, author = {Vandaele, Y and Pribut, HJ and Janak, PH}, title = {Lever Insertion as a Salient Stimulus Promoting Insensitivity to Outcome Devaluation.}, journal = {Frontiers in integrative neuroscience}, volume = {11}, number = {}, pages = {23}, pmid = {29021746}, issn = {1662-5145}, abstract = {Flexible and efficient decision-making in complex environments can be achieved through constant interactions between the goal-directed and habitual systems. While goal-directed behavior is considered dependent upon Response-Outcome (R-O) associations, habits instead rely on Stimulus-Response (S-R) associations. However, the stimuli that support the S-R association underlying habitual responding in typical instrumental procedures are poorly defined. To resolve this issue, we designed a discrete-trials procedure, in which rats must wait for lever insertion and complete a sequence of five lever presses to obtain a reward (20% sucrose or grain-based pellets). Lever insertion thus constituted an audio-visual stimulus signaling the opportunity for reward. Using sensory-specific satiety-induced devaluation, we found that rats trained with grain-based pellets remained sensitive to outcome devaluation over the course of training with this procedure whereas rats trained with a solution of 20% sucrose rapidly developed habit, and that insensitivity to outcome devaluation in rats trained with sucrose did not result from a bias in general satiety. Importantly, although rats trained with pellets were sensitive to satiety-induced devaluation, their performance was not affected by degradation of instrumental contingency and devaluation by conditioned taste aversion (CTA), suggesting that these rats may also have developed habitual responding. To test whether the discrete-trials procedure biases subjects towards habitual responding, we compared discrete-trials to free-running instrumental responding, and found that rats trained with sucrose in a fixed-ratio 5 (FR5) procedure with continuous presentation of the lever were goal-directed. Together, these results demonstrate that discrete presentations of a stimulus predictive of reward availability promoted the formation of S-R habit in rats trained with liquid sucrose. Further research is necessary to explain inconsistencies in sensitivity to outcome devaluation when rats are trained with grain-based pellets.}, } @article {pmid28955210, year = {2017}, author = {Sunada, H and Totani, Y and Nakamura, R and Sakakibara, M and Lukowiak, K and Ito, E}, title = {Two Strains of Lymnaea stagnalis and the Progeny from Their Mating Display Differential Memory-Forming Ability on Associative Learning Tasks.}, journal = {Frontiers in behavioral neuroscience}, volume = {11}, number = {}, pages = {161}, pmid = {28955210}, issn = {1662-5153}, abstract = {The pond snail Lymnaea stagnalis learns and forms long-term memory (LTM) following both operant conditioning of aerial respiratory behavior and classical conditioning of taste aversive behavior. In the present study, we examined whether there are interstrain differences in the ability to form LTM following these two types of conditioning. A strain of Lymnaea (TC1) collected in Alberta, Canada exhibits superior memory-forming ability following aerial respiratory operant conditioning compared to a laboratory-reared strain of Lymnaea from Netherlands known as the Dutch strain. We asked whether the offspring of the Canadian TC1 and Dutch snails (i.e., filial 1 (F1) cross snails) would have the superior memory ability and found, rather, that their memory ability was average like the Dutch snails. That is, the Canadian TC1 snails have superior ability for LTM formation following aerial respiratory operant conditioning, but the Dutch and the generated F1 cross have average ability for memory forming. We next examined the Canadian TC1, Dutch and F1 cross snails for their ability to learn and form memory following conditioned taste aversion (CTA). All three populations showed similar associative CTA responses. However, both LTM formation and the ratio of good-to-poor performers in the memory retention test were much better in the Dutch snails than the Canadian TC1 and F1 cross snails. The memory abilities of the Canadian TC1 and F1 cross snails were average. Our present findings, therefore, suggest that snails of different strains have different memory abilities, and the F1 cross snails do not inherit the memory ability from the smart strain. To our knowledge, there have been a limited number of studies examining differences in memory ability among invertebrate strains, with the exception of studies using mutant flies.}, } @article {pmid28861596, year = {2017}, author = {Molero-Chamizo, A and Rivera-Urbina, GN}, title = {Effects of lesions in different nuclei of the amygdala on conditioned taste aversion.}, journal = {Experimental brain research}, volume = {235}, number = {11}, pages = {3517-3526}, pmid = {28861596}, issn = {1432-1106}, mesh = {Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/pathology/*physiology ; Behavior, Animal/physiology ; Central Amygdaloid Nucleus/pathology/*physiology ; Conditioning, Classical/*physiology ; Corticomedial Nuclear Complex/pathology/*physiology ; Male ; Rats ; Rats, Wistar ; Taste Perception/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is an adaptive learning that depends on brain mechanisms not completely identified. The amygdala is one of the structures that make up these mechanisms, but the involvement of its nuclei in the acquisition of CTA is unclear. Lesion studies suggest that the basolateral complex of the amygdala, including the basolateral and lateral amygdala, could be involved in CTA. The central amygdala has also been considered as an important nucleus for the acquisition of CTA in some studies. However, to the best of our knowledge, the effect of lesions of the basolateral complex of the amygdala on the acquisition of CTA has not been directly compared with the effect of lesions of the central and medial nuclei of the amygdala. The aim of this study is to compare the effect of lesions of different nuclei of the amygdala (the central and medial amygdala and the basolateral complex) on the acquisition of taste aversion in male Wistar rats. The results indicate that lesions of the basolateral complex of the amygdala reduce the magnitude of the CTA when compared with lesions of the other nuclei and with animals without lesions. These findings suggest that the involvement of the amygdala in the acquisition of CTA seems to depend particularly on the integrity of the basolateral complex of the amygdala.}, } @article {pmid28856957, year = {2019}, author = {Kwok, DW and Boakes, RA}, title = {Situational relevance: Context as a factor in serial overshadowing of taste aversion learning.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {72}, number = {2}, pages = {263-273}, doi = {10.1080/17470218.2017.1338739}, pmid = {28856957}, issn = {1747-0226}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Male ; Rats ; Rats, Wistar ; Taste Perception/*physiology ; }, abstract = {In a serial overshadowing procedure, a target stimulus, A, is followed after an interval by a potentially interfering stimulus, B, and this is then followed by an unconditioned stimulus (US). An untested proposal from over four decades ago was that the degree to which B overshadows conditioning of A depends on whether or not the two events take place in the same context. To test this, two experiments used a 1-trial long-delay conditioned taste aversion (CTA) procedure: sucrose served as the target taste (A) and dilute hydrochloric acid (HCl) as the overshadowing taste (B), with lithium chloride injection providing the US. In Experiment 1, these tastes were novel: weaker overshadowing by HCl of an aversion to sucrose was found when the two tastes were presented in different contexts. Experiment 2 tested whether the effect of pre-exposure to HCl, thereby rendering it less effective in overshadowing a sucrose aversion, was also context dependent. In the conditioning session, rats again received either context-same or context-different presentations of sucrose and HCl. However, for some rats, HCl was pre-exposed in the same context to which it was later presented during conditioning (Consistent), while others were pre-exposed to HCl in a different context to the one in which it was presented during conditioning (Inconsistent). The Inconsistent group produced greater overshadowing than the Consistent group and thus confirmed that the latent inhibition effect was also context dependent. This study confirms the concept of situational relevance.}, } @article {pmid28807538, year = {2017}, author = {Arthurs, J and Lin, JY and Ocampo, R and Reilly, S}, title = {Lactose malabsorption and taste aversion learning.}, journal = {Physiology & behavior}, volume = {180}, number = {}, pages = {39-44}, pmid = {28807538}, issn = {1873-507X}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic/toxicity ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects ; Drinking Behavior/drug effects ; Eating/drug effects/*physiology ; Lactose/*metabolism ; Lithium Chloride/toxicity ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/drug effects/*physiology ; Water Deprivation ; }, abstract = {Consumption of foods can be suppressed by two feeding system defense mechanisms: conditioned taste aversion (CTA) or taste avoidance learning (TAL). There is a debate in the literature about which form of intake suppression is caused by various aversive stimuli. For instance, illness-inducing stimuli like lithium chloride are the gold standard for producing CTA and external (or peripheral) painful stimuli, such as footshock, are the traditional model of TAL. The distinction between CTA and TAL, which have identical effects on intake, is based on differential effects on palatability. That is, CTA involves a decrease in both intake and palatability, whereas TAL suppresses intake without influencing palatability. We evaluated whether lactose, which causes gastrointestinal pain in adult rats, produces CTA or TAL. Using lick pattern analysis to simultaneously measure intake and palatability (i.e., lick cluster size and initial lick rate), we found that pairing saccharin with intragastric infusions of lactose suppressed both the intake and palatability of saccharin. These results support the conclusion that gastrointestinal pain produced by lactose malabsorption produces a CTA, not TAL as had previously been suggested. Furthermore, these findings encourage the view that the CTA mechanism is broadly tuned to defend against the ingestion of foods with aversive post-ingestive effects.}, } @article {pmid28803978, year = {2017}, author = {Sasaki, T and Yasoshima, Y and Matsui, S and Yokota-Hashimoto, H and Kobayashi, M and Kitamura, T}, title = {Intraperitoneal injection of d-serine inhibits high-fat diet intake and preference in male mice.}, journal = {Appetite}, volume = {118}, number = {}, pages = {120-128}, doi = {10.1016/j.appet.2017.08.011}, pmid = {28803978}, issn = {1095-8304}, mesh = {Animals ; Brain/drug effects/metabolism ; Conditioning, Classical ; *Diet, High-Fat ; *Feeding Behavior ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, N-Methyl-D-Aspartate/agonists/metabolism ; Serine/*pharmacology ; Taste ; }, abstract = {d-serine is a co-agonist of the N-methyl d-aspartate (NMDA) receptor, an important modulator of glutamatergic excitatory synaptic transmission. We previously reported that oral d-serine ingestion inhibited the intake of highly preferred food and promoted the intake of less preferred food in mice. Here, we analyzed the effects of intraperitoneal (IP) d-serine injections on feeding behavior in mice. We assessed the effects of d-serine during both the acquisition and maintenance of a preference for high-fat diets (HFDs). Aversiveness of IP d-serine was analyzed in the conditioned taste aversion paradigm. The effects on food intake were assessed by providing liquid meals with different fat contents. Finally, we measured brain d-serine and l-serine levels after d-serine administration. We found that IP-injected d-serine effectively inhibited the acquisition of a HFD preference, but failed to prevent expression of a previously learned HFD preference. IP-injected d-serine was not sufficient to condition taste aversion. The effect on HFD preference acquisition was associated with increases in d-serine levels in the cerebral cortex, hypothalamus, and cerebellum. IP-injected d-serine most effectively inhibited the intake of liquid meals with high fat content. This effect was dose-dependent, but the responses varied significantly among male C57BL/6J mice. The differential responses to d-serine were consistent among multiple trials in each mouse. In summary, IP-injected d-serine inhibited HFD intake and the acquisition of an HFD preference. Individual mice with the same genetic background showed different sensitivities to d-serine; thus, d-serine sensitivity may be associated with unidentified traits.}, } @article {pmid28716589, year = {2017}, author = {Miranda, MI and Rangel-Hernández, JA and Vera-Rivera, G and García-Medina, NE and Soto-Alonso, G and Rodríguez-García, G and Núñez-Jaramillo, L}, title = {The role of dopamine D2 receptors in the nucleus accumbens during taste-aversive learning and memory extinction after long-term sugar consumption.}, journal = {Neuroscience}, volume = {359}, number = {}, pages = {142-150}, doi = {10.1016/j.neuroscience.2017.07.009}, pmid = {28716589}, issn = {1873-7544}, mesh = {Animals ; *Avoidance Learning ; Extinction, Psychological/*physiology ; Male ; Mental Recall/physiology ; Nucleus Accumbens/*physiology ; Rats, Wistar ; Receptors, Dopamine D2/*physiology ; Sugars/*administration & dosage ; Taste ; }, abstract = {The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. Thus, the objective of this work was to evaluate, after long-term exposure to sugar, the function of dopaminergic D2 receptors in the NAcc core during taste memory retrieval preference test, and during CTA. Adult rats were exposed during 14days to 10% sugar solution as a single liquid ad libitum. NAcc core bilateral injections of D2 dopamine receptor antagonist, haloperidol (1μg/μL), were made before third preference test and CTA acquisition. We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity.}, } @article {pmid28693705, year = {2017}, author = {Molero-Chamizo, A and Rivera-Urbina, GN}, title = {Effects of temporal contexts and contextual habituation on latent inhibition.}, journal = {Psicothema}, volume = {29}, number = {3}, pages = {346-351}, doi = {10.7334/psicothema2016.312}, pmid = {28693705}, issn = {1886-144X}, mesh = {Animals ; *Habituation, Psychophysiologic ; *Inhibition, Psychological ; Male ; Rats ; Rats, Wistar ; Taste ; Time Factors ; }, abstract = {BACKGROUND: Latent inhibition of conditioned taste aversion (CTA) is sensitive to external and internal cues. Time of day can serve as an internal cue, and latent inhibition may be reduced if the pre-exposure and conditioning stages occur at different times of day. This contextual cue attributed to a change in the time of day may reveal a temporal specificity of latent inhibition. Although the habituation period to spatial contexts is a determinant variable for the spatial specificity of latent inhibition of CTA, the influence of contextual-temporal familiarity (time of day) on latent inhibition of CTA has not been explored through direct comparisons between different periods of habituation to the temporal context.

METHOD: Two different periods of contextual habituation (short vs. long) previous to taste pre-exposures were compared in Wistar rats to analyze the influence of these periods on the temporal specificity of latent inhibition of CTA.

RESULTS: A long period of habituation, in relation to a short period, facilitated the effect of a change of the time of day between pre-exposure and conditioning on the magnitude of taste aversion.

CONCLUSIONS: A long habituation to temporal contexts facilitates the temporal specificity of latent inhibition of CTA.}, } @article {pmid28689966, year = {2017}, author = {Münster, M and Mohamed-Ahmed, AHA and Immohr, LI and Schoch, C and Schmidt, C and Tuleu, C and Breitkreutz, J}, title = {Comparative in vitro and in vivo taste assessment of liquid praziquantel formulations.}, journal = {International journal of pharmaceutics}, volume = {529}, number = {1-2}, pages = {310-318}, doi = {10.1016/j.ijpharm.2017.06.084}, pmid = {28689966}, issn = {1873-3476}, mesh = {2-Hydroxypropyl-beta-cyclodextrin/*chemistry ; Animals ; Electronic Nose ; Male ; Praziquantel/*pharmacology ; Rats, Sprague-Dawley ; Solubility ; *Taste ; beta-Cyclodextrins/*chemistry ; }, abstract = {The taste of pharmaceuticals strongly affects the compliance of patients. This study investigated the applicability of the electronic tongue and rodent brief-access taste aversion (BATA) model for the bitter compound praziquantel (PZQ) and taste masked liquid formulations for PZQ. In a comparative study maltodextrin (MD) Kleptose[®] linecaps 17 was selected as an alternative taste masking agent to two cyclodextrins; hydroxypropyl-beta-cyclodextrin (HP-β-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-β-CD). A phase solubility study showed the highest affinity and solubilization capabilities for SBE-β-CD over HP-β-CD and MD, suggesting the highest taste masking ability for SBE-β-CD. No reliable results were achieved for PZQ with the Insent electronic tongue. Thus this system was not used for further evaluation of solutions with MD and CDs to confirm the results of the solubility study. In contrast the BATA model demonstrated conclusive responses for the aversiveness of PZQ. The concentration of PZQ inhibiting 50% of water lick numbers (called IC50 value) was 0.06mg/ml. In contrast to the phase solubility study, the MD enabled an equal taste masking effect in vivo in comparison to both CDs. Moreover HP-β-CD showed superior taste masking capabilities for PZQ compared to SBE-β-CD as the SBE-β-CD itself was less acceptable for the rodents than HP-β-CD. In conclusion, the BATA model was identified as a more efficient taste assessment tool for the pure PZQ and liquid formulations in contrast to the electronic tongue and the phase solubility study.}, } @article {pmid28687346, year = {2018}, author = {Keating, AV and Soto, J and Tuleu, C and Forbes, C and Zhao, M and Craig, DQM}, title = {Solid state characterisation and taste masking efficiency evaluation of polymer based extrudates of isoniazid for paediatric administration.}, journal = {International journal of pharmaceutics}, volume = {536}, number = {2}, pages = {536-546}, doi = {10.1016/j.ijpharm.2017.07.008}, pmid = {28687346}, issn = {1873-3476}, mesh = {Animals ; Antitubercular Agents/administration & dosage/*chemistry ; Child ; Drug Compounding ; Drug Liberation ; Electronic Nose ; Hot Temperature ; Humans ; Isoniazid/administration & dosage/*chemistry ; Male ; Polyethylene Glycols/administration & dosage/*chemistry ; Polymethacrylic Acids/administration & dosage/*chemistry ; Polyvinyls/administration & dosage/*chemistry ; Rats, Sprague-Dawley ; Saliva, Artificial/chemistry ; Solubility ; *Taste ; }, abstract = {Hot melt extrusion has gained considerable attention as a novel technique for taste masking of bitter APIs. The aim of this study was to investigate whether hot melt extrusion could be used to develop taste masked formulations of isoniazid and also to evaluate and correlate different taste assessment methods Two polymers with different physico-chemical properties, Soluplus and Eudragit E-PO were chosen as carriers for the drug. Eudragit E-PO has already been widely used for taste masking due to its selective release properties, while Soluplus has not been studied in this regard but provides a useful comparator of a polymer that should release the drug reasonably efficiently. Polymeric formulations of isoniazid were produced with drug loadings of 20% and 30% w/w. The solid state characteristics of the formulations were assessed by differential scanning calorimetry and powder X-ray diffraction. The taste of isoniazid was assessed using the rodent Brief Access Taste Aversion (BATA) model, while formulations were assessed using the electronic tongue and dissolution under simulated oral conditions. Investigation into the drug loading effect with these two polymers showed that all Soluplus based extrudates with drug loading up to 30% w/w were fully amorphous while Eudragit E-PO based extrudates contained crystalline drug as demonstrated by both DSC and PXRD, dependent on loading. BATA testing of isoniazid gave an IC50 value, i.e. the dose of drug which inhibits 50% of licks, of 11.1mg/mL. Taste assessment of the formulations using both simulated oral drug release and the electronic tongue demonstrated that Eudragit E-PO based formulations had a better taste masking efficiency than Soluplus. This is due to the fact that significantly less isoniazid is released from the Eudragit E-PO based formulations under oral conditions.}, } @article {pmid28684275, year = {2017}, author = {Roman, CW and Sloat, SR and Palmiter, RD}, title = {A tale of two circuits: CCK[NTS] neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions.}, journal = {Neuroscience}, volume = {358}, number = {}, pages = {316-324}, pmid = {28684275}, issn = {1873-7544}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 DA024908/DA/NIDA NIH HHS/United States ; T32 DK007247/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/*genetics ; Avoidance Learning/physiology ; Channelrhodopsins/genetics/metabolism ; Cholecystokinin/genetics/*metabolism ; Conditioning, Operant/physiology ; Eating/genetics ; Luminescent Proteins/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Motivation/*physiology ; Neural Pathways/*physiology ; Oncogene Proteins v-fos/metabolism ; Optogenetics ; Parabrachial Nucleus/*physiology ; Paraventricular Hypothalamic Nucleus/*metabolism ; Solitary Nucleus/*cytology ; Taste/physiology ; Transduction, Genetic ; }, abstract = {Cholecystokinin (CCK)-expressing neurons within the nucleus of the solitary tract (CCK[NTS]) of the mouse are responsive to satiety signals and their chemogenetic activation suppresses appetite. Optogenetic activation of CCK[NTS] axon terminals within either the parabrachial nucleus (PBN) or the paraventricular nucleus of the hypothalamus (PVH) is sufficient to suppress feeding. An interesting dichotomy has been revealed when assessing the motivational valence of these two circuits. Activating CCK[NTS] cell bodies is aversive as demonstrated by conditioned taste aversion and place-preference assays. Activation of the CCK[NTS]→PBN pathway is also aversive; however, stimulating the CCK[NTS]→PVH pathway is appetitive when assayed using a real-time, place-preference task. Thus, these two projections from CCK[NTS] neurons reduce food intake through opposite motivational states; one pathway signals positive valence (CCK[NTS]→PVH) and the other signals negative valence (CCK[NTS]→PBN).}, } @article {pmid28667676, year = {2017}, author = {Shoshan, N and Segev, A and Abush, H and Mizrachi Zer-Aviv, T and Akirav, I}, title = {Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.}, journal = {Hippocampus}, volume = {27}, number = {10}, pages = {1093-1109}, doi = {10.1002/hipo.22755}, pmid = {28667676}, issn = {1098-1063}, mesh = {Amidohydrolases/antagonists & inhibitors/metabolism ; Amygdala/*drug effects/pathology/physiopathology ; Animals ; Avoidance Learning/drug effects/physiology ; Benzamides/pharmacology ; Benzoxazines/pharmacology ; Bromine/*pharmacology ; Cannabinoid Receptor Modulators/pharmacology ; Cannabinoids/*pharmacology ; Carbamates/pharmacology ; Disease Models, Animal ; Drug Combinations ; Electroshock ; Enzyme Inhibitors/pharmacology ; Fear/drug effects/physiology ; Glutamates/*pharmacology ; Hippocampus/*drug effects/pathology/physiopathology ; Magnesium/*pharmacology ; Male ; Memory/drug effects/physiology ; Morpholines/pharmacology ; Naphthalenes/pharmacology ; Neuronal Plasticity/drug effects/physiology ; Piperidines/pharmacology ; Pyrazoles/pharmacology ; Rats, Sprague-Dawley ; Receptors, Cannabinoid/*metabolism ; Stress Disorders, Post-Traumatic/*drug therapy/pathology/physiopathology/psychology ; }, abstract = {Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1 receptors, in the opposite effects of severe stress on memory and plasticity in the hippocampus and amygdala.}, } @article {pmid28663116, year = {2017}, author = {Fernández, MS and Báez, B and Bordón, A and Espinosa, L and Martínez, E and Pautassi, RM}, title = {Short-term selection for high and low ethanol intake yields differential sensitivity to ethanol's motivational effects and anxiety-like responses in adolescent Wistar rats.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {79}, number = {Pt B}, pages = {220-233}, doi = {10.1016/j.pnpbp.2017.06.027}, pmid = {28663116}, issn = {1878-4216}, mesh = {Alcohol-Related Disorders/physiopathology ; Animals ; Anxiety/*physiopathology ; Central Nervous System Depressants/*adverse effects ; Ethanol/*adverse effects ; Feeding Behavior/physiology ; Female ; *Genetic Predisposition to Disease ; Male ; Motivation/*drug effects/physiology ; Motor Activity/physiology ; Phenotype ; Rats, Wistar ; Saccharin ; Selective Breeding ; Time Factors ; }, abstract = {Alcohol use disorders are modulated by genetic factors, but the identification of specific genes and their concomitant biological changes that are associated with a higher risk for these disorders has proven difficult. Alterations in the sensitivity to the motivational effects of ethanol may be one way by which genes modulate the initiation and escalation of ethanol intake. Rats and mice have been selectively bred for high and low ethanol consumption during adulthood. However, selective breeding programs for ethanol intake have not focused on adolescence. This phase of development is associated with the initiation and escalation of ethanol intake and characterized by an increase in the sensitivity to ethanol's appetitive effects and a decrease in the sensitivity to ethanol's aversive effects compared with adulthood. The present study performed short-term behavioral selection to select rat lines that diverge in the expression of ethanol drinking during adolescence. A progenitor nucleus of Wistar rats (F0) and filial generation 1 (F1), F2, and F3 adolescent rats were derived from parents that were selected for high (STDRHI) and low (STDRLO) ethanol consumption during adolescence and were tested for ethanol intake and responsivity to ethanol's motivational effects. STDRHI rats exhibited significantly greater ethanol intake and preference than STDRLO rats. Compared with STDRLO rats, STDRHI F2 and F3 rats exhibited a blunted response to ethanol in the conditioned taste aversion test. F2 and F3 STDRHI rats but not STDRLO rats exhibited ethanol-induced motor stimulation. STDRHI rats exhibited avoidance of the white compartment of the light-dark box, a reduction of locomotion, and a reduction of saccharin consumption, suggesting an anxiety-prone phenotype. The results suggest that the genetic risk for enhanced ethanol intake during adolescence is associated with lower sensitivity to the aversive effects of ethanol, heightened reactivity to ethanol's stimulating effects, and enhanced innate anxiety.}, } @article {pmid28649917, year = {2019}, author = {Dwyer, DM and Gasalla, P and López, M}, title = {Partial reinforcement and conditioned taste aversion: No evidence for resistance to extinction.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {72}, number = {2}, pages = {274-284}, doi = {10.1080/17470218.2017.1347191}, pmid = {28649917}, issn = {1747-0226}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/physiology ; Generalization, Psychological/*physiology ; Male ; Rats ; *Reinforcement, Psychology ; Taste Perception/*physiology ; }, abstract = {The partial reinforcement extinction effect (PREE) is the observation that, following training in which a response is followed by reward on only a subset of trials, the response is more resistant to extinction following the total removal of reward than it is after training in which reward is presented on all trials. The PREE is almost ubiquitous in instrumental conditioning procedures but only inconsistently observed in Pavlovian conditioning. In his classic review of animal learning, Mackintosh attributes the bulk of the PREE to generalisation decrement relating to the fact that partial reinforcement typically ensures that acquisition of responding has taken place in conditions similar to that of extinction (e.g., in the absence of the reinforcer). We report here that extinction of a conditioned taste aversion is not retarded by partial reinforcement in terms of either consumption of the taste or hedonic reactions to it (assessed through the analysis of licking microstructure). These results are consistent with Mackintosh's analysis of the PREE and the way in which it might differ between instrumental and Pavlovian conditioning.}, } @article {pmid28623169, year = {2017}, author = {Blednov, YA and Borghese, CM and Ruiz, CI and Cullins, MA and Da Costa, A and Osterndorff-Kahanek, EA and Homanics, GE and Harris, RA}, title = {Mutation of the inhibitory ethanol site in GABAA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination.}, journal = {Neuropharmacology}, volume = {123}, number = {}, pages = {201-209}, pmid = {28623169}, issn = {1873-7064}, support = {R37 AA010422/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; U01 AA020889/AA/NIAAA NIH HHS/United States ; R01 AA010422/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholic Intoxication/*metabolism ; Animals ; Ataxia/*chemically induced/metabolism ; CRISPR-Cas Systems ; Central Nervous System Depressants/*pharmacology ; Cerebellum/drug effects/metabolism ; Ethanol/*pharmacology ; Female ; Humans ; Male ; Mice, Transgenic ; Motor Activity/drug effects/physiology ; Mutation ; Oocytes ; RNA, Messenger/metabolism ; Receptors, GABA-A/genetics/*metabolism ; Recovery of Function/physiology ; Xenopus laevis ; }, abstract = {Genes encoding the ρ1/2 subunits of GABAA receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine). We generated ρ1 (T6'Y) knockin (KI) mice using CRISPR/Cas9 to test the behavioral importance of the inhibitory actions of ethanol on this receptor. Both ρ1 KI and knockout (KO) mice showed faster recovery from acute ethanol-induced motor incoordination compared to WT mice. Both KI and KO mutant strains also showed increased tolerance to motor impairment produced by ethanol. The KI mice did not differ from WT mice in other behavioral actions, including ethanol intake and preference, conditioned taste aversion to ethanol, and duration of ethanol-induced loss of righting reflex. WT and KI mice did not differ in levels of ρ1 or ρ2 mRNA in cerebellum or in ethanol clearance. Our findings indicate that the inhibitory site for ethanol in GABAA ρ1 receptors regulates acute functional tolerance to moderate ethanol intoxication. We note that low sensitivity to alcohol intoxication has been linked to risk for development of alcohol dependence in humans.}, } @article {pmid28606627, year = {2017}, author = {He, AB and Chang, YC and Meng, AWY and Huang, ACW}, title = {Re-evaluation of the reward comparison hypothesis for alcohol abuse.}, journal = {Behavioural brain research}, volume = {332}, number = {}, pages = {218-222}, doi = {10.1016/j.bbr.2017.06.006}, pmid = {28606627}, issn = {1872-7549}, mesh = {Alcoholism/*psychology ; Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Psychological/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; *Models, Psychological ; Psychological Tests ; Random Allocation ; Rats, Wistar ; *Reward ; Saccharin ; Space Perception/drug effects ; }, abstract = {This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further.}, } @article {pmid28605507, year = {2017}, author = {Eddy, MC and Eschle, BK and Delay, ER}, title = {Comparison of the Tastes of L-Alanine and Monosodium Glutamate in C57BL/6J Wild Type and T1r3 Knockout Mice.}, journal = {Chemical senses}, volume = {42}, number = {7}, pages = {563-573}, doi = {10.1093/chemse/bjx037}, pmid = {28605507}, issn = {1464-3553}, mesh = {Alanine/*pharmacology ; Animals ; Discriminant Analysis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, G-Protein-Coupled/deficiency/genetics ; Sodium Glutamate/*pharmacology ; Taste/*drug effects ; Taste Threshold/drug effects ; }, abstract = {Previous research showed that L-alanine and monosodium L-glutamate elicit similar taste sensations in rats. This study reports the results of behavioral experiments designed to compare the taste capacity of C57BL/6J wild type and T1r3- mice for these 2 amino acids. In conditioned taste aversion (CTA) experiments, wild-type mice exhibited greater sensitivity than knockout mice for both L-amino acids, although knockout mice were clearly able to detect both amino acids at 50 mM and higher concentrations. Generalization of CTA between L-alanine and L-glutamate was bidirectionally equivalent for both mouse genotypes, indicating that both substances elicited similar tastes in both genotypes. This was verified by the discrimination experiments in which both mouse genotypes performed at or near chance levels at 75 and 150 mM. Above 150 mM, discrimination performance improved, suggesting the taste qualities of the 2 L-amino acids are not identical. No differences between knockout and wild-type mice in discrimination ability were detected. These results indicate that while the T1r3 receptor is important for tasting L-alanine and L-glutamate, other receptors are also important for tasting these amino acids.}, } @article {pmid28552029, year = {2017}, author = {Bala, M and Gupta, V and Prasad, J}, title = {A standardized Hippophae extract (SBL-1) counters neuronal tissue injuries and changes in neurotransmitters: implications in radiation protection.}, journal = {Pharmaceutical biology}, volume = {55}, number = {1}, pages = {1833-1842}, pmid = {28552029}, issn = {1744-5116}, mesh = {Amygdala/metabolism/pathology/radiation effects ; Animals ; Antioxidants/chemistry/standards/therapeutic use ; Behavior, Animal/radiation effects ; Brain Chemistry/radiation effects ; Cerebral Cortex/metabolism/pathology/radiation effects ; Cobalt Radioisotopes ; Conditioning, Classical ; *Dietary Supplements ; Hippocampus/metabolism/pathology/radiation effects ; Hippophae/*chemistry ; Male ; Neurons/*metabolism/pathology/radiation effects ; Neuroprotective Agents/chemistry/standards/therapeutic use ; Oxidative Stress/radiation effects ; Plant Extracts/chemistry/standards/*therapeutic use ; Plant Leaves/*chemistry ; Radiation Injuries, Experimental/metabolism/pathology/physiopathology/*prevention & control ; Radiation-Protective Agents/chemistry/standards/*therapeutic use ; Random Allocation ; Rats, Sprague-Dawley ; Taste Disorders/etiology/prevention & control ; }, abstract = {CONTEXT: Effects of a radioprotective, standardized leaf extract (code SBL-1) from traditional medicinal plant, sea buckthorn [Hippophae rhamnoides L. (Elaeagnaceae)], on neurotransmitters and brain injuries in rats showing radiation-induced conditioned taste aversion (CTA), are not known. Understanding CTA in rats is important because its process is considered parallel to nausea and vomiting in humans.

OBJECTIVE: This study investigated the levels of neurotransmitters, antioxidant defences and histological changes in rats showing radiation CTA, and their modification by SBL-1.

MATERIALS AND METHODS: The inbred male Sprague-Dawley rats (age 65 days, weighing 190 ± 10 g) were used. Saccharin-preferring rats were selected using standard procedure and divided into groups. Group I (untreated control) was administered sterile water, group II was [60]Co-γ-irradiated (2 Gy), and group III was administered SBL-1 before irradiation. Observations were recorded up to day 5.

RESULTS: Irradiation (2 Gy) caused (i) non-recoverable CTA (≥ 64.7 ± 5.0%); (ii) degenerative changes in cerebral cortex, amygdala and hippocampus; (iii) increases in brain dopamine (DA, 63.4%), norepinephrine (NE, 157%), epinephrine (E, 233%), plasma NE (103%) and E (160%); and (iv) decreases in brain superoxide dismutase (67%), catalase (60%) and glutathione (51%). SBL-1 treatment (12 mg/kg body weight) 30 min before irradiation (i) countered brain injuries, (ii) reduced CTA (38.7 ± 3.0%, day 1) and (iii) normalized brain DA, NE, E, superoxide dismutase, catalase and CTA from day 3 onwards.

DISCUSSION AND CONCLUSION: Radiation CTA was coupled with brain injuries, disturbances in neurotransmitters and antioxidant defences. SBL-1 pretreatment countered these disturbances, indicating neuroprotective action.}, } @article {pmid28549583, year = {2017}, author = {Sun, H and Yan, J and Sun, B and Song, L and Yan, J}, title = {Taste sensitivity to sucrose is lower in outbred Sprague-Dawley phenotypic obesity-prone rats than obesity-resistant rats.}, journal = {Biochemical and biophysical research communications}, volume = {489}, number = {2}, pages = {155-163}, doi = {10.1016/j.bbrc.2017.05.117}, pmid = {28549583}, issn = {1090-2104}, mesh = {Animals ; Behavior, Animal/drug effects ; Body Weight/drug effects ; *Diet, High-Fat ; Energy Intake/drug effects ; Male ; Obesity/*drug therapy/physiopathology ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Sucrose/administration & dosage/*pharmacology ; Taste/*drug effects ; Taste Threshold/drug effects ; }, abstract = {The purpose of the present study was to better understand the role of sweet taste perception in dietary behavior and body weight in outbred Sprague-Dawley phenotypic obesity-prone and obesity-resistant rats by measuring sucrose taste sensitivity using a conditioned taste aversion paradigm. Rats were given a high fat diet for 2 weeks and were assigned as obesity-prone (P, upper tertile) or obesity-resistant (R, lower tertile) based on weight gain. Each group was then given either chow (C, 10% fat) or the high fat diet (F, 46% fat) for the remainder of the experiment (∼18 weeks) such that there were four groups - obesity-prone on chow (C-P), obesity-prone on high fat (H-P), obesity-resistant on chow (C-R), obesity-resistant on high fat (H-R). The sucrose sensitivity of phenotypic obesity-prone rats is lower than that of obesity-resistant rats in either H-fed or C-fed group, and all H-fed rats were more sensitivity than their C-fed counterparts (H-P vs. C-P; H-R vs. C-R). Body weight gain and total calories intake of phenotypic obesity-prone rats are more than that of obesity-resistant rats. The results suggest that lower sucrose taste sensitivity may contribute to body weight gain and total calories intake of phenotypic obesity-prone rats compared to obesity-resistant rats, and there is correlation between the change in the sweet taste threshold and diet treatment.}, } @article {pmid28544245, year = {2017}, author = {Abegg, K and Bernasconi, L and Hutter, M and Whiting, L and Pietra, C and Giuliano, C and Lutz, TA and Riediger, T}, title = {Ghrelin receptor inverse agonists as a novel therapeutic approach against obesity-related metabolic disease.}, journal = {Diabetes, obesity & metabolism}, volume = {19}, number = {12}, pages = {1740-1750}, doi = {10.1111/dom.13020}, pmid = {28544245}, issn = {1463-1326}, mesh = {Animals ; Anti-Obesity Agents/adverse effects/pharmacology/*therapeutic use ; Arcuate Nucleus of Hypothalamus/drug effects/metabolism/pathology ; Diabetes Mellitus, Type 2/*drug therapy/metabolism/pathology/physiopathology ; Diet, High-Fat/adverse effects ; Drug Inverse Agonism ; Energy Intake/drug effects ; HEK293 Cells ; Humans ; Hyperlipidemias/etiology/*prevention & control ; Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use ; Islets of Langerhans/drug effects/metabolism/pathology ; Liver/drug effects/metabolism/pathology ; Mice ; Neurons/drug effects/metabolism/pathology ; Non-alcoholic Fatty Liver Disease/etiology/*prevention & control ; Obesity/*drug therapy/metabolism/pathology/physiopathology ; Random Allocation ; Rats ; Rats, Zucker ; Receptors, Ghrelin/*agonists/antagonists & inhibitors/metabolism ; Weight Gain/drug effects ; }, abstract = {AIMS: Ghrelin is implicated in the control of energy balance and glucose homeostasis. The ghrelin receptor exhibits ligand-independent constitutive activity, which can be pharmacologically exploited to induce inverse ghrelin actions. Because ghrelin receptor inverse agonists (GHSR-IA) might be effective for the treatment of obesity-related metabolic disease, we tested 2 novel synthetic compounds GHSR-IA1 and GHSR-IA2.

MATERIALS AND METHODS: In functional cell assays, electrophysiogical and immunohistochemical experiments, we demonstrated inverse agonist activity for GHSR-IA1 and GHSR-IA2. We used healthy mice, Zucker diabetic fatty (ZDF) rats and diet-induced obese (DIO) mice to explore effects on food intake (FI), body weight (BW), conditioned taste aversion (CTA), oral glucose tolerance (OGT), pancreatic islet morphology, hepatic steatosis (HS), and blood lipids.

RESULTS: Both compounds acutely reduced FI in mice without inducing CTA. Chronic GHSR-IA1 increased metabolic rate in chow-fed mice, suppressed FI, and improved OGT in ZDF rats. Moreover, the progression of islet hyperplasia to fibrosis in ZDF rats slowed down. GHSR-IA2 reduced FI and BW in DIO mice, and reduced fasting and stimulated glucose levels compared with pair-fed and vehicle-treated mice. GHSR-IA2-treated DIO mice showed decreased blood lipids. GHSR-IA1 treatment markedly decreased HS in DIO mice.

CONCLUSIONS: Our study demonstrates therapeutic actions of novel ghrelin receptor inverse agonists, suggesting a potential to treat obesity-related metabolic disorders including diabetes mellitus.}, } @article {pmid28476409, year = {2017}, author = {Rorabaugh, B and Seeley, S and Evans, M and Marengo, C and D'Souza, M}, title = {Differential behavioral effects of nicotine in adult male and female rats with a history of prenatal methamphetamine exposure.}, journal = {Neuroscience letters}, volume = {651}, number = {}, pages = {116-122}, doi = {10.1016/j.neulet.2017.05.002}, pmid = {28476409}, issn = {1872-7972}, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Central Nervous System Stimulants/*administration & dosage ; Conditioning, Classical ; Female ; Locomotion/drug effects ; Male ; Methamphetamine/*administration & dosage ; Nicotine/*administration & dosage ; Pregnancy ; Prenatal Exposure Delayed Effects/*psychology ; Rats, Sprague-Dawley ; }, abstract = {The goal of the current study was to assess the effects of prenatal methamphetamine (MA)/saline exposure on nicotine-induced stimulant and aversive effects in both male and female adult rats. The aversive effects of nicotine were assessed using the nicotine-induced conditioned taste aversion model (0.4mg/kg, base), while the stimulant effects of nicotine were measured by assessing changes in spontaneous locomotor activity after subcutaneous administration of different doses of nicotine (0, 0.1 & 0.4mg/kg, base). The aversive effects of nicotine were significantly decreased in male, but not in female rats with a history of prenatal MA exposure compared to respective saline controls. No influence of prenatal MA exposure was observed on nicotine-induced increase in locomotor activity in either male or female rats. In conclusion, males with a history of prenatal MA exposure may be more vulnerable to nicotine addiction due to a decrease in nicotine-induced aversive effects.}, } @article {pmid28450080, year = {2017}, author = {Aonuma, H and Kaneda, M and Hatakeyama, D and Watanabe, T and Lukowiak, K and Ito, E}, title = {Weak involvement of octopamine in aversive taste learning in a snail.}, journal = {Neurobiology of learning and memory}, volume = {141}, number = {}, pages = {189-198}, doi = {10.1016/j.nlm.2017.04.010}, pmid = {28450080}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Central Nervous System/*metabolism ; Food Deprivation/physiology ; Lymnaea/drug effects/physiology ; Octopamine/*metabolism/pharmacology ; Phentolamine/pharmacology ; Receptors, Biogenic Amine/agonists/antagonists & inhibitors ; Signal Transduction/drug effects/physiology ; Taste/*drug effects/physiology ; }, abstract = {The pond snail Lymnaea stagnalis is capable of learning taste aversion by pairing presentations of a sucrose solution and an electric shock and consolidating it into long-term memory (LTM), which is referred to as conditioned taste aversion (CTA). We asked here if the neurotransmitter octopamine is involved in CTA. We first determined the levels of octopamine and its catabolites in the central nervous system (CNS) of snails with varying degrees of food deprivation, because CTA grades are correlated with degrees of food deprivation. We next manipulated the octopamine signaling using both an agonist and an antagonist of octopamine receptors and correlated their respective effects with CTA grades. We found that snails with the least amount of food-deprivation obtained the best CTA grade and had low levels of octopamine; whereas the most severely food-deprived snails did not form CTA and had the highest CNS octopamine levels. In modestly food-deprived snails, octopamine application increased the basal level of feeding response to a sucrose solution, and it did not obstruct CTA formation. Application of phentolamine, an octopamine receptor antagonist, to the most severely food-deprived snails decreased the basal level of feeding elicited by sucrose, but it did not enhance CTA formation. We conclude that octopamine involvement in CTA formation in Lymnaea is at best weak, and that the changes in CNS octopamine content are an epiphenomenon.}, } @article {pmid28432009, year = {2017}, author = {Sheth, C and Furlong, TM and Keefe, KA and Taha, SA}, title = {The lateral hypothalamus to lateral habenula projection, but not the ventral pallidum to lateral habenula projection, regulates voluntary ethanol consumption.}, journal = {Behavioural brain research}, volume = {328}, number = {}, pages = {195-208}, pmid = {28432009}, issn = {1872-7549}, support = {R01 MH094870/MH/NIMH NIH HHS/United States ; }, mesh = {Alcohol Drinking/pathology/*physiopathology ; Animals ; Basal Forebrain/pathology/*physiopathology ; Central Nervous System Depressants/administration & dosage ; Drug-Seeking Behavior/physiology ; Ethanol/administration & dosage ; Habenula/pathology/*physiopathology ; Hypothalamic Area, Lateral/pathology/*physiopathology ; Male ; Neural Pathways/pathology/physiopathology ; Rats, Long-Evans ; Self Administration ; Volition ; }, abstract = {The lateral habenula (LHb) is an epithalamic brain region implicated in aversive processing via negative modulation of midbrain dopamine (DA) and serotonin (5-HT) systems. Given the role of the LHb in inhibiting DA and 5-HT systems, it is thought to be involved in various psychiatric pathologies, including drug addiction. In support, it has been shown that LHb plays a critical role in cocaine- and ethanol-related behaviors, most likely by mediating drug-induced aversive conditioning. In our previous work, we showed that LHb lesions increased voluntary ethanol consumption and operant ethanol self-administration and blocked yohimbine-induced reinstatement of ethanol self-administration. LHb lesions also attenuated ethanol-induced conditioned taste aversion suggesting that a mechanism for the increased intake of ethanol may be reduced aversion learning. However, whether afferents to the LHb are required for mediating effects of the LHb on these behaviors remained to be investigated. Our present results show that lesioning the fiber bundle carrying afferent inputs to the LHb, the stria medullaris (SM), increases voluntary ethanol consumption, suggesting that afferent structures projecting to the LHb are important for mediating ethanol-directed behaviors. We then chose two afferent structures as the focus of our investigation. We specifically studied the role of the inputs from the lateral hypothalamus (LH) and ventral pallidum (VP) to the LHb in ethanol-directed behaviors. Our results show that the LH-LHb projection is necessary for regulating voluntary ethanol consumption. These results are an important first step towards understanding the functional role of afferents to LHb with regard to ethanol consumption.}, } @article {pmid28383939, year = {2017}, author = {Gasalla, P and Soto, A and Dwyer, DM and López, M}, title = {Blocking of flavor-nausea learning by non-flavor cues: Assessment through orofacial reactivity responses.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {43}, number = {2}, pages = {171-182}, doi = {10.1037/xan0000135}, pmid = {28383939}, issn = {2329-8464}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; *Cues ; Nausea ; Rats ; Taste ; }, abstract = {We investigated, using orofacial reactivity assessment, whether nonflavor context cues can elicit conditioned aversive reactions, and also whether context cues interfere, through blocking, with the reduction in taste palatability during taste aversion conditioning. Experiment 1 showed that a context previously paired with LiCl evoked aversive orofacial reactions, and also attenuated the reduction in palatability of a saccharin solution which was paired with LiCl in that context. In Experiment 2, this blocking effect was abolished when the rats were given nonreinforced exposure to the previously LiCl-paired context (context extinction) before aversive conditioning of the saccharin in compound with the context. These results confirm that context stimuli can elicit conditioned aversive reactions in the absence of any flavor component, and demonstrate that context cues can interfere with the affective aspects of taste aversion learning. Thus nonflavor cues appear to engage the same processes as taste cues in aversion learning. These results are consistent with the idea that taste aversion learning is governed by general associative mechanisms and the special properties of nausea, rather than by a selective mechanism for poison-avoidance. (PsycINFO Database Record}, } @article {pmid28382659, year = {2017}, author = {Egervari, G and Rahman, T}, title = {Increased firing of lateral habenula neurons mediates ethanol aversion: potential implications for substance use disorders.}, journal = {The Journal of physiology}, volume = {595}, number = {13}, pages = {4135-4136}, pmid = {28382659}, issn = {1469-7793}, mesh = {*Ethanol ; *Habenula ; Humans ; Neurons ; Substance-Related Disorders ; Taste ; }, } @article {pmid31976952, year = {2017}, author = {Keenan, M}, title = {The Fuzzy Outline of an Operant.}, journal = {The Behavior analyst}, volume = {40}, number = {1}, pages = {187-191}, pmid = {31976952}, issn = {0738-6729}, } @article {pmid28323090, year = {2017}, author = {Soto, A and Gasalla, P and Begega, A and López, M}, title = {c-Fos activity in the insular cortex, nucleus accumbens and basolateral amygdala following the intraperitoneal injection of saccharin and lithium chloride.}, journal = {Neuroscience letters}, volume = {647}, number = {}, pages = {32-37}, doi = {10.1016/j.neulet.2017.03.025}, pmid = {28323090}, issn = {1872-7972}, mesh = {Animals ; Avoidance Learning ; Basolateral Nuclear Complex/*metabolism ; Cerebral Cortex/*metabolism ; Injections, Intraperitoneal ; Lithium Chloride/*administration & dosage ; Male ; Nucleus Accumbens/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats, Wistar ; Saccharin/*administration & dosage ; *Taste ; }, abstract = {This study examined c-Fos expression in selected brain areas consequent to intraperitoneal (IP) administration of saccharin and lithium chloride. Rats were tested for aversion to the saccharin as measured by flavor consumption and orofacial reactions in the taste reactivity (TR) test. It was found that intraperitoneal conditioning resulted in the reduction in voluntary consumption but not in the production of aversive orofacial responses to the saccharin. The immunohistochemistry quantification revealed increased c-Fos activity in the insular cortex, the shell and core regions of the nucleus accumbens, and the basolateral nucleus of the amygdala. These results show that a conditioned taste aversion can be induced without direct oropharyngeal gustatory stimulation at the time of conditioning. In addition, this study provide evidence of increased neural activity in response to intraperitoneal saccharin injections.}, } @article {pmid28234597, year = {2017}, author = {Huang, TN and Hsueh, YP}, title = {Calcium/calmodulin-dependent serine protein kinase (CASK), a protein implicated in mental retardation and autism-spectrum disorders, interacts with T-Brain-1 (TBR1) to control extinction of associative memory in male mice.}, journal = {Journal of psychiatry & neuroscience : JPN}, volume = {42}, number = {1}, pages = {37-47}, pmid = {28234597}, issn = {1488-2434}, mesh = {Amygdala/enzymology/pathology ; Animals ; *Association ; Autism Spectrum Disorder/*enzymology/pathology ; Conditioning, Psychological/physiology ; DNA-Binding Proteins/*metabolism ; Disease Models, Animal ; Extinction, Psychological/physiology ; Fear/physiology ; Guanylate Kinases/genetics/*metabolism ; Intellectual Disability/*enzymology/pathology ; Male ; Memory/*physiology ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Transgenic ; Receptors, N-Methyl-D-Aspartate/metabolism ; T-Box Domain Proteins ; Taste Perception/physiology ; }, abstract = {BACKGROUND: Human genetic studies have indicated that mutations in calcium/calmodulin-dependent serine protein kinase (CASK) result in X-linked mental retardation and autism-spectrum disorders. We aimed to establish a mouse model to study how Cask regulates mental ability.

METHODS: Because Cask encodes a multidomain scaffold protein, a possible strategy to dissect how CASK regulates mental ability and cognition is to disrupt specific protein-protein interactions of CASK in vivo and then investigate the impact of individual specific protein interactions. Previous in vitro analyses indicated that a rat CASK T724A mutation reduces the interaction between CASK and T-brain-1 (TBR1) in transfected COS cells. Because TBR1 is critical for glutamate receptor, ionotropic, N-methyl-D-aspartate receptor subunit 2B (Grin2b) expression and is a causative gene for autism and intellectual disability, we then generated CASK T740A (corresponding to rat CASK T724A) mutant mice using a gene-targeting approach. Immunoblotting, coimmunoprecipitation, histological methods and behavioural assays (including home cage, open field, auditory and contextual fear conditioning and conditioned taste aversion) were applied to investigate expression of CASK and its related proteins, the protein-protein interactions of CASK, and anatomic and behavioural features of CASK T740A mice.

RESULTS: The CASK T740A mutation attenuated the interaction between CASK and TBR1 in the brain. However, CASK T740A mice were generally healthy, without obvious defects in brain morphology. The most dramatic defect among the mutant mice was in extinction of associative memory, though acquisition was normal.

LIMITATIONS: The functions of other CASK protein interactions cannot be addressed using CASK T740A mice.

CONCLUSION: Disruption of the CASK and TBR1 interaction impairs extinction, suggesting the involvement of CASK in cognitive flexibility.}, } @article {pmid28222821, year = {2017}, author = {Albanell, E and Manuelian, CL and Rovai, M and Salama, AAK and Caja, G}, title = {Using long-term averted goats for selective grazing in olive groves.}, journal = {Animal : an international journal of animal bioscience}, volume = {11}, number = {10}, pages = {1832-1838}, doi = {10.1017/S1751731117000362}, pmid = {28222821}, issn = {1751-732X}, mesh = {Animal Feed ; Animal Husbandry ; Animals ; Avoidance Learning ; Conditioning, Psychological ; *Feeding Behavior ; Fruit ; Goats/*physiology/psychology ; Lithium Chloride/*administration & dosage ; Male ; *Olea ; Plant Leaves ; Taste ; }, abstract = {Conditioned taste aversion (CTA) is a useful tool to modify animal feed preferences, allowing the implementation of selective grazing to control weeds in tree orchards without damaging the trees or affecting fruit production. LiCl is commonly used for inducing CTA. However, studies investigating the long-term persistence of CTA by LiCl in small ruminants are scarce. With this aim, we evaluated the efficiency of two LiCl doses (AV1 and AV2, 175 and 200 mg/kg BW, respectively) and a control (C, 0 mg/kg BW) for averting non-lactating dairy goats (n=15) to olive tree leaves. Aversion induction was reinforced on day 9 in those goats that consumed >10 g of olive leaves. Mid-term aversion effectiveness was assessed by five double-choice feeding tests (days 16, 24, 31, 38 and 53) of 30 min each, where 100 g of olive leaves were offered side-by-side with 390 g of Italian rye-grass (as-fed). Long-term aversion effectiveness was assessed in C, AV1 and AV2 goats by grazing for 30 min in paddocks with a simulated olive tree (days 59, 90, 121, 182 and 420). Moreover, C and AV2 goats were compared under on-field conditions (days 143, 211 and 363) in a commercial olive grove also for 30 min. The CTA proved to be established with a single LiCl dose in all goats and persisted for 4 and 55 days in AV1 and AV2 goats, respectively (P<0.001). However, 80% AV1 and 20% AV2 goats needed to be reinforced at day 9. When grazing under simulated olive tree and commercial olive grove conditions, the CTA goats, especially AV2 group, avoided the contact with the olive trees and minimally used a bipedal stance to feed leaves, than control goats. On average, time proportion spent consuming olive leaves and sprouts was much greater (P<0.05) for C (50.7±9.1%) than for AV1 (14.4±3.9%) and AV2 (3.1±0.9%). In conclusion, the 200 mg LiCl/kg BW dose was more effective than the 175 mg LiCl/kg BW dose for inducing an effective long-term CTA to olive tree leaves in goats.}, } @article {pmid28218622, year = {2017}, author = {Gaykema, RP and Newmyer, BA and Ottolini, M and Raje, V and Warthen, DM and Lambeth, PS and Niccum, M and Yao, T and Huang, Y and Schulman, IG and Harris, TE and Patel, MK and Williams, KW and Scott, MM}, title = {Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight.}, journal = {The Journal of clinical investigation}, volume = {127}, number = {3}, pages = {1031-1045}, pmid = {28218622}, issn = {1558-8238}, support = {R00 DA024719/DA/NIDA NIH HHS/United States ; R01 DK101946/DK/NIDDK NIH HHS/United States ; F32 DK102294/DK/NIDDK NIH HHS/United States ; T32 GM007055/GM/NIGMS NIH HHS/United States ; R01 DK100699/DK/NIDDK NIH HHS/United States ; R01 NS075157/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Body Weight/*physiology ; Eating/*physiology ; Gluconeogenesis/genetics ; Hypothalamo-Hypophyseal System/*metabolism ; Mice ; Mice, Transgenic ; Neurons/*metabolism ; Pituitary-Adrenal System/*metabolism ; Proglucagon/genetics/*metabolism ; Rhombencephalon/metabolism ; }, abstract = {Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.}, } @article {pmid28216206, year = {2017}, author = {Lückemann, L and Unteroberdörster, M and Kirchhof, J and Schedlowski, M and Hadamitzky, M}, title = {Applications and limitations of behaviorally conditioned immunopharmacological responses.}, journal = {Neurobiology of learning and memory}, volume = {142}, number = {Pt A}, pages = {91-98}, doi = {10.1016/j.nlm.2017.02.012}, pmid = {28216206}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Humans ; Immunosuppressive Agents/*pharmacology ; Memory/*drug effects ; Memory Consolidation/*drug effects ; Rats ; }, abstract = {The importance of placebo responses for the treatment of various medical conditions has increasingly been recognized, whereas knowledge and systematic application in clinical settings are still sparse. One possible application for placebo responses in pharmacotherapy is given by learning paradigms, such as behaviorally conditioned immunosuppression, aiming at drug dose reduction while maintaining therapeutic efficacy of drug treatment. In an established learning paradigm of conditioned taste aversion/avoidance (CTA) in both, rats and humans, respectively, a novel-tasting drinking solution (conditioned stimulus, CS) is paired with an injection of the immunosuppressive drug cyclosporine A (CsA) as unconditioned stimulus (US). The conditioned response, evoked by re-presenting the CS alone at a later time, is reflected by avoidance behavior of consuming the solution (conditioned taste aversion; CTA) and a diminished interleukin (IL)-2 and interferon (IFN)-γ cytokine production as well as mRNA expression of rat splenic T cells or human peripheral T lymphocytes, closely mimicking the immunosuppressive effects of CsA. However, due to unreinforced CS-re-exposure conditioned responses progressively decreases over time (extinction), reflecting a considerable challenge for potential clinical applications of this learned immunosuppression. The present article discusses and critically reviews actual approaches, applications but also limitations of learning paradigms in immune pharmacotherapy.}, } @article {pmid28164781, year = {2017}, author = {Kim, H and Kirkhart, C and Scott, K}, title = {Long-range projection neurons in the taste circuit of Drosophila.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28164781}, issn = {2050-084X}, support = {R01 DC013280/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Brain Mapping ; Drosophila melanogaster/*anatomy & histology/*physiology ; Neural Pathways/*anatomy & histology/*physiology ; Neurons/*physiology ; *Taste Perception ; }, abstract = {Taste compounds elicit innate feeding behaviors and act as rewards or punishments to entrain other cues. The neural pathways by which taste compounds influence innate and learned behaviors have not been resolved. Here, we identify three classes of taste projection neurons (TPNs) in Drosophila melanogaster distinguished by their morphology and taste selectivity. TPNs receive input from gustatory receptor neurons and respond selectively to sweet or bitter stimuli, demonstrating segregated processing of different taste modalities. Activation of TPNs influences innate feeding behavior, whereas inhibition has little effect, suggesting parallel pathways. Moreover, two TPN classes are absolutely required for conditioned taste aversion, a learned behavior. The TPNs essential for conditioned aversion project to the superior lateral protocerebrum (SLP) and convey taste information to mushroom body learning centers. These studies identify taste pathways from sensory detection to higher brain that influence innate behavior and are essential for learned responses to taste compounds.}, } @article {pmid28148214, year = {2017}, author = {Sunada, H and Lukowiak, K and Ito, E}, title = {Cerebral Giant Cells are Necessary for the Formation and Recall of Memory of Conditioned Taste Aversion in Lymnaea.}, journal = {Zoological science}, volume = {34}, number = {1}, pages = {72-80}, doi = {10.2108/zs160152}, pmid = {28148214}, issn = {0289-0003}, mesh = {Animals ; Giant Cells/*physiology ; Lymnaea/*cytology/*physiology ; Memory/physiology ; Neurons/*physiology ; Taste/*physiology ; }, abstract = {The pond snail Lymnaea stagnalis can acquire conditioned taste aversion (CTA) as a long-term memory. CTA is caused by the temporal pairing of a stimulus, such as sucrose (the conditioned stimulus; CS), with another stimulus, such as electric shock (the unconditioned stimulus; US). Previous studies have demonstrated changes in both cellular and molecular properties in a pair of neurons known as the cerebral giant cells (CGCs), suggesting that these neurons play a key role in CTA. Here we examined the necessity of the pair of CGC somata for the learning, memory formation and memory recall of CTA by using the soma ablation technique. There was no difference in the feeding response elicited by the CS before and after ablation of the CGC somata. Ablation of the CGC somata before taste-aversion training resulted in the learning acquisition, but the memory formation was not observed 24 h later. We next asked whether memory was present when the CGC somata were ablated 24 h after taste-aversion training. The memory was present before performing the somata ablation. However, when we tested snails five days after somata ablation, the memory recall was not present. Together the data show that: 1) the somata of the CGCs are not necessary for learning acquisition; 2) the somata are necessary for memory formation; and 3) the somata are necessary for memory recall. That is, these results demonstrate that the CGCs function in the long-term memory of CTA in Lymnaea.}, } @article {pmid28127358, year = {2016}, author = {Veysi, A and Vatandoost, H and Yaghoobi-Ershadi, MR and Jafari, R and Arandian, MH and Hosseini, M and Fadaei, R and Ramazanpour, J and Heidari, K and Sadjadi, A and Shirzadi, MR and Akhavan, AA}, title = {Rodenticide Comparative Effect of Klerat® and Zinc Phosphide for Controlling Zoonotic Cutaneous Leishmaniasis in Central Iran.}, journal = {Iranian journal of parasitology}, volume = {11}, number = {4}, pages = {471-479}, pmid = {28127358}, issn = {1735-7020}, abstract = {BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is a neglected disease with public health importance that is common in many rural areas of Iran. In recent years, behavioral resistance and/or bait shyness against the common rodenticide among reservoir hosts of ZCL have been reported. The aim of this study was to evaluate the effectiveness of Klerat® and zinc phosphide against natural reservoir of ZCL.

METHODS: This survey was carried out in four villages located 45 to 95 km far from Esfahan City Esfahan province, central Iran from April to November 2011. The rodent burrows were counted destroyed and reopened holes baited around all villages. Effect of rodent control operation on the main vector density and incidence of ZCL were evaluated.

RESULTS: The reduction rate of rodent burrows after intervention calculated to be at 62.8% in Klerat® and 58.15% in zinc phosphide treated areas. Statistical analysis showed no difference between the densities of the vector in indoors and outdoors in intervention and control areas. The incidence of the disease between treated and control areas after intervention was statistically different (P< 0.05).

CONCLUSION: Klerat® could be a suitable alternative for zinc phosphide in a specific condition such as behavior resistance or occurrence of bait shyness.}, } @article {pmid28126819, year = {2017}, author = {Yokose, J and Okubo-Suzuki, R and Nomoto, M and Ohkawa, N and Nishizono, H and Suzuki, A and Matsuo, M and Tsujimura, S and Takahashi, Y and Nagase, M and Watabe, AM and Sasahara, M and Kato, F and Inokuchi, K}, title = {Overlapping memory trace indispensable for linking, but not recalling, individual memories.}, journal = {Science (New York, N.Y.)}, volume = {355}, number = {6323}, pages = {398-403}, doi = {10.1126/science.aal2690}, pmid = {28126819}, issn = {1095-9203}, mesh = {Amygdala/cytology/*physiology ; Animals ; Conditioning, Classical/drug effects/*physiology ; Cues ; Fear ; Freezing Reaction, Cataleptic ; Mental Recall/*physiology ; Mice ; Neurons/physiology ; Saccharin/pharmacology ; }, abstract = {Memories are not stored in isolation from other memories but are integrated into associative networks. However, the mechanisms underlying memory association remain elusive. Using two amygdala-dependent behavioral paradigms-conditioned taste aversion (CTA) and auditory-cued fear conditioning (AFC)-in mice, we found that presenting the conditioned stimulus used for the CTA task triggered the conditioned response of the AFC task after natural coreactivation of the memories. This was accompanied through an increase in the overlapping neuronal ensemble in the basolateral amygdala. Silencing of the overlapping ensemble suppressed CTA retrieval-induced freezing. However, retrieval of the original CTA or AFC memory was not affected. A small population of coshared neurons thus mediates the link between memories. They are not necessary for recalling individual memories.}, } @article {pmid28095308, year = {2017}, author = {Sanchís-Ollé, M and Ortega-Sánchez, JA and Belda, X and Gagliano, H and Nadal, R and Armario, A}, title = {Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {75}, number = {}, pages = {77-83}, doi = {10.1016/j.pnpbp.2017.01.006}, pmid = {28095308}, issn = {1878-4216}, mesh = {Adaptation, Physiological/*drug effects ; Adrenocorticotropic Hormone/blood ; Animals ; Antimanic Agents/*adverse effects ; Body Weight/drug effects ; Corticosterone/blood ; Disease Models, Animal ; Hypothalamo-Hypophyseal System/*drug effects ; Lithium Chloride/*adverse effects ; Male ; Pituitary-Adrenal System/*drug effects ; Radioimmunoassay ; Rats ; Rats, Sprague-Dawley ; Saccharin/metabolism ; Stress, Psychological/*drug therapy/metabolism ; Time Factors ; }, abstract = {We have recently demonstrated that adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated exposure to a stressor does not follow the rules of habituation and can be fully expressed after a single experience with severe stressors. In the present work we tested the hypothesis that adaptation could be impaired if animals experience malaise during initial exposure to the stressor. To this end, animals were allowed to drink saccharin for 30min before being exposed for 3h to immobilization on boards (IMO), a severe stressor; then they were given either saline or lithium ip after the first hour of IMO. Stress-naïve rats followed exactly the same procedure except IMO. Exposure to IMO caused a strong activation of the HPA axis whereas the effect of lithium was modest. Both IMO and lithium administration resulted in conditioned taste aversion to saccharin when evaluated 4days later. When all animals were exposed to IMO 6days later, reduced HPA response and less impact on body weight was observed in the two groups previously exposed to IMO as compared with stress-naïve rats. Therefore, lithium administration during the first IMO exposure did not affect adaptation of the HPA axis and weight gain. These results indicate that malaise per se only weakly activated the HPA axis and argue against the hypothesis that signs of physical malaise during exposure to the stressor could impair HPA adaptation.}, } @article {pmid28040488, year = {2017}, author = {Yamaguchi, E and Yasoshima, Y and Shimura, T}, title = {Systemic administration of anorexic gut peptide hormones impairs hedonic-driven sucrose consumption in mice.}, journal = {Physiology & behavior}, volume = {171}, number = {}, pages = {158-164}, doi = {10.1016/j.physbeh.2016.12.034}, pmid = {28040488}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Gastrointestinal Hormones/*pharmacology ; Glucagon-Like Peptide 1/pharmacology ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Peptide Fragments/pharmacology ; Peptide YY/pharmacology ; Philosophy ; Sincalide/pharmacology ; Sucrose/*administration & dosage ; Sweetening Agents/*administration & dosage ; Taste/drug effects ; Time Factors ; }, abstract = {A number of reports suggest that gut hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY(3-36) (PYY3-36), which are released postprandially, suppress homeostatic food intake and result in satiety and the termination of feeding. However, it remains unclear whether these peptide hormones also suppress non-homeostatic consumption of palatable foods or fluids. To examine whether gut hormones reduce hedonically motivated sugar consumption, we assessed the effects of intraperitoneal administration of these gut hormones on the consumption of a highly palatable sucrose solution, using a mouse model we previously established for binge-like sucrose overconsumption (Yasoshima and Shimura, 2015). To reduce homeostatic hunger, chow was available at nighttime prior to testing. After a limited-access training procedure for 10days, during which access to both sucrose and chow were controlled, on the test day, control mice injected with saline consumed significantly more sucrose than during the pre-training period. In contrast, sucrose consumption on the test day in the mice injected with CCK-8 (2 and 4μg/kg), GLP-1 (500 and 1000nmol/kg), or PYY3-36 (12.5 and 25nmol/kg) was significantly less than that in saline-injected mice. In a separate cohort of mice, the higher doses of CCK-8 and GLP-1 and a greater dose of PYY3-36 (50nmol/kg) did not produce conditioned taste aversion to saccharin, suggesting that the doses of exogenous hormones in the present study do not cause aversive visceral distress. The present findings suggest that the systemic administration of these three gut hormones suppresses hedonic-driven sugar consumption due to the anorexic, but not aversive-visceral, effects of these hormones.}, } @article {pmid28034786, year = {2017}, author = {Rodríguez-Durán, LF and Martínez-Moreno, A and Escobar, ML}, title = {Bidirectional modulation of taste aversion extinction by insular cortex LTP and LTD.}, journal = {Neurobiology of learning and memory}, volume = {142}, number = {Pt A}, pages = {85-90}, doi = {10.1016/j.nlm.2016.12.014}, pmid = {28034786}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Long-Term Potentiation/*physiology ; Long-Term Synaptic Depression/*physiology ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {The history of activity of a given neuron has been proposed to bidirectionally influence its future response to synaptic inputs. In particular, induction of synaptic plasticity expressions such as long-term potentiation (LTP) and long-term depression (LTD) modifies the performance of several behavioral tasks. Our previous studies in the insular cortex (IC), a neocortical region that has been related to acquisition and retention of conditioned taste aversion (CTA), have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC pathway before CTA training enhances the retention of this task. In addition, we reported that CTA training triggers a persistent impairment in the ability to induce in vivo LTP in the IC. The aim of the present study was to investigate whether LTD can be induced in the Bla-IC projection in vivo, as well as, whether the extinction of CTA is bidirectionally modified by previous synaptic plasticity induction in this pathway. Thus, rats received 900 train pulses (five 250μs pulses at 250Hz) delivered at 1Hz in the Bla-IC projection in order to induce LTD or 10 trains of 100Hz/1s with an intertrain interval of 20s in order to induce LTP. Seven days after surgery, rats were trained in the CTA task including the extinction trials. Our results show that the Bla-IC pathway is able to express in vivo LTD in an N-Methyl-D-aspartate (NMDA) receptor-dependent manner. Induction of LTD in the Bla-IC projection previous to CTA training facilitates the extinction of this task. Conversely, LTP induction enhances CTA retention. The present results show the bidirectional modulation of CTA extinction in response to IC-LTP and LTD, providing evidence of the homeostatic adaptation of taste learning.}, } @article {pmid27984199, year = {2017}, author = {Yasoshima, Y and Shimura, T}, title = {Midazolam impairs the retrieval of conditioned taste aversion via opioidergic transmission in mice.}, journal = {Neuroscience letters}, volume = {636}, number = {}, pages = {64-69}, doi = {10.1016/j.neulet.2016.10.055}, pmid = {27984199}, issn = {1872-7972}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical ; Eating/drug effects ; Male ; Mice, Inbred C57BL ; Midazolam/*pharmacology ; Naloxone/pharmacology ; Narcotic Antagonists/pharmacology ; Receptors, Opioid/*agonists/physiology ; *Taste ; }, abstract = {Midazolam is a benzodiazepine agonist that affects the acquisition, retention, and retrieval of malaise-induced conditioned taste aversion (CTA) in rats. Our previous study suggested that the palatability-enhancing rather than amnesic effects of midazolam were responsible for impaired retrieval of conditioned aversion to palatable conditioned stimuli (CSs). However, it remains unclear whether this effect is opioid-dependent. In the present study, we examined the involvement of opioid signaling with the ability of peripheral midazolam administration to transiently impair CTA retrieval in mice. CTA was established by pairing 5mM saccharin ingestion (conditioned stimulus, CS) with an intraperitoneal (i.p.) injection of 0.15M lithium chloride (LiCl, 2% body weight) (unconditioned stimulus) for two consecutive days. Conditioned mice that received midazolam (1.5mg/kg, i.p.) before the first retention test consumed significantly more saccharin (CS) than conditioned mice that received vehicle (phosphate-buffered physiological saline, PBS; i.p.). On the next day, both conditioned groups showed strong aversions to the CS. Next, naloxone, an opioid receptor antagonist, was peripherally administered prior to the midazolam injection before the retention test. Pre-administration of naloxone but not PBS attenuated midazolam-induced increases in CS intake. Finally, we examined aversive orofacial taste reactions (TRs) to an oral infusion of the CS with pre-administration of naloxone or PBS prior to midazolam using a taste reactivity test. Conditioned mice that received midazolam showed significantly longer latencies to express aversive orofacial TRs than those that received PBS. Pre-administration of naloxone eliminated the effect of midazolam on latency to express aversive TRs. Taken together, these data suggest that midazolam activates opioidergic transmission and opioid-dependent palatability enhancement of the CS to eliminate conditioned aversion to a sweet taste.}, } @article {pmid27980072, year = {2017}, author = {Osorio-Gómez, D and Guzmán-Ramos, K and Bermúdez-Rattoni, F}, title = {Memory trace reactivation and behavioral response during retrieval are differentially modulated by amygdalar glutamate receptors activity: interaction between amygdala and insular cortex.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {24}, number = {1}, pages = {14-23}, pmid = {27980072}, issn = {1549-5485}, mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology ; Amygdala/drug effects/*metabolism ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/*physiology ; Dopamine/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/metabolism ; Male ; Mental Recall/drug effects/*physiology ; Neural Pathways/drug effects/*physiology ; Norepinephrine/metabolism ; Rats ; Rats, Wistar ; Receptors, Glutamate/*metabolism ; Taste/drug effects/physiology ; Valine/analogs & derivatives/pharmacology ; }, abstract = {The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the gustatory zone of the IC during CTA retrieval. Additionally, it has been reported that the amygdala-IC interaction is highly involved in CTA memory establishment. Therefore, we evaluated the effects of infusions of an AMPA receptor antagonist (CNQX) and a NMDA receptor antagonist (APV) into the amygdala on CTA retrieval and IC neurotransmitter levels. Infusion of APV into the amygdala impaired glutamate augmentation within the IC, whereas dopamine and norepinephrine levels augmentation persisted and a reliable CTA expression was observed. Conversely, CNQX infusion into the amygdala impaired the aversion response, as well as norepinephrine and dopamine augmentations in the IC. Interestingly, CNQX infusion did not affect glutamate elevation in the IC. To evaluate the functional meaning of neurotransmitters elevations within the IC on CTA response, we infused specific antagonists for the AMPA, NMDA, D1, and β-adrenergic receptor before retrieval. Results showed that activation of AMPA, D1, and β-adrenergic receptors is necessary for CTA expression, whereas NMDA receptors are not involved in the aversion response.}, } @article {pmid27940259, year = {2017}, author = {Nilsson, A and Wilhelms, DB and Mirrasekhian, E and Jaarola, M and Blomqvist, A and Engblom, D}, title = {Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.}, journal = {Brain, behavior, and immunity}, volume = {61}, number = {}, pages = {236-243}, pmid = {27940259}, issn = {1090-2139}, mesh = {Animals ; Anorexia/chemically induced/genetics/*metabolism ; Avoidance Learning/drug effects/*physiology ; Cyclooxygenase 2/*genetics/metabolism ; Cyclooxygenase 2 Inhibitors ; Fever/chemically induced/genetics/*metabolism ; Inflammation/chemically induced/genetics/*metabolism ; Lipopolysaccharides ; Mice ; Taste/drug effects/*physiology ; }, abstract = {Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.}, } @article {pmid27924869, year = {2016}, author = {Li, WG and Liu, MG and Deng, S and Liu, YM and Shang, L and Ding, J and Hsu, TT and Jiang, Q and Li, Y and Li, F and Zhu, MX and Xu, TL}, title = {ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {13770}, pmid = {27924869}, issn = {2041-1723}, mesh = {Acid Sensing Ion Channels/deficiency/*metabolism ; Amino Acid Sequence ; Animals ; Avoidance Learning/drug effects ; Cerebral Cortex/drug effects/*metabolism ; *Conditioning, Classical/drug effects ; Electric Stimulation ; *Extinction, Psychological/drug effects ; Glutamates/metabolism ; Glycine/analogs & derivatives/pharmacology ; Glycogen Synthase Kinase 3 beta/metabolism ; *Long-Term Potentiation/drug effects ; Male ; Memory/drug effects ; Mice, Inbred C57BL ; Peptides/chemistry ; Resorcinols/pharmacology ; Signal Transduction/drug effects ; Synaptic Transmission/drug effects ; Taste/drug effects/*physiology ; }, abstract = {Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention. Extinction of taste aversive memory led to the reduced insular synaptic efficacy, which precluded further LTD induction. The impaired LTD and extinction learning in ASIC1a null mice were restored by virus-mediated expression of wild-type ASIC1a, but not its ion-impermeable mutant, in the insular cortices. Our data demonstrate the involvement of an ASIC1a-mediated insular synaptic depression mechanism in extinction learning, which raises the possibility of targeting ASIC1a to manage adaptive behaviours.}, } @article {pmid27906463, year = {2016}, author = {Gaillard, D and Stratford, JM}, title = {Measurement of Behavioral Taste Responses in Mice: Two-Bottle Preference, Lickometer, and Conditioned Taste-Aversion Tests.}, journal = {Current protocols in mouse biology}, volume = {6}, number = {4}, pages = {380-407}, pmid = {27906463}, issn = {2161-2617}, support = {P30 DC004657/DC/NIDCD NIH HHS/United States ; R01 DC012383/DC/NIDCD NIH HHS/United States ; R01 DC012931/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning ; Biological Assay/instrumentation/*methods ; *Conditioning, Classical ; *Food Preferences ; *Mice ; *Taste ; *Taste Perception ; }, abstract = {The natural like and dislike of foods based on taste is one of the most easily observed behaviors in animals. Animals eat palatable foods and reject aversive foods, which makes measurement of taste perception possible using various behavioral techniques. Three different methods to accurately measure taste behavior are described here. First, two-bottle preference tests evaluate whether a taste compound (tastant) is preferred over water. Second, lickometer tests quantify the like and dislike for multiple concentrations of the same tastant or multiple tastants at the same time. Finally, conditioned taste aversion tests accurately determine the perceived taste threshold for palatable tastants. Together, these diverse methods enable researchers to observe and measure behavioral taste responses in mice to any tastant. © 2016 by John Wiley & Sons, Inc.}, } @article {pmid27865867, year = {2017}, author = {Chan, J and Ni, Y and Zhang, P and Zhang, J and Chen, Y}, title = {D1-like dopamine receptor dysfunction in the lateral habenula nucleus increased anxiety-like behavior in rat.}, journal = {Neuroscience}, volume = {340}, number = {}, pages = {542-550}, doi = {10.1016/j.neuroscience.2016.11.005}, pmid = {27865867}, issn = {1873-7544}, mesh = {Animals ; Anxiety/*metabolism ; Catheters, Indwelling ; Depression/metabolism ; Dopamine Agents/pharmacology ; Habenula/drug effects/*metabolism ; Learning/drug effects/physiology ; Male ; Memory/drug effects/physiology ; Rats, Sprague-Dawley ; Receptors, Dopamine D1/agonists/antagonists & inhibitors/*metabolism ; Receptors, Dopamine D2/agonists/metabolism ; }, abstract = {Lateral habenula (LHb) is important for emotional processing. It is a link node between forebrain and midbrain. LHb is reciprocally connected with ventral tegmental area, acting as a regulatory center for the dopaminergic system. However, the role of dopamine receptors in the LHb in emotional processing is less clear. In the present study, the expression of dopamine D1 and D2 receptors in LHb was testified by western blot. In addition, D1- or D2-like receptor agonist or antagonist was bilaterally administered into the LHb, anxiety-like and depressive-like behaviors were tested 15min later in rats. In addition, the effects of LHb dopamine receptor activation and inactivation on aversive learning and memory were assessed. Our results showed that: (1) activation and inhibition of D1R but not D2R in LHb increased anxiety-like behavior but decreased depressive-like behavior in rats. (2) D1R activation and inactivation in LHb impaired aversive memory acquisition but not consolidation in rats, D1R agonist also impaired aversive memory retrieval in rats. These results might provide new clues about how LHb was involved in emotional processing.}, } @article {pmid27847246, year = {2017}, author = {Molero-Chamizo, A}, title = {Modulation of the magnitude of conditioned taste aversion in rats with excitotoxic lesions of the basolateral amygdala.}, journal = {Neurobiology of learning and memory}, volume = {137}, number = {}, pages = {56-64}, doi = {10.1016/j.nlm.2016.11.009}, pmid = {27847246}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Basolateral Nuclear Complex/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Hippocampus/drug effects/*physiology ; Male ; N-Methylaspartate/*toxicity ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {The amygdala is one of the structures involved in the acquisition of conditioned taste aversion (CTA). Nevertheless, the specific roles that the nuclei of this structure play in CTA learning are controversial. Electrolytic lesions applied to the basolateral nucleus of the amygdala can eliminate or reduce the acquisition of this learning. This effect has been attributed to the involvement of fibers that pass through this nucleus and connect with other structures that are critical for CTA. Excitotoxic lesions may allow a clearer insight as to the potential involvement of this nucleus in the acquisition of CTA. The few studies to date that have used this paradigm have shown effects on taste aversion learning after applying extensive lesions to the amygdala. Thus, the aim of the present study was to determine the effect of selective excitotoxic lesions of the basolateral amygdala on the acquisition of CTA. The effects of these lesions on learning were compared with the effects observed in animals with sham lesions and animals with lesions of the hippocampus, which is a structure apparently not involved in CTA. The results revealed a decreased aversion in animals with basolateral lesions compared with both the sham and hippocampus-lesioned groups. Based on these findings, the role of this specific nucleus of the amygdala in the acquisition of taste aversion is briefly discussed.}, } @article {pmid27837417, year = {2017}, author = {Molero-Chamizo, A}, title = {Circadian-temporal context and latent inhibition of conditioned taste aversion: Effect of restriction in the intake of the conditioned taste stimulus.}, journal = {Learning & behavior}, volume = {45}, number = {2}, pages = {157-163}, pmid = {27837417}, issn = {1543-4508}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; Conditioning, Psychological ; Rats ; Rats, Wistar ; Taste ; *Taste Perception ; }, abstract = {Latent inhibition of conditioned taste aversion (CTA) is sensitive to changes in the temporal context. A change in the time of day of conditioning with respect to the time of day of the preexposure can disrupt the latent inhibition. This contextual change in the time of day may reveal a temporal specificity of latent inhibition. The optimum procedure to induce this temporal specificity is not well established. For example, it has been shown that a long period of habituation to temporal contexts is one factor that can determine the effect. However, the experimental conditions on the conditioning day that facilitate this phenomenon are unknown. The aim of this study is to elucidate whether a restriction in the intake of the conditioned taste stimulus affects the temporal specificity of latent inhibition. Two main groups of Wistar rats were tested in a latent inhibition of CTA paradigm, in which the temporal specificity of this phenomenon was analyzed by a change in the time of day of conditioning. The intake of the taste stimulus was restricted in the conditioning day in one of the groups, but this restriction was not applied in the other group. The results indicated temporal specificity of latent inhibition only in the group without restriction, but not in the group with limitation in the intake of the taste stimulus during conditioning. These findings can help to elucidate the characteristics of the procedure to induce temporal specificity of latent inhibition.}, } @article {pmid27825896, year = {2017}, author = {Inui, T and Shimura, T}, title = {Activation of mu-opioid receptors in the ventral pallidum decreases the negative hedonic evaluation of a conditioned aversive taste in rats.}, journal = {Behavioural brain research}, volume = {320}, number = {}, pages = {391-399}, doi = {10.1016/j.bbr.2016.10.051}, pmid = {27825896}, issn = {1872-7549}, mesh = {Adjuvants, Immunologic/pharmacology ; Analgesics, Opioid/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects/physiology ; Conditioning, Psychological/drug effects ; Drinking/drug effects ; Drug Delivery Systems ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology ; Globus Pallidus/drug effects/*metabolism ; Lithium Chloride/pharmacology ; Male ; Microinjections ; Rats ; Rats, Wistar ; Receptors, Opioid, mu/genetics/*metabolism ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; Taste Perception/*drug effects/physiology ; }, abstract = {Conditioned taste aversion (CTA) causes a shift in the hedonic evaluation of a conditioned stimulus (CS) from positive to negative, and reduces the CS intake. Mu-opioid receptors (MORs) in the ventral pallidum (VP) are known to be involved in the hedonic evaluation of positive rewarding stimuli; however, their involvement in evaluation of a negative aversive stimulus is still unclear. To explore the neural mechanisms of the negative hedonic evaluation of the CS in CTA, we examined the effects of the activation of VP MORs on the behavioral responses of rats to a CS. Rats implanted with guide cannulae into the bilateral VP received a pairing of 5mM saccharin solution as a CS with an intraperitoneal injection of 0.15M lithium chloride as an unconditioned stimulus. On the test day, after microinjections of MOR agonist [D-Ala[2], N-MePhe[4], Gly-ol]-enkephalin (DAMGO) into the VP, we observed the behavioral responses to the intraorally infused CS solution. The DAMGO injections caused a larger number of ingestive taste reactivity responses to the CS solution. We also measured the consumption of the CS solution in a separate group of rats, using a single-bottle test. The DAMGO injected rats drank a higher volume of the CS solution than the saline injected rats. These results indicate that the activation of MORs in the VP results in the attenuation of aversion to the CS solution, thereby inducing the larger CS intake. Therefore, it is likely that VP MORs are involved in not only positive but also negative hedonic evaluation.}, } @article {pmid27815244, year = {2016}, author = {Aonuma, H and Kaneda, M and Hatakeyama, D and Watanabe, T and Lukowiak, K and Ito, E}, title = {Relationship between the grades of a learned aversive-feeding response and the dopamine contents in Lymnaea.}, journal = {Biology open}, volume = {5}, number = {12}, pages = {1869-1873}, pmid = {27815244}, issn = {2046-6390}, abstract = {The pond snail Lymnaea learns conditioned taste aversion (CTA) and remembers not to respond to food substances that initially cause a feeding response. The possible relationship between how well snails learn to follow taste-aversion training and brain dopamine contents is not known. We examined this relationship and found the following: first, snails in the act of eating just before the commencement of CTA training were poor learners and had the highest dopamine contents in the brain; second, snails which had an ad libitum access to food, but were not eating just before training, were average learners and had lower dopamine contents; third, snails food-deprived for one day before training were the best learners and had significantly lower contents of dopamine compared to the previous two cohorts. There was a negative correlation between the CTA grades and the brain dopamine contents in these three cohorts. Fourth, snails food-deprived for five days before training were poor learners and had higher dopamine contents. Thus, severe hunger increased the dopamine content in the brain. Because dopamine functions as a reward transmitter, CTA in the severely deprived snails (i.e. the fourth cohort) was thought to be mitigated by a high dopamine content.}, } @article {pmid27663886, year = {2016}, author = {Licursi, M and Alberto, CO and Dias, A and Hirasawa, K and Hirasawa, M}, title = {High-fat diet-induced downregulation of anorexic leukemia inhibitory factor in the brain stem.}, journal = {Obesity (Silver Spring, Md.)}, volume = {24}, number = {11}, pages = {2361-2367}, doi = {10.1002/oby.21647}, pmid = {27663886}, issn = {1930-739X}, support = {RNL‐132870//CIHR/Canada ; }, mesh = {Animals ; Anorexia/*physiopathology ; Body Weight/drug effects ; Brain Stem/*metabolism ; Diet, High-Fat/*adverse effects ; *Down-Regulation ; Eating/drug effects ; Hypothalamus/metabolism ; Inflammation/metabolism ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Leukemia Inhibitory Factor/administration & dosage/*physiology ; Male ; RNA, Messenger/metabolism ; Rats ; Solitary Nucleus/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {OBJECTIVE: High-fat diet (HFD) is known to induce low-grade hypothalamic inflammation. Whether inflammation occurs in other brain areas remains unknown. This study tested the effect of short-term HFD on cytokine gene expression and identified leukemia inhibitory factor (LIF) as a responsive cytokine in the brain stem. Thus, functional and cellular effects of LIF in the brain stem were investigated.

METHODS: Male rats were fed chow or HFD for 3 days, and then gene expression was analyzed in different brain regions for IL-1β, IL-6, TNF-α, and LIF. The effect of intracerebroventricular injection of LIF on chow intake and body weight was also tested. Patch clamp recording was performed in the nucleus tractus solitarius (NTS).

RESULTS: HFD increased pontine TNF-α mRNA while downregulating LIF in all major parts of the brain stem, but not in the hypothalamus or hippocampus. LIF injection into the cerebral aqueduct suppressed food intake without conditioned taste aversion, suggesting that LIF can induce anorexia via lower brain regions without causing malaise. In the NTS, a key brain stem nucleus for food intake regulation, LIF induced acute changes in neuronal excitability.

CONCLUSIONS: HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS.}, } @article {pmid27594096, year = {2016}, author = {Mahiout, S and Pohjanvirta, R}, title = {Aryl hydrocarbon receptor agonists trigger avoidance of novel food in rats.}, journal = {Physiology & behavior}, volume = {167}, number = {}, pages = {49-59}, doi = {10.1016/j.physbeh.2016.08.033}, pmid = {27594096}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Benzo(a)pyrene/metabolism/pharmacology ; Carbazoles/pharmacology ; Cytochrome P-450 CYP1A1/genetics/metabolism ; Cytochrome P-450 CYP2B1/genetics/metabolism ; Dose-Response Relationship, Drug ; Eating/drug effects ; Feeding Behavior/*drug effects ; Food Preferences/*drug effects ; Male ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Aryl Hydrocarbon/*agonists/metabolism ; Taste/*drug effects ; Time Factors ; beta-Naphthoflavone/pharmacology ; }, abstract = {The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of dioxins, but also plays important physiological roles, which are only beginning to unfold. Previous studies have surprisingly unveiled that low doses of the potent AHR agonist TCDD induce a strong and persistent avoidance of novel food items in rats. Here, we further examined the involvement of the AHR in the avoidance response in Sprague-Dawley rats with three established AHR agonists: 6-formylindolo(3,2-b)carbazole (FICZ), β-naphthoflavone (BNF) and benzo[a]pyrene (BaP); with a novel selective AHR modulator (C2); and with an activator of another nuclear receptor, CAR: 2,4,6-tryphenyldioxane-1,3 (TPD). As sensitive indices of AHR or CAR activity, we used Cyp1a1 and Cyp2b1 gene expression, as they are, respectively, the drug-metabolizing enzymes specifically regulated by them. We further attempted to address the roles played by enhanced neophobia and conditioned taste aversion (CTA) in the avoidance behaviour. All AHR agonists triggered practically total avoidance of novel chocolate, but the durations varied. Likewise, acutely subtoxic doses of C2, differing by 25-fold, all elicited a similar outcome. In contrast, TPD did not influence chocolate consumption at all. If rats were initially accustomed to chocolate for 6h after single FICZ or BNF exposure, avoidance was still clearly present two weeks later when chocolate was offered again. Hence, the avoidance response appears to specifically involve the AHR instead of being triggered by induction of intestinal or hepatic nuclear receptor signalling in general. It is also shared by both endogenous and exogenous AHR activators. Moreover, this behavioural change in rats seems to contain elements of both CTA and enhanced neophobia, but further clarification of this is still required.}, } @article {pmid27733615, year = {2016}, author = {Levitan, D and Fortis-Santiago, Y and Figueroa, JA and Reid, EE and Yoshida, T and Barry, NC and Russo, A and Katz, DB}, title = {Memory Retrieval Has a Dynamic Influence on the Maintenance Mechanisms That Are Sensitive to ζ-Inhibitory Peptide (ZIP).}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {36}, number = {41}, pages = {10654-10662}, pmid = {27733615}, issn = {1529-2401}, support = {R01 DC006666/DC/NIDCD NIH HHS/United States ; T32 MH019929/MH/NIMH NIH HHS/United States ; T32 NS007292/NS/NINDS NIH HHS/United States ; }, mesh = {Amnesia/chemically induced/psychology ; Animals ; Anisomycin/pharmacology ; Avoidance Learning/*drug effects ; Cell-Penetrating Peptides ; Conditioning, Classical/drug effects ; Female ; Lipopeptides/administration & dosage/*pharmacology ; Memory/*drug effects ; Mental Recall/*drug effects ; Microinjections ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Long-Evans ; Somatosensory Cortex/anatomy & histology/drug effects ; Taste/*drug effects ; }, abstract = {UNLABELLED: In neuroscientists' attempts to understand the long-term storage of memory, topics of particular importance and interest are the cellular and system mechanisms of maintenance (e.g., those sensitive to ζ-inhibitory peptide, ZIP) and those induced by memory retrieval (i.e., reconsolidation). Much is known about each of these processes in isolation, but less is known concerning how they interact. It is known that ZIP sensitivity and memory retrieval share at least some molecular targets (e.g., recycling α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA, receptors to the plasma membrane); conversely, the fact that sensitivity to ZIP emerges only after consolidation ends suggests that consolidation (and by extension reconsolidation) and maintenance might be mutually exclusive processes, the onset of one canceling the other. Here, we use conditioned taste aversion (CTA) in rats, a cortically dependent learning paradigm, to test this hypothesis. First, we demonstrate that ZIP infusions into gustatory cortex begin interfering with CTA memory 43-45 h after memory acquisition-after consolidation ends. Next, we show that a retrieval trial administered after this time point interrupts the ability of ZIP to induce amnesia and that ZIP's ability to induce amnesia is reengaged only 45 h after retrieval. This pattern of results suggests that memory retrieval and ZIP-sensitive maintenance mechanisms are mutually exclusive and that the progression from one to the other are similar after acquisition and retrieval. They also reveal concrete differences between ZIP-sensitive mechanisms induced by acquisition and retrieval: the latency with which ZIP-sensitive mechanisms are expressed differ for the two processes.

SIGNIFICANCE STATEMENT: Memory retrieval and the molecular mechanisms that are sensitive to ζ-inhibitory peptide (ZIP) are the few manipulations that have been shown to effect memory maintenance. Although much is known about their effect on maintenance separately, it is unknown how they interact. Here, we describe a model for the interaction between memory retrieval and ZIP-sensitive mechanisms, showing that retrieval trials briefly (i.e., for 45 h) interrupt these mechanisms. ZIP sensitivity emerges across a similar time window after memory acquisition and retrieval; the maintenance mechanisms that follow acquisition and retrieval differ, however, in the latency with which the impact of ZIP is expressed.}, } @article {pmid27733609, year = {2016}, author = {Ramírez-Lugo, L and Peñas-Rincón, A and Ángeles-Durán, S and Sotres-Bayon, F}, title = {Choice Behavior Guided by Learned, But Not Innate, Taste Aversion Recruits the Orbitofrontal Cortex.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {36}, number = {41}, pages = {10574-10583}, pmid = {27733609}, issn = {1529-2401}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Choice Behavior/drug effects/*physiology ; GABA Agonists/pharmacology ; Learning/drug effects/*physiology ; Male ; Memory/drug effects ; Muscimol/pharmacology ; Prefrontal Cortex/drug effects/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Wistar ; Receptors, GABA-A/drug effects ; Receptors, GABA-B/drug effects ; Taste/drug effects/*physiology ; Taste Perception ; }, abstract = {UNLABELLED: The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats. Interestingly, we found that inactivation of the orbitofrontal cortex (OFC), but not the dorsal or ventral medial prefrontal cortices, blocked retrieval of choice CTA. However, OFC inactivation left retrieval of no-choice CTA intact, suggesting its role in guiding choice, but not in retrieval of CTA memory. Consistently, OFC activity increased in the choice condition compared with no-choice, as measured with c-Fos immunolabeling. Notably, OFC inactivation did not affect choice behavior when it was guided by innate taste aversion. Consistent with an anterior insular cortex (AIC) involvement in storing taste memories, we found that AIC inactivation impaired retrieval of both choice and no-choice CTA. Therefore, this study provides evidence for OFC's role in guiding choice behavior and shows that this is dissociable from AIC-dependent taste aversion memory. Together, our results suggest that OFC is required and recruited to guide choice selection between options of taste associations relayed from AIC.

SIGNIFICANCE STATEMENT: Survival and mental health depend on being able to choose stimuli not associated with danger. This is particularly important when danger is associated with stimuli that we ingest. Although much is known about the brain mechanisms that underlie associations with dangerous taste stimuli, very little is known about how these stored emotional associations guide behavior when it involves choice. By combining pharmacological and immunohistochemistry tools with taste-guided tasks, our study provides evidence for the key role of orbitofrontal cortex activity in choice behavior and shows that this is dissociable from the adjacent insular cortex-dependent taste aversion memory. Understanding the brain mechanisms that underlie the impact that emotional associations have on survival choice behaviors may lead to better treatments for mental disorders characterized by emotional decision-making deficits.}, } @article {pmid27721985, year = {2016}, author = {Levitan, D and Gal-Ben-Ari, S and Heise, C and Rosenberg, T and Elkobi, A and Inberg, S and Sala, C and Rosenblum, K}, title = {The differential role of cortical protein synthesis in taste memory formation and persistence.}, journal = {NPJ science of learning}, volume = {1}, number = {}, pages = {16001}, pmid = {27721985}, issn = {2056-7936}, support = {GGP13187/TI_/Telethon/Italy ; }, abstract = {The current dogma suggests that the formation of long-term memory (LTM) is dependent on protein synthesis but persistence of the memory trace is not. However, many of the studies examining the effect of protein synthesis inhibitors (PSIs) on LTM persistence were performed in the hippocampus, which is known to have a time-dependent role in memory storage, rather than the cortex, which is considered to be the main structure to store long-term memories. Here we studied the effect of PSIs on LTM formation and persistence in male Wistar Hola (n ≥ 5) rats by infusing the protein synthesis inhibitor, anisomycin (100 μg, 1 μl), into the gustatory cortex (GC) during LTM formation and persistence in conditioned taste aversion (CTA). We found that local anisomycin infusion to the GC before memory acquisition impaired LTM formation (P = 8.9E - 5), but had no effect on LTM persistence when infused 3 days post acquisition (P = 0.94). However, when we extended the time interval between treatment with anisomycin and testing from 3 days to 14 days, LTM persistence was enhanced (P = 0.01). The enhancement was on the background of stable and non-declining memory, and was not recapitulated by another amnesic agent, APV (10 μg, 1 μl), an N-methyl-d-aspartate receptor antagonist (P = 0.54). In conclusion, CTA LTM remains sensitive to the action of PSIs in the GC even 3 days following memory acquisition. This sensitivity is differentially expressed between the formation and persistence of LTM, suggesting that increased cortical protein synthesis promotes LTM formation, whereas decreased protein synthesis promotes LTM persistence.}, } @article {pmid27682823, year = {2017}, author = {Tandon, S and Keefe, KA and Taha, SA}, title = {Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.}, journal = {The Journal of physiology}, volume = {595}, number = {4}, pages = {1393-1412}, pmid = {27682823}, issn = {1469-7793}, support = {R01 MH094870/MH/NIMH NIH HHS/United States ; }, mesh = {Alcohol Drinking/*physiopathology ; Animals ; Conditioning, Operant ; Ethanol/*toxicity ; *Evoked Potentials, Somatosensory ; Habenula/cytology/*physiology ; Male ; Neurons/*physiology ; Rats ; Rats, Long-Evans ; Taste Disorders/etiology/*physiopathology ; *Taste Perception ; }, abstract = {KEY POINTS: The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption.

ABSTRACT: Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg[-1] 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake.}, } @article {pmid27660150, year = {2017}, author = {St John, SJ}, title = {The Perceptual Characteristics of Sodium Chloride to Sodium-Depleted Rats.}, journal = {Chemical senses}, volume = {42}, number = {2}, pages = {93-103}, pmid = {27660150}, issn = {1464-3553}, mesh = {Amiloride/pharmacology ; Animals ; Appetite/drug effects/*physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium/*deficiency ; Sodium Chloride/*analysis ; Sodium Chloride, Dietary/administration & dosage/*pharmacology ; Sucrose/analysis/pharmacology ; Taste/*drug effects/*physiology ; Taste Perception/drug effects/physiology ; }, abstract = {Three experiments assessed potential changes in the rat's perception of sodium chloride (NaCl) during a state of sodium appetite. In Experiment 1, sodium-sufficient rats licking a range of NaCl concentrations (0.028-0.89M) in 15s trials showed an inverted U-shaped concentration response function peaking at 0.281M. Depleted rats (furosemide) showed an identical function, merely elevated, suggesting altered qualitative or hedonic perception but no change in perceived intensity. In Experiment 2, sodium-depleted rats were tested with NaCl, sodium gluconate, and potassium chloride (KCl; 0.028-0.89M) similar to Experiment 1. KCl was licked at the same rate as water except for a slight elevation at 0.158; sodium gluconate and NaCl were treated similarly, but rats showed more licking for hypertonic sodium gluconate than hypertonic NaCl. Sodium-depleted rats were also tested with NaCl mixed in amiloride (10-300 μM). Amiloride reduced licking but did not alter the shape of the concentration-response function. Collectively, these results suggest that transduction of sodium by epithelial sodium channels (which are blocked by amiloride and are more dominant in sodium gluconate than NaCl transduction) is crucial for the perception of sodium during physiological sodium depletion. In Experiment 3, sodium-deplete rats were tested with NaCl as in Experiment 1 but after taste aversion conditioning to 0.3M NaCl or sucrose. Rats conditioned to avoid NaCl but not sucrose failed to express a sodium appetite, strongly suggesting that NaCl does not undergo a change in taste quality during sodium appetite-rats show no confusion between sucrose and NaCl in this paradigm.}, } @article {pmid27643793, year = {2017}, author = {Ellis, JM and Galloway, AT and Webb, RM and Martz, DM}, title = {Measuring adult picky eating: The development of a multidimensional self-report instrument.}, journal = {Psychological assessment}, volume = {29}, number = {8}, pages = {955-966}, doi = {10.1037/pas0000387}, pmid = {27643793}, issn = {1939-134X}, mesh = {Adult ; Anxiety Disorders/diagnosis/psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Feeding and Eating Disorders/*diagnosis/*psychology ; Female ; Food Preferences/psychology ; Humans ; Male ; Psychometrics/*statistics & numerical data ; Quality of Life/psychology ; *Self Report ; *Surveys and Questionnaires ; Taste ; Young Adult ; }, abstract = {A brief multidimensional measure of adult picky eating (PE) behavior was developed using a large U.S. adult sample. In addition, the study explored associations between specific aspects of adult PE behavior and psychosocial impairment in effort to support the inclusion of adults in the Diagnostic and Statistical Manual for Mental Disorders-Fifth Edition (DSM-5) avoidant-restrictive food intake disorder (ARFID). The study included 3 phases of qualitative and quantitative data collection. Participants were 1,663 U.S. adults who completed online surveys. Exploratory and confirmatory factor analyses were used to develop PE subscales. Associations among the PE subscales and measures of psychosocial impairment were examined. Exploratory and confirmatory factor analysis supported a 16-item 4-factor model of adult PE that included subscales of meal presentation, food variety, meal disengagement, and taste aversion. The measure also demonstrated convergence with previous measures of PE. The meal disengagement and meal presentation subscales demonstrated significant associations with social eating anxiety, anxiety sensitivity, eating related quality of life (QOL), and psychological flexibility. Meal disengagement alone was significantly associated with depressive symptoms. The Adult Picky Eating Questionnaire (APEQ) demonstrated sound psychometric properties and may be used to further investigate adult PE behavior. The relationships between adult PE and psychological impairment, particularly social anxiety, support the inclusion of ARFID in the DSM-5. (PsycINFO Database Record}, } @article {pmid27624788, year = {2016}, author = {Katagawa, Y and Yasuo, T and Suwabe, T and Yamamura, T and Gen, K and Sako, N}, title = {Recognition by Rats of Binary Taste Solutions and Their Components.}, journal = {Chemical senses}, volume = {41}, number = {9}, pages = {795-801}, doi = {10.1093/chemse/bjw093}, pmid = {27624788}, issn = {1464-3553}, abstract = {This behavioral study investigated how rats conditioned to binary mixtures of preferred and aversive taste stimuli, respectively, responded to the individual components in a conditioned taste aversion (CTA) paradigm. The preference of stimuli was determined based on the initial results of 2 bottle preference test. The preferred stimuli included 5mM sodium saccharin (Sacc), 0.03M NaCl (Na), 0.1M Na, 5mM Sacc + 0.03M Na, and 5mM Sacc + 0.2mM quinine hydrochloride (Q), whereas the aversive stimuli tested were 1.0M Na, 0.2mM Q, 0.3mM Q, 5mM Sacc + 1.0M Na, and 5mM Sacc + 0.3mM Q. In CTA tests where LiCl was the unconditioned stimulus, the number of licks to the preferred binary mixtures and to all tested preferred components were significantly less than in control rats. No significant difference resulted between the number of licks to the aversive binary mixtures or to all tested aversive components. However, when rats pre-exposed to the aversive components contained of the aversive binary mixtures were conditioned to these mixtures, the number of licks to all the tested stimuli was significantly less than in controls. Rats conditioned to components of the aversive binary mixtures generalized to the binary mixtures containing those components. These results suggest that rats recognize and remember preferred and aversive taste mixtures as well as the preferred and aversive components of the binary mixtures, and that pre-exposure before CTA is an available method to study the recognition of aversive taste stimuli.}, } @article {pmid27579495, year = {2017}, author = {Ward-Fear, G and Thomas, J and Webb, JK and Pearson, DJ and Shine, R}, title = {Eliciting conditioned taste aversion in lizards: Live toxic prey are more effective than scent and taste cues alone.}, journal = {Integrative zoology}, volume = {12}, number = {2}, pages = {112-120}, doi = {10.1111/1749-4877.12226}, pmid = {27579495}, issn = {1749-4877}, mesh = {Animals ; *Avoidance Learning ; *Bufo marinus ; Cues ; Introduced Species ; Lithium Chloride ; Lizards/*physiology ; *Odorants ; Predatory Behavior ; *Taste ; Toxins, Biological/*toxicity ; Western Australia ; }, abstract = {Conditioned taste aversion (CTA) is an adaptive learning mechanism whereby a consumer associates the taste of a certain food with symptoms caused by a toxic substance, and thereafter avoids eating that type of food. Recently, wildlife researchers have employed CTA to discourage native fauna from ingesting toxic cane toads (Rhinella marina), a species that is invading tropical Australia. In this paper, we compare the results of 2 sets of CTA trials on large varanid lizards ("goannas," Varanus panoptes). One set of trials (described in this paper) exposed recently-captured lizards to sausages made from cane toad flesh, laced with a nausea-inducing chemical (lithium chloride) to reinforce the aversion response. The other trials (in a recently-published paper, reviewed herein) exposed free-ranging lizards to live juvenile cane toads. The effectiveness of the training was judged by how long a lizard survived in the wild before it was killed (fatally poisoned) by a cane toad. Both stimuli elicited rapid aversion to live toads, but the CTA response did not enhance survival rates of the sausage-trained goannas after they were released into the wild. In contrast, the goannas exposed to live juvenile toads exhibited higher long-term survival rates than did untrained conspecifics. Our results suggest that although it is relatively easy to elicit short-term aversion to toad cues in goannas, a biologically realistic stimulus (live toads, encountered by free-ranging predators) is most effective at buffering these reptiles from the impact of invasive toxic prey.}, } @article {pmid27579475, year = {2016}, author = {Drgonova, J and Walther, D and Hartstein, GL and Bukhari, MO and Baumann, MH and Katz, J and Hall, FS and Arnold, ER and Flax, S and Riley, A and Rivero-Martin, O and Lesch, KP and Troncoso, J and Ranscht, B and Uhl, GR}, title = {Cadherin 13: human cis-regulation and selectively-altered addiction phenotypes and cerebral cortical dopamine in knockout mice.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {22}, number = {}, pages = {537-547}, pmid = {27579475}, issn = {1528-3658}, support = {R21 HL102680/HL/NHLBI NIH HHS/United States ; }, abstract = {The cadherin 13 (CDH13) gene encodes a cell adhesion molecule likely to influence development and connections of brain circuits that modulate addiction, locomotion and cognition, including those that involve midbrain dopamine neurons. Human CDH13 mRNA expression differs by more than 80% in postmortem cerebral cortical samples from individuals with different CDH13 genotypes, supporting examination of mice with altered Cdh13 expression as models for common human variation at this locus. Constitutive cdh13 knockout mice display evidence for changed cocaine reward: shifted dose response relationship in tests of cocaine-conditioned place preference using doses that do not alter cocaine conditioned taste aversion. Reduced adult Cdh13 expression in conditional knockouts also alters cocaine reward in ways that correlate with individual differences in cortical Cdh13 mRNA levels. In control and comparison behavioral assessments, knockout mice display modestly-quicker acquisition of rotarod and water maze tasks, with a trend toward faster acquisition of 5 choice serial reaction time tasks that otherwise displayed no genotype-related differences. They display significant differences in locomotion in some settings, with larger effects in males. In assessments of brain changes that might contribute to these behavioral differences, there are selective alterations of dopamine levels, dopamine/metabolite ratios, dopaminergic fiber densities and mRNA encoding the activity dependent transcription factor npas4 in cerebral cortex of knockout mice. These novel data and previously reported human associations of CDH13 variants with addiction, individual differences in responses to stimulant administration and attention deficit hyperactivity disorder (ADHD) phenotypes suggest that levels of CDH13 expression, through mechanisms likely to include effects on mesocortical dopamine, influence stimulant reward and may contribute modestly to cognitive and locomotor phenotypes relevant to ADHD.}, } @article {pmid27566473, year = {2017}, author = {Deguchi, T and Tsutsui, S and Iwahashi, H and Nakagawa, Y and Yoshida, M}, title = {Efficacy and safety of novel high-frequency multi-train stimulation for recording transcranial motor evoked potentials in a rat model.}, journal = {Journal of clinical monitoring and computing}, volume = {31}, number = {5}, pages = {1053-1058}, pmid = {27566473}, issn = {1573-2614}, support = {26462248//Grants-in-Aid for Scientific Research in the Japanese Society for the Promotion of Science/United States ; 26462248//Grants-in-Aid for Scientific Research in the Japanese Society for the Promotion of Science/United States ; }, mesh = {Anesthesia, General ; Animals ; Behavior, Animal ; Brain ; Disease Models, Animal ; Electric Stimulation/*methods ; Evoked Potentials, Motor/*physiology ; Humans ; Male ; Monitoring, Intraoperative/*methods ; Muscle, Skeletal ; Neurophysiology ; Patient Safety ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Recently, low-frequency multi-train stimulation (MTS) was shown to effectively enhance transcranial motor-evoked potentials (TcMEPs). In contrast, high- frequency double-train stimulation was reported to elicit a marked facilitation. The aim of this study was to evaluate the efficacy of high-frequency MTS in the augmentation of potentials. In addition, we investigated the safety of high-frequency MTS, behaviorally and histologically. TcMEPs were recorded from the triceps surae muscle in 38 rats. A multipulse stimulus was delivered repeatedly at different rates (2, 5, 10, 20, and 50 Hz), and was defined as MTS. A conditioned taste aversion method was used to investigate the effect of high-frequency MTS on learning and memory function. Subsequently, animals were sacrificed, and the brains were removed and examined using the standard hematoxylin-eosin method. Compared with conventional single train stimulation, TcMEP amplitudes increased 1.3, 2.1, 1.9, and 2.0 times on average with 5, 10, 20, and 50 Hz stimulation, respectively. The aversion index was >0.8 in all animals after they received 100 high-frequency MTSs. Histologically, no pathological changes were evident in the rat brains. High-frequency MTS shows potential to effectively enhance TcMEP responses, and to be used safely in transcranial brain stimulation.}, } @article {pmid27553426, year = {2017}, author = {Kwok, DWS and Harris, JA and Boakes, RA}, title = {Timing of interfering events in one-trial serial overshadowing of a taste aversion.}, journal = {Learning & behavior}, volume = {45}, number = {2}, pages = {124-134}, pmid = {27553426}, issn = {1543-4508}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; Lithium Chloride ; Rats ; *Taste ; Taste Perception ; }, abstract = {This set of experiments examined the question of when a stimulus would be most effective in overshadowing the acquisition of long-delay taste aversion learning. In Experiment 1 rats drank sucrose, the target solution, followed by a hydrochloric acid (HCl) solution before lithium injection some time later; HCl was presented either early or late in the interval. The late condition produced greater overshadowing than the early condition. The importance of the HCl-injection interval was confirmed by Experiment 2, in which the sucrose-injection interval was varied. Experiment 3 found that even placement in a different context - an event that normally produces little overshadowing of a CTA - produced one-trial overshadowing of a sucrose aversion as long as the context was novel and exposure to it occurred immediately before lithium injection. No current theoretical account of one-trial overshadowing predicts that a late event produces more overshadowing than an early event. This result can, however, be accommodated within a modified version of the Rescorla-Wagner model.}, } @article {pmid27549757, year = {2016}, author = {Sheth, C and Furlong, TM and Keefe, KA and Taha, SA}, title = {Lesion of the rostromedial tegmental nucleus increases voluntary ethanol consumption and accelerates extinction of ethanol-induced conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {233}, number = {21-22}, pages = {3737-3749}, pmid = {27549757}, issn = {1432-2072}, support = {R01 MH094870/MH/NIMH NIH HHS/United States ; }, mesh = {Adrenergic alpha-2 Receptor Antagonists/pharmacology ; Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Classical/drug effects ; Conditioning, Operant ; Ethanol/*pharmacology ; Habenula ; Male ; Quinine ; Rats ; Rats, Long-Evans ; Saccharin ; Self Administration ; Sweetening Agents ; Taste/*drug effects ; *Tegmentum Mesencephali ; Yohimbine/pharmacology ; }, abstract = {RATIONALE: Ethanol has rewarding and aversive properties, and the balance of these properties influences voluntary ethanol consumption. Preclinical and clinical evidence show that the aversive properties of ethanol limit intake. The neural circuits underlying ethanol-induced aversion learning are not fully understood. We have previously shown that the lateral habenula (LHb), a region critical for aversive conditioning, plays an important role in ethanol-directed behaviors. However, the neurocircuitry through which LHb exerts its actions is unknown.

OBJECTIVE: In the present study, we investigate a role for the rostromedial tegmental nucleus (RMTg), a major LHb projection target, in regulating ethanol-directed behaviors.

METHODS: Rats received either sham or RMTg lesions and were studied during voluntary ethanol consumption; operant ethanol self-administration, extinction, and yohimbine-induced reinstatement of ethanol-seeking; and ethanol-induced conditioned taste aversion (CTA).

RESULTS: RMTg lesions increased voluntary ethanol consumption and accelerated extinction of ethanol-induced CTA.

CONCLUSIONS: The RMTg plays an important role in regulating voluntary ethanol consumption, possibly by mediating ethanol-induced aversive conditioning.}, } @article {pmid27535568, year = {2017}, author = {Okusha, Y and Hirai, Y and Maezawa, H and Hisadome, K and Inoue, N and Yamazaki, Y and Funahashi, M}, title = {Effects of intraperitoneally administered L-histidine on food intake, taste, and visceral sensation in rats.}, journal = {The journal of physiological sciences : JPS}, volume = {67}, number = {4}, pages = {467-474}, pmid = {27535568}, issn = {1880-6562}, mesh = {Animals ; Appetite Depressants/*administration & dosage ; Area Postrema/drug effects/metabolism/physiopathology ; Brain/*drug effects/metabolism/physiopathology ; Eating/*drug effects ; Feeding Behavior/*drug effects ; Histidine/*administration & dosage ; Injections, Intraperitoneal ; Nausea/chemically induced/physiopathology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats, Sprague-Dawley ; Solitary Nucleus/drug effects/metabolism/physiopathology ; Taste/*drug effects ; Time Factors ; Vagotomy ; Visceral Pain/*chemically induced/physiopathology/psychology ; }, abstract = {To evaluate relative factors for anorectic effects of L-histidine, we performed behavioral experiments for measuring food and fluid intake, conditioned taste aversion (CTA), taste disturbance, and c-Fos immunoreactive (Fos-ir) cells before and after i.p. injection with L-histidine in rats. Animals were injected with saline (9 ml/kg, i.p.) for a control group, and saline (9 ml/kg, i.p.) containing L-histidine (0.75, 1.5, 2.0 g/kg) for a L-histidine group. Injection of L-histidine decreased the average value of food intake, and statistically significant anorectic effects were found in animals injected with 1.5 or 2.0 g/kg L-histidine but not with 0.75 g/kg L-histidine. Taste abnormalities were not detected in any of the groups. Animals injected with 2.0 g/kg L-histidine were revealed to present with nausea by the measurement of CTA. In this group, a significant increase in the number of Fos-ir cells was detected both in the area postrema and the nucleus tractus solitarius (NTS). In the 0.75 g/kg L-histidine group, a significant increase in the number of Fos-ir cells was detected only in the NTS. When the ventral gastric branch vagotomy was performed, recovery from anorexia became faster than the sham-operated group, however, vagotomized rats injected with 2.0 g/kg L-histidine still acquired CTA. These data indicate that acute anorectic effects induced by highly concentrated L-histidine are partly caused by induction of nausea and/or visceral discomfort accompanied by neuronal activities in the NTS and the area postrema. We suggest that acute and potent effects of L-histidine on food intake require substantial amount of L-histidine in the diet.}, } @article {pmid27521755, year = {2016}, author = {Kosaki, Y and Watanabe, S}, title = {Impaired Pavlovian predictive learning between temporally phasic but not static events in autism-model strain mice.}, journal = {Neurobiology of learning and memory}, volume = {134 Pt B}, number = {}, pages = {304-316}, doi = {10.1016/j.nlm.2016.08.001}, pmid = {27521755}, issn = {1095-9564}, mesh = {Animals ; Association Learning/*physiology ; Autism Spectrum Disorder/*physiopathology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Autism-spectrum disorder (ASD) is a multi-aspect developmental disorder characterised by various social and non-social behavioural abnormalities. Using BTBR T+ tf mouse strain (BTBR), a promising animal model displaying a number of behavioural and neural characteristics associated with ASD, we tested the hypothesis that at the core of various symptoms of ASD lies a fundamental deficit in predictive learning between events. In five experiments, we conducted a variety of Pavlovian conditioning tasks, some requiring the establishment of associations between temporally phasic events and others involving static events. BTBR mice were impaired in the acquisition of conditioned magazine approach responses with an appetitive unconditioned stimulus (US) (Experiment 1) and conditioned freezing with an electric shock US (Experiment 2). Both of these tasks had temporally phasic conditioned stimuli (CSs). Conversely, these mice showed normal acquisition of conditioned place preference (CPP), whether the US was a systemic injection of methamphetamine (Experiment 3A) or the presence of food (Experiment 3B). Experiment 4 showed normal acquisition of conditioned taste aversion (CTA) to a flavour-taste compound CS, although BTBR mice still exhibited an abnormal stimulus selection when learning for each element of the compound CS was assessed separately. Experiment 5 revealed a weaker latent inhibition of CTA in BTBR mice. The BTBR mouse's impaired predictive learning between phasic events and intact associations between static events are discussed in terms of dysfunctional contingency-based, but not contiguity-based learning, which may accompany abnormal selective attention to relevant cues. We propose that such dysfunctional contingency learning mechanisms may underlie the development of various social and non-social symptoms of ASD.}, } @article {pmid27511277, year = {2016}, author = {Schier, LA and Spector, AC}, title = {Post-oral sugar detection rapidly and chemospecifically modulates taste-guided behavior.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {311}, number = {4}, pages = {R742-R755}, pmid = {27511277}, issn = {1522-1490}, support = {F32 DC013494/DC/NIDCD NIH HHS/United States ; R01 DC009821/DC/NIDCD NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Appetite Regulation/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical ; Dietary Sucrose/*metabolism/pharmacology ; Eating/*physiology ; Feeding Behavior/drug effects/*physiology ; Male ; Postprandial Period/physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; Taste Perception ; }, abstract = {Several recent studies have shown that post-oral sugar sensing rapidly stimulates ingestion. Here, we explored the specificity with which early-phase post-oral sugar sensing influenced ingestive motivation. In experiment 1, rats were trained to associate the consumption of 0.3 M sucrose with injections of LiCl (3.0 meq/kg ip, conditioned taste aversion) or given equivalent exposures to the stimuli, but in an unpaired fashion. Then, all rats were subjected to two brief-access tests to assess appetitive and consummatory responses to the taste properties of sucrose (0.01-1.0 M), 0.12 M NaCl, and dH2O (in 10-s trials in randomized blocks). Intraduodenal infusions of either 0.3 M sucrose or equiosmolar 0.15 M NaCl (3.0 ml) were administered, beginning just before each test. For unpaired rats, intraduodenal sucrose specifically enhanced licking for 0.03-1.0 M sucrose, with no effect on trial initiation, relative to intraduodenal NaCl. Rats with an aversion to sucrose suppressed licking responses to sucrose in a concentration-dependent manner, as expected, but the intraduodenal sucrose preload did not appear to further influence licking responses; instead, intraduodenal sucrose attenuated trial initiation. Using a serial taste reactivity (TR) paradigm, however, experiment 2 demonstrated that intraduodenal sucrose preloads suppressed ingestive oromotor responses to intraorally delivered sucrose in rats with a sucrose aversion. Finally, experiment 3 showed that intraduodenal sucrose preloads enhanced preferential licking to some representative tastants tested (sucrose, Polycose, and Intralipid), but not others (NaCl, quinine). Together, the results suggest that the early phase-reinforcing efficacy of post-oral sugar is dependent on the sensory and motivational properties of the ingesta.}, } @article {pmid27491591, year = {2016}, author = {Gasalla, P and Begega, A and Soto, A and Dwyer, DM and López, M}, title = {Functional brain networks underlying latent inhibition of conditioned disgust in rats.}, journal = {Behavioural brain research}, volume = {315}, number = {}, pages = {36-44}, doi = {10.1016/j.bbr.2016.07.051}, pmid = {27491591}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*enzymology ; Conditioning, Classical/*physiology ; Electron Transport Complex IV/*metabolism ; *Inhibition, Psychological ; Lithium Chloride/adverse effects ; Male ; Neural Pathways/*physiology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; *Taste ; }, abstract = {The present experiment examined the neuronal networks involved in the latent inhibition of conditioned disgust by measuring brain oxidative metabolism. Rats were given nonreinforced intraoral (IO) exposure to saccharin (exposed groups) or water (non-exposed groups) followed by a conditioning trial in which the animals received an infusion of saccharin paired (or unpaired) with LiCl. On testing, taste reactivity responses displayed by the rats during the infusion of the saccharin were examined. Behavioral data showed that preexposure to saccharin attenuated the development of LiCl-induced conditioned disgust reactions, indicating that the effects of taste aversion on hedonic taste reactivity had been reduced. With respect to cumulative oxidative metabolic activity across the whole study period, the parabrachial nucleus was the only single region examined which showed differential activity between groups which received saccharin-LiCl pairings with and without prior non-reinforced saccharin exposure, suggesting a key role in the effects of latent inhibition of taste aversion learning. In addition, many functional connections between brain regions were revealed through correlational analysis of metabolic activity, in particular an accumbens-amygdala interaction that may be involved in both positive and negative hedonic responses.}, } @article {pmid27485658, year = {2016}, author = {Preissmann, D and Dépré, M and Schenk, F and Gisquet-Verrier, P}, title = {Anxiety modulates cognitive deficits in a perinatal glutathione deficit animal model of schizophrenia.}, journal = {Brain research}, volume = {1648}, number = {Pt A}, pages = {459-468}, doi = {10.1016/j.brainres.2016.07.042}, pmid = {27485658}, issn = {1872-6240}, mesh = {Animals ; Anxiety/*chemically induced/complications ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Buthionine Sulfoximine/*administration & dosage/analogs & derivatives ; Cognitive Dysfunction/*chemically induced/complications ; *Disease Models, Animal ; Glutathione/*deficiency ; Locomotion/drug effects ; Male ; Prepulse Inhibition/drug effects ; Rats ; Rats, Wistar ; Reflex, Startle/drug effects ; Schizophrenia/chemically induced/*complications ; *Schizophrenic Psychology ; }, abstract = {In this study, we investigated long-term repercussion of early glutathione deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a "cognitive binding" process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia.}, } @article {pmid27481223, year = {2016}, author = {Rosenberg, T and Elkobi, A and Rosenblum, K}, title = {mAChR-dependent decrease in proteasome activity in the gustatory cortex is necessary for novel taste learning.}, journal = {Neurobiology of learning and memory}, volume = {135}, number = {}, pages = {115-124}, doi = {10.1016/j.nlm.2016.07.029}, pmid = {27481223}, issn = {1095-9564}, mesh = {Animals ; Behavior, Animal/drug effects/physiology ; Cerebral Cortex/drug effects/metabolism/*physiology ; Learning/drug effects/*physiology ; Male ; Muscarinic Antagonists/*pharmacology ; Proteasome Endopeptidase Complex/*metabolism ; Rats ; Rats, Wistar ; Receptors, Muscarinic/*metabolism ; Ribosomal Protein S6 Kinases, 70-kDa/*metabolism ; Scopolamine/pharmacology ; Taste Perception/drug effects/*physiology ; }, abstract = {Regulation of protein degradation via the ubiquitin proteasome system is crucial for normal learning and synaptic plasticity processes. While some studies reveal that increased proteasome degradation is necessary for different types of learning, others suggest the proteasome to be a negative regulator of plasticity. We aim to understand the molecular and cellular processes taking place in the gustatory cortex (GC), which underlie appetitive and aversive forms of taste learning. Previously, we have shown that N-methyl d-aspartic acid receptor (NMDAR)-dependent upregulation of proteasome activity 4h after novel taste learning is necessary for the association of novel taste with malaise and formation of conditioned taste aversion (CTA). Here, we first identify a correlative increase in proteasome activity in the GC immediately after novel taste learning and study the upstream and downstream effectors of this modulated proteasome activity. Interestingly, proteasome-mediated degradation was reduced in the GC, 20min after novel taste consumption in a muscarinic acetylcholine receptor (mAChR)-dependent and NMDAR-independent manner. This reduction in protein degradation led to an increased amount of p70 S6 kinase (p70S6k), which was abolished in the presence of mAChR antagonist scopolamine. Infusion of lactacystin, a proteasome inhibitor, to the GC precluded the amnestic effect of scopolamine. This study shows for the first time that following novel taste learning there is a cortical, mAChR-dependent reduced proteasome activity that enables the memory of taste familiarity. Moreover, inhibition of degradation in the GC attenuates novel taste learning and of p70 S6 kinase correlative increased expression. These results shed light on the complex regulation of protein synthesis and degradation machineries in the cortex following novel taste experience.}, } @article {pmid27472892, year = {2016}, author = {Sheng, Y and Soto, J and Orlu Gul, M and Cortina-Borja, M and Tuleu, C and Standing, JF}, title = {New generalized poisson mixture model for bimodal count data with drug effect: An application to rodent brief-access taste aversion experiments.}, journal = {CPT: pharmacometrics & systems pharmacology}, volume = {5}, number = {8}, pages = {427-436}, pmid = {27472892}, issn = {2163-8306}, support = {MR/M008665/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Databases, Factual/*statistics & numerical data ; *Models, Biological ; *Poisson Distribution ; Quinine/pharmacology ; Random Allocation ; Rats ; Taste/drug effects/physiology ; Taste Perception/drug effects/*physiology ; }, abstract = {Pharmacodynamic (PD) count data can exhibit bimodality and nonequidispersion complicating the inclusion of drug effect. The purpose of this study was to explore four different mixture distribution models for bimodal count data by including both drug effect and distribution truncation. An example dataset, which exhibited bimodal pattern, was from rodent brief-access taste aversion (BATA) experiments to assess the bitterness of ascending concentrations of an aversive tasting drug. The two generalized Poisson mixture models performed the best and was flexible to explain both under and overdispersion. A sigmoid maximum effect (Emax) model with logistic transformation was introduced to link the drug effect to the data partition within each distribution. Predicted density-histogram plot is suggested as a model evaluation tool due to its capability to directly compare the model predicted density with the histogram from raw data. The modeling approach presented here could form a useful strategy for modeling similar count data types.}, } @article {pmid27468916, year = {2017}, author = {Sánchez-Catalán, MJ and Faivre, F and Yalcin, I and Muller, MA and Massotte, D and Majchrzak, M and Barrot, M}, title = {Response of the Tail of the Ventral Tegmental Area to Aversive Stimuli.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {42}, number = {3}, pages = {638-648}, pmid = {27468916}, issn = {1740-634X}, mesh = {Animals ; Antimanic Agents/administration & dosage/pharmacology ; Behavior, Animal/drug effects/*physiology ; Carbolines/administration & dosage/pharmacology ; Conditioning, Classical/drug effects/*physiology ; Disease Models, Animal ; Lipopolysaccharides/administration & dosage/pharmacology ; Lithium Chloride/pharmacology ; Male ; Morphine Dependence/*physiopathology ; Naloxone/administration & dosage/pharmacology ; Narcotic Antagonists/administration & dosage/pharmacology ; Neuralgia/physiopathology ; Neurotoxins/administration & dosage/pharmacology ; Olfactory Perception/drug effects/*physiology ; Pain/chemically induced/*physiopathology ; Proto-Oncogene Proteins c-fos/*drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu/*drug effects ; Substance Withdrawal Syndrome/*physiopathology ; Ventral Tegmental Area/drug effects/*physiology ; }, abstract = {The GABAergic tail of the ventral tegmental area (tVTA), also named rostromedial tegmental nucleus (RMTg), exerts an inhibitory control on dopamine neurons of the VTA and substantia nigra. The tVTA has been implicated in avoidance behaviors, response to drugs of abuse, reward prediction error, and motor functions. Stimulation of the lateral habenula (LHb) inputs to the tVTA, or of the tVTA itself, induces avoidance behaviors, which suggests a role of the tVTA in processing aversive information. Our aim was to test the impact of aversive stimuli on the molecular recruitment of the tVTA, and the behavioral consequences of tVTA lesions. In rats, we assessed Fos response to lithium chloride (LiCl), β-carboline, naloxone, lipopolysaccharide (LPS), inflammatory pain, neuropathic pain, foot-shock, restraint stress, forced swimming, predator odor, and opiate withdrawal. We also determined the effect of tVTA bilateral ablation on physical signs of opiate withdrawal, and on LPS- and LiCl-induced conditioned taste aversion (CTA). Naloxone-precipitated opiate withdrawal induced Fos in μ-opioid receptor-positive (15%) and -negative (85%) tVTA cells, suggesting the presence of both direct and indirect mechanisms in tVTA recruitment during withdrawal. However, tVTA lesion did not impact physical signs of opiate withdrawal. Fos induction was also present with repeated, but not single, foot-shock delivery. However, such induction was mostly absent with other aversive stimuli. Moreover, tVTA ablation had no impact on CTA. Although stimulation of the tVTA favors avoidance behaviors, present findings suggest that this structure may be important to the response to some, but not all, aversive stimuli.}, } @article {pmid27388762, year = {2016}, author = {Glover, EJ and McDougle, MJ and Siegel, GS and Jhou, TC and Chandler, LJ}, title = {Role for the Rostromedial Tegmental Nucleus in Signaling the Aversive Properties of Alcohol.}, journal = {Alcoholism, clinical and experimental research}, volume = {40}, number = {8}, pages = {1651-1661}, pmid = {27388762}, issn = {1530-0277}, support = {T32 AA007474/AA/NIAAA NIH HHS/United States ; F32 AA022836/AA/NIAAA NIH HHS/United States ; R29 AA010983/AA/NIAAA NIH HHS/United States ; P50 AA010761/AA/NIAAA NIH HHS/United States ; U01 AA019967/AA/NIAAA NIH HHS/United States ; K99 AA024208/AA/NIAAA NIH HHS/United States ; R01 AA022701/AA/NIAAA NIH HHS/United States ; R01 AA010983/AA/NIAAA NIH HHS/United States ; P50 DA016511/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Ethanol/*administration & dosage ; Female ; Habenula/drug effects/physiology ; Lithium Chloride/administration & dosage ; Male ; Rats ; Rats, Long-Evans ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; Tegmentum Mesencephali/drug effects/*physiology ; }, abstract = {BACKGROUND: While the rewarding effects of alcohol contribute significantly to its addictive potential, it is becoming increasingly appreciated that alcohol's aversive properties also play an important role in the propensity to drink. Despite this, the neurobiological mechanism for alcohol's aversive actions is not well understood. The rostromedial tegmental nucleus (RMTg) was recently characterized for its involvement in aversive signaling and has been shown to encode the aversive properties of cocaine, yet its involvement in alcohol's aversive actions have not been elucidated.

METHODS: Adult male and female Long-Evans rats underwent conditioned taste aversion (CTA) procedures where exposure to a novel saccharin solution was paired with intraperitoneal administration of saline, lithium chloride (LiCl), or ethanol (EtOH). Control rats underwent the same paradigm except that drug and saccharin exposure were explicitly unpaired. Saccharin consumption was measured on test day in the absence of drug administration, and rats were sacrificed 90 to 105 minutes following access to saccharin. Brains were subsequently harvested and processed for cFos immunohistochemistry. The number of cFos-labeled neurons was counted in the RMTg and the lateral habenula (LHb)-a region that sends prominent glutamatergic input to the RMTg.

RESULTS: In rats that received paired drug and saccharin exposure, EtOH and LiCl induced significant CTA compared to saline to a similar degree in males and females. Both EtOH- and LiCl-induced CTA significantly enhanced cFos expression in the RMTg and LHb but not the hippocampus. Similar to behavioral measures, no significant effect of sex on CTA-induced cFos expression was observed. cFos expression in both the RMTg and LHb was significantly correlated with CTA magnitude with greater cFos being associated with more pronounced CTA. In addition, cFos expression in the RMTg was positively correlated with LHb cFos.

CONCLUSIONS: These data suggest that the RMTg and LHb are involved in the expression of CTA and are consistent with previous work implicating the RMTg in aversive signaling. Furthermore, increased cFos expression in the RMTg following EtOH-induced CTA suggests that this region plays a role in signaling alcohol's aversive properties.}, } @article {pmid27316343, year = {2016}, author = {Tuerkmen, A and Bösche, K and Lückemann, L and Engler, H and Schedlowski, M and Hadamitzky, M}, title = {Rats taste-aversive learning with cyclosporine a is not affected by contextual changes.}, journal = {Behavioural brain research}, volume = {312}, number = {}, pages = {169-173}, doi = {10.1016/j.bbr.2016.06.025}, pmid = {27316343}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cues ; Cyclosporine/*administration & dosage ; Extinction, Psychological/*drug effects ; *Immunosuppressive Agents ; Male ; Rats ; Saccharin/administration & dosage ; *Taste Perception ; }, abstract = {In conditioned taste aversion (CTA) rats associate a novel taste (conditioned stimulus; CS) with a treatment (unconditioned stimulus; US) that induces symptoms of malaise. During retrieval, animals learn that the CS no longer predicts the US, with the consequence that the behavior elicited by the CS extinguishes. Importantly, CTA data with lithium chloride (LiCl) as US indicate that extinction learning is affected by changing the physical context. However, if this is also the case in different taste-aversion paradigms employing compounds other than LiCL as US is unknown. Against this background the present study investigated in a CTA paradigm with saccharin as CS and the immunosuppressant cyclosporine A (CsA) as US the influence of contextual changes on CTA extinction. Our results show, that extinction of a learned CS-US association with CsA is not prone to contextual changes. Due to the direct effects of CsA on CNS functioning, CTA with this immunosuppressant apparently operates under different mechanisms compared to other drugs, such as LiCl. These data indicate that taste aversive learning and its extinction are not necessarily specific to the context in which it is learned but also depends, at least in part, on the physiological and neuropharmacological effects of the drug employed as US.}, } @article {pmid27311758, year = {2016}, author = {Hadamitzky, M and Orlowski, K and Schwitalla, JC and Bösche, K and Unteroberdörster, M and Bendix, I and Engler, H and Schedlowski, M}, title = {Transient inhibition of protein synthesis in the rat insular cortex delays extinction of conditioned taste aversion with cyclosporine A.}, journal = {Neurobiology of learning and memory}, volume = {133}, number = {}, pages = {129-135}, doi = {10.1016/j.nlm.2016.06.008}, pmid = {27311758}, issn = {1095-9564}, mesh = {Animals ; Anisomycin/administration & dosage/*pharmacology ; Behavior, Animal/*drug effects ; Cerebral Cortex/*drug effects ; Conditioning, Classical/*drug effects ; Cyclosporine/administration & dosage/*pharmacology ; Extinction, Psychological/*drug effects ; Immunosuppressive Agents/administration & dosage/*pharmacology ; Male ; Mental Recall/*drug effects ; Protein Biosynthesis/*drug effects ; Protein Synthesis Inhibitors/administration & dosage/*pharmacology ; Rats ; Time Factors ; }, abstract = {Conditioned responses gradually weaken and eventually disappear when subjects are repeatedly exposed to the conditioned stimulus (CS) in the absence of the unconditioned stimulus (US), a process called extinction. Studies have demonstrated that extinction of conditioned taste aversion (CTA) can be prevented by interfering with protein synthesis in the insular cortex (IC). However, it remained unknown whether it is possible to pharmacologically stabilize the taste aversive memory trace over longer periods of time. Thus, the present study aimed at investigating the time frame during which extinction of CTA can be efficiently prevented by blocking protein synthesis in the IC. Employing an established conditioning paradigm in rats with saccharin as CS, and the immunosuppressant cyclosporine A (CsA) as US, we show here that daily bilateral intra-insular injections of the protein synthesis inhibitor anisomycin (120μg/μl) immediately after retrieval significantly diminished CTA extinction over a period of five retrieval days and subsequently reached levels of saline-infused controls. These findings demonstrate that it is possible to efficiently delay but not to fully prevent CTA extinction during repeated retrieval trials by blocking protein translation with daily bilateral infusions of anisomycin in the IC. These data confirm and extent earlier reports indicating that the role of protein synthesis in CTA extinction learning is not limited to gastrointestinal malaise-inducing drugs such as lithium chloride (LiCl).}, } @article {pmid27301407, year = {2017}, author = {Lin, JY and Arthurs, J and Reilly, S}, title = {Conditioned taste aversions: From poisons to pain to drugs of abuse.}, journal = {Psychonomic bulletin & review}, volume = {24}, number = {2}, pages = {335-351}, pmid = {27301407}, issn = {1531-5320}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Association Learning ; *Avoidance Learning ; Child ; *Conditioning, Classical ; Conditioning, Operant ; Cues ; Food Preferences ; Humans ; *Illicit Drugs ; Male ; Mental Recall ; Pain/*psychology ; *Poisons ; Quality of Life ; Smell ; *Taste ; Time Factors ; }, abstract = {Learning what to eat and what not to eat is fundamental to our well-being, quality of life, and survival. In particular, the acquisition of conditioned taste aversions (CTAs) protects all animals (including humans) against ingesting foods that contain poisons or toxins. Counterintuitively, CTAs can also develop in situations in which we know with absolute certainty that the food did not cause the subsequent aversive systemic effect. Recent nonhuman animal research, analyzing palatability shifts, has indicated that a wider range of stimuli than has been traditionally acknowledged can induce CTAs. This article integrates these new findings with a reappraisal of some known characteristics of CTA and presents a novel conceptual analysis that is broader and more comprehensive than previous accounts of CTA learning.}, } @article {pmid27293152, year = {2016}, author = {O'Tousa, DS and Grahame, NJ}, title = {Long-Term Alcohol Drinking Reduces the Efficacy of Forced Abstinence and Conditioned Taste Aversion in Crossed High-Alcohol-Preferring Mice.}, journal = {Alcoholism, clinical and experimental research}, volume = {40}, number = {7}, pages = {1577-1585}, pmid = {27293152}, issn = {1530-0277}, support = {P50 AA007611/AA/NIAAA NIH HHS/United States ; P60 AA007611/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Abstinence/*psychology ; Alcohol Drinking/*psychology ; Animals ; Aversive Agents/pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Psychological ; Extinction, Psychological/drug effects ; Female ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Taste Perception ; Time Factors ; }, abstract = {BACKGROUND: Negative outcomes of alcoholism are progressively more severe as the duration of problem of alcohol use increases. Additionally, alcoholics demonstrate tendencies to neglect negative consequences associated with drinking and/or to choose to drink in the immediate presence of warning factors against drinking. The recently derived crossed high-alcohol-preferring (cHAP) mice, which volitionally drink to heavier intoxication (as assessed by blood ethanol [EtOH] concentration) than other alcohol-preferring populations, as well as spontaneously escalating their intake, may be a candidate to explore mechanisms underlying long-term excessive drinking. Here, we hypothesized that an extended drinking history would reduce the ability of 2 manipulations (forced abstinence [FA] and conditioned taste aversion [CTA]) to attenuate drinking.

METHODS: Experiment 1 examined differences between groups drinking for either 14 or 35 days, half of each subjected to 7 days of FA and half not, to characterize the potential changes in postabstinence drinking resulting from an extended drinking history. Experiment 2 used a CTA procedure to assess stimulus specificity of the ability of an aversive flavorant to decrease alcohol consumption. Experiment 3 used this taste aversion procedure to assess differences among groups drinking for 1, 14, or 35 days in their propensity to overcome this aversion when the flavorant was mixed with either EtOH or water.

RESULTS: Experiment 1 demonstrated that although FA decreased alcohol consumption in mice with a 14-day drinking history, it failed to do so in mice drinking alcohol for 35 days. Experiment 2 showed that the addition of a flavorant only suppressed alcohol drinking if an aversion to the flavorant was previously established. Experiment 3 demonstrated that an extended drinking history expedited extinction of suppressed alcohol intake caused by a conditioned aversive flavor.

CONCLUSIONS: These data show that a history of long-term drinking in cHAP mice attenuates the efficacy of interventions that normally reduce drinking. Analogous to alcoholics who may encounter difficulties in limiting their intake, cHAP mice with long drinking histories are relatively insensitive to both abstinence and signals of harmful consequences. We propose that the cHAP line may be a valid model for adaptations that occur following the extended heavy alcohol drinking.}, } @article {pmid27260351, year = {2016}, author = {Osorio-Gómez, D and Guzmán-Ramos, K and Bermúdez-Rattoni, F}, title = {Corrigendum to "Differential involvement of glutamatergic and catecholaminergic activity within the amygdala during taste aversion retrieval on memory expression and updating" [Behav. Brain Res. 307 (2016) 120-125].}, journal = {Behavioural brain research}, volume = {311}, number = {}, pages = {441}, doi = {10.1016/j.bbr.2016.05.053}, pmid = {27260351}, issn = {1872-7549}, } @article {pmid27227028, year = {2015}, author = {Rudd, JA and Nalivaiko, E and Matsuki, N and Wan, C and Andrews, PL}, title = {The involvement of TRPV1 in emesis and anti-emesis.}, journal = {Temperature (Austin, Tex.)}, volume = {2}, number = {2}, pages = {258-276}, pmid = {27227028}, issn = {2332-8940}, abstract = {Diverse transmitter systems (e.g. acetylcholine, dopamine, endocannabinoids, endorphins, glutamate, histamine, 5-hydroxytryptamine, substance P) have been implicated in the pathways by which nausea and vomiting are induced and are targets for anti-emetic drugs (e.g. 5-hydroxytryptamine3 and tachykinin NK1 antagonists). The involvement of TRPV1 in emesis was discovered in the early 1990s and may have been overlooked previously as TRPV1 pharmacology was studied in rodents (mice, rats) lacking an emetic reflex. Acute subcutaneous administration of resiniferatoxin in the ferret, dog and Suncus murinus revealed that it had "broad-spectrum" anti-emetic effects against stimuli acting via both central (vestibular system, area postrema) and peripheral (abdominal vagal afferents) inputs. One of several hypotheses discussed here is that the anti-emetic effect is due to acute depletion of substance P (or another peptide) at a critical site (e.g. nucleus tractus solitarius) in the central emetic pathway. Studies in Suncus murinus revealed a potential for a long lasting (one month) effect against the chemotherapeutic agent cisplatin. Subsequent studies using telemetry in the conscious ferret compared the anti-emetic, hypothermic and hypertensive effects of resiniferatoxin (pungent) and olvanil (non-pungent) and showed that the anti-emetic effect was present (but reduced) with olvanil which although inducing hypothermia it did not have the marked hypertensive effects of resiniferatoxin. The review concludes by discussing general insights into emetic pathways and their pharmacology revealed by these relatively overlooked studies with TRPV1 activators (pungent an non-pungent; high and low lipophilicity) and antagonists and the potential clinical utility of agents targeted at the TRPV1 system.}, } @article {pmid27167860, year = {2016}, author = {Manuelian, CL and Albanell, E and Rovai, M and Caja, G}, title = {How to Create Conditioned Taste Aversion for Grazing Ground Covers in Woody Crops with Small Ruminants.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {110}, pages = {}, pmid = {27167860}, issn = {1940-087X}, mesh = {Animal Husbandry/*methods ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Crops, Agricultural ; Feeding Behavior/*drug effects ; Goats ; Lithium Chloride/*administration & dosage ; Sheep ; Taste ; }, abstract = {Conditioned taste aversion (CTA) is a learning behavior process where animals are trained to reject certain feed after gastrointestinal discomfort has been produced. Lithium chloride (LiCl) is the preferred agent used in livestock to induce CTA because it specifically stimulates the vomit center. In addition, LiCl is commercially available, and easy to prepare and administer using a drenching gun. Nevertheless, some factors have to be considered to obtain an effective long-lasting CTA, which allows small ruminants to graze during the cropping season. A key aspect is to use animals with no previous contact with the target plant (the plant chosen to be avoided; new feed). Due to their native neophobic feeding behavior, small ruminants can easily associate the negative feedback effects with the new feed, resulting in a strong and persistent CTA. The recommended doses are 200 and 225 mg LiCl/kg body weight (BW) for goats and sheep, respectively. To induce CTA, 100 g of the target plant should be individually offered for at least 30 min, and LiCl administered thereafter if the intake is greater than 10 g. Each time the animal eats the target plant without negative consequences, the CTA becomes weaker. Consequently, to minimize the risk of target plant consumption, it is essential to have sufficient palatable ground cover available. The presence of an alternative feed (of quality and quantity) prevents the accidental consumption of the target plant. A close monitoring of the flock is recommended to remove and re-dose any animal consuming more than 4 bites or 10 g of the target plant. At the beginning of each grazing season, check the CTA status of each animal before moving them to the crop.}, } @article {pmid27144301, year = {2016}, author = {Choi, H and Conole, D and Atkinson, DJ and Laita, O and Jay-Smith, M and Pagano, MA and Ribaudo, G and Cavalli, M and Bova, S and Hopkins, B and Brimble, MA and Rennison, D}, title = {Fatty Acid-Derived Pro-Toxicants of the Rat Selective Toxicant Norbormide.}, journal = {Chemistry & biodiversity}, volume = {13}, number = {6}, pages = {762-775}, doi = {10.1002/cbdv.201500241}, pmid = {27144301}, issn = {1612-1880}, mesh = {Animals ; Male ; Molecular Structure ; Neovascularization, Pathologic/*chemically induced/pathology ; Norbornanes/chemical synthesis/*chemistry/*toxicity ; Prodrugs/*chemistry ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; }, abstract = {Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, as an acute vasoactive, NRB has a rapid onset of action which makes it relatively unpalatable to rats, often leading to sublethal uptake and accompanying bait shyness. A series of NRB-derived pro-toxicants (3a - i, 4a - i, and 5a - i) were prepared in an effort to 'mask' this acute response and improve both palatability and efficacy. Their synthesis, in vitro biological evaluation (vasocontractile response in rat vasculature, stability in selected rat media) and palatability/efficacy in Sprague-Dawley, wild Norway, and wild ship rats is described. Most notably, pro-toxicant 3d was revealed to be free of all pre-cleavage vasoconstrictory activity in rat caudal artery and was subsequently demonstrated to release NRB in the presence of rat blood, liver, and pancreatic enzymes. Moreover, it consistently displayed a high level of acceptance by rats in a two-choice bait-palatability and efficacy trial, with accompanying high mortality. On this evidence, fatty acid ester prodrugs would appear to offer a promising platform for the further development of NRB-derived toxicants with enhanced palatability and efficacy profiles.}, } @article {pmid27114001, year = {2016}, author = {Herisson, FM and Waas, JR and Fredriksson, R and Schiöth, HB and Levine, AS and Olszewski, PK}, title = {Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.}, journal = {Journal of neuroendocrinology}, volume = {28}, number = {4}, pages = {}, doi = {10.1111/jne.12381}, pmid = {27114001}, issn = {1365-2826}, mesh = {Animals ; Appetite ; Camphanes/pharmacology ; Eating/*physiology ; Feeding Behavior/physiology ; Food Deprivation/physiology ; Male ; Microinjections ; Neurons/physiology ; Nucleus Accumbens/*physiology ; Oxytocin/administration & dosage/antagonists & inhibitors/biosynthesis/*physiology ; Paraventricular Hypothalamic Nucleus/physiology ; Piperazines/pharmacology ; Rats ; Social Behavior ; Supraoptic Nucleus/physiology ; }, abstract = {Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting.}, } @article {pmid27084929, year = {2016}, author = {Flores, VL and Moran, A and Bernstein, M and Katz, DB}, title = {Preexposure to salty and sour taste enhances conditioned taste aversion to novel sucrose.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {23}, number = {5}, pages = {221-228}, pmid = {27084929}, issn = {1549-5485}, support = {R01DC6666/DC/NIDCD NIH HHS/United States ; R01 DC006666/DC/NIDCD NIH HHS/United States ; R01 DC007703/DC/NIDCD NIH HHS/United States ; T32 GM084907/GM/NIGMS NIH HHS/United States ; R01DC7703/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Female ; Rats ; Rats, Long-Evans ; Sucrose/*administration & dosage ; Sweetening Agents/*administration & dosage ; Taste/*physiology ; Taste Perception/drug effects/*physiology ; Time Factors ; Water Deprivation/physiology ; }, abstract = {Conditioned taste aversion (CTA) is an intensively studied single-trial learning paradigm whereby animals are trained to avoid a taste that has been paired with malaise. Many factors influence the strength of aversion learning; prominently studied among these is taste novelty-the fact that preexposure to the taste conditioned stimulus (CS) reduces its associability. The effect of exposure to tastes other than the CS has, in contrast, received little investigation. Here, we exposed rats to sodium chloride (N) and citric acid (C), either before or within a conditioning session involving novel sucrose (S). Presentation of this taste array within the conditioning session weakened the resultant S aversion, as expected. The opposite effect, however, was observed when exposure to the taste array was provided in sessions that preceded conditioning: such experience enhanced the eventual S aversion-a result that was robust to differences in CS delivery method and number of tastes presented in conditioning sessions. This "non-CS preexposure effect" scaled with the number of tastes in the exposure array (experience with more stimuli was more effective than experience with fewer) and with the amount of exposure sessions (three preexposure sessions were more effective than two). Together, our results provide evidence that exposure and experience with the realm of tastes changes an animal's future handling of even novel tastes.}, } @article {pmid27083122, year = {2016}, author = {Twining, RC and Freet, CS and Wheeler, RA and Reich, CG and Tompers, DA and Wolpert, SE and Grigson, PS}, title = {The role of dose and restriction state on morphine-, cocaine-, and LiCl-induced suppression of saccharin intake: A comprehensive analysis.}, journal = {Physiology & behavior}, volume = {161}, number = {}, pages = {104-115}, pmid = {27083122}, issn = {1873-507X}, support = {R01 DA009815/DA/NIDA NIH HHS/United States ; R37 DA009815/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/*pharmacology ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Dose-Response Relationship, Drug ; Eating/drug effects ; Food Deprivation ; Food Preferences ; Lithium Chloride/*pharmacology ; Male ; Morphine/*pharmacology ; Narcotics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/*administration & dosage ; Vasoconstrictor Agents/*pharmacology ; Water Deprivation ; }, abstract = {Rats avoid intake of a taste cue when paired with a drug of abuse or with the illness-inducing agent, lithium chloride (LiCl). Although progress has been made, it is difficult to compare the suppressive effects of abused agents and LiCl on intake of a gustatory conditioned stimulus (CS) because of the cross-laboratory use of different CSs, different unconditioned stimuli (USs), and different doses of the drugs, different conditioning regimens, and different restriction states. Here we have attempted to unify these variables by comparing the suppressive effects of a range of doses of morphine, cocaine, and LiCl on intake of a saccharin CS using a common regimen in non-restricted, food restricted, or water restricted male Sprague-Dawley rats. The results showed that, while the putatively aversive agent, LiCl, was effective in suppressing intake of the taste cue across nearly all doses, regardless of restriction state, the suppressive effects of both morphine and cocaine were greatly reduced when evaluated in either food or water restricted rats. Greater sensitivity to drug was revealed, at very low doses, when testing occurred in the absence of need (i.e., when the rats were non-restricted). Together, these results provide the first uniform and comprehensive analysis of the suppressive effects of morphine, cocaine, and LiCl as a function of dose and restriction state. In the present case, the suppressive effects of morphine and cocaine are found to differ from those of LiCl and, in some respects, from one another as well.}, } @article {pmid27079998, year = {2016}, author = {Haus, DL and López-Velázquez, L and Gold, EM and Cunningham, KM and Perez, H and Anderson, AJ and Cummings, BJ}, title = {Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.}, journal = {Experimental neurology}, volume = {281}, number = {}, pages = {1-16}, doi = {10.1016/j.expneurol.2016.04.008}, pmid = {27079998}, issn = {1090-2430}, mesh = {Animals ; Antigens, CD/metabolism ; Brain Injuries, Traumatic/*complications/pathology/surgery ; Cell Differentiation ; Cognition Disorders/*etiology/*surgery ; Conditioning, Classical ; Disease Models, Animal ; Escape Reaction/physiology ; Exploratory Behavior/physiology ; Hippocampus/pathology ; Humans ; Male ; Maze Learning/physiology ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells/metabolism/*transplantation ; Neurogenesis ; Neurons/metabolism/pathology ; Rats ; Rats, Nude ; Recognition, Psychology/physiology ; Spatial Behavior ; }, abstract = {Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically <1month post-injury and cell transplantation. Additionally, human cell engraftment and long-term survival in rodent models of TBI has been difficult to achieve due to host immunorejection of the transplanted human cells, which confounds conclusions pertaining to transplant-mediated behavioral improvement. To overcome these shortfalls, we have developed a novel TBI xenotransplantation model that utilizes immunodeficient athymic nude (ATN) rats as the host recipient for the post-TBI transplantation of human embryonic stem cell (hESC) derived NSCs and have evaluated cognition in these animals at long-term (≥2months) time points post-injury. We report that immunodeficient ATN rats demonstrate hippocampal-dependent spatial memory deficits (Novel Place, Morris Water Maze), but not non-spatial (Novel Object) or emotional/anxiety-related (Elevated Plus Maze, Conditioned Taste Aversion) deficits, at 2-3months post-TBI, confirming that ATN rats recapitulate some of the cognitive deficits found in immunosufficient animal strains. Approximately 9-25% of transplanted hNSCs survived for at least 5months post-transplantation and differentiated into mature neurons (NeuN, 18-38%), astrocytes (GFAP, 13-16%), and oligodendrocytes (Olig2, 11-13%). Furthermore, while this model of TBI (cortical impact) targets primarily cortex and the underlying hippocampus and generates a large lesion cavity, hNSC transplantation facilitated cognitive recovery without affecting either lesion volume or total spared cortical or hippocampal tissue volume. Instead, we have found an overall increase in host hippocampal neuron survival in hNSC transplanted animals and demonstrate that a correlation exists between hippocampal neuron survival and cognitive performance. Together, these findings support the use of immunodeficient rodents in models of TBI that involve the transplantation of human cells, and suggest that hNSC transplantation may be a viable, long-term therapy to restore cognition after brain injury.}, } @article {pmid27053000, year = {2016}, author = {Zheng, F and Kim, YJ and Moran, TH and Li, H and Bi, S}, title = {Central transthyretin acts to decrease food intake and body weight.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {24238}, pmid = {27053000}, issn = {2045-2322}, support = {R01 DK087888/DK/NIDDK NIH HHS/United States ; R01 DK104867/DK/NIDDK NIH HHS/United States ; DK104867/DK/NIDDK NIH HHS/United States ; DK087888/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Arcuate Nucleus of Hypothalamus/drug effects/metabolism ; Blotting, Western ; Body Weight/*drug effects ; Cells, Cultured ; Eating/*drug effects ; Gene Expression Profiling/methods ; Hyperphagia/metabolism/*prevention & control ; Hypothalamus/drug effects/metabolism ; Infusions, Intraventricular ; Male ; Neuropeptide Y/metabolism ; Obesity/metabolism/*prevention & control ; Oligonucleotide Array Sequence Analysis ; Prealbumin/administration & dosage/*pharmacology/physiology ; Rats, Inbred OLETF ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Transthyretin (TTR) is a blood and cerebrospinal fluid transporter of thyroxine and retinol. Gene expression profiling revealed an elevation of Ttr expression in the dorsomedial hypothalamus (DMH) of rats with exercise-induced anorexia, implying that central TTR may also play a functional role in modulating food intake and energy balance. To test this hypothesis, we have examined the effects of brain TTR on food intake and body weight and have further determined hypothalamic signaling that may underlie its feeding effect in rats. We found that intracerebroventricular (icv) administration of TTR in normal growing rats decreased food intake and body weight. This effect was not due to sickness as icv TTR did not cause a conditioned taste aversion. ICV TTR decreased neuropeptide Y (NPY) levels in the DMH and the paraventricular nucleus (P < 0.05). Chronic icv infusion of TTR in Otsuka Long-Evans Tokushima Fatty rats reversed hyperphagia and obesity and reduced DMH NPY levels. Overall, these results demonstrate a previously unknown anorectic action of central TTR in the control of energy balance, providing a potential novel target for treating obesity and its comorbidities.}, } @article {pmid27027859, year = {2016}, author = {Dannenhoffer, CA and Spear, LP}, title = {Age differences in conditioned place preferences and taste aversions to nicotine.}, journal = {Developmental psychobiology}, volume = {58}, number = {5}, pages = {660-666}, doi = {10.1002/dev.21400}, pmid = {27027859}, issn = {1098-2302}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/drug effects/*physiology ; Conditioning, Classical/*physiology ; Cotinine/blood ; Male ; Nicotine/administration & dosage/*pharmacology ; Nicotinic Agonists/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; *Reward ; Taste/physiology ; }, abstract = {Adolescents and adults differ in their behavioral sensitivities to drugs of abuse, including nicotine. Studies have shown that both rewarding and aversive properties of drugs of abuse can exist concomitantly. The present study investigated the ontogeny of these opposing qualities across a range of doses using a combined conditioned taste aversion and place preference paradigm in pair-housed rats that were not deprived of food or water. Results indicated that adolescents were more sensitive to the rewarding properties of nicotine than adults. In contrast, although all doses produced a taste aversion at both ages in the same rats, the aversion was weaker at lower than high doses in adolescents whereas adults showed strong aversion at all doses, suggesting modest attenuation in nicotine's aversive properties among adolescents relative to adults. Thus, attenuated aversive and accented appetitive sensitivities of adolescents to nicotine can be experienced simultaneously in the same animals. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 660-666, 2016.}, } @article {pmid27018173, year = {2016}, author = {Osorio-Gómez, D and Guzmán-Ramos, K and Bermúdez-Rattoni, F}, title = {Differential involvement of glutamatergic and catecholaminergic activity within the amygdala during taste aversion retrieval on memory expression and updating.}, journal = {Behavioural brain research}, volume = {307}, number = {}, pages = {120-125}, doi = {10.1016/j.bbr.2016.03.038}, pmid = {27018173}, issn = {1872-7549}, mesh = {Amygdala/drug effects/*metabolism ; Animals ; Avoidance Learning/drug effects/*physiology ; Catecholamines/*metabolism ; Cobalt/pharmacology ; Conditioning, Psychological/drug effects ; Excitatory Amino Acid Agents/pharmacology ; Exploratory Behavior/drug effects ; Glutamic Acid/*metabolism ; Immobility Response, Tonic/drug effects ; Male ; Mental Recall/drug effects/*physiology ; Microdialysis ; N-Methylaspartate/pharmacology ; Nitric Oxide Synthase Type I/metabolism ; Rats ; Rats, Wistar ; Swimming/psychology ; Taste/drug effects/*physiology ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology ; }, abstract = {During memory retrieval, consolidated memories are expressed and destabilized in order to maintain or update information through a memory reconsolidation process. Despite the key role of the amygdala during memory acquistion and consolidation, the participation of neurotransmitter signals in memory retrieval is poorly understood. Hence, we used conditioned taste aversion and in vivo microdialysis to evaluate changes in glutamate, norepinephrine and dopamine concentrations within the amygdala during memory retrieval. We observed that exposure to an aversive-conditioned stimulus induced an augmentation in glutamate, norepinephrine and dopamine levels within the amygdala, while exposure to a familiar and safe stimulus did not induce changes in these neurotransmitters levels. Also, we evaluated the amygdalar blockade of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), β-adrenergic and dopamine D1 receptors in memory retrieval and updating. Results showed that during retrieval, behavioural expression was impaired by intra-amygdalar blockade of AMPA and β-adrenergic receptors, whereas NMDA, D1 and β-adrenergic receptors blockade hindered memory updating. In summary, during conditioned taste aversion retrieval there was an increase in the extracellular levels of glutamate, norepinephrine and dopamine within the amygdala, and their receptors activity were differentially involved in the behavioural expression and memory updating during retrieval.}, } @article {pmid27014009, year = {2016}, author = {Villain, H and Benkahoul, A and Drougard, A and Lafragette, M and Muzotte, E and Pech, S and Bui, E and Brunet, A and Birmes, P and Roullet, P}, title = {Effects of Propranolol, a β-noradrenergic Antagonist, on Memory Consolidation and Reconsolidation in Mice.}, journal = {Frontiers in behavioral neuroscience}, volume = {10}, number = {}, pages = {49}, pmid = {27014009}, issn = {1662-5153}, abstract = {Memory reconsolidation impairment using the β-noradrenergic receptor blocker propranolol is a promising novel treatment avenue for patients suffering from pathogenic memories, such as post-traumatic stress disorder (PTSD). However, in order to better inform targeted treatment development, the effects of this compound on memory need to be better characterized via translational research. We examined the effects of systemic propranolol administration in mice undergoing a wide range of behavioral tests to determine more specifically which aspects of the memory consolidation and reconsolidation are impaired by propranolol. We found that propranolol (10 mg/kg) affected memory consolidation in non-aversive tasks (object recognition and object location) but not in moderately (Morris water maze (MWM) to highly (passive avoidance, conditioned taste aversion) aversive tasks. Further, propranolol impaired memory reconsolidation in the most and in the least aversive tasks, but not in the moderately aversive task, suggesting its amnesic effect was not related to task aversion. Moreover, in aquatic object recognition and location tasks in which animals were forced to behave (contrary to the classic versions of the tasks); propranolol did not impair memory reconsolidation. Taken together our results suggest that the memory impairment observed after propranolol administration may result from a modification of the emotional valence of the memory rather than a disruption of the contextual component of the memory trace. This is relevant to the use of propranolol to block memory reconsolidation in individuals with PTSD, as such a treatment would not erase the traumatic memory but only reduce the emotional valence associated with this event.}, } @article {pmid26992702, year = {2016}, author = {Dyr, W and Wyszogrodzka, E and Paterak, J and Siwińska-Ziółkowska, A and Małkowska, A and Polak, P}, title = {Ethanol-induced conditioned taste aversion in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {51}, number = {}, pages = {63-69}, doi = {10.1016/j.alcohol.2015.11.011}, pmid = {26992702}, issn = {1873-6823}, mesh = {Alcohol Drinking/*genetics ; Alcoholism/genetics ; Animals ; Avoidance Learning/drug effects/*physiology ; Choice Behavior/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Ethanol/*administration & dosage ; Male ; Rats ; Saccharin/administration & dosage ; Taste/*genetics ; }, abstract = {The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post-conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post-conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats.}, } @article {pmid26975440, year = {2016}, author = {Hurley, MM and Resch, JM and Maunze, B and Frenkel, MM and Baker, DA and Choi, S}, title = {N-acetylcysteine decreases binge eating in a rodent model.}, journal = {International journal of obesity (2005)}, volume = {40}, number = {7}, pages = {1183-1186}, pmid = {26975440}, issn = {1476-5497}, support = {R01 DK074734/DK/NIDDK NIH HHS/United States ; R21 DA035088/DA/NIDA NIH HHS/United States ; }, mesh = {Acetylcysteine/*pharmacology ; Animals ; Binge-Eating Disorder/*drug therapy ; Conditioning, Operant/drug effects ; Diet, High-Fat ; *Disease Models, Animal ; Feeding Behavior/*drug effects/*psychology ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Binge-eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetylcysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically, we monitored consumption of standard chow and a high-fat, high carbohydrate western diet (WD) in a rodent limited-access binge paradigm. Before each session, rats received either a systemic or intraventricular injection of NAC. Both systemic and central administration of NAC resulted in significant reductions of binge eating the WD without decreasing standard chow consumption. The reduction in WD was not attributable to general malaise as NAC did not produce condition taste aversion. These results are consistent with the clinical evidence of NAC to reduce or reverse compulsive behaviors, such as, drug addiction, skin picking and hair pulling.}, } @article {pmid26961783, year = {2016}, author = {Kislal, S and Blizard, DA}, title = {Conditioned context aversion learning in the laboratory mouse.}, journal = {Learning & behavior}, volume = {44}, number = {4}, pages = {309-319}, pmid = {26961783}, issn = {1543-4508}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; Conditioning, Psychological ; Drinking ; Lithium Chloride ; Mice ; Rats ; Taste ; }, abstract = {It is well known that pairing of large contextual changes with illness can cause conditioned context aversion in laboratory rats. The aim of present study was to develop a paradigm to study this phenomenon in laboratory mice, a species widely employed in neurobehavioral studies. Genetically heterogeneous mice, drinking from plastic bottles in the colony room, learned to avoid glass bottles after a single conditioning trial when drinking from these was paired with injections of lithium chloride. The aversion was independent of any difference in the taste of water in plastic vs. glass bottles. When the variation in the visual stimulus was less distinct, development of a strong aversion required two conditioning trials and was not retained as well. The results also showed that conditioned context aversion, just like conditioned taste aversion, could also be developed across a 30-minute CS-UCS delay. The fact that taste was not a factor in distinguishing drinking from glass and plastic water bottles raises the possibility that, contextual stimuli, not taste, may have been the CS when rats (in Garcia's original experiments) avoided drinking from plastic bottles that had been paired with radiation. The development of contextual aversion conditioning protocols for mice will enable the molecular resources available for this species to be exploited. Furthermore, representation of the CS by discrete rather than the multimodal CSs typically used in most studies on contextual conditioning offers more focus when considering its neuroanatomical basis.}, } @article {pmid26885512, year = {2016}, author = {Albores-Garcia, D and Acosta-Saavedra, LC and Hernandez, AJ and Loera, MJ and Calderón-Aranda, ES}, title = {Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats.}, journal = {BioMed research international}, volume = {2016}, number = {}, pages = {6532108}, pmid = {26885512}, issn = {2314-6141}, mesh = {Age Factors ; Animals ; Female ; Humans ; Learning/*drug effects/physiology ; Male ; Memory/*drug effects/physiology ; Methylmercury Compounds/*toxicity ; Pregnancy ; Rats ; }, abstract = {Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined.}, } @article {pmid26857541, year = {2016}, author = {Blednov, YA and Black, M and Benavidez, JM and Stamatakis, EE and Harris, RA}, title = {PPAR Agonists: II. Fenofibrate and Tesaglitazar Alter Behaviors Related to Voluntary Alcohol Consumption.}, journal = {Alcoholism, clinical and experimental research}, volume = {40}, number = {3}, pages = {563-571}, pmid = {26857541}, issn = {1530-0277}, support = {AA013520/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; AA006399/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*drug therapy/psychology ; Alkanesulfonates/*pharmacology/therapeutic use ; Animals ; Avoidance Learning/drug effects/physiology ; Conditioning, Classical/drug effects/physiology ; Female ; Fenofibrate/*pharmacology/therapeutic use ; Locomotion/drug effects ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; PPAR alpha/*agonists/*physiology ; Phenylpropionates/*pharmacology/therapeutic use ; Reflex, Righting/drug effects/physiology ; Taste/drug effects/physiology ; }, abstract = {BACKGROUND: In the accompanying article, we showed that activation of peroxisome proliferator-activated receptor alpha (PPARα) signaling by fenofibrate and tesaglitazar decreases ethanol (EtOH) consumption in mice. In this study, we determined the role of these PPAR agonists in EtOH-related behaviors and other actions that may be important in regulating EtOH consumption.

METHODS: The effects of fenofibrate (150 mg/kg) and tesaglitazar (1.5 mg/kg) were examined on the following responses in male and female C57BL/6J (B6) and B6 × 129S4 mice: preference for saccharin, EtOH-induced conditioned place preference (CPP), conditioned taste aversion (CTA), loss of righting reflex, and withdrawal, acoustic startle reflex, response to novelty, and EtOH clearance. Because the B6 inbred strain usually displays weak EtOH-induced CPP and weak EtOH-induced acute withdrawal, B6 × 129S4 mice were also studied.

RESULTS: Fenofibrate and tesaglitazar decreased the novelty response and increased acute EtOH withdrawal severity, and fenofibrate increased EtOH-induced CTA. Two important factors for EtOH consumption (saccharin preference and EtOH-induced CPP) were not altered by fenofibrate or tesaglitazar. EtOH clearance was increased by both fenofibrate and tesaglitazar. Response to novelty, acute withdrawal, and EtOH clearance show sex differences and could contribute to the reduced EtOH consumption following fenofibrate administration.

CONCLUSIONS: These studies indicate the complexity of EtOH-dependent and EtOH-independent behaviors that are altered by PPAR agonists and provide evidence for novel behavioral actions of these drugs that may contribute to PPAR-mediated effects on alcohol drinking.}, } @article {pmid26854904, year = {2016}, author = {Rivera-Olvera, A and Rodríguez-Durán, LF and Escobar, ML}, title = {Conditioned taste aversion prevents the long-lasting BDNF-induced enhancement of synaptic transmission in the insular cortex: A metaplastic effect.}, journal = {Neurobiology of learning and memory}, volume = {130}, number = {}, pages = {71-76}, doi = {10.1016/j.nlm.2016.01.014}, pmid = {26854904}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain-Derived Neurotrophic Factor/*pharmacology ; Cerebral Cortex/*drug effects/physiology ; Conditioning, Classical/*physiology ; Male ; Neuronal Plasticity/*drug effects/physiology ; Rats ; Rats, Wistar ; Synaptic Transmission/*drug effects/physiology ; Taste/*physiology ; Taste Perception/physiology ; }, abstract = {Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength.}, } @article {pmid26833633, year = {2016}, author = {Tracy, AL and Schurdak, JD and Chambers, JB and Benoit, SC}, title = {Aversion learning can reduce meal size without taste avoidance in rats.}, journal = {Obesity (Silver Spring, Md.)}, volume = {24}, number = {3}, pages = {606-614}, doi = {10.1002/oby.21379}, pmid = {26833633}, issn = {1930-739X}, mesh = {Adjuvants, Immunologic/administration & dosage/*toxicity ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Body Weight/drug effects ; Eating/*drug effects ; Lithium Chloride/*administration & dosage/toxicity ; Rats ; Taste/*drug effects ; }, abstract = {OBJECTIVE: Nausea and aversive food responses are commonly reported following bariatric surgery, along with post-surgical reduction in meal size. This study investigates whether a meal size limit can be conditioned by associating large meals with aversive outcomes.

METHODS: In rats, the intake of meals exceeding a pre-defined size threshold was paired with lithium chloride-induced gastric illness, and the effects on self-determined food intakes and body weight were measured.

RESULTS: Rats given LiCl contingent on the intake of a large meal learned to reliably reduce intake below this meal size threshold, while post-meal saline or LiCl before meals did not change meal size. It was further demonstrated that this is not a conditioned taste aversion and that this effect transferred to foods not explicitly trained. Finally, when rats received LiCl following all large meals, the number of small meals increased, but total food intake and body weight decreased.

CONCLUSIONS: While further work is needed, this is the first demonstration that meal size may be conditioned, using an aversion procedure, to remain under a target threshold and that this effect is distinct from taste avoidance. Corresponding reduction in food intake and body weight suggests that this phenomenon may have implications for developing weight loss strategies and understanding the efficacy of bariatric surgery.}, } @article {pmid26785229, year = {2016}, author = {Rosenberg, T and Elkobi, A and Dieterich, DC and Rosenblum, K}, title = {NMDAR-dependent proteasome activity in the gustatory cortex is necessary for conditioned taste aversion.}, journal = {Neurobiology of learning and memory}, volume = {130}, number = {}, pages = {7-16}, doi = {10.1016/j.nlm.2016.01.002}, pmid = {26785229}, issn = {1095-9564}, mesh = {Acetylcysteine/analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Cysteine Proteinase Inhibitors/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Male ; Proteasome Endopeptidase Complex/*metabolism ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism ; Somatosensory Cortex/drug effects/*metabolism ; Taste/drug effects/physiology ; Taste Perception/drug effects/*physiology ; Valine/analogs & derivatives/pharmacology ; }, abstract = {Taste information is processed in different brain structures in the mammalian brain, including the gustatory cortex (GC), which resides within the insular cortex. N-methyl-d-aspartate receptor (NMDAR) activity in the GC is necessary for the acquisition of conditioned taste aversion (CTA) but not positive novel taste learning. Previous studies have shown that taste memory consolidation requires intact protein synthesis in the GC. In addition, the direct involvement of translation initiation and elongation factors was documented in the GC during taste learning. However, protein expression is defined by protein synthesis, degradation, and localization. Protein degradation is critical for the consolidation and reconsolidation of other forms of learning, such as fear learning and addiction behavior, but its role in cortical-dependent learning is not clear. Here, we show for the first time that proteasome activity is specifically increased in the GC 4h following experiencing of a novel taste. This increase in proteasome activity was abolished by local administration to the GC of the NMDA antagonist, APV, as well as a CaMKII inhibitor, at the time of acquisition. In addition, local application of lactacystin, a proteasome inhibitor, resulted in impaired CTA, but not novel taste learning. These results suggest that NMDAR-dependent proteasome activity in the GC participates in the association process between novel taste experience and negative visceral sensation.}, } @article {pmid26783230, year = {2016}, author = {Feifel, D and Shilling, PD and Fazlinejad, AA and Melendez, G}, title = {Antipsychotic drug-like facilitation of latent inhibition by a brain-penetrating neurotensin-1 receptor agonist.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {30}, number = {3}, pages = {312-317}, doi = {10.1177/0269881115625360}, pmid = {26783230}, issn = {1461-7285}, support = {R01MH080910/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Antipsychotic Agents/*pharmacology ; Avoidance Learning/drug effects ; Brain/*drug effects ; Conditioning, Classical/drug effects ; Conditioning, Psychological/drug effects ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Brattleboro ; Receptors, Neurotensin/*agonists ; Schizophrenia/drug therapy ; }, abstract = {Latent inhibition (LI) is a measure of cognitive gating and refers to reduced conditioned learning when there is pre-exposure to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (US). Dysregulation of LI is associated with some neuropsychiatric disorders, including schizophrenia, and the ability to facilitate LI in rodents is a reasonably good predictive test for antipsychotic drugs. Converging evidence supports neurotensin-1 receptor (NTS1) agonists as novel drugs for schizophrenia. Therefore, we investigated the ability of a brain-penetrating, selective NTS1 agonist, PD149163, to facilitate LI in heterozygous Brattleboro rats, a strain that exhibits naturally low LI. Conditioned taste aversion to flavored water (FW; 0.1% saccharin) was induced by pairing it with malaise-inducing injections of lithium chloride (LiCl). Prior to LiCl-FW pairing, rats received subcutaneous injections of saline, or PD149163 (100 µg/kg or 200 µg/kg). Half the rats in each drug group had been allowed to drink FW the day before the LiCl-FW pairing (pre-exposed rats). Two days after pairing, the amount of FW each rat consumed was recorded. LI, defined as significantly greater FW drinking in the pre-exposed group compared with the non pre-exposed group, was exhibited only among rats that received 200 µg/kg of PD149163. These results further support NTS1 agonists as potentially novel drugs for the treatment of schizophrenia.}, } @article {pmid26774181, year = {2016}, author = {Saalfield, J and Spear, L}, title = {The ontogeny of ethanol aversion.}, journal = {Physiology & behavior}, volume = {156}, number = {}, pages = {164-170}, pmid = {26774181}, issn = {1873-507X}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; P50AA017823/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Ethanol/*pharmacology ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; *Taste ; }, abstract = {Recent work has suggested separate developmental periods within the broader framework of adolescence, with data suggesting distinct alterations and vulnerabilities within these intervals. While previous research has suggested reduced sensitivity to the aversive effects of alcohol in adolescence relative to adults, a more detailed ontogeny of this effect has yet to be conducted. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion. The current study aimed to determine the ontogeny of ethanol aversion by utilizing a conditioned taste aversion procedure at six different ages to test the hypothesis that the transitions into, through, and out of adolescence are associated with ontogenetic alterations in sensitivity to the aversive properties of ethanol. Non-deprived animals given Boost® as the conditioned stimulus (CS) were used in Experiment 1, whereas Experiment 2 used water-restricted animals provided with a saccharin/sucrose solution as the CS. In both experiments, an attenuated sensitivity to the aversive properties of ethanol was evident in adolescents compared to adults, although more age differences were apparent in water deprived animals than when a highly palatable CS was given to ad libitum animals. Overall, the data suggest an attenuated sensitivity to the aversive properties of ethanol that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults.}, } @article {pmid26752235, year = {2016}, author = {Kwok, DW and Sun, Q and Boakes, RA}, title = {Mediated overshadowing and potentiation of long-delay taste aversion learning: Two versus six cue-taste pairings.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {42}, number = {1}, pages = {106-115}, doi = {10.1037/xan0000088}, pmid = {26752235}, issn = {2329-8464}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; Cues ; Lithium Chloride ; Male ; Rats ; Rats, Wistar ; Sucrose ; *Taste Perception ; Time Factors ; }, abstract = {Mediated overshadowing occurs when an evoked representation of one stimulus interferes with the formation of an association between two other stimuli. This study tested whether such an effect can be found in long-delay taste aversion learning. The general methodology was to pair a cue with a sour taste (hydrochloric acid [HCl]) and then introduce the cue during the delay between the target taste, sucrose, and injection with lithium chloride (LiCl). Either 2 or 6 cue-HCl pairings were given. In Experiment 1, introduction of the cue, an almond flavor, produced overshadowing of the sucrose aversion in the group given 2 cue-HCl pairings (Paired-2), relative to an unpaired control, but potentiation of the sucrose aversion in the group given 6 cue-HCl pairings (Paired-6). This confirms that few pairings can be better than many in determining whether representation-mediated effects occur (Holland, 1990). A possible explanation for the Paired-6 results is that almond evoked an aversive response rather than memory of the sour HCl and that this added to the aversion produced by the sucrose-lithium pairing. Experiment 2 obtained similar results when a context was used as the cue intended to evoke an HCl representation.}, } @article {pmid26740565, year = {2016}, author = {Ward-Fear, G and Pearson, DJ and Brown, GP and Rangers, B and Shine, R}, title = {Ecological immunization: in situ training of free-ranging predatory lizards reduces their vulnerability to invasive toxic prey.}, journal = {Biology letters}, volume = {12}, number = {1}, pages = {20150863}, pmid = {26740565}, issn = {1744-957X}, mesh = {Animals ; Avoidance Learning ; *Bufo marinus ; Introduced Species ; Lizards/*physiology ; *Predatory Behavior ; Toxins, Biological/toxicity ; Western Australia ; }, abstract = {In Australia, large native predators are fatally poisoned when they ingest invasive cane toads (Rhinella marina). As a result, the spread of cane toads has caused catastrophic population declines in these predators. Immediately prior to the arrival of toads at a floodplain in the Kimberley region, we induced conditioned taste aversion in free-ranging varanid lizards (Varanus panoptes), by offering them small cane toads. By the end of the 18-month study, only one of 31 untrained lizards had survived longer than 110 days, compared to more than half (nine of 16) of trained lizards; the maximum known survival of a trained lizard in the presence of toads was 482 days. In situ aversion training (releasing small toads in advance of the main invasion front) offers a logistically simple and feasible way to buffer the impact of invasive toads on apex predators.}, } @article {pmid26731530, year = {2016}, author = {Kim, HJ and Koh, HY}, title = {Impaired Reality Testing in Mice Lacking Phospholipase Cβ1: Observed by Persistent Representation-Mediated Taste Aversion.}, journal = {PloS one}, volume = {11}, number = {1}, pages = {e0146376}, pmid = {26731530}, issn = {1932-6203}, mesh = {Animals ; Avoidance Learning/*physiology ; Disease Models, Animal ; Mice ; Mice, Knockout ; Phospholipase C beta/genetics/*metabolism ; *Reality Testing ; Schizophrenia/physiopathology ; Taste/*physiology ; Taste Perception/*physiology ; }, abstract = {Hallucinations and delusions are the most prominent symptoms of schizophrenia and characterized by impaired reality testing. Representation-mediated taste aversion (RMTA) has been proposed as a potential behavioral assessment of reality testing and has been applied to a neurodevelopmental rat model of schizophrenia. However, the theory underlying this approach has not been generalized yet with any demonstration of impaired reality testing in other animal models of schizophrenia, such as genetically-modified mice. We devised a RMTA procedure for mice that combines a Pavlovian association protocol pairing odor conditioned stimulus (CS) with sugar reward unconditioned stimulus (US), and a conditioned taste aversion (CTA) method. In this RMTA paradigm, we compared performances of wild-type (PLCβ1+/+) mice and phospholipase C β1 knock-out (PLCβ1-/-) mice which are known as one of the genetic models for schizophrenia. With a minimal amount of initial odor-sugar associative training, both PLCβ1+/+ and PLCβ1-/- mice were able to form an aversion to the sugar reward when the odor CS predicting sugar was paired with nausea. With an extended initial training, however, only PLCβ1-/- mice could form a RMTA. This persistent RMTA displayed by PLCβ1-/- mice shows their inability to distinguish real sugar from the CS-evoked representation of sugar at a stage in associative learning where wild-type mice normally could differentiate the two. These results demonstrate an impaired reality testing first observed in a genetic mouse model of schizophrenia, and suggest that RMTA paradigm may, with general applicability, allow diverse biological approaches to impaired reality testing.}, } @article {pmid26708104, year = {2016}, author = {Cocorocchio, M and Ives, R and Clapham, D and Andrews, PL and Williams, RS}, title = {Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays.}, journal = {ALTEX}, volume = {33}, number = {3}, pages = {225-236}, doi = {10.14573/altex.1509011}, pmid = {26708104}, issn = {1868-8551}, support = {NC/S01201/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; }, mesh = {Animal Testing Alternatives ; Animals ; Chemotaxis ; Dictyostelium/*drug effects/*physiology ; Humans ; Movement ; Rats ; *Taste ; Time ; }, abstract = {Treatment compliance is reduced when pharmaceutical compounds have a bitter taste and this is particularly marked for paediatric medications. Identification of bitter taste liability during drug discovery utilises the rat in vivo brief access taste aversion (BATA) test which apart from animal use is time consuming with limited throughput. We investigated the suitability of using a simple, non-animal model, the amoeba Dictyostelium discoideum to investigate taste-related responses and particularly identification of compounds with a bitter taste liability. The effect of taste-related compounds on Dictyostelium behaviour following acute exposure (15 minutes) was monitored. Dictyostelium did not respond to salty, sour, umami or sweet tasting compounds, however, cells rapidly responded to bitter tastants. Using time-lapse photography and computer-generated quantification to monitor changes in cell membrane movement, we developed an assay to assess the response of Dictyostelium to a wide range of structurally diverse known bitter compounds and blinded compounds. Dictyostelium showed varying responses to the bitter tastants, with IC50 values providing a rank order of potency. Comparison of Dictyostelium IC50 values to those observed in response to a similar range of compounds in the rat in vivo brief access taste aversion test showed a significant (p = 0.0172) positive correlation between the two models, and additionally a similar response to that provided by a human sensory panel assessment test. These experiments demonstrate that Dictyostelium may provide a suitable model for early prediction of bitterness for novel tastants and drugs. Interestingly, a response to bitter tastants appears conserved from single-celled amoebae to humans.}, } @article {pmid26651338, year = {2015}, author = {Xu, LH and Tang, GR and Yang, JJ and Liu, HX and Li, JC and Jiang, ZL}, title = {AVP modulation of the vestibular nucleus via V1b receptors potentially contributes to the development of motion sickness in rat.}, journal = {Molecular brain}, volume = {8}, number = {}, pages = {86}, pmid = {26651338}, issn = {1756-6606}, mesh = {Afferent Pathways/physiopathology ; Animals ; Antidiuretic Hormone Receptor Antagonists/therapeutic use ; Arginine Vasopressin/biosynthesis/genetics/*physiology/toxicity ; Axonal Transport ; Calcium Channels, L-Type/physiology ; Calcium Signaling ; Cells, Cultured ; Conditioning, Classical ; Disease Models, Animal ; Dysgeusia/chemically induced/physiopathology ; Female ; Indoles/pharmacology/therapeutic use ; Male ; Microinjections ; Motion Sickness/genetics/*physiopathology/prevention & control ; Nerve Endings/chemistry ; Paraventricular Hypothalamic Nucleus/metabolism/*physiopathology ; Polymorphism, Single Nucleotide ; Pyrrolidines/pharmacology/therapeutic use ; RNA, Messenger/biosynthesis/genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/physiology ; Receptors, Vasopressin/biosynthesis/genetics/*physiology ; Rotation ; Saccharin ; Synaptophysin/analysis ; Vestibular Nuclei/cytology/metabolism/*physiopathology ; }, abstract = {BACKGROUND: Arginine vasopressin (AVP) is considered to be an etiologic hormone in motion sickness (MS). The present study was designed to investigate whether individual differences in AVP expression in the paraventricular nucleus (PVN) and in modulation on the vestibular nucleus (VN) are involved in MS. Systemic application or microinjection of AVP into rat VN and rotatory stimulus were used to induce conditioned taste aversion (CTA) to 0.15 % saccharin sodium solution as a model of MS.

RESULTS: Intra-VN use of SSR149415, an antagonist of V1b receptors (V1bRs), blunted CTA. AVP inhibited Ca(2+) influxes through L-type Ca(2+) channels and NMDA receptor channels in cultured VN neurones, but antagonised by SSR149415. More AVP and V1bRs were expressed respectively in the PVN and VN after rotatory stimulus, especially in rats susceptible to MS. In the VN, AVP content was low, the AVP mRNA was less expressed, a few AVP-positive fibres were sparsely distributed, and fewer AVP/synaptophysin-positive terminals were identified. Almost no fluoro-ruby-labelled AVP-positive neurones in the PVN were found with retrograde tracing from the VN. SNP analysis of the reported 9 sites of the AVP gene showed significant difference between the groups susceptible and insusceptible to MS at the site rs105235842 in the allele frequencies and genotypes. However, there was not any difference between these two groups in the SNP of the reported 38 sites of V1bR gene.

CONCLUSIONS: AVP, through its modulatory, possibly humoral action on the VN neurones via the mediation of V1bR, may contribute to the development of motion sickness in rats; AVP gene polymorphisms may contribute to the individual difference in the responsive expression of AVP in the PVN; and higher expressions of AVP in the PVN and V1bRs in the VN may contribute to the development of motion sickness in rats after vestibular stimulation.}, } @article {pmid26650928, year = {2016}, author = {Daniel, C}, title = {Economic constraints on taste formation and the true cost of healthy eating.}, journal = {Social science & medicine (1982)}, volume = {148}, number = {}, pages = {34-41}, pmid = {26650928}, issn = {1873-5347}, support = {UL1 TR001102/TR/NCATS NIH HHS/United States ; 8UL1TR000170-05/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Boston ; Child ; Child, Preschool ; Choice Behavior ; Diet/*economics/*psychology ; *Feeding Behavior ; Female ; Food Preferences ; *Health Behavior ; Health Status Disparities ; Humans ; Male ; Middle Aged ; Parents/psychology ; Qualitative Research ; Socioeconomic Factors ; *Taste ; Young Adult ; }, abstract = {This article shows how an interaction between economic constraints and children's taste preferences shapes low-income families' food decisions. According to studies of eating behavior, children often refuse unfamiliar foods 8 to 15 times before accepting them. Using 80 interviews and 41 grocery-shopping observations with 73 primary caregivers in the Boston area in 2013-2015, I find that many low-income respondents minimize the risk of food waste by purchasing what their children like--often calorie-dense, nutrient-poor foods. High-income study participants, who have greater resources to withstand the cost of uneaten food, are more likely to repeatedly introduce foods that their children initially refuse. Several conditions moderate the relationship between children's taste aversion and respondents' risk aversion, including household-level food preferences, respondents' conceptions of adult authority, and children's experiences outside of the home. Low-income participants' risk aversion may affect children's taste acquisition and eating habits, with implications for socioeconomic disparities in diet quality. This article proposes that the cost of providing children a healthy diet may include the possible cost of foods that children waste as they acquire new tastes.}, } @article {pmid26615907, year = {2016}, author = {Itoga, CA and Berridge, KC and Aldridge, JW}, title = {Ventral pallidal coding of a learned taste aversion.}, journal = {Behavioural brain research}, volume = {300}, number = {}, pages = {175-183}, pmid = {26615907}, issn = {1872-7549}, support = {R01 MH063649/MH/NIMH NIH HHS/United States ; R01 DA015188/DA/NIDA NIH HHS/United States ; EY017878/EY/NEI NIH HHS/United States ; DA017752/DA/NIDA NIH HHS/United States ; T32 DA007281/DA/NIDA NIH HHS/United States ; R01 DA017752/DA/NIDA NIH HHS/United States ; DA007281/DA/NIDA NIH HHS/United States ; T32 NS076401/NS/NINDS NIH HHS/United States ; MH63649/MH/NIMH NIH HHS/United States ; T32 EY017878/EY/NEI NIH HHS/United States ; DA015188/DA/NIDA NIH HHS/United States ; }, mesh = {Action Potentials/physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Basal Forebrain/*physiology ; Catheters, Indwelling ; Conditioning, Classical/*physiology ; Dietary Sucrose/administration & dosage ; Electrodes, Implanted ; Glucans/administration & dosage ; Lithium Chloride ; Male ; Motor Activity ; Nausea ; Neurons/*physiology ; Rats, Sprague-Dawley ; Reward ; Saccharin/administration & dosage ; Taste Perception/*physiology ; }, abstract = {The hedonic value of a sweet food reward, or how much a taste is 'liked', has been suggested to be encoded by neuronal firing in the posterior ventral pallidum (VP). Hedonic impact can be altered by psychological manipulations, such as taste aversion conditioning, which can make an initially pleasant sweet taste become perceived as disgusting. Pairing nausea-inducing LiCl injection as a Pavlovian unconditioned stimulus (UCS) with a novel taste that is normally palatable as the predictive conditioned stimulus (CS+) suffices to induce a learned taste aversion that changes orofacial 'liking' responses to that sweet taste (e.g., lateral tongue protrusions) to 'disgust' reactions (e.g., gapes) in rats. We used two different sweet tastes of similar initial palatability (a sucrose solution and a polycose/saccharin solution, CS ± assignment was counterbalanced across groups) to produce a discriminative conditioned aversion. Only one of those tastes (arbitrarily assigned and designated as CS+) was associatively paired with LiCl injections as UCS to form a conditioned aversion. The other taste (CS-) was paired with mere vehicle injections to remain relatively palatable as a control sweet taste. We recorded the neural activity in VP in response to each taste, before and after aversion training. We found that the safe and positively hedonic taste always elicited excitatory increases in firing rate of VP neurons. By contrast, aversion learning reversed the VP response to the 'disgusting' CS+ taste from initial excitation into a conditioned decrease in neuronal firing rate after training. Such neuronal coding of hedonic impact by VP circuitry may contribute both to normal pleasure and disgust, and disruptions of VP coding could result in affective disorders, addictions and eating disorders.}, } @article {pmid26599914, year = {2015}, author = {Bales, MB and Schier, LA and Blonde, GD and Spector, AC}, title = {Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0143419}, pmid = {26599914}, issn = {1932-6203}, support = {R01 DC009821/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Anatomic Landmarks ; Anatomy, Artistic ; Animals ; Atlases as Topic ; Behavior, Animal ; Cerebral Cortex/drug effects/*pathology/surgery ; Conditioning, Classical ; Male ; Potassium Chloride/*pharmacology ; Quinine/*pharmacology ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Sucrose/*pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Recently, we reported that large bilateral gustatory cortex (GC) lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX) and in sham-operated controls (SHAM). Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p.), but postsurgical tests indicated a weak conditioned taste aversion (CTA) even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average). For KCl, there was a significant rightward shift (ΔEC50 = 0.57 log10 units; p<0.001) in the GCX psychometric function relative to SHAM, replicating our prior work. There was also a significant lesion-induced impairment (ΔEC50 = 0.41 log10 units; p = 0.006) in quinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and/or perceptual features of the stimulus.}, } @article {pmid26524511, year = {2016}, author = {Rebecca Glatt, A and St John, SJ and Lu, L and Boughter, JD}, title = {Temporal and qualitative dynamics of conditioned taste aversions in C57BL/6J and DBA/2J mice self-administering LiCl.}, journal = {Physiology & behavior}, volume = {153}, number = {}, pages = {97-108}, doi = {10.1016/j.physbeh.2015.10.033}, pmid = {26524511}, issn = {1873-507X}, support = {DC000353/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Drinking Behavior/*drug effects/physiology ; Extinction, Psychological ; Female ; Generalization, Psychological ; Lithium Chloride/*administration & dosage/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Self Administration ; Sodium Chloride/pharmacology ; Taste/*drug effects/physiology ; Time Factors ; }, abstract = {Self-administration of LiCl solution has been shown to result in the formation of a conditioned taste aversion (CTA) that generalizes to NaCl in rats. This paradigm may have considerable ecological validity as it models CTA learning in natural settings, and also allows for the investigation of drinking microstructure as an assay of potential shifts in stimulus palatability. We used this paradigm to examine possible mouse strain differences in CTA acquisition, generalization, and extinction. In the first experiment, C57BL/6J (B6) and DBA/2J (D2) mice self-administered LiCl (or control NaCl) over a 20-minute free access acquisition period and were tested on the following day with a panel of taste solutions available in brief (5-s) trials delivered in random order. In the second experiment, mice again self-administered LiCl or NaCl (at low, 0.12 M, or high, 0.24 M concentrations) in a 20-minute session, and on the following day received a 20-minute free access period to equimolar NaCl. Strain differences were found for aspects of ingestive behavior, with B6 mice showing greater consumption of all stimuli, including water, while D2 mice lick faster, in less frequent but longer bursts. We did not, however, find evidence of a robust strain difference in taste aversion learning. Both strains demonstrated profound alterations in licking microstructure in the generalization session relative to controls. We suggest that a decrease in "lick efficiency" (the percentage of inter-lick intervals within a burst of short duration vs. longer duration) reflects avoidance behavior, and signals a shift in palatability of a stimulus following CTA.}, } @article {pmid26524411, year = {2015}, author = {Jahng, JW and Lee, JH}, title = {Activation of the hypothalamic-pituitary-adrenal axis in lithium-induced conditioned taste aversion learning.}, journal = {European journal of pharmacology}, volume = {768}, number = {}, pages = {182-188}, doi = {10.1016/j.ejphar.2015.10.052}, pmid = {26524411}, issn = {1879-0712}, mesh = {Adrenal Glands/*drug effects/metabolism/physiology ; Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects ; Hypothalamo-Hypophyseal System/*drug effects/metabolism/physiology ; Lithium/*pharmacology ; Taste/*physiology ; }, abstract = {Intraperitoneal injections (ip) of lithium chloride at large doses induce c-Fos expression in the brain regions implicated in conditioned taste aversion (CTA) learning, and also activate the hypothalamic-pituitary-adrenal (HPA) axis and increase the plasma corticosterone levels in rats. A pharmacologic treatment blunting the lithium-induced c-Fos expression in the brain regions, but not the HPA axis activation, induced CTA formation. Synthetic glucocorticoids at conditioning, but not glucocorticoid antagonist, attenuated the lithium-induced CTA acquisition. The CTA acquisition by ip lithium was not affected by adrenalectomy regardless of basal corticosterone supplement, but the extinction was delayed in the absence of basal corticosterone. Glucocorticoids overloading delayed the extinction memory formation of lithium-induced CTA. ip lithium consistently induced the brain c-Fos expression, the HPA activation and CTA formation regardless of the circadian activation of the HPA axis. Intracerebroventricular (icv) injections of lithium at day time also increased the brain c-Fos expression, activated the HPA axis and induced CTA acquisition. However, icv lithium at night, when the HPA axis shows its circadian activation, did not induce CTA acquisition nor activate the HPA axis, although it increased the brain c-Fos expression. These results suggest that the circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA learning in rats, and the HPA axis activation may be necessary for the central effect of lithium in CTA formation. Also, glucocorticoids may be required for a better extinction; however, increased glucocorticoids hinder both the acquisition and the extinction of lithium-induced CTA.}, } @article {pmid26497913, year = {2015}, author = {Lemay, F and Doré, FY and Beaulieu, JM}, title = {Increased ethanol consumption despite taste aversion in mice with a human tryptophan hydroxylase 2 loss of function mutation.}, journal = {Neuroscience letters}, volume = {609}, number = {}, pages = {194-197}, doi = {10.1016/j.neulet.2015.10.045}, pmid = {26497913}, issn = {1872-7972}, mesh = {Alcohol Drinking/genetics/*psychology ; Animals ; Avoidance Learning ; Ethanol/administration & dosage ; Humans ; Mice, Mutant Strains ; Motivation ; Mutation ; Self Administration ; *Taste ; Tryptophan ; Tryptophan Hydroxylase/*genetics ; }, abstract = {Polymorphisms in the gene encoding the brain serotonin synthesis enzyme Tph2 have been identified in mental illnesses, with co-morbidity of substance use disorder. However, little is known about the impact of Tph2 gene variants on addiction. Mice expressing a human Tph2 loss of function variant were used to investigate consequences of aversive conditions on ethanol intake. Mice were familiarized either with ethanol or a solution containing both ethanol and the bittering agent quinine. Effect of familiarization to ethanol or an ethanol-quinine solution was then evaluated using a two-bottles preference test in Tph2-KI and control littermates. Mice from both genotypes displayed similar levels of ethanol consumption and quinine avoidance when habituated to ethanol alone. In contrast, addition of quinine to ethanol during the familiarization period resulted in a reduction of avoidance for the quinine-ethanol solution only in mutant mice. These results indicate that loss of function mutation in Tph2 results in greater motivation for ethanol consumption under aversive conditions and may confer enhanced sensitivity to alcohol use disorder.}, } @article {pmid26496996, year = {2016}, author = {Aranda-Fernandez, PE and Gaztañaga, M and Arias, C and Chotro, MG}, title = {Conditioned inhibition in preweanling rats.}, journal = {Developmental psychobiology}, volume = {58}, number = {1}, pages = {98-106}, doi = {10.1002/dev.21359}, pmid = {26496996}, issn = {1098-2302}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Extinction, Psychological/drug effects/physiology ; Female ; Male ; *Odorants ; Rats ; Rats, Sprague-Dawley ; Saccharin/*pharmacology ; Taste/drug effects/physiology ; }, abstract = {Inhibitory conditioning is a very well established phenomenon in associative learning that has been demonstrated in both humans and adult animals. But in spite of the fact that this topic has generated much empirical and theoretical work, there are no published studies assessing inhibitory learning during the early ontogeny of the rat. In this study we test the possibility of finding conditioned inhibition in infant rats (Day 10) using a conditioned taste aversion procedure. We tested whether the consumption of saccharin (A) was reduced when paired with a LiCl injection compared to the presentation of saccharin in compound with a lemon odor (AX) without any aversive consequence. After training, retardation, and summation tests were conducted in order to evaluate the inhibitory properties of the lemon odor (X). The results of this study showed that in male pups, after conditioned inhibition training, stimulus X passed both retardation and summation tests. These results indicate that conditioned inhibition can be established in the early development of the rat, suggesting that animals at this stage of ontogeny have the capacity to acquire and to express inhibitory conditioning, although this effect appears to be sex-dependent.}, } @article {pmid26493441, year = {2015}, author = {Gonzalez, MC and Villar, ME and Igaz, LM and Viola, H and Medina, JH}, title = {Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.}, journal = {Neurobiology of learning and memory}, volume = {126}, number = {}, pages = {1-6}, doi = {10.1016/j.nlm.2015.10.007}, pmid = {26493441}, issn = {1095-9564}, mesh = {Animals ; Benzylamines/administration & dosage ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology ; Conditioning, Psychological/drug effects/physiology ; Emetine/administration & dosage ; GABA-A Receptor Agonists/administration & dosage ; Male ; Memory Consolidation/drug effects/*physiology ; Mental Recall/drug effects/*physiology ; Muscimol/administration & dosage ; Prefrontal Cortex/drug effects/metabolism/*physiology ; Protein Synthesis Inhibitors/administration & dosage ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/physiology ; Signal Transduction/drug effects ; Sulfonamides/administration & dosage ; Taste Perception/drug effects/*physiology ; Valine/administration & dosage/analogs & derivatives ; }, abstract = {The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions.}, } @article {pmid26462569, year = {2016}, author = {Valenza, M and DiLeo, A and Steardo, L and Cottone, P and Sabino, V}, title = {Ethanol-related behaviors in mice lacking the sigma-1 receptor.}, journal = {Behavioural brain research}, volume = {297}, number = {}, pages = {196-203}, pmid = {26462569}, issn = {1872-7549}, support = {R01 DA030425/DA/NIDA NIH HHS/United States ; DA023680/DA/NIDA NIH HHS/United States ; R00 DA023680/DA/NIDA NIH HHS/United States ; K99 AA016731/AA/NIAAA NIH HHS/United States ; AA016731/AA/NIAAA NIH HHS/United States ; R01 MH091945/MH/NIMH NIH HHS/United States ; R00 AA016731/AA/NIAAA NIH HHS/United States ; DA030425/DA/NIDA NIH HHS/United States ; MH093650/MH/NIMH NIH HHS/United States ; MH091945/MH/NIMH NIH HHS/United States ; K99 DA023680/DA/NIDA NIH HHS/United States ; R01 MH093650/MH/NIMH NIH HHS/United States ; }, mesh = {Alcohol Drinking/*metabolism ; Alcohol-Related Disorders/*metabolism ; Animals ; Ataxia/chemically induced/metabolism ; Avoidance Learning/drug effects/physiology ; Body Temperature/drug effects/physiology ; Central Nervous System Depressants/*pharmacology ; Choice Behavior/drug effects/physiology ; Disease Models, Animal ; Ethanol/*pharmacology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects/physiology ; Receptors, sigma/genetics/*metabolism ; Taste/drug effects/physiology ; Taste Perception/drug effects/physiology ; }, abstract = {RATIONALE: The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents.

OBJECTIVES: The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors.

METHODS: We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed.

RESULTS: Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants.

CONCLUSIONS: Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol.}, } @article {pmid26454025, year = {2015}, author = {Vishnoi, S and Raisuddin, S and Parvez, S}, title = {Modulatory effects of an NMDAR partial agonist in MK-801-induced memory impairment.}, journal = {Neuroscience}, volume = {311}, number = {}, pages = {22-33}, doi = {10.1016/j.neuroscience.2015.10.008}, pmid = {26454025}, issn = {1873-7544}, mesh = {Acetylcholinesterase/metabolism ; Animals ; Avoidance Learning/drug effects/physiology ; Conditioning, Psychological/drug effects/physiology ; Cycloserine/*pharmacology ; Disease Models, Animal ; Dizocilpine Maleate ; Dopamine/metabolism ; Exploratory Behavior/drug effects/physiology ; Female ; Memory Disorders/*drug therapy/metabolism ; Monoamine Oxidase/metabolism ; Nootropic Agents/*pharmacology ; Prefrontal Cortex/drug effects/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*agonists/metabolism ; Recognition, Psychology/drug effects/physiology ; Taste Perception/drug effects/physiology ; }, abstract = {RATIONALE: Acute administration of the N-methyl-d-aspartate (NMDA) non-competitive antagonist, MK-801, impairs novel object recognition (NOR), locomotor activity in open field (OF) and conditioned taste aversion (CTA) in rodents. NMDAR partial agonist d-cycloserine (DCS) reverses these effects in NOR and CTA via modulation of glutamatergic, cholinergic and dopaminergic systems.

OBJECTIVES AND METHODS: To test this hypothesis, we investigated the effects of DCS, a partial NMDAR agonist, on NOR memory, locomotor activity, and CTA memory in Wistar rats on NMDA-glutamate receptor antagonism by MK-801. The potential involvement of dopaminergic and cholinergic systems in improving cognitive functions was explored. MK-801-induced cognitive deficits were assessed using NOR, OF and CTA paradigms. MK-801-induced dopamine release increase in acetylcholinesterase (AChE), mono amine oxidase (MAO) activity and increase in c-fos expression were also investigated.

RESULTS: The effects caused by MK-801 (0.2 mg/kg) were inhibited by administration of the NMDA receptor agonist DCS (15 mg/kg). NOR and CTA paradigms inhibited by MK-801 were attenuated by DCS administration. Moreover, DCS also blocked the MK-801-induced abnormal increase in dopamine content, AChE activity and MAO activity. However, c-fos overexpression was controlled to some extent only.

CONCLUSIONS: Based on the NMDAR hypo function hypothesis in some neuropsychiatric disorders, our finding suggests that improving NMDAR hypo function by agonist DCS may play a significant role.}, } @article {pmid26452094, year = {2015}, author = {Adaikkan, C and Rosenblum, K}, title = {A molecular mechanism underlying gustatory memory trace for an association in the insular cortex.}, journal = {eLife}, volume = {4}, number = {}, pages = {e07582}, pmid = {26452094}, issn = {2050-084X}, mesh = {Animals ; *Avoidance Learning ; Cerebral Cortex/*physiology ; Conditioning, Classical ; *Memory ; Rats ; *Taste ; }, abstract = {Events separated in time are associatively learned in trace conditioning, recruiting more neuronal circuits and molecular mechanisms than in delay conditioning. However, it remains unknown whether a given sensory memory trace is being maintained as a unitary item to associate. Here, we used conditioned taste aversion learning in the rat model, wherein animals associate a novel taste with visceral nausea, and demonstrate that there are two parallel memory traces of a novel taste: a short-duration robust trace, lasting approximately 3 hr, and a parallel long-duration weak one, lasting up to 8 hr, and dependent on the strong trace for its formation. Moreover, only the early robust trace is maintained by a NMDAR-dependent CaMKII- AMPAR pathway in the insular cortex. These findings suggest that a memory trace undergoes rapid modifications, and that the mechanisms underlying trace associative learning differ when items in the memory are experienced at different time points.}, } @article {pmid26433146, year = {2016}, author = {Martínez-Moreno, A and Rodríguez-Durán, LF and Escobar, ML}, title = {Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.}, journal = {Behavioural brain research}, volume = {297}, number = {}, pages = {1-4}, doi = {10.1016/j.bbr.2015.09.034}, pmid = {26433146}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Brain-Derived Neurotrophic Factor/*pharmacology ; Catheters, Indwelling ; Conditioning, Psychological/drug effects/physiology ; Lithium Chloride ; Male ; Memory/*drug effects/physiology ; Microinjections ; Neocortex/*drug effects/physiology ; Nootropic Agents/*pharmacology ; Rats, Wistar ; Taste Perception/*drug effects/physiology ; Water Deprivation ; }, abstract = {Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace.}, } @article {pmid26403065, year = {2015}, author = {Bernal-Gamboa, R and Nieto, J and Rosas, JM}, title = {Context specificity of taste aversion is boosted by pre-exposure and conditioning with a different taste.}, journal = {Behavioural processes}, volume = {120}, number = {}, pages = {111-115}, doi = {10.1016/j.beproc.2015.09.008}, pmid = {26403065}, issn = {1872-8308}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Cues ; Extinction, Psychological ; Male ; Rats ; Rats, Wistar ; Sodium Chloride/*pharmacology ; Sucrose/*pharmacology ; Taste/*physiology ; Taste Perception/physiology ; }, abstract = {Recent reports in the literature show that an extinction treatment makes subsequently learned information context-specific. An experiment in conditioned taste aversion evaluated whether pre-exposure and conditioning with a given flavor would make conditioning of a different flavor context specific as well. Rats received conditioning with taste Y in context A, before being tested in extinction either in context A or in a different but equally familiar context (context B). Half of the animals received a pre-exposure and conditioning treatment with a different flavor (X), while the other half only received conditioning. The context change at testing led to higher consumption of Y in the animals that had received previous pre-exposure and conditioning with X. The implications of these results for the mechanisms underlying context-switch effects are discussed.}, } @article {pmid26393333, year = {2015}, author = {Wang, S and Zhuang, L and Yang, X and Li, Q and Xue, Q and Luo, Y and Zhang, F and Yu, B}, title = {Impaired acquisition of conditioned taste aversion memory induced by isoflurane is accompanied with calcineurin activation and Egr-1 down-regulation in amygdala in rats.}, journal = {Neuroscience letters}, volume = {607}, number = {}, pages = {114-119}, doi = {10.1016/j.neulet.2015.09.022}, pmid = {26393333}, issn = {1872-7972}, mesh = {Amygdala/*drug effects/metabolism ; Anesthetics, Inhalation/*adverse effects ; Animals ; Avoidance Learning/*drug effects ; Calcineurin/*metabolism ; Conditioning, Psychological ; Down-Regulation ; Early Growth Response Protein 1/*metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Isoflurane/*adverse effects ; Male ; Memory/*drug effects ; Phosphorylation ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Compared to neutral memory, emotional memory is extremely strong and persistent immediately after acquisition, therefore it may recruit specific mechanisms during acquisition. The calcineurin-dependent mechanisms engaging early growth response 1 (Egr-1) have been proved to determine the strength of emotional memory during establishment. Isoflurane, a widely used inhalation anesthetic, can interfere with the acquisition of emotional memory. We hypothesized that isoflurane impairs the acquisition of conditioned taste aversion (CTA) memory in rats and the Egr-1 expression regulation via calcineurin (CaN) and ERK signaling pathway is involved in isoflurane-induced repression of CTA memory. To examine this, we investigated the influence of isoflurane on CTA memory and the expression and activity of CaN, the phosphorylation level of ERK and the expression of Egr-1 in amygdala in response to CTA training in rats. The results showed that isoflurane exposure (1.5%, 2h) before training impaired the acquisition of CTA memory in rats. Isoflurane exposure increased the CaN activity and decreased the p-ERK and Egr-1 in amygdala in rats. These findings suggest that isoflurane can disrupt the establishment of aversion memory, and CaN activation associating with p-ERK and Egr-1 down-regulation may contribute to the isoflurane induced impairment of aversion memory acquisition.}, } @article {pmid26386321, year = {2016}, author = {Hadamitzky, M and Bösche, K and Wirth, T and Buck, B and Beetz, O and Christians, U and Schniedewind, B and Lückemann, L and Güntürkün, O and Engler, H and Schedlowski, M}, title = {Memory-updating abrogates extinction of learned immunosuppression.}, journal = {Brain, behavior, and immunity}, volume = {52}, number = {}, pages = {40-48}, doi = {10.1016/j.bbi.2015.09.009}, pmid = {26386321}, issn = {1090-2139}, mesh = {Amygdala/immunology/physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/physiology ; Cyclosporine/pharmacology ; Extinction, Psychological/drug effects/*physiology ; Fear/physiology ; Immune Tolerance/physiology ; Immunosuppressive Agents/pharmacology ; Interferon-gamma/immunology ; Interleukin-2/immunology ; Male ; Mental Recall/drug effects/*physiology ; Rats ; Rats, Inbred Strains ; Taste/physiology ; }, abstract = {When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats memory-updating in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning.}, } @article {pmid26374758, year = {2016}, author = {Pennell, CG and Popay, AJ and Rolston, MP and Townsend, RJ and Lloyd-West, CM and Card, SD}, title = {Avanex Unique Endophyte Technology: Reduced Insect Food Source at Airports.}, journal = {Environmental entomology}, volume = {45}, number = {1}, pages = {101-108}, doi = {10.1093/ee/nvv145}, pmid = {26374758}, issn = {1938-2936}, mesh = {Airports ; Animals ; *Endophytes ; Epichloe/*physiology ; Insecta/*microbiology ; New Zealand ; *Pest Control, Biological ; Poaceae/*microbiology ; }, abstract = {Birds and other forms of wildlife are a major issue for airport authorities worldwide, as they can create hazards to operating aircraft. Wildlife "strikes," the majority caused by birds, can cause damage to operating aircraft and in severe cases lead to a loss of human life. Many airfields contain large areas of ground cover herbage alongside their runways that consist of mixtures of grasses, legumes, and weeds that can harbor many invertebrates. Many airfields use insecticides to control insect populations; however, mounting pressure from regional councils and water boards aim to reduce this practice due to ground water runoff and contamination concerns. Avanex Unique Endophyte Technology, a product specifically developed to reduce the attractiveness of airports and surrounding areas to birds, is based on a novel association between a selected strain of Epichloë endophyte and a turf-type tall fescue cultivar. This grass-endophyte association acts through a direct mechanism whereby a negative response in birds is created through taste aversion and postingestion feedback as well as an indirect mechanism by deterring many invertebrates, a food source of many bird species.}, } @article {pmid26365026, year = {2016}, author = {Lueckemann, L and Bösche, K and Engler, H and Schwitalla, JC and Hadamitzky, M and Schedlowski, M}, title = {Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats.}, journal = {Brain, behavior, and immunity}, volume = {51}, number = {}, pages = {252-257}, doi = {10.1016/j.bbi.2015.09.005}, pmid = {26365026}, issn = {1090-2139}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/*drug effects ; Cyclosporine/*administration & dosage ; *Immunosuppression Therapy ; Immunosuppressive Agents/*administration & dosage ; Male ; Rats ; Taste/physiology ; }, abstract = {In order to analyze the effects of pre-exposure to either the unconditioned (US) or conditioned stimulus (CS) on learned immunosuppression, we employed an established conditioned taste aversion (CTA) paradigm in rats. In our model, a sweet-tasting drinking solution (saccharin) serves as CS and injection of the immunosuppressive drug cyclosporine A (CsA) is used as US. The conditioned response is reflected by a pronounced CTA and diminished cytokine production by anti-CD3 stimulated splenic T cells. In the present study, experimental animals were exposed either to the US or the CS three times prior to the acquisition phase. On the behavioral level, we found a significantly diminished CTA when animals were pre-exposed to the US or the CS before acquisition. In contrast, US or CS pre-exposure did not affect the behaviorally conditioned suppression of interleukin (IL)-2 production. From the clinical perspective, our data may suggest that conditioning paradigms could be systemically integrated as supportive therapeutic interventions in patients that are already on immunosuppressive therapy or have had previous contact to the gustatory stimulus. Such supportive therapies to pharmacological regimens could not only help to reduce the amount of medication needed and, thus, unwanted toxic side effects, but may also maximize the therapeutic outcome.}, } @article {pmid26302696, year = {2016}, author = {Braquet, P and Mercier, G and Reynes, J and Jeandel, C and Pinzani, V and Guilpain, P and Rivière, S and Le Quellec, A}, title = {[Diagnostic value of selective anorexia in pathological weight loss].}, journal = {La Revue de medecine interne}, volume = {37}, number = {2}, pages = {84-90}, doi = {10.1016/j.revmed.2015.07.007}, pmid = {26302696}, issn = {1768-3122}, mesh = {Aged ; Aged, 80 and over ; Anorexia/classification/*etiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Surveys and Questionnaires ; *Symptom Assessment ; *Taste ; *Weight Loss ; }, abstract = {PURPOSE: The diagnostic value of selective anorexia is debated. Some authors have suggested an association between meat aversion and cancer, but most do not use it as a diagnostic tool. We aimed to characterize anorexia of different diseases to search for an association between selective aversions and diagnostic groups.

METHODS: All the patients admitted to three departments of a teaching hospital were included consecutively for 22months if they had more than 10 % weight loss in less than one year. Patients were excluded if history taking was not reliable, or if they suffered from anorexia nervosa. We compiled diagnoses at discharge and validated them six months later. We used logistic regression to identify independent factors associated with selective anorexia.

RESULTS: Inclusion criteria were met in 106patients (female 44 %, median age 65years). Most frequent diagnoses were: cancer (36 %), infection (35 %), digestive diseases (19 %), non organic diseases (21 %). Recent selective anorexia was found in 46 % of the cases. It was significantly associated with female gender (P=0.002), marginally with young age (P=0.069) and long duration of weight loss (P=0.079). Opioid use at admission was negatively associated with selective anorexia (P=0.001). No specific diagnostic category was found to be associated.

CONCLUSION: Selective anorexia does not appear to be a useful symptom to investigate pathological weight loss. It behaves more like a non-specific reactivation by current disease of earlier latent personal food aversions.}, } @article {pmid26298172, year = {2015}, author = {Lin, SF and Tsai, YF and Tai, MY and Yeh, KY}, title = {Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats.}, journal = {Die Naturwissenschaften}, volume = {102}, number = {9-10}, pages = {52}, pmid = {26298172}, issn = {1432-1904}, mesh = {Animals ; Drug Combinations ; Estradiol/*analogs & derivatives/pharmacology ; Estrogens/pharmacology ; Lithium Chloride/*toxicity ; Male ; Orchiectomy ; Progesterone/*pharmacology ; Random Allocation ; Rats ; Taste/*drug effects ; }, abstract = {The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.}, } @article {pmid26291688, year = {2015}, author = {Molero-Chamizo, A and Morón, I}, title = {Latent inhibition of conditioned taste aversion in rats with excitotoxic dorsal hippocampal lesions.}, journal = {Journal of neuroscience research}, volume = {93}, number = {11}, pages = {1740-1747}, doi = {10.1002/jnr.23633}, pmid = {26291688}, issn = {1097-4547}, mesh = {Animals ; Association Learning/*physiology ; Conditioning, Classical ; Disease Models, Animal ; Hippocampus/*injuries/*physiopathology ; Male ; Neural Inhibition/*physiology ; Rats ; Rats, Wistar ; Taste ; }, abstract = {The hippocampus plays crucial roles for the acquisition of latent inhibition in different associative learning procedures, such as fear conditioning. However, the involvement of the hippocampus in the latent inhibition of conditioned taste aversion (CTA) is uncertain. Because different subregions of the hippocampus are associated with distinct functions, it is possible that specific regions of this structure are selectively involved in this learning. To explore the relationship between the dorsal hippocampal region and the latent inhibition of CTA, we analyzed the behavioral effects of excitotoxic lesions of the dorsal hippocampus vs. sham lesions in this paradigm. The results provide no evidence that the latent inhibition of CTA is compromised in rats with excitotoxic dorsal hippocampal lesions. The differential involvement of specific hippocampal regions in the latent inhibition of other associative learning paradigms is briefly discussed.}, } @article {pmid26290239, year = {2015}, author = {Gisquet-Verrier, P and Lynch, JF and Cutolo, P and Toledano, D and Ulmen, A and Jasnow, AM and Riccio, DC}, title = {Integration of New Information with Active Memory Accounts for Retrograde Amnesia: A Challenge to the Consolidation/Reconsolidation Hypothesis?.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {35}, number = {33}, pages = {11623-11633}, pmid = {26290239}, issn = {1529-2401}, mesh = {Amnesia, Retrograde/*physiopathology ; Animals ; Brain/*physiopathology ; *Cognition ; Male ; *Memory ; Nerve Tissue Proteins/*metabolism ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; *Retention, Psychology ; }, abstract = {UNLABELLED: Active (new and reactivated) memories are considered to be labile and sensitive to treatments disrupting the time-dependent consolidation/reconsolidation processes required for their stabilization. Active memories also allow the integration of new information for updating memories. Here, we investigate the possibility that, when active, the internal state provided by amnesic treatments is represented and integrated within the initial memory and that amnesia results from the absence of this state at testing. We showed in rats that the amnesia resulting from systemic, intracerebroventricular and intrahippocampal injections of the protein synthesis inhibitor cycloheximide, administered after inhibitory avoidance training or reactivation, can be reversed by a reminder, including re-administration of the same drug. Similar results were obtained with lithium chloride (LiCl), which does not affect protein synthesis, when delivered systemically after training or reactivation. However, LiCl can induce memory given that a conditioned taste aversion was obtained for a novel taste, presented just before conditioning or reactivation. These results indicate that memories can be established and maintained without de novo protein synthesis and that experimental amnesia may not result from a disruption of memory consolidation/reconsolidation. The findings more likely support the integration hypothesis: posttraining/postreactivation treatments induce an internal state, which becomes encoded with the memory, and should be present at the time of testing to ensure a successful retrieval. This integration concept includes most of the previous explanations of memory recovery after retrograde amnesia and critically challenges the traditional memory consolidation/reconsolidation hypothesis, providing a more dynamic and flexible view of memory.

SIGNIFICANCE STATEMENT: This study provides evidence challenging the traditional consolidation/reconsolidation hypotheses that have dominated the literature over the past 50 years. Based on amnesia studies, that hypothesis states that active (i.e., new and reactivated) memories are similarly labile and (re)established in a time-dependent manner within the brain through processes that require de novo protein synthesis. Our data show that new/reactivated memories can be formed without protein synthesis and that amnesia can be induced by drugs that do not affect protein synthesis. We propose that amnesia results from memory integration of the internal state produced by the drug that is subsequently necessary for retrieval of the memory. This interpretation gives a dynamic view of memory, rapidly stored and easily updated when active.}, } @article {pmid26253212, year = {2015}, author = {Bortolatto, CF and Heck, SO and Zborowski, VA and Gai, BM and Neto, JS and Nogueira, CW}, title = {Evidence for the contribution of multiple mechanisms in the feeding pattern of rats exposed to p-chloro-diphenyl diselenide-supplemented diets.}, journal = {Physiology & behavior}, volume = {151}, number = {}, pages = {298-307}, doi = {10.1016/j.physbeh.2015.07.029}, pmid = {26253212}, issn = {1873-507X}, mesh = {Adipose Tissue ; Animals ; Avoidance Learning ; Body Weight ; Choice Behavior ; Conditioning, Psychological ; *Diet ; *Dietary Supplements ; *Feeding Behavior/physiology ; Male ; Motor Activity ; Organoselenium Compounds/*administration & dosage ; Rats, Wistar ; Satiation/physiology ; Taste Perception ; Time Factors ; }, abstract = {Preliminary findings suggest that food intake reduction induced by p-chloro-diphenyl diselenide [(p-ClPhSe)2] in rats is mediated by a satiating action; however, additional experiments are necessary to clarify its actions. The purpose of this study was to investigate the effects of diets supplemented with (p-ClPhSe)2 on feeding behavior of rats as well as the (p-ClPhSe)2 effectiveness in producing aversive reactions or specific flavor. The results demonstrated that behavioral satiety sequence (BSS) was preserved in animals exposed to (p-ClPhSe)2-supplemented diets (0.01 and 0.1%) and associated with a shift of the onset of resting to the left indicating a satiating action at the first contact. In addition, the frequency, the mean duration and the mean size of meals were decreased in rats exposed to a 0.1% (p-ClPhSe)2 diet. Alternatively, a second contact with a 0.01% (p-ClPhSe)2 diet caused disruption of BSS and pronounced changes in the meal pattern, suggesting that it produces aversiveness. In fact, rats developed a significant taste aversion to the saccharin solution after receiving the administration of (p-ClPhSe)2 (1 and 10mg/kg; i.p.). Lastly, a diet containing 0.1% of (p-ClPhSe)2 seems to alter the palatability of food given that rats had a preference for the control diet. The findings of the present study suggest that (p-ClPhSe)2 reduced the food intake of rats by inducing a satiating action at the first contact, but it also produced aversive reactions when rats were re-exposed to it. A specific flavor seems also to contribute to (p-ClPhSe)2 suppressant effects on feeding.}, } @article {pmid26233474, year = {2015}, author = {Kojima, S and Sunada, H and Mita, K and Sakakibara, M and Lukowiak, K and Ito, E}, title = {Function of insulin in snail brain in associative learning.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {201}, number = {10}, pages = {969-981}, pmid = {26233474}, issn = {1432-1351}, support = {MOP 64339//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Association Learning/*physiology ; Brain/*metabolism ; Insulins/*metabolism ; Snails/*physiology ; }, abstract = {Insulin is well known as a hormone regulating glucose homeostasis across phyla. Although there are insulin-independent mechanisms for glucose uptake in the mammalian brain, which had contributed to a perception of the brain as an insulin-insensitive organ for decades, the finding of insulin and its receptors in the brain revolutionized the concept of insulin signaling in the brain. However, insulin's role in brain functions, such as cognition, attention, and memory, remains unknown. Studies using invertebrates with their open blood-vascular system have the promise of promoting a better understanding of the role played by insulin in mediating/modulating cognitive functions. In this review, the relationship between insulin and its impact on long-term memory (LTM) is discussed particularly in snails. The pond snail Lymnaea stagnalis has the ability to undergo conditioned taste aversion (CTA), that is, it associatively learns and forms LTM not to respond with a feeding response to a food that normally elicits a robust feeding response. We show that molluscan insulin-related peptides are up-regulated in snails exhibiting CTA-LTM and play a key role in the causal neural basis of CTA-LTM. We also survey the relevant literature of the roles played by insulin in learning and memory in other phyla.}, } @article {pmid26192710, year = {2015}, author = {Huang, AC and Wang, CC and Wang, S}, title = {Examinations of the reward comparison hypothesis: The modulation of gender and footshock.}, journal = {Physiology & behavior}, volume = {151}, number = {}, pages = {129-138}, doi = {10.1016/j.physbeh.2015.07.022}, pmid = {26192710}, issn = {1873-507X}, mesh = {Animals ; Central Nervous System Stimulants/pharmacology ; Conditioning, Psychological/*drug effects/physiology ; *Electroshock ; Female ; Foot ; Illicit Drugs/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Methamphetamine/pharmacology ; *Models, Psychological ; Morphine/pharmacology ; Motor Activity/drug effects/physiology ; Narcotics/pharmacology ; Psychotropic Drugs/pharmacology ; Random Allocation ; Rats, Wistar ; *Reward ; Saccharin ; *Sex Characteristics ; }, abstract = {The reward comparison hypothesis suggests that drugs of abuse-induced conditioned saccharin suppression intake is due to the reward value of drugs of abuse that outweighs that of a saccharin solution dissociating from the aversive LiCl-induced conditioned taste aversion (CTA). Huang and Hsiao (2008) provided some conflict data to challenge the reward comparison hypothesis. Whether the rewarding drugs of abuse-induced conditioned suppression and the aversive LiCl-induced CTA resulted from aversion or reward should be addressed. The present study investigated how gender and footshock affect aversive LiCl- and rewarding morphine- and methamphetamine (MAMPH)-induced conditioned suppression to re-examine the reward comparison hypothesis. The results indicated that gender and footshock did not directly influence the aversive LiCl-induced CTA or rewarding morphine- and MAMPH-induced conditioned suppression. The gender effect interacted with the drug effect in the aversive LiCl- and rewarding MAMPH-induced conditioned suppression but did not interact with the drug effect in the rewarding morphine-induced conditioned suppression. Footshock interacted with the drug effect in rewarding morphine- and MAMPH-induced conditioned suppression, but footshock did not interact with the drug effect in the aversive LiCl-induced CTA. Therefore, the gender and footshock effects might play a modulatory (but not a mediating) role with the drug effect. The present data indicated that footshock modulates drugs of abuse-induced conditioned suppression, which is consistent with the reward comparison hypothesis, but our findings with regard to the modulatory role of the gender effect and the drug effect do not support this hypothesis. The reward comparison hypothesis should be discussed and possibly reconsidered.}, } @article {pmid26165136, year = {2015}, author = {Dines, M and Grinberg, S and Vassiliev, M and Ram, A and Tamir, T and Lamprecht, R}, title = {The roles of Eph receptors in contextual fear conditioning memory formation.}, journal = {Neurobiology of learning and memory}, volume = {124}, number = {}, pages = {62-70}, doi = {10.1016/j.nlm.2015.07.003}, pmid = {26165136}, issn = {1095-9564}, mesh = {Animals ; Conditioning, Classical/*physiology ; Fear/*physiology ; Memory, Long-Term/*physiology ; Mice ; Mice, Knockout ; Prosencephalon/*physiology ; Receptor, EphA4/genetics/*physiology ; Receptor, EphB2/genetics/*physiology ; Signal Transduction ; }, abstract = {Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner.}, } @article {pmid26157056, year = {2015}, author = {Sasaki, T and Kinoshita, Y and Matsui, S and Kakuta, S and Yokota-Hashimoto, H and Kinoshita, K and Iwasaki, Y and Kinoshita, T and Yada, T and Amano, N and Kitamura, T}, title = {N-methyl-d-aspartate receptor coagonist d-serine suppresses intake of high-preference food.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {309}, number = {5}, pages = {R561-75}, doi = {10.1152/ajpregu.00083.2015}, pmid = {26157056}, issn = {1522-1490}, mesh = {Agouti-Related Protein/metabolism ; Animals ; Appetite Depressants/*pharmacology ; Choice Behavior ; Conditioning, Psychological ; Diet, High-Fat ; Down-Regulation ; Eating/*drug effects ; Excitatory Amino Acid Agonists/*pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Feeding Behavior/*drug effects ; Food Preferences/*drug effects ; Hypothalamus/drug effects/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Neuropeptide Y/metabolism ; Receptors, N-Methyl-D-Aspartate/*agonists/metabolism ; Sensory System Agents ; Serine/*pharmacology ; Time Factors ; }, abstract = {d-Serine is abundant in the forebrain and physiologically important for modulating excitatory glutamatergic neurotransmission as a coagonist of synaptic N-methyl-d-aspartate (NMDA) receptor. NMDA signaling has been implicated in the control of food intake. However, the role of d-serine on appetite regulation is unknown. To clarify the effects of d-serine on appetite, we investigated the effect of oral d-serine ingestion on food intake in three different feeding paradigms (one-food access, two-food choice, and refeeding after 24-h fasting) using three different strains of male mice (C57Bl/6J, BKS, and ICR). The effect of d-serine was also tested in leptin signaling-deficient db/db mice and sensory-deafferented (capsaicin-treated) mice. The expression of orexigenic neuropeptides [neuropeptide Y (Npy) and agouti-related protein (Agrp)] in the hypothalamus was compared in fast/refed experiments. Conditioned taste aversion for high-fat diet (HFD) was tested in the d-serine-treated mice. Under the one-food-access paradigm, some of the d-serine-treated mice showed starvation, but not when fed normal chow. HFD feeding with d-serine ingestion did not cause aversion. Under the two-food-choice paradigm, d-serine suppressed the intake of high-preference food but not normal chow. d-Serine also effectively suppressed HFD intake but not normal chow in db/db mice and sensory-deafferented mice. In addition, d-serine suppressed normal chow intake after 24-h fasting despite higher orexigenic gene expression in the hypothalamus. d-Serine failed to suppress HFD intake in the presence of L-701,324, the selective and full antagonist at the glycine-binding site of the NMDA receptor. Therefore, d-serine suppresses the intake of high-preference food through coagonism toward NMDA receptors.}, } @article {pmid26141191, year = {2015}, author = {Ripley, TL and Sanchez-Roige, S and Bullmore, ET and Mugnaini, M and Maltby, K and Miller, SR and Wille, DR and Nathan, P and Stephens, DN}, title = {The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.}, journal = {Psychopharmacology}, volume = {232}, number = {18}, pages = {3431-3441}, pmid = {26141191}, issn = {1432-2072}, mesh = {Alcohol Drinking ; Alcoholism/drug therapy ; Animals ; Autoradiography ; Behavior, Animal/*drug effects ; Central Nervous System Depressants/*administration & dosage ; Cross-Over Studies ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; Ethanol/*administration & dosage ; Indans/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Naltrexone/*pharmacology ; Narcotic Antagonists/*pharmacology ; Radiopharmaceuticals ; Receptors, Opioid, mu/*antagonists & inhibitors ; Self Administration ; Triazoles/*pharmacology ; Tritium ; }, abstract = {RATIONALE: Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice.

OBJECTIVE: We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy.

METHODS: Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding.

RESULTS: Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75% receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection.

CONCLUSIONS: Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone.}, } @article {pmid26136115, year = {2015}, author = {May, CE and Haun, HL and Griffin, WC}, title = {Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice.}, journal = {Alcoholism, clinical and experimental research}, volume = {39}, number = {8}, pages = {1443-1452}, pmid = {26136115}, issn = {1530-0277}, support = {P50 AA010761/AA/NIAAA NIH HHS/United States ; R01 AA018036/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Ataxia/chemically induced/prevention & control ; Caffeine/*administration & dosage/toxicity ; *Drug Tolerance/physiology ; Ethanol/*administration & dosage/toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/*drug effects/physiology ; }, abstract = {BACKGROUND: Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol [EtOH]) on conditioned taste aversion (CTA), ataxia, and locomotor activity (LA) after repeated exposure.

METHODS: Four groups of mice were exposed by oral gavage twice daily to vehicle, EtOH (4 g/kg), caffeine (15 mg/kg), or the EtOH/caffeine combination. CTA to saccharin and ataxia in the parallel rod task was evaluated after 8 or 16 gavages, respectively, using EtOH (1 to 3 g/kg) or EtOH/caffeine (3 mg/kg + 2 g/kg) challenges. In addition, LA was evaluated initially and after repeated exposure to oral gavage of these drugs and doses.

RESULTS: Repeated oral gavage of EtOH produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/EtOH combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated EtOH exposure, there was significant tolerance to EtOH in the CTA and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced EtOH-induced CTA. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/EtOH combination and appeared to reduce the ataxic response to high doses of EtOH.

CONCLUSIONS: The data support the general hypothesis that repeated exposure to caffeine influences the response to EtOH. Together with previously published work, these data indicate that caffeine influences some EtOH-related behaviors, notably locomotion and ataxia, but appears not to influence the expression of conditioned behaviors.}, } @article {pmid26126924, year = {2015}, author = {Hadamitzky, M and Bösche, K and Engler, A and Schedlowski, M and Engler, H}, title = {Extinction of conditioned taste aversion is related to the aversion strength and associated with c-fos expression in the insular cortex.}, journal = {Neuroscience}, volume = {303}, number = {}, pages = {34-41}, doi = {10.1016/j.neuroscience.2015.06.040}, pmid = {26126924}, issn = {1873-7544}, mesh = {Amygdala/metabolism ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*metabolism ; Conditioning, Classical ; Cyclosporine ; Extinction, Psychological/*physiology ; Male ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Saccharin ; Taste Perception/*physiology ; }, abstract = {Taste aversion learning is a type of conditioning where animals learn to associate a novel taste (conditioned stimulus; CS) with a stimulus inducing symptoms of poisoning or illness (unconditioned stimulus; US). As a consequence animals later avoid this taste, a reaction known as conditioned taste aversion (CTA). An established CTA extinguishes over time when the CS is repeatedly presented in the absence of the US. However, inter-individual differences in CTA extinction do exist. Using a model of behavioral conditioning with saccharin as CS and the immunosuppressant cyclosporine A as US, the present study aimed at further elucidating the factors underlying individual differences in extinction learning by investigating whether extinction of an established CTA is related to the strength of the initially acquired CS-US association. In addition, we analyzed the expression of the neuronal activation marker c-fos in brain structures relevant for acquisition and retrieval of the CTA, such as the insular cortex and the amygdala. We here show that animals, displaying a strong CS-US association during acquisition, maintained a strong CTA during unreinforced CS re-exposures, in contrast to animals with moderate CS-US association. Moreover, the latter animals showed increased c-fos mRNA expression in the insular cortex. Our data indicate that CTA extinction apparently depends on the strength of the initially learned CS-US association. In addition, these findings provide further evidence that the memory for the initial excitatory conditioning and its subsequent extinction is probably stored in those structures that participate in the processing of the CS and the US.}, } @article {pmid26097499, year = {2015}, author = {Pittman, DW and Hansen, DR and Gilbertson, TA}, title = {High-Fat Diet Alters the Orosensory Sensitivity to Fatty Acids in Obesity-Resistant but not Obesity-Prone Rats.}, journal = {Journal of molecular and genetic medicine : an international journal of biomedical research}, volume = {9}, number = {2}, pages = {}, pmid = {26097499}, issn = {1747-0862}, support = {R01 DC013318/DC/NIDCD NIH HHS/United States ; R01 DK059611/DK/NIDDK NIH HHS/United States ; R56 DK059611/DK/NIDDK NIH HHS/United States ; }, abstract = {Gene-environment interactions play a role in the development of obesity but specific effects of diet on the orosensory detection of fatty acids have yet to be clarified. The objective of this study is to characterize the effect of prolonged (5-week) exposure to a high-fat (60%) diet on the behavioral sensitivity to the fatty acid linoleate following a conditioned taste aversion in obesity-prone and obesity-resistant rats. Exposure to the high-fat diet significantly enhanced the sensitivity of obesity-resistant (S5B/Pl) rats to linoleate while producing no effect on the fatty acid sensitivity for obesity-prone rats. Specifically, high-fat diet fed S5B/Pl rats showed stronger initial avoidance of linoleate and slower extinction rates than their normal diet cohorts. Our study suggests that prolonged dietary fat consumption may alter the behavioral sensitivity to fatty acids particularly in obesity-resistant animals.}, } @article {pmid26067784, year = {2015}, author = {Kwok, DW and Boakes, RA}, title = {Proximal, but not distal, pre-exposure reduces serial overshadowing in one-trial taste aversion learning.}, journal = {Behavioural processes}, volume = {118}, number = {}, pages = {111-114}, doi = {10.1016/j.beproc.2015.06.006}, pmid = {26067784}, issn = {1872-8308}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Hydrochloric Acid/pharmacology ; Inhibition, Psychological ; Lithium Compounds/pharmacology ; Male ; Rats ; Rats, Wistar ; Sucrose/pharmacology ; Taste/*drug effects ; }, abstract = {This experiment tested whether pre-exposing a taste would reduce its ability to overshadow conditioning to a target taste and whether this effect would depend on the delay between pre-exposure and conditioning. Two groups of rats were pre-exposed to an interfering taste (HCl) either a week before conditioning (Group Distal) or the day preceding conditioning (Group Proximal). In the single conditioning trial, rats were given the target taste (sucrose) and 65min later were injected with lithium. The groups differed as to what they were given to drink 50min after sucrose: The Distal, Proximal and Novel groups were given HCl, while the Control group was given water. Pre-exposure to HCl reduced overshadowing of the sucrose aversion by HCl in Group Proximal but not in Group Distal. Possible explanations for the latter result include extinction of the context-HCl association and loss of context control over an HCl-no outcome association.}, } @article {pmid26053891, year = {2016}, author = {Schier, LA and Blonde, GD and Spector, AC}, title = {Bilateral lesions in a specific subregion of posterior insular cortex impair conditioned taste aversion expression in rats.}, journal = {The Journal of comparative neurology}, volume = {524}, number = {1}, pages = {54-73}, pmid = {26053891}, issn = {1096-9861}, support = {F32 DC013494/DC/NIDCD NIH HHS/United States ; R01 DC009821/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/drug effects/pathology/*physiology/physiopathology ; Choice Behavior/physiology ; Conditioning, Psychological/*physiology ; Dietary Sucrose ; Food Preferences/*physiology ; Ibotenic Acid/toxicity ; Male ; Neuropsychological Tests ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary ; Taste Perception/*physiology ; }, abstract = {The gustatory cortex (GC) is widely regarded for its integral role in the acquisition and retention of conditioned taste aversions (CTAs) in rodents, but large lesions in this area do not always result in CTA impairment. Recently, using a new lesion mapping system, we found that severe CTA expression deficits were associated with damage to a critical zone that included the posterior half of GC in addition to the insular cortex (IC) that is just dorsal and caudal to this region (visceral cortex). Lesions in anterior GC were without effect. Here, neurotoxic bilateral lesions were placed in the anterior half of this critical damage zone, at the confluence of the posterior GC and the anterior visceral cortex (termed IC2), the posterior half of this critical damage zone that contains just VC (termed IC3), or both of these subregions (IC2 + IC3). Then, pre- and postsurgically acquired CTAs (to 0.1 M NaCl and 0.1 M sucrose, respectively) were assessed postsurgically in 15-minute one-bottle and 96-hour two-bottle tests. Li-injected rats with histologically confirmed bilateral lesions in IC2 exhibited the most severe CTA deficits, whereas those with bilateral lesions in IC3 were relatively normal, exhibiting transient disruptions in the one-bottle sessions. Groupwise lesion maps showed that CTA-impaired rats had more extensive damage to IC2 than did unimpaired rats. Some individual differences in CTA expression among rats with similar lesion profiles were observed, suggesting idiosyncrasies in the topographic representation of information in the IC. Nevertheless, this study implicates IC2 as the critical zone of the IC for normal CTA expression.}, } @article {pmid26003276, year = {2015}, author = {Kim, YS and Yoo, SB and Ryu, V and Kim, KN and Kim, BT and Lee, JH and Jahng, JW}, title = {Circadian activation of the hypothalamic-pituitary-adrenal axis may affect central, but not peripheral, effect of lithium in conditioned taste aversion learning in rats.}, journal = {European journal of pharmacology}, volume = {762}, number = {}, pages = {11-17}, doi = {10.1016/j.ejphar.2015.05.029}, pmid = {26003276}, issn = {1879-0712}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Circadian Rhythm/*drug effects ; Conditioning, Psychological/*drug effects ; Cyclic AMP Response Element Modulator/metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation/drug effects ; Hypothalamo-Hypophyseal System/*drug effects/*physiology ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste Perception/drug effects/*physiology ; }, abstract = {Activation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in conditioned taste aversion (CTA) learning induced by lithium chloride. This study investigated if circadian activation of the HPA axis affects the lithium-induced CTA formation. The pairing of conditioned stimulus (sucrose) and unconditioned stimulus (lithium chloride) was performed at night (shortly after light-off) when the HPA activity shows its circadian increase. Intraperitoenal injection of lithium chloride (0.15M, 3ml/kg or 12ml/kg) at night induced CTA formation and the HPA axis activation and increased c-Fos expression in both the parabrachial nucleus (PBN) and the nucleus tractus of solitarius (NTS) in a dose dependent manner. However, intracerebroventricular lithium (0.6M, 5µl) at night failed to induce CTA or the HPA axis activation, although it increased c-Fos expression in the PBN and NTS. Results suggest that circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA formation, and the lithium-induced c-Fos expression in brain regions may not be effective to induce CTA unless it is coupled with the HPA axis activation. It is concluded that the HPA axis activation may play an important role mediating not only peripheral but also central effect of lithium in CTA formation.}, } @article {pmid25972577, year = {2015}, author = {Kalyanasundar, B and Perez, CI and Luna, A and Solorio, J and Moreno, MG and Elias, D and Simon, SA and Gutierrez, R}, title = {D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell.}, journal = {Journal of neurophysiology}, volume = {114}, number = {1}, pages = {585-607}, pmid = {25972577}, issn = {1522-1598}, mesh = {Action Potentials/drug effects/physiology ; Animals ; Appetite Depressants/adverse effects/*pharmacology ; Benzazepines/pharmacology ; Bupropion/adverse effects/pharmacology ; Diethylpropion/adverse effects/pharmacology ; Dopamine D2 Receptor Antagonists/*pharmacology ; Drug Interactions ; Eating/drug effects/physiology ; Locomotion/drug effects/physiology ; Male ; Nucleus Accumbens/*drug effects/physiology ; Phentermine/adverse effects/pharmacology ; Raclopride/pharmacology ; Random Allocation ; Rats, Sprague-Dawley ; Receptors, Dopamine D1/*antagonists & inhibitors/metabolism ; Receptors, Dopamine D2/metabolism ; Sleep Initiation and Maintenance Disorders/chemically induced ; Stereotyped Behavior/drug effects/physiology ; Weight Loss/drug effects/physiology ; }, abstract = {Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.}, } @article {pmid25950618, year = {2016}, author = {Boutros, N and Semenova, S and Markou, A}, title = {Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.}, journal = {Addiction biology}, volume = {21}, number = {4}, pages = {826-834}, pmid = {25950618}, issn = {1369-1600}, support = {U01 AA019970/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking ; Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Classical/drug effects ; Disease Models, Animal ; Ethanol/*pharmacology ; Male ; Nicotine/*pharmacology ; Rats ; Rats, Wistar ; }, abstract = {Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28-53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking.}, } @article {pmid25907741, year = {2016}, author = {Miranda-Morales, RS and Pautassi, RM}, title = {Pharmacological characterization of the nociceptin/orphanin FQ receptor on ethanol-mediated motivational effects in infant and adolescent rats.}, journal = {Behavioural brain research}, volume = {298}, number = {Pt A}, pages = {88-96}, doi = {10.1016/j.bbr.2015.04.016}, pmid = {25907741}, issn = {1872-7549}, mesh = {Aging/*drug effects/metabolism/psychology ; Alcohol Drinking/physiopathology ; Animals ; Anxiety/drug therapy/physiopathology ; Choice Behavior/drug effects/physiology ; Conditioning, Psychological/drug effects/physiology ; Ethanol/*pharmacology ; Female ; Imidazoles/pharmacology ; Male ; Motivation/*drug effects/physiology ; Motor Activity/drug effects/physiology ; Neuropsychological Tests ; Opioid Peptides/pharmacology ; Psychotropic Drugs/*pharmacology ; Rats, Wistar ; Receptors, Opioid/agonists/*metabolism ; Saccharin ; Spiro Compounds/pharmacology ; Taste Perception/drug effects/physiology ; }, abstract = {Activation of nociceptin/orphanin FQ (NOP) receptors attenuates ethanol drinking and prevents relapse in adult rodents. In younger rodents (i.e., infant rats), activation of NOP receptors blocks ethanol-induced locomotor activation but does not attenuate ethanol intake. The aim of the present study was to extend the analysis of NOP modulation of ethanol's effects during early ontogeny. Aversive and anxiolytic effects of ethanol were measured in infant and adolescent rats via conditioned taste aversion and the light-dark box test; whereas ethanol-induced locomotor activity and ethanol intake was measured in adolescents only. Before these tests, infant rats were treated with the natural ligand of NOP receptors, nociceptin (0.0, 0.5 or 1.0 μg) and adolescent rats were treated with the specific agonist Ro 64-6198 (0.0, 0.1 or 0.3 mg/kg). The activation of NOP receptors attenuated ethanol-induced anxiolysis in adolescents only, and had no effect on ethanol's aversive effects. Administration of Ro 64-6198 blocked ethanol-induced locomotor activation but did not modify ethanol intake patterns. The attenuation of ethanol stimulating and anxiolytic effect by activation of NOP receptors indicates a modulatory role of this receptor on ethanol effects, which is expressed early in ontogeny.}, } @article {pmid25883377, year = {2015}, author = {Ito, E and Yamagishi, M and Hatakeyama, D and Watanabe, T and Fujito, Y and Dyakonova, V and Lukowiak, K}, title = {Memory block: a consequence of conflict resolution.}, journal = {The Journal of experimental biology}, volume = {218}, number = {Pt 11}, pages = {1699-1704}, doi = {10.1242/jeb.120329}, pmid = {25883377}, issn = {1477-9145}, support = {MOP 64339//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Avoidance Learning ; Conditioning, Classical ; Food Deprivation ; Lymnaea/*physiology ; Memory, Long-Term ; Taste/physiology ; }, abstract = {Food deprivation for 1 day in the pond snail Lymnaea stagnalis before aversive classical conditioning results in optimal conditioned taste aversion (CTA) and long-term memory (LTM) formation, whereas 5-day food deprivation before training does not. We hypothesize that snails do in fact learn and form LTM when trained after prolonged food deprivation, but that severe food deprivation blocks their ability to express memory. We trained 5-day food-deprived snails under various conditions, and found that memory was indeed formed but is overpowered by severe food deprivation. Moreover, CTA-LTM was context dependent and was observed only when the snails were in a context similar to that in which the training occurred.}, } @article {pmid25878268, year = {2015}, author = {Kirkhart, C and Scott, K}, title = {Gustatory learning and processing in the Drosophila mushroom bodies.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {35}, number = {15}, pages = {5950-5958}, pmid = {25878268}, issn = {1529-2401}, support = {R01 DC013280/DC/NIDCD NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Afferent Pathways/*physiology ; Animals ; Animals, Genetically Modified ; Calcium/metabolism ; Conditioning, Classical/*physiology ; Drosophila ; Drosophila Proteins/genetics/metabolism ; Female ; Functional Laterality ; Ion Channels ; Memory, Short-Term/*physiology ; Mushroom Bodies/*physiology ; Nerve Tissue Proteins/metabolism ; Receptors, Odorant/genetics/metabolism ; Sensory Receptor Cells/*physiology ; TRPA1 Cation Channel ; TRPC Cation Channels/genetics/metabolism ; Taste/*physiology ; Tyrosine 3-Monooxygenase/metabolism ; }, abstract = {The Drosophila mushroom bodies are critical association areas whose role in olfactory associative learning has been well characterized. Recent behavioral studies using a taste association paradigm revealed that gustatory conditioning also requires the mushroom bodies (Masek and Scott, 2010; Keene and Masek, 2012). Here, we examine the representations of tastes and the neural sites for taste associations in the mushroom bodies. Using molecular genetic approaches to target different neuronal populations, we find that the gamma lobes of the mushroom bodies and a subset of dopaminergic input neurons are required for taste associative learning. Monitoring responses to taste compounds in the mushroom body calyx with calcium imaging reveals sparse, taste-specific and organ-specific activation in the Kenyon cell dendrites of the main calyx and the dorsal accessory calyx. Our work provides insight into gustatory representations in the mushroom bodies, revealing the essential role of gustatory inputs not only as rewards and punishments but also as adaptive cues.}, } @article {pmid25839897, year = {2015}, author = {Blednov, YA and Benavidez, JM and Black, M and Mayfield, J and Harris, RA}, title = {Role of interleukin-1 receptor signaling in the behavioral effects of ethanol and benzodiazepines.}, journal = {Neuropharmacology}, volume = {95}, number = {}, pages = {309-320}, pmid = {25839897}, issn = {1873-7064}, support = {AA013520/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; AA006399/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/metabolism ; Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/*drug effects/physiology ; Benzodiazepines/*pharmacology ; Ethanol/*pharmacology ; Female ; Flurazepam/pharmacology ; Hypnotics and Sedatives/*pharmacology ; Interleukin 1 Receptor Antagonist Protein/genetics/*metabolism/pharmacology ; Ketamine/pharmacology ; Male ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects/physiology ; Pentobarbital/pharmacology ; Receptors, Interleukin-1 Type I/genetics/*metabolism ; Severity of Illness Index ; Substance Withdrawal Syndrome/metabolism ; Taste Perception/drug effects/physiology ; }, abstract = {Gene expression studies identified the interleukin-1 receptor type I (IL-1R1) as part of a pathway associated with a genetic predisposition to high alcohol consumption, and lack of the endogenous IL-1 receptor antagonist (IL-1ra) strongly reduced ethanol intake in mice. Here, we compared ethanol-mediated behaviors in mice lacking Il1rn or Il1r1. Deletion of Il1rn (the gene encoding IL-1ra) increases sensitivity to the sedative/hypnotic effects of ethanol and flurazepam and reduces severity of acute ethanol withdrawal. Conversely, deletion of Il1r1 (the gene encoding the IL-1 receptor type I, IL-1R1) reduces sensitivity to the sedative effects of ethanol and flurazepam and increases the severity of acute ethanol withdrawal. The sedative effects of ketamine and pentobarbital were not altered in the knockout (KO) strains. Ethanol intake and preference were not changed in mice lacking Il1r1 in three different tests of ethanol consumption. Recovery from ethanol-induced motor incoordination was only altered in female mice lacking Il1r1. Mice lacking Il1rn (but not Il1r1) showed increased ethanol clearance and decreased ethanol-induced conditioned taste aversion. The increased ethanol- and flurazepam-induced sedation in Il1rn KO mice was decreased by administration of IL-1ra (Kineret), and pre-treatment with Kineret also restored the severity of acute ethanol withdrawal. Ethanol-induced sedation and withdrawal severity were changed in opposite directions in the null mutants, indicating that these responses are likely regulated by IL-1R1 signaling, whereas ethanol intake and preference do not appear to be solely regulated by this pathway.}, } @article {pmid25820205, year = {2015}, author = {Saites, LN and Goldsmith, Z and Densky, J and Guedes, VA and Boughter, JD}, title = {Mice perceive synergistic umami mixtures as tasting sweet.}, journal = {Chemical senses}, volume = {40}, number = {5}, pages = {295-303}, pmid = {25820205}, issn = {1464-3553}, support = {DC000353/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Female ; *Glutamic Acid/administration & dosage ; *Inositol Phosphates/administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Sucrose/administration & dosage ; Taste/*physiology ; }, abstract = {Previous electrophysiological investigation shows that combinations of compounds classified by humans as umami-tasting, such as glutamate salts and 5'-ribonucleotides, elicit synergistic responses in neurons throughout the rodent taste system and produce a pattern that resembles responses to sweet compounds. The current study tested the hypothesis that a synergistic mixture of monopotassium glutamate (MPG) and inositol monophosphate (IMP) possesses perceptual similarity to sucrose in mice. We estimated behavioral similarity among these tastants and the individual umami compounds using a series of conditioned taste aversion (CTA) tests, a procedure that measures whether a CTA formed to one stimulus generalizes to another. Our primary finding was that a CTA to a synergistic mixture of MPG + IMP generalizes to sucrose, and vice-versa. This indicates umami synergistic mixtures are perceived as having a sweet, or at least sucrose-like, taste to mice. Considering other recent studies, our data argue strongly in favor of multiple receptor mechanisms for umami detection, and complexity in taste perception models for rodents.}, } @article {pmid25788675, year = {2015}, author = {Carter, ME and Han, S and Palmiter, RD}, title = {Parabrachial calcitonin gene-related peptide neurons mediate conditioned taste aversion.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {35}, number = {11}, pages = {4582-4586}, pmid = {25788675}, issn = {1529-2401}, support = {P30 DK017047/DK/NIDDK NIH HHS/United States ; R01 DA024908/DA/NIDA NIH HHS/United States ; DA024908/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Calcitonin Gene-Related Peptide/*physiology ; Conditioning, Psychological/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Parabrachial Nucleus/*physiology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is a phenomenon in which an individual forms an association between a novel tastant and toxin-induced gastrointestinal malaise. Previous studies showed that the parabrachial nucleus (PBN) contains neurons that are necessary for the acquisition of CTA, but the specific neuronal populations involved are unknown. Previously, we identified calcitonin gene-related peptide (CGRP)-expressing neurons in the external lateral subdivision of the PBN (PBel) as being sufficient to suppress appetite and necessary for the anorexigenic effects of appetite-suppressing substances including lithium chloride (LiCl), a compound often used to induce CTA. Here, we test the hypothesis that PBel CGRP neurons are sufficient and necessary for CTA acquisition in mice. We show that optogenetic activation of these neurons is sufficient to induce CTA in the absence of anorexigenic substances, whereas genetically induced silencing of these neurons attenuates acquisition of CTA upon exposure to LiCl. Together, these results demonstrate that PBel CGRP neurons mediate a gastrointestinal distress signal required to establish CTA.}, } @article {pmid25778639, year = {2015}, author = {Tiunova, AA and Bezryadnov, DV and Anokhin, KV}, title = {Involvement of protein kinase Mζ in the maintenance of long-term memory for taste aversion learning in young chicks.}, journal = {Bulletin of experimental biology and medicine}, volume = {158}, number = {5}, pages = {592-594}, doi = {10.1007/s10517-015-2813-0}, pmid = {25778639}, issn = {1573-8221}, mesh = {Animals ; Avoidance Learning/drug effects ; Chickens ; Memory, Long-Term/drug effects ; Peptides/pharmacology ; Protein Kinase C/antagonists & inhibitors/*metabolism ; Taste/physiology ; }, abstract = {The effects of an inhibitor of protein kinase Mζ on long-term memory were studied using the model of taste aversion in newborn chicks. Memory was impaired by intracerebral injection of 10 or 20 nmol of ζ-inhibiting peptide 24 h after training. Memory impairment was found 2 h after peptide administration, and repeated examination 24 h after treatment showed no recovery. Memory impairment was not observed 24 h after inhibitor administration if the testing 2 h after treatment was not performed. The results indicate the contribution of protein kinase Mζ in the maintenance of long-term memory in the avian brain. These data confirm the hypothesis of several authors that inhibition of protein kinase Mζ does not abolish memory, but rather interacts with processes of memory retrieval and/or reconsolidation.}, } @article {pmid25761841, year = {2015}, author = {Malcolm, E and Carroll, FI and Blough, B and Damaj, MI and Shoaib, M}, title = {Examination of the metabolite hydroxybupropion in the reinforcing and aversive stimulus effects of nicotine in rats.}, journal = {Psychopharmacology}, volume = {232}, number = {15}, pages = {2763-2771}, pmid = {25761841}, issn = {1432-2072}, mesh = {Animals ; Antidepressive Agents/therapeutic use ; Avoidance Learning/drug effects ; Bupropion/*analogs & derivatives/pharmacology ; Male ; Nicotine/*administration & dosage ; Rats ; Receptors, Nicotinic/*physiology ; *Reward ; Self Administration ; *Smoking Cessation ; Tobacco Use Disorder ; }, abstract = {BACKGROUND: Preclinical studies with bupropion in rodent models of nicotine dependence have generated equivocal findings with regard to translating the clinical efficacy of the antidepressant as a smoking cessation agent.

OBJECTIVE: Given that rats are poor metabolizers of bupropion, the present experiments examined (2S,3S)-hydroxybupropion, the major active metabolite, on the positive reinforcing and aversive stimulus properties of nicotine in rats.

METHODS: In male hooded Lister rats, (2S,3S)-hydroxybupropion (1.0-10.0 mg/kg IP) was tested on intravenous nicotine (0.03 mg/kg/inf) self-administration behaviour for three sessions (n = 8), and in another experiment, the same doses of (2S,3S)-hydroxybupropion were tested in a conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake.

RESULTS: (2S,3S)-hydroxybupropion attenuated nicotine intake in a manner similar to that produced by mecamylamine pretreatment (1.0 mg/kg SC). This effect on nicotine-taking was specific since these doses had no effect on responding maintained by sucrose presented orally (200 μl of 5 % w/v). (2S,3S)-hydroxybupropion (1, 3 and 10 mg/kg IP) pretreatment failed to modify the aversive effects produced by a small dose of nicotine (0.1 mg/kg SC).

CONCLUSIONS: These results demonstrate this metabolite to specifically modify the positive reinforcing effects of nicotine without affecting its aversive motivational effects. We propose that the clinical efficacy of bupropion may be due to a combination of effects produced by bupropion and/or its active metabolite (2S,3S)-hydroxybupropion involving the inhibition of reuptake of dopamine and noradrenaline in reward centres of the brain and the noncompetitive antagonism of neuronal nicotinic receptors.}, } @article {pmid25740289, year = {2015}, author = {Harkness, JH and Shi, X and Janowsky, A and Phillips, TJ}, title = {Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {40}, number = {9}, pages = {2175-2184}, pmid = {25740289}, issn = {1740-634X}, support = {T32 DA007262/DA/NIDA NIH HHS/United States ; P50 DA018165/DA/NIDA NIH HHS/United States ; I01 BX002758/BX/BLRD VA/United States ; I01 BX002106/BX/BLRD VA/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Body Temperature/drug effects/genetics ; Central Nervous System Stimulants/*administration & dosage ; Choice Behavior/*drug effects ; Conditioning, Operant/*drug effects ; Cyclic AMP/metabolism ; Dose-Response Relationship, Drug ; HEK293 Cells ; Humans ; Methamphetamine/administration & dosage/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Models, Molecular ; Mutation/genetics ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Taste/drug effects/genetics ; Transfection ; }, abstract = {Continued methamphetamine (MA) use is dependent on a positive MA experience and is likely attenuated by sensitivity to the aversive effects of MA. Bidirectional selective breeding of mice for high (MAHDR) or low (MALDR) voluntary consumption of MA demonstrates a genetic influence on MA intake. Quantitative trait locus (QTL) mapping identified a QTL on mouse chromosome 10 that accounts for greater than 50% of the genetically-determined differences in MA intake in the MAHDR and MALDR lines. The trace amine-associated receptor 1 gene (Taar1) is within the confidence interval of the QTL and encodes a receptor (TAAR1) that modulates monoamine neurotransmission and at which MA serves as an agonist. We demonstrate the existence of a non-functional allele of Taar1 in the DBA/2J mouse strain, one of the founder strains of the selected lines, and show that this non-functional allele co-segregates with high MA drinking and with reduced sensitivity to MA-induced conditioned taste aversion (CTA) and hypothermia. The functional Taar1 allele, derived from the other founder strain, C57BL/6J, segregates with low MA drinking and heightened sensitivity to MA-induced CTA and hypothermia. A role for TAAR1 in these phenotypes is corroborated in Taar1 transgenic mice: Taar1 knockout mice consume more MA and exhibit insensitivity to MA-induced CTA and hypothermia, compared with Taar1 wild-type mice. These are the first data to show that voluntary MA consumption is, in part, regulated by TAAR1 function. Behavioral and physiological studies indicate that TAAR1 function increases sensitivity to aversive effects of MA, and may thereby protect against MA use.}, } @article {pmid25703200, year = {2015}, author = {Swick, JC and Alhadeff, AL and Grill, HJ and Urrea, P and Lee, SM and Roh, H and Baird, JP}, title = {Parabrachial Nucleus Contributions to Glucagon-Like Peptide-1 Receptor Agonist-Induced Hypophagia.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {40}, number = {8}, pages = {2001-2014}, pmid = {25703200}, issn = {1740-634X}, support = {R01 DK021397/DK/NIDDK NIH HHS/United States ; R15 DC007389/DC/NIDCD NIH HHS/United States ; 52006280//Howard Hughes Medical Institute/United States ; DC07389/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Antimanic Agents/pharmacology ; Appetitive Behavior/drug effects ; Brain Injuries/chemically induced/*pathology ; Eating/drug effects ; Excitatory Amino Acid Agonists/toxicity ; Exenatide ; Feeding and Eating Disorders/*chemically induced ; Glucagon-Like Peptide-1 Receptor/agonists/metabolism ; Hypoglycemic Agents/*toxicity ; Ibotenic Acid/toxicity ; Lithium Chloride/administration & dosage ; Male ; Parabrachial Nucleus/drug effects/*pathology ; Peptides/*toxicity ; Rats ; Rats, Sprague-Dawley ; Sucrose/administration & dosage ; Taste/drug effects ; Venoms/*toxicity ; Water Deprivation ; }, abstract = {Exendin-4 (Ex4), a glucagon-like peptide-1 receptor (GLP-1R) agonist approved to treat type 2 diabetes mellitus, is well known to induce hypophagia in human and animal models. We evaluated the contributions of the hindbrain parabrachial nucleus (PBN) to systemic Ex4-induced hypophagia, as the PBN receives gustatory and visceral afferent relays and descending input from several brain nuclei associated with feeding. Rats with ibotenic-acid lesions targeted to the lateral PBN (PBNx) and sham controls received Ex4 (1 μg/kg) before 24 h home cage chow or 90 min 0.3 M sucrose access tests, and licking microstructure was analyzed to identify components of feeding behavior affected by Ex4. PBN lesion efficacy was confirmed using conditioned taste aversion (CTA) tests. As expected, sham control but not PBNx rats developed a CTA. In sham-lesioned rats, Ex4 reduced chow intake within 4 h of injection and sucrose intake within 90 min. PBNx rats did not show reduced chow or sucrose intake after Ex4 treatment, indicating that the PBN is necessary for Ex4 effects under the conditions tested. In sham-treated rats, Ex4 affected licking microstructure measures associated with hedonic taste evaluation, appetitive behavior, oromotor coordination, and inhibitory postingestive feedback. Licking microstructure responses in PBNx rats after Ex4 treatment were similar to sham-treated rats with the exception of inhibitory postingestive feedback measures. Together, the results suggest that the PBN critically contributes to the hypophagic effects of systemically delivered GLP-1R agonists by enhancing visceral feedback.}, } @article {pmid25698309, year = {2015}, author = {Saalfield, J and Spear, L}, title = {Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.}, journal = {Developmental cognitive neuroscience}, volume = {16}, number = {}, pages = {174-182}, pmid = {25698309}, issn = {1878-9307}, support = {R01 AA018026/AA/NIAAA NIH HHS/United States ; U01 AA019972/AA/NIAAA NIH HHS/United States ; R01-AA018026/AA/NIAAA NIH HHS/United States ; UO1-AA019972-01/AA/NIAAA NIH HHS/United States ; }, mesh = {Aging/psychology ; Animals ; Avoidance Learning/drug effects ; Central Nervous System Depressants/administration & dosage/*pharmacology ; Conditioning, Operant/*drug effects ; Cues ; Dose-Response Relationship, Drug ; Ethanol/administration & dosage/*pharmacology ; Injections, Intraperitoneal ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.}, } @article {pmid25678534, year = {2015}, author = {Blednov, YA and Benavidez, JM and Black, M and Leiter, CR and Osterndorff-Kahanek, E and Harris, RA}, title = {Glycine receptors containing α2 or α3 subunits regulate specific ethanol-mediated behaviors.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {353}, number = {1}, pages = {181-191}, pmid = {25678534}, issn = {1521-0103}, support = {R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; R01-AA006399/AA/NIAAA NIH HHS/United States ; R01-AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Brain/metabolism ; Drinking Behavior/drug effects ; Ethanol/*pharmacology ; Food Preferences/drug effects ; Mice, Knockout ; Motor Activity/drug effects ; Mutation ; RNA, Messenger/metabolism ; Receptors, Glycine/genetics/*metabolism ; Reflex, Startle/drug effects ; }, abstract = {Glycine receptors (GlyRs) are broadly expressed in the central nervous system. Ethanol enhances the function of brain GlyRs, and the GlyRα1 subunit is associated with some of the behavioral actions of ethanol, such as loss of righting reflex. The in vivo role of GlyRα2 and α3 subunits in alcohol responses has not been characterized despite high expression levels in the nucleus accumbens and amygdala, areas that are important for the rewarding properties of drugs of abuse. We used an extensive panel of behavioral tests to examine ethanol actions in mice lacking Glra2 (the gene encoding the glycine receptor alpha 2 subunit) or Glra3 (the gene encoding the glycine receptor alpha 3 subunit). Deletion of Glra2 or Glra3 alters specific ethanol-induced behaviors. Glra2 knockout mice demonstrate reduced ethanol intake and preference in the 24-hour two-bottle choice test and increased initial aversive responses to ethanol and lithium chloride. In contrast, Glra3 knockout mice show increased ethanol intake and preference in the 24-hour intermittent access test and increased development of conditioned taste aversion to ethanol. Mutants and wild-type mice consumed similar amounts of ethanol in the limited access drinking in the dark test. Other ethanol effects, such as anxiolysis, motor incoordination, loss of righting reflex, and acoustic startle response, were not altered in the mutants. The behavioral changes in mice lacking GlyRα2 or α3 subunits were distinct from effects previously observed in mice with knock-in mutations in the α1 subunit. We provide evidence that GlyRα2 and α3 subunits may regulate ethanol consumption and the aversive response to ethanol.}, } @article {pmid25658323, year = {2015}, author = {Blonde, GD and Bales, MB and Spector, AC}, title = {Extensive lesions in rat insular cortex significantly disrupt taste sensitivity to NaCl and KCl and slow salt discrimination learning.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117515}, pmid = {25658323}, issn = {1932-6203}, support = {R01 DC009821/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; R01-DC-DC009821/DC/NIDCD NIH HHS/United States ; T32-DC-000044/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Cerebral Cortex/drug effects/*physiopathology ; Discrimination Learning/drug effects/*physiology ; Ibotenic Acid/toxicity ; Male ; Potassium Chloride/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/*administration & dosage ; Taste/drug effects/*physiology ; Taste Perception/drug effects/*physiology ; }, abstract = {While studies of the gustatory cortex (GC) mostly focus on its role in taste aversion learning and memory, the necessity of GC for other fundamental taste-guided behaviors remains largely untested. Here, rats with either excitotoxic lesions targeting GC (n = 26) or sham lesions (n = 14) were assessed for postsurgical retention of a presurgically LiCl-induced conditioned taste aversion (CTA) to 0.1M sucrose using a brief-access taste generalization test in a gustometer. The same animals were then trained in a two-response operant taste detection task and psychophysically tested for their salt (NaCl or KCl) sensitivity. Next, the rats were trained and tested in a NaCl vs. KCl taste discrimination task with concentrations varied. Rats meeting our histological inclusion criterion had large lesions (resulting in a group averaging 80% damage to GC and involving surrounding regions) and showed impaired postsurgical expression of the presurgical CTA (LiCl-injected, n = 9), demonstrated rightward shifts in the NaCl (0.54 log10 shift) and KCl (0.35 log10 shift) psychometric functions, and displayed retarded salt discrimination acquisition (n = 18), but eventually learned and performed the discrimination comparable to sham-operated animals. Interestingly, the degree of deficit between tasks correlated only modestly, if at all, suggesting that idiosyncratic differences in insular cortex lesion topography were the root of the individual differences in the behavioral effects demonstrated here. This latter finding hints at some degree of interanimal variation in the functional topography of insular cortex. Overall, GC appears to be necessary to maintain normal taste sensitivity to NaCl and KCl and for salt discrimination learning. However, higher salt concentrations can be detected and discriminated by rats with extensive damage to GC suggesting that the other resources of the gustatory system are sufficient to maintain partial competence in these tasks, supporting the view that such basic sensory-discriminative taste functions involve distributed processes among central gustatory structures.}, } @article {pmid25629943, year = {2015}, author = {Niikura, R and Nozawa, T and Yamada, K and Kato, K and Ichitani, Y}, title = {Latent inhibition in rats neonatally treated chronically with MK-801: differential effects on conditioned taste aversion and conditioned emotional response.}, journal = {Behavioural brain research}, volume = {283}, number = {}, pages = {102-107}, doi = {10.1016/j.bbr.2015.01.029}, pmid = {25629943}, issn = {1872-7549}, mesh = {Animals ; Animals, Newborn ; Auditory Perception/drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Conditioning, Classical/*drug effects/physiology ; Dietary Sucrose/administration & dosage ; Dizocilpine Maleate/*pharmacology ; Electroshock ; Emotions/drug effects/physiology ; Excitatory Amino Acid Antagonists/*pharmacology ; Foot ; *Inhibition, Psychological ; Lithium Chloride/administration & dosage ; Male ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Taste Perception/drug effects/physiology ; }, abstract = {Chronic neonatal blockade of N-methyl-d-aspartate (NMDA) receptors produces various abnormal behaviors in adulthood animals. This study investigated the effects of neonatal treatment chronically with MK-801 in rats on the preexposure-induced retardation of CS-US association, i.e. latent inhibition (LI), of two aversive classical conditioning tasks in adulthood. In conditioned taste aversion (CTA) using sucrose taste and LiCl, neonatal chronic MK-801 (0.4 mg/kg twice/day) treatment attenuated the inhibitory effect of sucrose preexposure on the aversive conditioning, although the treatment did not affect CTA conditioning itself. On the other hand, in conditioned emotional response (CER) using tone and electrical foot shock, rats neonatally treated with MK-801 showed the same degree of inhibitory effect of tone preexposure on the aversive conditioning compared with neonatally vehicle-treated rats, and also showed the same level of CER conditioning itself. Thus, the effect of chronic neonatal blockade of NMDA receptors on the LI of classical conditioning in adulthood was differentiated by the task employed. Results suggest that LI of CTA paradigm compared with that of CER is more sensitive to abnormal development after chronic neonatal blockade of NMDA receptors as an index of cognitive/attentional deficits caused by the treatment.}, } @article {pmid25619919, year = {2015}, author = {Soto, J and Sheng, Y and Standing, JF and Orlu Gul, M and Tuleu, C}, title = {Development of a model for robust and exploratory analysis of the rodent brief-access taste aversion data.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {91}, number = {}, pages = {47-51}, doi = {10.1016/j.ejpb.2015.01.016}, pmid = {25619919}, issn = {1873-3441}, support = {MR/M008665/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Algorithms ; Animals ; Behavior, Animal/*drug effects ; *Drug Evaluation, Preclinical ; Drugs, Investigational/*adverse effects ; Flavoring Agents/toxicity ; Male ; *Models, Statistical ; Monitoring, Ambulatory ; Osmolar Concentration ; Quinine/toxicity ; Rats, Sprague-Dawley ; Taste ; Taste Buds/*drug effects ; *Tongue Habits ; }, abstract = {The rodent brief-access taste aversion (BATA) model is an efficient in vivo screening tool for taste assessment. A new E(max) (maximum effect attributable to the drug) model was developed and further investigated in comparison with three previously published models for analysing the rodent BATA data; the robustness of all the models was discussed. The rodent BATA data were obtained from a series of experiments conducted with a bitter reference compound, quinine hydrochloride dihydrate (QHD). A new E(max) model that could be applied to both "lick numbers" and "lick ratios" was built and three published models that used lick ratios were employed for analysing the BATA data. IC50, the concentration that inhibits 50% of the maximum lick numbers, quantified the oral aversiveness of QHD. One thousand bootstrap datasets were generated from the original data. All models were applied to estimate the confidence intervals of the IC50s without symmetric assumption. The IC50 value obtained from the new E(max) model was 0.0496 mM (95% CI 0.0297-0.0857) using the lick numbers for analysis, while an IC50 of 0.0502 mM (95% CI 0.0267-0.0859) was acquired with the lick ratios. Except one published model, the IC50 values have a similar range for the 95% CI. The new E(max) model enabled the analysis of both "lick numbers" and "lick ratios" whereas other models could only handle data presented as "lick ratios". IC50s obtained with these two types of datasets showed similarity among all models thereby justified the robustness of the new E(max) model.}, } @article {pmid25617666, year = {2015}, author = {Lin, JY and Arthurs, J and Reilly, S}, title = {Gustatory insular cortex, aversive taste memory and taste neophobia.}, journal = {Neurobiology of learning and memory}, volume = {119}, number = {}, pages = {77-84}, pmid = {25617666}, issn = {1095-9564}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Conditioning, Psychological ; Male ; Memory/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; Taste Perception/*physiology ; }, abstract = {Prior research indicates a role for the gustatory insular cortex (GC) in taste neophobia. Rats with lesions of the GC show much weaker avoidance to a novel and potentially dangerous taste than do neurologically intact animals. The current study used the retention of conditioned taste aversion (CTA) as a tool to determine whether the GC modulates neophobia by processing taste novelty or taste danger. The results show that GC lesions attenuate CTA retention (Experiment 1) and impair taste neophobia (Experiment 2). Given that normal CTA retention does not involve the processing of taste novelty, the pattern of results suggests that the GC is involved in taste neophobia via its function in processing the danger conveyed by a taste stimulus.}, } @article {pmid25604941, year = {2015}, author = {Delay, ER and Kondoh, T}, title = {Dried bonito dashi: taste qualities evaluated using conditioned taste aversion methods in wild-type and T1R1 knockout mice.}, journal = {Chemical senses}, volume = {40}, number = {2}, pages = {125-140}, doi = {10.1093/chemse/bju067}, pmid = {25604941}, issn = {1464-3553}, mesh = {Amiloride/pharmacology ; Amino Acids/*pharmacology ; Animals ; Avoidance Learning ; Citric Acid/pharmacology ; Conditioning, Classical ; Cooking ; Dose-Response Relationship, Drug ; *Food ; Glutamic Acid/pharmacology ; Hydrogen-Ion Concentration ; Inosine Monophosphate/*pharmacology ; Lactic Acid/pharmacology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Quinine/pharmacology ; Receptors, G-Protein-Coupled/*genetics/metabolism ; Sodium Glutamate/pharmacology ; Sucrose/pharmacology ; Taste Perception/drug effects/*physiology ; }, abstract = {The primary taste of dried bonito dashi is thought to be umami, elicited by inosine 5'-monphosphate (IMP) and L-amino acids. The present study compared the taste qualities of 25% dashi with 5 basic tastes and amino acids using conditioned taste aversion methods. Although wild-type C57BL/6J mice with compromised olfactory systems generalized an aversion of dashi to all 5 basic tastes, generalization was greater to sucrose (sweet), citric acid (sour), and quinine (bitter) than to NaCl (salty) or monosodium L-glutamate (umami) with amiloride. At neutral pH (6.5-6.9), the aversion generalized to l-histidine, L-alanine, L-proline, glycine, L-aspartic acid, L-serine, and monosodium L-glutamate, all mixed with IMP. Lowering pH of the test solutions to 5.7-5.8 (matching dashi) with HCl decreased generalization to some amino acids. However, adding lactic acid to test solutions with the same pH increased generalization to 5'-inosine monophosphate, L-leucine, L-phenylalanine, L-valine, L-arginine, and taurine but eliminated generalization to L-histidine. T1R1 knockout mice readily learned the aversion to dashi and generalized the aversion to sucrose, citric acid, and quinine but not to NaCl, glutamate, or any amino acid. These results suggest that dashi elicits a complex taste in mice that is more than umami, and deleting T1R1 receptor altered but did not eliminate their ability to taste dashi. In addition, lactic acid may alter or modulate taste transduction or cell-to-cell signaling.}, } @article {pmid25592442, year = {2015}, author = {Huang, AC and Wang, S and Wu, JJ and Wang, CC}, title = {Footshock facilitates methamphetamine-induced conditioned suppression through HPA axis, not dopamine.}, journal = {Physiology & behavior}, volume = {141}, number = {}, pages = {78-84}, doi = {10.1016/j.physbeh.2015.01.013}, pmid = {25592442}, issn = {1873-507X}, mesh = {Animals ; Conditioning, Classical/*drug effects/physiology ; Corticosterone/blood ; Dexamethasone/pharmacology ; Dopamine/*metabolism ; Dopamine Antagonists/pharmacology ; Dopamine Uptake Inhibitors/*pharmacology ; Electroshock ; Female ; Glucocorticoids/pharmacology ; Haloperidol/pharmacology ; Hypothalamo-Hypophyseal System/*drug effects/metabolism ; Methamphetamine/*pharmacology ; Pituitary-Adrenal System/*drug effects/metabolism ; Rats ; Rats, Wistar ; }, abstract = {The present study examined whether footshock can enhance methamphetamine (MAMPH)-induced conditioned suppression and whether this effect involves the dopamine (DA) reward system or hypothalamic-pituitary-adrenal (HPA) axis. We also examined whether the footshock-induced enhancements of MAMPH-induced conditioned suppression are attributable to MAMPH's rewarding or aversive properties. During the footshock phase, all female rats received 0.1mg/kg haloperidol (HAL) and its vehicle (2% tartaric acid solution), or low and high doses of dexamethasone (DEX; 0.5 and 1.0mg/kg) and its vehicle before each footshock (1mA, 2s), or no footshock, in seven trials once per day. The control group did not receive any drugs or footshocks. All of the rats were then allowed 15min access to a 0.1% saccharin solution and then received 2mg/kg MAMPH in five trials once per day. Footshock exhibited an increase in MAMPH-induced taste suppression. The low- and high-dose DEX groups but not the HAL group exhibited a blocking effect of the footshock enhancements of MAMPH-induced taste suppression. The low- and high-dose DEX groups exhibited a significant decrease in corticosterone levels during the footshock treatment phase but not during the testing phase. Altogether, the HPA stress system and not the DA reward system, particularly D2 receptors, appear to mediate the footshock-induced enhancements of MAMPH-induced conditioned taste suppression, which may result from the aversive and not the rewarding properties of MAMPH. The present findings may provide some clinical implications for alternating aversively classical conditioning for psychiatric disorders.}, } @article {pmid25557105, year = {2015}, author = {Seraydar, KR and Kaufman, PE}, title = {Does behaviour play a role in house fly resistance to imidacloprid-containing baits?.}, journal = {Medical and veterinary entomology}, volume = {29}, number = {1}, pages = {60-67}, doi = {10.1111/mve.12095}, pmid = {25557105}, issn = {1365-2915}, mesh = {Animals ; Biological Evolution ; Feeding Behavior/drug effects ; Female ; Houseflies/drug effects/genetics/*physiology ; Imidazoles/*pharmacology ; Insect Control/methods ; *Insecticide Resistance ; Insecticides/*pharmacology ; Male ; Neonicotinoids ; Nitro Compounds/*pharmacology ; Selection, Genetic/*drug effects ; }, abstract = {The objective of this research was to examine the role and type of behavioural mechanisms that function in house fly, Musca domestica L. (Diptera: Muscidae), resistance to an imidacloprid-containing commercial fly bait, QuickBayt(®) , using an insecticide-susceptible and an imidacloprid-resistant strain. Mortality and feeding behaviour were observed through choice bioassays of three post-imidacloprid selected house fly generations to determine whether flies would consume the bait in the presence of an alternative food source. Mortality rates in choice containers progressively decreased in post-selection flies as QuickBayt(®) no-choice selections proceeded. There were no differences between the proportions of flies observed contacting QuickBayt(®) and sugar, respectively, a finding that eliminates repellency as a mechanism of stimulus-dependent behavioural resistance. However, differences in QuickBayt(®) consumption and subsequent mortality between choice and no-choice containers provided strong support for the evolution of consumption irritancy- or taste aversion-related behavioural resistance. The results of this study support the responsible rotation of insecticide bait formulations for house fly control.}, } @article {pmid25548209, year = {2015}, author = {Manuelian, CL and Albanell, E and Rovai, M and Caja, G and Guitart, R}, title = {Kinetics of lithium as a lithium chloride dose suitable for conditioned taste aversion in lactating goats and dry sheep.}, journal = {Journal of animal science}, volume = {93}, number = {2}, pages = {562-569}, doi = {10.2527/jas.2014-8223}, pmid = {25548209}, issn = {1525-3163}, mesh = {Animals ; Cattle ; Feces/chemistry ; Female ; Food Preferences/*drug effects ; Goats ; Kinetics ; Lactation/metabolism ; Lithium/blood/metabolism/urine ; Lithium Chloride/administration & dosage/*pharmacokinetics/pharmacology ; Milk/chemistry ; Ruminants/*metabolism ; Sheep, Domestic ; Spectrophotometry, Atomic ; Taste/*drug effects ; Time Factors ; }, abstract = {Lithium chloride (LiCl) is widely used for inducing conditioned taste aversion (CTA) so that livestock will reduce or avoid ingestion of toxic plants and graze groundcover mingled with valuable crops. However, pharmacokinetic studies of LiCl at effective CTA doses are lacking. With this aim, 6 Murciano-Grandina dairy does during late lactation and 6 dry Manchega dairy ewes were orally dosed with 200 and 225 mg LiCl/kg BW, respectively. Does were placed in metabolism cages whereas ewes were group fed in pens. Lithium was measured over 168 (does) and 192 h (ewes) at predefined intervals in plasma, urine, feces, and milk using flame atomic absorption spectroscopy. Plasma Li concentrations reached a maximum at 4 h in does (13.4 ± 1.35 mg Li/L) and 12 h in ewes (17.7 ± 0.8 mg Li/L). The calculated plasma half-lives were 40.3 ± 3.8 and 30.9 ± 2.1 h for does and ewes, respectively. In goats, all Li administered was recovered at 96 h (92 ± 4% in urine, 6.5 ± 1.3% in feces, and 2.8 ± 0.4% in milk); however, the estimated clearance time in feces was 11 and 9 d for does and ewes, respectively. Additionally, maximum Li excretion in doe milk was 15.6 ± 0.5 mg/L, which was approximately half of the calculated effective dose for a 5-kg BW sucking kid. In conclusion, Li kinetics in goats and sheep were similar to cattle and elimination took longer than in monogastric species. The low concentration of Li in feces, urine, and milk, as well as the complete elimination of Li from the body after 1.5 wk allows us to conclude that LiCl is safe and suitable for inducing CTA in ruminants.}, } @article {pmid25546096, year = {2014}, author = {Boakes, RA and Costa, DS}, title = {Temporal contiguity in associative learning: Interference and decay from an historical perspective.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {40}, number = {4}, pages = {381-400}, doi = {10.1037/xan0000040}, pmid = {25546096}, issn = {2329-8464}, mesh = {Animals ; *Association Learning ; Behavior, Animal/*physiology ; Humans ; *Reinforcement, Psychology ; *Time ; }, abstract = {The greater the separation in time between 2 events, A followed by B, the less likely they are to become associated. The dominant explanation of this temporal contiguity effect has been trace decay: During the interval between A and B, the trace left by A becomes too weak by the time B occurs for an association to be formed between them. Pavlov adopted this idea in the context of classical conditioning and Hull used it to account for the deleterious effect of delaying reinforcement on the acquisition of instrumental responses. By 1960 various studies supported the conclusion that animals could not learn to associate 2 events separated by more than around 45 s. Research on human skill acquisition with delayed feedback and later studies using causal or predictive judgment tasks indicated that explicit cognitive processing is generally involved when humans associate events separated by more than a few seconds. The discovery of long-delay taste aversion learning prompted Revusky's (1971) alternative analysis of contiguity effects in terms of interference: The greater the separation between A and B, the more likely that extraneous events compete for association with A and B. Although the analysis of overshadowing provided by associative learning theories provides a context for this account, none of these theories provide a satisfactory account of evidence on temporal contiguity from a wide range of animal studies. Alternative timing theories are arguably also unsatisfactory.}, } @article {pmid25540931, year = {2015}, author = {Grigson, PS and Colechio, EM and Power, ML and Schulkin, J and Norgren, R}, title = {Parabrachial lesions in rats disrupt sodium appetite induced by furosemide but not by calcium deprivation.}, journal = {Physiology & behavior}, volume = {140}, number = {}, pages = {172-179}, pmid = {25540931}, issn = {1873-507X}, support = {R01 DC000240/DC/NIDCD NIH HHS/United States ; DC05435/DC/NIDCD NIH HHS/United States ; R01 DC005435/DC/NIDCD NIH HHS/United States ; DC00240/DC/NIDCD NIH HHS/United States ; R01 DA012473/DA/NIDA NIH HHS/United States ; DA012473/DA/NIDA NIH HHS/United States ; R37 DA009815/DA/NIDA NIH HHS/United States ; DA009815/DA/NIDA NIH HHS/United States ; R01 DA009815/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Appetite/*drug effects ; Calcium/*deficiency ; Calcium Chloride/administration & dosage ; Conditioning, Psychological/drug effects ; Desoxycorticosterone Acetate/pharmacology ; Disease Models, Animal ; Diuretics/*pharmacology ; Excitatory Amino Acid Agonists/toxicity ; Furosemide/*pharmacology ; Ibotenic Acid/toxicity ; Parabrachial Nucleus/*injuries/physiology ; Polyethylene Glycols ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/*administration & dosage ; }, abstract = {An appetite for CaCl2 and NaCl occurs in young rats after they are fed a diet lacking Ca or Na, respectively. Bilateral lesions of the parabrachial nuclei (PBN) disrupt normal taste aversion learning and essentially eliminate the expression of sodium appetite. Here we tested whether similar lesions of the PBN would disrupt the calcium-deprivation-induced appetite for CaCl2 or NaCl. Controls and rats with PBN lesions failed to exhibit a calcium-deprivation-induced appetite for CaCl2. Nevertheless, both groups did exhibit a significant calcium-deprivation-induced appetite for 0.5M NaCl. Thus, while damage to the second central gustatory relay in the PBN disrupts the appetite for 0.5M NaCl induced by furosemide, deoxycorticosterone acetate, and polyethylene glycol, the sodium appetite induced by dietary CaCl2 depletion remains intact.}, } @article {pmid25524986, year = {2015}, author = {Ito, E and Yamagishi, M and Takigami, S and Sakakibara, M and Fujito, Y and Lukowiak, K}, title = {The Yerkes-Dodson law and appropriate stimuli for conditioned taste aversion in Lymnaea.}, journal = {The Journal of experimental biology}, volume = {218}, number = {Pt 3}, pages = {336-339}, doi = {10.1242/jeb.113266}, pmid = {25524986}, issn = {1477-9145}, mesh = {Animals ; Avoidance Learning ; Conditioning, Classical ; Electric Stimulation ; Lymnaea/*physiology ; Memory/physiology ; Sucrose ; Taste ; }, abstract = {The pond snail Lymnaea stagnalis can learn conditioned taste aversion and then consolidate it into long-term memory (LTM). A high-voltage electric shock was used as the unconditioned stimulus, where we have previously used KCl. We varied the strength of both the conditioned and unconditioned stimuli to determine whether the so-called Yerkes-Dodson law prevailed. This is an empirical relationship between the state of arousal and LTM formation, showing that there is an optimal level of arousal leading to memory formation. However, too little or too much arousal results in poorer LTM. We found here that the most appropriate stimuli to use in taste aversion training in Lymnaea were a 10 mmol l(-1) sucrose solution as the conditioned stimulus and a 3 s electric shock as the unconditioned stimulus.}, } @article {pmid25506318, year = {2014}, author = {Gonzalez, MC and Kramar, CP and Tomaiuolo, M and Katche, C and Weisstaub, N and Cammarota, M and Medina, JH}, title = {Medial prefrontal cortex dopamine controls the persistent storage of aversive memories.}, journal = {Frontiers in behavioral neuroscience}, volume = {8}, number = {}, pages = {408}, pmid = {25506318}, issn = {1662-5153}, abstract = {Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus.}, } @article {pmid25489006, year = {2015}, author = {Ancel, D and Bernard, A and Subramaniam, S and Hirasawa, A and Tsujimoto, G and Hashimoto, T and Passilly-Degrace, P and Khan, NA and Besnard, P}, title = {The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice.}, journal = {Journal of lipid research}, volume = {56}, number = {2}, pages = {369-378}, pmid = {25489006}, issn = {1539-7262}, mesh = {Animals ; Calcium/metabolism ; Dietary Fats/*metabolism ; Food Preferences/drug effects/physiology ; Immunohistochemistry ; Male ; Mice ; Receptors, G-Protein-Coupled/agonists/*metabolism ; Taste Buds/cytology/drug effects/*metabolism ; }, abstract = {Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the "taste of fat", the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca(2+)]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca(2+)]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice.}, } @article {pmid25454591, year = {2014}, author = {Sano, Y and Shobe, JL and Zhou, M and Huang, S and Shuman, T and Cai, DJ and Golshani, P and Kamata, M and Silva, AJ}, title = {CREB regulates memory allocation in the insular cortex.}, journal = {Current biology : CB}, volume = {24}, number = {23}, pages = {2833-2837}, pmid = {25454591}, issn = {1879-0445}, support = {R01 AG013622/AG/NIA NIH HHS/United States ; R37 AG013622/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Cerebral Cortex/*physiology ; Conditioning, Classical/physiology ; Cyclic AMP Response Element-Binding Protein/*physiology ; Gene Silencing ; Humans ; In Situ Hybridization, Fluorescence ; Lithium Chloride/pharmacology ; Memory/*physiology ; Mice, Inbred C57BL ; Neurons/physiology ; Taste ; }, abstract = {The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cyclic-AMP-response-element-binding protein (CREB) are more likely to be recruited into encoding and storing fear memory. To determine whether specific mechanisms also regulate memory allocation in other brain regions and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (conditioned stimulus [CS]) with the experience of malaise (such as that induced by LiCl; unconditioned stimulus [US]). The insular cortex is required for CTA memory formation and retrieval. CTA learning activates a subpopulation of neurons in this structure, and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc fluorescence in situ hybridization (FISH), and designer receptors exclusively activated by designer drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory.}, } @article {pmid25451308, year = {2014}, author = {Rodríguez-Serrano, LM and Ramírez-León, B and Rodríguez-Durán, LF and Escobar, ML}, title = {Acute infusion of brain-derived neurotrophic factor in the insular cortex promotes conditioned taste aversion extinction.}, journal = {Neurobiology of learning and memory}, volume = {116}, number = {}, pages = {139-144}, doi = {10.1016/j.nlm.2014.10.007}, pmid = {25451308}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain-Derived Neurotrophic Factor/*pharmacology ; Cerebral Cortex/*drug effects ; Conditioning, Classical/*drug effects ; Extinction, Psychological/*drug effects ; Male ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Brain-derived neurotrophic factor (BDNF) has emerged as one of the most potent molecular mediators not only for synaptic plasticity, but also for the behavioral organism-environment interactions. Our previous studies in the insular cortex (IC), a neocortical region that has been related with acquisition and retention of conditioned taste aversion (CTA), have demonstrated that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the basolateral amygdaloid nucleus (Bla)-IC projection and enhances the retention of CTA memory of adult rats in vivo. The aim of the present study was to analyze whether acute BDNF-infusion in the IC modifies the extinction of CTA. Accordingly, animals were trained in the CTA task and received bilateral IC microinfusions of BDNF before extinction training. Our results showed that taste aversion was significantly reduced in BDNF rats from the first extinction trial. Additionally, we found that the effect of BDNF on taste aversion did not require extinction training. Finally we showed that the BDNF effect does not degrade the original taste aversion memory trace. These results emphasize that BDNF activity underlies memory extinction in neocortical areas and support the idea that BDNF is a key regulator and mediator of long-term synaptic modifications.}, } @article {pmid25451307, year = {2014}, author = {Mita, K and Yamagishi, M and Fujito, Y and Lukowiak, K and Ito, E}, title = {An increase in insulin is important for the acquisition conditioned taste aversion in Lymnaea.}, journal = {Neurobiology of learning and memory}, volume = {116}, number = {}, pages = {132-138}, doi = {10.1016/j.nlm.2014.10.006}, pmid = {25451307}, issn = {1095-9564}, support = {MOP 64339//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Classical/*drug effects/physiology ; Food Deprivation/physiology ; Glucose/analysis ; Hemolymph/chemistry ; Hypoglycemic Agents/*pharmacology ; Insulin/*pharmacology ; Lymnaea ; Motivation/drug effects/physiology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) in Lymnaea is brought about by pairing a sucrose solution (the conditioned stimulus, CS) with an electric shock (the unconditioned stimulus, US). Following repeated CS-US pairings, CTA occurs and it is consolidated into long-term memory (LTM). The best CTA is achieved, if snails are food-deprived for 1 day before training commences. With a longer period of food deprivation (5 days), learning and memory formation does not occur. It has been hypothesized that the levels of insulin in the central nervous system (CNS) are very important for CTA to occur. To test his hypothesis, we injected insulin directly into 5-day food-deprived snails. The injection of insulin, as expected, resulted in a decrease in hemolymph glucose concentration. Consistent with our hypothesis with insulin injection, learning and memory formation of CTA occurred. That is, the 'insulin spike' is more important than an increase in hemolymph glucose concentration for CTA-LTM. If we injected an insulin receptor antibody into the snails before the insulin injection, learning was formed but memory formation was not, which is consistent with our previous study. Therefore, a rise in the insulin concentration (i.e., insulin spike) in the CNS is considered to be a key determining factor in the process of CTA-LTM.}, } @article {pmid25447753, year = {2015}, author = {Tsuboi, H and Hirai, Y and Maezawa, H and Notani, K and Inoue, N and Funahashi, M}, title = {Effects of treadmill exercise on the LiCl-induced conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {138}, number = {}, pages = {1-5}, doi = {10.1016/j.physbeh.2014.10.015}, pmid = {25447753}, issn = {1873-507X}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Drinking Behavior ; Drinking Water ; *Extinction, Psychological ; Lithium Chloride/administration & dosage ; Male ; *Motor Activity ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; *Taste Perception ; Time Factors ; }, abstract = {Studies have shown that exercise can enhance learning and memory. Conditioned taste aversion (CTA) is an avoidance behavior induced by associative memory of the taste sensation for something pleasant or neutral with a negative visceral reaction caused by the coincident action of a toxic substance that is tasteless or administered systemically. We sought to measure the effects of treadmill exercise on CTA in rats by investigating the effects of exercise on acquisition, extinction and spontaneous recovery of CTA. We made two groups of rats: an exercise group that ran on a treadmill, and a control group that did not have structured exercise periods. To condition rats to disfavor a sweet taste, consumption of a 0.1% saccharin solution in place of drinking water was paired with 0.15M LiCl (2% body weight, i.p.) to induce visceral discomfort. We measured changes of saccharin consumption during acquisition and extinction of CTA. The exercise and no-exercise groups both acquired CTA to similar levels and showed maximum extinction of CTA around 6 days after acquisition. This result indicates that exercise affects neither acquisition nor extinction of CTA. However, in testing for preservation of CTA after much longer extinction periods that included exercise or not during the intervening period, exercising animals showed a significantly lower saccharin intake, irrespective of having exercised or not during the conditioning phase of the trial. This result suggests that exercise may help to preserve aversive memory (taste aversion in this example) as evidence by the significant spontaneous recovery of aversion in exercising animals.}, } @article {pmid25447516, year = {2015}, author = {Hishimura, Y}, title = {Interactions with conspecific attenuate conditioned taste aversions in mice.}, journal = {Behavioural processes}, volume = {111}, number = {}, pages = {34-36}, doi = {10.1016/j.beproc.2014.11.006}, pmid = {25447516}, issn = {1872-8308}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/*physiology ; Drinking ; *Interpersonal Relations ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Saccharin/pharmacology ; Stress, Psychological/psychology ; Sweetening Agents/pharmacology ; Taste/*physiology ; }, abstract = {Social animals both increase and decrease their stress levels by interacting with conspecifics. The present study examines the effect of interaction with a conspecific on conditioned taste aversion in 32 male mice. Subjects were injected with lithium chloride immediately after drinking saccharin solution for 30 min. They were then exposed to a male conspecific for 3h following the poisoning. In the subsequent three consecutive days of two-bottle tests involving a choice between saccharin solution and water, they showed attenuated conditioned taste aversion compared with controls exposed to no conspecific after poisoning. These results confirm social interaction with a conspecific reduces conditioned taste aversion in mice. The implications of these findings are discussed with regard to social buffering effect and stress-induced analgesia.}, } @article {pmid25447298, year = {2015}, author = {Feifel, D and Shilling, PD and Hillman, J and Maisel, M and Winfield, J and Melendez, G}, title = {Peripherally administered oxytocin modulates latent inhibition in a manner consistent with antipsychotic drugs.}, journal = {Behavioural brain research}, volume = {278}, number = {}, pages = {424-428}, pmid = {25447298}, issn = {1872-7549}, support = {R01 MH080910/MH/NIMH NIH HHS/United States ; R01 MH103421/MH/NIMH NIH HHS/United States ; R01MH080910/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Antipsychotic Agents/*administration & dosage ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Dose-Response Relationship, Drug ; Drug Administration Routes ; Food Deprivation ; *Inhibition, Psychological ; Lithium Chloride/pharmacology ; Oxytocin/*administration & dosage ; Rats ; Reflex, Startle/*drug effects ; }, abstract = {BACKGROUND: Peripherally administered oxytocin (OT) has produced antipsychotic drug (APD)-like effects in animal tests that are predictive of APD efficacy. However, these effects have mainly been demonstrated using animal models of schizophrenia-like deficits in prepulse inhibition (PPI) of the startle reflex. Another schizophrenia-relevant abnormality that is the basis of a predictive animal test for APD efficacy is deficient latent inhibition (LI). LI is the normal suppression of a classically conditioned response when the subject is pre-exposed to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (UCS). Conditioned taste aversion (CTA), the normal avoidance of ingesting a food or liquid by animals when its taste is associated with an aversive experience, was used to test whether OT facilitates LI consistent with APDs.

METHODS: Brown Norway rats, known to naturally display attenuated LI, were aversively conditioned on two consecutive exposures to flavored drinking water (0.1% saccharin) by pairing it with malaise-inducing lithium chloride injections. Concurrent with conditioning, rats received subcutaneous OT (0.02, 0.1, 0.5mg/kg) or saline. Some rats were pre-exposed to the flavored water prior to its aversive conditioning (pre-exposed) while others were not (non pre-exposed). Two days after aversive conditioning the amount of flavored water consumed during a 20-min session was recorded.

RESULTS: As expected, LI, defined as greater consumption by pre-exposed vs. non pre-exposed rats was only weakly exhibited in Brown Norway rats and OT enhanced LI by reducing CTA in pre-exposed rats in a dose-dependent manner, with the 0.02 mg/kg dose producing the strongest effect.

CONCLUSIONS: The facilitation of LI by OT is consistent with the effects produced by APDs and provides further support for the notion that OT has therapeutic potential for schizophrenia.}, } @article {pmid25416606, year = {2015}, author = {Arriola, N and Alonso, G and Vázquez, GA and Rodríguez, G}, title = {Pavlovian discrimination in rats using voluntary exposure to a lithium chloride procedure.}, journal = {Laboratory animals}, volume = {49}, number = {3}, pages = {201-208}, doi = {10.1177/0023677214558702}, pmid = {25416606}, issn = {1758-1117}, mesh = {Animals ; *Conditioning, Classical ; Drinking/drug effects ; Lithium Chloride/*pharmacology ; Male ; Random Allocation ; Rats/*physiology ; Rats, Sprague-Dawley ; Sucrose/*pharmacology ; *Taste ; }, abstract = {In a conditioned taste aversion (CTA) procedure, the consumption of a flavor is followed by the administration of a toxin (e.g. lithium chloride, LiCl), resulting in the future avoidance of the flavor. CTA studies typically make use of forced-exposure paradigms where a volume of the toxin dependent upon the weight of the animal is injected. The use of forced paradigms can be problematic when extended training is required, such as in stimulus discrimination training involving similar flavors, since the animals can be exposed to a high amount of the toxin. In the present study we confirmed the viability of an alternative voluntary-exposure paradigm that more closely mimics natural conditions and is more considerate of the welfare of the animals as a useful tool for investigating discrimination training. In three experiments, rats received free access to either a flavor (sucrose in Experiments 1a and 1b, and saccharin in Experiment 2) or a compound of the flavor mixed with LiCl. The presence of LiCl in the compound induced post-consumption illness. Rats acquired an aversion to the flavor + LiCl compound, thus reducing both their consumption of, and exposure to, LiCl, and gradually increased their consumption of the flavor alone. The present paradigm is more similar to natural conditions than the forced-exposure paradigm as it allows the animals to experience a direct relationship between the amount of the flavor consumed and the magnitude of the illness induced by the toxin.}, } @article {pmid25367561, year = {2015}, author = {Gaztañaga, M and Aranda-Fernández, PE and Díaz-Cenzano, E and Chotro, MG}, title = {Latent inhibition and facilitation of conditioned taste aversion in preweanling rats.}, journal = {Developmental psychobiology}, volume = {57}, number = {1}, pages = {96-104}, doi = {10.1002/dev.21263}, pmid = {25367561}, issn = {1098-2302}, mesh = {Animals ; Animals, Newborn ; *Avoidance Learning ; *Conditioning, Psychological ; Female ; *Inhibition, Psychological ; Male ; Rats ; Rats, Wistar ; Taste ; }, abstract = {Early in ontogeny, taste preexposure has been found to induce latent inhibition as well as produce a facilitation of conditioned taste aversion (CTA). In this study, the effect of taste preexposure on CTA was investigated in 13-14 day old rats as a function of taste preexposure (0, 1, or 3 trials) and unconditioned stimulus intensity (LiCl: 0, 0.15, or 0.30 M). After one conditioning trial, with the low intensity US, an aversion was only observed after taste preexposure (facilitation). When using the strong US, an aversion was found without preexposure while latent inhibition was observed with 3 preexposure trials. In conclusion, stimulus preexposure can either facilitate conditioning or produce latent inhibition in infant rats, depending on the amount of stimulus preexposure and the intensity of the US.}, } @article {pmid25355215, year = {2014}, author = {Ounallah-Saad, H and Sharma, V and Edry, E and Rosenblum, K}, title = {Genetic or pharmacological reduction of PERK enhances cortical-dependent taste learning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {34}, number = {44}, pages = {14624-14632}, pmid = {25355215}, issn = {1529-2401}, mesh = {Adenine/analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/drug effects/physiology ; Cerebral Cortex/drug effects/*physiology ; Eukaryotic Initiation Factor-2/metabolism ; Indoles/pharmacology ; Learning/drug effects/*physiology ; Mice ; Phosphorylation ; RNA, Small Interfering ; Rats ; Taste/drug effects/*physiology ; eIF-2 Kinase/antagonists & inhibitors/genetics/*metabolism ; }, abstract = {Protein translation initiation is controlled by levels of eIF2α phosphorylation (p-eIF2α) on Ser51. In addition, increased p-eIF2α levels impair long-term synaptic plasticity and memory consolidation, whereas decreased levels enhance them. Levels of p-eIF2α are determined by four kinases, of which protein kinase RNA-activated (PKR), PKR-like endoplastic reticulum kinase (PERK), and general control nonderepressible 2 are extensively expressed in the mammalian mature brain. Following identification of PERK as the major kinase to determine basal levels of p-eIF2α in primary neuronal cultures, we tested its function as a physiological constraint of memory consolidation in the cortex, the brain structure suggested to store, at least in part, long-term memories in the mammalian brain. To that aim, insular cortex (IC)-dependent positive and negative forms of taste learning were used. Genetic reduction of PERK expression was accomplished by local microinfusion of a lentivirus harboring PERK Short hairpin RNA, and pharmacological inhibition was achieved by local microinfusion of a PERK-specific inhibitor (GSK2606414) to the rat IC. Both genetic reduction of PERK expression and pharmacological inhibition of its activity reduced p-eIF2α levels and enhanced novel taste learning and conditioned taste aversion, but not memory retrieval. Moreover, enhanced extinction was observed together with enhanced associative memory, suggesting increased cortical-dependent behavioral plasticity. The results suggest that, by phosphorylating eIF2α, PERK functions in the cortex as a physiological constraint of memory consolidation, and its downregulation serves as cognitive enhancement.}, } @article {pmid25324744, year = {2014}, author = {Joels, G and Lamprecht, R}, title = {Fear memory formation can affect a different memory: fear conditioning affects the extinction, but not retrieval, of conditioned taste aversion (CTA) memory.}, journal = {Frontiers in behavioral neuroscience}, volume = {8}, number = {}, pages = {324}, pmid = {25324744}, issn = {1662-5153}, abstract = {The formation of fear memory to a specific stimulus leads to subsequent fearful response to that stimulus. However, it is not apparent whether the formation of fear memory can affect other memories. We study whether specific fearful experience leading to fear memory affects different memories formation and extinction. We revealed that cued fear conditioning, but not unpaired or naïve training, inhibited the extinction of conditioned taste aversion (CTA) memory that was formed after fear conditioning training in rats. Fear conditioning had no effect on retrieval of CTA memory but specifically impaired its extinction. Extinguished fear memory, after fear extinction training, had no effect on future CTA memory extinction. Fear conditioning had no effect on CTA memory extinction if CTA memory was formed before fear conditioning. Conditioned taste aversion had no effect on fear conditioning memory extinction. We conclude that active cued fear conditioning memory can affect specifically the extinction, but not the formation, of future different memory.}, } @article {pmid25300672, year = {2014}, author = {Parkes, SL and De la Cruz, V and Bermúdez-Rattoni, F and Coutureau, E and Ferreira, G}, title = {Differential role of insular cortex muscarinic and NMDA receptors in one-trial appetitive taste learning.}, journal = {Neurobiology of learning and memory}, volume = {116}, number = {}, pages = {112-116}, doi = {10.1016/j.nlm.2014.09.008}, pmid = {25300672}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Cerebral Cortex/*drug effects/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Male ; Muscarinic Antagonists/pharmacology ; Rats ; Rats, Wistar ; Receptors, Muscarinic/*metabolism ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Saccharin/pharmacology ; Scopolamine/pharmacology ; Taste/*physiology ; Valine/analogs & derivatives/pharmacology ; }, abstract = {Our current understanding of the neurobiology of taste learning and memory has been greatly facilitated by the use of a reliable behavioural model, conditioned taste aversion (CTA). This model has revealed that the insular cortex (IC), specifically muscarinic and N-methyl-d-aspartate (NMDA) receptor activation in the IC, is critical for the formation of aversive taste memories. In contrast, current models of appetitive taste learning are less adequate, relying on the use of neophobic tastes (attenuation of neophobia) or on the integration of appetitive and aversive taste memories (latent inhibition of CTA). While these models have implicated IC muscarinic receptors, the involvement of NMDA receptors in the IC remains unclear. Here, we examined the role of both muscarinic and NMDA receptors in appetitive taste learning using a simple paradigm that is independent of neophobic and aversive components. First, we demonstrated that a single exposure to a novel taste, saccharin 0.1%, is sufficient to promote an appetitive taste memory as revealed by an increase in saccharin consumption during the second presentation. This increase was blocked by bilateral infusion in the IC of the muscarinic receptor antagonist, scopolamine. In contrast, infusion of the NMDA receptor antagonist, AP5, did not block appetitive taste learning but did abolish CTA. Therefore, common and distinct molecular substrates within the IC mediate appetitive versus aversive learning about the same taste.}, } @article {pmid25289087, year = {2014}, author = {Shi, J}, title = {Evaluating the various phases of cisplatin-induced emesis in rats.}, journal = {Oncology letters}, volume = {8}, number = {5}, pages = {2017-2022}, pmid = {25289087}, issn = {1792-1074}, abstract = {Use of cisplatin as a chemotherapeutic agent causes acute and delayed emesis. Kaolin, saccharin solution and normal feed consumption have been evaluated as an index of cisplatin-induced emesis in rats; however, the most preferable of these methods for evaluating the various phases of emesis remains unclear. In the current study, kaolin, saccharin solution and normal feed consumption following cisplatin administration (6 mg/kg intraperitoneally) were simultaneously investigated in rats. Kaolin consumption increased significantly following cisplatin administration and was attenuated by granisetron administration 0-24 h following the injection. Saccharin solution consumption, however, decreased significantly 0-48 h following cisplatin administration, however, was attenuated by administration of granisetron within 0-24 h only. A reduced intake of normal feed was observed in the control group and was reversed by granisetron within the 0-72 h period. The present study indicates that kaolin consumption may be evaluated as an index of cisplatin-induced acute emesis and saccharin solution consumption may be evaluated as an index of delayed emesis, while normal feed consumption as an indicator of anorexia nervosa may be suitable to evaluate all phases of emesis and serve as an indicator of quality of life.}, } @article {pmid25282171, year = {2014}, author = {Ouhaz, Z and Ba-M'hamed, S and Bennis, M}, title = {Haloperidol treatment at pre-exposure phase reduces the disturbance of latent inhibition in rats with neonatal ventral hippocampus lesions.}, journal = {Comptes rendus biologies}, volume = {337}, number = {10}, pages = {561-570}, doi = {10.1016/j.crvi.2014.07.005}, pmid = {25282171}, issn = {1768-3238}, mesh = {Animals ; *Animals, Newborn ; Antipsychotic Agents ; Behavior, Animal ; Conditioning, Psychological ; Disease Models, Animal ; Haloperidol/*administration & dosage ; Hippocampus/*drug effects/*growth & development ; Lidocaine/administration & dosage ; Motor Activity ; Rats ; Rats, Sprague-Dawley ; Schizophrenia/*chemically induced/prevention & control ; Schizotypal Personality Disorder/prevention & control ; Taste ; }, abstract = {Animals with neonatal ventral hippocampal lesions develop during or after adolescence abnormal behaviors related to schizophrenia such as anxiety and latent inhibition disruption. The aim of this study was to test whether haloperidol injection prior to pre-exposure session in the latent inhibition test would facilitate latent inhibition. Lesioned animals showed a significant decrease in the number and duration of social interactions, a decrease in the marbles buried, a significant increase in locomotor activity, and a disruption of latent inhibition. In the conditioned taste aversion test, injection of haloperidol produced the recovery of latent inhibition. These findings demonstrate that neonatal lidocaine lesion of the ventral hippocampus can induce behavioral changes related to schizophrenia, and injection of haloperidol, when restricted only to a three-day pre-exposure, is sufficient to facilitate latent inhibition.}, } @article {pmid25269859, year = {2015}, author = {Molero-Chamizo, A}, title = {Excitotoxic lesion of the posterior part of the dorsal striatum does not affect the typically dopaminergic phenomenon of latent inhibition in conditioned taste aversion.}, journal = {Neuroscience research}, volume = {91}, number = {}, pages = {8-12}, doi = {10.1016/j.neures.2014.09.006}, pmid = {25269859}, issn = {1872-8111}, mesh = {Animals ; *Avoidance Learning ; Behavior, Animal ; Conditioning, Psychological ; Corpus Striatum/*physiology ; Dopamine/*physiology ; Feeding Behavior ; *Inhibition, Psychological ; Male ; Rats, Wistar ; *Taste ; }, abstract = {The stimulation or blockade of dopaminergic activity interrupts or increases, respectively, the phenomenon of latent inhibition in different paradigms. Furthermore, the involvement of the nucleus accumbens in latent inhibition has been demonstrated in several learning paradigms, including conditioned taste aversion. However, the role of the dorsal striatum in the pre-exposure effect on the acquisition of taste aversion remains unclear. In order to determine whether this region of the striatum is a structure necessary for latent inhibition of conditioned taste aversion, excitotoxic lesions were made in the posterior part of the dorsal striatum of Wistar rats. Subsequently, half of the animals was pre-exposed to the flavor, and the magnitude of the taste aversion was compared to that of sham animals pre-exposed and non-pre-exposed to the same flavor. The results showed that the excitotoxic lesion in this area of the dorsal striatum, compared to sham animals, left latent inhibition of the conditioned taste aversion intact. These data suggest that the posterior part of the dorsal striatum is not necessary for the acquisition of latent inhibition, at least in the conditioned taste aversion paradigm.}, } @article {pmid25251840, year = {2015}, author = {García-Medina, NE and Vera, G and Miranda, MI}, title = {Chemical stimulation or glutamate injections in the nucleus of solitary tract enhance conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {278}, number = {}, pages = {202-209}, doi = {10.1016/j.bbr.2014.09.023}, pmid = {25251840}, issn = {1872-7549}, mesh = {Animals ; Basolateral Nuclear Complex/*drug effects/*metabolism ; Conditioning, Classical/drug effects ; Glutamic Acid/metabolism ; Injections, Intraperitoneal ; Lithium Chloride/administration & dosage/pharmacology ; Male ; Memory/*drug effects ; Microdialysis ; Norepinephrine/metabolism ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/drug effects/*metabolism ; Stimulation, Chemical ; Taste/*drug effects ; }, abstract = {Taste memory depends on motivational and post-ingestional consequences after a single taste-illness pairing. During conditioned taste aversion (CTA), the taste and visceral pathways reach the nucleus of the solitary tract (NTS), which is the first relay in the CNS and has a vital function in receiving vagal chemical stimuli and humoral signals from the area postrema that receives peripheral inputs also via vagal afferent fibers. The specific aim of the present set of experiments was to determine if the NTS is involved in the noradrenergic and glutamatergic activation of the basolateral amygdala (BLA) during CTA. Using in vivo microdialysis, we examined whether chemical NTS stimulation induces norepinephrine (NE) and/or glutamate changes in the BLA during visceral stimulation with intraperitoneal (i.p.) injections of low (0.08 M) and high (0.3 M) concentrations of lithium chloride (LiCl) during CTA training. The results showed that strength of CTA can be elicited by chemical NTS stimulation (Ringer's high potassium solution; 110 mM KCl) and by intra-NTS microinjections of glutamate, immediately after, but not before, low LiCl i.p. injections that only induce a week aversive memory. However visceral stimulation (with low or high i.p. LiCl) did not induce significantly more NE release in the amygdala compared with the NE increment induced by NTS potassium depolarization. In contrast, high i.p. concentrations of LiCl and chemical NTS stimulation induced a modest glutamate sustained release, that it is not observed with low LiCl i.p. injections. These results indicate that the NTS mainly mediates the visceral stimulus processing by sustained releasing glutamate in the BLA, but not by directly modulating NE release in the BLA during CTA acquisition, providing new evidence that the NTS has an important function in the transmission of signals from the periphery to brain systems that process aversive memory formation.}, } @article {pmid25241211, year = {2014}, author = {Quintero, E and Vargas, JP and Diaz, E and Escarabajal, MD and Carrasco, M and López, JC}, title = {c-Fos positive nucleus reveals that contextual specificity of latent inhibition is dependent of insular cortex.}, journal = {Brain research bulletin}, volume = {108}, number = {}, pages = {74-79}, doi = {10.1016/j.brainresbull.2014.08.008}, pmid = {25241211}, issn = {1873-2747}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/metabolism/*physiology ; Conditioning, Psychological ; *Inhibition, Psychological ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats, Wistar ; Taste Perception/*physiology ; }, abstract = {The present study analyzed the functional activity of granular and agranular insular cortices in contextual specificity of latent inhibition using a conditioned taste aversion paradigm. c-Fos immunolabeling was examined in insular cortex in preexposed and no preexposed groups under similar and different context conditions. Result showed that the exposition to a novel taste increased c-fos activity in insular cortex. However, a context shift caused an increase in immunolabeling in animals preexposed to saccharine. These results suggest insular cortex is part of a complex system to evaluate taste-response, and it may read the meaning of taste stimuli depending on the context.}, } @article {pmid25232100, year = {2014}, author = {Kimbrough, A and Biggs, LM}, title = {BDNF signaling potentiates transmission of information from the basolateral amygdala to infralimbic prefrontal cortex during conditioned taste aversion extinction.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {34}, number = {38}, pages = {12617-12618}, pmid = {25232100}, issn = {1529-2401}, support = {T32 DC000044/DC/NIDCD NIH HHS/United States ; T32-00044//PHS HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain-Derived Neurotrophic Factor/*metabolism ; Extinction, Psychological/*physiology ; Humans ; Male ; Prefrontal Cortex/*physiology ; Signal Transduction/*physiology ; Taste/*physiology ; }, } @article {pmid25231850, year = {2014}, author = {Hurtado, MM and García, R and Puerto, A}, title = {Tiapride impairs the aversive effect of electrical stimulation of the parabrachial complex in a conditioned place task.}, journal = {Acta neurobiologiae experimentalis}, volume = {74}, number = {3}, pages = {307-316}, pmid = {25231850}, issn = {1689-0035}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal/drug effects ; Brain/*drug effects/pathology ; Conditioning, Psychological/*physiology ; Dopamine/metabolism ; *Electric Stimulation ; Male ; Rats, Wistar ; Reward ; Tiapride Hydrochloride/administration & dosage/*pharmacology ; }, abstract = {The parabrachial complex has been related to various rewarding or aversive behavioral processes, including taste aversion learning and conditioned place aversion. This study examined the effect of tiapride, an antagonist of D2/D3 dopaminergic receptors, on place aversion induced by electrical stimulation of the external lateral parabrachial (LPBe) nucleus. Results obtained show that brain-stimulated animals avoid the area of the maze associated with electrical stimulation but show no such behavioral rejection when they receive an injection of 30 mg/kg tiapride. Furthermore, tiapride did not appear to affect the horizontal motor activity (crossing) of the animals. These results are discussed in the context of the different natural and artificial modalities used to induce aversive behavior and their relationship with dopamine systems.}, } @article {pmid25223979, year = {2014}, author = {Risco, S and Mediavilla, C}, title = {Orexin-1 receptor antagonist in central nucleus of the amygdala attenuates the acquisition of flavor-taste preference in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {126}, number = {}, pages = {7-12}, doi = {10.1016/j.pbb.2014.09.002}, pmid = {25223979}, issn = {1873-5177}, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Benzoxazoles/administration & dosage/*pharmacology ; Central Amygdaloid Nucleus/*drug effects/physiology ; Food Preferences/*drug effects/physiology ; Lithium Chloride/pharmacology ; Male ; Microinjections ; Naphthyridines ; *Orexin Receptor Antagonists ; Orexin Receptors/physiology ; Rats ; Saccharin/pharmacology ; Taste Perception/*drug effects ; Urea/administration & dosage/*analogs & derivatives/pharmacology ; }, abstract = {Previous studies demonstrated that the intracerebroventricular administration of SB-334867-A, a selective antagonist of orexin OX1R receptors, blocks the acquisition of saccharin-induced conditioned flavor preference (CFP) but not LiCl-induced taste aversion learning (TAL). Orexinergic fibers from the lateral hypothalamus end in the central nucleus of the amygdala (CeA), which expresses orexin OX1R receptors. Taste and sensory inputs also are present in CeA, which may contribute to the development of taste learning. This study analyzed the effect of two doses (1.5 and 6μg/0.5μl) of SB-334867-A administered into the CeA on flavor-taste preference induced by saccharin and on TAL induced by a single administration of LiCl (0.15M, 20ml/kg, i.p.). Outcomes indicate that inactivation of orexinergic receptors in the CeA attenuates flavor-taste preference in a two-bottle test (saccharin vs. water). Intra-amygdalar SB-334867-A does not affect gustatory processing or the preference for the sweet taste of saccharin given that SB-334867-A- and DMSO-treated groups (control animals) increased the intake of the saccharin-associated flavor across training acquisition sessions. Furthermore, SB-334867-A in the CeA does not block TAL acquisition ruling out the possibility that functional inactivation of OX1R receptors interferes with taste processing. Orexin receptors in the CeA appear to intervene in the association of a flavor with orosensory stimuli, e.g., a sweet and pleasant taste, but could be unnecessary when the association is established with visceral stimuli, e.g., lithium chloride. These data suggest that orexinergic projections to the CeA may contribute to the reinforcing signals facilitating the acquisition of taste learning and the change in hedonic evaluation of the taste, which would have important implications for the OX1R-targeted pharmacological treatment of eating disorders.}, } @article {pmid25209712, year = {2014}, author = {Revillo, DA and Gaztañaga, M and Aranda, E and Paglini, MG and Chotro, MG and Arias, C}, title = {Context-dependent latent inhibition in preweanling rats.}, journal = {Developmental psychobiology}, volume = {56}, number = {7}, pages = {1507-1517}, doi = {10.1002/dev.21236}, pmid = {25209712}, issn = {1098-2302}, mesh = {Age Factors ; Animals ; Conditioning, Classical/*physiology ; *Inhibition, Psychological ; Learning/*physiology ; Rats ; }, abstract = {Preexposure to a conditioned stimulus (CS) usually weakens conditioning, an effect known as latent inhibition. Similar to other learning interference effects, latent inhibition has been characterized as context-dependent, which means that the magnitude of this effect can be attenuated by changing the context between the different phases of the procedure (e.g., preexposure and conditioning). Latent inhibition has been found with a variety of procedures in infant rats, but the few studies that examined the context-dependency of this phenomenon during this ontogenetic period found no context-change effect. The present study explored the context-dependency of latent inhibition during infancy using a conditioned taste aversion preparation and employing contexts enriched with distinctive odors to increase the possible efficacy of the context manipulation. Experiment 1 showed that three preexposures to the CS (saccharin) were sufficient to retard conditioning to the same CS, although this effect was also observed in a control group preexposed to an alternative taste stimulus (saline), in comparison with a non-preexposed control group. In Experiment 2a, the CS-preexposure effect was found to be specific to the preexposed CS when the number of preexposures was increased. This effect was revealed as context-dependent in Experiment 2b, since it was attenuated by changing the context between preexposure and conditioning. The present result is consistent with recent studies showing the context-dependency of extinction in preweanling rats, thus demonstrating these animals' capacity to learn about context early on in their development.}, } @article {pmid25173061, year = {2014}, author = {Nakajima, S and Katayama, T}, title = {Running-based pica in rats. Evidence for the gastrointestinal discomfort hypothesis of running-based taste aversion.}, journal = {Appetite}, volume = {83}, number = {}, pages = {178-184}, doi = {10.1016/j.appet.2014.08.031}, pmid = {25173061}, issn = {1095-8304}, mesh = {Abdominal Pain/chemically induced/etiology/*physiopathology/prevention & control ; Aluminum Silicates/administration & dosage ; Animals ; *Avoidance Learning ; Behavior, Animal ; Clay ; *Disease Models, Animal ; Dysgeusia/chemically induced/*etiology/physiopathology/prevention & control ; Emetics/administration & dosage/toxicity ; Injections, Intraperitoneal ; Kaolin/administration & dosage ; Lithium Chloride/administration & dosage/toxicity ; Male ; *Models, Biological ; Motor Activity ; Nausea/chemically induced/etiology/physiopathology/prevention & control ; Physical Exertion ; Pica/*etiology ; Rats, Wistar ; *Stress, Physiological ; }, abstract = {Voluntary running in an activity wheel establishes aversion to paired taste in rats. A proposed mechanism underlying this taste aversion learning is gastrointestinal discomfort caused by running. We tested this hypothesis by measuring the pica behavior (kaolin clay intake) of rats, because it is known that rats engage in pica behavior after various nausea-inducing treatments including irradiation, motion sickness, and injection of emetic drugs such as lithium chloride (LiCl). Following a demonstration of the already-known phenomenon of LiCl-based pica in Experiment 1, we successfully showed running-based pica behavior in Experiment 2 where the running treatment was compared with a non-running control treatment (i.e., confinement in a locked wheel). These results suggest that not only LiCl but also running induces nausea in rats, supporting the gastrointestinal discomfort hypothesis of running-based taste aversion learning.}, } @article {pmid25128878, year = {2014}, author = {Gramsch, C and Kattoor, J and Icenhour, A and Forsting, M and Schedlowski, M and Gizewski, ER and Elsenbruch, S}, title = {Learning pain-related fear: neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain.}, journal = {Neurobiology of learning and memory}, volume = {116}, number = {}, pages = {36-45}, doi = {10.1016/j.nlm.2014.08.003}, pmid = {25128878}, issn = {1095-9564}, mesh = {Adult ; Brain/*physiopathology ; Brain Mapping ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Fear/*physiology/psychology ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Neurons/physiology ; Visceral Pain/*physiopathology/psychology ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: There exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS-US learning trials ("rapid conditioning"), and explored the underlying neural substrates of these learning and memory processes.

METHODS: In N=24 healthy men and women, "rapid" fear acquisition was accomplished by pairing visual conditioned stimuli (CS(+)) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US (differential delay conditioning with five CS(+) and five CS(-) presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS-US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p<.001 uncorrected) and in regions-of-interest analyses with familywise error correction of alpha (pFWE<.05). Differential neural activation in response to the CS during each experimental phase (i.e., CS(+)>CS(-); CS(+)
RESULTS: A significant valence change (i.e. increased CS(+) unpleasantness) was observed following acquisition, indicating successful differential aversive learning. On the other hand, CS-US contingency awareness was not fully established. These behavioral results were paralleled by differential activation of the putamen (pFWE<.05), insula (pFWE<.05) and secondary somatosensory cortex (S2, p<.001 uncorrected) in response to the CS(+) during acquisition. The same analysis with a linear parametric modulation confirmed but also strengthened the resulting activations, which were all highly significant in ROI analyses at pFWE<.05. Extinction and reinstatement involved differential activation in response to the CS(-), involving the cingulate cortex and primary motor cortex (M1) during extinction and the posterior cingulate cortex (PCC) during reinstatement (all p<.001 uncorrected), without obvious effects upon linear parametric modulation analysis.

CONCLUSIONS: Abdominal pain stimuli are effective US that elicit conditioned pain-related fear even after very few learning experiences without full contingency awareness. These findings extend similar evidence of "rapid learning" in response to interoceptive US (e.g., conditioned taste aversion, conditioned nausea), and have implications for the pathophysiology and treatment of chronic abdominal pain such as in IBS.}, } @article {pmid25076870, year = {2014}, author = {Burke, CJ and Dreher, JC and Seymour, B and Tobler, PN}, title = {State-dependent value representation: evidence from the striatum.}, journal = {Frontiers in neuroscience}, volume = {8}, number = {}, pages = {193}, pmid = {25076870}, issn = {1662-4548}, } @article {pmid24990860, year = {2014}, author = {Noble, EE and Billington, CJ and Kotz, CM and Wang, C}, title = {Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {307}, number = {6}, pages = {R737-45}, pmid = {24990860}, issn = {1522-1490}, support = {T32 DK083250/DK/NIDDK NIH HHS/United States ; T32DK-083250/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Obesity Agents/*administration & dosage ; Dose-Response Relationship, Drug ; Eating/drug effects ; Energy Metabolism/*drug effects ; Fasting ; Feeding Behavior/*drug effects ; Injections, Intraventricular ; Male ; Motor Activity/drug effects ; Oxytocin/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Satiety Response/drug effects ; Time Factors ; Ventromedial Hypothalamic Nucleus/*drug effects/metabolism ; }, abstract = {Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin.}, } @article {pmid24974748, year = {2014}, author = {Neuwirthová, J and Gál, B and Smilek, P and Kostřica, R}, title = {[Importance of taste in maintaining homeostasis and pathological impact of orosensory reflexes distraction in relation to sweet taste after non-caloric sweeteners consumption].}, journal = {Vnitrni lekarstvi}, volume = {60}, number = {5-6}, pages = {454-457}, pmid = {24974748}, issn = {0042-773X}, mesh = {Appetite Regulation ; Homeostasis ; Humans ; *Sweetening Agents ; *Taste ; }, abstract = {Taste signals and their reflexes have important signalling function in nature. They protect organism against toxic substances in food with help of taste aversion, they help to cope nutrition deficiencies through taste preferences, on the other hand, they act in many postprandial reflexes to maintain energy homeostasis. It is well-known that sweet taste is important oro-sensory stimulus for mammals. It acts as predictor of caloric food intake even before its entry into stomach and circulation. Taste and other oro-sensory signals from oral cavity affect not only the intake regulation, but also influence hormonal, neural and metabolic pathways to maintain homeostasis. The aim is to utilize effectively food energy and prevent energy instability of organism. Oro-sensory reflexes mediated by taste cells develop naturally from the first contact with sweet breast milk in infancy. It has been proven that the attenuation of reflexes due to the use of artificial sweeteners that don´t bring any caloric value to human body leads to hormonal and energetic dysregulation of organism and may contribute to metabolic syndrome.}, } @article {pmid24853379, year = {2014}, author = {Sanjuán, Mdel C and Nelson, JB and Alonso, G}, title = {An easy-to-hard effect after nonreinforced preexposure in a sweetness discrimination.}, journal = {Learning & behavior}, volume = {42}, number = {3}, pages = {209-214}, pmid = {24853379}, issn = {1543-4508}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Discrimination Learning/*physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Experiments 1A and 1B used a taste-aversion procedure with rats to demonstrate that exposure to easily discriminated flavors along a dimension (1 % and 10 % sucrose) can facilitate learning a subsequent hard discrimination (4 % and 7 % sucrose) when one of those flavors is paired with illness. Experiment 1A compared the effects of preexposure to the easily discriminated flavors against exposure to the same stimuli used in the discrimination training or no exposure at all. Experiment 1B replicated the conditions in Experiment 1A, with 2 additional days of training and unrestricted access to the flavors on CS+/CS- trials in discrimination training. Contrary to findings with multidimensional stimuli (Scahill & Mackintosh, Journal of Experimental Psychology: Animal Behavior Processes, 30, 96-103, 2004; Suret & McLaren, The Quarterly Journal of Experimental Psychology, 56B, 30-42, 2003), we found that preexposure to the easily discriminable stimuli varying along a single dimension of sweetness facilitated subsequent discrimination training over the other conditions in each experiment. We discuss the results in terms of the ideas presented by Gibson (1969) and Mackintosh (Psychological Review, 82, 276-298, 1975) and in terms of hedonic variables not considered by theories of perceptual learning.}, } @article {pmid24849362, year = {2014}, author = {Xin, J and Ma, L and Zhang, TY and Yu, H and Wang, Y and Kong, L and Chen, ZY}, title = {Involvement of BDNF signaling transmission from basolateral amygdala to infralimbic prefrontal cortex in conditioned taste aversion extinction.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {34}, number = {21}, pages = {7302-7313}, pmid = {24849362}, issn = {1529-2401}, mesh = {Amygdala/drug effects/*physiology ; Animals ; Antibodies/pharmacology ; Avoidance Learning/drug effects/*physiology ; Brain-Derived Neurotrophic Factor/genetics/immunology/*metabolism/pharmacology ; Carbazoles/pharmacology ; Enzyme Inhibitors/pharmacology ; Extinction, Psychological/drug effects/*physiology ; Gene Expression Regulation/drug effects ; Humans ; Indole Alkaloids/pharmacology ; Male ; Prefrontal Cortex/drug effects/*physiology ; Rats ; Rats, Wistar ; Receptor, trkB/genetics/metabolism ; Signal Transduction/*physiology ; Taste/*physiology ; Time Factors ; }, abstract = {Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator.}, } @article {pmid24847227, year = {2014}, author = {Marotta, R and Fenu, S and Scheggi, S and Vinci, S and Rosas, M and Falqui, A and Gambarana, C and De Montis, MG and Acquas, E}, title = {Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens.}, journal = {Frontiers in behavioral neuroscience}, volume = {8}, number = {}, pages = {153}, pmid = {24847227}, issn = {1662-5153}, abstract = {Conditioned taste aversion (CTA) can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK) in the prefrontal cortex (PFCx) and nucleus accumbens (Acb) of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1) and Thr(34)- and Thr(75-Dopamine-and-cAMP-Regulated) PhosphoProtein (DARPP-32). CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1) in the PFCx, whereas p-GluR1, p-Thr(34)- and p-Thr(75)-DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh) and core (AcbC) but left unmodified p-NR1, p-GluR1, p-Thr(34)- and p-Thr(75-DARPP-32) levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.}, } @article {pmid24841742, year = {2014}, author = {Cunningham, CL}, title = {Genetic relationship between ethanol-induced conditioned place preference and other ethanol phenotypes in 15 inbred mouse strains.}, journal = {Behavioral neuroscience}, volume = {128}, number = {4}, pages = {430-445}, pmid = {24841742}, issn = {1939-0084}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; R01AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Conditioning, Classical/*drug effects ; Ethanol/*pharmacology ; *Genotype ; Male ; Mice ; Mice, Inbred Strains ; Motor Activity/drug effects ; *Phenotype ; Reward ; }, abstract = {The genetic relationships between different behaviors used to index the rewarding or reinforcing effects of alcohol are poorly understood. To address this issue, ethanol-induced conditioned place preference (CPP) was tested in a genetically diverse panel of inbred mouse strains, and strain means from this study and other inbred strain studies were used to examine the genetic correlation between CPP and several ethanol-related phenotypes, including activity measures recorded during CPP training and testing. Mice from each strain were exposed to a well-characterized unbiased place conditioning procedure using ethanol doses of 2 or 4 g/kg; an additional group from each strain was exposed to saline alone on all trials. Genotype had a significant effect on CPP, basal locomotor activity, ethanol-stimulated activity, and the effect of repeated ethanol exposure on activity. Correlational analyses showed significant negative genetic correlations between CPP and sweetened ethanol intake and between CPP and test session activity, as well as a significant positive genetic correlation between CPP and chronic ethanol withdrawal severity. Moreover, there was a trend toward a positive genetic correlation between CPP and ethanol-induced conditioned taste aversion. These genetic correlations suggest overlap in the genetic mechanisms underlying CPP and each of these traits. The patterns of genetic relationships suggest a greater impact of ethanol's aversive effects on drinking and a greater impact of ethanol's rewarding effects on CPP. Overall, these data support the idea that genotype influences ethanol's rewarding effect, a factor that may contribute importantly to addictive vulnerability.}, } @article {pmid24840626, year = {2015}, author = {Gámiz, F and Recio, SA and Iliescu, AF and Gallo, M and de Brugada, I}, title = {Effects of dietary choline availability on latent inhibition of flavor aversion learning.}, journal = {Nutritional neuroscience}, volume = {18}, number = {6}, pages = {275-280}, doi = {10.1179/1476830514Y.0000000129}, pmid = {24840626}, issn = {1476-8305}, mesh = {Animals ; Behavior, Animal/drug effects ; Choline/*administration & dosage ; Conditioning, Classical/*drug effects ; Diet ; *Inhibition, Psychological ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {OBJECTIVE: It has been previously reported that dietary choline supplementation might affect latent inhibition (LI) using a conditioned suppression procedure in rats. We have assessed the effect of dietary choline on LI of flavor aversion learning.

METHOD: Adult male Wistar rats received a choline supplemented (5 g/kg), deficient (0 g/kg), or standard (1.1 g/kg) diet for 3 months. After this supplementation period, all rats went through a conditioned taste aversion (CTA) procedure, half of them being pre-exposed to the conditioned stimulus before the conditioning.

RESULTS: The results indicated that choline deficiency prevents LI of conditioned flavor aversion to cider vinegar (3%) induced by a LiCl (0.15 M; 2% body weight) intraperitoneal injection, while choline supplementation enhances CTA leading to slower extinction.

DISCUSSION: The role of the brain systems modulating attentional processes is discussed.}, } @article {pmid24819821, year = {2014}, author = {Sullivan, RM and Dufresne, MM and Siontas, D and Chehab, S and Townsend, J and Laplante, F}, title = {Mesocortical dopamine depletion and anxiety-related behavior in the rat: sex and hemisphere differences.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {54}, number = {}, pages = {59-66}, doi = {10.1016/j.pnpbp.2014.05.002}, pmid = {24819821}, issn = {1878-4216}, support = {MOP-93589//Canadian Institutes of Health Research/Canada ; }, mesh = {Adrenocorticotropic Hormone/blood ; Animals ; Anxiety/pathology/*physiopathology ; Dietary Sucrose/administration & dosage ; Dopamine/*metabolism ; Estrous Cycle/physiology ; Exploratory Behavior/physiology ; Functional Laterality/*physiology ; Maze Learning/physiology ; Motor Activity/physiology ; Neuropsychological Tests ; Oxidopamine ; Predatory Behavior ; Prefrontal Cortex/pathology/*physiopathology ; Rats, Sprague-Dawley ; Restraint, Physical ; *Sex Characteristics ; Stress, Psychological/physiopathology ; Taste Perception/physiology ; }, abstract = {The mesocortical dopamine (DA) system of the rat plays an important role in prefrontal cortex (PFC) regulation of stress and emotion and exhibits functional hemispheric asymmetry for such processing. Since few studies examine sex differences in this context, we compared the effects of left vs. right unilateral PFC DA depletion in males and females in several behavioral situations associated with anxiety or aversion. Adult rats received unilateral injections of 6-hydroxydopamine (6-OHDA) or vehicle in the ventromedial (vm) PFC. Behavioral tests included a predator odor burying test, elevated plus maze and sucrose consumption with simple taste aversion. Tissue analysis confirmed that vmPFCs injected with 6-OHDA were depleted of DA (75-85%) compared to controls. Burying behavior and sucrose consumption were affected only by left lesions, similarly in both sexes. However, risk assessment behaviors were affected by right lesions in opposite directions in males and females. Behaviors modified preferentially by the left cortex thus showed less evidence of sex differences than those modulated by the right. While mesocortical DA depletion effects are lateralized, the nature of these effects can vary with sex and specific behavior. Such findings may be clinically significant, given the large gender differences in the incidence of mood and anxiety disorders, which also show many lateralized prefrontal abnormalities.}, } @article {pmid24813806, year = {2014}, author = {Lin, JY and Arthurs, J and Reilly, S}, title = {Conditioned taste aversion, drugs of abuse and palatability.}, journal = {Neuroscience and biobehavioral reviews}, volume = {45}, number = {}, pages = {28-45}, pmid = {24813806}, issn = {1873-7528}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Food Preferences/*drug effects/physiology/psychology ; Humans ; Illicit Drugs ; Substance-Related Disorders/*physiopathology/psychology ; Taste Perception/*drug effects/physiology ; }, abstract = {We consider conditioned taste aversion to involve a learned reduction in the palatability of a taste (and hence in amount consumed) based on the association that develops when a taste experience is followed by gastrointestinal malaise. The present article evaluates the well-established finding that drugs of abuse, at doses that are otherwise considered rewarding and self-administered, cause intake suppression. Our recent work using lick pattern analysis shows that drugs of abuse also cause a palatability downshift and, therefore, support conditioned taste aversion learning.}, } @article {pmid24813701, year = {2014}, author = {Wang, Y and Song, Z and Everaert, N and De Ketelaere, B and Willemsen, H and Decuypere, E and Buyse, J}, title = {The anorectic effects of alpha-lipoicacid are mediated by central AMPK and are not due to taste aversion in chicken (Gallus gallus).}, journal = {Physiology & behavior}, volume = {132}, number = {}, pages = {66-72}, doi = {10.1016/j.physbeh.2014.04.047}, pmid = {24813701}, issn = {1873-507X}, mesh = {AMP-Activated Protein Kinases/genetics/*metabolism ; Agouti-Related Protein/metabolism ; Animals ; Appetite Depressants/*pharmacology ; Avoidance Learning/*drug effects ; Chickens ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Gene Expression Regulation/drug effects ; Hypothalamus/drug effects/*enzymology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Male ; Neuropeptide Y/metabolism ; Pro-Opiomelanocortin/metabolism ; Protein Subunits/genetics/metabolism ; RNA, Messenger/metabolism ; Taste/*drug effects ; Thioctic Acid/*pharmacology ; Thyrotropin-Releasing Hormone/metabolism ; Time Factors ; }, abstract = {AMP-activated protein kinase (AMPK) is an evolutionary conserved cellular energy sensor, which plays a pivotal role in mammalian energy homeostasis. The present study was aimed to explore the possible involvement of hypothalamic AMPK in feed intake regulation of broiler chickens. Hence, diets with 0, 0.05% or 0.1% α-lipoicacid (α-LA), a known AMPK inhibitor in mammals, were provided to broiler chicks for 7days. Alpha-LA exerted an anorectic effect, and the conditioned taste aversion test demonstrated that the effect was due to the alteration in satiety and not taste effects. However, the curtailed feed intake induced by α-LA disappeared on day 7. Hypothalamic AMPKα1 mRNA levels were significantly decreased by the dietary α-LA in concert with the reduced abundance in total AMPKα protein. The phosphorylated AMPKα was also decreased to a similar extend, resulting in an unaltered phosphorylated AMPKα/total AMPKα ratio. In addition, hypothalamic corticotropin releasing hormone mRNA levels were enhanced by α-LA. Interestingly, the mRNA expressions of hypothalamic orexigenic agouti-related peptide and neuropeptide Y were up-regulated, while the anorexigenic proopiomelanocortin and its transcription regulator hypoxia-inducible factor-1α were down-regulated, probably as a physiological reaction in order to counteract the altered energy balance. In conclusion, dietary α-LA decreased feed intake of broiler chicks. The anorectic effect was due to the reduced hypothalamic phosphorylated AMPKα as reflected in its decreased mRNA and protein levels. However, the anorectic effect of α-LA was progressively diminished after 7days of treatment, likely by a physiological counteractive feedback via changing neuropeptides involved in energy balance regulation.}, } @article {pmid24762441, year = {2014}, author = {Sisley, S and Gutierrez-Aguilar, R and Scott, M and D'Alessio, DA and Sandoval, DA and Seeley, RJ}, title = {Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect.}, journal = {The Journal of clinical investigation}, volume = {124}, number = {6}, pages = {2456-2463}, pmid = {24762441}, issn = {1558-8238}, support = {DK093848/DK/NIDDK NIH HHS/United States ; 1F32DK091077-01A1/DK/NIDDK NIH HHS/United States ; DK082480/DK/NIDDK NIH HHS/United States ; R01 DK093848/DK/NIDDK NIH HHS/United States ; R01 DK057900/DK/NIDDK NIH HHS/United States ; R01 DK082480/DK/NIDDK NIH HHS/United States ; F32 DK091077/DK/NIDDK NIH HHS/United States ; DK057900/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite Depressants/*pharmacology ; Body Weight/drug effects ; Central Nervous System/drug effects/physiology ; Diet, High-Fat ; Eating/drug effects ; Glucagon-Like Peptide 1/*analogs & derivatives/pharmacology ; Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents/pharmacology ; Liraglutide ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Peripheral Nerves/drug effects/physiology ; Receptors, Glucagon/deficiency/genetics/*physiology ; }, abstract = {Glucose control and weight loss are cornerstones of type 2 diabetes treatment. Currently, only glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance. Both glucose and body weight are regulated by the brain, which contains GLP1 receptors (GLP1R). Even though the brain is poised to mediate the effects of GLP1 analogs, it remains unclear whether the glucose- and body weight-lowering effects of long-acting GLP1R agonists are via direct action on CNS GLP1R or the result of downstream activation of afferent neuronal GLP1R. We generated mice with either neuronal or visceral nerve-specific deletion of Glp1r and then administered liraglutide, a long-acting GLP1R agonist. We found that neither reduction of GLP1R in the CNS nor in the visceral nerves resulted in alterations in body weight or food intake in animals fed normal chow or a high-fat diet. Liraglutide treatment provided beneficial glucose-lowering effects in both chow- and high-fat-fed mice lacking GLP1R in the CNS or visceral nerves; however, liraglutide was ineffective at altering food intake, body weight, or causing a conditioned taste aversion in mice lacking neuronal GLP1R. These data indicate that neuronal GLP1Rs mediate body weight and anorectic effects of liraglutide, but are not required for glucose-lowering effects.}, } @article {pmid24739358, year = {2014}, author = {Inui, T and Shimura, T}, title = {Delta-opioid receptor blockade in the ventral pallidum increases perceived palatability and consumption of saccharin solution in rats.}, journal = {Behavioural brain research}, volume = {269}, number = {}, pages = {20-27}, doi = {10.1016/j.bbr.2014.04.005}, pmid = {24739358}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Basal Forebrain/*drug effects/physiology ; Conditioning, Psychological/drug effects/physiology ; Dose-Response Relationship, Drug ; Drinking/drug effects/physiology ; Eating/*drug effects/physiology ; Male ; Motor Activity/drug effects/physiology ; Naltrexone/*analogs & derivatives/pharmacology ; Narcotic Antagonists/*pharmacology ; Rats, Wistar ; Receptors, Opioid, delta/*antagonists & inhibitors/metabolism ; Saccharin/administration & dosage ; Taste Perception/*drug effects/physiology ; }, abstract = {The ventral pallidum (VP) is involved in ingestive behaviour. It receives dense GABAergic projections from the nucleus accumbens. GABAergic terminals in the VP co-express enkephalin, an endogenous ligand of delta-opioid receptors. The role of the delta-opioid receptors in the VP in the context of ingestive behaviour remains unclear, in contrast to the well-understood involvement of the mu-opioid receptors. We used the single-bottle test to examine the effects of VP microinjections of the delta-opioid receptor antagonist naltrindole on consumption of a saccharin solution. Naltrindole injections significantly increased the intake of saccharin, but not water, during a 2-h test session. We also investigated perceived palatability of saccharin using a taste reactivity test. The drug treatments increased ingestive responses to intraorally infused saccharin. Further experimentation explored the role of VP delta-opioid receptors in behavioural responses to saccharin that were previously paired with malaise upon the retrieval of conditioned taste aversion (CTA). Naltrindole-injected rats exhibited longer latency for the first occurrence of aversive responses than vehicle-injected control rats. However, there was no between-group difference in total aversive responses. These results suggest that naltrindole injections into the VP induce an enhancement of perceived palatability of a normally preferred saccharin solution, and thereby facilitate consumption of the solution. On the other hand, delayed aversive responses to the conditioned aversive saccharin suggest that the delta-opioid receptors in the VP mediate the initiation of aversive taste reactivity responses to the conditioned stimulus upon CTA retrieval.}, } @article {pmid24735672, year = {2015}, author = {Uematsu, A and Kitamura, A and Iwatsuki, K and Uneyama, H and Tsurugizawa, T}, title = {Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and Agranular Insular Cortex During Taste Memory Formation.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {25}, number = {9}, pages = {2719-2728}, doi = {10.1093/cercor/bhu069}, pmid = {24735672}, issn = {1460-2199}, mesh = {Animals ; Avoidance Learning/drug effects ; Basolateral Nuclear Complex/blood supply/drug effects/*physiology ; Cerebral Cortex/blood supply/drug effects/*physiology ; Cholera Toxin/metabolism ; Diffusion Magnetic Resonance Imaging ; Glutamate Decarboxylase/metabolism ; Image Processing, Computer-Assisted ; Limbic Lobe/blood supply/drug effects/*physiology ; Lithium Chloride/pharmacology ; Magnetic Resonance Imaging ; Male ; Memory/drug effects/*physiology ; Oxygen/blood ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Wistar ; Statistics as Topic ; Taste/drug effects/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning.}, } @article {pmid24695107, year = {2014}, author = {Haack, AK and Sheth, C and Schwager, AL and Sinclair, MS and Tandon, S and Taha, SA}, title = {Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e92701}, pmid = {24695107}, issn = {1932-6203}, support = {R01 MH094870/MH/NIMH NIH HHS/United States ; MH094870/MH/NIMH NIH HHS/United States ; }, mesh = {Adrenergic alpha-2 Receptor Antagonists/*pharmacology ; *Alcohol Drinking/adverse effects/physiopathology ; Animals ; Behavior, Animal/*drug effects ; Central Nervous System Depressants/*adverse effects ; Ethanol/*adverse effects ; Habenula/pathology/*physiopathology ; Male ; Rats ; Rats, Long-Evans ; *Taste Disorders/chemically induced/physiopathology ; Yohimbine/*pharmacology ; }, abstract = {The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.}, } @article {pmid24631645, year = {2014}, author = {Garcia-Delatorre, P and Pérez-Sánchez, C and Guzmán-Ramos, K and Bermúdez-Rattoni, F}, title = {Role of glutamate receptors of central and basolateral amygdala nuclei on retrieval and reconsolidation of taste aversive memory.}, journal = {Neurobiology of learning and memory}, volume = {111}, number = {}, pages = {35-40}, doi = {10.1016/j.nlm.2014.03.003}, pmid = {24631645}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Basolateral Nuclear Complex/*physiology ; Central Amygdaloid Nucleus/*physiology ; Male ; Memory/*physiology ; Mental Recall/physiology ; Rats, Wistar ; Receptors, Ionotropic Glutamate/*physiology ; Taste/physiology ; }, abstract = {There are a number of experiments showing an important involvement of amygdala N-methyl-d-aspartate (NMDA) glutamate receptors on consolidation of conditioned taste aversion (CTA) memory. Interestingly, recent evidence has shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors are particularly involved in CTA retrieval. Memory reconsolidation has been proposed as a destabilization and re-stabilization process induced by memory reactivation. We have recently suggested that reconsolidation could be enabled in the absence of retrieval. Hence, we decided to analyze the participation of AMPA and NMDA receptors of the central (CeA) and basolateral amygdala (BLA) in CTA memory retrieval and reconsolidation. To do so, we tested whether administrations of an AMPA receptor blocker (NBQX) or an NMDA receptor blocker (APV) 15 min before a second acquisition trial could have effects on taste aversion. We found that administration of NBQX in the BLA blocked retrieval, whereas APV blocked reconsolidation in the BLA, and consolidation in the CeA. When we administered both NBQX and APV into the BLA before the second acquisition trial, results showed impairment of both retrieval and reconsolidation. These results further support the idea that reconsolidation is independent of retrieval, since retrieval blockade in the BLA did not impair memory reconsolidation. These results suggest that glutamate receptors have different participation on retrieval and reconsolidation of CTA and further support the hypothesis that these two processes could be independent.}, } @article {pmid24631390, year = {2014}, author = {Rodríguez-Durán, LF and Escobar, ML}, title = {NMDA receptor activation and PKC but not PKA lead to the modification of the long-term potentiation in the insular cortex induced by conditioned taste aversion: differential role of kinases in metaplasticity.}, journal = {Behavioural brain research}, volume = {266}, number = {}, pages = {58-62}, doi = {10.1016/j.bbr.2014.02.049}, pmid = {24631390}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Benzophenanthridines/pharmacology ; Carbazoles/pharmacology ; Cerebral Cortex/drug effects/*physiology ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Electric Stimulation ; Enzyme Inhibitors/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Long-Term Potentiation/drug effects/*physiology ; Male ; Piperazines/pharmacology ; Protein Kinase C/metabolism ; Pyrroles/pharmacology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Taste/drug effects/*physiology ; }, abstract = {It has been reported that training in behavioral tasks modifies the ability to induce long-term potentiation (LTP) in an N-methyl-D-aspartate receptor (NMDAR)-dependent manner. This receptor leads to calcium entry into neuronal cells, promoting the activation of protein kinases as protein kinase A (PKA) and protein kinase C (PKC), which contribute significantly to the formation of different types of memories and play a pivotal role in the expression of LTP. Our previous studies involving the insular cortex (IC) have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (BLA)-IC projection prior to conditioned taste aversion (CTA) training enhances the retention of this task. Recently, we showed that CTA training triggers a persistent impairment in the ability to induce subsequent synaptic plasticity on the BLA-IC pathway in a protein synthesis-dependent manner, but the underlying molecular mechanisms remain unclear. In the present study we investigated whether the blockade of NMDAR, as well as the inhibition of PKC and PKA affects the CTA-dependent impairment of the IC-LTP. Thus, CTA-trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48 h after the aversion test. The NMDAR antagonist CPP and the specific inhibitors for PKC (chelerythrine) and PKA (KT-5720) were intracortically administered during the acquisition session. Our results show that the blockade of NMDAR and the inhibition of PKC activity prevent the CTA memory-formation as well as the IC-LTP impairment. Nevertheless, PKA inhibition prevents the memory formation of taste aversion but produces no interference with the CTA-dependent impairment of the IC-LTP. These findings reveal the differential roles of protein kinases on CTA-dependent modification of IC-LTP enhancing our understanding of the effects of memory-related changes on synaptic function.}, } @article {pmid24625748, year = {2014}, author = {Purón-Sierra, L and Miranda, MI}, title = {Histaminergic modulation of cholinergic release from the nucleus basalis magnocellularis into insular cortex during taste aversive memory formation.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e91120}, pmid = {24625748}, issn = {1932-6203}, mesh = {Acetylcholine/chemistry ; Animals ; *Avoidance Learning ; Basal Nucleus of Meynert/*drug effects/*metabolism ; Cerebral Cortex/*drug effects ; Conditioning, Classical ; Histamine/*chemistry ; Male ; Memory ; Microdialysis ; Microscopy, Confocal ; Microscopy, Fluorescence ; Pyrilamine/chemistry ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA/metabolism ; Taste ; Taste Perception/*physiology ; }, abstract = {The ability of acetylcholine (ACh) to alter specific functional properties of the cortex endows the cholinergic system with an important modulatory role in memory formation. For example, an increase in ACh release occurs during novel stimulus processing, indicating that ACh activity is critical during early stages of memory processing. During novel taste presentation, there is an increase in ACh release in the insular cortex (IC), a major structure for taste memory recognition. There is extensive evidence implicating the cholinergic efferents of the nucleus basalis magnocellularis (NBM) in cortical activity changes during learning processes, and new evidence suggests that the histaminergic system may interact with the cholinergic system in important ways. However, there is little information as to whether changes in cholinergic activity in the IC are modulated during taste memory formation. Therefore, in the present study, we evaluated the influence of two histamine receptor subtypes, H1 in the NBM and H3 in the IC, on ACh release in the IC during conditioned taste aversion (CTA). Injection of the H3 receptor agonist R-α-methylhistamine (RAMH) into the IC or of the H1 receptor antagonist pyrilamine into the NBM during CTA training impaired subsequent CTA memory, and simultaneously resulted in a reduction of ACh release in the IC. This study demonstrated that basal and cortical cholinergic pathways are finely tuned by histaminergic activity during CTA, since dual actions of histamine receptor subtypes on ACh modulation release each have a significant impact during taste memory formation.}, } @article {pmid24625557, year = {2014}, author = {Hyatt, WS and Fantegrossi, WE}, title = {Δ9-THC exposure attenuates aversive effects and reveals appetitive effects of K2/'Spice' constituent JWH-018 in mice.}, journal = {Behavioural pharmacology}, volume = {25}, number = {3}, pages = {253-257}, pmid = {24625557}, issn = {1473-5849}, support = {P20 RR020146/RR/NCRR NIH HHS/United States ; P30 GM110702/GM/NIGMS NIH HHS/United States ; RR029884/RR/NCRR NIH HHS/United States ; RR020146/RR/NCRR NIH HHS/United States ; UL1 RR029884/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Appetite/*drug effects ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Dronabinol/*pharmacology ; Drug Interactions ; Indoles/*pharmacology ; Male ; Mice ; Naphthalenes/*pharmacology ; Reinforcement Schedule ; }, abstract = {The emergence of high-efficacy synthetic cannabinoids as drugs of abuse in readily available K2/'Spice' smoking blends has exposed users to much more potent and effective substances than the phytocannabinoids present in cannabis. Increasing reports of adverse reactions, including dependence and withdrawal, are appearing in the clinical literature. Here we investigated whether the effects of one such synthetic cannabinoid, 1-pentyl-3-(1-naphthoyl)indole (JWH-018), would be altered by a prior history of Δ9-tetrahydrocannabinol (Δ9-THC) exposure, in assays of conditioned taste aversion and conditioned place preference. In the conditioned taste aversion procedure, JWH-018 induced marked and persistent aversive effects in mice with no previous cannabinoid history, but the magnitude and duration of these aversive effects were significantly blunted in mice previously treated with an ascending dose regimen of Δ9-THC. Similarly, in the conditioned place preference procedure, JWH-018 induced dose-dependent aversive effects in mice with no previous drug history, but mice exposed to Δ9-THC before place conditioning showed reduced aversions at a high JWH-018 dose and apparent rewarding effects at a low dose of JWH-018. These findings suggest that a history of Δ9-THC exposure 'protects' against aversive effects and 'unmasks' appetitive effects of the high-efficacy synthetic cannabinoid JWH-018 in mice. This pattern of results implies that cannabinoid-naive individuals administering K2/'Spice' products for the first-time may be at an increased risk for adverse reactions, whereas those with a history of marijuana use may be particularly sensitive to the reinforcing effects of high-efficacy cannabinoids present in these commercial smoking blends.}, } @article {pmid24595359, year = {2014}, author = {Saitou, K and Lees, JN and Tordoff, MG}, title = {Taste hedonics influence the disposition of fat by modulating gastric emptying in rats.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e90717}, pmid = {24595359}, issn = {1932-6203}, mesh = {Animals ; Carbohydrates/administration & dosage/pharmacology ; Carbon Radioisotopes/metabolism ; Catheterization ; Fatty Acids, Nonesterified/blood/metabolism/*pharmacokinetics ; Gastric Emptying/*physiology ; Intestinal Absorption/*drug effects ; Male ; Quinine/administration & dosage/pharmacology ; Rats ; Taste/*physiology ; Triglycerides/blood/metabolism/*pharmacokinetics ; Triolein/metabolism/pharmacokinetics ; }, abstract = {We investigated how preferred and nonpreferred tastes influence the disposition of fat. Adult male Sprague Dawley rats were infused with 5 ml of 20% intralipid through an intragastric catheter and with 0.3 ml of a taste solution through an intraoral catheter. At 120 min postinfusion, plasma concentrations of fat fuels (triglycerides and non-esterified fatty acids) were either unchanged or slightly higher after rats tasted a preferred sweet taste solution (0.125% saccharin +3% glucose) than after they tasted water. They were markedly lower after rats tasted a non-preferred solution-either a bitter solution (0.15% quinine hydrochloride) or a sweet solution that had previously been the conditioned stimulus for lithium-induced taste aversion. The distribution of 14C-triolein mixed with the gastric load was determined at 4 h postinfusion. Rats that received a non-preferred bitter taste had significantly more 14C remaining in the stomach than did those that received a preferred sweet taste. These results suggest that taste hedonics--either unconditioned or conditioned aversive tastes--influence fat disposition by altering gastric emptying.}, } @article {pmid24582760, year = {2014}, author = {Kim, KN and Kim, BT and Kim, YS and Lee, JH and Jahng, JW}, title = {Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion.}, journal = {European journal of pharmacology}, volume = {730}, number = {}, pages = {14-19}, doi = {10.1016/j.ejphar.2014.02.017}, pmid = {24582760}, issn = {1879-0712}, mesh = {Adrenalectomy ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Dexamethasone/pharmacology ; Drinking ; Extinction, Psychological/*drug effects ; Glucocorticoids/*pharmacology ; Hypothalamo-Hypophyseal System/drug effects/physiology ; Lithium/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Mifepristone/pharmacology ; Paraventricular Hypothalamic Nucleus/drug effects/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Sucrose/pharmacology ; Taste/*drug effects/physiology ; }, abstract = {Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA.}, } @article {pmid24550067, year = {2014}, author = {Walewski, JL and Ge, F and Lobdell, H and Levin, N and Schwartz, GJ and Vasselli, JR and Pomp, A and Dakin, G and Berk, PD}, title = {Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity.}, journal = {Obesity (Silver Spring, Md.)}, volume = {22}, number = {7}, pages = {1643-1652}, pmid = {24550067}, issn = {1930-739X}, support = {R01 DK052401/DK/NIDDK NIH HHS/United States ; U01-DK-66667/DK/NIDDK NIH HHS/United States ; R01-DK-52401/DK/NIDDK NIH HHS/United States ; DK072526-04ES1/DK/NIDDK NIH HHS/United States ; DK-72526/DK/NIDDK NIH HHS/United States ; DK-26687/DK/NIDDK NIH HHS/United States ; R01 DK072526/DK/NIDDK NIH HHS/United States ; P30 DK026687/DK/NIDDK NIH HHS/United States ; U01 DK066667/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipocytes/*metabolism ; Animals ; Body Weight/drug effects ; Down-Regulation ; Eating/drug effects ; Energy Intake/*physiology ; Fatty Acids/*pharmacokinetics ; Feeding Behavior ; Humans ; Leptin/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/*metabolism ; Oleic Acid/metabolism ; Peptide Hormones/*pharmacology ; Protein Array Analysis ; Rats ; Rats, Wistar ; Weight Loss/*physiology ; }, abstract = {OBJECTIVE: Microarray studies identified Ch12:orf39 (Spexin) as the most down-regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.

METHODS: Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet-induced obesity (DIO). Its effects on adipocyte [(3)H]-oleate uptake were determined.

RESULTS: In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = -0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects.

CONCLUSIONS: Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.}, } @article {pmid24467279, year = {2014}, author = {D'Souza, MS and Markou, A}, title = {Differential role of N-methyl-D-aspartate receptor-mediated glutamate transmission in the nucleus accumbens shell and core in nicotine seeking in rats.}, journal = {The European journal of neuroscience}, volume = {39}, number = {8}, pages = {1314-1322}, doi = {10.1111/ejn.12491}, pmid = {24467279}, issn = {1460-9568}, support = {DA11946/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Drug-Seeking Behavior ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/*metabolism ; Isoquinolines/pharmacology ; Male ; Nicotine/administration & dosage/*pharmacology ; Nucleus Accumbens/drug effects/*metabolism/physiology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism ; Self Administration ; *Synaptic Transmission ; }, abstract = {Nicotine, a major psychoactive component of tobacco smoke, increases glutamate transmission in the nucleus accumbens (NAcc). However, the role of the N-methyl-D-aspartate (NMDA)-mediated glutamatergic neurotransmission in the NAcc shell and core subdivisions in nicotine-dependent behaviors has not been studied. The present study evaluated, in rats, the effects of bilateral administration of the competitive NMDA receptor antagonist LY235959 (0, 0.1, 1, and 10 ng/0.5 μL/side) into the NAcc shell or core on intravenous nicotine (fixed- and progressive-ratio schedules) and food (fixed-ratio schedule) self-administration, and cue-induced reinstatement of nicotine-seeking behavior. In addition, the effects of LY235959 injections in the NAcc shell were evaluated on nicotine-induced conditioned taste aversion, a procedure that assesses the aversive effects of nicotine. LY235959 injections into the NAcc shell significantly increased nicotine self-administration under both fixed- and progressive-ratio schedules, and decreased food self-administration, but had no effect on nicotine-induced conditioned taste aversion or cue-induced nicotine seeking. Furthermore, injections of LY235959 in the lateral septal nucleus, originally intended as an anatomical control site for the NAcc shell, increased nicotine self-administration and decreased food self-administration under the fixed-ratio schedule. In contrast, LY235959 injections into the NAcc core increased the cue-induced reinstatement of nicotine seeking and decreased food self-administration, but had no effect on nicotine self-administration. The present data suggest that NMDA receptor-mediated glutamatergic neurotransmission in the NAcc shell and core differentially regulates food- and nicotine-maintained responding. Importantly, the data suggest an inhibitory role for NMDA-mediated glutamatergic neurotransmission in the NAcc shell and core in nicotine self-administration and the cue-induced reinstatement of nicotine seeking, respectively.}, } @article {pmid24459870, year = {2013}, author = {Kozyrev, SA and Nikitin, VP}, title = {[Different mechanisms of long-term synaptic facilitation during associative learning and sensitization].}, journal = {Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova}, volume = {99}, number = {5}, pages = {599-611}, pmid = {24459870}, issn = {0869-8139}, mesh = {Animals ; Beverages ; *Conditioning, Classical ; Cycloheximide/pharmacology ; Dactinomycin/pharmacology ; Daucus carota/chemistry ; Helix, Snails/drug effects/*physiology ; Neuronal Plasticity/*physiology ; Neurons/drug effects/physiology ; Nucleic Acid Synthesis Inhibitors/pharmacology ; Protein Synthesis Inhibitors/pharmacology ; Quinine/pharmacology ; Reinforcement, Psychology ; Synaptic Transmission ; Taste Perception/drug effects/*physiology ; }, abstract = {The translation and transcription processes involved in mechanisms of synaptic plasticity during the development of conditional taste aversion were studied in command neurons LP11 and PP11 of defensive behavior in snail Helix lucorum. In control snails it was found that the combined presentation of gustatory (carrot juice) and supporting (concentrated solution of quinine) stimulus led to a change in neuron's responses to sensory stimulus, which are typical as to conditioning and also to the corresponding sensitization. 1 h after the start of training it was occurred facilitation of the responses to sensory chemical stimulus (weak solution of quinine) whereas 1.5 hour--reactions to the conditioned food stimulus. Application of the protein synthesis inhibitor cycloheximide during conditioning led to the suppression of response facilitation to both stimulus--weak solution of quinine and the conditioned food stimulus. However, application of the RNA synthesis inhibitor actinomycin D to the neurons caused selective suppression of synaptic facilitation in responses to sensory stimulation with a weak solution of quinine, but it had no effect on synaptic facilitation in the responses to the conditioned stimulus. It has been suggested that the development of conditioned taste aversion in snails causes a long-term synaptic facilitation in nerve cells LP11 and PP11 typical to the process of conditioning and sensitization, for the induction of which the variety of molecular genetic mechanisms are necessary.}, } @article {pmid24454882, year = {2014}, author = {Blednov, YA and Benavidez, JM and Black, M and Leiter, CR and Osterndorff-Kahanek, E and Johnson, D and Borghese, CM and Hanrahan, JR and Johnston, GA and Chebib, M and Harris, RA}, title = {GABAA receptors containing ρ1 subunits contribute to in vivo effects of ethanol in mice.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e85525}, pmid = {24454882}, issn = {1932-6203}, support = {AA06399/AA/NIAAA NIH HHS/United States ; AA013520/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Anxiety/psychology ; Cells, Cultured ; Central Nervous System Depressants/metabolism/*pharmacology ; Ethanol/metabolism/*pharmacology ; Female ; GABA Agonists/pharmacology ; GABA-A Receptor Antagonists/pharmacology ; Ketamine/pharmacology ; Male ; Mice ; Mice, Transgenic ; Motor Activity/drug effects ; Phosphinic Acids/pharmacology ; Protein Subunits/genetics/metabolism ; Receptors, GABA-A/*genetics/metabolism ; Reflex, Righting/drug effects ; Reflex, Startle/drug effects ; Rotarod Performance Test ; Xenopus laevis ; gamma-Aminobutyric Acid/pharmacology ; }, abstract = {GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ1" antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ2" antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.}, } @article {pmid24453316, year = {2014}, author = {Moran, A and Katz, DB}, title = {Sensory cortical population dynamics uniquely track behavior across learning and extinction.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {34}, number = {4}, pages = {1248-1257}, pmid = {24453316}, issn = {1529-2401}, support = {R01 DC006666/DC/NIDCD NIH HHS/United States ; R01 DC007703/DC/NIDCD NIH HHS/United States ; DC006666/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Cerebral Cortex/*physiology ; Electrophysiology ; Extinction, Psychological/*physiology ; Female ; Learning/*physiology ; Neurons/*physiology ; Rats ; }, abstract = {Neural responses in many cortical regions encode information relevant to behavior: information that necessarily changes as that behavior changes with learning. Although such responses are reasonably theorized to be related to behavior causation, the true nature of that relationship cannot be clarified by simple learning studies, which show primarily that responses change with experience. Neural activity that truly tracks behavior (as opposed to simply changing with experience) will not only change with learning but also change back when that learning is extinguished. Here, we directly probed for this pattern, recording the activity of ensembles of gustatory cortical single neurons as rats that normally consumed sucrose avidly were trained first to reject it (i.e., conditioned taste aversion learning) and then to enjoy it again (i.e., extinction), all within 49 h. Both learning and extinction altered cortical responses, consistent with the suggestion (based on indirect evidence) that extinction is a novel form of learning. But despite the fact that, as expected, postextinction single-neuron responses did not resemble "naive responses," ensemble response dynamics changed with learning and reverted with extinction: both the speed of stimulus processing and the relationships among ensemble responses to the different stimuli tracked behavioral relevance. These data suggest that population coding is linked to behavior with a fidelity that single-neuron coding is not.}, } @article {pmid24432359, year = {2014}, author = {Nakajima, S}, title = {Running-based taste aversion learning in five strains of rats.}, journal = {Physiology & behavior}, volume = {123}, number = {}, pages = {200-213}, pmid = {24432359}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Choice Behavior/drug effects ; Conditioning, Psychological/drug effects/*physiology ; Flavoring Agents/administration & dosage ; Locomotion/*physiology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Rats, Wistar ; Saccharin/administration & dosage ; Sodium Glutamate/administration & dosage ; Species Specificity ; Sweetening Agents/administration & dosage ; Taste/*physiology ; Time Factors ; }, abstract = {Although it is well known that voluntary wheel running works as an effective unconditioned stimulus to cause conditioned taste aversion (CTA) in several strains of rats, there is no study that explores strain differences in running-based CTA. The present study examines this issue with regard to five frequently used rat strains. Experiment 1 compared Sprague–Dawley versus Wistar rats from two suppliers, with the target taste being salty (NaCl + MSG) and then sweet (saccharin). Experiments 2, 3, and 4 tested rats of Wistar versus Long-Evans, Lewis versus Fischer, and Sprague–Dawley versus Lewis strains, respectively, with sweet and then salty solutions. None of the experiments showed any reliable strain differences in the strength of running-based CTA, suggesting the robustness of this learning phenomenon.}, } @article {pmid24430885, year = {2014}, author = {Horn, CC and Meyers, K and Lim, A and Dye, M and Pak, D and Rinaman, L and Yates, BJ}, title = {Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {306}, number = {5}, pages = {R341-51}, pmid = {24430885}, issn = {1522-1490}, support = {R01MH059911/MH/NIMH NIH HHS/United States ; R01DK065971/DK/NIDDK NIH HHS/United States ; R01 DC003732/DC/NIDCD NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; P40 RR018604/RR/NCRR NIH HHS/United States ; R01DC003732/DC/NIDCD NIH HHS/United States ; P40RR018604/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Copper Sulfate/*toxicity ; Emetics/*toxicity ; Female ; Herpesvirus 1, Human/classification/physiology ; Male ; Motion Sickness ; Nicotine/toxicity ; Rats ; Rats, Sprague-Dawley ; Shrews/*physiology ; Stomach/innervation/virology ; Vagotomy ; Vagus Nerve/*physiology ; Vomiting/*chemically induced ; }, abstract = {Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew.}, } @article {pmid24406726, year = {2014}, author = {Morales, M and Schatz, KC and Anderson, RI and Spear, LP and Varlinskaya, EI}, title = {Conditioned taste aversion to ethanol in a social context: impact of age and sex.}, journal = {Behavioural brain research}, volume = {261}, number = {}, pages = {323-327}, pmid = {24406726}, issn = {1872-7549}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; R01 AA017355/AA/NIAAA NIH HHS/United States ; U01 AA019972/AA/NIAAA NIH HHS/United States ; U01 AA19972/AA/NIAAA NIH HHS/United States ; }, mesh = {Aging/*physiology ; Analysis of Variance ; Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects ; Ethanol/*pharmacology ; Female ; *Interpersonal Relations ; Male ; Rats ; Saccharin/administration & dosage ; *Sex Characteristics ; Sweetening Agents/administration & dosage ; Taste/*drug effects ; }, abstract = {Given that human adolescents place a high value on social interactions-particularly while consuming alcohol-the current study utilized a novel social drinking paradigm to examine rewarding and aversive properties of ethanol in non-water deprived rats that were housed and tested in groups of five same-sex littermates. On postnatal day P34 (adolescents) or P69 (adults), rats were habituated to the testing apparatus for 30 min. On the next day, animals were placed into the test apparatus and given 30 min access to a supersaccharin solution (3% sucrose; 0.125% saccharin), followed immediately by an intraperitoneal injection of ethanol (0, 0.25, 0.5, 1.0, 1.5 g/kg). Subsequent intake of the supersacharrin solution was assessed on three consecutive test days. Adolescent males were less sensitive to ethanol's aversive effects than adult males, with adolescent males maintaining an aversion on all three test days only at the 1.5 g/kg dose, whereas adults demonstrated aversions across test days to 1 and 1.5 g/kg. Adolescent females maintained aversions to 1 and 1.5 g/kg across days, whereas adult females continued to show an aversion to the 1.5 g/kg dose only. These opposite patterns of sensitivity that emerged among males and females at each age in the propensity to maintain an ethanol-induced taste aversion under social conditions may contribute to age- and sex-related differences in ethanol intake. Testing in social groups may be useful for future work when studying rodent models of adolescent alcohol use given the importance that human adolescents place on drinking in social settings.}, } @article {pmid24395785, year = {2014}, author = {Schier, LA and Hashimoto, K and Bales, MB and Blonde, GD and Spector, AC}, title = {High-resolution lesion-mapping strategy links a hot spot in rat insular cortex with impaired expression of taste aversion learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {3}, pages = {1162-1167}, pmid = {24395785}, issn = {1091-6490}, support = {T32-DC-000044/DC/NIDCD NIH HHS/United States ; R01 DC009821/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; F32-DC-013494/DC/NIDCD NIH HHS/United States ; F32 DC013494/DC/NIDCD NIH HHS/United States ; R01-DC-DC009821/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping/*methods ; Cerebral Cortex/*pathology ; Conditioning, Psychological ; Excitatory Amino Acid Agonists/chemistry ; Ibotenic Acid/chemistry ; Image Processing, Computer-Assisted ; Male ; Microscopy ; Models, Neurological ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {Gustatory cortex (GC), an assemblage of taste-responsive neurons in insular cortex, is widely regarded as integral to conditioned taste aversion (CTA) retention, a link that has been primarily established using lesion approaches in rats. In contrast to this prevailing view, we found that even the most complete bilateral damage to GC produced by ibotenic acid was insufficient to disrupt postsurgical expression of a presurgical CTA; nor were such lesions sufficient to disrupt postsurgical acquisition and initial expression of a second CTA. However, some rats with lesions were significantly impaired on these tests. Further examination of all conditioned rats with lesions, regardless of the lesion topography, revealed a significant positive association between damage in the posterior portion of GC and especially within adjacent posterior regions of insular cortex. Accordingly, we developed a high-resolution lesion-mapping program that permitted the overlay of the individual lesion maps from rats with CTA impairments to produce a groupwise aggregate lesion map. Comparison of this map with one derived from the unimpaired counterparts indicated a specific lesion "hot spot" associated with CTA deficits that included the most posterior end of GC and overlying granular layer and encompassed an area provisionally referred to in the literature as visceral cortex. Thus, the detailed mapping of the lesion in behaviorally defined subgroups of rats allowed us to exploit the variability in performance to uncloak an important potential component of the functional topography of insular cortex; such an approach could have general applicability to other brain structure-function endeavors as well.}, } @article {pmid24337340, year = {2015}, author = {Bi, AL and Wang, Y and Zhang, S and Li, BQ and Sun, ZP and Bi, HS and Chen, ZY}, title = {Myosin II regulates actin rearrangement-related structural synaptic plasticity during conditioned taste aversion memory extinction.}, journal = {Brain structure & function}, volume = {220}, number = {2}, pages = {813-825}, doi = {10.1007/s00429-013-0685-5}, pmid = {24337340}, issn = {1863-2661}, mesh = {Actins/*metabolism ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Extinction, Psychological/*physiology ; Male ; Myosin Type II/*metabolism ; *Neuronal Plasticity ; Phosphorylation ; Prefrontal Cortex/*physiology/ultrastructure ; Rats, Wistar ; Synapses/metabolism/ultrastructure ; Taste ; }, abstract = {Similar to memory formation, memory extinction is also a new learning process that requires synaptic plasticity. Actin rearrangement is fundamental for synaptic plasticity, however, whether actin rearrangement in the infralimbic cortex (IL) plays a role in memory extinction, as well as the mechanisms underlying it, remains unclear. Here, using a conditioned taste aversion (CTA) paradigm, we demonstrated increased synaptic density and actin rearrangement in the IL during the extinction of CTA. Targeted infusion of an actin rearrangement inhibitor, cytochalasin D, into the IL impaired memory extinction and de novo synapse formation. Notably, we also found increased myosin II phosphorylation in the IL during the extinction of CTA. Microinfusion of a specific inhibitor of the myosin II ATPase, blebbistatin (Blebb), into the IL impaired memory extinction as well as the related actin rearrangement and changes in synaptic density. Moreover, the extinction deficit and the reduction of synaptic density induced by Blebb could be rescued by the actin polymerization stabilizer jasplakinolide (Jasp), suggesting that myosin II acts via actin filament polymerization to stabilize synaptic plasticity during the extinction of CTA. Taken together, we conclude that myosin II may regulate the plasticity of actin-related synaptic structure during memory extinction. Our studies provide a molecular mechanism for understanding the plasticity of actin rearrangement-associated synaptic structure during memory extinction.}, } @article {pmid24323127, year = {2014}, author = {Núñez-Jaramillo, L and Reyes-López, J and Miranda, MI}, title = {Sodium butyrate into the insular cortex during conditioned taste-aversion acquisition delays aversive taste memory extinction.}, journal = {Neuroreport}, volume = {25}, number = {6}, pages = {386-390}, doi = {10.1097/WNR.0000000000000103}, pmid = {24323127}, issn = {1473-558X}, mesh = {Animals ; Antimanic Agents/administration & dosage/pharmacology ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Butyric Acid/administration & dosage/*pharmacology ; Cerebral Cortex/*drug effects/pathology/surgery ; Conditioning, Classical/drug effects ; Extinction, Psychological/drug effects ; Histamine Antagonists/administration & dosage/*pharmacology ; Learning/*drug effects ; Lithium Chloride/administration & dosage/pharmacology ; Male ; Memory/drug effects ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Histone acetylation is one mechanism that promotes gene expression, and it increases during learning of various tasks. Specifically, novel taste consumption produces an increased acetylation of histone lysine residues in the insular cortex (IC), where protein synthesis is crucial during memory consolidation of conditioned taste aversion (CTA). However, the role of this elevated histone acetylation during CTA learning has not been examined directly. Thus, the present study investigated the effects of sodium butyrate (NaBu), a histone deacetylase inhibitor, injected into the IC during CTA acquisition. Male Wistar rats, IC bilaterally implanted, were injected 60 min before saccharine presentation, with a total volume of 0.5 µl of NaBu solution (100, 500, and 10 µg/0.5 µl) or saline; 30 min later animals were injected intraperitoneally with lithium chloride, a malaise-inducing drug. The next day, CTA retrieval was tested. No effects of NaBu were observed during acquisition or retrieval, but during extinction trials, a significant delay in aversive memory extinction was observed in the group injected with the lowest NaBu dose. This result indicates that NaBu in the IC strengthens CTA and delays aversive memory extinction, and suggests that histone acetylation could increase long-term taste-aversive memory strength.}, } @article {pmid24296461, year = {2014}, author = {Moraga-Amaro, R and Cortés-Rojas, A and Simon, F and Stehberg, J}, title = {Role of the insular cortex in taste familiarity.}, journal = {Neurobiology of learning and memory}, volume = {109}, number = {}, pages = {37-45}, doi = {10.1016/j.nlm.2013.11.012}, pmid = {24296461}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Inhibition, Psychological ; Male ; Rats ; Rats, Wistar ; Recognition, Psychology/*physiology ; Taste Perception/*physiology ; }, abstract = {Determining the role of the main gustatory cortical area within the insular cortex (IC), in conditioned taste aversion (CTA) has been elusive due to effective compensatory mechanisms that allow animals to learn in spite of lacking IC. IC lesions performed before CTA training induces mild if any memory impairments, while IC lesions done weeks after CTA produce amnesia. IC lesions before taste presentation have also been shown not to affect taste familiarity learning (attenuation of neophobia). This lack of effect could be either explained by compensation from other brain areas or by a lack of involvement of the IC in taste familiarity. To assess this issue, rats were bilaterally IC lesioned with ibotenic acid (200-300 nl.; 15 mg/ml) one week before or after taste familiarity, using either a preferred (0.1%) or a non-preferred (0.5%) saccharin solution. Rats lesioned before familiarity showed a decrease in neophobia to both solutions but no difference in their familiarity curve or their slope. When animals were familiarized and then IC lesioned, both IC lesioned groups treated the solutions as familiar, showing no differences from sham animals in their retention of familiarity. However, both lesioned groups showed increased latent inhibition (or impaired CTA) when CTA trained after repeated pre-exposures. The role of the IC in familiarity was also assessed using temporary inactivation of the IC, using bilateral micro-infusions of sodium channel blocker bupivacaine before each of 3 saccharin daily presentations. Intra-insular bupivacaine had no effects on familiarity acquisition, but did impair CTA learning in a different group of rats micro-infused before saccharin presentation in a CTA training protocol. Our data indicate that the IC is not essentially involved in acquisition or retention of taste familiarity, suggesting regional dissociation of areas involved in CTA and taste familiarity.}, } @article {pmid24291574, year = {2014}, author = {García, R and Simon, MJ and Puerto, A}, title = {Rewarding effects of the electrical stimulation of the parabrachial complex: taste or place preference?.}, journal = {Neurobiology of learning and memory}, volume = {107}, number = {}, pages = {101-107}, doi = {10.1016/j.nlm.2013.11.010}, pmid = {24291574}, issn = {1095-9564}, mesh = {Animals ; Discrimination Learning ; Electric Stimulation ; Food Preferences/*physiology ; Male ; Pons/*physiology ; Rats ; Rats, Wistar ; *Reward ; Spatial Behavior/*physiology ; Taste/physiology ; }, abstract = {The lateral parabrachial complex has been related to various emotional-affective processes. It has been shown that electrical stimulation of the external Lateral Parabrachial (LPBe) nucleus can induce reinforcing effects in place preference and taste discrimination tasks but does not appear to support self-stimulation. This study examined the relative relevance of place and taste stimuli after electrical stimulation of the LPBe nucleus. A learning discrimination task was conducted that simultaneously included both sensory indexes (taste and place) in order to determine the preference of animals for one or the other. After a taste stimulus reversal task, the rewarding effect of stimulation was found to be preferentially associated with place. These results are discussed in the context of the rewarding action and biological constraints induced by different natural and artificial reinforcing agents.}, } @article {pmid24289793, year = {2014}, author = {Wang, T and Han, W and Wang, B and Jiang, Q and Solberg-Woods, LC and Palmer, AA and Chen, H}, title = {Propensity for social interaction predicts nicotine-reinforced behaviors in outbred rats.}, journal = {Genes, brain, and behavior}, volume = {13}, number = {2}, pages = {202-212}, pmid = {24289793}, issn = {1601-183X}, support = {P50 MH094267/MH/NIMH NIH HHS/United States ; DK-088975/DK/NIDDK NIH HHS/United States ; DA-026894/DA/NIDA NIH HHS/United States ; P50MH94267/MH/NIMH NIH HHS/United States ; R01 DK088975/DK/NIDDK NIH HHS/United States ; R21 DA026894/DA/NIDA NIH HHS/United States ; P50 DA037844/DA/NIDA NIH HHS/United States ; R01 DA021336/DA/NIDA NIH HHS/United States ; DA021336/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Depression/genetics ; Female ; Male ; Nicotine/administration & dosage/*pharmacology ; Phenotype ; Propensity Score ; Rats ; Rats, Sprague-Dawley ; *Reinforcement, Psychology ; Self Administration ; Sex Characteristics ; *Social Behavior ; Substance-Related Disorders/*genetics/psychology ; }, abstract = {Social and genetic factors can influence smoking behavior. Using olfactogustatory stimuli as the sensory cue for intravenous nicotine self-administration (SA), we previously showed that social learning of nicotine contingent odor cue prevented rats from developing conditioned taste aversion and allowed them to instead establish stable nicotine SA. We hypothesized that genetic factors influenced socially acquired nicotine SA. A heterogeneous stock (HS; N/NIH) of outbred rats was trained to self-administer nicotine using the social learning protocol. Both male and female HS rats acquired nicotine SA, but females self-administered more nicotine than males. After extinction, the context previously paired with nicotine SA, in conjunction with socially transmitted drug cues, was sufficient to cause reinstatement of drug-seeking behavior. Wide variation in both nicotine intake and reinstatement was observed. Using multiple regression analysis, we found that measures of social interaction were significant predictors of nicotine intake and reinstatement of drug seeking in both males and females. Furthermore, measures of depression were predictors of nicotine intake in both males and females, anxiety was a predictor only in males and response to novelty was a predictor only in females. In males, measures of both depression and anxiety predicted nicotine reinstatement. Together, these data supported the ideas that genetically determined propensities for emotional and social phenotypes are significant determinants for nicotine-reinforced behavior, and that the HS rat is a suitable tool for dissecting genetic mechanisms that may underlie the interaction between social behavior, anxiety, depression and smoking.}, } @article {pmid24288036, year = {2014}, author = {Bernal-Gamboa, R and Rosas, JM and Callejas-Aguilera, JE}, title = {Experiencing extinction within a task makes nonextinguished information learned within a different task context-dependent.}, journal = {Psychonomic bulletin & review}, volume = {21}, number = {3}, pages = {803-808}, pmid = {24288036}, issn = {1531-5320}, mesh = {Animals ; Association ; Attention/*physiology ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Extinction, Psychological/*physiology ; Female ; Learning/*physiology ; Rats ; Rats, Wistar ; }, abstract = {In two experiments with rats, we analyzed the effect of experiencing extinction in one task on the context specificity of a new association learned within a different task. Rats were trained to run in a runway for water in Task 1, and received taste aversion conditioning in Task 2 (the tasks were reversed in Exp. 2). Half of the rats received conditioning and extinction of Task 1 in Context A, whereas the other half received no extinction. Then all animals received training in the alternate task in Context B, prior to testing in Context C. When they were tested in Context C, Task 2 performance was attenuated if Task 1 had been extinguished prior to Task 2. These results are similar to those we have reported in humans, and consistent with the idea that extinction prompts attention to contexts, regardless of whether or not the contexts were involved in extinction.}, } @article {pmid24259562, year = {2013}, author = {Hurtado, MD and Sergeyev, VG and Acosta, A and Spegele, M and La Sala, M and Waler, NJ and Chiriboga-Hurtado, J and Currlin, SW and Herzog, H and Dotson, CD and Gorbatyuk, OS and Zolotukhin, S}, title = {Salivary peptide tyrosine-tyrosine 3-36 modulates ingestive behavior without inducing taste aversion.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {33}, number = {47}, pages = {18368-18380}, pmid = {24259562}, issn = {1529-2401}, support = {R01 DK062302/DK/NIDDK NIH HHS/United States ; 1R01DC012819-01A1/DC/NIDCD NIH HHS/United States ; R01 DC012819/DC/NIDCD NIH HHS/United States ; 1R01DK62302-01/DK/NIDDK NIH HHS/United States ; P30 DC010763/DC/NIDCD NIH HHS/United States ; 5P30DC010763-02/DC/NIDCD NIH HHS/United States ; }, mesh = {Aminophylline ; Animals ; Conditioning, Psychological/drug effects ; Eating/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Feeding Behavior/*drug effects ; Gene Expression Regulation/drug effects/genetics ; Glucagon-Like Peptide 1/metabolism ; Humans ; Iodine Isotopes/pharmacokinetics ; Male ; Mice ; Mice, Inbred C57BL ; Oxytocin/metabolism ; Peptide Fragments/*pharmacology ; Peptide YY/chemistry/*deficiency ; Proto-Oncogene Proteins c-fos/metabolism ; Saliva/*enzymology ; Satiation/drug effects ; Tyrosine 3-Monooxygenase/metabolism ; Vasopressins/metabolism ; alpha-MSH/metabolism ; }, abstract = {Hormone peptide tyrosine-tyrosine (PYY) is secreted into circulation from the gut L-endocrine cells in response to food intake, thus inducing satiation during interaction with its preferred receptor, Y2R. Clinical applications of systemically administered PYY for the purpose of reducing body weight were compromised as a result of the common side effect of visceral sickness. We describe here a novel approach of elevating PYY in saliva in mice, which, although reliably inducing strong anorexic responses, does not cause aversive reactions. The augmentation of salivary PYY activated forebrain areas known to mediate feeding, hunger, and satiation while minimally affecting brainstem chemoreceptor zones triggering nausea. By comparing neuronal pathways activated by systemic versus salivary PYY, we identified a metabolic circuit associated with Y2R-positive cells in the oral cavity and extending through brainstem nuclei into hypothalamic satiety centers. The discovery of this alternative circuit that regulates ingestive behavior without inducing taste aversion may open the possibility of a therapeutic application of PYY for the treatment of obesity via direct oral application.}, } @article {pmid24259462, year = {2014}, author = {Dayawansa, S and Ruch, S and Norgren, R}, title = {Parabrachial-hypothalamic interactions are required for normal conditioned taste aversions.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {306}, number = {3}, pages = {R190-200}, pmid = {24259462}, issn = {1522-1490}, support = {R01 DC000240/DC/NIDCD NIH HHS/United States ; R01 DC005435/DC/NIDCD NIH HHS/United States ; DC-008937/DC/NIDCD NIH HHS/United States ; DC-000240/DC/NIDCD NIH HHS/United States ; DC-05435/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/pathology/*surgery ; Animals ; Avoidance Learning/physiology ; Conditioning, Classical/*physiology ; Hypothalamus/metabolism/pathology/*surgery ; Male ; Neural Pathways/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {Rats with bilateral excitotoxic lesions of the parabrachial nuclei (PBN) fail to acquire a conditioned taste aversion (CTA), yet they retain the ability to express a CTA learned prior to incurring the damage. Rats with bilateral electrolytic lesions of the lateral hypothalamus (LH) also have CTA learning deficits. The PBN have reciprocal neural connections with the LH. This suggests that these CTA deficits may be functionally related. Electrolytic lesions damage fibers of passage, as well as intrinsic neurons. Thus, these LH lesions might also interrupt reciprocal connections between the PBN and other ventral forebrain areas, such as the amygdala and bed nucleus of the stria terminalis. To distinguish the source of the LH-lesion deficit, we tested for CTA first after bilateral excitotoxic lesions of LH and subsequently with a second set of animals that had asymmetric excitotoxic PBN and LH lesions. The rats with bilateral excitotoxic LH lesions showed deficits when acquiring a postlesion CTA. The asymmetrical PBN-LH lesions not only slowed acquisition of a CTA but also sped up extinction. This implies that interaction between the two structures, at minimum, facilitates CTA learning and may have a role in its consolidation.}, } @article {pmid24244696, year = {2013}, author = {den Hartog, CR and Beckley, JT and Smothers, TC and Lench, DH and Holseberg, ZL and Fedarovich, H and Gilstrap, MJ and Homanics, GE and Woodward, JJ}, title = {Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e80541}, pmid = {24244696}, issn = {1932-6203}, support = {R37 AA009986/AA/NIAAA NIH HHS/United States ; R37 AA010422/AA/NIAAA NIH HHS/United States ; R37AA10422/AA/NIAAA NIH HHS/United States ; R37AA009986/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/drug effects ; Blotting, Western ; Cell Line ; Electrophysiology ; Ethanol/*pharmacology ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Motor Activity/*drug effects/*genetics ; Receptors, N-Methyl-D-Aspartate/genetics/*metabolism ; }, abstract = {Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p.) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.}, } @article {pmid24226296, year = {2014}, author = {Hashimoto, K and Spector, AC}, title = {Extensive lesions in the gustatory cortex in the rat do not disrupt the retention of a presurgically conditioned taste aversion and do not impair unconditioned concentration-dependent licking of sucrose and quinine.}, journal = {Chemical senses}, volume = {39}, number = {1}, pages = {57-71}, pmid = {24226296}, issn = {1464-3553}, support = {R01 DC009821/DC/NIDCD NIH HHS/United States ; R01-DC009821/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal ; Cerebral Cortex/drug effects/*pathology ; Conditioning, Classical/drug effects ; Male ; Quinine/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Sucrose/*pharmacology ; Taste ; Taste Perception/drug effects ; }, abstract = {Although damage to gustatory cortex (GC) in the rat has been reported to severely impair, if not eliminate, retention of a presurgically conditioned taste aversion (CTA), it has equivocal effects on taste preference as measured by intake tests. Because intake tests can be influenced by nongustatory (e.g., postingestive) factors, we employed the brief-access taste test to assess the effects of ibotenic acid-induced lesions targeting the GC on unconditioned licking to a sucrose and then a quinine concentration series in a specialized lickometer. As a functional lesion assessment, a presurgical CTA to 0.1M NaCl was established in thirsty rats by following 15-min intake with intraperitoneal administration of either LiCl (or NaCl for control) on 2 occasions. Both conditioned sham-operated (SHAM) rats and rats with histologically confirmed extensive damage to the GC (GCX) avoided a NaCl concentration series relative to unconditioned controls in a postsurgical brief-access CTA test, with no difference between the surgical groups in their responses to NaCl or similar concentrations of KCl. GCX rats also did not differ from SHAM rats in the EC50 of concentration-response functions for sucrose or quinine. Clearly, the critical cortical area required for the retention of a presurgical CTA falls outside of the extensive area of damage, which was well centered within the conventionally defined gustatory zone of the insular cortex. The absence of an effect on unconditioned responsiveness to sucrose and quinine suggests that the damaged region is also unnecessary for the normal expression of affective licking responses to tastants.}, } @article {pmid24189487, year = {2014}, author = {Witkin, JM and Statnick, MA and Rorick-Kehn, LM and Pintar, JE and Ansonoff, M and Chen, Y and Tucker, RC and Ciccocioppo, R}, title = {The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence.}, journal = {Pharmacology & therapeutics}, volume = {141}, number = {3}, pages = {283-299}, pmid = {24189487}, issn = {1879-016X}, support = {R01 AA014351/AA/NIAAA NIH HHS/United States ; R01 AA017447/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Anxiety/drug therapy/physiopathology ; *Drug Design ; Humans ; Mice ; Mood Disorders/drug therapy/physiopathology ; Narcotic Antagonists ; Obesity/drug therapy/physiopathology ; Opioid Peptides/*metabolism ; Rats ; Receptors, Opioid/agonists/*metabolism ; Stress, Psychological/drug therapy/physiopathology ; Substance-Related Disorders/drug therapy/physiopathology ; }, abstract = {Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995. The generation of specific agonists, antagonists and receptor deficient mice and rats has enabled progress in elucidating the biological functions of N/OFQ. Additionally, radio-imaging technologies have been advanced for investigation of this system in animals and humans. Together with traditional neurobehavioral techniques, these tools have been utilized to identify the biological significance of the N/OFQ system and its interacting partners. The present review focuses on the role of N/OFQ in the regulation of feeding, body weight homeostasis, stress, the stress-related psychiatric disorders of depression and anxiety, and in drug and alcohol dependence. Critical evaluation of the current scientific preclinical literature suggests that small molecule modulators of nociceptin opioid peptide receptors (NOP) might be useful in the treatment of diseases related to these biological functions. In particular, the literature data suggest that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans. However, there are also contradictory data discussed. The current literature on the role of N/OFQ in anxiety and addiction, on the other hand points primarily to a role of agonist modulation being potentially therapeutic. Some drug-like molecules that function either as agonists or antagonists of NOP receptors have been optimized for human clinical study to test some of these hypotheses. The discovery of PET ligands for NOP receptors, combined with the pharmacological tools and burgeoning preclinical data set discussed here bodes well for a rapid advancement of clinical understanding and potential therapeutic benefit.}, } @article {pmid24176925, year = {2014}, author = {Mita, K and Okuta, A and Okada, R and Hatakeyama, D and Otsuka, E and Yamagishi, M and Morikawa, M and Naganuma, Y and Fujito, Y and Dyakonova, V and Lukowiak, K and Ito, E}, title = {What are the elements of motivation for acquisition of conditioned taste aversion?.}, journal = {Neurobiology of learning and memory}, volume = {107}, number = {}, pages = {1-12}, doi = {10.1016/j.nlm.2013.10.013}, pmid = {24176925}, issn = {1095-9564}, support = {MOP64339//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Blood Glucose/analysis ; Conditioning, Classical/*physiology ; Food Deprivation/*physiology ; Glucose/pharmacology ; Hemolymph/chemistry ; Lymnaea ; Memory/drug effects/physiology ; Motivation/*physiology ; Sucrose/pharmacology ; Taste/*physiology ; }, abstract = {The pond snail Lymnaea stagnalis is capable of being classically conditioned to avoid food and to consolidate this aversion into a long-term memory (LTM). Previous studies have shown that the length of food deprivation is important for both the acquisition of taste aversion and its consolidation into LTM, which is referred to as conditioned taste aversion (CTA). Here we tested the hypothesis that the hemolymph glucose concentration is an important factor in the learning and memory of CTA. One-day food deprivation resulted in the best learning and memory, whereas more prolonged food deprivation had diminishing effects. Five-day food deprivation resulted in snails incapable of learning or remembering. During this food deprivation period, the hemolymph glucose concentration decreased. If snails were fed for 2days following the 5-day food deprivation, their glucose levels increased significantly and they exhibited both learning and memory, but neither learning nor memory was as good as with the 1-day food-deprived snails. Injection of the snails with insulin to reduce glucose levels resulted in better learning and memory. Insulin is also known to cause a long-term enhancement of synaptic transmission between the feeding-related neurons. On the other hand, injection of glucose into 5-day food-deprived snails did not alter their inability to learn and remember. However, if these snails were fed on sucrose for 3min, they then exhibited learning and memory formation. Our data suggest that hemolymph glucose concentration is an important factor in motivating acquisition of CTA in Lymnaea and that the action of insulin in the brain and the feeding behavior are also important factors.}, } @article {pmid24164956, year = {2014}, author = {Legastelois, R and Botia, B and Coune, F and Jeanblanc, J and Naassila, M}, title = {Deciphering the relationship between vulnerability to ethanol-induced behavioral sensitization and ethanol consumption in outbred mice.}, journal = {Addiction biology}, volume = {19}, number = {2}, pages = {210-224}, doi = {10.1111/adb.12104}, pmid = {24164956}, issn = {1369-1600}, mesh = {Alcohol Drinking/*physiopathology ; Analysis of Variance ; Animals ; Animals, Outbred Strains ; Central Nervous System Depressants/administration & dosage/metabolism/*pharmacology ; Choice Behavior/drug effects ; Compulsive Behavior ; Conditioning, Psychological ; Disease Susceptibility ; Dose-Response Relationship, Drug ; Ethanol/administration & dosage/metabolism/*pharmacology ; Female ; *Food Preferences ; Injections, Intraperitoneal ; Linear Models ; Mice ; Motor Activity/*drug effects ; Quinine/administration & dosage ; Self Administration ; Sodium Chloride/administration & dosage ; Species Specificity ; }, abstract = {Ethanol (EtOH)-induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of alcohol dependence, but its impact on alcohol abuse is not clear. EIBS development is dependent upon animal species, strain and also individual factors. We proposed here to decipher the co-expression of EIBS and EtOH intake in individual animals among outbred Swiss mice, which exhibit heterogeneity that parallels what may occur in humans. To do so, mice were exposed to a two-bottle choice with free access to water or 10% EtOH for 6 days just before and immediately after chronic intraperitoneal 2.5 g/kg ethanol injections once a day for 10 consecutive days. Based on their sensitization scores, mice were split into resistant and sensitized animals. First, we showed that individual susceptibility to EIBS is inversely correlated with voluntary EtOH consumption. Exposure to repeated EtOH during EIBS development increased subsequent EtOH intake among the entire population. Very interestingly, subsequent analyses suggested that the less the mice are sensitized the more they increase their EtOH intake; however, resistant mice were sensitive to EtOH adulteration with quinine, whereas sensitized ones maintained their EtOH intake levels, therefore exhibiting a compulsive-like drinking pattern. In addition, we showed that resistant mice do not exhibit a weaker sensitivity to the aversive properties of EtOH that may contribute to their higher level of EtOH intake compared to sensitized mice. This study confirms and extends previous data showing a deep relationship between propensity for EtOH consumption and susceptibility to EIBS in Swiss mice.}, } @article {pmid24158502, year = {2014}, author = {Schramm-Sapyta, NL and Francis, R and MacDonald, A and Keistler, C and O'Neill, L and Kuhn, CM}, title = {Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.}, journal = {Psychopharmacology}, volume = {231}, number = {8}, pages = {1831-1839}, pmid = {24158502}, issn = {1432-2072}, support = {R01 AA017621/AA/NIAAA NIH HHS/United States ; T34 GM008718/GM/NIGMS NIH HHS/United States ; }, mesh = {Aging ; Alcohol Drinking/*physiopathology ; Animals ; Animals, Outbred Strains ; Avoidance Learning/drug effects/*physiology ; Central Nervous System Depressants/administration & dosage ; Conditioning, Psychological/drug effects/*physiology ; Dose-Response Relationship, Drug ; Drinking Water/administration & dosage ; Ethanol/administration & dosage ; Female ; Male ; Rats ; Saccharin/administration & dosage ; Sex Characteristics ; Taste Perception/drug effects/*physiology ; Volition ; }, abstract = {RATIONALE: Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse.

OBJECTIVES: This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development.

METHODS: Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats.

RESULTS: CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns.

CONCLUSIONS: These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.}, } @article {pmid24157981, year = {2014}, author = {Andrews, PL and Sanger, GJ}, title = {Nausea and the quest for the perfect anti-emetic.}, journal = {European journal of pharmacology}, volume = {722}, number = {}, pages = {108-121}, doi = {10.1016/j.ejphar.2013.09.072}, pmid = {24157981}, issn = {1879-0712}, mesh = {Animals ; Antiemetics/adverse effects/*pharmacology/therapeutic use ; Disease Models, Animal ; Drug Discovery/*methods ; Humans ; Nausea/diagnosis/*drug therapy/metabolism/physiopathology ; Translational Research, Biomedical ; Vomiting/diagnosis/drug therapy/metabolism/physiopathology ; }, abstract = {The discovery of anti-emetic agents is reviewed to illustrate the large database (>129,000 papers in PubMed) available for potential data mining and to provide a background to the shift in interest to nausea from vomiting. Research on nausea extends to identification of biomarkers for diagnosis/clinical trials and to understanding why nausea is such a common dose-limiting toxicity of diverse therapeutic agents. The lessons learned for translation from animals to humans, from the discovery of the anti-vomiting effects of 5-HT3 and NK1 receptor antagonists, is discussed in terms of the similarities between the emetic pathways and their pharmacology, and also in terms of the limitations of rodent models of "nausea" (pica, conditioned taste aversion, conditioned gaping and disgust). The review focuses on the established view that anti-emetics are more efficacious against vomiting than nausea. In particular we examine studies of 5-HT3, NK1 and D2 receptor antagonists, gabapentin and various receptor agonists. The potential for targeting anti-nausea agents is then considered, by targeting mechanisms which correct delayed gastric emptying (prokinetics), the rise in plasma vasopressin (AVP) and/or act at central targets revealed by the growing knowledge of cortical regions activated/inhibited in subjects reporting nausea. Modulation of the projections from the brainstem to the cortical areas responsible for the genesis of the sensation of nausea provides the most likely approach to a target at which an anti-nausea drug could be targeted with the expectation that it would affect nausea from multiple causes.}, } @article {pmid24157975, year = {2014}, author = {Parker, LA}, title = {Conditioned flavor avoidance and conditioned gaping: rat models of conditioned nausea.}, journal = {European journal of pharmacology}, volume = {722}, number = {}, pages = {122-133}, doi = {10.1016/j.ejphar.2013.09.070}, pmid = {24157975}, issn = {1879-0712}, mesh = {Animals ; *Avoidance Learning/drug effects ; *Behavior, Animal/drug effects ; *Conditioning, Psychological/drug effects ; Disease Models, Animal ; Humans ; Nausea/drug therapy/*psychology ; Rats ; *Taste ; }, abstract = {Although rats are incapable of vomiting, they demonstrate profound avoidance of a flavor previously paired with an emetic drug. They also display conditioned gaping reactions during re-exposure to the flavor. This robust learning occurs in a single trial and with long delays (hours) between consumption of a novel flavor and the emetic treatment. However, conditioned flavor avoidance learning is not a selective measure of the emetic properties of drugs, because non-emetic treatments (even highly rewarding treatments) produce conditioned avoidance, and anti-emetic treatments are generally ineffective in suppressing conditioned avoidance produced by an emetic drug. On the other hand, conditioned gaping reactions are consistently produced by emetic drugs and are prevented by anti-emetic drugs, indicating that they may be a more selective measure of conditioned malaise in rats. Here we review the literature on the use of conditioned flavor avoidance and conditioned gaping reactions as rat measures of conditioned nausea, as well as the neuropharmacology and neuroanatomy of conditioned gaping reactions in rats.}, } @article {pmid24122728, year = {2014}, author = {Merluzzi, AP and Hurwitz, ZE and Briscione, MA and Cobuzzi, JL and Wetzell, B and Rice, KC and Riley, AL}, title = {Age-dependent MDPV-induced taste aversions and thermoregulation in adolescent and adult rats.}, journal = {Developmental psychobiology}, volume = {56}, number = {5}, pages = {943-954}, pmid = {24122728}, issn = {1098-2302}, support = {Z99 DA999999//Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects/physiology ; Benzodioxoles/*pharmacology ; Body Temperature Regulation/*drug effects/physiology ; Designer Drugs/*pharmacology ; Male ; Pyrrolidines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; }, abstract = {Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of "bath salts," the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8, or 3.2 mg/kg), a common constituent in "bath salts," in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population.}, } @article {pmid24082961, year = {2012}, author = {Fujiwara, H and Sawa, K and Takahashi, M and Lauwereyns, J and Tsukada, M and Aihara, T}, title = {Context and the renewal of conditioned taste aversion: the role of rat dorsal hippocampus examined by electrolytic lesion.}, journal = {Cognitive neurodynamics}, volume = {6}, number = {5}, pages = {399-407}, pmid = {24082961}, issn = {1871-4080}, abstract = {An extinguished conditioned response can sometimes be restored. Previous research has shown that this renewal effect depends on the context in which conditioning versus extinction takes place. Here we provide evidence that the dorsal hippocampus is critically involved in the representation of context that underscores the renewal effect. We performed electrolytic lesions in dorsal hippocampus, before or after extinction, in a conditioned taste aversion paradigm with rats. Rats that underwent all conditioning, extinction and testing procedures in the same experimental context showed no renewal during testing in the original context. In contrast, rats that underwent extinction procedures in a different experimental context than the one in which they had acquired the conditioned response, showed a reliable renewal effect during testing in the original context. When electrolytic lesion was performed prior to extinction, the context-dependent renewal effect was disrupted. When electrolytic lesion was undertaken after extinction, we observed a complex pattern of data including the blockage of the conventional renewal effect, and the appearance of an unconventional renewal effect. The implications of these results are discussed with respect to current views on the role of the dorsal hippocampus in processing context information.}, } @article {pmid24064183, year = {2013}, author = {Dill, MJ and Shaw, J and Cramer, J and Sindelar, DK}, title = {5-HT1A receptor antagonists reduce food intake and body weight by reducing total meals with no conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {112}, number = {}, pages = {1-8}, doi = {10.1016/j.pbb.2013.09.003}, pmid = {24064183}, issn = {1873-5177}, mesh = {Animals ; *Avoidance Learning ; Body Weight/*drug effects ; Conditioning, Classical ; Energy Intake/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Receptor, Serotonin, 5-HT1A/*drug effects ; Serotonin Antagonists/pharmacokinetics/*pharmacology ; *Taste ; }, abstract = {Serotonin acts through receptors controlling several physiological functions, including energy homeostasis regulation and food intake. Recent experiments demonstrated that 5-HT1A receptor antagonists reduce food intake. We sought to examine the microstructure of feeding with 5-HT1A receptor antagonists using a food intake monitoring system. We also examined the relationship between food intake, inhibition of binding and pharmacokinetic (PK) profiles of the antagonists. Ex vivo binding revealed that, at doses used in this study to reduce food intake, inhibition of binding of a 5-HT1A agonist by ~40% was reached in diet-induced obese (DIO) mice with a trend for higher binding in DIO vs. lean animals. Additionally, PK analysis detected levels from 2 to 24h post-compound administration. Male DIO mice were administered 5-HT1A receptor antagonists LY439934 (10 or 30 mg/kg, p.o.), WAY100635 (3 or 10mg/kg, s.c.), SRA-333 (10 or 30 mg/kg, p.o.), or NAD-299 (3 or 10mg/kg, s.c.) for 3 days and meal patterns were measured. Analyses revealed that for each antagonist, 24-h food intake was reduced through a specific decrease in the total number of meals. Compared to controls, meal number was decreased 14-35% in the high dose. Average meal size was not changed by any of the compounds. The reduction in food intake reduced body weight 1-4% compared to Vehicle controls. Subsequently, a conditioned taste aversion (CTA) assay was used to determine whether the feeding decrease might be an indicator of aversion, nausea, or visceral illness caused by the antagonists. Using a two bottle preference test, it was found that none of the compounds produced a CTA. The decrease in food intake does not appear to be a response to nausea or malaise. These results indicate that 5-HT1A receptor antagonist suppresses feeding, specifically by decreasing the number of meals, and induce weight loss without an aversive side effect.}, } @article {pmid24063812, year = {2013}, author = {Olszewski, PK and Waas, JR and Brooks, LL and Herisson, F and Levine, AS}, title = {Oxytocin receptor blockade reduces acquisition but not retrieval of taste aversion and blunts responsiveness of amygdala neurons to an aversive stimulus.}, journal = {Peptides}, volume = {50}, number = {}, pages = {36-41}, doi = {10.1016/j.peptides.2013.09.008}, pmid = {24063812}, issn = {1873-5169}, mesh = {Administration, Oral ; Amygdala/*drug effects/metabolism ; Animals ; Brain Mapping ; Camphanes/pharmacology ; Conditioning, Psychological ; Hypothalamus/*drug effects/metabolism ; Injections, Intraperitoneal ; Lithium Chloride/administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/*drug effects/metabolism ; Oxytocin/*antagonists & inhibitors/biosynthesis ; Piperazines/pharmacology ; Receptors, Oxytocin/*antagonists & inhibitors/metabolism ; Saccharin/administration & dosage ; Taste/*drug effects/physiology ; }, abstract = {When gastrointestinal sickness induced by toxin injection is associated with exposure to novel food, the animal acquires a conditioned taste aversion (CTA). Malaise is accompanied by a surge in oxytocin release and in oxytocin neuronal activity; however, it is unclear whether oxytocin is a key facilitator of aversion or merely its marker. Herein we investigated whether blockade of the oxytocin receptor with the blood-brain barrier penetrant oxytocin receptor antagonist L-368,899 is detrimental for the acquisition and/or retrieval of lithium chloride (LiCl)-dependent CTA to a saccharin solution in mice. We also examined whether L-368,899 given prior to LiCl affects neuronal activity defined through c-Fos immunohistochemistry in select brain sites facilitating CTA acquisition. L-368,899 given prior to LiCl caused a 30% increase in saccharin solution intake in a two-bottle test, but when the antagonist was administered before the two-bottle test, it failed to diminish the retrieval of an existing CTA. LiCl administration increased c-Fos expression in the hypothalamic paraventricular and supraoptic nuclei, area postrema, nucleus of the solitary tract and basolateral and central (CNA) nuclei of the amygdala. L-368,899 injected before LiCl reduced the number of c-Fos positive CNA neurons and brought it down to levels similar to those observed in mice treated only with L-368,899. We conclude that oxytocin is one of the key components in acquisition of LiCl-induced CTA and the aversive response can be alleviated by the oxytocin receptor blockade. Oxytocin receptor antagonism blunts responsiveness of CNA to peripherally injected LiCl.}, } @article {pmid24058712, year = {2013}, author = {Latorre, L and Larrinaga, AR and Santamaría, L}, title = {Rats and seabirds: effects of egg size on predation risk and the potential of conditioned taste aversion as a mitigation method.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e76138}, pmid = {24058712}, issn = {1932-6203}, mesh = {Animals ; *Charadriiformes ; *Eggs ; *Food Chain ; *Introduced Species ; Mediterranean Islands ; Mice ; *Predatory Behavior ; *Rats ; }, abstract = {Seabirds nesting on islands are threatened by invasive rodents, such as mice and rats, which may attack eggs, chicks and even adults. The low feasibility of rat eradications on many islands makes the development of alternate control plans necessary. We used a combination of field experiments on a Mediterranean island invaded by black rats (Rattusrattus) to evaluate (1) the predation risk posed to different-sized seabird eggs and (2), the potential of two deterrent methods (electronic and chemical) to reduce its impact. Rats were able to consume eggs of all sizes (12 to 68 g), but survival increased 13 times from the smallest to the largest eggs (which also had more resistant eggshells). Extrapolation to seabird eggs suggests that the smallest species (Hydrobatespelagicus) suffer the most severe predation risk, but even the largest (Larusmichahellis) could suffer >60% mortality. Nest attack was not reduced by the deterrents. However, chemical deterrence (conditioned taste aversion by lithium chloride) slowed the increase in predation rate over time, which resulted in a three-fold increase in egg survival to predation as compared to both control and electronic deterrence. At the end of the experimental period, this effect was confirmed by a treatment swap, which showed that conferred protection remains at least 15 days after cessation of the treatment. Results indicate that small seabird species are likely to suffer severe rates of nest predation by rats and that conditioned taste aversion, but not electronic repellents, may represent a suitable method to protect colonies when eradication or control is not feasible or cost-effective.}, } @article {pmid24055778, year = {2013}, author = {Inui, T and Inui-Yamamoto, C and Yoshioka, Y and Ohzawa, I and Shimura, T}, title = {Activation of efferents from the basolateral amygdala during the retrieval of conditioned taste aversion.}, journal = {Neurobiology of learning and memory}, volume = {106}, number = {}, pages = {210-220}, doi = {10.1016/j.nlm.2013.09.003}, pmid = {24055778}, issn = {1095-9564}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Choice Behavior/drug effects/physiology ; Conditioning, Psychological/drug effects/*physiology ; Lithium Chloride/administration & dosage ; Magnetic Resonance Imaging ; Male ; Neural Pathways/drug effects/physiology ; Neurons, Efferent/drug effects/*physiology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {The basolateral amygdala (BLA) is critical in the retrieval of conditioned taste aversion (CTA). Although BLA neurons have axonal connections with several brain regions, it is unclear which efferent pathways are functional in CTA. The present study investigated the involvement of efferents from BLA in CTA retrieval with manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI). Rats receiving intraoral saccharin infusion paired with intraperitoneal administration of lithium chloride (LiCl) were presented with saccharin (C-S and BC-S groups) or water (C-W group) on the test day. The BC-S group was administered with LiCl 15 min before saccharin presentation on the conditioning day (backward conditioning, BC). Another two groups were injected with saline (S-S and S-W groups) instead of LiCl. On the test day, 50 nL of 40-mM manganese chloride (MnCl2) was injected into BLA before the intraoral fluid infusion. Using MRI, we analyzed Mn(2+) movements, which indicated the activation of efferent neurons. The C-S group showed the highest activities in several efferents from BLA. Of them, the activities of the efferents to the nucleus accumbens core (NAcC), the anterior part of the bed nucleus of the stria terminalis (aBNST), and the central amygdala (CeA) were larger in the C-S group than in the Q group, which was presented with a normally aversive quinine solution. Although rats equivalently rejected conditioned aversive saccharin and quinine, the aversive responses in the C-S group, and not the Q group, were due to CTA retrieval. Therefore, our results indicated that BLA efferents to NAcC, aBNST, and CeA were specifically activated during CTA retrieval, suggesting that these efferents are key components in the neural mechanisms of CTA.}, } @article {pmid24035915, year = {2013}, author = {Lo, AC and Tesseur, I and Scopes, DI and Nerou, E and Callaerts-Vegh, Z and Vermaercke, B and Treherne, JM and De Strooper, B and D'Hooge, R}, title = {Dose-dependent improvements in learning and memory deficits in APPPS1-21 transgenic mice treated with the orally active Aβ toxicity inhibitor SEN1500.}, journal = {Neuropharmacology}, volume = {75}, number = {}, pages = {458-466}, doi = {10.1016/j.neuropharm.2013.08.030}, pmid = {24035915}, issn = {1873-7064}, mesh = {Administration, Oral ; Alzheimer Disease/*complications/genetics ; Amyloid beta-Peptides/*antagonists & inhibitors ; Amyloid beta-Protein Precursor/genetics ; Aniline Compounds/chemistry/pharmacology/therapeutic use ; Animals ; Avoidance Learning/drug effects ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Humans ; Learning Disabilities/*drug therapy/*etiology ; Maze Learning/drug effects ; Memory Disorders/*etiology ; Mice ; Mice, Transgenic ; Mutation/genetics ; Nitriles/*administration & dosage/chemistry ; Peptide Fragments/*antagonists & inhibitors ; Presenilin-1/genetics ; Pyrimidines/administration & dosage/chemistry/pharmacology/therapeutic use ; Synaptophysin/metabolism ; Taste/drug effects ; }, abstract = {In the Alzheimer's disease (AD) brain, accumulation of Aβ1-42 peptides is suggested to initiate a cascade of pathological events. To date, no treatments are available that can reverse or delay AD-related symptoms in patients. In the current study, we introduce a new Aβ toxicity inhibitor, SEN1500, which in addition to its block effect on Aβ1-42 toxicity in synaptophysin assays, can be administered orally and cross the blood-brain barrier without adverse effects in mice. In a different set of animals, APPPS1-21 mice were fed with three different doses of SEN1500 (1 mg/kg, 5 mg/kg and 20 mg/kg) for a period of 5 months. Cognition was assessed in a variety of behavioral tests (Morris water maze, social recognition, conditioned taste aversion and passive avoidance). Results suggest a positive effect on cognition with 20 mg/kg SEN1500 compared to control APPPS1-21 mice. However, no changes in soluble or insoluble Aβ1-40 and Aβ1-42 were detected in the brains of SEN1500-fed mice. SEN1500 also attenuated the effect of Aβ1-42 on synaptophysin levels in mouse cortical neurons, which indicated that the compound blocked the synaptic toxicity of Aβ1-42. In vitro and in vivo effects presented here suggest that SEN1500 could be an interesting AD therapeutic.}, } @article {pmid23994231, year = {2013}, author = {Gubner, NR and Reed, C and McKinnon, CS and Phillips, TJ}, title = {Unique genetic factors influence sensitivity to the rewarding and aversive effects of methamphetamine versus cocaine.}, journal = {Behavioural brain research}, volume = {256}, number = {}, pages = {420-427}, pmid = {23994231}, issn = {1872-7549}, support = {F31 AA020732/AA/NIAAA NIH HHS/United States ; P50 DA018165/DA/NIDA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; F31AA020732/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Central Nervous System Stimulants/*pharmacology ; Cocaine/*pharmacology ; Female ; Male ; Methamphetamine/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Motor Activity/*drug effects/genetics ; *Reward ; Species Specificity ; }, abstract = {Genetic factors significantly influence addiction-related phenotypes. This is supported by the successful bidirectional selective breeding of two replicate sets of mouse lines for amount of methamphetamine consumed. Some of the same genetic factors that influence methamphetamine consumption have been previously found also to influence sensitivity to the conditioned rewarding and aversive effects of methamphetamine. The goal of the current studies was to determine if some of the same genetic factors influence sensitivity to the conditioned rewarding and aversive effects of cocaine. Cocaine conditioned reward was examined in methamphetamine high drinking and low drinking line mice using a conditioned place preference procedure and cocaine conditioned aversion was measured using a conditioned taste aversion procedure. In addition, a general sensitivity measure, locomotor stimulant response to cocaine, was assessed in these lines; previous data indicated no difference between the selected lines in sensitivity to methamphetamine-induced stimulation. In contrast to robust differences for methamphetamine, the methamphetamine high and low drinking lines did not differ in sensitivity to either the rewarding or aversive effects of cocaine. They also exhibited comparable sensitivity to cocaine-induced locomotor stimulation. These data suggest that the genetic factors that influence sensitivity to the conditioned rewarding and aversive effects of methamphetamine in these lines of mice do not influence sensitivity to these effects of cocaine. Thus, different genetic factors may influence risk for methamphetamine versus cocaine use.}, } @article {pmid23973606, year = {2013}, author = {Molero-Chamizo, A}, title = {Excitotoxic lesion of the hippocampus of Wistar rats disrupts the circadian control of the latent inhibition of taste aversion learning.}, journal = {Brain research}, volume = {1533}, number = {}, pages = {105-113}, doi = {10.1016/j.brainres.2013.08.030}, pmid = {23973606}, issn = {1872-6240}, mesh = {Amygdala/*physiology ; Animals ; *Circadian Rhythm ; Conditioning, Classical/*physiology ; Drinking Behavior ; Hippocampus/*physiology ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; Time Factors ; }, abstract = {Previous experiments have shown that changes in the time of day between taste pre-exposure and conditioning prevent the latent inhibition of conditioning taste aversion. The effect of these changes in circadian context between pre-exposure and conditioning on the magnitude of the learned aversion appears to be similar to the effect of changes in spatial context on this type of learning. To elucidate the brain areas involved in this circadian dependence of latent inhibition of conditioning taste aversion, the effect of excitotoxic lesions of the hippocampus, a region related to spatial-contextual modulation in this learning process, was analyzed. The latent inhibition of conditioning taste aversion in animals with hippocampal lesions, that were pre-exposed and conditioned to the same or different time of day, was compared with the response of animals exposed to either conditions ("same" or "different") but had undergone amygdala lesions or sham lesions. The results showed that selective dorsal hippocampus lesion eliminated the circadian dependence of latent inhibition of taste aversion. A change in the time of day between pre-exposure and conditioning did not prevent latent inhibition in animals with hippocampal lesions. In contrast, this change prevented latent inhibition in the amygdala-lesioned and sham groups. These findings suggest that the hippocampus contains a selective mechanism that modulates the contextual dependency of the latent inhibition of conditioning taste aversion without interfering with the effect of taste pre-exposure itself. This study may help to understand the possible common involvement of the hippocampus in different types of contextual control of associative learning.}, } @article {pmid23958943, year = {2013}, author = {Fowler, CD and Tuesta, L and Kenny, PJ}, title = {Role of α5* nicotinic acetylcholine receptors in the effects of acute and chronic nicotine treatment on brain reward function in mice.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, pmid = {23958943}, issn = {1432-2072}, support = {K99 DA032543/DA/NIDA NIH HHS/United States ; R01 DA020686/DA/NIDA NIH HHS/United States ; R01 DA030929/DA/NIDA NIH HHS/United States ; }, abstract = {OBJECTIVE: Allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) subunit gene, CHRNA5, increases vulnerability to tobacco addiction. Here, we investigated the role of α5* nAChRs in the effects of nicotine on brain reward systems.

MATERIALS AND METHODS: Effects of acute (0.03125-0.5 mg/kg SC) or chronic (24 mg/kg per day; osmotic minipump) nicotine and mecamylamine-precipitated withdrawal on intracranial self-stimulation (ICSS) thresholds were assessed in wild-type and α5 nAChR subunit knockout mice. Noxious effects of nicotine were further investigated using a conditioned taste aversion procedure.

RESULTS: Lower nicotine doses (0.03125-0.125 mg/kg) decreased ICSS thresholds in wild-type and α5 knockout mice. At higher doses (0.25-0.5 mg/kg), threshold-lowering effects of nicotine were diminished in wild-type mice, whereas nicotine lowered thresholds across all doses tested in α5 knockout mice. Nicotine (1.5 mg/kg) conditioned a taste aversion to saccharine equally in both genotypes. Mecamylamine (5 mg/kg) elevated ICSS thresholds by a similar magnitude in wild-type and α5 knockout mice prepared with minipumps delivering nicotine. Unexpectedly, mecamylamine also elevated thresholds in saline-treated α5 knockout mice.

CONCLUSION: α5* nAChRs are not involved in reward-enhancing effects of lower nicotine doses, the reward-inhibiting effects of nicotine withdrawal, or the general noxious effects of higher nicotine doses. Instead, α5* nAChRs regulate the reward-inhibiting effects nicotine doses that oppose the reward-facilitating effects of the drug. These data suggest that disruption of α5* nAChR signaling greatly expands the range of nicotine doses that facilitate brain reward activity, which may help explain the increased tobacco addiction vulnerability associated with CHRNA5 risk alleles.}, } @article {pmid23943541, year = {2013}, author = {King, HE and Riley, AL}, title = {A history of morphine-induced taste aversion learning fails to affect morphine-induced place preference conditioning in rats.}, journal = {Learning & behavior}, volume = {41}, number = {4}, pages = {433-442}, pmid = {23943541}, issn = {1543-4508}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; *Morphine/pharmacology ; Rats ; Reward ; Saccharin/pharmacology ; *Taste ; }, abstract = {Drugs of abuse have both rewarding and aversive effects, as indexed by the fact that they support place preferences and taste aversions, respectively. In the present study, we explored whether having a history with the aversive effects of morphine (via taste aversion conditioning) impacted the subsequent rewarding effects of morphine, as measured in the place preference design. In Experiment 1, rats were exposed to a taste aversion procedure in which saccharin was followed by morphine. Place preference conditioning was then initiated in which animals were injected with morphine and placed on one side of a two-chambered apparatus. Animals with a taste aversion history acquired place preferences to the same degree as controls without such a history, suggesting that morphine's affective properties condition multiple effects, dependent on the specific stimuli present during conditioning. To determine whether these results were a reflection of processes operating in traditional associative conditioning, in a modified blocking procedure, place preference conditioning was attempted in the presence of a taste previously associated with morphine (Exp. 2). Under these conditions, animals still acquired morphine-induced place preferences comparable to those of animals without a morphine or conditioning history. These results are consistent with the position that drugs of abuse have multiple stimulus effects (positive and negative) that are differentially associated with specific stimuli (environmental and taste) that drive different behavioral responses (approach and avoidance).}, } @article {pmid23910826, year = {2015}, author = {Barkley-Levenson, AM and Cunningham, CL and Smitasin, PJ and Crabbe, JC}, title = {Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice.}, journal = {Addiction biology}, volume = {20}, number = {1}, pages = {80-90}, pmid = {23910826}, issn = {1369-1600}, support = {AA13519/AA/NIAAA NIH HHS/United States ; P50 AA010760/AA/NIAAA NIH HHS/United States ; T32 AA007468/AA/NIAAA NIH HHS/United States ; AA007468/AA/NIAAA NIH HHS/United States ; R37 AA007702/AA/NIAAA NIH HHS/United States ; U01 AA013519/AA/NIAAA NIH HHS/United States ; R24 AA020245/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; AA020245/AA/NIAAA NIH HHS/United States ; I01 BX000313/BX/BLRD VA/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Behavior, Animal/*drug effects ; Central Nervous System Depressants/*pharmacology ; Conditioning, Classical/*drug effects ; Ethanol/*pharmacology ; Genetics, Behavioral ; Mice ; Mice, Inbred Strains ; *Punishment ; *Reward ; }, abstract = {Both rewarding and aversive effects contribute to alcohol consumption. Animals genetically predisposed to be high drinkers show reduced sensitivity to the aversive effects of alcohol, and in some instances, increased sensitivity to alcohol's rewarding effects. The present studies tested the high drinking in the dark (HDID) selected lines, a genetic model of drinking to intoxication, to determine whether intake in these mice was genetically related to sensitivity to alcohol aversion or reward. Male HDID mice from the first and second replicate lines (HDID-1 and HDID-2, respectively) and mice from the heterogeneous progenitor control population (HS/Npt, or HS) were conditioned for a taste aversion to a salt solution using two doses of alcohol, and lithium chloride (LiCl) and saline controls. In separate experiments, male and female HDID-1, HDID-2 and HS mice were conditioned for place preference using alcohol. HDID mice were found to have an attenuated sensitivity to alcohol at a moderate (2 g/kg) dose compared to HS mice, but did not differ on conditioned taste aversion to a high (4 g/kg) dose or LiCl or saline injections. HDID and HS mice showed comparable development of alcohol-induced conditioned place preference. These results indicate that high blood alcohol levels after drinking in the HDID mice is genetically related to attenuated aversion to alcohol, while sensitivity to alcohol reward is not altered in these mice. Thus, HDID mice may find a moderate dose of alcohol to be less aversive than control mice and consequently may drink more because of this reduced aversive sensitivity.}, } @article {pmid23891910, year = {2013}, author = {Revillo, DA and Molina, JC and Paglini, MG and Arias, C}, title = {A sensory-enhanced context allows renewal of an extinguished fear response in the infant rat.}, journal = {Behavioural brain research}, volume = {253}, number = {}, pages = {173-177}, doi = {10.1016/j.bbr.2013.07.027}, pmid = {23891910}, issn = {1872-7549}, mesh = {Analysis of Variance ; Animals ; Conditioning, Operant/physiology ; Cues ; Data Interpretation, Statistical ; Extinction, Psychological/*physiology ; Fear/*psychology ; Odorants ; Photic Stimulation ; Rats ; Rats, Wistar ; }, abstract = {Studies of extinction in preweanling rats have failed to find ABA-renewal in a fear conditioning paradigm. This result supports the hypothesis postulating ontogenetic qualitative differences in experimental extinction. A similar result in adult rats led to the conclusion that ABA-renewal requires contexts A and B to differ in several types of features, including odor cues. Recently we reported experimental evidence of the renewal of an extinguished taste aversion response in infant rats employing contexts which differ in their odor content. The present study examines the possibility of renewing an extinguished fear response in infant rats when contexts A and B do not include (Experiment 1) or include (Experiment 2) an explicit odor. Results showed absence of renewal when using standard contexts (without explicit odors, Experiment 1). However, when contexts A and B varied also in their odor content, the ABA-renewal procedure was effective in reinstating the extinguished CR (Experiment 2). Thus, it can be concluded that the sensory content of the context determines the observation of renewal in the infant rat, a result that is coherent with previous observations in the adult rat. As a whole, these results challenge our understanding of extinction as a learning process that is qualitatively different in preweanling rats than in later stages of ontogeny.}, } @article {pmid23827202, year = {2013}, author = {Klakotskaia, D and Ramsey, AK and Fowler, SW and Serfozo, P and Simonyi, A and Schachtman, TR}, title = {Effects of group II and III metabotropic glutamate receptor ligands on conditioned taste aversion learning.}, journal = {Behavioural brain research}, volume = {253}, number = {}, pages = {9-16}, doi = {10.1016/j.bbr.2013.06.032}, pmid = {23827202}, issn = {1872-7549}, mesh = {Amino Acids/pharmacology ; Anilides/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Benzhydryl Compounds/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Cues ; Cyclohexanecarboxylic Acids/pharmacology ; Excitatory Amino Acid Agents/*pharmacology ; Ligands ; Male ; Pyridones/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/*agonists/*antagonists & inhibitors/*metabolism ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {Metabotropic glutamate (mGlu) receptors impact learning and memory. Although some evidence indicates the importance of these receptors in conditioned taste aversion (CTA), the subtype-specific involvement of mGlu receptors in this associative learning task remains to be determined. These experiments examined the effects of (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), a selective group II mGlu receptor agonist, cis-2-[[(3,5-dichlorophenyl)amino]carbonyl]cyclohexanecarboxylic acid (VU0155041), a mGlu4 positive allosteric modulator, N,N'-dibenzhydrylethane-1,2-diamine (AMN082), a mGlu7 allosteric agonist, and 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a mGlu7 negative allosteric modulator, on the acquisition of CTA using male Sprague-Dawley rats. Systemic injections of LY379268, AMN082, and MMPIP prior to conditioning decreased the acquisition of CTA, revealing that mGlu2/3 and mGlu7 are involved in CTA learning.}, } @article {pmid23824960, year = {2013}, author = {Kim, HJ and Park, EY and Oh, MJ and Park, SS and Shin, KH and Choi, SH and Chun, BG and Kim, DH}, title = {Central administration of metformin into the third ventricle of C57BL/6 mice decreases meal size and number and activates hypothalamic S6 kinase.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {305}, number = {5}, pages = {R499-505}, doi = {10.1152/ajpregu.00099.2013}, pmid = {23824960}, issn = {1522-1490}, mesh = {Animals ; Appetite Regulation/*drug effects/*physiology ; Enzyme Activation ; Hypoglycemic Agents/administration & dosage ; Hypothalamus/drug effects/*enzymology ; Infusions, Intraventricular ; Male ; Meals/*drug effects/*physiology ; Metformin/*administration & dosage ; Mice ; Mice, Inbred C57BL ; Ribosomal Protein S6 Kinases/*biosynthesis ; Third Ventricle/drug effects/physiology ; }, abstract = {Administration of metformin is known to reduce both body weight and food intake. Although the hypothalamus is recognized as a critical regulator of energy balance and body weight, there is currently no evidence for an effect of metformin in the hypothalamus. Therefore, we sought to determine the central action of metformin on energy balance and body weight, as well as its potential involvement with key hypothalamic energy sensors, including adenosine monophosphate-activated protein kinase (AMPK) and S6 kinase (S6K). We used meal pattern analysis and a conditioned taste aversion (CTA) test and measured energy expenditure in C56BL/6 mice administered metformin (0, 7.5, 15, or 30 μg) into the third ventricle (I3V). Furthermore, we I3V-administered either control or metformin (30 μg) and compared the phosphorylation of AMPK and S6K in the mouse mediobasal hypothalamus. Compared with the control, I3V administration of metformin decreased body weight and food intake in a dose-dependent manner and did not result in CTA. Furthermore, the reduction in food intake induced by I3V administration of metformin was accomplished by decreases in both nocturnal meal size and number. Compared with the control, I3V administration of metformin significantly increased phosphorylation of S6K at Thr(389) and AMPK at Ser(485/491) in the mediobasal hypothalamus, while AMPK phosphorylation at Thr(172) was not significantly altered. Moreover, I3V rapamycin pretreatment restored the metformin-induced anorexia and weight loss. These results suggest that the reduction in food intake induced by the central administration of metformin in the mice may be mediated by activation of S6K pathway.}, } @article {pmid23813056, year = {2013}, author = {Dwyer, DM and Gasalla, P and López, M}, title = {Nonreinforced flavor exposure attenuates the effects of conditioned taste aversion on both flavor consumption and cue palatability.}, journal = {Learning & behavior}, volume = {41}, number = {4}, pages = {390-401}, pmid = {23813056}, issn = {1543-4508}, mesh = {Animals ; *Avoidance Learning/drug effects ; Conditioning, Classical ; Cues ; Flavoring Agents ; *Taste/drug effects ; }, abstract = {Nonreinforced exposure to a cue tends to attenuate subsequent conditioning with that cue-an effect referred to as latent inhibition (LI). In the two experiments reported here, we examined LI effects in the context of conditioned taste aversion by examining both the amount of consumption and the microstructure of the consummatory behavior (in terms of the mean size of lick clusters). The latter measure can be taken to reflect affective responses to, or the palatability of, the solution being consumed. In both experiments, exposure to a to-be-conditioned flavor prior to pairing the flavor with nausea produced by lithium chloride attenuated both the reduction in consumption and the reduction in lick cluster sizes typically produced by taste aversion learning. In addition, we observed a tendency (especially in the lick cluster measure) for nonreinforced exposure to reduce neophobic responses to the test flavors. Taken together, these results reinforce the suggestion from previous experiments using taste reactivity methods that LI attenuates the effects of taste aversion on both consumption and cue palatability. The present results also support the suggestion that the failure in previous studies to see concurrent LI effects on consumption and palatability was due to a context specificity produced by the oral taste infusion methods required for taste reactivity analyses. Finally, the fact that the pattern of extinction of conditioned changes in consumption and in lick cluster sizes was not affected by preexposure to the cue flavors suggests that LI influenced the quantity but not the quality of conditioned taste aversion.}, } @article {pmid23789439, year = {2013}, author = {Solntseva, SV and Storozheva, ZI and Nikitin, VP and Sherstnev, VV}, title = {[Spontaneous enhancement of long-term memory retrieval during a few days after training].}, journal = {Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova}, volume = {99}, number = {3}, pages = {362-371}, pmid = {23789439}, issn = {0869-8139}, mesh = {Animals ; Electric Stimulation ; Helix, Snails/*physiology ; Hippocampus/physiology ; Male ; Maze Learning/*physiology ; Memory, Long-Term/*physiology ; Neurons/physiology ; Rats ; Rats, Wistar ; Space Perception/physiology ; Taste Perception ; Time Factors ; }, abstract = {The dynamics of long-term memory retrieval on the 1st and 5th days after rat training in spatial Morris water maze and snail conditioned taste aversion models was studied. It was found that animals trained for several days displayed stable and high level of memory retrieval both on 1st and on 5th days after training. Under conditions of single-session training the rate of memory retrieval in snails and rats on the 5th day was higher than on the 1st day after training. It has been proposed that spontaneous enhancement of habit retrieval during 5-days time interval after training is a result of "lingering" memory consolidation processes, which includes trace reorganization in particular molecular and morphological changes in animal brain neurons.}, } @article {pmid23783889, year = {2013}, author = {Charlu, S and Wisotsky, Z and Medina, A and Dahanukar, A}, title = {Acid sensing by sweet and bitter taste neurons in Drosophila melanogaster.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2042}, pmid = {23783889}, issn = {2041-1723}, support = {R21 DC012408/DC/NIDCD NIH HHS/United States ; R21DC012408/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; Carbohydrates/*pharmacology ; Carboxylic Acids/*pharmacology ; Drosophila melanogaster/drug effects/genetics/*metabolism ; Fruit/chemistry ; Genotype ; Hydrochloric Acid/pharmacology ; Hydrogen-Ion Concentration ; Mutant Proteins/metabolism ; Neurons/drug effects/*metabolism ; Physical Stimulation ; Receptors, G-Protein-Coupled/metabolism ; Sensilla/drug effects/metabolism ; Sucrose/pharmacology ; Taste/*drug effects ; }, abstract = {Drosophila melanogaster can taste various compounds and separate them into few basic categories such as sweet, bitter and salt taste. Here we investigate mechanisms underlying acid detection in Drosophila and report that the fly displays strong taste aversion to common carboxylic acids. We find that acid tastants act by the activation of a subset of bitter neurons and inhibition of sweet neurons. Bitter neurons begin to respond at pH 5 and show an increase in spike frequency as the extracellular pH drops, which does not rely on previously identified chemoreceptors. Notably, sweet neuron activity depends on the balance of sugar and acid tastant concentrations. This is independent of bitter neuron firing, and allows the fly to avoid acid-laced food sources even in the absence of functional bitter neurons. The two mechanisms may allow the fly to better evaluate the risk of ingesting acidic foods and modulate its feeding decisions accordingly.}, } @article {pmid23775255, year = {2014}, author = {Cobuzzi, JL and Siletti, KA and Hurwitz, ZE and Wetzell, B and Baumann, MH and Riley, AL}, title = {Age differences in (±) 3,4-methylenedioxymethamphetamine (MDMA)-induced conditioned taste aversions and monoaminergic levels.}, journal = {Developmental psychobiology}, volume = {56}, number = {4}, pages = {635-646}, pmid = {23775255}, issn = {1098-2302}, support = {ZIA DA000523-06/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects ; Biogenic Monoamines/*metabolism ; Brain/*drug effects/metabolism ; Conditioning, Psychological/*drug effects ; Male ; N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Preclinical work indicates that adolescent rats appear more sensitive to the rewarding effects and less sensitive to the aversive effects of abused drugs. The present investigation utilized the conditioned taste aversion (CTA) design to measure the relative aversive effects of (±)3,4-methylenedioxymethamphetamine (MDMA; 0, 1.0, 1.8, or 3.2 mg/kg) in adolescent and adult Sprague-Dawley rats. After behavioral testing was complete, monoamine and associated metabolite levels in discrete brain regions were quantified using high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) to determine if adolescent animals displayed a different neurochemical profile than did adult animals after being exposed to subcutaneous low doses of MDMA. Adolescent rats displayed less robust MDMA-induced taste aversions than adults during acquisition and on a final two-bottle aversion test. MDMA at these doses had no consistent effect on monoamine levels in either age group, although levels did vary with age. The relative insensitivity of adolescents to MDMA's aversive effects may engender an increased vulnerability to MDMA abuse in this specific population.}, } @article {pmid23769688, year = {2013}, author = {Lin, JY and Arthurs, J and Reilly, S}, title = {Reduced palatability in pain-induced conditioned taste aversions.}, journal = {Physiology & behavior}, volume = {119}, number = {}, pages = {79-85}, pmid = {23769688}, issn = {1873-507X}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning/drug effects ; *Conditioning, Classical ; Feeding Behavior/*drug effects ; Gallamine Triethiodide/pharmacology ; Male ; Pain/chemically induced/*psychology ; Rats ; Saccharin/pharmacology ; Saline Solution, Hypertonic/pharmacology ; *Taste ; }, abstract = {The current study investigated whether internal pain-inducing agents can modulate palatability of a tastant in the same way as illness-inducing agents (e.g., lithium chloride). Similar to traditional conditioned taste aversion (CTA) experiments, during conditioning the rats were exposed to a saccharin solution followed by intraperitoneal injections of either gallamine (Experiment 1) or hypertonic sodium chloride (NaCl; Experiments 1 and 2). In addition to the total amount consumed, the time of each lick was recorded for lick pattern analysis. The results showed that both gallamine and hypertonic NaCl caused suppression in saccharin intake. Importantly, both lick cluster size and initial lick rate (the measures of taste palatability) were reduced as well. This pattern of results suggests that these pain-inducing agents reduce the hedonic value of the associated tastant and thus CTA is acquired. The current finding serves as evidence supporting the view that CTA is a broadly tuned mechanism that can be triggered by changes in internal body states following consummatory experience.}, } @article {pmid23765264, year = {2014}, author = {Revillo, DA and Castello, S and Paglini, G and Arias, C}, title = {Reacquisition, reinstatement, and renewal of a conditioned taste aversion in preweanling rats.}, journal = {Developmental psychobiology}, volume = {56}, number = {4}, pages = {713-725}, doi = {10.1002/dev.21140}, pmid = {23765264}, issn = {1098-2302}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Pavlovian extinction is defined as a reduction of the conditioned response (CR) as a consequence of repeated and nonreinforced presentations of the conditioned stimulus (CS). This phenomenon has been explained through two nonexclusive associative hypotheses. One of them proposes that the CS-unconditioned stimulus (US) association is weakened during extinction, while the second one explains extinction by the formation of a new inhibitory association between the CS, and the US (CS-noUS) which competes with the excitatory one acquired at conditioning (CS-US). Research supporting this second hypothesis is based on the demonstration that the CR can be recovered after extinction. However, in preweanling rats, renewal, and reinstatement treatments have failed to recover a conditioned fear response, suggesting that extinction during this ontogenetic period may involve erasure of the CS-US association. The goal of the present study was to explore whether this conclusion can be extended to the extinction of a conditioned taste aversion by evaluating infant rats in three different procedures (reacquisition, ABA renewal, and reinstatement). The results are consistent with the idea that extinction of a taste aversive memory during infancy involves relearning about the relationship between the CS and the US, with the initial CS-US association remaining relatively intact. Extinction of a taste aversive memory and a fear memory may involve different biological mechanisms during infancy. The conclusion that the only psychological mechanism for extinction during infancy is unlearning should be confined to a particular type of memory.}, } @article {pmid23762368, year = {2013}, author = {Song, L and Zhu, Q and Liu, T and Yu, M and Xiao, K and Kong, Q and Zhao, R and Li, GD and Zhou, Y}, title = {Ghrelin modulates lateral amygdala neuronal firing and blocks acquisition for conditioned taste aversion.}, journal = {PloS one}, volume = {8}, number = {6}, pages = {e65422}, pmid = {23762368}, issn = {1932-6203}, mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology ; Action Potentials/*drug effects ; Amygdala/*cytology ; Animals ; Cell Count ; Conditioning, Psychological/*drug effects ; Ghrelin/*pharmacology ; Humans ; Immunoglobulin G/administration & dosage/pharmacology ; In Vitro Techniques ; Male ; Memory/drug effects ; Neurons/drug effects/*physiology ; Oligopeptides/pharmacology ; Rats ; Rats, Wistar ; Receptors, Ghrelin/antagonists & inhibitors/metabolism ; Taste/*drug effects ; }, abstract = {Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. An increasing number of studies have reported that ghrelin and its identified receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), produces remarkably wide and complex functions and biological effects on specific populations of neurons in central nervous system. In this study, we sought to explore the in vivo effects of acute ghrelin exposure on lateral amygdala (LA) neurons at the physiological and behavioral levels. In vivo extracellular single-unit recordings showed that ghrelin with the concentration of several nanomolars (nM) stimulated spontaneous firing of the LA neurons, an effect that was dose-dependent and could be blocked by co-application of a GHS-R1a antagonist D-Lys3-GHRP-6. We also found that D-Lys3-GHRP-6 inhibited spontaneous firing of the LA neurons in a dose-dependent manner, revealing that tonic GHS-R1a activity contributes to orchestrate the basal activity of the LA neurons. Behaviorally, we found that microinfusion of ghrelin (12 ng) into LA before training interfered with the acquisition of conditioned taste aversion (CTA) as tested at 24 h after conditioning. Pre-treatment with either purified IgG against GHS-R1a or GHS-R1a antagonist blocked ghrelin's effect on CTA memory acquisition. Ghrelin (12 ng) had no effect on CTA memory consolidation or the expression of acquired CTA memory; neither did it affect the total liquid consumption of tested rats. Altogether, our data indicated that ghrelin locally infused into LA blocks acquisition of CTA and its modulation effects on neuronal firing may be involved in this process.}, } @article {pmid23720615, year = {2013}, author = {Boyer, B and Ernest, S and Rosa, F}, title = {Egr-1 induction provides a genetic response to food aversion in zebrafish.}, journal = {Frontiers in behavioral neuroscience}, volume = {7}, number = {}, pages = {51}, pmid = {23720615}, issn = {1662-5153}, abstract = {As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labeling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labeled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labeling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.}, } @article {pmid23720133, year = {2013}, author = {Houpt, TA and Kwon, B and Houpt, CE and Neth, B and Smith, JC}, title = {Orientation within a high magnetic field determines swimming direction and laterality of c-Fos induction in mice.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {305}, number = {7}, pages = {R793-803}, pmid = {23720133}, issn = {1522-1490}, support = {R01 DC-4607/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Behavior, Animal ; Functional Laterality ; *Magnetic Fields ; Male ; Mice ; Mice, Inbred C57BL ; *Orientation ; Proto-Oncogene Proteins c-fos/*metabolism ; *Swimming ; Time Factors ; Up-Regulation ; Vestibular Nuclei/*metabolism ; Vestibule, Labyrinth/*physiology ; }, abstract = {High-strength static magnetic fields (>7 tesla) perturb the vestibular system causing dizziness, nystagmus, and nausea in humans; and head motion, locomotor circling, conditioned taste aversion, and c-Fos induction in brain stem vestibular nuclei in rodents. To determine the role of head orientation, mice were exposed for 15 min within a 14.1-tesla magnet at six different angles (mice oriented parallel to the field with the head toward B+ at 0°; or pitched rostrally down at 45°, 90°, 90° sideways, 135°, and 180°), followed by a 2-min swimming test. Additional mice were exposed at 0°, 90°, and 180° and processed for c-Fos immunohistochemistry. Magnetic field exposure induced circular swimming that was maximal at 0° and 180° but attenuated at 45° and 135°. Mice exposed at 0° and 45° swam counterclockwise, whereas mice exposed at 135° and 180° swam clockwise. Mice exposed at 90° (with their rostral-caudal axis perpendicular to the magnetic field) did not swim differently than controls. In parallel, exposure at 0° and 180° induced c-Fos in vestibular nuclei with left-right asymmetries that were reversed at 0° vs. 180°. No significant c-Fos was induced after 90° exposure. Thus, the optimal orientation for magnetic field effects is the rostral-caudal axis parallel to the field, such that the horizontal canal and utricle are also parallel to the field. These results have mechanistic implications for modeling magnetic field interactions with the vestibular apparatus of the inner ear (e.g., the model of Roberts et al. of an induced Lorenz force causing horizontal canal cupula deflection).}, } @article {pmid23719976, year = {2013}, author = {Seyfried, F and Miras, AD and Bueter, M and Prechtl, CG and Spector, AC and le Roux, CW}, title = {Effects of preoperative exposure to a high-fat versus a low-fat diet on ingestive behavior after gastric bypass surgery in rats.}, journal = {Surgical endoscopy}, volume = {27}, number = {11}, pages = {4192-4201}, pmid = {23719976}, issn = {1432-2218}, support = {G0902002/MRC_/Medical Research Council/United Kingdom ; R21 DC012751/DC/NIDCD NIH HHS/United States ; R21-DC012751/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Body Weight/physiology ; Diet ; *Diet, Fat-Restricted ; Diet, High-Fat ; Dietary Fats/metabolism ; Disease Models, Animal ; Energy Intake/physiology ; *Feeding Behavior/physiology ; *Food Preferences/physiology ; *Gastric Bypass ; Humans ; Male ; Obesity/prevention & control/*surgery ; Postoperative Care/*methods ; Random Allocation ; Rats ; Rats, Wistar ; Weight Loss ; }, abstract = {BACKGROUND: The consumption of high fat and sugar diets is decreased after gastric bypass surgery (GB). The mechanisms remain unclear, with tests of motivated behavior toward fat and sugar producing conflicting results in a rat model. These discrepancies may be due to differences in presurgical maintenance diets. The authors used their GB rat model to determine whether the fat content of preoperative maintenance diets affects weight loss, calorie intake, and macronutrient selection after surgery.

METHODS: Male Wistar rats were either low-fat diet fed (LFDF) with normal chow or high-fat diet fed (HFDF) before randomization to GB or sham surgery. In food preference test 1, the animals were offered the choice of a vegetable drink (V8) or a high-calorie liquid (Ensure), and in food preference test 2, they could choose normal chow or a solid high-fat diet.

RESULTS: The GB groups did not differ significantly in terms of body weight loss or caloric intake. In food preference test 1, both groups responded similarly by reducing their preference for Ensure and increasing their preference for V8. In food preference test 2, the HFDF-GB rats reduced their preference for a solid high-fat diet gradually compared with the immediate reduction observed in the LFDF-GB rats.

CONCLUSION: The consumption of presurgical maintenance diets with different fat contents did not affect postoperative weight loss outcomes. Both the LFDF-GB and HFDF-GB rats exhibited behaviors consistent with the possible expression of a conditioned taste aversion to a high-fat stimulus. These results suggest that for some physiologic parameters, low-fat-induced obesity models can be used for the study of changes after GB and have relevance to many obese humans who consume high-calorie but low-fat diets.}, } @article {pmid23710281, year = {2013}, author = {Hatakeyama, D and Okuta, A and Otsuka, E and Lukowiak, K and Ito, E}, title = {Consolidation of long-term memory by insulin in Lymnaea is not brought about by changing the number of insulin receptors.}, journal = {Communicative & integrative biology}, volume = {6}, number = {3}, pages = {e23955}, pmid = {23710281}, issn = {1942-0889}, abstract = {The pond snail Lymnaea stagnalis learns taste aversion and consolidates it into long-term memory (LTM). This is referred to as conditioned taste aversion (CTA). The superfusion of molluscan insulin-related peptides (MIPs) over the isolated snail brain causes a long-term enhancement of synaptic input between the cerebral giant cell and the B1 buccal motor neuron. This enhancement is hypothesized to underlie CTA. The synaptic enhancement caused by the superfusion of MIPs can be blocked by the application of human insulin receptor antibody, which recognizes the extracellular domain of human insulin receptor and acts as an antagonist even for MIP receptors. An injection of the human insulin receptor antibody into the abdominal cavity of trained snails blocks the consolidation process leading to LTM, even though the snails acquire taste aversion. Here, we examined whether or not taste-aversion training changes the mRNA expression level of MIP receptor in the snail brain and found that it does not. This result, taken together with previous findings, suggest that the MIPs' effect on synaptic function in the snail brain is attributable to a change in the MIP concentration, and not to a change in the mRNA expression level of MIP receptor, which is thought to reflect the number of MIP receptors.}, } @article {pmid23658873, year = {2013}, author = {Kozyrev, SA and Nikitin, VP}, title = {Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.}, journal = {Bulletin of experimental biology and medicine}, volume = {154}, number = {5}, pages = {584-587}, doi = {10.1007/s10517-013-2004-9}, pmid = {23658873}, issn = {1573-8221}, mesh = {Animals ; Avoidance Learning ; *Conditioning, Classical ; Cycloheximide/pharmacology ; Dactinomycin/pharmacology ; Dichlororibofuranosylbenzimidazole/pharmacology ; Enzyme Inhibitors/pharmacology ; Helix, Snails/drug effects/*genetics/*physiology ; Memory, Long-Term/drug effects/*physiology ; *Protein Biosynthesis ; Protein Synthesis Inhibitors/pharmacology ; RNA, Messenger/genetics/metabolism ; RNA, Messenger, Stored/genetics/metabolism ; Taste ; *Transcription, Genetic ; }, abstract = {We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.}, } @article {pmid23627795, year = {2013}, author = {Li, KC and Hsiao, S and Li, JS}, title = {Conditioned taste aversion as instrumental punishment.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {39}, number = {3}, pages = {294-297}, doi = {10.1037/a0031822}, pmid = {23627795}, issn = {1939-2184}, mesh = {Animals ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Conditioning, Operant/*physiology ; Lithium Chloride/administration & dosage ; Male ; Neuropsychological Tests ; Punishment/*psychology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/administration & dosage ; Sucrose/administration & dosage ; Taste/*physiology ; Time Factors ; }, abstract = {Conditioned taste aversion (CTA) is traditionally viewed as an instance of pavlovian conditioning. This interpretation rests on the lack of an instrumental contingency between the tastant and the gastric malaise in a standard procedure of CTA. To investigate a role for instrumental punishment in CTA, we present 2 tastants sequentially ("sucrose then NaCl" or "NaCl then sucrose") in a daily alternating and counterbalanced order to rats with an explicit positive contingency between the dosage of the lithium chloride (LiCl) administered and the amount of 1 tastant drunk on that trial. In the beginning of experiment, rats suppressed their intake of both tastants. With the increase of conditioning trials, rats gradually learned to resume the intake of noncontingent solution while selectively suppressing the intake of LiCl-contingent solution. This selective suppression in CTA is the first report indicating that rats are sensitive to the subtle cues related to the covariations between the magnitude of stimulus and the magnitude of responses in a punishment paradigm involving a long delay between the gustatory stimulus of tastant ingestion and the aversive effect of LiCl injection.}, } @article {pmid23604334, year = {2014}, author = {Anderson, RI and Morales, M and Spear, LP and Varlinskaya, EI}, title = {Pharmacological activation of kappa opioid receptors: aversive effects in adolescent and adult male rats.}, journal = {Psychopharmacology}, volume = {231}, number = {8}, pages = {1687-1693}, pmid = {23604334}, issn = {1432-2072}, support = {P50 AA017823/AA/NIAAA NIH HHS/United States ; R01 AA012453/AA/NIAAA NIH HHS/United States ; AA012453/AA/NIAAA NIH HHS/United States ; AA017823/AA/NIAAA NIH HHS/United States ; }, mesh = {Aging ; Animals ; Avoidance Learning/*drug effects/*physiology ; Conditioning, Psychological/*drug effects/*physiology ; Dose-Response Relationship, Drug ; Male ; Narcotics/pharmacology ; Pyrrolidines/*pharmacology ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa/*agonists/metabolism ; Saccharin/administration & dosage ; Space Perception/drug effects/physiology ; Taste Perception/drug effects/physiology ; }, abstract = {RATIONALE: The dynorphin (DYN)/kappa opioid receptor (KOR) system is involved in the dysphoric properties of drugs of abuse. Given that adolescents show reduced sensitivity to aversive effects of many drugs, alterations in the DYN/KOR system may contribute to the prevalence of drug use during adolescence.

OBJECTIVES: The present study was designed to assess dysphoric properties of a selective kappa agonist, U62,066, in adolescent and adult rats using both conditioned taste aversion (CTA) and conditioned place aversion (CPA) paradigms.

METHODS: For CTA, water-restricted rats were administered U62,066 following 30 min access to a saccharin solution, with subsequent saccharin consumption used to index aversion. For CPA, animals were allowed access to both compartments of a two-compartment chamber for a 15-min pre- and post-conditioning test. For conditioning, subjects were administered U62,066 prior to confinement to one side of the chamber and saline prior to confinement to the other side for a total of four pairings.

RESULTS: Overall, adolescents displayed reduced sensitivity to the kappa agonist relative to adults. Adults demonstrated taste aversions to the 0.2 and 0.3 mg/kg doses of U62,066, whereas adolescents did not display aversions to any tested doses. Adults demonstrated a place aversion to the 0.1 and 0.2 mg/kg dose of U62,066 when paired with the preferred side of the conditioning chamber. Adolescents did not display aversions to any of the doses tested.

CONCLUSIONS: Reduced sensitivity to DYN/KOR system activation during adolescence may be a contributing factor to the age-typical insensitivity to aversive properties of drugs commonly abused by adolescents.}, } @article {pmid23575838, year = {2013}, author = {Morris, MJ and Mahgoub, M and Na, ES and Pranav, H and Monteggia, LM}, title = {Loss of histone deacetylase 2 improves working memory and accelerates extinction learning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {33}, number = {15}, pages = {6401-6411}, pmid = {23575838}, issn = {1529-2401}, support = {R01 MH081060/MH/NIMH NIH HHS/United States ; MH081060/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Brain/metabolism/physiology ; Conditioning, Psychological/*physiology ; Dendritic Spines/genetics ; Extinction, Psychological/*physiology ; Hippocampus/physiology ; Histone Deacetylase 1/genetics/metabolism/*physiology ; Histone Deacetylase 2/genetics/metabolism/*physiology ; Memory, Short-Term/*physiology ; Mice ; Mice, Knockout ; Motor Activity/physiology ; Neuronal Plasticity/genetics/physiology ; Neurons/physiology ; Rotarod Performance Test/methods ; }, abstract = {Histone acetylation and deacetylation can be dynamically regulated in response to environmental stimuli and play important roles in learning and memory. Pharmacological inhibition of histone deacetylases (HDACs) improves performance in learning tasks; however, many of these classical agents are "pan-HDAC" inhibitors, and their use makes it difficult to determine the roles of specific HDACs in cognitive function. We took a genetic approach using mice lacking the class I HDACs, HDAC1 or HDAC2, in postmitotic forebrain neurons to investigate the specificity or functional redundancy of these HDACs in learning and synaptic plasticity. We show that selective knock-out of Hdac2 led to a robust acceleration of the extinction rate of conditioned fear responses and a conditioned taste aversion as well as enhanced performance in an attentional set-shifting task. Hdac2 knock-out had no impact on episodic memory or motor learning, suggesting that the effects are task-dependent, with the predominant impact of HDAC2 inhibition being an enhancement in an animal's ability to rapidly adapt its behavioral strategy as a result of changes in associative contingencies. Our results demonstrate that the loss of HDAC2 improves associative learning, with no effect in nonassociative learning tasks, suggesting a specific role for HDAC2 in particular types of learning. HDAC2 may be an intriguing target for cognitive and psychiatric disorders that are characterized by an inability to inhibit behavioral responsiveness to maladaptive or no longer relevant associations.}, } @article {pmid23539343, year = {2013}, author = {Suzuki, E and Eda-Fujiwara, H and Satoh, R and Saito, R and Miyamoto, T}, title = {The effect of androgen on the retention of extinction memory after conditioned taste aversion in mice.}, journal = {The journal of physiological sciences : JPS}, volume = {63}, number = {3}, pages = {171-181}, pmid = {23539343}, issn = {1880-6562}, mesh = {Animals ; Avoidance Learning/*drug effects ; Castration ; Conditioning, Classical/*drug effects ; Dihydrotestosterone/pharmacology ; Extinction, Psychological/*drug effects ; Female ; Male ; Memory/drug effects ; Mice ; Taste/drug effects ; Testosterone/blood/*pharmacology ; Water Deprivation ; }, abstract = {Conditioned taste aversion (CTA) induced by the application of a novel taste such as sodium saccharin (Sac) as the conditioned stimulus (CS) and a malaise-inducing agent as the unconditioned stimulus (US), results in acquisition of CTA memory to Sac. In contrast, CTA is extinguished by repeated presentations of the CS without the US, resulting in acquisition of the extinction memory. We examined the effects of androgenic hormones on acquisition and retention of extinction memory in mice. We gonadectomized sexually immature mice and continuously administered androgens to these animals. After sexual maturation, the mice underwent a conditioning period followed by an extinction period. Retrieval tests revealed that the androgen-treated group showed significantly greater retention of extinction memory than the non-treated group 5 weeks later, whereas such significant difference was not observed in acquisition of extinction memory. These results demonstrate the enhancing effect of androgens on retention of extinction memory.}, } @article {pmid23532964, year = {2014}, author = {Mickley, GA and Hoxha, Z and DiSorbo, A and Wilson, GN and Remus, JL and Biesan, O and Ketchesin, KD and Ramos, L and Luchsinger, JR and Prodan, S and Rogers, M and Wiles, NR and Hoxha, N}, title = {Latent inhibition of a conditioned taste aversion in fetal rats.}, journal = {Developmental psychobiology}, volume = {56}, number = {3}, pages = {435-447}, doi = {10.1002/dev.21110}, pmid = {23532964}, issn = {1098-2302}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Classical/*drug effects/physiology ; Disulfides ; Excitatory Amino Acid Antagonists/*pharmacology ; Female ; *Inhibition, Psychological ; Ketamine/*pharmacology ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Sulfinic Acids/*pharmacology ; }, abstract = {The etiology of schizophrenia's cognitive symptoms may have its basis in prenatal alterations of glutamate N-methyl-D-aspartate (NMDA) receptor functioning. Therefore, the current study investigated the effects of ketamine (an NMDA receptor blocking drug) on both a conditioned taste aversion (CTA) and latent inhibition (LI; a model of attentional capacity) in rat fetuses. We first sought to determine if a CTA could be diminished by nonreinforced preexposure to a CS in fetal rats (i.e., LI). We injected E18 pregnant Sprague-Dawley rats with 100% allicin (garlic taste) or an equal volume of saline. Some of the pregnant dams also received ketamine (100 mg/kg, i.p.). One day later (E19), the dams received a second injection of the CS, followed by either lithium chloride (the US) or saline. Finally, on E21 pups received oral lavage with allicin and observations of ingestive orofacial motor responses were recorded. When allicin had been paired with LiCl in utero, E21 fetuses exhibited a conditioned suppression of orofacial movements, indicative of an aversion to this taste. Preexposure to the garlic taste on E18 produced a LI of this CTA. Ketamine significantly disrupted the formation of the CTA and had some impact on LI. However, the direct effect of ketamine on LI is less certain since the drug also blocked the original CTA.}, } @article {pmid23498685, year = {2013}, author = {Rudnitskaya, A and Kirsanov, D and Blinova, Y and Legin, E and Seleznev, B and Clapham, D and Ives, RS and Saunders, KA and Legin, A}, title = {Assessment of bitter taste of pharmaceuticals with multisensor system employing 3 way PLS regression.}, journal = {Analytica chimica acta}, volume = {770}, number = {}, pages = {45-52}, doi = {10.1016/j.aca.2013.02.006}, pmid = {23498685}, issn = {1873-4324}, mesh = {Adult ; Animals ; Biosensing Techniques/*methods/trends ; Caffeine/chemistry/pharmacology ; Electronics ; Female ; Humans ; Hydrogen-Ion Concentration ; Male ; Middle Aged ; Models, Biological ; *Pharmaceutical Preparations/chemistry ; Phthalazines/chemistry/pharmacology ; Potentiometry ; Rats ; *Taste ; }, abstract = {The application of the potentiometric multisensor system (electronic tongue, ET) for quantification of the bitter taste of structurally diverse active pharmaceutical ingredients (API) is reported. The measurements were performed using a set of bitter substances that had been assessed by a professional human sensory panel and the in vivo rat brief access taste aversion (BATA) model to produce bitterness intensity scores for each substance at different concentrations. The set consisted of eight substances, both inorganic and organic - azelastine, caffeine, chlorhexidine, potassium nitrate, naratriptan, paracetamol, quinine, and sumatriptan. With the aim of enhancing the response of the sensors to the studied APIs, measurements were carried out at different pH levels ranging from 2 to 10, thus promoting ionization of the compounds. This experiment yielded a 3 way data array (samples×sensors×pH levels) from which 3wayPLS regression models were constructed with both human panel and rat model reference data. These models revealed that artificial assessment of bitter taste with ET in the chosen set of API's is possible with average relative errors of 16% in terms of human panel bitterness score and 25% in terms of inhibition values from in vivo rat model data. Furthermore, these 3wayPLS models were applied for prediction of the bitterness in blind test samples of a further set of API's. The results of the prediction were compared with the inhibition values obtained from the in vivo rat model.}, } @article {pmid23486966, year = {2013}, author = {Hashikawa, K and Naka, M and Nakayama, D and Matsumoto, N and Neve, R and Matsuki, N}, title = {Blockade of stimulus convergence in amygdala neurons disrupts taste associative learning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {33}, number = {11}, pages = {4958-4963}, pmid = {23486966}, issn = {1529-2401}, mesh = {Amygdala/*cytology ; Analysis of Variance ; Animals ; Association Learning/drug effects/*physiology ; CREB-Binding Protein/genetics/metabolism ; Conditioning, Classical/physiology ; Cytoskeletal Proteins/genetics/metabolism ; Genetic Vectors/physiology ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; In Vitro Techniques ; Male ; Membrane Potentials/drug effects/genetics ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/drug effects/*physiology ; Neuropeptides/pharmacology ; Patch-Clamp Techniques ; Receptors, Neuropeptide/genetics/metabolism ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {Humans and non-human animals learn associations of temporally contingent stimuli to better cope with the changing environment. In animal models of classical conditioning, a neutral conditioned stimulus (CS) predicts an aversive unconditioned stimulus (US). Several lines of indirect evidence indicate that this learning may rely on stimulus convergence in a subset of neurons, but this hypothesis has not been directly tested. In the current study, we tested this hypothesis using a pharmacogenetic approach, the cAMP response element-binding protein (CREB)/Allatostatin Receptor system, to target a subset of amygdala neurons receiving convergent stimuli in mice during conditioned taste aversion. Virally infected basolateral amygdala neurons with higher CREB levels were predominantly active during CS presentation. Blocking stimulus convergence in infected neurons by silencing them during US disrupted taste associative memory. Moreover, silencing infected neurons only during CS also disrupted associative memory formation. These results provide support for the notion that convergent inputs of CS and US in a subpopulation of neurons are critical for associative memory formation.}, } @article {pmid23474371, year = {2013}, author = {Mickley, GA and Hoxha, N and Luchsinger, JL and Rogers, MM and Wiles, NR}, title = {Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {106}, number = {}, pages = {16-26}, pmid = {23474371}, issn = {1873-5177}, support = {R15 MH063720/MH/NIMH NIH HHS/United States ; 2-R15-MH063720-03/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Butyrates/administration & dosage/*pharmacology ; *Diet ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Elevation of brain magnesium enhances synaptic plasticity and extinction of conditioned fear memories. This experiment examined the generalizability of this phenomenon by studying the effects of a novel magnesium compound, magnesium-L-threonate (MgT), on conditioned taste aversion (CTA) extinction and spontaneous recovery (SR). Adult male Sprague-Dawley rats were maintained on a 23-hour water deprivation cycle and acquired a CTA following the taste of a CS [0.3% saccharin+16 mg/ml MgT (SAC+MgT)] paired with a US [81 mg/kg (i.p.) lithium chloride (LiCl)]. Following CTA acquisition, rats drank a water+MgT solution for up to 1 hour/day over the next 31 days. For 14 additional days, some animals continued water+MgT treatment, but others drank water only to allow MgT to be eliminated from the body. We then employed 2 different extinction paradigms: (1) CS-Only (CSO), in which SAC was presented, every-other day, or (2) Explicitly Unpaired (EU), in which both SAC and LiCl were presented, but on alternate days. EU extinction procedures have been shown to speed CTA extinction and reduce spontaneous recovery of the aversion. Throughout extinction, half of the rats in each group continued to drink MgT (now in SAC or supplemental water+MgT solution), whereas the other half drank SAC only/water only until SAC drinking reached ≥90% of baseline (asymptotic extinction). Rats receiving MgT just before/during extinction drank less SAC on the first day of extinction suggesting that they had retained a stronger CTA. MgT enhanced the rate of extinction. Furthermore, the MgT-treated rats showed a relatively modest SR of the CTA 30 days later - indicating that the extinction procedure was more effective for these animals. Our data suggest that long-term dietary MgT may enhance the consolidation/retention of a CTA, speed extinction, and inhibit SR of this learned aversion.}, } @article {pmid23398436, year = {2013}, author = {Stricker, EM and Grigson, PS and Norgren, R}, title = {Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration.}, journal = {Behavioral neuroscience}, volume = {127}, number = {2}, pages = {275-284}, pmid = {23398436}, issn = {1939-0084}, support = {R01 DA012473/DA/NIDA NIH HHS/United States ; R01 DC005435/DC/NIDCD NIH HHS/United States ; DC005435/DC/NIDCD NIH HHS/United States ; DA012473/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Appetite/*drug effects/physiology ; Avoidance Learning/*drug effects/physiology ; Diuretics/pharmacology ; Furosemide/pharmacology ; Ibotenic Acid/toxicity ; Male ; Neurons/drug effects/physiology ; Pons/*drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/*administration & dosage ; Taste/*drug effects/physiology ; }, abstract = {Previous studies have demonstrated that bilateral lesions of the gustatory (medial) zone of the parabrachial nucleus (PBN) in the pons eliminate the salt (sodium chloride; NaCl) appetite induced in rats by treatment with the diuretic drug, furosemide. The present studies reexamined NaCl intake of rats with PBN lesions induced by ibotenic acid, using multiple models of salt appetite. The impairment of a conditioned taste aversion, an established consequence of PBN damage, was used as an initial screen with which to assess the effectiveness of the lesions. Rats with PBN lesions did not drink either 0.3 of a molar (M) solution of NaCl or 0.5 M NaCl in response to daily treatment with desoxycorticosterone acetate. These findings suggest that the excitatory stimulus of salt appetite mediated by mineralocorticoids is abolished by PBN lesions. In contrast, rats with PBN lesions drank some 0.5 M NaCl and more 0.3 M NaCl, in addition to water, in response to hypovolemia induced by subcutaneous injection of 30% polyethylene glycol solution. Those findings suggest that an excitatory stimulus of salt appetite, presumably mediated by Angiotensin II, is not abolished by PBN lesions. These and other observations indicate that lesions of the gustatory PBN in rats may or may not eliminate salt appetite, depending on which model is used and which concentration of NaCl solution is available.}, } @article {pmid23393274, year = {2013}, author = {Murakami, J and Okada, R and Fujito, Y and Sakakibara, M and Lukowiak, K and Ito, E}, title = {Paired pulse ratio analysis of insulin-induced synaptic plasticity in the snail brain.}, journal = {The Journal of experimental biology}, volume = {216}, number = {Pt 10}, pages = {1771-1773}, doi = {10.1242/jeb.083469}, pmid = {23393274}, issn = {1477-9145}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Brain/drug effects/*physiology ; Excitatory Postsynaptic Potentials/physiology ; Insulin/*pharmacology ; Lymnaea/drug effects/*physiology ; Motor Neurons/drug effects/physiology ; Neuronal Plasticity/*drug effects ; Synapses/drug effects/*physiology ; }, abstract = {Insulin's action in the brain can directly alter cognitive functioning. We have recently shown that molluscan insulin-related peptides are upregulated following a conditioned taste aversion (CTA) training procedure. In addition, when mammalian insulin is superfused over the isolated Lymnaea stagnalis central nervous system, it elicits long-term synaptic enhancement at the monosynaptic connection between the cerebral giant cell and the buccal 1 (B1) motor neuron. This synaptic enhancement is thought to be a neural correlate of CTA. Here, we examined whether the observed changes in synaptic plasticity were the result of presynaptic and/or postsynaptic alterations using the paired pulse procedure. The paired pulse ratio was unaltered following insulin application, suggesting that insulin's effects on synaptic plasticity are mediated postsynaptically in the B1 motor neuron. Thus, it was suggested that postsynaptic changes need to be considered when insulin's actions on synaptic plasticity are examined.}, } @article {pmid23391573, year = {2013}, author = {Kim, HJ and Zhang, XH and Park, EY and Shin, KH and Choi, SH and Chun, BG and Kim, DH}, title = {Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice.}, journal = {Physiology & behavior}, volume = {110-111}, number = {}, pages = {213-220}, doi = {10.1016/j.physbeh.2013.01.011}, pmid = {23391573}, issn = {1873-507X}, mesh = {Animals ; Avoidance Learning/drug effects ; Body Weight/drug effects ; Circadian Rhythm/drug effects ; Dietary Fats/pharmacology ; Eating/*drug effects ; Energy Intake/drug effects ; Energy Metabolism/drug effects ; Genes, fos/*drug effects ; Hypoglycemic Agents/*pharmacology ; Immunohistochemistry ; Male ; Metformin/*pharmacology ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Obesity/metabolism/*psychology ; Rhombencephalon/drug effects/metabolism ; Solitary Nucleus/*drug effects/metabolism ; Taste/drug effects ; }, abstract = {Metformin is widely used to treat obese diabetics because of its beneficial effects on body weight, energy intake, and glucose regulation. However, it has not been investigated how oral metformin affects meal patterns, or whether the reduced food intake is associated with neuronal activation in the hindbrain. Accordingly, we investigated how orally administered metformin (150 or 300 mg/kg daily for 4 or 7 days) reduces body weight in obese mice on a high-fat diet by continuously measuring meal patterns, energy expenditure, and locomotor activity, and whether oral metformin (300 mg/kg daily for 3 days) increases c-Fos expression in the nucleus tractus solitarius (NTS) and area postrema. Furthermore, we determined whether oral metformin produces a conditioned taste aversion (CTA) in obese mice administered a single dose of metformin (75, 150, or 300 mg/kg, p.o.). Metformin (300 mg/kg daily for 7 days) reduced body weight and adiposity by decreasing nocturnal energy intake but did not significantly change energy expenditure or locomotor activity relative to vehicle, and it transiently decreased nocturnal meal size and reduced meal number throughout the experiments. Furthermore, metformin significantly increased c-Fos immunoreactivity within the NTS of obese mice compared to that in controls and pair-fed group, and induced a CTA at doses of 150 or 300 mg/kg. These results indicate that metformin-induced weight loss is associated with a sustained reduction in energy intake maintained by a reduction in meal size and number, and that oral administration of metformin causes visceral illness and neuronal activation in the NTS.}, } @article {pmid23385661, year = {2013}, author = {Slouzkey, I and Rosenblum, K and Maroun, M}, title = {Memory of conditioned taste aversion is erased by inhibition of PI3K in the insular cortex.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {38}, number = {7}, pages = {1143-1153}, pmid = {23385661}, issn = {1740-634X}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/metabolism/*physiology ; Chromones/administration & dosage/pharmacology ; Conditioning, Classical/drug effects/*physiology ; Enzyme Inhibitors/pharmacology ; Extinction, Psychological/physiology ; Male ; Memory/drug effects/*physiology ; Microinjections ; Morpholines/administration & dosage/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; *Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; }, abstract = {The conditioned taste aversion (CTA) paradigm, in which association between a novel taste and visceral malaise is formed, gives a unique experimental setting to examine the mechanisms underlying memory acquisition and extinction processes. AKT is a main kinase of the phosphoinositide 3-kinase cascade (PI3K) and has been implicated in long-term memory. We have recently reported that blockade of PI3K in the basolateral amygdala (BLA) before retrieval of fear memory was associated with long-term reduction in fear responses, suggesting a possible role of PI3K inhibition in fear erasure. In this study, we aimed to elucidate whether PI3K has a similar role in the insular cortex (IC), which has a crucial role in CTA acquisition, consolidation, maintenance, and extinction. To that end, we (1) monitored AKT phosphorylation in the IC following CTA acquisition and extinction and (2) inhibited PI3K by local microinjection of the PI3K inhibitor LY294002 at different stages of CTA acquisition and extinction. Our results show that while AKT phosphorylation is increased following CTA learning, it is decreased following CTA extinction. Inhibition of AKT phosphorylation in the IC before or after the first CTA retrieval test resulted in reduction in the aversion index. This reduction in aversion is due to the erasure of the original CTA trace memory, as re-application of the unconditioned stimulus (lithium chloride) did not induce the recovery of aversion in LY294002-treated animals. Our present data add new evidence to suggest that PI3K is engaged in consolidation of aversive memories, as its inhibition is associated with erasure of CTA memory.}, } @article {pmid23339178, year = {2013}, author = {Kusuhara, Y and Yoshida, R and Ohkuri, T and Yasumatsu, K and Voigt, A and Hübner, S and Maeda, K and Boehm, U and Meyerhof, W and Ninomiya, Y}, title = {Taste responses in mice lacking taste receptor subunit T1R1.}, journal = {The Journal of physiology}, volume = {591}, number = {7}, pages = {1967-1985}, pmid = {23339178}, issn = {1469-7793}, mesh = {Animals ; Behavior, Animal ; Chorda Tympani Nerve/physiology ; Female ; Glossopharyngeal Nerve/physiology ; Glutamic Acid/pharmacology ; Male ; Mice ; Mice, Transgenic ; Protein Subunits/physiology ; Receptors, G-Protein-Coupled/*physiology ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/*physiology ; Taste/*physiology ; Taste Buds/physiology ; }, abstract = {The T1R1 receptor subunit acts as an umami taste receptor in combination with its partner, T1R3. In addition, metabotropic glutamate receptors (brain and taste variants of mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate the function of T1R1 and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock-out (T1R1(-/-)) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1-expressing cells. Gustatory nerve recordings demonstrated that T1R1(-/-) mice exhibited a serious deficit in inosine monophosphate-elicited synergy but substantial residual responses to glutamate alone in both chorda tympani and glossopharyngeal nerves. Interestingly, chorda tympani nerve responses to sweeteners were smaller in T1R1(-/-) mice. Taste cell recordings demonstrated that many mCherry-expressing taste cells in T1R1(+/-) mice responded to sweet and umami compounds, whereas those in T1R1(-/-) mice responded to sweet stimuli. The proportion of sweet-responsive cells was smaller in T1R1(-/-) than in T1R1(+/-) mice. Single-cell RT-PCR demonstrated that some single mCherry-expressing cells expressed all three T1R subunits. Chorda tympani and glossopharyngeal nerve responses to glutamate were significantly inhibited by addition of mGluR antagonists in both T1R1(-/-) and T1R1(+/-) mice. Conditioned taste aversion tests demonstrated that both T1R1(-/-) and T1R1(+/-) mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1-expressing cells mainly contribute to umami taste synergism and partly to sweet sensitivity and that mGluRs are involved in the detection of umami compounds.}, } @article {pmid23318254, year = {2013}, author = {Grasby, K and Talk, A}, title = {The anterior claustrum and spatial reversal learning in rats.}, journal = {Brain research}, volume = {1499}, number = {}, pages = {43-52}, doi = {10.1016/j.brainres.2013.01.014}, pmid = {23318254}, issn = {1872-6240}, mesh = {Animals ; Basal Ganglia/*physiology ; Conditioning, Operant ; Male ; Maze Learning/*physiology ; Memory/*physiology ; Rats ; Rats, Wistar ; Reversal Learning/*physiology ; }, abstract = {The claustrum is a small structure of poorly understood function situated subcortically in the basal forebrain. The fact that it is extensively and reciprocally connected with the cerebral cortex has led to suggestions that it is involved in coordination of cortical activity. In this study, we created excitotoxic lesions to the anterior claustrum of rats and tested performance on three tasks that involve neural processing in one or more frontal and limbic cortical structures. We tested reversal learning and spatial working memory in a water maze and tested latent inhibition using conditioned taste aversion. Lesioned rats were not impaired at acquiring the initial location of the platform in a water maze, but were impaired at acquiring a switched location in the reversal phase. The lesioned rats also exhibited an increased rate of perseverance errors compared to control rats during reversal. Lesioned rats were not impaired in the working memory task or latent inhibition. These results indicate that cell loss in the claustrum may lead to deficits in behavioral flexibility, and are consistent with theories of claustral function that suggest it may help coordinate information necessary for at least some cortical-dependent tasks.}, } @article {pmid23293775, year = {2012}, author = {Veysi, A and Vatandoost, H and Yaghoobi-Ershadi, M and Arandian, M and Jafari, R and Hosseini, M and Abdoli, H and Rassi, Y and Heidari, K and Sadjadi, A and Fadaei, R and Ramazanpour, J and Aminian, K and Shirzadi, M and Akhavan, A}, title = {Comparative study on the effectiveness of coumavec® and zinc phosphide in controlling zoonotic cutaneous leishmaniasis in a hyperendemic focus in central iran.}, journal = {Journal of arthropod-borne diseases}, volume = {6}, number = {1}, pages = {18-27}, pmid = {23293775}, issn = {2322-1984}, abstract = {BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is an increasing health problems in many rural areas of Iran. The aim of this study was to introduce a new alternative rodenticide to control the reservoirs of ZCL, its effect on the vector density and the incidence of the disease in hyperendemic focus of Esfahan County, central Iran.

METHODS: The study was carried out from January 2011 to January 2012. In intervention areas, rodent control operation was conducted using zinc phosphide or Coumavec®. Active case findings were done by house-to-house visits once every season during 2011-2012. To evaluate the effect of rodent control operation on the vector density, sand flies were collected twice a month using sticky traps.

RESULTS: The reduction rate of rodent holes in intervention areas with Coumavec® and zinc phosphide were 48.46% and 58.15% respectively, whereas in control area results showed 6.66 folds intensification. The Incidence of ZCL significantly reduced in the treated areas. Totally, 3200 adult sand flies were collected and identified in the intervention and control areas. In the treated area with zinc phosphide, the density of Phlebotomus papatasi was higher in outdoors in contrast with the treated area by Coumavec® which the density of the sand fly was higher in indoors.

CONCLUSION: Both rodenticides were effective on the incidence of ZCL and the population of the reservoirs as well. Coumavec® seems to be effective on the outdoor density of the vector. This combination of rodenticide-insecticide could be a suitable alternative for zinc phosphide while bait shyness or behavioral resistance is occurred.}, } @article {pmid23287538, year = {2013}, author = {Alaux-Cantin, S and Warnault, V and Legastelois, R and Botia, B and Pierrefiche, O and Vilpoux, C and Naassila, M}, title = {Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens.}, journal = {Neuropharmacology}, volume = {67}, number = {}, pages = {521-531}, doi = {10.1016/j.neuropharm.2012.12.007}, pmid = {23287538}, issn = {1873-7064}, mesh = {Adaptation, Physiological/drug effects/*physiology ; Age Factors ; Alcohol Drinking/metabolism/psychology ; Alcoholic Intoxication/*metabolism/psychology ; Animals ; Choice Behavior/drug effects/*physiology ; Conditioning, Operant/drug effects/physiology ; Ethanol/*administration & dosage ; Male ; Motivation/*physiology ; Nucleus Accumbens/drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism. However, mechanisms underlying this susceptibility remain unknown. We evaluated the effect of adolescent binge-like ethanol intoxication on vulnerability to alcohol abuse in Sprague-Dawley rats. To model binge-like ethanol intoxication, every 2 days, rats received an ethanol injection (3.0 g/kg) for 2 consecutive days across 14 days either from postnatal day 30 (PND30) to 43 (early adolescence) or from PND 45 to PND 58 (late adolescence). In young adult animals, we measured free ethanol consumption in the two-bottle choice paradigm, motivation for ethanol in the operant self-administration task and both ethanol's rewarding and aversive properties in the conditioned place preference (CPP) and taste aversion (CTA) paradigms. While intermittent ethanol intoxications (IEI) during late adolescence had no effect on free-choice 10% ethanol consumption, we found that IEI during early adolescence promoted free-choice 10% ethanol consumption, enhanced motivation for ethanol in the self-administration paradigm and induced a loss of both ethanol-induced CPP and CTA in young adults. No modification in either sucrose self-administration or amphetamine-induced CPP was observed. As the nucleus accumbens (Nac) is particularly involved in addictive behavior, we analyzed IEI-induced long-term neuroadaptations in the Nac using c-Fos immunohistochemistry and an array of neurotransmission-related genes. This vulnerability to ethanol abuse was associated with a lower c-Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission-related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism.}, } @article {pmid23283349, year = {2013}, author = {Murakami, J and Okada, R and Sadamoto, H and Kobayashi, S and Mita, K and Sakamoto, Y and Yamagishi, M and Hatakeyama, D and Otsuka, E and Okuta, A and Sunada, H and Takigami, S and Sakakibara, M and Fujito, Y and Awaji, M and Moriyama, S and Lukowiak, K and Ito, E}, title = {Involvement of insulin-like peptide in long-term synaptic plasticity and long-term memory of the pond snail Lymnaea stagnalis.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {33}, number = {1}, pages = {371-383}, pmid = {23283349}, issn = {1529-2401}, support = {MOP 64339//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Conditioning, Classical/drug effects/physiology ; Insulin/pharmacology ; Lymnaea/drug effects/*physiology ; Memory, Long-Term/drug effects/*physiology ; Neuronal Plasticity/drug effects/*physiology ; Neurons/drug effects/physiology ; Neuropeptides/genetics/*metabolism ; Synapses/drug effects/*metabolism ; Taste/drug effects/physiology ; }, abstract = {The pond snail Lymnaea stagnalis is capable of learning taste aversion and consolidating this learning into long-term memory (LTM) that is called conditioned taste aversion (CTA). Previous studies showed that some molluscan insulin-related peptides (MIPs) were upregulated in snails exhibiting CTA. We thus hypothesized that MIPs play an important role in neurons underlying the CTA-LTM consolidation process. To examine this hypothesis, we first observed the distribution of MIP II, a major peptide of MIPs, and MIP receptor and determined the amounts of their mRNAs in the CNS. MIP II was only observed in the light green cells in the cerebral ganglia, but the MIP receptor was distributed throughout the entire CNS, including the buccal ganglia. Next, when we applied exogenous mammalian insulin, secretions from MIP-containing cells or partially purified MIPs, to the isolated CNS, we observed a long-term change in synaptic efficacy (i.e., enhancement) of the synaptic connection between the cerebral giant cell (a key interneuron for CTA) and the B1 motor neuron (a buccal motor neuron). This synaptic enhancement was blocked by application of an insulin receptor antibody to the isolated CNS. Finally, injection of the insulin receptor antibody into the snail before CTA training, while not blocking the acquisition of taste aversion learning, blocked the memory consolidation process; thus, LTM was not observed. These data suggest that MIPs trigger changes in synaptic connectivity that may be correlated with the consolidation of taste aversion learning into CTA-LTM in the Lymnaea CNS.}, } @article {pmid23283174, year = {2013}, author = {Volk, LJ and Bachman, JL and Johnson, R and Yu, Y and Huganir, RL}, title = {PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory.}, journal = {Nature}, volume = {493}, number = {7432}, pages = {420-423}, pmid = {23283174}, issn = {1476-4687}, support = {P30 NS050274/NS/NINDS NIH HHS/United States ; T32 MH015330/MH/NIMH NIH HHS/United States ; R01 NS036715/NS/NINDS NIH HHS/United States ; T32 EY017203/EY/NEI NIH HHS/United States ; T32MH15330/MH/NIMH NIH HHS/United States ; NS36715/NS/NINDS NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/physiology ; Cell-Penetrating Peptides ; Conditioning, Classical ; Fear ; Female ; Hippocampus/drug effects/*physiology ; Isoenzymes/deficiency/genetics/metabolism ; Lipopeptides/pharmacology ; Long-Term Potentiation/drug effects/genetics/physiology ; Male ; Memory, Long-Term/drug effects/*physiology ; Mice ; Mice, Knockout ; Neuronal Plasticity/genetics/*physiology ; Protein Kinase C/antagonists & inhibitors/deficiency/genetics/*metabolism ; Synapses/drug effects/*metabolism ; Synaptic Transmission/drug effects ; }, abstract = {Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral-CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ.}, } @article {pmid23276674, year = {2013}, author = {Anderson, RI and Agoglia, AE and Morales, M and Varlinskaya, EI and Spear, LP}, title = {Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.}, journal = {Neuroscience}, volume = {249}, number = {}, pages = {214-222}, pmid = {23276674}, issn = {1873-7544}, support = {R01 AA012453/AA/NIAAA NIH HHS/United States ; AA017355/AA/NIAAA NIH HHS/United States ; AA012453/AA/NIAAA NIH HHS/United States ; R01 AA017355/AA/NIAAA NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; AA017823/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects/*physiology ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage ; Male ; Pyrrolidines/administration & dosage ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa/*agonists/*metabolism ; Taste/drug effects/physiology ; }, abstract = {Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by nor-binaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances.}, } @article {pmid23276608, year = {2013}, author = {Singer, P and Wei, CJ and Chen, JF and Boison, D and Yee, BK}, title = {Deletion of striatal adenosine A(2A) receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learning.}, journal = {Behavioural brain research}, volume = {242}, number = {}, pages = {54-61}, pmid = {23276608}, issn = {1872-7549}, support = {R01 MH083973/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/physiology ; Corpus Striatum/*metabolism ; Homeodomain Proteins/genetics ; *Inhibition, Psychological ; Learning Disabilities/*genetics/physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Activity/genetics ; Psychoacoustics ; Receptor, Adenosine A2A/*deficiency ; Reflex, Acoustic/genetics ; Sensory Gating/*genetics ; Taste/genetics ; }, abstract = {Following early clinical leads, the adenosine A(2A)R receptor (A(2A)R) has continued to attract attention as a potential novel target for treating schizophrenia, especially against the negative and cognitive symptoms of the disease because of A(2A)R's unique modulatory action over glutamatergic in addition to dopaminergic signaling. Through (i) the antagonistic interaction with the dopamine D(2) receptor, and (ii) the regulation of glutamate release and N-methyl-d-aspartate receptor function, striatal A(2A)R is ideally positioned to fine-tune the dopamine-glutamate balance, the disturbance of which is implicated in the pathophysiology of schizophrenia. However, the precise function of striatal A(2A)Rs in the regulation of schizophrenia-relevant behavior is poorly understood. Here, we tested the impact of conditional striatum-specific A(2A)R knockout (st-A(2A)R-KO) on latent inhibition (LI) and prepulse inhibition (PPI) - behavior that is tightly regulated by striatal dopamine and glutamate. These are two common cross-species translational tests for the assessment of selective attention and sensorimotor gating deficits reported in schizophrenia patients; and enhanced performance in these tests is associated with antipsychotic drug action. We found that neither LI nor PPI was significantly affected in st-A(2A)R-KO mice, although a deficit in active avoidance learning was identified in these animals. The latter phenotype, however, was not replicated in another form of aversive conditioning - namely, conditioned taste aversion. Hence, the present study shows that neither learned inattention (as measured by LI) nor sensory gating (as indexed by PPI) requires the integrity of striatal A(2A)Rs - a finding that may undermine the hypothesized importance of A(2A)R in the genesis and/or treatment of schizophrenia.}, } @article {pmid27493554, year = {2013}, author = {Otsuka, E and Matsunaga, M and Okada, R and Yamagishi, M and Okuta, A and Lukowiak, K and Ito, E}, title = {Increase in cyclic AMP concentration in a cerebral giant interneuron mimics part of a memory trace for conditioned taste aversion of the pond snail.}, journal = {Biophysics (Nagoya-shi, Japan)}, volume = {9}, number = {}, pages = {161-166}, pmid = {27493554}, issn = {1349-2942}, abstract = {Conditioned taste aversion (CTA) can be classically conditioned in the pond snail Lymnaea stagnalis and subsequently be consolidated into long-term memory (LTM). The neural trace that subserves CTA-LTM can be summarized as follows: A polysynaptic inhibitory postsynaptic potential recorded in the neuron 1 medial (N1M) cell in the conditioned snails as a result of activation of the cerebral giant cell (CGC) is larger and lasts longer than that in control snails. The N1M cell is ultimately activated by the CGC via the neuron 3 tonic (N3t) cell. That is, the inhibitory monosynaptic inputs from the N3t cell to the N1M cell are facilitated. The N1M and N3t cells are the members of feeding central pattern generator, whereas the CGC is a multimodal interneuron thought to play a key role in feeding behavior. Here we examined the involvement of a second messenger, cAMP, in the establishment of the memory trace. We injected cAMP into the CGC and monitored the potentials of the B3 motor neuron activated by the CGC. B3 activity is used as an index for the synaptic inputs from the N3t cell to the N1M cell. We found that the B3 potentials were transiently enlarged. Thus, when the cAMP concentration is increased in the CGC by taste aversion training, cAMP-induced changes may play a key role in the establishment of a memory trace in the N3t cell.}, } @article {pmid26317099, year = {2013}, author = {Panguluri, SK and Kuwabara, N and Cooper, N and Tipparaju, SM and Sneed, KB and Lundy, RF}, title = {Gene Network Analysis in Amygdala following Taste Aversion Learning in Rats.}, journal = {Neuroscience journal}, volume = {2013}, number = {}, pages = {739764}, pmid = {26317099}, issn = {2314-4262}, abstract = {Conditioned taste aversion (CTA) is an adaptive behavior that benefits survival of animals including humans and also serves as a powerful model to study the neural mechanisms of learning. Memory formation is a necessary component of CTA learning and involves neural processing and regulation of gene expression in the amygdala. Many studies have been focused on the identification of intracellular signaling cascades involved in CTA, but not late responsive genes underlying the long-lasting behavioral plasticity. In this study, we explored in silico experiments to identify persistent changes in gene expression associated with CTA in rats. We used oligonucleotide microarrays to identify 248 genes in the amygdala regulated by CTA. Pathway Studio and IPA software analyses showed that the differentially expressed genes in the amygdala fall in diverse functional categories such as behavior, psychological disorders, nervous system development and function, and cell-to-cell signaling. Conditioned taste aversion is a complex behavioral trait which involves association of visceral and taste inputs, consolidation of taste and visceral information, memory formation, retrieval of stored information, and extinction phase. In silico analysis of differentially expressed genes is therefore necessary to manipulate specific phase/stage of CTA to understand the molecular insight.}, } @article {pmid23274135, year = {2013}, author = {Wheeler, DS and Chang, SE and Holland, PC}, title = {Odor-mediated taste learning requires dorsal hippocampus, but not basolateral amygdala activity.}, journal = {Neurobiology of learning and memory}, volume = {101}, number = {}, pages = {1-7}, pmid = {23274135}, issn = {1095-9564}, support = {F32 NS061587/NS/NINDS NIH HHS/United States ; R01 MH065879/MH/NIMH NIH HHS/United States ; NS061587/NS/NINDS NIH HHS/United States ; MH65879/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Hippocampus/*physiology ; Male ; *Odorants ; Olfactory Perception/*physiology ; Rats ; Rats, Long-Evans ; Taste Perception/*physiology ; }, abstract = {Mediated learning is a unique cognitive phenomenon in which mental representations of physically absent stimuli enter into associations with directly-activated representations of physically present stimuli. Three experiments investigated the functional physiology of mediated learning involving the use of odor-taste associations. In Experiments 1a and 1b, basolateral amygdala lesions failed to attenuate mediated taste aversion learning. In Experiment 2, dorsal hippocampus inactivation impaired mediated learning, but left direct learning intact. Considered with past studies, the results implicate the dorsal hippocampus in mediated learning generally, and suggest a limit on the importance of the basolateral amygdala.}, } @article {pmid23268328, year = {2013}, author = {Rasoamanana, R and Even, PC and Darcel, N and Tomé, D and Fromentin, G}, title = {Dietary fibers reduce food intake by satiation without conditioned taste aversion in mice.}, journal = {Physiology & behavior}, volume = {110-111}, number = {}, pages = {13-19}, doi = {10.1016/j.physbeh.2012.12.008}, pmid = {23268328}, issn = {1873-507X}, mesh = {Animals ; Avoidance Learning ; Carbon Dioxide/metabolism ; Conditioning, Operant ; Data Interpretation, Statistical ; Diet ; Dietary Fiber/administration & dosage/*pharmacology ; Eating/*drug effects ; Energy Metabolism/drug effects ; Immunohistochemistry ; Intubation, Gastrointestinal ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/physiology ; Oxygen Consumption/drug effects ; Proto-Oncogene Proteins c-fos/metabolism ; Respiratory Mechanics/drug effects ; Satiation/*drug effects ; Solitary Nucleus/drug effects/metabolism ; Taste/*drug effects ; }, abstract = {It is well known that intake of dietary fiber (DF) potently decreases food intake and feelings of hunger and/or promotes satiety ratings. However, the mechanisms explaining these effects are not well characterized. This work was performed to determine which of satiation and/or satiety mechanisms provoke the decrease of food intake induced by DF in mice. We tested in an intra-group protocol a low-viscosity (LV, fructo-oligosaccharide), a viscous (VP, guar gum) and a high-viscosity (HV, mixture of guar gum and fructo-oligosaccharide) preload. These were given to mice by intra-gastric gavage. It appeared that viscous preloads such as VP and HV reduced the daily energy intake by 14% and 21% respectively. The strong effect of HV was mainly due to a large decrease of meal size (by 57%) and meal duration (by 65%) with no effect on ingestion rate during the first 30 min after administration. Therefore, the DF-induced decrease of energy intake was due to a satiation mechanism. This is further supported by a 3-fold increased sensitization of neurons in the nucleus of the solitary tract as observed by c-Fos protein immunolabelling. No compensation of food intake was observed during the rest of the day, a phenomenon that may be explained by the fact that metabolic rate remained high despite the lower food intake. We have also shown that the DF-induced inhibition of food intake was not paired with a conditioned taste aversion. To conclude, this work demonstrates that DF inhibits food intake by increasing satiation during ~1h after administration.}, } @article {pmid23185492, year = {2012}, author = {Wang, Y and Zhang, TY and Xin, J and Li, T and Yu, H and Li, N and Chen, ZY}, title = {Differential involvement of brain-derived neurotrophic factor in reconsolidation and consolidation of conditioned taste aversion memory.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e49942}, pmid = {23185492}, issn = {1932-6203}, mesh = {Animals ; *Brain-Derived Neurotrophic Factor/metabolism/physiology ; *Cerebral Cortex/metabolism/physiology ; Conditioning, Classical/physiology ; Memory/*physiology ; Rats ; Rats, Wistar ; Synapses/metabolism/physiology ; Taste/*physiology ; }, abstract = {Consolidated memory can re-enter states of transient instability following reactivation, which is referred to as reconsolidation, and the exact molecular mechanisms underlying this process remain unexplored. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity and memory processes. We have recently observed that BDNF signaling in the central nuclei of the amygdala (CeA) and insular cortex (IC) was involved in the consolidation of conditioned taste aversion (CTA) memory. However, whether BDNF in the CeA or IC is required for memory reconsolidation is still unclear. In the present study, using a CTA memory paradigm, we observed increased BDNF expression in the IC but not in the CeA during CTA reconsolidation. We further determined that BDNF synthesis and signaling in the IC but not in the CeA was required for memory reconsolidation. The differential, spatial-specific roles of BDNF in memory consolidation and reconsolidation suggest that dissociative molecular mechanisms underlie reconsolidation and consolidation, which might provide novel targets for manipulating newly encoded and reactivated memories without causing universal amnesia.}, } @article {pmid23183173, year = {2013}, author = {Santollo, J and Marshall, A and Daniels, D}, title = {Activation of membrane-associated estrogen receptors decreases food and water intake in ovariectomized rats.}, journal = {Endocrinology}, volume = {154}, number = {1}, pages = {320-329}, pmid = {23183173}, issn = {1945-7170}, support = {R01 HL091911/HL/NHLBI NIH HHS/United States ; HL-091911/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Drinking/*drug effects ; Eating/*drug effects ; Estradiol/administration & dosage/*pharmacology ; Female ; Ovariectomy ; Rats ; Rats, Long-Evans ; Receptors, Estrogen/*metabolism ; }, abstract = {Estradiol (E2) decreases food and water intake in a variety of species, including rats. Available evidence suggests that this is mediated by genomic mechanisms that are most often attributed to nuclear estrogen receptors. More recent studies indicate that membrane-associated estrogen receptors (mERs) also can influence gene expression through the activation of transcription factors, yet it is unclear whether mERs are involved in mediating the hypophagic and antidipsetic effects of E2. In the present experiments, we injected E2 or a membrane-impermeable form of E2 (E2-BSA) into the lateral cerebral ventricle of ovariectomized female rats and evaluated the effect on 23 h food and water intake. First, we found that higher doses of E2 were necessary to reduce water intake than were sufficient to reduce food intake. Analysis of drinking microstructure revealed that the decrease in water intake after E2 treatment was mediated by both a decrease in burst number and burst size. Next, the activation of mERs with E2-BSA decreased both overnight food and water intake and analysis of drinking microstructure indicated that the decreased water intake resulted from a decrease in burst number. Finally, E2-BSA did not condition a taste aversion, suggesting that the inhibitory effects on food and water intake were not secondary to malaise. Together these findings suggest that activation of mERs is sufficient to decrease food and water intake in female rats.}, } @article {pmid23183042, year = {2013}, author = {Mickley, GA and Ketchesin, KD and Ramos, L and Luchsinger, JR and Rogers, MM and Wiles, NR and Hoxha, N}, title = {Stimulation of the dorsal periaqueductal gray enhances spontaneous recovery of a conditioned taste aversion.}, journal = {Brain research}, volume = {1493}, number = {}, pages = {27-39}, pmid = {23183042}, issn = {1872-6240}, support = {R15 MH063720/MH/NIMH NIH HHS/United States ; 2-R15-MH063720-03/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Conditioning, Psychological/*physiology ; Electric Stimulation ; Electrodes, Implanted ; Extinction, Psychological/*physiology ; Male ; Periaqueductal Gray/*physiology ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Taste/*physiology ; }, abstract = {Due to its relevance to clinical practice, extinction of learned fears has been a major focus of recent research. However, less is known about the means by which conditioned fears re-emerge (i.e., spontaneously recover) as time passes or contexts change following extinction. The periaqueductal gray represents the final common pathway mediating defensive reactions to fear and we have reported previously that the dorsolateral PAG (dlPAG) exhibits a small but reliable increase in neural activity (as measured by c-fos protein immunoreactivity) when spontaneous recovery (SR) of a conditioned taste aversion (CTA) is reduced. Here we extend these correlational studies to determine if inducing dlPAG c-fos expression through electrical brain stimulation could cause a reduction in SR of a CTA. Male Sprague-Dawley rats acquired a strong aversion to saccharin (conditioned stimulus; CS) and then underwent CTA extinction through multiple non-reinforced exposures to the CS. Following a 30-day latency period after asymptotic extinction was achieved; rats either received stimulation of the dorsal PAG (dPAG) or stimulation of closely adjacent structures. Sixty minutes following the stimulation, rats were again presented with the saccharin solution as we tested for SR of the CTA. The brain stimulation evoked c-fos expression around the tip of the electrodes. However, stimulation of the dPAG failed to reduce SR of the previously extinguished CTA. In fact, dPAG stimulation caused rats to significantly suppress their saccharin drinking (relative to controls) - indicating an enhanced SR. These data refute a cause-and-effect relationship between enhanced dPAG c-fos expression and a reduction in SR. However, they highlight a role for the dPAG in modulating SR of extinguished CTAs.}, } @article {pmid23171343, year = {2013}, author = {Moore, EM and Forrest, RD and Boehm, SL}, title = {Genotype modulates age-related alterations in sensitivity to the aversive effects of ethanol: an eight inbred strain analysis of conditioned taste aversion.}, journal = {Genes, brain, and behavior}, volume = {12}, number = {1}, pages = {70-77}, pmid = {23171343}, issn = {1601-183X}, support = {R01 AA016789/AA/NIAAA NIH HHS/United States ; AA018910/AA/NIAAA NIH HHS/United States ; AA015434/AA/NIAAA NIH HHS/United States ; F31 AA018910/AA/NIAAA NIH HHS/United States ; K01 AA015434/AA/NIAAA NIH HHS/United States ; AA016789/AA/NIAAA NIH HHS/United States ; L40 AA017849/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Conditioning, Classical/*drug effects ; Ethanol/*toxicity ; *Genotype ; Male ; Mice ; Mice, Inbred Strains ; Species Specificity ; Taste Perception/*drug effects/genetics/physiology ; }, abstract = {Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Currently there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in eight inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T(+) tf/J, C3H/HeJ and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1 h. Immediately following access mice were administered ethanol (0, 1.5, 2.25 and 3 g/kg, ip). This procedure was repeated in 72 h intervals for a total of five CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain.}, } @article {pmid23147414, year = {2013}, author = {Blednov, YA and Benavidez, JM and Black, M and Chandra, D and Homanics, GE and Rudolph, U and Harris, RA}, title = {Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.}, journal = {Neuropharmacology}, volume = {67}, number = {}, pages = {46-56}, pmid = {23147414}, issn = {1873-7064}, support = {R37 AA010422/AA/NIAAA NIH HHS/United States ; K08 DE014184/DE/NIDCR NIH HHS/United States ; R01 AA013004/AA/NIAAA NIH HHS/United States ; A06399//PHS HHS/United States ; AA13004/AA/NIAAA NIH HHS/United States ; DE14184/DE/NIDCR NIH HHS/United States ; AA U01 13520-INIA/AA/NIAAA NIH HHS/United States ; R01 AA010422/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; AA10422/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Acute Disease ; Alcoholic Intoxication/*genetics ; Animals ; Avoidance Learning/drug effects/*physiology ; Ethanol/administration & dosage/toxicity ; Genetic Linkage/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, GABA-A/*genetics ; Recovery of Function/*drug effects/genetics ; Taste/drug effects/*genetics ; }, abstract = {GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABA(A)-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011). All together, they indicate that aversive property of ethanol is dependent on ethanol action on α2-containing GABA(A)-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABA(A)-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 (-/-) and α3 (-/Y) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism.}, } @article {pmid23096103, year = {2012}, author = {Ángeles-Durán, S and Ramos-Languren, LE and Escobar, ML}, title = {PKMζ inhibition prevents the metaplastic change induced by conditioned taste aversion on insular cortex long-term potentiation in vivo.}, journal = {Reviews in the neurosciences}, volume = {23}, number = {5-6}, pages = {473-480}, doi = {10.1515/revneuro-2012-0048}, pmid = {23096103}, issn = {0334-1763}, mesh = {Amygdala/drug effects/physiology ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Biophysics ; Cerebral Cortex/*metabolism ; Conditioning, Psychological/drug effects/physiology ; Electric Stimulation ; Enzyme Inhibitors/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Long-Term Potentiation/drug effects/*physiology ; Male ; Neural Pathways/drug effects/physiology ; Oligopeptides/pharmacology ; Protein Kinase C/antagonists & inhibitors/*metabolism ; Rats ; Rats, Wistar ; Taste/drug effects/*physiology ; }, abstract = {The activity history of a given neuron or pathway has been suggested to influence its future responses to synaptic inputs. In particular, training in several learning tasks produces a metaplastic change, that is, a change in the ability to induce subsequent synaptic plasticity. Experimental evidence shows that the maintenance of long term memory and long-term potentiation (LTP) requires the persistent action of the atypical protein kinase Cisoform, protein kinase M ζ (PKM ζ). Recent work has demonstrated that the inactivation of PKM ζ in the insular cortex (IC) abolishes conditioned taste aversion (CTA) long term memory. Our previous studies in the IC have demonstrated that the induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to CTA training enhances the retention of this task. Moreover, recently, we have observed that CTA training blocks the subsequent induction of LTP in the Bla-IC projection. The aim of the present study was to investigate the participation of PKM ζon the CTA-dependent modification of the ability to induce subsequent LTP in the Bla-IC projection in vivo . Thus, we have delivered high-frequency stimulation in the Bla-IC projection in order to induce in vivo IC-LTP in the rats that underwent or did not have an impairment of CTA retention due to the intracortical administration of the selective PKM ζ pseudosubstrate inhibitory peptide, ZIP. Our results show that the microinfusion of ZIP into the IC of the behaving rats impairs long-term memory of CTA and prevents its effects on IC-LTP. These results indicate that PKM ζ is a key component of the cellular mechanisms necessary for the persistence of lasting memory traces as well as for those underlying metaplastic changes in neocortex, contributing to the persistence of aversive memories.}, } @article {pmid23088962, year = {2013}, author = {Shehadi, K and Maroun, M}, title = {Different effects of low frequency stimulation to infralimbic prefrontal cortex on extinction of aversive memories.}, journal = {Brain research}, volume = {1490}, number = {}, pages = {111-116}, doi = {10.1016/j.brainres.2012.10.026}, pmid = {23088962}, issn = {1872-6240}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Electric Stimulation ; Electrodes, Implanted ; Electroshock ; Extinction, Psychological/*physiology ; Fear/psychology ; Limbic System/*physiology ; Male ; Memory/*physiology ; Prefrontal Cortex/*physiology ; Rats ; Taste/physiology ; }, abstract = {Experimental extinction is a behavioral technique in which animals learn to extinguish previously learned fear responses. The infralimbic cortex (IL) of the medial prefrontal cortex has an important role in extinction of aversive memories. We have recently shown that electrical stimulation of the IL in a form of high-frequency stimulation (HFS), which induces potentiation in the IL, was associated with enhanced ability to extinguish aversive memory in two aversive paradigms, the fear conditioning and the conditioned taste aversion paradigms. These results suggest that the induction of potentiation in the IL is associated with better ability to extinguish. In the present study we examined the opposite hypothesis that inducing depression in the IL by the application of low-frequency stimulation (LFS) will result in impairments in extinction. Our results show that the application of LFS to the IL retards extinction of fear conditioning only, suggesting that the application of LFS to the IL results in impairments in extinction of conditioned fear. In the conditioned taste aversion paradigm (CTA), LFS to the IL was associated with delayed enhancement of extinction of CTA that was apparent 48 h following stimulation. These results suggest that localized electrical stimulation to the IL may be an effective method for manipulating learned fear and affecting the ability to extinguish aversive associations.}, } @article {pmid23076252, year = {2013}, author = {Fatima, A and Andrabi, S and Wolf, G and Engelmann, M and Spina, MG}, title = {Urocortin 1 administered into the hypothalamic supraoptic nucleus inhibits food intake in freely fed and food-deprived rats.}, journal = {Amino acids}, volume = {44}, number = {3}, pages = {879-885}, doi = {10.1007/s00726-012-1415-7}, pmid = {23076252}, issn = {1438-2199}, mesh = {Animals ; Appetite/*drug effects ; Down-Regulation/drug effects ; Eating/*drug effects ; Feeding Behavior/drug effects ; Food Deprivation ; Hypothalamus/drug effects ; Male ; Rats ; Rats, Wistar ; Supraoptic Nucleus/*drug effects ; Urocortins/*administration & dosage ; }, abstract = {Peptides of the corticotropin-releasing hormone/Urocortin (CRH/Ucn) family are known to suppress appetite primarily via CRH(2) receptors. In the rat hypothalamic supraoptic nucleus (SON), synthesis of both Ucn1 and CRH(2) receptors has been reported, yet little is known about the effects of Ucn1 in the SON on feeding behaviour. We first established the dose-related effects of Ucn1 injected into the SON on the feeding response in both freely fed and 24-h food-deprived rats. A conditioned taste avoidance paradigm was performed to investigate possible generalised effects of local Ucn1 treatment. Administration of Ucn1 into the SON at doses equal to or higher than 0.5 μg significantly decreased food intake in both freely fed and food-deprived rats. The Ucn1-mediated suppression of food intake was delayed in freely fed as compared to food-deprived animals. Conditioning for taste aversion to saccharine appeared at 0.5 and 1 μg of Ucn1. Both the early and the delayed onset of anorexia observed after intra-SON injection of Ucn1 under fasting and fed conditions, respectively, suggest the possible involvement of different CRH receptor subtypes in the two conditions, while the conditioned taste aversion seems to be responsible for the initial latency to eat the first meal in these animals.}, } @article {pmid23067064, year = {2013}, author = {Chapman, HA and Johannes, K and Poppenk, JL and Moscovitch, M and Anderson, AK}, title = {Evidence for the differential salience of disgust and fear in episodic memory.}, journal = {Journal of experimental psychology. General}, volume = {142}, number = {4}, pages = {1100-1112}, doi = {10.1037/a0030503}, pmid = {23067064}, issn = {1939-2222}, mesh = {Adolescent ; Arousal/physiology ; Attention/*physiology ; Discrimination, Psychological ; Emotions/*physiology ; Fear/physiology/*psychology ; Female ; Humans ; Male ; *Memory, Episodic ; Photic Stimulation ; Young Adult ; }, abstract = {Studies of emotional memory typically focus on the memory-enhancing effects of emotional dimensions such as arousal and valence. However, it is unclear to what extent different emotional categories could have distinct effects on memory over and above these dimensional influences. We tested this possibility by investigating the impact of two negative, highly arousing, and withdrawal-related emotions-disgust and fear--on attention and subsequent memory. To index differential attention during encoding, participants performed a speeded line discrimination task (LDT) while viewing disgusting and fearful photographs of similar valence and arousal, which were assessed for later memory. LDT performance was slower, and subsequent recall and recognition were greater, for disgusting compared to both fearful and neutral images. Disgust enhancement of memory remained significant even when controlling for attention at encoding and for arousal, visual salience, and conceptual distinctiveness. Receiver-operating curve analyses indicated that disgust enhancement of memory was due to increased sensitivity, rather than response bias. Thus, disgust appears to have a special salience in memory relative to certain other emotions, suggesting that a purely dimensional model of emotional influences on cognition is inadequate to account for their effects. We speculate that disgust enhancement of memory could arise from an origin in conditioned taste aversion, a highly enduring form of implicit memory.}, } @article {pmid23055953, year = {2012}, author = {McCutcheon, JE and Ebner, SR and Loriaux, AL and Roitman, MF}, title = {Encoding of aversion by dopamine and the nucleus accumbens.}, journal = {Frontiers in neuroscience}, volume = {6}, number = {}, pages = {137}, pmid = {23055953}, issn = {1662-453X}, support = {R01 DA025634/DA/NIDA NIH HHS/United States ; }, abstract = {Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such discrimination leads to the generation of either an approach or rejection response, as appropriate, and enables organisms to maximize reward and minimize punishment. Classically, the nucleus accumbens (NAc) and the dopamine projection to it are considered an integral part of the brain's reward circuit, i.e., they direct approach and consumption behaviors and underlie positive reinforcement. This reward-centered framing ignores important evidence about the role of this system in encoding aversive events. One reason for bias toward reward is the difficulty in designing experiments in which animals repeatedly experience punishments; another is the challenge in dissociating the response to an aversive stimulus itself from the reward/relief experienced when an aversive stimulus is terminated. Here, we review studies that employ techniques with sufficient time resolution to measure responses in ventral tegmental area and NAc to aversive stimuli as they are delivered. We also present novel findings showing that the same stimulus - intra-oral infusion of sucrose - has differing effects on NAc shell dopamine release depending on the prior experience. Here, for some rats, sucrose was rendered aversive by explicitly pairing it with malaise in a conditioned taste aversion paradigm. Thereafter, sucrose infusions led to a suppression of dopamine with a similar magnitude and time course to intra-oral infusions of a bitter quinine solution. The results are discussed in the context of regional differences in dopamine signaling and the implications of a pause in phasic dopamine release within the NAc shell. Together with our data, the emerging literature suggests an important role for differential phasic dopamine signaling in aversion vs. reward.}, } @article {pmid23054171, year = {2012}, author = {Smith, KR and Treesukosol, Y and Paedae, AB and Contreras, RJ and Spector, AC}, title = {Contribution of the TRPV1 channel to salt taste quality in mice as assessed by conditioned taste aversion generalization and chorda tympani nerve responses.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {303}, number = {11}, pages = {R1195-205}, pmid = {23054171}, issn = {1522-1490}, support = {R01 DC004574/DC/NIDCD NIH HHS/United States ; R01-DC004574/DC/NIDCD NIH HHS/United States ; R01-DC004785/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/pharmacology ; Animals ; Chorda Tympani Nerve/*physiology ; Genotype ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Sodium Chloride/*pharmacology ; TRPV Cation Channels/genetics/*metabolism ; *Taste ; Water/chemistry ; }, abstract = {In rodents, at least two transduction mechanisms are involved in salt taste: 1) the sodium-selective epithelial sodium channel, blocked by topical amiloride administration, and 2) one or more amiloride-insensitive cation-nonselective pathways. Whereas electrophysiological evidence from the chorda tympani nerve (CT) has implicated the transient receptor potential vanilloid-1 (TRPV1) channel as a major component of amiloride-insensitive salt taste transduction, behavioral results have provided only equivocal support. Using a brief-access taste test, we examined generalization profiles of water-deprived C57BL/6J (WT) and TRPV1 knockout (KO) mice conditioned (via LiCl injection) to avoid 100 μM amiloride-prepared 0.25 M NaCl and tested with 0.25 M NaCl, sodium gluconate, KCl, NH(4)Cl, 6.625 mM citric acid, 0.15 mM quinine, and 0.5 M sucrose. Both LiCl-injected WT and TRPV1 KO groups learned to avoid NaCl+amiloride relative to controls, but their generalization profiles did not differ; LiCl-injected mice avoided the nonsodium salts and quinine suggesting that a TRPV1-independent pathway contributes to the taste quality of the amiloride-insensitive portion of the NaCl signal. Repeating the experiment but doubling all stimulus concentrations revealed a difference in generalization profiles between genotypes. While both LiCl-injected groups avoided the nonsodium salts and quinine, only WT mice avoided the sodium salts and citric acid. CT responses to these stimuli and a concentration series of NaCl and KCl with and without amiloride did not differ between genotypes. Thus, in our study, TRPV1 did not appear to contribute to sodium salt perception based on gustatory signals, at least in the CT, but may have contributed to the oral somatosensory features of sodium.}, } @article {pmid23001315, year = {2012}, author = {Guzman-Ramos, K and Bermudez-Rattoni, F}, title = {Interplay of amygdala and insular cortex during and after associative taste aversion memory formation.}, journal = {Reviews in the neurosciences}, volume = {23}, number = {5-6}, pages = {463-471}, doi = {10.1515/revneuro-2012-0056}, pmid = {23001315}, issn = {0334-1763}, mesh = {Amygdala/*physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Humans ; Memory/*physiology ; Neural Pathways/physiology ; Taste/*physiology ; }, abstract = {The formation and storage of aversively motivated memories is based on plastic changes within the amygdala and other brain structures that are modulated by its activity. One of these structures is the insular cortex,which integrates environmental and interoceptive information such that memory traces can be efficient and rapidly stored. A great example of an aversively motivated learning is the taste aversion paradigm, which involves several changes at the cellular level of the amygdala and the insular cortex in order to be acquired and consolidated.So far, the interplay of these structures was described in terms of their participation during exposure to the stimuli to be associated; however, because of the cellular properties and interconnections between them, their functional interplay may go beyond the acquisition stage and the learning experience might trigger an ongoing engagement of amygdala-insular cortex reactivations in order to store the information.}, } @article {pmid22981693, year = {2012}, author = {Marriott, AL and Ryan, CL and Doucette, TA}, title = {Neonatal domoic acid treatment produces alterations to prepulse inhibition and latent inhibition in adult rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {103}, number = {2}, pages = {338-344}, doi = {10.1016/j.pbb.2012.08.022}, pmid = {22981693}, issn = {1873-5177}, mesh = {Animals ; Animals, Newborn ; *Behavior, Animal ; Disease Models, Animal ; Female ; Kainic Acid/*analogs & derivatives/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Schizophrenia/*physiopathology ; }, abstract = {Schizophrenia is a complex and severe mental disorder characterized by positive, negative and cognitive symptoms. Characteristic behavioral alterations reflecting these categories of symptoms have been observed in many animal models of this disorder, and are consistent with those manifested in the clinical population. The purpose of this study was to determine whether early alterations in glutamate signaling would result in alterations to prepulse inhibition (PPI) and latent inhibition (LI); two assessments used for evaluating putative novel animal models with relevance to schizophrenia. In the present experiment, daily subcutaneous (s.c.) injections of 20μg/kg of domoic acid (DOM) were administered to rat pups from postnatal days (PND) 8-14. When tested as adults, DOM treated rats displayed deficits in PPI that were dependant on both sex and time of day. No differences in startle amplitude, habituation, or movement were found during any test, indicating that the PPI deficits seen could not be attributed to baseline startle differences. Deficits in LI were also apparent when adult rats were tested using a conditioned taste aversion task, with DOM-treated animals displaying a significantly suppressed LI. These results suggest that early treatment with DOM may serve as a useful tool to model schizophrenia which in turn may lead to a better understanding of the contribution of glutamate, and in particular, kainate receptors, to the development and/or manifestation of schizophrenia or schizophrenia-like symptoms in the clinical population.}, } @article {pmid22776493, year = {2012}, author = {Ito, E and Okada, R and Sakamoto, Y and Otshuka, E and Mita, K and Okuta, A and Sunada, H and Sakakibara, M}, title = {Insulin and memory in Lymnaea.}, journal = {Acta biologica Hungarica}, volume = {63 Suppl 2}, number = {}, pages = {194-201}, doi = {10.1556/ABiol.63.2012.Suppl.2.25}, pmid = {22776493}, issn = {0236-5383}, mesh = {Animals ; Conditioning, Classical ; Insulin/metabolism ; Long-Term Potentiation ; Lymnaea/*metabolism ; *Memory, Long-Term ; Neuropeptides/*metabolism ; Receptor, Insulin/*metabolism ; Synapses/*metabolism ; }, abstract = {The pond snail, Lymnaea stagnalis, is capable of learning conditioned taste aversion (CTA) and consolidating this CTA into long-term memory (LTM). The DNA microarray experiments showed that some of molluscan insulin-related peptides (MIPs) were up-regulated in snails exhibiting CTA-LTM. On the other hand, the electrophysiological experiments showed that application of secretions from the MIPs-containing cells evoked long-term potentiation (LTP) at the synapses between the cerebral giant cell (a key interneuron for CTA) and the B1 motoneuron (a buccal motoneuron). We thus hypothesized that MIPs and MIP receptors play an important role at the synapses, probably underlying the CTA-LTM consolidation process. To examine this hypothesis, we applied the antibody, which recognizes the binding site of mammalian insulin receptors and is thought to cross-react MIP receptors, to the Lymnaea CNS. Our present data showed that an application of the antibody for insulin receptors to the isolated CNS blocked LTP, and that an injection of the antibody into the Lymnaea abdominal cavity inhibited LTM consolidation, but not CTA formation.}, } @article {pmid22776492, year = {2012}, author = {Sunada, H and Lukowiak, K and Sakakibara, M}, title = {In vitro aversion conditioning in Lymnaea. Short communication.}, journal = {Acta biologica Hungarica}, volume = {63 Suppl 2}, number = {}, pages = {190-193}, doi = {10.1556/ABiol.63.2012.Suppl.2.24}, pmid = {22776492}, issn = {0236-5383}, mesh = {Animals ; *Conditioning, Classical ; *Feeding Behavior ; In Vitro Techniques ; *Lymnaea ; }, abstract = {In an in vitro semi-intact Lymnaea preparation we were successful in using a training procedure to bring about Conditioning Taste Aversion (CTA). Following paired presentation of the CS (sucrose) and US (tactile), the CS no longer elicits feeding. We can use sucrose to the lips in the semi-intact preparation as the CS; while we use direct current injection to depolarize RPeD11 as the US. Following pairing of these stimuli, the CS no longer elicits fictive feeding. We can determine the changes in synaptic input to neurons that play key roles in controlling feeding behavior.}, } @article {pmid22921283, year = {2012}, author = {Verendeev, A and Riley, AL}, title = {Conditioned taste aversion and drugs of abuse: history and interpretation.}, journal = {Neuroscience and biobehavioral reviews}, volume = {36}, number = {10}, pages = {2193-2205}, doi = {10.1016/j.neubiorev.2012.08.004}, pmid = {22921283}, issn = {1873-7528}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Psychological/*physiology ; Food Preferences ; Humans ; *Substance-Related Disorders ; *Taste ; }, abstract = {Conditioned taste aversion (CTA) learning describes a phenomenon wherein an animal learns to avoid consumption of a particular taste or food following its pairing with an aversive stimulus. Although initially demonstrated with radiation and classical emetics, CTAs have also been shown with drugs of abuse. The ability of rewarding drugs to support CTA learning was described as paradoxical by many investigators, and a number of attempts have been made to resolve this paradox. The present review offers a historical perspective on the CTA literature with a particular focus on CTAs induced by self-administered drugs. Specifically, this review describes and summarizes several interpretations of CTA learning that offer possible mechanisms by which drugs of abuse support CTAs, including sickness, drug novelty, reward comparison and conditioned fear. It is concluded that the reported "paradox" is no paradox at all in that drugs of abuse are complex pharmacological compounds that produce multiple stimulus effects, not all of which are positive reinforcing. Finally, a possible role of drug aversion in drug self-administration is discussed.}, } @article {pmid22910716, year = {2012}, author = {Rodriguez-Ortiz, CJ and Balderas, I and Garcia-DeLaTorre, P and Bermudez-Rattoni, F}, title = {Taste aversion memory reconsolidation is independent of its retrieval.}, journal = {Neurobiology of learning and memory}, volume = {98}, number = {3}, pages = {215-219}, doi = {10.1016/j.nlm.2012.08.002}, pmid = {22910716}, issn = {1095-9564}, mesh = {Amygdala/drug effects/physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Male ; Memory/drug effects/*physiology ; Microinjections ; Quinoxalines/pharmacology ; Rats ; Rats, Wistar ; Receptors, AMPA/antagonists & inhibitors ; Taste/drug effects/*physiology ; }, abstract = {Reconsolidation refers to the destabilization/re-stabilization memory process upon its activation. However, the conditions needed to undergo reconsolidation, as well as its functional significance is quite unclear and a matter of intense investigation. Even so, memory retrieval is held as requisite to initiate reconsolidation. Therefore, in the present work we examined whether transient pharmacological disruption of memory retrieval impedes reconsolidation of stored memory in the widely used associative conditioning task, taste aversion. We found that AMPA receptors inhibition in the amygdala impaired retrieval of taste aversion memory. Furthermore, AMPA receptors blockade impeded retrieval regardless of memory strength. However, inhibition of retrieval did not affect anisomycin-mediated disruption of reconsolidation. These results indicate that retrieval is a dispensable condition to undergo reconsolidation and provide evidence of molecular dissociation between retrieval and activation of memory in the non-declarative memory model taste aversion.}, } @article {pmid22900097, year = {2012}, author = {Ito, E and Otsuka, E and Hama, N and Aonuma, H and Okada, R and Hatakeyama, D and Fujito, Y and Kobayashi, S}, title = {Memory trace in feeding neural circuitry underlying conditioned taste aversion in Lymnaea.}, journal = {PloS one}, volume = {7}, number = {8}, pages = {e43151}, pmid = {22900097}, issn = {1932-6203}, mesh = {Animals ; Central Pattern Generators ; *Conditioning, Classical ; Excitatory Postsynaptic Potentials/physiology ; *Feeding Behavior ; Learning ; Lymnaea/*physiology ; *Memory, Long-Term ; Motor Neurons/physiology ; Neural Networks, Computer ; Taste/*physiology ; }, abstract = {BACKGROUND: The pond snail Lymnaea stagnalis can maintain a conditioned taste aversion (CTA) as a long-term memory. Previous studies have shown that the inhibitory postsynaptic potential (IPSP) evoked in the neuron 1 medial (N1M) cell by activation of the cerebral giant cell (CGC) in taste aversion-trained snails was larger and lasted longer than that in control snails. The N1M cell is one of the interneurons in the feeding central pattern generator (CPG), and the CGC is a key regulatory neuron for the feeding CPG.

Previous studies have suggested that the neural circuit between the CGC and the N1M cell consists of two synaptic connections: (1) the excitatory connection from the CGC to the neuron 3 tonic (N3t) cell and (2) the inhibitory connection from the N3t cell to the N1M cell. However, because the N3t cell is too small to access consistently by electrophysiological methods, in the present study the synaptic inputs from the CGC to the N3t cell and those from the N3t cell to the N1M cell were monitored as the monosynaptic excitatory postsynaptic potential (EPSP) recorded in the large B1 and B3 motor neurons, respectively. The evoked monosynaptic EPSPs of the B1 motor neurons in the brains isolated from the taste aversion-trained snails were identical to those in the control snails, whereas the spontaneous monosynaptic EPSPs of the B3 motor neurons were significantly enlarged.

CONCLUSION/SIGNIFICANCE: These results suggest that, after taste aversion training, the monosynaptic inputs from the N3t cell to the following neurons including the N1M cell are specifically facilitated. That is, one of the memory traces for taste aversion remains as an increase in neurotransmitter released from the N3t cell. We thus conclude that the N3t cell suppresses the N1M cell in the feeding CPG, in response to the conditioned stimulus in Lymnaea CTA.}, } @article {pmid22843139, year = {2013}, author = {Koch, CE and Göddeke, S and Krüger, M and Tups, A}, title = {Effect of central and peripheral leucine on energy metabolism in the Djungarian hamster (Phodopus sungorus).}, journal = {Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology}, volume = {183}, number = {2}, pages = {261-268}, pmid = {22843139}, issn = {1432-136X}, mesh = {Administration, Oral ; Analysis of Variance ; Animals ; Blood Glucose/metabolism ; Body Weight/drug effects ; Cricetinae ; *Dietary Supplements ; Dose-Response Relationship, Drug ; Drinking Water/analysis ; Eating/drug effects ; Energy Metabolism/drug effects/*physiology ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Leucine/administration & dosage/*metabolism/pharmacology ; Male ; Phodopus ; }, abstract = {Branched-chain amino acids, particularly leucine, are thought to activate nutrient sensing pathways in the hypothalamus that regulate food intake and energy homeostasis. In the light of recent controversial findings of leucine's effect on energy homeostasis further clarification of the metabolic impact of dietary leucine supplementation is required. We examined the pharmacological and dietary effects of leucine on energy metabolism in the Djungarian hamster (Phodopus sungorus), a well-established model for studies of alterations in leptin sensitivity and energy metabolism. We acutely administered leucine into the lateral ventricle (1.1 μg) of hamsters to characterize whether leucine exhibits anorexigenic properties in this species as has been described in other rodents. Next the catabolic effect of dietary administered leucine via supplemented rodent diet (15 % leucine), drinking water (17 g/L leucine) and oral gavages (10 mg/day); as well as the effect of subcutaneously (0.1 and 3 mg/day) and intraperitoneally (0.1, 3 and 6 mg/day) injected leucine which avoids the gastrointestinal-track was analyzed. Centrally administered leucine reduced 24 h food intake (by 32 %) and body weight. Both parameters were also reduced in hamsters with leucine supplemented diet, but this catabolic response was based on a pronounced taste aversion to the leucine-diet. In all other experiments, dietary leucine and peripheral injections of leucine had no effect on food intake, body weight and basal blood glucose levels. Our data suggest that in the Djungarian hamster dietary leucine fails to exhibit catabolic effects that would override the evolutionary conserved adaptations of the species which is critical for its survival.}, } @article {pmid22796484, year = {2012}, author = {Li, J and Yan, J and Chen, K and Lu, B and Wang, Q and Yan, W and Zhao, X}, title = {Lesions of the central nucleus of the amygdala decrease taste threshold for sodium chloride in rats.}, journal = {Brain research bulletin}, volume = {89}, number = {1-2}, pages = {8-15}, doi = {10.1016/j.brainresbull.2012.06.013}, pmid = {22796484}, issn = {1873-2747}, mesh = {Amygdala/drug effects/pathology/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/*administration & dosage ; Taste Threshold/drug effects/*physiology ; }, abstract = {Previous studies reported that NaCl intake was down-regulated in rats with bilateral lesions of the central nucleus of the amygdala (CeA). In line with the evidence from anatomical and physiological studies, such an inhibition could be the result of altered taste threshold for NaCl, one of the important factors in assessing taste functions. To assess the effect of CeA on the taste threshold for NaCl, a conditioned taste aversion (CTA) to a suprathreshold concentration of NaCl (0.1M) in rats with bilateral lesions of CeA or sham lesions was first established. And then, two-bottle choice tests between water and a series of concentrations of NaCl were conducted. The taste threshold for NaCl is defined as the lowest concentration at which there is a reliable difference scores between conditioned and control subjects. Rats with CeA lesions acquired a taste aversion for 0.1M NaCl when it was paired with LiCl and still retained the aversion after the two-bottle choice test. The results of the two-bottle choice test showed that the taste threshold for NaCl was 0.0006M in rats with CeA lesions, whereas in rats with sham lesions the threshold was 0.005M, which was identical to that of normal rats. The conditioned results confirm the claim that CeA is not essential in the profile of conditioned taste aversion. Our findings demonstrate that lesions of the CeA increased the sensitivity to NaCl taste in rats, indicating that the CeA may be involved in encoding the intensity of salty gustation elicited by NaCl.}, } @article {pmid22791465, year = {2013}, author = {Hadamitzky, M and Engler, H and Schedlowski, M}, title = {Learned immunosuppression: extinction, renewal, and the challenge of reconsolidation.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {8}, number = {1}, pages = {180-188}, pmid = {22791465}, issn = {1557-1904}, mesh = {Animals ; Avoidance Learning/physiology ; Behavior/physiology ; Brain/physiology ; Conditioning, Psychological/physiology ; Cyclosporine/pharmacology ; *Extinction, Psychological ; Humans ; Immune Tolerance/drug effects/*physiology ; Immunosuppressive Agents/pharmacology ; Learning/drug effects/*physiology ; Neural Pathways/immunology/physiology ; Rats ; Taste/immunology/physiology ; }, abstract = {Behavioral conditioning of immune responses is one of the most impressive examples for the bidirectional communication among the nervous and immune systems. We established a model of behaviorally conditioned immunosuppression employing a conditioned taste aversion (CTA) paradigm in the rat pairing a novel taste (saccharin) as a conditioned stimulus (CS) with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US). By re-presenting the CS during evocation, rats avoid drinking the saccharin. Concomitantly animals display an immunosuppression reflected by an ex vivo reduction in splenic T cell proliferation as well as diminished interleukin-2 and interferon-γ production and cytokine mRNA expression, mimicking the actual effect of the US (CsA). Due to the fact that the kinetics of this behaviorally conditioned immunosuppression are completely unknown, extinction of the conditioned response on the behavioral level (CTA) as well as in the immune response needs to be elucidated together with the neural processes mediating the extinction process.}, } @article {pmid22789403, year = {2012}, author = {Miranda-Morales, RS and Spear, NE and Nizhnikov, ME and Molina, JC and Abate, P}, title = {Role of mu, delta and kappa opioid receptors in ethanol-reinforced operant responding in infant rats.}, journal = {Behavioural brain research}, volume = {234}, number = {2}, pages = {267-277}, pmid = {22789403}, issn = {1872-7549}, support = {R37 MH035219/MH/NIMH NIH HHS/United States ; AA11960/AA/NIAAA NIH HHS/United States ; R01 AA011960/AA/NIAAA NIH HHS/United States ; AA013098/AA/NIAAA NIH HHS/United States ; R01 MH035219/MH/NIMH NIH HHS/United States ; MH035219/MH/NIMH NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; AA015992/AA/NIAAA NIH HHS/United States ; R01 AA013098/AA/NIAAA NIH HHS/United States ; R01 AA015992/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Analysis of Variance ; Animals ; Animals, Newborn ; Avoidance Learning/drug effects ; Central Nervous System Depressants/*administration & dosage ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage ; Extinction, Psychological/drug effects ; Female ; Male ; Motor Activity/drug effects ; Narcotic Antagonists/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/*metabolism ; Receptors, Opioid, delta/metabolism ; Receptors, Opioid, kappa/metabolism ; Receptors, Opioid, mu/metabolism ; *Reinforcement, Psychology ; Self Administration ; Taste/drug effects ; }, abstract = {We recently observed that naloxone, a non-specific opioid antagonist, attenuated operant responding to ethanol in infant rats. Through the use of an operant conditioning technique, we aimed to analyze the specific participation of mu, delta, and kappa opioid receptors on ethanol reinforcement during the second postnatal week. In Experiment 1, infant rats (PDs 14-17) were trained to obtain 5, 7.5, 10, or 15% ethanol, by operant nose-poking. Experiment 2 tested blood ethanol levels (BELs) attained by operant behavior. In Experiment 3, at PDs 16-18, rats received CTOP (mu antagonist: 0.1 or 1.0 mg/kg), naltrindole (delta antagonist: 1.0 or 5.0 mg/kg) or saline before training. In Experiment 4, rats received nor-binaltorphimine (kappa antagonist: 10.0 or 30.0 mg/kg, a single injection after completion of PD 15 operant training), spiradoline mesylate (kappa agonist: 1.0 or 5.0 mg/kg; at PDs 16-18) or saline (PDs 16-18), before the conditioning. Experiments 5 and 6 assessed possible side effects of opioid drugs in locomotor activity (LA) and conditioned taste aversion (CTA). Ethanol at 7.5 and 10% promoted the highest levels of operant responding. BELs were 12-15 mg/dl. In Experiment 3 naltrindole (dose-response effect) and CTOP (the lowest dose) were effective in decreasing operant responding. Nor-binaltorphimine at 10.0 mg/kg and spiradoline at 5.0 mg/kg also blocked ethanol responding. The effects of opioid drugs on ethanol reinforcement cannot be explained by effects on LA or CTA. Even though particular aspects of each opioid receptor require further testing, a fully functional opioid system seems to be necessary for ethanol reinforcement, during early ontogeny.}, } @article {pmid22776132, year = {2012}, author = {Rachubinski, AL and Maclean, KN and Evans, JR and Bjugstad, KB}, title = {Modulating cognitive deficits and tau accumulation in a mouse model of aging Down syndrome through neonatal implantation of neural progenitor cells.}, journal = {Experimental gerontology}, volume = {47}, number = {9}, pages = {723-733}, doi = {10.1016/j.exger.2012.06.013}, pmid = {22776132}, issn = {1873-6815}, support = {F31 NS060517/NS/NINDS NIH HHS/United States ; TL1 RR025778/RR/NCRR NIH HHS/United States ; R01 HD045224/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Animals, Newborn ; Avoidance Learning/physiology ; Behavior, Animal/physiology ; Brain/*metabolism ; Cells, Cultured ; Cognition Disorders/metabolism/pathology/*prevention & control ; Disease Models, Animal ; Down Syndrome/metabolism/pathology/*psychology ; Hippocampus/metabolism/physiology ; Immunohistochemistry ; Mice ; Neural Stem Cells/*transplantation ; Recognition, Psychology/physiology ; tau Proteins/*metabolism ; }, abstract = {Although Down syndrome (DS) is primarily considered as a pediatric disorder, all DS patients incur Alzheimer's disease (AD)-like pathology and about 60% develop an additional AD-like dementia by 30-40 years of age. Cognitive and neuroanatomical changes in DS are least compromised perinatally, indicating there may be an opportunity to modulate their cognitive and neuroanatomical development during aging, preventing or postponing the onset of AD. To this end, neural progenitor cells (NPC) or saline were implanted into the hippocampus of neonatal DS-modeling (trisomic Ts65Dn) mice and non-DS (disomic Ts65Dn) age-matched mice. Twelve months later, implanted and unimplanted mice were assessed for long-term survival of NPC, for cognitive function, hippocampal cell density, and the presence of extracellular tau accumulation. Implantation of NPC in trisomic mice improved learning and memory as assessed by conditioned taste aversion testing, but not on the novel object recognition task. Trisomic mice given saline control injections improved performance on both cognitive tasks compared to unimplanted trisomic mice. In contrast, disomic mice, implanted with either saline or NPC, were impaired in both tasks. Long-term surviving NPC were found in 7 out of 11 disomic brains and 4 out of 5 trisomic brains, with an average survival rate of 3.1% and 5.9% respectively. Extracellular tau aggregations were elevated in trisomic mice, but implantation with NPC was associated with significantly fewer aggregations. This was also seen in disomic mice. Saline injections significantly elevated tau presence in both karyotypes. Based on these results, we conclude that the modest effects of a few surviving NPC cannot be distinguished from those induced by the implant procedure. However, the changes prompted by neonatal treatment were detectable in aged animals. Collectively, our data are consistent with the hypothesis that neonatal therapeutic intervention in DS has the potential to exert positive lasting effects in the later stages of life but that NPC or the implantation approach may not be the most effective strategy and alternative stem cell types or delivery systems merit further investigation.}, } @article {pmid22737908, year = {2012}, author = {Wu, XW and Xin, B and Zou, JF and Yan, ZW and Qiu, Y and Liu, SY}, title = {[Effect of rotation stimulation on the anesthetic sensitivity of sevoflurane in rats].}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {28}, number = {2}, pages = {114-117}, pmid = {22737908}, issn = {1000-6834}, mesh = {Anesthetics/*pharmacology ; Animals ; Cerebral Cortex/drug effects/metabolism ; *Gravity, Altered ; Hippocampus/drug effects/metabolism ; Male ; Methyl Ethers/*pharmacology ; Neurotransmitter Agents/analysis ; Norepinephrine/analysis ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; *Rotation ; Sevoflurane ; Thalamus/drug effects/metabolism ; gamma-Aminobutyric Acid/analysis ; }, abstract = {OBJECTIVE: To explore the effect of simulated navigation stimulation on the anesthetic sensitivity of sevoflurane in rats, so as to provide basis for rational using sevoflurane during navigation.

METHODS: SD rats were stimulated by Crampton model and the conditioned taste aversion (CTA) was regarded as criterion of motion sickness. (1) 60 rats were randomly divided into control (n = 15) and rotation group (n = 45). The changes of behavior and autonomic activity, sevoflurane concentration achieved sleep and anesthesia states, and the revitalization time were observed in two group rats. (2) 32 rats were randomly divided into control (I), rotation (II), anesthesia (III) and rotation plus anesthesia (IV) group (n = 8). The acetylcholine (Ach), norepinephrine (NE), r-aminobutyric acid (GABA), glutamic acid (Glu) of brain cortex, thalamus and hippocampus were determined respectively in the four group rats.

RESULTS: In control group, the sevoflurane concentration achieved sleep and anesthesia states were 1.74% +/- 0.05% and 3.54% +/- 0.05% respectively, but, those concentrations were 1.51% +/- 0.06% and 3.14% +/- 0.08% in rotation group. There were lower significantly in rotation group than those in control group (P < 0.01). It was a major characteristic that all of the neurotransmitters were reduced significantly in II group, this was even more in brain cortex and thalamus (P < 0.01). In II group, Ach was upward in brain cortex, NE and GABA were reduced in hippocampus obviously. The change tendency of neurotransmitters in IV group was more close to II group, that was, the effect of rotation stimulation was more obvious.

CONCLUSION: The anesthetic sensitivity of sevoflurane could be obvious increased in rats simulated navigation stimulation.}, } @article {pmid22722099, year = {2012}, author = {Shinpo, K and Hirai, Y and Maezawa, H and Totsuka, Y and Funahashi, M}, title = {The role of area postrema neurons expressing H-channels in the induction mechanism of nausea and vomiting.}, journal = {Physiology & behavior}, volume = {107}, number = {1}, pages = {98-103}, doi = {10.1016/j.physbeh.2012.06.002}, pmid = {22722099}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Apomorphine/adverse effects ; Area Postrema/*pathology ; Avoidance Learning/drug effects ; Conditioning, Classical/physiology ; Cyclic Nucleotide-Gated Cation Channels/*metabolism ; Dopamine Agonists/pharmacology ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Feeding Behavior/drug effects ; Food Preferences/drug effects ; Gene Expression Regulation/drug effects/physiology ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Nausea/chemically induced/*pathology ; Neurons/*metabolism ; Potassium Channels/*metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Pyrimidines/adverse effects ; Rats ; Rats, Wistar ; Taste/drug effects/physiology ; Vomiting/chemically induced/*pathology ; }, abstract = {The area postrema is one of the circumventricular organs, lacks a blood-brain barrier, and is well known as the chemoreceptor trigger zone for emesis. Area postrema neurons are sensitive to emetic chemical substances carried in the blood plasma. Our previous study demonstrated the presence of 3 types of neurons characterized by different ion channels expressed in each cell type, but the type or types of area postrema neurons involved in the induction of nausea and/or emesis have remained unclear. To clarify the role of the most populous cells, which express the hyperpolarization-activated cation channel (H-channel), in induction of nausea and/or emesis, we investigated the effects of ZD7288 (an H-channel inhibitor) on apomorphine-induced conditioned taste aversion (CTA) to saccharin and c-Fos expression in the area postrema. We found that ZD7288 inhibited the acquisition of CTA and reduced apomorphine-induced c-Fos expression in the area postrema, indicating the involvement of the cells expressing H-channels in the induction of nausea and/or emesis. Finally, we discuss the role of cells expressing H-channels in the mechanism of nausea and/or vomiting.}, } @article {pmid22719728, year = {2012}, author = {Harrod, SB and Lacy, RT and Morgan, AJ}, title = {Offspring of Prenatal IV Nicotine Exposure Exhibit Increased Sensitivity to the Reinforcing Effects of Methamphetamine.}, journal = {Frontiers in pharmacology}, volume = {3}, number = {}, pages = {116}, pmid = {22719728}, issn = {1663-9812}, support = {R01 DA021287/DA/NIDA NIH HHS/United States ; }, abstract = {Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intravenous (IV) exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection) or prenatal saline (PS) 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1) or METH-induced conditioned taste aversion (CTA; experiment 2) procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/infusion; fixed-ratio 3) and they were tested on varying doses of the reinforcer (0.0005-1.0 mg/kg/infusion). For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc) followed by 14 daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal's curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that IV PN-exposed adult offspring exhibited increased sensitivity to IV METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.}, } @article {pmid22698870, year = {2012}, author = {Pautassi, RM and Nizhnikov, ME and Spear, NE and Molina, JC}, title = {Prenatal ethanol exposure leads to greater ethanol-induced appetitive reinforcement.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {46}, number = {6}, pages = {585-593}, pmid = {22698870}, issn = {1873-6823}, support = {AA011960/AA/NIAAA NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; AA018164/AA/NIAAA NIH HHS/United States ; AA017823/AA/NIAAA NIH HHS/United States ; R21 AA018164/AA/NIAAA NIH HHS/United States ; AA01309/AA/NIAAA NIH HHS/United States ; R01 AA011960/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/*drug effects ; Ethanol/*pharmacology ; Female ; Male ; Motivation ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; Receptors, Opioid, kappa/antagonists & inhibitors ; *Reinforcement, Psychology ; }, abstract = {Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of 'this effect of prenatal ethanol on the sensitivity to ethanol's reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol's aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30-45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance.}, } @article {pmid22687147, year = {2012}, author = {Nyland, JE and Alexander, DN and Liang, NC and Grigson, PS}, title = {Bilateral lesions of the thalamic trigeminal orosensory area dissociate natural from drug reward in contrast paradigms.}, journal = {Behavioral neuroscience}, volume = {126}, number = {4}, pages = {538-550}, pmid = {22687147}, issn = {1939-0084}, support = {R01 DA012473/DA/NIDA NIH HHS/United States ; F31 DA029369/DA/NIDA NIH HHS/United States ; R01 DA009815/DA/NIDA NIH HHS/United States ; DA 012473/DA/NIDA NIH HHS/United States ; F31-DA 029369/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Antimanic Agents/pharmacology ; Association Learning/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Cocaine/administration & dosage ; Conditioning, Classical/drug effects ; Conditioning, Operant/drug effects/physiology ; Dopamine Uptake Inhibitors/administration & dosage ; Eating/drug effects ; Excitatory Amino Acid Agonists/toxicity ; Food Preferences/drug effects ; Ibotenic Acid/toxicity ; Lithium Chloride/pharmacology ; Male ; Morphine/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Reaction Time/drug effects ; *Reward ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; Thalamus/*injuries ; }, abstract = {Substance abuse and addiction are associated with an apparent devaluation of, and inattention to, natural rewards. This consequence of addiction can be modeled using a reward comparison paradigm where rats avoid intake of a palatable taste cue that comes to predict access to a drug of abuse. Evidence suggests rats avoid intake following such pairings, at least in part, because the taste cue pales in comparison to the highly rewarding drug expected in the near future. In accordance, lesions of the gustatory thalamus or cortex eliminate avoidance of a taste cue when paired with either a drug of abuse or a rewarding sucrose solution, but not when paired with the aversive agent, LiCl. The present study used bilateral ibotenic acid lesions to evaluate the role of a neighboring thalamic structure, the trigeminal orosensory area (TOA), in avoidance of a gustatory cue when paired with sucrose (experiment 1), morphine (experiment 2), cocaine (experiment 3), or LiCl (experiment 4). The results show that the TOA lesion disrupts, but does not eliminate avoidance of a taste cue that predicts access to a preferred sucrose solution and leaves intact the development of a LiCl-induced conditioned taste aversion. The lesion does, however, eliminate the suppression of intake of a taste cue when paired with experimenter-administered morphine or cocaine using our standard parameters. As such, this is the first manipulation found to dissociate avoidance of a taste cue when mediated by a sweet or by a drug of abuse.}, } @article {pmid22666196, year = {2012}, author = {Weiss, MS and Di Lorenzo, PM}, title = {Not so fast: taste stimulus coding time in the rat revisited.}, journal = {Frontiers in integrative neuroscience}, volume = {6}, number = {}, pages = {27}, pmid = {22666196}, issn = {1662-5145}, support = {R01 DC006914/DC/NIDCD NIH HHS/United States ; }, abstract = {Behavioral and electrophysiological studies suggest that rats can identify a taste stimulus with a single lick, in <200 ms. However, the conditions under which these conclusions were drawn varied widely across experiments. We designed a series of experiments to assess the effects of the number of licks of a tastant that are available, tastant concentration and prior learning experience on the speed with which a tastant can modify behavior. To accomplish this we tested exemplars of four basic taste qualities (quinine, 0.1 mM; NaCl, 100 mM; saccharin, 4 mM, or sucrose, 100 mM; citric acid, 10 mM) in rats that were conditioned to avoid quinine. Taste stimuli were available for one, two, or three licks on separate days. All tastants were presented in a randomized order interspersed with water rinse licks presented on a variable ratio schedule. A tastant-specific significant increase in the proportion of long pauses in licking following quinine presentation was defined as evidence of "behavioral identification." Rats with aversion training given three licks of all taste stimuli paused significantly more often after quinine by the fourth interlick interval, ~580 ms. Control rats showed no evidence of quinine (0.1 mM) identification. When rats in all conditioning groups were tested with a high concentration of quinine (10 mM), a single lick was sufficient to produce significant pausing after quinine, but not until the fourth interlick interval, i.e., ~580 ms. Testing rats with only two tastants rather than four in a session had no effect on the speed of quinine identification. Present data confirm that a single lick is sufficient for rats to identify a taste stimulus, but that additional licks occur before evidence of identification is apparent. Furthermore, learning, tastant concentration and motivation to drink can all modify the speed of behavioral identification.}, } @article {pmid22618163, year = {2012}, author = {Gyekis, JP and Dingman, MA and Revitsky, AR and Bryant, BP and Vandenbergh, DJ and Frank, ME and Blizard, DA}, title = {Gustatory, trigeminal, and olfactory aspects of nicotine intake in three mouse strains.}, journal = {Behavior genetics}, volume = {42}, number = {5}, pages = {820-829}, doi = {10.1007/s10519-012-9546-x}, pmid = {22618163}, issn = {1573-3297}, support = {R01 DC004099/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Operant/drug effects ; Data Interpretation, Statistical ; Generalization, Psychological ; Male ; Memory/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Nicotine/*pharmacology ; Nicotinic Agonists/*pharmacology ; Receptors, Nicotinic/genetics/physiology ; Smell/*genetics/physiology ; Taste/*genetics/physiology ; Trigeminal Nerve/*physiology ; }, abstract = {Studies of nicotine consumption in rodents often intend to investigate nicotine's post-absorptive effects, yet little is known about the pre-absorptive sensory experience of nicotine drinking, including gustatory, trigeminal, and olfactory influences. We conditioned taste aversion (CTA) to nicotine in males of 3 inbred mouse strains: C57BL/6J, DBA/2J, and 129X1/SvJ by repeatedly pairing 150 μg/ml nicotine drinking with lithium chloride injections. Generalization to a variety of bitter, sour, sweet, salty, and irritant solutions and to nicotine odor was then examined. Nicotine CTA generalized to the bitter stimulus quinine hydrochloride and the chemosensory irritant spilanthol in all strains. It also showed strain specificity, generalizing to hydrogen peroxide (an activator of TRPA1) in C57BL/6J mice and to the olfactory cue of nicotine in DBA/2J mice. These behavioral assays demonstrate that the sensory properties of nicotine are complex and include multiple gustatory, irritant, and olfactory components. How these qualities combine at the level of perception remains to be assessed, but sensory factors clearly exert an important influence on nicotine ingestion and their contribution to net intake of nicotine should not be neglected in animal or human studies.}, } @article {pmid22592597, year = {2013}, author = {Acevedo, MB and Nizhnikov, ME and Spear, NE and Molina, JC and Pautassi, RM}, title = {Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion.}, journal = {Developmental psychobiology}, volume = {55}, number = {4}, pages = {429-442}, pmid = {22592597}, issn = {1098-2302}, support = {R01 AA011960/AA/NIAAA NIH HHS/United States ; AA011960/AA/NIAAA NIH HHS/United States ; AA013098/AA/NIAAA NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; R21 AA018164/AA/NIAAA NIH HHS/United States ; R01 AA015992/AA/NIAAA NIH HHS/United States ; AA018164/AA/NIAAA NIH HHS/United States ; AA015992/AA/NIAAA NIH HHS/United States ; AA017823/AA/NIAAA NIH HHS/United States ; R01 AA013098/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Behavior, Animal/*drug effects ; Conditioning, Classical/*drug effects ; Ethanol/administration & dosage/*pharmacology ; Female ; Male ; Motor Activity/*drug effects ; Neuropsychological Tests ; Rats ; Rats, Wistar ; *Reinforcement, Psychology ; Taste/drug effects ; }, abstract = {Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol's motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference (CPP) by ethanol at this age. The present study assessed age-related differences in ethanol's motor stimulating effects and analyzed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol's aversive reinforcement, but they also exhibited CPP. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA.}, } @article {pmid22590456, year = {2012}, author = {Gautam, SH and Rebello, MR and Verhagen, JV}, title = {Taste quality and intensity of 100 stimuli as reported by rats: the taste-location association task.}, journal = {Frontiers in behavioral neuroscience}, volume = {6}, number = {}, pages = {19}, pmid = {22590456}, issn = {1662-5153}, support = {R01 DC009994/DC/NIDCD NIH HHS/United States ; R01 DC011286/DC/NIDCD NIH HHS/United States ; }, abstract = {The interpretation of neural activity related to sensory stimulation requires an understanding of the subject's perception of the stimulation. Previous methods used to evaluate the perception of chemosensory stimuli by rodents have distinct limitations. We developed a novel behavioral paradigm, the taste-location association task, to complement these methods. First we tested if rats are able to learn associations between five basic taste stimuli and their spatial locations. This spatial task was based on four prototypical tastants and water. All four rats trained to perform the task reached levels of performance well above chance. Control trials demonstrated that the rats used only taste cues. Further, the learned stimulus set was resistant to interference, allowing for generalization experiments performed subsequently. We tested the rats' gustatory generalizations of 100 tastants to the five trained stimuli, both regarding their taste qualities as well as intensity ratings. The taste profiles generated by these experiments contribute to the understanding of how perception of the specific taste stimuli relate to the perception of the five basic taste qualities in intact behaving rats. In this large taste space we found that intensity plays a major role. Furthermore, umami stimuli were not reported as being similar to other basic tastants. Our new paradigm enables neurophysiological studies of taste-based learning and memory in awake, freely moving animals.}, } @article {pmid22589279, year = {2012}, author = {Guzmán-Ramos, K and Osorio-Gómez, D and Moreno-Castilla, P and Bermúdez-Rattoni, F}, title = {Post-acquisition release of glutamate and norepinephrine in the amygdala is involved in taste-aversion memory consolidation.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {19}, number = {6}, pages = {231-238}, doi = {10.1101/lm.024703.111}, pmid = {22589279}, issn = {1549-5485}, mesh = {Adrenergic beta-Antagonists/pharmacology ; Amygdala/drug effects/*metabolism ; Analysis of Variance ; Animals ; Area Under Curve ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Dopamine/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/*metabolism ; Lithium Chloride/administration & dosage ; Male ; Memory/*physiology ; Microdialysis ; Norepinephrine/*metabolism ; Propranolol/pharmacology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; *Taste/drug effects ; Valine/analogs & derivatives/pharmacology ; }, abstract = {Amygdala activity mediates the acquisition and consolidation of emotional experiences; we have recently shown that post-acquisition reactivation of this structure is necessary for the long-term storage of conditioned taste aversion (CTA). However, the specific neurotransmitters involved in such reactivation are not known. The aim of the present study was to investigate extracellular changes of glutamate, norepinephrine, and dopamine within the rat amygdala using in vivo microdialysis during the acquisition and 1-h post-acquisition of CTA paradigm. Microdialysis monitoring showed a significant norepinephrine increase related to novel taste exposure and a glutamate increase after gastric malaise induction by i.p. LiCl administration. Interestingly, we found a spontaneous concomitant increase of glutamate and norepinephrine, but not dopamine, 45 min after conditioning, suggesting the presence of aversive learning-dependent post-acquisition signals in the amygdala. These signals seem to be involved in CTA consolidation process, since post-trial blockade of N-methyl-D-aspartate or β-adrenergic receptors impaired long- but not short-term memory. These data suggest that CTA long-term storage involves post-acquisition release of glutamate and norepinephrine in the amygdala.}, } @article {pmid22586453, year = {2012}, author = {Maroun, M and Kavushansky, A and Holmes, A and Wellman, C and Motanis, H}, title = {Enhanced extinction of aversive memories by high-frequency stimulation of the rat infralimbic cortex.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e35853}, pmid = {22586453}, issn = {1932-6203}, mesh = {Animals ; Brain Mapping ; Conditioning, Classical/physiology ; Conditioning, Psychological/*physiology ; Electric Stimulation ; Extinction, Psychological ; Fear/*psychology ; Male ; Memory/*physiology ; Prefrontal Cortex/*physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; }, abstract = {Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including the infralimbic cortex (IL), immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS) of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA). IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion.}, } @article {pmid22579912, year = {2012}, author = {Serafine, KM and Briscione, MA and Rice, KC and Riley, AL}, title = {Dopamine mediates cocaine-induced conditioned taste aversions as demonstrated with cross-drug preexposure to GBR 12909.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {102}, number = {2}, pages = {269-274}, pmid = {22579912}, issn = {1873-5177}, support = {Z99 DA999999//Intramural NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning ; Cocaine/*pharmacology ; *Conditioning, Classical ; Dopamine/*pharmacology ; Dopamine Uptake Inhibitors/*pharmacology ; Male ; Piperazines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. It has been suggested that its inhibitory effects at one of the monoamine transporters may be mediating this suppression. Using the cross-drug preexposure preparation, the present series of studies examined a possible role of dopamine (DA) in this effect. Male Sprague-Dawley rats were exposed to cocaine (18 mg/kg; Experiment 1) or the selective DA transporter (DAT) inhibitor GBR 12909 (50 mg/kg; Experiment 2) prior to the pairing of a novel saccharin solution with injections of GBR 12909 (32 mg/kg), cocaine (18 mg/kg) or vehicle in a conditioned taste aversion (CTA) procedure. Preexposure to cocaine attenuated aversions induced by itself but not aversions induced by GBR 12909 (Experiment 1). Conversely, preexposure to GBR 12909 attenuated aversions induced by itself and cocaine (Experiment 2). This asymmetry suggests that cocaine and GBR 12909 induce CTAs via similar, but non-identical, mechanisms. These data are discussed in the context of previous work demonstrating roles for dopamine, norepinephrine and serotonin in cocaine-induced CTAs.}, } @article {pmid22529783, year = {2012}, author = {Núñez-Jaramillo, L and Rangel-Hernández, JA and Burgueño-Zúñiga, B and Miranda, MI}, title = {Activation of nucleus accumbens NMDA receptors differentially affects appetitive or aversive taste learning and memory.}, journal = {Frontiers in behavioral neuroscience}, volume = {6}, number = {}, pages = {13}, pmid = {22529783}, issn = {1662-5153}, abstract = {Taste memory depends on motivational and post-ingestional consequences; thus, it can be aversive (e.g., conditioned taste aversion, CTA) if a novel, palatable taste is paired with visceral malaise, or it can be appetitive if no intoxication appears after novel taste consumption, and a taste preference is developed.The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli, and recent findings suggest that reward and aversion are differentially encoded by the activity of NAc neurons. The present study examined whether the requirement for N-methyl-D-aspartate (NMDA) receptors in the NAc core during rewarding appetitive taste learning differs from that during aversive taste conditioning, as well as during retrieval of appetitive vs. aversive taste memory, using the taste preference or CTA model, respectively. Bilateral infusions of NMDA (1 μg/μl, 0.5 μl) into the NAc core were performed before acquisition or before retrieval of taste preference or CTA. Activation of NMDA receptors before taste preference training or CTA acquisition did not alter memory formation. Furthermore, NMDA injections before aversive taste retrieval had no effect on taste memory; however, 24 h later, CTA extinction was significantly delayed. Also, NMDA injections, made before familiar appetitive memory retrieval, interrupted the development of taste preference and produced a preference delay 24 h later. These results suggest that memory formation for a novel taste produces neurochemical changes in the NAc core that have differential requirements for NMDA receptors during retrieval of appetitive or aversive memory.}, } @article {pmid22509372, year = {2012}, author = {Chaperon, F and Fendt, M and Kelly, PH and Lingenhoehl, K and Mosbacher, J and Olpe, HR and Schmid, P and Sturchler, C and McAllister, KH and van der Putten, PH and Gee, CE}, title = {Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.}, journal = {PloS one}, volume = {7}, number = {4}, pages = {e34963}, pmid = {22509372}, issn = {1932-6203}, mesh = {Amygdala/metabolism/*physiology ; Animals ; Bombesin/analogs & derivatives/chemistry/pharmacology ; Conditioning, Classical/physiology ; Fear/*physiology ; Gastrin-Releasing Peptide/antagonists & inhibitors/genetics/*metabolism ; Gene Expression Regulation ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism/physiology ; Peptide Fragments/chemistry ; Pyramidal Cells/metabolism/physiology ; Receptors, Bombesin/antagonists & inhibitors/genetics/*metabolism ; Signal Transduction ; }, abstract = {Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe(6), Leu-NHEt(13), des-Met(14))-Bombesin (6-14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders.}, } @article {pmid22465170, year = {2012}, author = {Revillo, DA and Fernandez, G and Castello, S and Paglini, MG and Arias, C}, title = {Odor-avoidance or odor-preference induced by amphetamine in the infant rat depending on the dose and testing modality.}, journal = {Behavioural brain research}, volume = {231}, number = {1}, pages = {201-207}, doi = {10.1016/j.bbr.2012.03.018}, pmid = {22465170}, issn = {1872-7549}, mesh = {Amphetamine/*pharmacology ; Animals ; Animals, Newborn ; Association Learning/*drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Memory/drug effects ; Motor Activity/drug effects ; Odorants ; Rats ; Rats, Wistar ; }, abstract = {By the second postnatal week of life infant rats can acquire taste avoidance induced by amphetamine. Psychostimulant drugs supports appetitive and aversive learning in adult rats. Their appetitive effects are more likely to become associated with contextual cues, while the aversive ones have been consistently found in taste aversion learning. To explain this paradox, it has been proposed that rats would avoid a taste that predicts a change in their homeostasis because this species cannot vomit. In this study we assessed the motivational properties of amphetamine in preweanling rats by means of an odor conditioning preparation, which enables the analysis of the hedonic value of the memory by means of a consumption test or in terms of locomotor approach to the odor. Results indicate that regardless of the amphetamine dose (1 or 5 mg/kg), when animals were evaluated in the intake test, subjects avoided the odor. However, the outcome in the locomotor avoidance test varied as a function of the amphetamine dose. Rats trained with the low dose (1 mg/kg) showed odor preference, while the highest amphetamine dose (5 mg/kg) induced odor avoidance. When LiCl was employed as an unconditioned stimulus (US), rats showed avoidance in the intake and locomotor activity tests. These data indicate that amphetamine, like other drugs of abuse, supports appetitive conditioning in preweanling rats. Interestingly, infant rats expressed conditioned odor avoidance or preference depending on the dose and testing modality. Results were discussed considering current theories of avoidance learning induced by rewarding drugs.}, } @article {pmid22432774, year = {2011}, author = {Gupta, V and Bala, M and Prasad, J and Singh, S and Gupta, M}, title = {Leaves of Hippophae rhamnoides prevent taste aversion in gamma-irradiated rats.}, journal = {Journal of dietary supplements}, volume = {8}, number = {4}, pages = {355-368}, doi = {10.3109/19390211.2011.621929}, pmid = {22432774}, issn = {1939-022X}, mesh = {Animals ; Antiemetics/pharmacology ; Antioxidants/*pharmacology ; Behavior, Animal/*drug effects/radiation effects ; Conditioning, Classical/drug effects ; Corticosterone/blood ; Dietary Supplements ; Food Preferences ; Gamma Rays ; *Hippophae ; Humans ; Jejunum/metabolism ; Male ; Nausea ; Ondansetron/pharmacology ; Oxidative Stress/drug effects ; *Phytotherapy ; Plant Extracts/pharmacology/therapeutic use ; Plant Leaves ; Radiation Injuries, Experimental/*drug therapy ; Radiation-Protective Agents/pharmacology/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Serotonin/metabolism ; Taste/*drug effects/radiation effects ; Vomiting ; }, abstract = {Hippophae rhamnoides (Sea buckthorn), a traditionally known plant for nutritional and therapeutic values, is under active investigation for radioprotective properties. This study investigated effects of aqueous leaf extract from H. rhamnoides on (60)Co-γ-radiation induced changes in behavior, oxidative stress and serotonin levels in jejunum and plasma of rats. Conditioned taste aversion (CTA) was chosen as the assay to record behavioral changes and was assessed in terms of saccharine preference ratio (SPR). Whole body (60)Co-γ-irradiation (2 Gy) induced significant nonrecoverable CTA (25.6 ± 3.6% SPR, t(6) = 3.499, p < .05) and loss in body weight (b.w.). One time treatment with leaf extract before irradiation, countered radiation induced CTA and loss in body weight. The 12 mg/kg b.w. concentration of leaf extract caused complete extinction of CTA [100.3 ± 6.4% SPR, t(6) = 5.879, p < .01] after day 3 and the effect was significantly higher than positive control, Ondansetrone (70.0 ± 8.9% SPR). Treatment with leaf extract before irradiation significantly countered radiation induced (1) decrease in antioxidant protection, (2) increase in levels of corticosterone (CS) in plasma, (3) increase in levels of serotonin in jejunum and plasma. Present investigation demonstrated that H. rhamnoides leaf extract prevented behavioral changes induced at clinical radiation doses. Hippophae leaves are nontoxic and are being consumed as tea and other beverages. CTA in rats is a considered parallel process to nausea and vomiting in human beings. These findings, put together, suggest that dietary supplements from Hippophae leaves could be developed for preventing behavioral changes in subjects exposed to radiation.}, } @article {pmid22428901, year = {2012}, author = {Lin, JY and Arthurs, J and Amodeo, LR and Reilly, S}, title = {Reduced palatability in drug-induced taste aversion: I. Variations in the initial value of the conditioned stimulus.}, journal = {Behavioral neuroscience}, volume = {126}, number = {3}, pages = {423-432}, pmid = {22428901}, issn = {1939-0084}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R01 DC006456-01/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Amphetamine/*administration & dosage ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Food Preferences/drug effects/physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/*physiology ; }, abstract = {Like illness-inducing agents (e.g., lithium chloride), drugs of abuse also suppress intake of a taste solution. To explore the nature of this drug-induced intake reduction, in the current study three aqueous stimuli with different initial values served as the conditioned stimuli (CSs) that were paired with a standard dose of amphetamine in a voluntary intake procedure and lick patterns were analyzed. Consistent with earlier studies, amphetamine significantly reduced intake of all three CSs (quinine, sodium chloride, and orange odor). In contrast to studies that analyze orofacial responses, we found that lick cluster size was significantly lowered by amphetamine, indicating that the psychoactive drug induced a conditioned reduction in taste palatability.}, } @article {pmid22422670, year = {2012}, author = {Schier, LA and Davidson, TL and Powley, TL}, title = {Rapid stimulus-bound suppression of intake in response to an intraduodenal nonnutritive sweetener after training with nutritive sugars predicting malaise.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {302}, number = {11}, pages = {R1351-63}, pmid = {22422670}, issn = {1522-1490}, support = {R37 DK027627/DK/NIDDK NIH HHS/United States ; P01-HD-05211/HD/NICHD NIH HHS/United States ; R01 DK-027627/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*drug effects/physiology ; Carbohydrates/*pharmacology ; Feeding Behavior/*drug effects/physiology ; Intestines/drug effects/physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Stomach/drug effects/physiology ; Sucrose/pharmacology ; Sweetening Agents/*pharmacology ; Taste/*physiology ; }, abstract = {In a previous report (Schier et al., Am J Physiol Regul Integr Comp Physiol 301: R1557-R1568, 2011), we demonstrated with a new behavioral procedure that rats exhibit stimulus-bound suppression of intake in response to an intraduodenal (ID) bitter tastant predicting subsequent malaise. With the use of the same modified taste aversion procedure, the present experiments evaluated whether the sweet taste properties of ID stimuli are likewise detected and encoded. Thirsty rats licked at sipper spouts for hypotonic NaCl for 30 min and received brief (first 6 min) yoked ID infusions of either the same NaCl or an isomolar lithium chloride (LiCl) solution in each session. An intestinal taste cue was mixed directly into the LiCl infusate for aversion training. Results showed that rats failed to detect intestinal sweet taste alone (20 mM Sucralose) but clearly suppressed licking in response to a nutritive sweet taste stimulus (234 mM sucrose) in the intestine that had been repeatedly paired with LiCl. Rats trained with ID sucrose in LiCl subsequently generalized responding to ID Sucralose alone at test. Replicating this, rats trained with ID Sucralose in compound with 80 mM Polycose rapidly suppressed licking to the 20 mM Sucralose alone in a later test. Furthermore, ID sweet taste signaling did not support the rapid negative feedback of sucrose or Polycose on intake when their digestion and transport were blocked. Together, these results suggest that other signaling pathways and/or transporters engaged by caloric carbohydrate stimuli potentiate detection of sweet taste signals in the intestine.}, } @article {pmid22409975, year = {2012}, author = {Stover, KR and Brown, RE}, title = {Age-related changes in visual acuity, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease.}, journal = {Behavioural brain research}, volume = {231}, number = {1}, pages = {75-85}, doi = {10.1016/j.bbr.2012.02.044}, pmid = {22409975}, issn = {1872-7549}, mesh = {Aging/*physiology/psychology ; Alzheimer Disease/genetics/*physiopathology/psychology ; Amyloid beta-Protein Precursor/genetics ; Animals ; Avoidance Learning/physiology ; Conditioning, Psychological/*physiology ; Disease Models, Animal ; Female ; Male ; Maze Learning/*physiology ; Memory/*physiology ; Mice ; Mice, Transgenic ; Presenilin-1/genetics ; Visual Acuity/*physiology ; }, abstract = {Mouse models of Alzheimer's disease (AD) are often tested for learning and memory deficits using visuo-spatial tasks such as the Morris water maze. Performance on these tasks is dependent on vision and the APPswe/PS1dE9 mouse model has amyloid beta plaques in their retinas which might influence their performance in these tasks. In a visual learning task, old (20-26 months) transgenic mice and their wildtype littermates of both sexes had poorer visual ability than young (5-8 months) mice and old transgenic mice had poorer visual acuity than old wildtype mice. Old transgenic mice also had deficits in visuo-spatial learning and memory on the Morris water maze. The transgenic mice had no deficits in the conditioned odour preference or conditioned taste aversion memory tests at any age. These results indicate that the old APPswe/PS1dE9 mice and their wildtype littermates both have a deficit in their visual ability and that visually dependent measures alone should not be used to assess learning and memory in this strain.}, } @article {pmid22409482, year = {2012}, author = {Arthurs, J and Lin, JY and Amodeo, LR and Reilly, S}, title = {Reduced palatability in drug-induced taste aversion: II. Aversive and rewarding unconditioned stimuli.}, journal = {Behavioral neuroscience}, volume = {126}, number = {3}, pages = {433-444}, pmid = {22409482}, issn = {1939-0084}, support = {R01 DC006456/DC/NIDCD NIH HHS/United States ; R01 DC006456-01/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Amphetamine/*administration & dosage ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Food Preferences/drug effects/physiology ; Male ; Morphine/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; *Reward ; Saccharin/administration & dosage ; Sucrose/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {Drugs of abuse are known to reduce intake of a taste conditioned stimulus (conditional stimulus, CS), a behavioral response sometimes seen as paradoxical because the same drugs also serve as rewards in other behavioral procedures. In the present study we compared patterns of intake and palatability (assessed using microstructural analysis of licking) for a standard saccharin CS paired with the following: lithium chloride, morphine, amphetamine, or sucrose. We found that morphine and amphetamine, like lithium-induced illness, each suppressed CS intake and caused a reduction in saccharin palatability. Sucrose, a rewarding stimulus, did not reduce the palatability of the saccharin CS. We interpret these finds as evidence that drugs of abuse induce conditioned taste aversions.}, } @article {pmid22405477, year = {2012}, author = {Blednov, YA and Mayfield, RD and Belknap, J and Harris, RA}, title = {Behavioral actions of alcohol: phenotypic relations from multivariate analysis of mutant mouse data.}, journal = {Genes, brain, and behavior}, volume = {11}, number = {4}, pages = {424-435}, pmid = {22405477}, issn = {1601-183X}, support = {R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399-30/AA/NIAAA NIH HHS/United States ; R01 AA006399-29/AA/NIAAA NIH HHS/United States ; U01 AA013520-10/AA/NIAAA NIH HHS/United States ; R01 AA012404/AA/NIAAA NIH HHS/United States ; AA13520/AA/NIAAA NIH HHS/United States ; AA06399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Behavior, Animal/drug effects/*physiology ; Choice Behavior/drug effects/*physiology ; Ethanol/*pharmacology ; Genotype ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Phenotype ; Taste/genetics ; }, abstract = {Behavioral studies on genetically diverse mice have proven powerful for determining relationships between phenotypes and have been widely used in alcohol research. Most of these studies rely on naturally occurring genetic polymorphisms among inbred strains and selected lines. Another approach is to introduce variation by engineering single-gene mutations in mice. We have tested 37 different mutant mice and their wild-type controls for a variety (31) of behaviors and have mined this data set by K-means clustering and analysis of correlations. We found a correlation between a stress-related response (activity in a novel environment) and alcohol consumption and preference for saccharin. We confirmed several relationships detected in earlier genetic studies, including positive correlation of alcohol consumption with saccharin consumption and negative correlations with conditioned taste aversion and alcohol withdrawal severity. Introduction of single-gene mutations either eliminated or greatly diminished these correlations. The three tests of alcohol consumption used (continuous two-bottle choice and two limited access tests: drinking in the dark and sustained high alcohol consumption) share a relationship with saccharin consumption, but differ from each other in their correlation networks. We suggest that alcohol consumption is controlled by multiple physiological systems where single-gene mutations can disrupt the networks of such systems.}, } @article {pmid22366775, year = {2012}, author = {Gildish, I and Manor, D and David, O and Sharma, V and Williams, D and Agarwala, U and Wang, X and Kenney, JW and Proud, CG and Rosenblum, K}, title = {Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {19}, number = {3}, pages = {116-125}, pmid = {22366775}, issn = {1549-5485}, support = {BB/I004483/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Association Learning/*physiology ; Behavior, Animal/*physiology ; Brain Chemistry/*genetics/physiology ; Conditioning, Psychological/physiology ; Elongation Factor 2 Kinase/*deficiency/*genetics/metabolism ; Magnetic Resonance Imaging/methods ; Manganese ; Memory/physiology ; Mice ; Phosphorylation/genetics ; Taste Perception/*genetics/physiology ; }, abstract = {Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment.}, } @article {pmid22334194, year = {2013}, author = {Wilson-Pérez, HE and Chambers, AP and Sandoval, DA and Stefater, MA and Woods, SC and Benoit, SC and Seeley, RJ}, title = {The effect of vertical sleeve gastrectomy on food choice in rats.}, journal = {International journal of obesity (2005)}, volume = {37}, number = {2}, pages = {288-295}, pmid = {22334194}, issn = {1476-5497}, support = {DK82480/DK/NIDDK NIH HHS/United States ; T32 HD007463/HD/NICHD NIH HHS/United States ; T32 HD07463/HD/NICHD NIH HHS/United States ; DK54890/DK/NIDDK NIH HHS/United States ; R01 DK093848/DK/NIDDK NIH HHS/United States ; R01 DK082480/DK/NIDDK NIH HHS/United States ; R01 DK054890/DK/NIDDK NIH HHS/United States ; R01 DK054890-11/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Body Weight ; Choice Behavior ; Dietary Fats/*metabolism ; Energy Metabolism ; *Food Preferences ; *Gastric Bypass ; *Gastroplasty ; Male ; Obesity/*surgery ; Physical Conditioning, Animal ; Rats ; Rats, Long-Evans ; Reward ; Taste ; }, abstract = {OBJECTIVE: Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y gastric bypass (RYGB), humans and rodents select or prefer foods that are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, vertical sleeve gastrectomy (VSG), causes a similar reduction of fat intake/preference.

RESEARCH DESIGN AND METHODS: Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio (PR) and conditioned taste aversion paradigms, we further asked whether surgically induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG- and RYGB-operated rats.

RESULTS: VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a PR schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not.

CONCLUSIONS: VSG and RYGB, two anatomically distinct bariatric procedures, produce similar changes in food choice.}, } @article {pmid22319481, year = {2011}, author = {Gal-Ben-Ari, S and Rosenblum, K}, title = {Molecular mechanisms underlying memory consolidation of taste information in the cortex.}, journal = {Frontiers in behavioral neuroscience}, volume = {5}, number = {}, pages = {87}, pmid = {22319481}, issn = {1662-5153}, abstract = {The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex (GC) specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste-memory consolidation in the GC. Specifically, the roles of neurotransmitters, neuromodulators, immediate early genes, and translation regulation are addressed.}, } @article {pmid22310470, year = {2013}, author = {Liang, NC and Bello, NT and Moran, TH}, title = {Additive feeding inhibitory and aversive effects of naltrexone and exendin-4 combinations.}, journal = {International journal of obesity (2005)}, volume = {37}, number = {2}, pages = {272-278}, pmid = {22310470}, issn = {1476-5497}, support = {R01 DK019302/DK/NIDDK NIH HHS/United States ; R01 DK019302-35A1/DK/NIDDK NIH HHS/United States ; R56 DK019302/DK/NIDDK NIH HHS/United States ; DK19302/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite Depressants/*pharmacology ; Body Weight/drug effects ; Drug Interactions ; Drug Therapy, Combination ; Eating/*drug effects ; Exenatide ; Hypoglycemic Agents/*pharmacology ; Male ; Naltrexone/*pharmacology ; Obesity/*drug therapy/prevention & control ; Peptides/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; Venoms/*pharmacology ; Weight Loss/drug effects ; }, abstract = {OBJECTIVE: One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve weight loss with fewer adverse effects. The purpose of this study was to determine whether the combination of naltrexone (Nal), an opioid antagonist acting on the reward system, and exendin-4 (Ex-4), a glucagon-like peptide 1 agonist acting on satiety signaling, would produce larger reductions in food intake than either alone in rats. Because the anorectic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined.

METHODS: In Experiment 1, the acute anorectic effects of Nal (0.32-3.2 mg kg(-1); intraperitoneally (i.p.)) and Ex-4 (1-10 μg kg(-1); i.p.) were assessed alone or in combination. Combinational doses were further investigated by the repeated daily administration of 1 mg kg(-1) Nal+3.2 μg kg(-1) Ex-4 for 4 days. In Experiment 2, both compounds alone or in combination were used as unconditioned stimuli in a series of CTA tests.

RESULTS: Nal and Ex-4, alone or in combination, suppressed food intake in a dose-dependent manner, and the interaction on food intake between Nal and Ex-4 was additive. In the CTA paradigm, Nal (1 mg kg(-1)) alone did not support acquisition, whereas a CTA was evident with doses of Ex-4 (1 or 3.2 μg kg(-1)). Combinations of Nal and Ex-4 also resulted in a more rapid and robust acquisition of a CTA.

CONCLUSION: Given that the Nal and Ex-4 combination produces additive effects on not only food intake reduction but also food aversion learning, this specific drug combination does not have the benefit of minimizing the adverse effects associated with each individual drug. These data suggest that it is necessary to evaluate both the positive and adverse effects at early stages of combinational drug development.}, } @article {pmid22309159, year = {2012}, author = {Lopez, MF and Griffin, WC and Melendez, RI and Becker, HC}, title = {Repeated cycles of chronic intermittent ethanol exposure leads to the development of tolerance to aversive effects of ethanol in C57BL/6J mice.}, journal = {Alcoholism, clinical and experimental research}, volume = {36}, number = {7}, pages = {1180-1187}, pmid = {22309159}, issn = {1530-0277}, support = {P50 AA010761/AA/NIAAA NIH HHS/United States ; R01 AA018036/AA/NIAAA NIH HHS/United States ; P50 AA10716/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/physiopathology/*psychology/*trends ; Animals ; Avoidance Learning/*drug effects/physiology ; *Drug Tolerance/physiology ; Ethanol/*administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Time Factors ; }, abstract = {BACKGROUND: Repeated cycles of chronic intermittent ethanol (CIE) exposure lead to increased voluntary ethanol (EtOH) intake in C57BL/6J mice. This study evaluates the development of tolerance to EtOH's aversive effects in CIE exposure.

METHODS: Adult male C57BL/6J mice were trained to drink 15% EtOH (vs. water) in a limited access procedure and then exposed to CIE (EtOH mice) or air (control [CTL] mice) for 5 cycles alternating with weekly access to EtOH drinking. Following the 4th CIE cycle, the aversive effects of EtOH were evaluated using a conditioned taste aversion (CTA) paradigm with 1% saccharin as the conditioned stimulus. Several doses of EtOH (0, 1, 2, and 3 g/kg) and LiCl (0.4 M, 0.02 ml/g) served as unconditioned stimuli. Finally, mice underwent a 5th CIE cycle to measure blood and brain concentrations following a 2 g/kg EtOH dose.

RESULTS: CIE exposure increased EtOH drinking in EtOH mice while drinking in CTL mice remained stable. The lowest EtOH dose (1 g/kg) did not induce CTA in either group, but the highest dose (3 g/kg) produced CTA in both groups (49% reduction for CTL vs. 25% reduction for EtOH) although the group differences were not statistically significant. However, the 2 g/kg EtOH dose induced a significant aversion in CTL mice (27% reduction) but not in EtOH mice (20% increase), indicating tolerance to EtOH's aversive effects. LiCl caused a similar aversion in CTL and EtOH mice (50% reduction). Finally, blood and brain ethanol concentrations were not different between CTL and EtOH mice following a 2 g/kg EtOH dose.

CONCLUSIONS: The data indicate that CIE exposure produces tolerance to the aversive effects of 2 g/kg EtOH. This effect does not appear to be related to a learning deficit or altered EtOH pharmacokinetics. These data support the notion that tolerance to EtOH's aversive effects may contribute to excessive EtOH drinking in EtOH-dependent mice.}, } @article {pmid22297300, year = {2012}, author = {Serrano, A and Pavón, FJ and Suarez, J and Rivera, P and Vida, M and Bermúdez-Silva, FJ and Alonso, M and Martínez, A and López-Ogalla, J and Alonso-Gascón, M and Santamaría, G and Romero-Cuevas, M and Pérez-Valero, V and Baixeras, E and Rodríguez de Fonseca, F}, title = {Adiponectin promoter activator NP-1 reduces body weight and hepatic steatosis in high-fat diet-fed animals.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {302}, number = {7}, pages = {E817-30}, doi = {10.1152/ajpendo.00468.2011}, pmid = {22297300}, issn = {1522-1555}, mesh = {Adiponectin/blood/*metabolism ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects ; Blotting, Western ; Body Weight/*drug effects ; Cell Line ; Diet, High-Fat ; Dietary Fats/*adverse effects ; Eating/drug effects ; Fatty Liver/*drug therapy ; Glucose Tolerance Test ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Male ; Myoblasts/metabolism ; Non-alcoholic Fatty Liver Disease ; RNA/biosynthesis/genetics/isolation & purification ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Taste/drug effects ; Thiazoles/*pharmacology ; Weight Gain/drug effects ; }, abstract = {Enhancement of adiponectin level has been shown to have beneficial effects, including antiobesity, antidiabetic, and hepatoprotective effects. This evidence supports the therapeutic utility of adiponectin in complicated obesity. The present study characterized the in vivo effects of sustained adiponectin release by NP-1, a new class of thiazol derivative that increases adiponectin levels. Acute administration of NP-1 reduced feeding, increased plasma adiponectin, and improved insulin sensitivity without inducing malaise, as revealed by conditioned taste aversion studies. Short-term (7 days) treatment with NP-1 also reduced feeding and body weight gain and increased phosphorylation of AMPK in muscle, a main intracellular effector of adiponectin. NP-1 was also evaluated in diet-induced obesity, and adult male Wistar rats were fed two different types of diet: a standard high-carbohydrate/low-fat diet (SD) and a high-fat diet (HFD). Once obesity was established, animals were treated daily with NP-1 (5 mg/kg) for 14 consecutive days. Chronic NP-1 induced body weight loss and reduction of food intake and resulted in both a marked decrease in liver steatosis and an improvement of biochemical indexes of liver damage in HFD-fed rats. However, a marked induction of tolerance in adiponectin gene transcription and release was observed after chronic NP-1 with respect to the acute actions of this drug. The present results support the role of adiponectin signaling in diet-induced obesity and set in place a potential use of compounds able to induce adiponectin release for the treatment of obesity and nonalcoholic fatty liver, with the limits imposed by the induction of pharmacological tolerance.}, } @article {pmid22293826, year = {2012}, author = {Morani, AS and Schenk, S and Prisinzano, TE and Kivell, BM}, title = {A single injection of a novel κ opioid receptor agonist salvinorin A attenuates the expression of cocaine-induced behavioral sensitization in rats.}, journal = {Behavioural pharmacology}, volume = {23}, number = {2}, pages = {162-170}, pmid = {22293826}, issn = {1473-5849}, support = {R01 DA018151/DA/NIDA NIH HHS/United States ; R01 DA018151-01A2/DA/NIDA NIH HHS/United States ; DA018151/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Central Nervous System Sensitization/*drug effects ; Cocaine/*antagonists & inhibitors/pharmacology ; Conditioning, Psychological/drug effects ; Diterpenes, Clerodane/*pharmacology ; Immobility Response, Tonic/*drug effects ; Male ; Motor Activity/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa/*agonists ; Stereotyped Behavior/drug effects ; }, abstract = {Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse side-effects such as sedation, dysphoria, and depression limit their therapeutic use. Recently, salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaine-induced drug seeking in a model of relapse in rats. The present study evaluated the effects of acute Sal A exposure on cocaine-induced hyperactivity and cocaine sensitization in rats. Acute treatment with a dose of Sal A that decreased drug seeking in a previous study (0.3 mg/kg) significantly attenuated the expression of cocaine sensitization. This dose of Sal A failed to affect spontaneous locomotion or to produce a conditioned taste aversion to a novel-tasting saccharin solution. However, Sal A decreased climbing and swimming time and increased time spent immobile in the forced swim test. These findings indicate that Sal A, just like traditional KOPr agonists, attenuates cocaine-induced behavioral sensitization but does not produce the adverse effect of conditioned aversion, suggesting improved potential compliance. However, prodepressive effects were also produced and these effects may limit the therapeutic potential.}, } @article {pmid22274636, year = {2012}, author = {Lin, PY and Fang, YY and Wang, SP and Tai, MY and Tsai, YF}, title = {Different mechanisms of extinction of conditioned taste aversion are dependent on time intervals of extinction following conditioning.}, journal = {Die Naturwissenschaften}, volume = {99}, number = {3}, pages = {185-189}, pmid = {22274636}, issn = {1432-1904}, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Psychological/*physiology ; Extinction, Psychological/*physiology ; Male ; Rats ; Rats, Long-Evans ; Sucrose ; *Taste ; Time Factors ; }, abstract = {After extinction, the reappearance of a conditioned response induced by an unconditioned stimulus which is weaker than that used during the conditioning training indicates that the extinction procedure does not eliminate the original conditioned memory. Recent studies on fear conditioning have shown that rats exhibited little or no recovery of conditioned responding if the time interval between fear acquisition and extinction was short, suggesting that the extinction process may erase the original conditioning trace in this situation. In the present study, a saving experiment was conducted in rats to investigate whether an aversive response could be recovered following extinction training with different time intervals after acquisition of conditioned taste aversion (CTA). Male Long-Evans rats developed CTA by associating a 0.2% sucrose solution with malaise induced by intraperitoneal injection of 4 ml/kg 0.15 M LiCl and were subjected to extinction training with an interval of 5 h (5H group) or 24 h (24H group) after acquisition of CTA. Rats in the 5H group, but not in the 24H group, exhibited no aversive responding to the sucrose solution followed by the injection of a lower dose of LiCl (1 ml/kg). These findings indicate that the extinction procedure administered at different time points following the acquisition of CTA affects recovery of extinguished aversive memory and suggest that an unlearning process may be involved in the mechanisms of CTA extinction with short intervals between acquisition and extinction.}, } @article {pmid22260873, year = {2012}, author = {Davis, CM and Cobuzzi, JL and Riley, AL}, title = {Assessment of the aversive effects of peripheral mu opioid receptor agonism in Fischer 344 and Lewis rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {101}, number = {2}, pages = {181-186}, doi = {10.1016/j.pbb.2012.01.001}, pmid = {22260873}, issn = {1873-5177}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Loperamide/*pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Receptors, Opioid, mu/*agonists ; Species Specificity ; Taste/*drug effects ; }, abstract = {The Fischer 344 (F344) and Lewis (LEW) inbred rat strains differ on a host of biochemical, neuroanatomical, immunological and behavioral endpoints. One behavioral difference of interest is their differential reactivity to the aversive effects of morphine as indexed by the conditioned taste aversion preparation (aversions acquired by F344 rats are significantly greater than those acquired by the LEW strain). This differential effect appears to be specific to opioids that work primarily on the mu opioid receptor. Given that morphine works systemically, it is unknown whether these differential effects in F344 and LEW animals are centrally or peripherally mediated. To address this issue, the present study investigated the ability of the peripherally acting mu preferring opioid agonist loperamide to induce differential taste aversions in F344 and LEW animals. Both F344 and LEW animals acquired dose-dependent taste aversions to the loperamide-associated solution with no difference between them. Additionally, control animals initially injected with vehicle during aversion training with loperamide and subsequently conditioned with morphine displayed the typical aversive profile to morphine (F344>LEW). Although the basis for the present data is unknown, their relation to morphine-induced taste aversions and the role of the interaction of stimulus effects of drugs that produce differential abuse liability were discussed.}, } @article {pmid22252883, year = {2013}, author = {Revillo, DA and Arias, C and Spear, NE}, title = {The unconditioned stimulus pre-exposure effect in preweanling rats in taste aversion learning: role of the training context and injection cues.}, journal = {Developmental psychobiology}, volume = {55}, number = {2}, pages = {193-204}, pmid = {22252883}, issn = {1098-2302}, support = {R37 MH035219/MH/NIMH NIH HHS/United States ; R01 AA006634-04/AA/NIAAA NIH HHS/United States ; R01 AA011960/AA/NIAAA NIH HHS/United States ; R01 AA011960-06/AA/NIAAA NIH HHS/United States ; AA013098/AA/NIAAA NIH HHS/United States ; MH035219/MH/NIMH NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; AA015992/AA/NIAAA NIH HHS/United States ; R01 AA013098/AA/NIAAA NIH HHS/United States ; R01 AA010223-04S1/AA/NIAAA NIH HHS/United States ; R01 AA015992/AA/NIAAA NIH HHS/United States ; AA11960/AA/NIAAA NIH HHS/United States ; R01 AA013098-01A1/AA/NIAAA NIH HHS/United States ; R01 AA011960-02/AA/NIAAA NIH HHS/United States ; R01 MH035219/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; *Cues ; Extinction, Psychological/drug effects/physiology ; Lithium Chloride/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {The unconditioned stimulus pre-exposure effect (US-PE) refers to the interference paradigm in which acquisition of the conditioned response is retarded due to prior experience with the US. Most studies analyzing the psychological mechanisms underlying this effect have been conducted with adult rats. The most widely accepted hypothesis explains this effect as a contextual blocking effect. Contextual cues associated with the US block the conditioned stimulus (CS)-US association during conditioning. The modulatory role of a context devoid of distinctive olfactory attributes is not observable until approximately PD23 in rats, including modulation of interference paradigms such as latent inhibition or extinction. In this study, we analyzed US-PE in preweanling rats along with the role of the training context in this effect in terms of conditioned taste aversion preparation. Pre-exposure to LiCl before conditioning retarded the acquisition of taste aversion. The US-PE was observed in preweanling rats when, during pre-exposure, subjects were exposed to the conditioning context, and this effect was not attenuated either by the administration of the US in a familiar environment (Experiment 1a), or by the presence of an alternative, more salient context during pre-exposure (Experiment 1b). Additionally, the US-PE was still observed when the route by which the US was administered was changed between the pre-exposure and conditioning phases (Experiment 2a) as well as when the injection cues were removed during conditioning (Experiment 2b). These experiments show a strong US-PE in preweanling rats and fail to support the contextual blocking hypothesis, at least in this stage of ontogeny.}, } @article {pmid22234615, year = {2012}, author = {Kwok, DW and Livesey, EJ and Boakes, RA}, title = {Serial overshadowing of taste aversion learning by stimuli preceding the target taste.}, journal = {Learning & behavior}, volume = {40}, number = {4}, pages = {427-438}, pmid = {22234615}, issn = {1543-4508}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Operant/drug effects/*physiology ; Cues ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Wistar ; Taste/drug effects/*physiology ; Taste Perception/drug effects/*physiology ; }, abstract = {Three experiments tested whether events taking place before a rat has access to a target taste, sucrose, can proactively interfere with the acquisition of a sucrose aversion when sucrose is followed by a lithium chloride injection. Using a serial overshadowing procedure with various delays before lithium injection, proactive interference by a taste (Experiments 1 and 3) and by a novel context (Experiment 2) was found following two conditioning sessions, but not after a single conditioning session. Conversely, overshadowing by a taste given after the target was detectable after a single conditioning trial (Experiment 3) and, thus, indicated that retroactive interference involves a process different from that producing proactive interference. A simulation confirmed that the results are consistent with a modified Rescorla and Wagner (1972) interpretation of Revusky's (1971) concurrent interference theory of delay learning.}, } @article {pmid22213476, year = {2012}, author = {Castello, S and Bobbio, A and Orellana, E and Arias, C}, title = {Signaling the unconditioned stimulus during the preexposure phase does not attenuate the unconditioned stimulus preexposure effect in preweanling rats.}, journal = {Developmental psychobiology}, volume = {54}, number = {8}, pages = {808-817}, doi = {10.1002/dev.21001}, pmid = {22213476}, issn = {1098-2302}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Cues ; Extinction, Psychological/drug effects/physiology ; Female ; Lithium Chloride/pharmacology ; Male ; Odorants ; Rats ; Taste/drug effects/*physiology ; }, abstract = {The unconditioned stimulus preexposure effect (US-PE) is defined as an attenuation of the conditioned response after preexposure to the US prior to conditioning. Evidence exists that this effect can be weakened or eliminated by the presence of a signal predicting the US during the preexposure phase. This evidence has been found consistently across a variety of procedures in adult rats. The aim of the present study was to evaluate whether, in infant rats, signaling the US (LiCl) during preexposure with a salient cue (almond odor) attenuates the US-PE. During the preexposure phase, preweanling rats received three (Experiment 1) or one (Experiment 2) preexposures to LiCl, preceded by exposure to almond odor. Appropriate control groups were also included in these experiments. After preexposure, two conditioning trials were carried out in which subjects were given LiCl after saccharin consumption. During preexposure, three (Experiment 1a), although not one (Experiment 2a), contingent exposures to almond odor and LiCl resulted in a strong odor aversion. Extinction of the learned taste aversion was facilitated by prior experience with LiCl (Experiments 1b and 2b). This effect was observed regardless of whether or not LiCl was signaled by the almond odor. These results do not coincide with the associative hypotheses proposed to explain the US-PE, nor are they concurrent with alternative explanations based on the learned helplessness phenomenon.}, } @article {pmid22170968, year = {2012}, author = {Tokita, K and Yamamoto, T and Boughter, JD}, title = {Gustatory neural responses to umami stimuli in the parabrachial nucleus of C57BL/6J mice.}, journal = {Journal of neurophysiology}, volume = {107}, number = {6}, pages = {1545-1555}, pmid = {22170968}, issn = {1522-1598}, support = {R01 DC000353/DC/NIDCD NIH HHS/United States ; DC000353/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Citric Acid/pharmacology ; Inosine Monophosphate/*pharmacology ; Male ; Mice ; Neurons/*drug effects/physiology ; Pons/*drug effects/physiology ; Quinine/pharmacology ; Sodium Glutamate/*pharmacology ; Sucrose/pharmacology ; Taste/drug effects/physiology ; Taste Buds/*drug effects/physiology ; Taste Perception/*drug effects/physiology ; }, abstract = {Umami is considered to be the fifth basic taste quality and is elicited by glutamate. The mouse is an ideal rodent model for the study of this taste quality because of evidence that suggests that this species, like humans, may sense umami-tasting compounds as unique from other basic taste qualities. We performed single-unit recording of taste responses in the parabrachial nucleus (PbN) of anesthetized C57BL/6J mice to investigate the central representation of umami taste. A total of 52 taste-responsive neurons (22 sucrose-best, 19 NaCl-best, 5 citric acid-best, and 6 quinine-best) were recorded from stimulation period with a large panel of basic and umami-tasting stimuli. No neuron responded best to monopotassium glutamate (MPG) or inosine 5'-monophosphate (IMP), suggesting convergence of input in the central nervous system. Synergism induced by an MPG-IMP mixture was observed in all sucrose-best and some NaCl-best neurons that possessed strong sensitivity to sucrose. In more than half of sucrose-best neurons, the MPG-IMP mixture evoked stronger responses than those elicited by their best stimulus. Furthermore, hierarchical cluster analysis and multidimensional analysis indicated close similarity between sucrose and the MPG-IMP mixture. These results strongly suggest the mixture tastes sweet to mice, a conclusion consistent with previous findings that show bidirectional generalization of conditioned taste aversion between sucrose and umami mixtures, and suppression of taste responses to both sucrose and mixtures by the antisweet polypeptide gurmarin in the chorda tympani nerve. The distribution pattern of reconstructed recording sites of specific neuron types suggested chemotopic organization in the PbN.}, } @article {pmid22152100, year = {2011}, author = {Wilson, GN and Biesan, OR and Remus, JL and Mickley, GA}, title = {Baclofen alters gustatory discrimination capabilities and induces a conditioned taste aversion (CTA).}, journal = {BMC research notes}, volume = {4}, number = {}, pages = {527}, pmid = {22152100}, issn = {1756-0500}, abstract = {BACKGROUND: Studies intending to measure drug-induced changes in learning and memory are challenged to parse out the effects of drugs on sensory, motor, and associative systems in the brain. In the context of conditioned taste aversion (CTA), drugs that alter the sensorium of subjects and affect their ability to taste and/or feel malaise may limit the ability of investigators to make conclusions about associative effects of these substances. Since the GABAergic system is implicated in inhibition, the authors were hopeful to use the GABA agonist, baclofen (BAC), to enhance extinction of a CTA, but first a preliminary evaluation of BAC's peripheral effects on animals' sensorium had to be completed due to a lack of published literature in this area.

FINDINGS: Our first experiment aimed to evaluate the extent to which the GABAB agonist, BAC, altered the ability of rats to differentiate between 0.3% and 0.6% saccharin (SAC) in a two bottle preference test. Here we report that 2 or 3 mg/kg (i.p.) BAC, but not 1 mg/kg BAC, impaired animals' gustatory discrimination abilities in this task. Furthermore, when SAC consumption was preceded by 2 or 3 mg/kg (i.p.) BAC, rats depressed their subsequent SAC drinking.A second experiment evaluated if the suppression of SAC and water drinking (revealed in Experiment 1) was mediated by amnesiac effects of BAC or whether BAC possessed US properties in the context of the CTA paradigm. The time necessary to reach an asymptotic level of CTA extinction was not significantly different in those animals that received the 3 mg/kg dose of BAC compared to more conventionally SAC + lithium chloride (LiCl, 81 mg/kg) conditioned animals.

CONCLUSIONS: Our findings were not consistent with a simple amnesia-of-neophobia explanation. Instead, results indicated that 2 and 3 mg/kg (i.p.) BAC were capable of inducing a CTA, which was extinguishable via repeated presentations of SAC only. Our data indicate that, depending on the dose, BAC can alter SAC taste discrimination and act as a potent US in the context of a CTA paradigm.}, } @article {pmid22144949, year = {2011}, author = {Neseliler, S and Narayanan, D and Fortis-Santiago, Y and Katz, DB and Birren, SJ}, title = {Genetically induced cholinergic hyper-innervation enhances taste learning.}, journal = {Frontiers in systems neuroscience}, volume = {5}, number = {}, pages = {97}, pmid = {22144949}, issn = {1662-5137}, support = {R01 NS057305/NS/NINDS NIH HHS/United States ; T32 MH019929/MH/NIMH NIH HHS/United States ; P30 NS045713/NS/NINDS NIH HHS/United States ; R01 DC006666/DC/NIDCD NIH HHS/United States ; R01 DC007703/DC/NIDCD NIH HHS/United States ; }, abstract = {Acute inhibition of acetylcholine (ACh) has been shown to impair many forms of simple learning, and notably conditioned taste aversion (CTA). The most adhered-to theory that has emerged as a result of this work - that ACh increases a taste's perceived novelty, and thereby its associability - would be further strengthened by evidence showing that enhanced cholinergic function improves learning above normal levels. Experimental testing of this corollary hypothesis has been limited, however, by side-effects of pharmacological ACh agonism and by the absence of a model that achieves long-term increases in cholinergic signaling. Here, we present this further test of the ACh hypothesis, making use of mice lacking the p75 pan-neurotrophin receptor gene, which show a resultant over-abundance of cholinergic neurons in sub-regions of the basal forebrain (BF). We first demonstrate that the p75-/- abnormality directly affects portions of the CTA circuit, locating mouse gustatory cortex (GC) using a functional assay and then using immunohistochemisty to demonstrate cholinergic hyper-innervation of GC in the mutant mice - hyper-innervation that is unaccompanied by changes in cell numbers or compensatory changes in muscarinic receptor densities. We then demonstrate that both p75-/- and wild-type (WT) mice learn robust CTAs, which extinguish more slowly in the mutants. Further testing to distinguish effects on learning from alterations in memory retention demonstrate that p75-/- mice do in fact learn stronger CTAs than WT mice. These data provide novel evidence for the hypothesis linking ACh and taste learning.}, } @article {pmid22133633, year = {2012}, author = {Traverso, LM and Ruiz, G and De la Casa, LG}, title = {MK-801 induces a low intensity conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {100}, number = {3}, pages = {645-651}, doi = {10.1016/j.pbb.2011.11.012}, pmid = {22133633}, issn = {1873-5177}, mesh = {Animals ; Behavior, Animal/drug effects ; Conditioning, Psychological ; Discrimination Learning ; Dizocilpine Maleate/administration & dosage/*adverse effects ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Dysgeusia/*chemically induced/physiopathology ; Excitatory Amino Acid Antagonists/administration & dosage/*adverse effects ; Lithium Chloride/adverse effects ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Saccharin/pharmacology ; Severity of Illness Index ; Sweetening Agents/pharmacology ; }, abstract = {N-methyl-D-aspartate (NMDA) receptor antagonists are often used to assess the role of NMDA receptors in learning and memory processes. However, few studies have explored the possibility that the antagonists may induce a conditioned aversion when administered following flavor consumption. We report five experiments with rats intended to evaluate the MK-801 capacity to induce conditioned taste aversion. Our findings suggest that: i) MK-801 produces a low-intensity aversion following repeated pairings with saccharin (Experiments 1 and 2); ii) such aversion was not the result of a non-associative process (Experiment 3); and iii) pre-exposure to MK-801 does not interact with conditioned taste aversion induced by lithium chloride (Experiments 4 and 5). These findings suggest that MK-801 induces a low-intensity aversion, although the underlying mechanisms of this aversion may differ from those of a conditioned aversion produced by lithium chloride.}, } @article {pmid22131967, year = {2011}, author = {Scott, TR}, title = {Learning through the taste system.}, journal = {Frontiers in systems neuroscience}, volume = {5}, number = {}, pages = {87}, pmid = {22131967}, issn = {1662-5137}, abstract = {Taste is the final arbiter of which chemicals from the environment will be admitted to the body. The action of swallowing a substance leads to a physiological consequence of which the taste system should be informed. Accordingly, taste neurons in the central nervous system are closely allied with those that receive input from the viscera so as to monitor the impact of a recently ingested substance. There is behavioral, anatomical, electrophysiological, gene expression, and neurochemical evidence that the consequences of ingestion influence subsequent food selection through development of either a conditioned taste aversion (CTA) (if illness ensues) or a conditioned taste preference (CTP) (if nutrition). This ongoing communication between taste and the viscera permits the animal to tailor its taste system to its individual needs over a lifetime.}, } @article {pmid22119580, year = {2012}, author = {Panguluri, SK and Kuwabara, N and Kang, Y and Cooper, N and Lundy, RF}, title = {Conditioned taste aversion dependent regulation of amygdala gene expression.}, journal = {Physiology & behavior}, volume = {105}, number = {4}, pages = {996-1006}, pmid = {22119580}, issn = {1873-507X}, support = {P20 RR016481/RR/NCRR NIH HHS/United States ; R56 DC010171-01A1/DC/NIDCD NIH HHS/United States ; R01 DC006698/DC/NIDCD NIH HHS/United States ; P20RR16481/RR/NCRR NIH HHS/United States ; R01 DC006698-06/DC/NIDCD NIH HHS/United States ; 5R01DC006698/DC/NIDCD NIH HHS/United States ; 1R56DC010171/DC/NIDCD NIH HHS/United States ; R56 DC010171/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/metabolism/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Extinction, Psychological/physiology ; Gene Expression/physiology ; Insulin/genetics/*physiology ; Lithium Chloride/pharmacology ; Male ; Microinjections ; Oligonucleotide Array Sequence Analysis/methods/statistics & numerical data ; Peptides/administration & dosage/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Insulin/antagonists & inhibitors/*physiology ; Taste/*physiology ; }, abstract = {The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning.}, } @article {pmid22085742, year = {2012}, author = {Mediavilla, C and Mahía, J and Bernal, A and Puerto, A}, title = {The D2/D3-receptor antagonist tiapride impairs concurrent but not sequential taste aversion learning.}, journal = {Brain research bulletin}, volume = {87}, number = {2-3}, pages = {346-349}, doi = {10.1016/j.brainresbull.2011.10.022}, pmid = {22085742}, issn = {1873-2747}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Discrimination, Psychological/*drug effects ; Disease Models, Animal ; Dopamine Antagonists/*toxicity ; Drug Administration Schedule ; Learning Disabilities/*chemically induced ; Male ; Rats ; Rats, Wistar ; Serial Learning/drug effects ; Taste/*drug effects ; Tiapamil Hydrochloride/*toxicity ; Time Factors ; Water Deprivation/physiology ; }, abstract = {Taste aversion learning (TAL) is a learning modality in which the animals reject a gustatory stimulus associated with the administration of noxious visceral substances. This learning can be established by concurrent or sequential procedures that involve different anatomical and functional mechanisms and may constitute distinct learning modalities. The dopaminergic system has been related to various learning processes and goal-directed behaviours. The present study examined the effect of the administration of tiapride, a D(2)/D(3) dopaminergic antagonist, on concurrent and sequential TAL. Results obtained showed that pre-treatment with tiapride blocks the acquisition of concurrent TAL but does not affect sequential TAL, including reversal learning tasks. These results demonstrate the involvement of the D(2)/D(3) dopaminergic receptors in the former but not the latter learning process. The dopaminergic system appears to participate in concurrent TAL, an "implicit" learning modality, but not in sequential TAL, which is considered a relational/explicit acquisition process.}, } @article {pmid22085719, year = {2012}, author = {Kwon, B and Houpt, TA}, title = {Mitogen-activated protein kinase in the amygdala plays a critical role in lithium chloride-induced taste aversion learning.}, journal = {Neurobiology of learning and memory}, volume = {97}, number = {1}, pages = {132-139}, pmid = {22085719}, issn = {1095-9564}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; R01 DC003198-08/DC/NIDCD NIH HHS/United States ; R01DC03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Aminoacetonitrile/analogs & derivatives/pharmacology ; Amygdala/drug effects/metabolism/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Lithium Chloride/pharmacology ; Male ; Microinjections ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphorylation/drug effects/physiology ; Protease Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/metabolism ; Taste/*physiology ; }, abstract = {The intracellular mitogen-activated protein kinase (MAPK) pathway in the brain is necessary for the formation of a variety of memories including conditioned taste aversion (CTA) learning. However, the functional role of MAPK activation in the amygdala during lithium chloride (LiCl)-induced CTA learning has not been established. In the present study, we investigated if local microinjection of SL327, a MAPK kinase inhibitor, into the rat amygdala could alleviate LiCl-induced CTA learning. Our results revealed that acute administration of a high dose of LiCl (0.15M, 12 ml/kg, i.p.) rapidly increased the level of phosphorylated MAPK (pMAPK)-positive cells in the central nucleus of the amygdala (CeA) and nucleus of the solitary tract (NTS) of rats as measured by immunohistochemistry. Local microinjection of SL327 (1 μg/0.5 μl/hemisphere) into the CeA 10 min before LiCl administration decreased both the strength of LiCl-induced CTA paired with 0.125% saccharin and the level of LiCl-induced pMAPK-positive cells in the CeA, but not in the NTS. Our data suggest that the intracellular signaling cascade of the MAPK pathway in the CeA plays a critical role in the processing of visceral information induced by LiCl for CTA learning.}, } @article {pmid22073032, year = {2011}, author = {Gámiz, F and Gallo, M}, title = {Taste learning and memory: a window on the study of brain aging.}, journal = {Frontiers in systems neuroscience}, volume = {5}, number = {}, pages = {91}, pmid = {22073032}, issn = {1662-5137}, abstract = {Taste aversion learning exhibits advantages for research on memory brain systems and its reorganization throughout life. A review of the effects of aging on taste memory abilities offers a complex picture showing preserved, impaired, and enhanced functions. Some of the age-related changes in taste memory seem to be associated with an altered temporal processing. Longer taste-illness delays can be introduced for acquisition of conditioned taste aversions and the modulation of taste learning by the temporal context is absent in naïve old rats. It is suggested that an altered hippocampal function is involved in the peculiar performance of these rats. Evidence is also presented which suggests that hippocampal-dependent taste memory can be reactivated by previous learning experiences in old rats. Results obtained after reversible inactivation of the dorsal Hippocampus by tetrodotoxin (TTX) in old rats support such a view. Therefore, the interaction between the previous experience and acute brain interventions should be taken into account when studying the effect of aging on taste memory.}, } @article {pmid22061838, year = {2012}, author = {Kwok, DW and Boakes, RA}, title = {Blocking of acquisition of a taste aversion by a context experienced prior to the taste.}, journal = {Behavioural processes}, volume = {89}, number = {1}, pages = {27-29}, doi = {10.1016/j.beproc.2011.10.008}, pmid = {22061838}, issn = {1872-8308}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Cues ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Wistar ; Sucrose/pharmacology ; Taste/drug effects/*physiology ; Taste Perception/drug effects/physiology ; }, abstract = {This experiment tested the proposal that events taking place before a rat has access to a taste can proactively interfere with acquisition of an aversion to the taste when this has been followed by lithium chloride injection. Rats were initially given context discrimination whereby placement in one distinctive context (target) was followed by lithium injection, while placement in a second context (safe) was followed by saline injection. In the subsequent 1-trial taste conditioning session, rats were first placed in either their target context (Blocking group), their safe context (Control-Safe group) or a neutral context (Control-Neutral group), then given access to sucrose and 30 min later were injected with lithium. Subsequent tests of sucrose intakes revealed a blocking effect. These results indicate that proactive interference with taste aversion learning by a context can occur that is unlikely to be based on generalization decrement.}, } @article {pmid22056436, year = {2011}, author = {Narukawa, M and Morita, K and Uemura, M and Kitada, R and Oh, SH and Hayashi, Y}, title = {Nerve and behavioral responses of mice to various umami substances.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {75}, number = {11}, pages = {2125-2131}, doi = {10.1271/bbb.110401}, pmid = {22056436}, issn = {1347-6947}, mesh = {Animals ; Betaine/*chemistry ; Cranial Nerves/*physiology ; *Feeding Behavior ; Glutamates/chemistry ; Inosine Monophosphate/*chemistry ; Mice ; Mice, Inbred C57BL ; Sodium Glutamate/*chemistry ; *Taste Perception ; }, abstract = {Food contains various taste substances. Among them, umami substances play an important role with regard to the perception of the taste of food, but, few studies have examined the taste characteristics of representative umami substances other than monosodium L-glutamate (MSG). By conducting mouse behavioral studies (the 48-h 2-bottle preference test and the conditioned taste aversion test) and assessing gustatory nerve responses, we investigated the taste characteristics of unique umami substances, including sodium succinate, L-theanine, betaine, and the enantiomer of MSG, D-MSG. Furthermore, we examined the synergy of umami with inosine 5'-monophoshate (IMP). In the case of the mice, sodium succinate had an umami taste and showed strong synergy with IMP. L-theanine showed synergy with IMP but did not have an umami taste without IMP. In contrast, betaine did not have an umami taste or synergy with IMP. D-MSG might have weak synergy with IMP.}, } @article {pmid22008743, year = {2012}, author = {Nakashima, K and Eddy, MC and Katsukawa, H and Delay, ER and Ninomiya, Y}, title = {Behavioral responses to glutamate receptor agonists and antagonists implicate the involvement of brain-expressed mGluR4 and mGluR1 in taste transduction for umami in mice.}, journal = {Physiology & behavior}, volume = {105}, number = {3}, pages = {709-719}, doi = {10.1016/j.physbeh.2011.09.028}, pmid = {22008743}, issn = {1873-507X}, support = {R15 DC005962/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects ; Brain/*drug effects ; Dose-Response Relationship, Drug ; Drug Interactions ; Excitatory Amino Acid Agonists/*pharmacology ; Excitatory Amino Acid Antagonists/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Propionates/pharmacology ; Receptors, Metabotropic Glutamate/*metabolism ; Signal Transduction/drug effects ; Sodium Glutamate/pharmacology ; Taste/*drug effects ; Taste Threshold/*drug effects ; }, abstract = {Recent molecular studies have identified many candidate receptors for umami, typically the taste of monosodium glutamate (MSG). The candidate receptors, including taste-mGluR4, T1R1+T1R3, and truncated mGluR1, respond to MSG in the millimolar concentration range. Expression of brain-expressed mGluR4 and mGluR1 with much higher sensitivities to glutamate has also been reported in taste papillae. To test the involvement of brain-expressed mGluRs in umami taste, we tested glutamate agonists and antagonists at concentration ranges relevant to both types of the receptors using a combination of a detection threshold and conditioned taste aversion (CTA) methods in mice. The detection threshold experiment showed that mice could detect the group III mGluR agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4) taste thresholds at 0.0009-0.0019 mM. Mice conditioned using CTA methods to avoid either MSG or MPG showed aversive responses to MSG with and without amiloride or to MPG, respectively, at concentrations of 0.0001 mM and above. A CTA to L-AP4 or MSG showed comparable concentration-response ranges for L-AP4 and MSG. The Group III mGluR antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), and the mGluR1 antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA), suppressed aversive responses to glutamate agonists at concentrations between 0.0001 and 100mM in the CTA experiments. Our results suggest the possibility that brain-expressed mGluR4 and mGluR1 may contribute to umami taste in mice.}, } @article {pmid22000083, year = {2011}, author = {Mickley, GA and Wilson, GN and Remus, JL and Ramos, L and Ketchesin, KD and Biesan, OR and Luchsinger, JR and Prodan, S}, title = {Periaqueductal gray c-Fos expression varies relative to the method of conditioned taste aversion extinction employed.}, journal = {Brain research}, volume = {1423}, number = {}, pages = {17-29}, pmid = {22000083}, issn = {1872-6240}, support = {2-R15-MH063720-03/MH/NIMH NIH HHS/United States ; R15 MH063720-03S1/MH/NIMH NIH HHS/United States ; 2-R15-MH063720-03S1/MH/NIMH NIH HHS/United States ; R15 MH063720-03/MH/NIMH NIH HHS/United States ; R15 MH063720/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Cell Count ; Conditioning, Psychological/*physiology ; Extinction, Psychological/*physiology ; Gene Expression Regulation ; Lithium Chloride/administration & dosage ; Male ; Periaqueductal Gray/cytology/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/*physiology ; Time Factors ; }, abstract = {A conditioned taste aversion (CTA) is acquired when an animal consumes a novel taste (CS) and then experiences the symptoms of poisoning (US). Following CTA training, animals will avoid the taste that was previously associated with malaise. This defensive reaction to a learned fear can be extinguished by repeated exposure to the CS alone (CS-only; CSO-EXT). However, following a latency period in which the CS is not presented, the CTA will spontaneously recover (SR). Through the use of an explicitly unpaired extinction procedure (EU-EXT) we have shown that we can speed up extinction and attenuate SR of the CTA. Here we compared and contrasted the ability of CSO and EU extinction procedures to affect c-Fos expression in the periaqueductal gray (PAG). Fluid-deprived Sprague-Dawley rats acquired a strong CTA [via 3 pairings of 0.3% oral saccharin (SAC; the CS) and 81mg/kg i.p. lithium chloride (LiCl; the US)] followed by extinction trials consisting of multiple exposures to either, (a) the CS every-other day (CSO-EXT), or (b) CS and US on alternate days (EU-EXT). A different group of rats did not receive multiple CS exposures and served as a "no extinction" (NE) control. Both extinction procedures resulted in ≥90% reacceptance of SAC (achieving asymptotic extinction). Some of the animals were sacrificed for c-Fos immunohistochemical analysis following asymptotic extinction. Other rats entered a 30-day latency period where they drank water only. These remaining animals were then tested for SR with a final exposure to SAC before being sacrificed for c-Fos immunohistochemistry. As reported previously, rats in the CS-only group exhibited a significant SR of the CTA. However, animals in the EU extinction group reached asymptotic extinction more rapidly than did CSO rats and they did not show SR of the CTA. As compared to rats that retained their CTA, both groups of extinguished rats showed suppression in the number of c-Fos-labeled neurons in all 4 longitudinal columns of the PAG. The number of c-Fos-labeled cells in the PAG was generally low but there was a reliable increase in c-Fos expression in dorsolateral PAG (dlPAG) following the SR test in the brains of rats that went through the EU-EXT procedure as compared with those that either went through the more-traditional CSO extinction procedure or experienced no extinction at all. The number of c-Fos-labeled neurons in the dlPAG was significantly correlated with the amount of SAC consumed at the SR test. Surprisingly, the brains of EU-extinguished rats and CSO extinguished rats did not differ in the number of c-Fos-labeled neurons in gustatory neocortex, medial prefrontal cortex, basolateral amygdala, or the central nucleus of the amygdala. Thus, behavioral differences in SR between the EU and CSO extinction animals were not represented by corresponding changes in the neural activity of several brain nuclei classically associated with extinction learning. However a detailed analysis of PAG c-Fos expression provided hints about some of the physiological changes evoked by these 2 extinction paradigms that produce very different behavioral outcomes. The findings are clinically relevant as we seek the development of treatments for deficits in fear extinction (e.g. PTSD, phobias).}, } @article {pmid21994361, year = {2011}, author = {Dossat, AM and Lilly, N and Kay, K and Williams, DL}, title = {Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {31}, number = {41}, pages = {14453-14457}, pmid = {21994361}, issn = {1529-2401}, support = {K99 DK078779/DK/NIDDK NIH HHS/United States ; R00 DK078779/DK/NIDDK NIH HHS/United States ; R00 DK078779-05/DK/NIDDK NIH HHS/United States ; DK078779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects/*physiology ; Gene Expression Regulation/drug effects ; Glucagon-Like Peptide 1/metabolism/pharmacology ; Glucagon-Like Peptide-1 Receptor ; Injections, Intraventricular/methods ; Male ; Nucleus Accumbens/drug effects/*metabolism ; Peptide Fragments/pharmacology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Wistar ; Receptors, Glucagon/antagonists & inhibitors/*physiology ; Saccharin/administration & dosage ; Stilbamidines ; Sweetening Agents/administration & dosage ; Taste/drug effects ; Time Factors ; }, abstract = {Central glucagon-like peptide 1 receptor (GLP-1R) stimulation suppresses food intake, and hindbrain GLP-1 neurons project to numerous feeding-relevant brain regions. One such region is the nucleus accumbens (NAc), which plays a role in reward and motivated behavior. Using immunohistochemical and retrograde tracing techniques in rats, we identified a robust projection from GLP-1 neurons in the nucleus of the solitary tract to the NAc. We hypothesized that activation of NAc GLP-1Rs suppresses feeding. When injected into the NAc core of rats at doses subthreshold for effect when administered to the lateral ventricle, GLP-1 significantly reduced food intake relative to vehicle at 1, 2, and 24 h posttreatment. The same doses had no effect when injected into the NAc shell. NAc core treatment with ventricle-subthreshold doses of the GLP-1R antagonist exendin (9-39) caused significant hyperphagia at 2 h posttreatment, suggesting that endogenous stimulation of NAc core GLP-1Rs plays a role in limiting food intake. It has been suggested that GLP-1 can cause nausea, but we found that NAc core administration of GLP-1 did not cause a conditioned taste aversion to saccharin, suggesting that the anorexic effect of NAc core GLP-1 is not caused by malaise. Finally, we observed that NAc core injection of GLP-1 significantly increased c-Fos expression in the NAc core. We conclude that that GLP-1Rs in the NAc play a physiologic role in food intake control, and suggest that the GLP-1 projection to NAc core may link satiation signal processing in the hindbrain with forebrain processing of food reward.}, } @article {pmid21991247, year = {2011}, author = {Guzmán-Ramos, K and Bermúdez-Rattoni, F}, title = {Post-learning molecular reactivation underlies taste memory consolidation.}, journal = {Frontiers in systems neuroscience}, volume = {5}, number = {}, pages = {79}, pmid = {21991247}, issn = {1662-5137}, abstract = {It is considered that memory consolidation is a progressive process that requires post-trial stabilization of the information. In this regard, it has been speculated that waves of receptors activation, expression of immediate early genes, and replenishment of receptor subunit pools occur to induce functional or morphological changes to maintain the information for longer periods. In this paper, we will review data related to neuronal changes in the post-acquisition stage of taste aversion learning that could be involved in further stabilization of the memory trace. In order to achieve such stabilization, evidence suggests that the functional integrity of the insular cortex (IC) and the amygdala (AMY) is required. Particularly the increase of extracellular levels of glutamate and activation of N-methyl-d-aspartate (NMDA) receptors within the IC shows a main role in the consolidation process. Additionally the modulatory actions of the dopaminergic system in the IC appear to be involved in the mechanisms that lead to taste aversion memory consolidation through the activation of pathways related to enhancement of protein synthesis such as the Protein Kinase A pathway. In summary, we suggest that post-acquisition molecular and neuronal changes underlying memory consolidation are dependent on the interactions between the AMY and the IC.}, } @article {pmid21987728, year = {2012}, author = {Eddy, MC and Eschle, BK and Peterson, D and Lauras, N and Margolskee, RF and Delay, ER}, title = {A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.}, journal = {Chemical senses}, volume = {37}, number = {5}, pages = {391-401}, pmid = {21987728}, issn = {1464-3553}, support = {R01 DC003055/DC/NIDCD NIH HHS/United States ; R01 DK081421/DK/NIDDK NIH HHS/United States ; R01 DC003155/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Choice Behavior/drug effects/physiology ; Conditioning, Psychological/drug effects ; Dysgeusia/genetics/physiopathology ; Guanidines/*administration & dosage ; Lithium Chloride/administration & dosage ; Mice ; Mice, Knockout ; Odorants ; Pentanols/administration & dosage ; Signal Transduction/drug effects/physiology ; Smell/drug effects/physiology ; Sucrose/*administration & dosage ; Sweetening Agents/*administration & dosage ; TRPM Cation Channels/*deficiency/genetics ; Taste/drug effects/*physiology ; Taste Perception/drug effects/*physiology ; }, abstract = {Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.}, } @article {pmid21960964, year = {2011}, author = {Martínez-Moreno, A and Rodríguez-Durán, LF and Escobar, ML}, title = {Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement.}, journal = {Frontiers in behavioral neuroscience}, volume = {5}, number = {}, pages = {61}, pmid = {21960964}, issn = {1662-5153}, abstract = {It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.}, } @article {pmid21931717, year = {2011}, author = {Robery, S and Mukanowa, J and Percie du Sert, N and Andrews, PL and Williams, RS}, title = {Investigating the effect of emetic compounds on chemotaxis in Dictyostelium identifies a non-sentient model for bitter and hot tastant research.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e24439}, pmid = {21931717}, issn = {1932-6203}, support = {/WT_/Wellcome Trust/United Kingdom ; G0900775/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; 082640/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Capsaicin/pharmacology ; Cell Movement ; *Chemotaxis ; Dictyostelium/*metabolism ; Dose-Response Relationship, Drug ; Emetics ; Genome ; Inhibitory Concentration 50 ; Movement ; Proteins/chemistry ; Quinine/pharmacology ; Stomach/drug effects ; *Taste ; }, abstract = {Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds--denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers--capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC(50) = 11.9 ± 4.0 µM) > quinine hydrochloride (IC(50) = 44.3 ± 6.8 µM) > denatonium benzoate (IC(50) = 129 ± 4 µM) > phenylthiourea (IC(50) = 366 ± 5 µM) > copper sulphate (IC(50) = 1433 ± 3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general.}, } @article {pmid21928874, year = {2011}, author = {Foo, H and Mason, P}, title = {Ingestion analgesia occurs when a bad taste turns good.}, journal = {Behavioral neuroscience}, volume = {125}, number = {6}, pages = {956-961}, pmid = {21928874}, issn = {1939-0084}, support = {R01 DA022978/DA/NIDA NIH HHS/United States ; R01 DA022978-06A1/DA/NIDA NIH HHS/United States ; DA022978/DA/NIDA NIH HHS/United States ; }, mesh = {Analgesia/*methods ; Animals ; Eating/drug effects/*physiology ; Feeding Behavior/physiology ; Male ; Pain Measurement/drug effects/*methods ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {During ingestion of water, chocolate, sucrose, and saccharin, pain-related behaviors are suppressed. This ingestion analgesic effect is reversed when the hedonic valence of a food is switched from "good" to "bad" as occurs during conditioned taste aversion. Here, we tested the converse hedonic shift to determine if ingestion analgesia occurs when 0.3 M NaCl is made palatable by inducing a sodium appetite. In Experiment 1, sham- and sodium-depleted rats were tested for paw withdrawal and lick latencies to brief noxious heat during quiet wake and intraoral NaCl ingestion. Only sodium-depleted rats showed a suppression of heat-evoked reactions during NaCl ingestion. In Experiment 2, we tested whether this analgesic effect is mediated by the brainstem nucleus raphe magnus (NRM). Inactivation of NRM with muscimol blocked ingestion analgesia during NaCl ingestion by sodium-depleted rats. This attenuation was not due to a hyperalgesic effect of NRM inactivation. Muscimol microinjections into a nearby region, the nucleus raphe obscurus (NRO), were ineffective. The present findings demonstrate that the internal milieu of an animal can modify ingestion analgesia, and that the analgesia during NaCl ingestion by sodium hungry rats is mediated by NRM.}, } @article {pmid21927632, year = {2011}, author = {Drescher, C and Foscue, EP and Kuhn, CM and Schramm-Sapyta, NL}, title = {Individual differences in cocaine conditioned taste aversion are developmentally stable and independent of locomotor effects of cocaine.}, journal = {Developmental cognitive neuroscience}, volume = {1}, number = {4}, pages = {600-605}, pmid = {21927632}, issn = {1878-9307}, support = {K01 DA020729/DA/NIDA NIH HHS/United States ; K01 DA020729-05/DA/NIDA NIH HHS/United States ; DA 020729/DA/NIDA NIH HHS/United States ; }, mesh = {Aging/drug effects/physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Cocaine/*pharmacology ; Conditioning, Psychological/drug effects/*physiology ; *Individuality ; Motor Activity/drug effects/*physiology ; Rats ; Taste/drug effects/*physiology ; }, abstract = {Drugs of abuse induce complex motivational states in their users which have been shown to vary developmentally. In addition to developmental variation, interindividual variation in the rewarding and aversive effects of drugs of abuse is an important consideration. A rat model was used to assess whether the conditioned rewarding/aversive effects of cocaine were maintained as individuals matured from adolescence into adulthood. We tested rats in the cocaine conditioned taste aversion task as adolescents and again in adulthood. We observed a wide range of approach/avoidance behaviors in this task, and also observed that the relative interindividual differences in approach/avoidance are remarkably stable across the two developmental stages. Furthermore, we observed that these interindividual differences are not attributable to individual differences in cocaine-induced locomotor effects or individual differences in blood or brain cocaine levels. Taken together, these findings indicate that sensitivity to cocaine’s motivational effects is stable across development and part of a unique neurological process.}, } @article {pmid21925200, year = {2012}, author = {Mitra, A and Klockars, A and Gosnell, BA and Le Grevès, M and Olszewski, PK and Levine, AS and Schiöth, HB}, title = {Expression levels of genes encoding melanin concentrating hormone (MCH) and MCH receptor change in taste aversion, but MCH injections do not alleviate aversive responses.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {100}, number = {3}, pages = {581-586}, pmid = {21925200}, issn = {1873-5177}, support = {P30 DK050456/DK/NIDDK NIH HHS/United States ; T32DE007288/DE/NIDCR NIH HHS/United States ; R01DA021280/DA/NIDA NIH HHS/United States ; T32 DE007288-07A1/DE/NIDCR NIH HHS/United States ; T32 DE007288/DE/NIDCR NIH HHS/United States ; R01 DA021280/DA/NIDA NIH HHS/United States ; R01 DA021280-05/DA/NIDA NIH HHS/United States ; P30 DK050456-06/DK/NIDDK NIH HHS/United States ; P30DK50456/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Brain/*metabolism ; Brain Stem/metabolism ; Conditioning, Psychological ; Dysgeusia/drug therapy/*metabolism ; *Gene Expression Regulation ; Hypothalamic Hormones/administration & dosage/genetics/*metabolism/therapeutic use ; Hypothalamus/metabolism ; Injections, Intraventricular ; Male ; Melanins/administration & dosage/genetics/*metabolism/therapeutic use ; Nerve Tissue Proteins/administration & dosage/genetics/*metabolism/therapeutic use ; Neurons/*metabolism ; Organ Specificity ; Pituitary Hormones/administration & dosage/genetics/*metabolism/therapeutic use ; RNA, Messenger/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors, Somatostatin/genetics/*metabolism ; Up-Regulation ; }, abstract = {Melanin concentrating hormone (MCH) stimulates feeding driven by energy needs and reward and modifies anxiety behavior. Orexigenic peptides of similar characteristics, including nociceptin/orphanin FQ, Agouti-related protein and opioids, increase consumption also by reducing avoidance of potentially tainted food in animals displaying a conditioned taste aversion (CTA). Herein, using real-time PCR, we assessed whether expression levels of genes encoding MCH and its receptor, MCHR1, were affected in CTA in the rat. We also investigated whether injecting MCH intracerebroventricularly (ICV) during the acquisition and retrieval of LiCl-induced CTA, would alleviate aversive responses. MCHR1 gene was upregulated in the hypothalamus and brain stem of aversive animals, MCH mRNA was significantly higher in the hypothalamus, whereas a strong trend suggesting upregulation of MCH and MCHR1 genes was detected in the amygdala. Despite these expression changes associated with aversion, MCH injected prior to the induction of CTA with LiCl as well as later, during the CTA retrieval upon subsequent presentations of the aversive tastant, did not reduce the magnitude of CTA. We conclude that MCH and its receptor form an orexigenic system whose expression is affected in CTA. This altered MCH expression may contribute to tastant-targeted hypophagia in CTA. However, changing the MCH tone in the brain by exogenous peptide was insufficient to prevent the onset or facilitate extinction of LiCl-induced CTA. This designates MCH as one of many accessory molecules associated with shaping an aversive response, but not a critical one for LiCl-dependent CTA to occur.}, } @article {pmid21925192, year = {2012}, author = {Mickley, GA and Remus, JL and Ramos, L and Wilson, GN and Biesan, OR and Ketchesin, KD}, title = {Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {105}, number = {2}, pages = {417-427}, pmid = {21925192}, issn = {1873-507X}, support = {2-R15-MH063720-03/MH/NIMH NIH HHS/United States ; 3-R15-MH063720-03S1/MH/NIMH NIH HHS/United States ; R15 MH063720-03S1/MH/NIMH NIH HHS/United States ; R15 MH063720-03/MH/NIMH NIH HHS/United States ; R15 MH063720/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Antimanic Agents/administration & dosage ; Antimetabolites/*pharmacology ; Avoidance Learning/*physiology ; Conditioning, Classical/*drug effects ; Cycloserine/*pharmacology ; Dose-Response Relationship, Drug ; Extinction, Psychological/*drug effects ; Lithium Chloride/administration & dosage ; Male ; Rats ; Rats, Sprague-Dawley ; *Taste/drug effects ; Time Factors ; }, abstract = {D-cycloserine, the glutamate N-methyl-D-aspartate receptor partial agonist, has been reported to facilitate the extinction of learned fears acquired in both naturalistic and laboratory settings. The current study extended this literature by evaluating the ability of either chronic or acute administrations of DCS to modulate the extinction and spontaneous recovery of a conditioned taste aversion (CTA). Twenty-three hour fluid-deprived Sprague-Dawley rats acquired a strong CTA following 3 pairings of a conditioned stimulus (CS; 0.3% oral saccharin)+unconditioned stimulus [US; 81 mg/kg (i.p.) lithium chloride (LiCl)]. In separate groups of rats, we then employed 2 different extinction paradigms: (1) CS-only (CSO-EXT) in which saccharin was presented every-other day, or (2) Explicitly Unpaired (EU-EXT) in which both saccharin and LiCl were presented but on alternate days. Previous studies have indicated that the EU-EXT procedure speeds up the extinction process. Further, spontaneous recovery of a CTA emerges following CSO-EXT but the EU-EXT paradigm causes a suppression of spontaneous recovery. DCS (15 mg/kg, i.p.) was administered immediately after daily liquid presentations (saccharin or water, alternate days) during the extinction period. In an acute drug manipulation, DCS (15 mg/kg, i.p.) or saline control injections were administered for 4 days only. This was done during one of 3 different phases of extinction [i.e., static (2-5%), early dynamic (8-16%), or middle dynamic (20-40%) saccharin reacceptance]. Other animals assigned to the chronic DCS condition received daily DCS (15 mg/kg, i.p.) throughout extinction. Changes in saccharin drinking in these animals were compared to the data from rats that received no drug (saline controls). Once rats met our criterion for asymptotic extinction (90% reacceptance of the CS) they entered a 30-day latency period during which they received water for 1 h/day. The day after the completion of the latency period, a final opportunity to drink saccharin was provided (spontaneous recovery test). Saline-treated control rats that went through the EU-EXT procedure achieved asymptotic extinction more quickly than did the CSO-EXT rats and did not exhibit a spontaneous recovery of the CTA. Chronic DCS treatments did not significantly reduce the time to achieve asymptotic CTA extinction in rats exposed to either CSO or EU extinction methods. Further, animals treated with DCS throughout EU-EXT exhibited a spontaneous recovery of the CTA whereas the saline-treated, EU-EXT rats did not. Thus, chronic DCS treatment did not shorten the time to extinguish a CTA and this treatment eliminated the ability of EU-EXT to block spontaneous recovery of the CTA. Acute DCS treatments were more effective in reducing the time required to extinguish a CTA than were chronic drug treatments. Moreover, the timing of these acute DCS treatments affected spontaneous recovery of the CTA depending on the extinction method employed. Acute DCS administrations later in extinction were more effective in reducing spontaneous recovery than were early administrations if the rats went through the CSO-EXT procedure. However, late-in-extinction administrations of DCS facilitated spontaneous recovery of the CTA in rats that experienced the EU-EXT method. These data agree with other findings suggesting that DCS treatments are more effective when administered a limited number of times. Our data extend these findings to the CTA paradigm and further suggest that, depending on the extinction paradigm employed, acute exposure to DCS can speed up CTA extinction and reduce spontaneous recovery of the aversion. The timing of the acute DCS treatment during extinction is generally less important than its duration in predicting the rate of CTA extinction. However, the timing of acute DCS treatments during extinction and the method of extinction employed can interact to affect spontaneous recovery of a CTA.}, } @article {pmid21922004, year = {2011}, author = {Yamamoto, T and Ueji, K}, title = {Brain mechanisms of flavor learning.}, journal = {Frontiers in systems neuroscience}, volume = {5}, number = {}, pages = {76}, pmid = {21922004}, issn = {1662-5137}, abstract = {Once the flavor of the ingested food (conditioned stimulus, CS) is associated with a preferable (e.g., good taste or nutritive satisfaction) or aversive (e.g., malaise with displeasure) signal (unconditioned stimulus, US), animals react to its subsequent exposure by increasing or decreasing ingestion to the food. These two types of association learning (preference learning vs. aversion learning) are known as classical conditioned reactions which are basic learning and memory phenomena, leading selection of food and proper food intake. Since the perception of flavor is generated by interaction of taste and odor during food intake, taste and/or odor are mainly associated with bodily signals in the flavor learning. After briefly reviewing flavor learning in general, brain mechanisms of conditioned taste aversion is described in more detail. The CS-US association leading to long-term potentiation in the amygdala, especially in its basolateral nucleus, is the basis of establishment of conditioned taste aversion. The novelty of the CS detected by the cortical gustatory area may be supportive in CS-US association. After the association, CS input is conveyed through the amygdala to different brain regions including the hippocampus for contextual fear formation, to the supramammillary and thalamic paraventricular nuclei for stressful anxiety or memory dependent fearful or stressful emotion, to the reward system to induce aversive expression to the CS, or hedonic shift from positive to negative, and to the CS-responsive neurons in the gustatory system to enhance the responsiveness to facilitate to detect the harmful stimulus.}, } @article {pmid21921211, year = {2011}, author = {Jonkman, S and Everitt, BJ}, title = {Dorsal and ventral striatal protein synthesis inhibition affect reinforcer valuation but not the consolidation of instrumental learning.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {18}, number = {10}, pages = {617-624}, pmid = {21921211}, issn = {1549-5485}, support = {G0001354/MRC_/Medical Research Council/United Kingdom ; G0600196/MRC_/Medical Research Council/United Kingdom ; G1002231/MRC_/Medical Research Council/United Kingdom ; 9536855/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Analysis of Variance ; Animals ; Anisomycin/pharmacology ; Conditioning, Operant/drug effects/*physiology ; Corpus Striatum/drug effects/*metabolism ; Male ; Nucleus Accumbens/drug effects ; Polysaccharides/administration & dosage ; Protein Synthesis Inhibitors/pharmacology ; Rats ; *Reinforcement, Psychology ; Time Factors ; }, abstract = {The evidence for a role of the striatum in the acquisition of uncued instrumental responding is ambiguous. It has been shown that post-session infusions of anisomycin into the core of the nucleus accumbens (NAcc) impaired instrumental acquisition, but pre-training lesions of the NAcc suggest that it is not necessary. Recently, we demonstrated that the infusion of anisomycin into the anterior cingulate cortex impaired instrumental acquisition indirectly through a taste aversion. Thus, we hypothesized that post-session anisomycin infusions into the NAcc affected instrumental acquisition through an effect on reinforcer valuation. For the dorsal striatum, both post-session infusions of anisomycin and pre-training lesion studies suggest that neither the dorsolateral nor the dorsomedial striatum is necessary for the acquisition of instrumental responding. However, it has not been attempted to block plasticity in both regions concurrently, and we hypothesized that both regions independently contribute to acquisition through goal-directed and habitual learning. In the current experiments, we first replicated the effect of unprotected post-session anisomycin infusions into the NAcc on instrumental acquisition. Subsequently, we investigated the effect of protein synthesis inhibition in the NAcc and dorsomedial and dorsolateral striatum concurrently on instrumental acquisition, critically controlling for effects on reinforcer valuation. The anisomycin infusions induced an aversive state, but did not affect instrumental acquisition.}, } @article {pmid21907816, year = {2012}, author = {Sweetat, S and Rosenblum, K and Lamprecht, R}, title = {Rho-associated kinase in the gustatory cortex is involved in conditioned taste aversion memory formation but not in memory retrieval or relearning.}, journal = {Neurobiology of learning and memory}, volume = {97}, number = {1}, pages = {1-6}, doi = {10.1016/j.nlm.2011.08.007}, pmid = {21907816}, issn = {1095-9564}, mesh = {Amides/pharmacology ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Male ; Memory/drug effects/*physiology ; Pyridines/pharmacology ; Rats ; Rats, Wistar ; Taste/drug effects/physiology ; rho-Associated Kinases/*metabolism ; }, abstract = {Rho-associated kinase (ROCK) is intimately involved in cortical neuronal morphogenesis. The present study explores the roles of ROCK in conditioned taste aversion (CTA) memory formation in gustatory cortex (GC) in adult rat. Microinjection of the ROCK inhibitor Y-27632 into the GC 30 min before CTA training or 10 min after the conditioned stimulus (CS) impaired long-term CTA memory (LTM) formation. ROCK inhibitor had no effect on taste aversion when injected before the first LTM test day and did not alter taste aversion on subsequent test days. Microinjection of ROCK inhibitor into GC 30 min before preexposure to the taste CS had no effect on latent inhibition of CTA learning suggesting that ROCK is involved in CS-US association rather than taste learning per se. Cumulatively, these results show that ROCK is needed for normal CTA memory formation but not retrieval, relearning or incidental taste learning.}, } @article {pmid21889521, year = {2012}, author = {Spencer, CM and Eckel, LA and Nardos, R and Houpt, TA}, title = {Area postrema lesions attenuate LiCl-induced c-Fos expression correlated with conditioned taste aversion learning.}, journal = {Physiology & behavior}, volume = {105}, number = {2}, pages = {151-160}, pmid = {21889521}, issn = {1873-507X}, support = {R01 DC003198-08/DC/NIDCD NIH HHS/United States ; R01DC03198/DC/NIDCD NIH HHS/United States ; T32DC00044/DC/NIDCD NIH HHS/United States ; R01 DC003198/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic/*pharmacology ; Analysis of Variance ; Animals ; Area Postrema/*injuries/physiology ; Avoidance Learning/drug effects ; Conditioning, Psychological/*drug effects ; Gene Expression Regulation/*drug effects ; Lithium Chloride/*pharmacology ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/metabolism ; Sucrose/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {Lesions of the area postrema (AP) block many of the behavioral and physiological effects of lithium chloride (LiCl) in rats, including formation of conditioned taste aversions (CTAs). Systemic administration of LiCl induces c-Fos immunoreactivity in several brain regions, including the AP, nucleus of the solitary tract (NTS), lateral parabrachial nucleus (latPBN), supraoptic nucleus (SON), paraventricular nucleus (PVN), and central nucleus of the amygdala (CeA). To determine which of these brain regions may be activated in parallel with the acquisition of LiCl-induced CTAs, we disrupted CTA learning in rats by ablating the AP and then quantified c-Fos-positive cells in these brain regions in sham- and AP-lesioned rats 1 h following LiCl or saline injection. Significant c-Fos induction after LiCl was observed in the CeA and SON of AP-lesioned rats, demonstrating activation independent of an intact AP. LiCl-induced c-Fos was significantly attenuated in the NTS, latPBN, PVN and CeA of AP-lesioned rats, suggesting that these regions are dependent on AP activation. Almost all of the lesioned rats showed some damage to the subpostremal NTS, and some rats also had damage to the dorsal motor nucleus of the vagus; this collateral damage in the brainstem may have contributed to the deficits in c-Fos response. Because c-Fos induction in several regions was correlated with magnitude of CTA acquisition, these regions are implicated in the central mediation of lithium effects during CTA learning.}, } @article {pmid21865540, year = {2011}, author = {Schier, LA and Davidson, TL and Powley, TL}, title = {Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal "bitter taste" cue.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {301}, number = {5}, pages = {R1557-68}, pmid = {21865540}, issn = {1522-1490}, support = {R37 DK027627/DK/NIDDK NIH HHS/United States ; R01 DK-027627/DK/NIDDK NIH HHS/United States ; P01 HD05211/HD/NICHD NIH HHS/United States ; }, mesh = {Afferent Pathways/drug effects/metabolism ; Animals ; Appetite Regulation/*drug effects ; Behavior, Animal/*drug effects ; Cholecystokinin/metabolism ; Conditioning, Psychological/drug effects ; *Cues ; Devazepide/administration & dosage ; Duodenum/*innervation ; Eating/*drug effects ; Hormone Antagonists/administration & dosage ; Intubation, Gastrointestinal ; Male ; Quaternary Ammonium Compounds/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptor, Cholecystokinin A/antagonists & inhibitors/metabolism ; Receptors, G-Protein-Coupled/*drug effects/metabolism ; Saccharin/administration & dosage ; Signal Transduction/drug effects ; Sweetening Agents/administration & dosage ; Taste/*drug effects ; Time Factors ; }, abstract = {The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral "taste" receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants-and concentrations of tastants-in the lumen of the gut can control ingestion.}, } @article {pmid21855644, year = {2011}, author = {Mizoguchi, N and Fujita, S and Koshikawa, N and Kobayashi, M}, title = {Spatiotemporal dynamics of long-term potentiation in rat insular cortex revealed by optical imaging.}, journal = {Neurobiology of learning and memory}, volume = {96}, number = {3}, pages = {468-478}, doi = {10.1016/j.nlm.2011.07.003}, pmid = {21855644}, issn = {1095-9564}, mesh = {Analysis of Variance ; Animals ; Cerebral Cortex/anatomy & histology/drug effects/*physiology ; Cholinergic Agents/pharmacology ; Electric Stimulation ; Excitatory Amino Acid Antagonists/pharmacology ; Long-Term Potentiation/drug effects/*physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Refractory Period, Electrophysiological ; Taste Perception/*physiology ; Voltage-Sensitive Dye Imaging ; }, abstract = {Long-term potentiation (LTP) of the gustatory cortex (GC), a part of the insular cortex (IC) around the middle cerebral artery, is a key process of gustatory learning and memory, including conditioned taste aversion learning. The rostral (rGC) and caudal GC (cGC) process different tastes; the rGC responds to hedonic and the cGC responds to aversive tastes. However, plastic changes of spatial interaction of excitatory propagation between the rGC and cGC remain unknown. The present study aimed to elucidate spatiotemporal profiles of excitatory propagation, induced by electrical stimulation (five train pulses) of the rGC/cGC before and after LTP induction, using in vivo optical imaging with a voltage-sensitive dye. We demonstrated that tetanic stimulation of the cGC induced long-lasting expansion of the excitation responding to five train stimulation of the cGC, and an increase in amplitude of optical signals in the IC. Excitatory propagation after LTP induction spread preferentially toward the rostral IC: the length constant (λ) of excitation, obtained by fitting optical signals with a monoexponential curve, was increased to 121.9% in the rostral direction, whereas λ for the caudal, dorsal, and ventral directions were 48.9%, 44.2%, and 62.5%, respectively. LTP induction was prevented by pre-application of D-APV, an NMDA receptor antagonist, or atropine, a muscarinic receptor antagonist, to the cortical surface. In contrast, rGC stimulation induced only slight LTP without direction preference. Considering the different roles of the rGC and cGC in gustatory processing, these characteristic patterns of LTP in the GC may be involved in a mechanism underlying conversion of palatability.}, } @article {pmid21843567, year = {2011}, author = {Nakajima, S}, title = {Calorie supply does not alleviate running-based taste aversion learning in rats.}, journal = {Appetite}, volume = {57}, number = {3}, pages = {605-614}, doi = {10.1016/j.appet.2011.08.001}, pmid = {21843567}, issn = {1095-8304}, mesh = {Animals ; Conditioning, Classical/*drug effects ; Cyclophosphamide ; Energy Intake/*drug effects ; Energy Metabolism ; Male ; Rats ; Rats, Wistar ; Reproducibility of Results ; Research Design ; Running/*physiology ; Saccharin/administration & dosage ; Sucrose/administration & dosage ; *Taste ; }, abstract = {Voluntary running establishes aversion to the paired taste in rats. A proposed mechanism underlying this taste aversion learning is energy expenditure caused by the running. The energy expenditure hypothesis predicts that running-based taste aversion should be alleviated by a calorie supply since this would compensate for the energy expended by running. Accordingly, running-based taste aversion would be less readily established to a caloric substance (20% sucrose solution) than to a noncaloric substance (0.2% sodium saccharin solution). Because the sucrose and saccharin aversions were equivalent in Experiment 1, the validity of the energy expenditure hypothesis was questioned. Experiments 2 and 3 also pose a problem for this hypothesis, as post-session calorie supply by glucose tablets failed to alleviate running-based aversion to salty water.}, } @article {pmid21824258, year = {2011}, author = {Jensen, PB and Larsen, PJ and Karlsen, C and Jensen, HI and Holst, JJ and Madsen, OD}, title = {Foetal proglucagon processing in relation to adult appetite control: lessons from a transplantable rat glucagonoma with severe anorexia.}, journal = {Diabetes, obesity & metabolism}, volume = {13 Suppl 1}, number = {}, pages = {60-68}, doi = {10.1111/j.1463-1326.2011.01439.x}, pmid = {21824258}, issn = {1463-1326}, mesh = {Animals ; Anorexia/chemically induced/*metabolism ; Appetite Regulation/drug effects ; Glucagon-Like Peptide 1/adverse effects/*blood ; Glucagon-Like Peptide-1 Receptor ; Glucagonoma/complications/*metabolism ; Male ; Neoplasm Transplantation ; Pancreatic Neoplasms/*metabolism ; Peptide Fragments/administration & dosage ; Proglucagon/*metabolism ; Rats ; Receptors, Glucagon/*antagonists & inhibitors ; *Taste ; }, abstract = {We have previously reported severe anorexia abruptly induced in rats 2-3 weeks after they have been transplanted subcutaneously with the glucagonoma MSL-G-AN. Vagotomy did not affect the time of onset and severity of anorexia, and the anorectic state resembles hunger with strongly elevated neuropeptide Y (NPY) mRNA levels in the nucleus arcuatus. We now show that circulating levels of bioactive glucagon-like peptide-1 (GLP-1) (7-36amide) start to increase above control levels exactly at the time of onset of anorexia. At this time-point, bioactive glucagon as well as total glucagon precursors and GLP-1 metabolites are already vastly elevated compared to controls. We further show that intravenous administration of very high concentrations of GLP-1 to hungry schedule-fed rats causes anorexia in a dose-dependent manner, which is blocked by the GLP-1 receptor antagonist exendin (9-39). GLP-1 (7-36amide) has a well-characterized anorectic effect but also causes taste aversion when administered centrally. The anorectic effect is blocked in rats treated neonatally by monosodium glutamate (MSG). We show that MSG treatment does not prevent the MSL-G-AN-induced anorexia, thereby suggesting a different type of anorectic function. We show a very strong component of taste aversion as anorectic rats, when presented to novel or known alternative food items, will resume normal feeding for 1 day, and then redevelop anorexia. We hypothetize that the anorexia in MSL-G-AN tumour-bearing rats correlates with a foetal processing pattern of proglucagon to both glucagon and GLP-1 (7-36amide), and is due to taste aversion. The sudden onset is characterized by a dramatic increase in circulating levels of biologically active GLP-1 (7-36amide), suggesting eventual saturation of proteolytic inactivation of its N-terminus.}, } @article {pmid21808604, year = {2011}, author = {Horn, CC and Henry, S and Meyers, K and Magnusson, MS}, title = {Behavioral patterns associated with chemotherapy-induced emesis: a potential signature for nausea in musk shrews.}, journal = {Frontiers in neuroscience}, volume = {5}, number = {}, pages = {88}, pmid = {21808604}, issn = {1662-453X}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 DK065971/DK/NIDDK NIH HHS/United States ; R01 DK065971-06/DK/NIDDK NIH HHS/United States ; }, abstract = {Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model. Indeed investigating the effects of anti-nausea drugs in pre-clinical models is difficult because the primary readout is often emesis. It is known that animals show a behavioral profile of sickness, associated with reduced feeding and movement, and possibly these general measures are signs of nausea. Studies attempting to relate the occurrence of additional behaviors to emesis have produced mixed results. Here we applied a statistical method, temporal pattern (t-pattern) analysis, to determine patterns of behavior associated with emesis. Musk shrews were injected with the chemotherapy agent cisplatin (a gold standard in emesis research) to induce acute (<24 h) and delayed (>24 h) emesis. Emesis and other behaviors were coded and tracked from video files. T-pattern analysis revealed hundreds of non-random patterns of behavior associated with emesis, including sniffing, changes in body contraction, and locomotion. There was little evidence that locomotion was inhibited by the occurrence of emesis. Eating, drinking, and other larger body movements including rearing, grooming, and body rotation, were significantly less common in emesis-related behavioral patterns in real versus randomized data. These results lend preliminary evidence for the expression of emesis-related behavioral patterns, including reduced ingestive behavior, grooming, and exploratory behaviors. In summary, this statistical approach to behavioral analysis in a pre-clinical emesis research model could be used to assess the more global effects and limitations of drugs used to control nausea and its potential correlates, including reduced feeding and activity levels.}, } @article {pmid21798517, year = {2011}, author = {McDannald, MA and Whitt, JP and Calhoon, GG and Piantadosi, PT and Karlsson, RM and O'Donnell, P and Schoenbaum, G}, title = {Impaired reality testing in an animal model of schizophrenia.}, journal = {Biological psychiatry}, volume = {70}, number = {12}, pages = {1122-1126}, pmid = {21798517}, issn = {1873-2402}, support = {T32-NS-07375/NS/NINDS NIH HHS/United States ; R01-DA-015718/DA/NIDA NIH HHS/United States ; R01-MH-57683/MH/NIMH NIH HHS/United States ; R01 DA015718-08/DA/NIDA NIH HHS/United States ; R01 MH057683/MH/NIMH NIH HHS/United States ; R01 DA015718/DA/NIDA NIH HHS/United States ; T32 NS007375/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn/surgery ; Association Learning/physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Discrimination, Psychological/*physiology ; Disease Models, Animal ; Hallucinations/physiopathology ; Hippocampus/*physiology/physiopathology ; Male ; Rats ; Rats, Long-Evans ; *Reality Testing ; Schizophrenia/*physiopathology ; Schizophrenic Psychology ; Taste ; }, abstract = {BACKGROUND: Schizophrenia is a chronic and devastating brain disorder characterized by hallucinations and delusions, symptoms reflecting impaired reality testing. Although animal models have captured negative symptoms and cognitive deficits associated with schizophrenia, none have addressed these defining, positive symptoms.

METHODS: Here we tested the performance of adults given neonatal ventral hippocampal lesions (NVHL), a neurodevelopmental model of schizophrenia, in two taste aversion procedures.

RESULTS: Normal and NVHL rats formed aversions to a palatable food when the food was directly paired with nausea, but only NVHL rats formed a food aversion when the cue predicting that food was paired with nausea. The failure of NVHL rats to discriminate fully real from imagined food parallels the failure of people with schizophrenia to differentiate internal thoughts and beliefs from reality.

CONCLUSIONS: These results further validate the NVHL model of schizophrenia and provide a means to assess impaired reality testing in variety of animal models.}, } @article {pmid21796102, year = {2011}, author = {Chen, H and Sharp, BM and Matta, SG and Wu, Q}, title = {Social interaction promotes nicotine self-administration with olfactogustatory cues in adolescent rats.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {36}, number = {13}, pages = {2629-2638}, pmid = {21796102}, issn = {1740-634X}, support = {R21 DA026894/DA/NIDA NIH HHS/United States ; DA-026894/DA/NIDA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Behavior, Animal/drug effects/physiology ; Disease Models, Animal ; Female ; Nicotine/*adverse effects ; Rats ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Self Administration/psychology ; Smell/drug effects/*physiology ; Smoking/physiopathology/psychology ; *Social Behavior ; Taste/drug effects/*physiology ; Tobacco Use Disorder/*physiopathology/psychology ; }, abstract = {Cigarette smoking is a social behavior. Smoking is also accompanied by distinctive gustatory and olfactory stimulation. However, none of these factors affecting nicotine intake are modeled in existing preclinical studies. We report a novel model of adolescent nicotine self-administration (SA) in rats where licking on drinking spouts was used as the operant behavior to activate the concurrent delivery of nicotine (i.v.) and an appetitive olfactogustatory (OG) cue, and social interaction was required for stable SA. The operant chamber was divided by a panel that separated the SA rat and another rat serving as the demonstrator, who had free access to the OG cue but did not receive nicotine. Orofacial contacts were permitted by the divider. Conditioned taste aversion prevented solo rats to self-administer nicotine. However, stable nicotine (15-30 μg/kg, free base) SA was established in the presence of demonstrator rats with free access to the OG cue. Omitting the olfactory component of the cue prevented the acquisition of nicotine SA. Mecamylamine, a nicotinic antagonist, reduced licking behavior. Familiar peers were more effective demonstrators in facilitating the acquisition of nicotine SA than were unfamiliar rats. No sex difference in nicotine intake was found. These data indicate that the contingent OG cue is associated with the aversive property of nicotine that prevents subsequent drug intake. Social information encoded in olfaction not only permits the establishment of stable nicotine SA but also enhances nicotine intake. These findings implicate adolescent social interactions in promoting smoking behavior by surmounting the aversive property of nicotine.}, } @article {pmid21784922, year = {2011}, author = {Gámiz, F and Gallo, M}, title = {Intra-amygdala ZIP injections impair the memory of learned active avoidance responses and attenuate conditioned taste-aversion acquisition in rats.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {18}, number = {8}, pages = {529-533}, doi = {10.1101/lm.2253311}, pmid = {21784922}, issn = {1549-5485}, mesh = {Amygdala/*drug effects/physiology ; Animals ; Avoidance Learning/drug effects ; Cell-Penetrating Peptides ; Conditioning, Classical/drug effects ; Conditioning, Operant/drug effects ; Conditioning, Psychological/*drug effects ; Disease Models, Animal ; Drug Administration Routes ; Food Preferences/drug effects ; Lipopeptides/pharmacology ; Male ; Memory Disorders/*chemically induced ; Oligopeptides/*pharmacology ; Protein Kinase C/*antagonists & inhibitors/chemistry ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Taste/*drug effects ; }, abstract = {We have investigated the effect of protein kinase Mzeta (PKMζ) inhibition in the basolateral amygdala (BLA) upon the retention of a nonspatial learned active avoidance response and conditioned taste-aversion (CTA) acquisition in rats. ZIP (10 nmol/μL) injected into the BLA 24 h after training impaired retention of a learned avoidance-jumping response assessed 7 d later when compared with control groups injected with scrambled-ZIP. Nevertheless, a retraining session applied 24 h later indicated no differences between the groups. Additionally, a similar ZIP injection into the BLA during the conditioned stimulus-unconditioned stimulus (CS-US) interval attenuated CTA acquisition. These findings support the BLA PKMζ role in various forms of memory.}, } @article {pmid21767576, year = {2011}, author = {Sherrill, LK and Berthold, C and Koss, WA and Juraska, JM and Gulley, JM}, title = {Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.}, journal = {Behavioural brain research}, volume = {225}, number = {1}, pages = {104-109}, pmid = {21767576}, issn = {1872-7549}, support = {R21 AA017354/AA/NIAAA NIH HHS/United States ; R21 AA017354-02/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Analysis of Variance ; Animals ; Blinking/drug effects ; Central Nervous System Depressants/*pharmacology ; Conditioning, Classical/*drug effects ; Ethanol/*pharmacology ; Female ; Food Preferences/drug effects ; Humans ; Male ; Rats ; Rats, Long-Evans ; Saccharin/administration & dosage ; *Sex Characteristics ; Sweetening Agents/administration & dosage ; Taste/*drug effects ; }, abstract = {Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females.}, } @article {pmid21734019, year = {2011}, author = {le Roux, CW and Bueter, M and Theis, N and Werling, M and Ashrafian, H and Löwenstein, C and Athanasiou, T and Bloom, SR and Spector, AC and Olbers, T and Lutz, TA}, title = {Gastric bypass reduces fat intake and preference.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {301}, number = {4}, pages = {R1057-66}, pmid = {21734019}, issn = {1522-1490}, support = {BB/E52708X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; DHCS/05/05/DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Dietary Fats/*metabolism ; Eating/*physiology ; Energy Intake/physiology ; Female ; Food Preferences/*physiology ; *Gastric Bypass ; *Gastroplasty ; Glucagon-Like Peptide 1/metabolism ; Humans ; Male ; Models, Animal ; Obesity/*surgery ; Rats ; Rats, Wistar ; Saccharin/metabolism ; Taste/physiology ; Time Factors ; }, abstract = {Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.}, } @article {pmid21689770, year = {2011}, author = {Martín, I and Gómez, A and Salas, C and Puerto, A and Rodríguez, F}, title = {Dorsomedial pallium lesions impair taste aversion learning in goldfish.}, journal = {Neurobiology of learning and memory}, volume = {96}, number = {2}, pages = {297-305}, doi = {10.1016/j.nlm.2011.06.003}, pmid = {21689770}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Cerebellum/drug effects/physiopathology ; Goldfish ; Lithium Chloride/pharmacology ; Memory/drug effects/physiology ; Taste/drug effects/*physiology ; Telencephalon/drug effects/*physiopathology ; }, abstract = {The present work shows that the dorsomedial telencephalic pallium of teleost fish, proposed as homologous to the amygdala of mammals, is involved in taste aversion learning (TAL). To analyze the behavioral properties of TAL in goldfish, in Experiment 1, we used a delayed procedure similar to that employed with mammals, which consists of the presentation of two flavors on different days, one followed by lithium chloride and the other by saline, both after a 10-min delay. The results showed that goldfish developed a strong aversion to the gustatory stimulus followed by visceral discomfort and that, as in mammals, this learning was rapidly acquired, highly flexible and maintained for a long time. Experiment 2 showed that dorsomedial pallium lesions and the ablation of the telencephalic lobes impaired the acquisition of taste aversion in goldfish, whereas damage to the dorsolateral pallium (hippocampus homologue) or cerebellar corpus did not produce significant changes in this learning. Experiment 3 showed that these TAL deficits were not due to a lesion-related disruption of taste discrimination; goldfish with telencephalon ablation were able to learn to distinguish between the two tested flavors in a differential conditioning procedure. These functional data demonstrate that the dorsomedial pallium in teleosts is, like the amygdala, an essential component of the telencephalon-dependent taste aversion memory system and provide further support concerning the homology between both structures.}, } @article {pmid21633328, year = {2011}, author = {Deacon, RM}, title = {Hyponeophagia: a measure of anxiety in the mouse.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {51}, pages = {}, pmid = {21633328}, issn = {1940-087X}, support = {WT084655MA//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Anxiety/*diagnosis ; Feeding Behavior/*psychology ; Food Preferences/psychology ; Mice ; Rats ; }, abstract = {Before the present day, when fast-acting and potent rodenticides such as alpha-chloralose were not yet in use, the work of pest controllers was often hampered by a phenomenon known as "bait shyness". Mice and rats cannot vomit, due to the tightness of the cardiac sphincter of the stomach, so to overcome the problem of potential food toxicity they have evolved a strategy of first ingesting only very small amounts of novel substances. The amounts ingested then gradually increase until the animal has determined whether the substance is safe and nutritious. So the old rat-catchers would first put a palatable substance such as oatmeal, which was to be the vehicle for the toxin, in the infested area. Only when large amounts were being readily consumed would they then add the poison, in amounts calculated not to affect the taste of the vehicle. The poisoned bait, which the animals were now readily eating in large amounts, would then swiftly perform its function. Bait shyness is now used in the behavioural laboratory as a way of measuring anxiety. A highly palatable but novel substance, such as sweet corn, nuts or sweetened condensed milk, is offered to the mice (or rats) in a novel situation, such as a new cage. The latency to consume a defined amount of the new food is then measured.}, } @article {pmid21627635, year = {2011}, author = {Fekete, EM and Zhao, Y and Szücs, A and Sabino, V and Cottone, P and Rivier, J and Vale, WW and Koob, GF and Zorrilla, EP}, title = {Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress.}, journal = {British journal of pharmacology}, volume = {164}, number = {8}, pages = {1959-1975}, pmid = {21627635}, issn = {1476-5381}, support = {R01 DA030425/DA/NIDA NIH HHS/United States ; DK026741/DK/NIDDK NIH HHS/United States ; P01 DK026741/DK/NIDDK NIH HHS/United States ; DK070118/DK/NIDDK NIH HHS/United States ; DK64871/DK/NIDDK NIH HHS/United States ; K99 DA023680/DA/NIDA NIH HHS/United States ; R01 DK070118/DK/NIDDK NIH HHS/United States ; R03 DK064871/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Corticosterone/blood ; Corticotropin-Releasing Hormone/*analogs & derivatives/physiology ; *Feeding Behavior ; Female ; Male ; Mice ; Mice, Knockout ; Peptides, Cyclic/*physiology ; Rats ; Rats, Wistar ; Receptors, Corticotropin-Releasing Hormone/genetics/*physiology ; *Stress, Physiological ; Urocortins/*physiology ; }, abstract = {BACKGROUND AND PURPOSE: Infusion of corticotropin-releasing factor (CRF)/urocortin (Ucn) family peptides suppresses feeding in mice. We examined whether rats show peripheral CRF/Ucn-induced anorexia and determined its behavioural and pharmacological bases.

EXPERIMENTAL APPROACH: Male Wistar rats (n= 5-12 per group) were administered (i.p.) CRF receptor agonists with different subtype affinities. Food intake, formation of conditioned taste aversion and corticosterone levels were assessed. In addition, Ucn 1- and Ucn 2-induced anorexia was studied in fasted CRF(2) knockout (n= 11) and wild-type (n= 13) mice.

KEY RESULTS: Ucn 1, non-selective CRF receptor agonist, reduced food intake most potently (~0.32 nmol·kg(-1)) and efficaciously (up to 70% reduction) in fasted and fed rats. The peptides' rank-order of anorexic potency was Ucn 1 ≥ Ucn 2 > >stressin(1) -A > Ucn 3, and efficacy, Ucn 1 > stressin(1) -A > Ucn 2 = Ucn 3. Ucn 1 reduced meal frequency and size, facilitated feeding bout termination and slowed eating rate. Stressin(1) -A (CRF(1) agonist) reduced meal size; Ucn 2 (CRF(2) agonist) reduced meal frequency. Stressin(1) -A and Ucn 1, but not Ucn 2, produced a conditioned taste aversion, reduced feeding efficiency and weight regain and elicited diarrhoea. Ucn 1, but not Ucn 2, also increased corticosterone levels. Ucn 1 and Ucn 2 reduced feeding in wild-type, but not CRF(2) knockout, mice.

CONCLUSIONS AND IMPLICATIONS: CRF(1) agonists, Ucn 1 and stressin(1) -A, reduced feeding and induced interoceptive stress, whereas Ucn 2 potently suppressed feeding via a CRF(2) -dependent mechanism without eliciting malaise. Consistent with their pharmacological differences, peripheral urocortins have diverse effects on appetite.}, } @article {pmid21596065, year = {2011}, author = {Norris, JN and Ortega, LA and Papini, MR}, title = {Posttrial d-cycloserine enhances the emotional memory of an incentive downshift event.}, journal = {Behavioural brain research}, volume = {223}, number = {2}, pages = {348-355}, doi = {10.1016/j.bbr.2011.05.001}, pmid = {21596065}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Operant/drug effects ; Consummatory Behavior/drug effects ; Corticosterone/pharmacology ; Cycloserine/*pharmacology ; Dose-Response Relationship, Drug ; Emotions/*drug effects ; Excitatory Amino Acid Agonists/*pharmacology ; Male ; Memory/*drug effects ; Motivation ; Rats ; Rats, Long-Evans ; Receptors, Glycine/drug effects ; Receptors, N-Methyl-D-Aspartate/*agonists ; Sucrose/pharmacology ; Taste ; }, abstract = {The present research was designed to determine whether an incentive downshift event induces an emotional memory that can be modulated by d-cycloserine (DCS), a partial agonist at the glycine site of N-methyl-d-aspartate receptor (NMDAR). DCS has been reported to have memory-enhancing properties in other training situations. Experiments 1 and 2 involved a consummatory successive negative contrast (cSNC) situation in which animals are exposed to an incentive downshift involving sucrose solutions of different concentrations. DCS administration (30 mg/kg, ip) immediately after the first 32-to-4% sucrose downshift trial (Experiment 1) retarded recovery of consummatory behavior, but immediately after the first 32-to-6% sucrose downshift trial (Experiment 2) did not affect recovery. There was no evidence that DCS affected consummatory behavior in the absence of an incentive downshift in a manner analogous to a conditioned taste aversion (Experiment 3). These results suggest that activation of NMDARs via the glycine modulatory site enhances the emotional memory triggered by exposure to an incentive downshift event.}, } @article {pmid21576927, year = {2011}, author = {Chung, WC and Huang, TN and Hsueh, YP}, title = {Targeted deletion of CASK-interacting nucleosome assembly protein causes higher locomotor and exploratory activities.}, journal = {Neuro-Signals}, volume = {19}, number = {3}, pages = {128-141}, doi = {10.1159/000327819}, pmid = {21576927}, issn = {1424-8638}, mesh = {Animals ; Avoidance Learning/physiology ; Brain/anatomy & histology/embryology/growth & development/metabolism ; Conditioning, Classical/physiology ; Exploratory Behavior/*physiology ; Fear/physiology ; Female ; Gene Expression Regulation, Developmental/genetics ; Locomotion/*genetics ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins/*deficiency/genetics ; Nuclear Proteins/*deficiency/genetics ; Receptors, N-Methyl-D-Aspartate/genetics/metabolism ; Recognition, Psychology/physiology ; Sequence Deletion/*genetics ; Taste/genetics ; }, abstract = {CASK-interacting nucleosome assembly protein (CINAP) has been shown to interact with the calcium/calmodulin-dependent serine kinase (CASK) and the T-box transcription factor T-brain-1 (Tbr1) thus modulating the expression of N-methyl-D-aspartic acid receptor subunit 2b (NMDAR2b) in cultured hippocampal neurons. To explore the physiological significance of CINAP in vivo, CINAP knockout mice were generated and subjected to biochemical, anatomical, and behavioral analyses. Unexpectedly, CINAP deletion did not impact NMDAR2b expression, and these CINAP knockout mice were consistently comparable to wild-type littermates in terms of immediate memory (assessed with the Y maze) and associative memory (evaluated by conditioned taste aversion and contextual and auditory fear conditioning). Although CINAP deletion did not obviously influence learning and memory behaviors, CINAP knockout mice exhibited higher locomotor and exploratory activities. Compared with wild-type littermates, the horizontal and vertical movements of the CINAP knockout mice were higher in a novel environment; in home cages, rearing, sniffing, and jumping also occurred more frequently in CINAP knockout mice. These observations suggest that although CINAP deletion in mice does not influence learning and memory behaviors, CINAP is required for restriction of locomotor and exploratory activities.}, } @article {pmid21576517, year = {2011}, author = {Chung, A and Barot, SK and Kim, JJ and Bernstein, IL}, title = {Biologically predisposed learning and selective associations in amygdalar neurons.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {18}, number = {6}, pages = {371-374}, pmid = {21576517}, issn = {1549-5485}, support = {R01 MH064457/MH/NIMH NIH HHS/United States ; R01 NS037040/NS/NINDS NIH HHS/United States ; R01 NS37040/NS/NINDS NIH HHS/United States ; R01 MH64457/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*cytology ; Analysis of Variance ; Animals ; Apoptosis Regulatory Proteins/genetics/metabolism ; Association Learning/*physiology ; Avoidance Learning/physiology ; Conditioning, Classical/*physiology ; Diterpenes/administration & dosage ; Electroshock/adverse effects ; Fear ; Furans/administration & dosage ; Lithium Chloride/administration & dosage ; Male ; Muscle Proteins/genetics/metabolism ; Neurons/*physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Taste/physiology ; }, abstract = {Modern views on learning and memory accept the notion of biological constraints-that the formation of association is not uniform across all stimuli. Yet cellular evidence of the encoding of selective associations is lacking. Here, conditioned stimuli (CSs) and unconditioned stimuli (USs) commonly employed in two basic associative learning paradigms, fear conditioning and taste aversion conditioning, were delivered in a manner compatible with a functional cellular imaging technique (Arc cellular compartmental analysis of temporal gene transcription by fluorescence in situ hybridization [catFISH]) to identify biological constraints on CS-US convergence at the level of neurons in basolateral amygdala (BLA). Results indicate coincident Arc mRNA activation within BLA neurons after CS-US combinations that yield rapid, efficient learning, but not after CS-US combinations that do not.}, } @article {pmid21575017, year = {2011}, author = {Holstein, SE and Spanos, M and Hodge, CW}, title = {Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking.}, journal = {Alcoholism, clinical and experimental research}, volume = {35}, number = {10}, pages = {1842-1851}, pmid = {21575017}, issn = {1530-0277}, support = {R01 AA016629/AA/NIAAA NIH HHS/United States ; R01 AA016629-03/AA/NIAAA NIH HHS/United States ; AA007573/AA/NIAAA NIH HHS/United States ; P60 AA011605-14/AA/NIAAA NIH HHS/United States ; P60 AA011605/AA/NIAAA NIH HHS/United States ; R01 AA014983-05/AA/NIAAA NIH HHS/United States ; AA014983/AA/NIAAA NIH HHS/United States ; AA011605/AA/NIAAA NIH HHS/United States ; R01 AA016629-04/AA/NIAAA NIH HHS/United States ; P60 AA011605-12/AA/NIAAA NIH HHS/United States ; R01 AA014983/AA/NIAAA NIH HHS/United States ; R37 AA014983/AA/NIAAA NIH HHS/United States ; AA016629/AA/NIAAA NIH HHS/United States ; R01 AA014983-03/AA/NIAAA NIH HHS/United States ; R01 AA014983-04/AA/NIAAA NIH HHS/United States ; P50 AA011605/AA/NIAAA NIH HHS/United States ; P60 AA011605-13/AA/NIAAA NIH HHS/United States ; T32 AA007573/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Alcohol Drinking/blood/*pathology/psychology ; Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/blood/pharmacology/*poisoning ; Conditioning, Psychological/*drug effects ; Disease Models, Animal ; Dysgeusia ; Ethanol/blood/pharmacology/*poisoning ; Extinction, Psychological ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA).

METHODS: Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl).

RESULTS: Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice.

CONCLUSIONS: These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol.}, } @article {pmid21565224, year = {2011}, author = {Mediavilla, C and Bernal, A and Mahía, J and Puerto, A}, title = {Nucleus of the solitary tract and flavor aversion learning: relevance in concurrent but not sequential behavioral test.}, journal = {Behavioural brain research}, volume = {223}, number = {2}, pages = {287-292}, doi = {10.1016/j.bbr.2011.04.044}, pmid = {21565224}, issn = {1872-7549}, mesh = {Animals ; Area Postrema/physiology ; Avoidance Learning/*physiology ; Conditioning, Operant/physiology ; Discrimination Learning/physiology ; Male ; Rats ; Rats, Wistar ; Saline Solution, Hypertonic/pharmacology ; Sodium Chloride/pharmacology ; Solitary Nucleus/*physiology ; Stomach/physiology ; Taste/*physiology ; Vagus Nerve/physiology ; }, abstract = {Theories relating the nucleus of the solitary tract to taste aversion learning (TAL) have received their main support from immunohistochemical research. In the present study, a behavioral analysis was performed on the effect of lesions of the intermediate nucleus of the solitary tract (iNST) on concurrent and sequential flavor aversion learning tasks. Bilateral lesions of the iNST impaired concurrent flavor learning, in which animals must discriminate between two simultaneously presented flavors paired with intragastric administration of a noxious or innocuous substance, respectively. However, the same iNST lesions did not interrupt the development of sequential flavor aversion learning, in which each flavor is offered individually on consecutive alternate days. These results behaviorally confirm the relevance of the nucleus of the solitary tract in TAL and suggest a functional dissociation between the neural systems underlying concurrent and sequential flavor aversion learning.}, } @article {pmid21549734, year = {2011}, author = {Taylor, KM and Mark, GP and Hoebel, BG}, title = {Conditioned taste aversion from neostigmine or methyl-naloxonium in the nucleus accumbens.}, journal = {Physiology & behavior}, volume = {104}, number = {1}, pages = {82-86}, doi = {10.1016/j.physbeh.2011.04.050}, pmid = {21549734}, issn = {1873-507X}, support = {DA10608/DA/NIDA NIH HHS/United States ; NS 30697/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Cholinesterase Inhibitors/*pharmacology ; Conditioning, Psychological/*drug effects ; Male ; Morphine/pharmacology ; Naloxone/analogs & derivatives/*pharmacology ; Narcotic Antagonists/*pharmacology ; Neostigmine/*pharmacology ; Nucleus Accumbens/*drug effects ; Opioid-Related Disorders/physiopathology ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome ; }, abstract = {An opioid antagonist injected in the nucleus accumbens of a morphine-dependent rat will lower extracellular dopamine and release acetylcholine (ACh), as also seen in opiate withdrawal. It was hypothesized that raising extracellular ACh experimentally would be aversive as reflected by the induction of a conditioned taste aversion. Rats were implanted with cannulas aimed above the nucleus accumbens (NAc) for injection of the opiate antagonist methyl-naloxonium in morphine-dependent animals or neostigmine to increase ACh in drug naïve animals. Experiment 1 in addicted rats showed that local morphine withdrawal by local injection of methyl-naloxonium paired with the taste of saccharin induces a conditioned taste aversion. Experiment 2 in non-addicted rats demonstrated the same learned aversion after local administration of the cholinergic agonist neostigmine in the NAc. These results suggest that ACh released in the NAc during opiate withdrawal contributes to the dysphoric, aversive state characteristic of withdrawal. This accumbens system is implicated in the mechanism for generating the memory of an aversive event that is expressed as learned taste aversion.}, } @article {pmid21546172, year = {2011}, author = {Awasaki, Y and Nojima, H and Nishida, N}, title = {Application of the conditioned taste aversion paradigm to assess discriminative stimulus properties of psychostimulants in rats.}, journal = {Drug and alcohol dependence}, volume = {118}, number = {2-3}, pages = {288-294}, doi = {10.1016/j.drugalcdep.2011.04.007}, pmid = {21546172}, issn = {1879-0046}, mesh = {Animals ; Avoidance Learning/*drug effects ; Central Nervous System Stimulants/*administration & dosage ; Cocaine/*administration & dosage ; Conditioning, Psychological/*drug effects ; Discrimination Learning/drug effects ; Male ; Methamphetamine/*administration & dosage ; Rats ; Saccharin/administration & dosage ; Taste/drug effects ; }, abstract = {BACKGROUND: The conditioned taste aversion (CTA) paradigm is one of the reliable methods to evaluate the discriminative stimulus properties of drugs and is characterized by a short conditioning period and no need for special equipment. This method, however, has not yet been fully investigated for psychostimulants such as cocaine and methamphetamine.

METHODS: In the present study, rats were trained to discriminate between cocaine and a vehicle using CTA and substitution tests with various psychostimulants were conducted to evaluate the usefulness of the method for assessing the discriminative stimulus properties of this pharmacological class. Male rats received an intraperitoneal (i.p.) injection of cocaine (10mg/kg) 10 min prior to access saccharin for 20-min, and immediately after the saccharin access they received an i.p. dose of LiCl (1.8 mEq; n=8, Group CL) or the vehicle (n=8, Group CW) on the day of conditioning; on the other days (2 or 3 days between the cocaine conditioning days), they were injected with saline prior to access to saccharin without the LiCl or vehicle injection after the access.

RESULTS: By the fifteenth cocaine conditioning trial, all animals acquired discrimination. In the substitution test, cocaine dose dependently decreased saccharin consumption. The psychostimulants, methamphetamine, methylphenidate, bupropion and sibutramine, substituted for cocaine, whereas the opioid μ agonist morphine and the cannabinoid agonist, Δ9-tetrahydrocannabinol, did not substitute for cocaine. Mazindol did not substitute for cocaine although it has CNS stimulant activities.

CONCLUSION: These results suggest that discriminative stimulus properties of psychostimulants can be evaluated using the CTA paradigm.}, } @article {pmid21540449, year = {2011}, author = {Roy, C and Roy, MC and Gauvreau, D and Poulin, AM and Tom, FQ and Timofeeva, E and Richard, D and Cianflone, K}, title = {Acute injection of ASP in the third ventricle inhibits food intake and locomotor activity in rats.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {301}, number = {1}, pages = {E232-41}, doi = {10.1152/ajpendo.00476.2010}, pmid = {21540449}, issn = {1522-1555}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Anorexia/chemically induced/genetics/metabolism ; Cerebrospinal Fluid/physiology ; Complement C3 ; Down-Regulation/drug effects ; Eating/*drug effects ; Gene Expression Regulation/drug effects ; Humans ; Injections, Intraventricular ; Intercellular Signaling Peptides and Proteins/*administration & dosage/adverse effects/*pharmacology ; Male ; Motor Activity/*drug effects/physiology ; Oxygen Consumption/drug effects/physiology ; Pro-Opiomelanocortin/genetics/metabolism ; Rats ; Rats, Wistar ; Recombinant Proteins/administration & dosage/pharmacology ; Time Factors ; }, abstract = {Acylation-stimulating protein (ASP; also known as C3adesArg) stimulates triglyceride synthesis and glucose transport via interaction with its receptor C5L2, which is expressed peripherally (adipose tissue, muscle) and centrally. Previous studies have shown that ASP-deficient mice (C3KO) and C5L2-deficient mice (C5L2KO) are hyperphagic (59 to 229% increase, P < 0.0001), which is counterbalanced by increased energy expenditure measured as oxygen consumption (Vo(2)) and a lower RQ. The aim of the present study was to evaluate ASP's effect on food intake, energy expenditure, and neuropeptide expression. Male rats were surgically implanted with intracerebroventricular (icv) cannulas directed toward the third ventricle. After a 5-h fast, rats were injected, and food intake was assessed at 0.5, 1, 2, 4, 16, 24, and 48 h, with a 5- to 7-day washout period between each injection. Acute icv injections of ASP (0.3-1,065 pmol) had a time-dependent effect on decreasing food intake by 20 to 57% (P < 0.05). Decreases were detected by 30 min (maximum 57%, P < 0.01) and at the highest dose effects extended to 48 h (19%, P < 0.05, 24- to 48-h period). Daily body weight gain was decreased by 131% over the first 24 h and 29% over the second 24 h (P < 0.05). A conditioned taste aversion test indicated that there was no malaise. Furthermore, acute ASP injection affected energy substrate usage, demonstrated by decreased Vo(2) and RQ (P < 0.05; implicating greater fatty acid usage), with a 49% decrease in total activity over 24 h (P < 0.05). ASP administration also increased anorexic neuropeptide POMC expression (44%) in the arcuate nucleus, with no change in NPY. Altogether ASP may have central in addition to peripheral effects.}, } @article {pmid21524709, year = {2011}, author = {Miranda, MI and González-Cedillo, FJ and Díaz-Muñoz, M}, title = {Intracellular calcium chelation and pharmacological SERCA inhibition of Ca2+ pump in the insular cortex differentially affect taste aversive memory formation and retrieval.}, journal = {Neurobiology of learning and memory}, volume = {96}, number = {2}, pages = {192-198}, doi = {10.1016/j.nlm.2011.04.010}, pmid = {21524709}, issn = {1095-9564}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Calcium/*metabolism ; Cerebral Cortex/drug effects/*physiology ; Chelating Agents/pharmacology ; Egtazic Acid/analogs & derivatives/pharmacology ; Enzyme Inhibitors/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/*antagonists & inhibitors ; Taste/drug effects/*physiology ; Thapsigargin/pharmacology ; }, abstract = {Variation in intracellular calcium concentration regulates the induction of long-term synaptic plasticity and is associated with a variety of memory/retrieval and learning paradigms. Accordingly, impaired calcium mobilization from internal deposits affects synaptic plasticity and cognition in the aged brain. During taste memory formation several proteins are modulated directly or indirectly by calcium, and recent evidence suggests the importance of calcium buffering and the role of intracellular calcium deposits during cognitive processes. Thus, the main goal of this research was to study the consequence of hampering changes in cytoplasmic calcium and inhibiting SERCA activity by BAPTA-AM and thapsigargin treatments, respectively, in the insular cortex during different stages of taste memory formation. Using conditioned taste aversion (CTA), we found differential effects of BAPTA-AM and thapsigargin infusions before and after gustatory stimulation, as well as during taste aversive memory consolidation; BAPTA-AM, but not thapsigargin, attenuates acquisition and/or consolidation of CTA, but neither compound affects taste aversive memory retrieval. These results point to the importance of intracellular calcium dynamics in the insular cortex during different stages of taste aversive memory formation.}, } @article {pmid21497596, year = {2011}, author = {Ossenkopp, KP and Biagi, E and Cloutier, CJ and Chan, MY and Kavaliers, M and Cross-Mellor, SK}, title = {Acute corticosterone increases conditioned spontaneous orofacial behaviors but fails to influence dose related LiCl-induced conditioned "gaping" responses in a rodent model of anticipatory nausea.}, journal = {European journal of pharmacology}, volume = {660}, number = {2-3}, pages = {358-362}, doi = {10.1016/j.ejphar.2011.03.049}, pmid = {21497596}, issn = {1879-0712}, mesh = {Animals ; Anticipation, Psychological/*drug effects/physiology ; Behavior, Animal/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Corticosterone/*pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Face/physiology ; Lithium Chloride/*pharmacology ; Male ; Mouth/*drug effects/physiology ; Movement/drug effects ; Nausea/*chemically induced/physiopathology ; Rats ; Rats, Long-Evans ; }, abstract = {Acute administration of corticosterone has been shown to facilitate learning in a number of associative paradigms, including LiCl-induced conditioned taste aversion learning. The present study examined the effects of acute corticosterone on LiCl-induced conditioned anticipatory nausea in male rats. Anticipatory nausea is produced by pairing a novel distinctive context with the nausea-inducing effects of a toxin, such as LiCl. Following a number of pairings of the context with the effects of the toxin, rats will display a distinctive conditioned "gaping" response when placed into the context in a drug free state. Adult male Long-Evans rats were injected (intraperitoneal, ip) with a LiCl solution (32, 64, or 128 mg/kg, 0.15M) or saline (NaCl, 0.15 M) followed 10 min later by either corticosterone (5 mg/kg) or β-cyclodextrin vehicle (45%) prior to placement in a distinctive context on four conditioning days (72 h apart) for 30 min. On the conditioning test day rats were placed in the distinctive context in a drug-free state and orofacial and somatic responses were video-recorded for 10 min. Gaping responses increased with increasing doses of LiCl in a linear fashion (P<0.01) but were not significantly influenced by the corticosterone treatment. In contrast, significant increases in the frequency of conditioned spontaneous orofacial behaviors on the drug free test day were produced by the corticosterone treatment during the acquisition phase, whereas LiCl treatment during acquisition had no significant effect on these behaviors. Thus, acute corticosterone did not alter the strength of conditioning of anticipatory nausea in rats.}, } @article {pmid21490364, year = {2011}, author = {Kuhajda, FP and Aja, S and Tu, Y and Han, WF and Medghalchi, SM and El Meskini, R and Landree, LE and Peterson, JM and Daniels, K and Wong, K and Wydysh, EA and Townsend, CA and Ronnett, GV}, title = {Pharmacological glycerol-3-phosphate acyltransferase inhibition decreases food intake and adiposity and increases insulin sensitivity in diet-induced obesity.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {301}, number = {1}, pages = {R116-30}, pmid = {21490364}, issn = {1522-1490}, support = {R01 NS041079/NS/NINDS NIH HHS/United States ; }, mesh = {Adiposity/drug effects/*physiology ; Agouti-Related Protein/metabolism ; Animals ; Dietary Fats/adverse effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Eating/drug effects/*physiology ; Enzyme Inhibitors/*pharmacology ; Fatty Liver/metabolism/physiopathology ; Glycerol-3-Phosphate O-Acyltransferase/*antagonists & inhibitors/physiology ; Insulin Resistance/*physiology ; Mice ; Mice, Inbred Strains ; Mitochondria, Liver/drug effects/enzymology ; Neuropeptide Y/metabolism ; Obesity/etiology/metabolism/*physiopathology ; Oxygen Consumption/drug effects/physiology ; Thinness/metabolism/physiopathology ; Triglycerides/metabolism ; }, abstract = {Storage of excess calories as triglycerides is central to obesity and its associated disorders. Glycerol-3-phosphate acyltransferases (GPATs) catalyze the initial step in acylglyceride syntheses, including triglyceride synthesis. We utilized a novel small-molecule GPAT inhibitor, FSG67, to investigate metabolic consequences of systemic pharmacological GPAT inhibition in lean and diet-induced obese (DIO) mice. FSG67 administered intraperitoneally decreased body weight and energy intake, without producing conditioned taste aversion. Daily FSG67 (5 mg/kg, 15.3 μmol/kg) produced gradual 12% weight loss in DIO mice beyond that due to transient 9- to 10-day hypophagia (6% weight loss in pair-fed controls). Continued FSG67 maintained the weight loss despite return to baseline energy intake. Weight was lost specifically from fat mass. Indirect calorimetry showed partial protection by FSG67 against decreased rates of oxygen consumption seen with hypophagia. Despite low respiratory exchange ratio due to a high-fat diet, FSG67-treated mice showed further decreased respiratory exchange ratio, beyond pair-fed controls, indicating enhanced fat oxidation. Chronic FSG67 increased glucose tolerance and insulin sensitivity in DIO mice. Chronic FSG67 decreased gene expression for lipogenic enzymes in white adipose tissue and liver and decreased lipid accumulation in white adipose, brown adipose, and liver tissues without signs of damage. RT-PCR showed decreased gene expression for orexigenic hypothalamic neuropeptides AgRP or NPY after acute and chronic systemic FSG67. FSG67 given intracerebroventricularly (100 and 320 nmol icv) produced 24-h weight loss and feeding suppression, indicating contributions from direct central nervous system sites of action. Together, these data point to GPAT as a new potential therapeutic target for the management of obesity and its comorbidities.}, } @article {pmid21483781, year = {2011}, author = {Singh, T and Jones, JL and McDannald, MA and Haney, RZ and Cerri, DH and Schoenbaum, G}, title = {Normal Aging does Not Impair Orbitofrontal-Dependent Reinforcer Devaluation Effects.}, journal = {Frontiers in aging neuroscience}, volume = {3}, number = {}, pages = {4}, pmid = {21483781}, issn = {1663-4365}, support = {R01 AG027097/AG/NIA NIH HHS/United States ; }, abstract = {Normal aging is associated with deficits in cognitive flexibility thought to depend on prefrontal regions such as the orbitofrontal cortex (OFC). Here, we used Pavlovian reinforcer devaluation to test whether normal aging might also affect the ability to use outcome expectancies to guide appropriate behavioral responding, which is also known to depend on the OFC. Both young and aged rats were trained to associate a 10-s conditioned stimulus (CS+) with delivery of a sucrose pellet. After training, half of the rats in each age group received the sucrose pellets paired with illness induced by LiCl injections; the remaining rats received sucrose and illness explicitly unpaired. Subsequently, responding to the CS+ was assessed in an extinction probe test. Although aged rats displayed lower responding levels overall, both young and aged rats conditioned to the CS+ and developed a conditioned taste aversion following reinforcer devaluation. Furthermore, during the extinction probe test, both young and aged rats spontaneously attenuated conditioned responding to the cue as a result of reinforcer devaluation. These data show that normal aging does not affect the ability to use expected outcome value to appropriately guide Pavlovian responding. This result indicates that deficits in cognitive flexibility are dissociable from other known functions of prefrontal - and particularly orbitofrontal - cortex.}, } @article {pmid21471379, year = {2011}, author = {Li, YQ and Xue, YX and He, YY and Li, FQ and Xue, LF and Xu, CM and Sacktor, TC and Shaham, Y and Lu, L}, title = {Inhibition of PKMzeta in nucleus accumbens core abolishes long-term drug reward memory.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {31}, number = {14}, pages = {5436-5446}, pmid = {21471379}, issn = {1529-2401}, support = {R37 MH057068/MH/NIMH NIH HHS/United States ; R29 MH053576/MH/NIMH NIH HHS/United States ; R01 MH053576/MH/NIMH NIH HHS/United States ; ZIA DA000434-11/ImNIH/Intramural NIH HHS/United States ; R01 MH057068/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Behavior, Animal/drug effects ; Cocaine/pharmacology ; Conditioning, Operant/drug effects/*physiology ; Dopamine Uptake Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Endocytosis/drug effects ; Enzyme Inhibitors/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Male ; Memory/drug effects/*physiology ; Morphine/adverse effects ; Naloxone/pharmacology ; Narcotic Antagonists/pharmacology ; Narcotics/adverse effects ; Nucleus Accumbens/drug effects/*enzymology ; Oligopeptides/pharmacology ; Organophosphonates/pharmacology ; Piperazines/pharmacology ; Protein Kinase C/*antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; *Reward ; Substance Withdrawal Syndrome/enzymology/physiopathology ; Time Factors ; Valine/analogs & derivatives/pharmacology ; }, abstract = {During abstinence, memories of drug-associated cues persist for many months, and exposure to these cues often provokes relapse to drug use. The mechanisms underlying the maintenance of these memories are unknown. A constitutively active atypical protein kinase C (PKC) isozyme, protein kinase M ζ (PKMζ), is required for maintenance of spatial memory, conditioned taste aversion, and other memory forms. We used conditioned place preference (CPP) and conditioned place aversion (CPA) procedures to study the role of nucleus accumbens PKMζ in the maintenance of drug reward and aversion memories in rats. Morphine CPP training (10 mg/kg, 4 pairings) increased PKMζ levels in accumbens core but not shell. Injections of the PKMζ inhibitor ζ inhibitory peptide (ZIP) into accumbens core but not shell after CPP training blocked morphine CPP expression for up to 14 d after injections. This effect was mimicked by the PKC inhibitor chelerythrine, which inhibits PKMζ, but not by the conventional and novel PKC inhibitor staurosporine, which does not effectively inhibit PKMζ. ZIP injections into accumbens core after training also blocked the expression of cocaine (10 mg/kg) and high-fat food CPP but had no effect on CPA induced by naloxone-precipitated morphine withdrawal. Accumbens core injections of Tat-GluR2(3Y), which inhibits GluR2-dependent AMPA receptor endocytosis, prevented the impairment in morphine CPP induced by local ZIP injections, indicating that the persistent effect of PKMζ is on GluR2-containing AMPA receptors. Results indicate that PKMζ activity in accumbens core is a critical cellular substrate for the maintenance of memories of relapse-provoking reward cues during prolonged abstinence periods.}, } @article {pmid24331060, year = {2011}, author = {Noma, K and Toshinai, K and Koshinaka, K and Nakazato, M}, title = {Telmisartan suppresses food intake in mice via the melanocortin pathway.}, journal = {Obesity research & clinical practice}, volume = {5}, number = {2}, pages = {e79-e156}, doi = {10.1016/j.orcp.2010.11.003}, pmid = {24331060}, issn = {1871-403X}, abstract = {Telmisartan, an angiotensin type 1 receptor blocker, is widely used for the treatment of hypertension and related cardiovascular and organ damage. We here describe the effects of telmisartan on food intake and body weight using C57BL/6N mice, KKAy mice that overexpress agouti protein (a mouse model of type 2 diabetes with obesity), and mice deficient for angiotensin II-1a receptor. Telmisartan combined with a high-fat diet significantly reduced food intake and body weight gain in the three groups of mice compared with respective control animals that were fed the high-fat diet without telmisartan. Telmisartan did not induce taste aversion or affect energy expenditure. Intracerebroventricular administration of agouti-related protein, a potent antagonist of the melanocortin 3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R), did not stimulate feeding in telmisartan-treated mice. Telmisartan administration enhanced the alpha-melanocyte stimulating hormone-induced suppression of food intake. This study highlights a potential role for telmisartan in hypothalamic feeding regulation, including melanocortin receptors-mediated suppression of food intake and body weight gain.:}, } @article {pmid21447397, year = {2011}, author = {Stehberg, J and Moraga-Amaro, R and Simon, F}, title = {The role of the insular cortex in taste function.}, journal = {Neurobiology of learning and memory}, volume = {96}, number = {2}, pages = {130-135}, doi = {10.1016/j.nlm.2011.03.005}, pmid = {21447397}, issn = {1095-9564}, mesh = {Animals ; Cerebral Cortex/drug effects/*physiology/physiopathology ; Conditioning, Psychological/physiology ; Ibotenic Acid/toxicity ; Male ; Rats ; Rats, Wistar ; Retention, Psychology/physiology ; Taste/*physiology ; Taste Perception/*physiology ; }, abstract = {In spite of over 30 years of research, the role of the Insular Cortex (IC) in taste memory still remains elusive. To study the role of the IC in taste memory, we used conditioned taste aversion (CTA) for two different concentrations of saccharin; 0.1% which is highly preferred, and 0.5% which is non-preferred. Rats that had been IC lesioned bilaterally with ibotenic acid (15 mg/ml) before CTA showed significant learning impairments for saccharin 0.1% but not for saccharin 0.5%. To test CTA memory retention, rats lesioned a week after CTA training became completely amnesic for saccharin 0.1% yet only mildly impaired for saccharin 0.5%. Interestingly, the resulting preference for either concentration matched that of IC lesioned animals when exposed to either saccharin solution for the first time, but not those of sham animals, implying that IC lesions after CTA for either saccharin solution rendered complete amnesia, irrespective of the original preference. Our data indicate that an intact IC is essential for CTA learning and retention, as well as for an early neophobic response, but not for taste preference itself. Our data supports a model where the IC is involved in general taste rejection.}, } @article {pmid21440652, year = {2011}, author = {Rodríguez-Durán, LF and Castillo, DV and Moguel-González, M and Escobar, ML}, title = {Conditioned taste aversion modifies persistently the subsequent induction of neocortical long-term potentiation in vivo.}, journal = {Neurobiology of learning and memory}, volume = {95}, number = {4}, pages = {519-526}, doi = {10.1016/j.nlm.2011.03.003}, pmid = {21440652}, issn = {1095-9564}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Long-Term Potentiation/*physiology ; Male ; Neocortex/physiology ; Neural Inhibition/*physiology ; Rats ; Rats, Wistar ; Retention, Psychology/physiology ; Synaptic Transmission/*physiology ; Taste ; }, abstract = {The ability of neurons to modify their synaptic strength in an activity-dependent manner has a crucial role in learning and memory processes. It has been proposed that homeostatic forms of plasticity might provide the global regulation necessary to maintain synaptic strength and plasticity within a functional dynamic range. Similarly, it is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. In particular, training in several behavioral tasks modifies the possibility to induce long-term potentiation (LTP). Our previous studies in the insular cortex (IC) have shown that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to conditioned taste aversion (CTA) training enhances the retention of this task. The aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, CTA trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48, 72, 96 and 120 h after the aversion test. Our results show that CTA training prevents the subsequent induction of LTP in the Bla-IC projection, for at least 120 h after CTA training. We also showed that pharmacological inhibition of CTA consolidation with anisomycin (1 μl/side; 100 μg/μl) prevents the CTA effect on IC-LTP. These findings reveal that CTA training produces a persistent change in the ability to induce subsequent LTP in the Bla-IC projection in a protein-synthesis dependent manner, suggesting that changes in the ability to induce subsequent synaptic plasticity contribute to the formation and persistence of aversive memories.}, } @article {pmid21420998, year = {2011}, author = {Rinker, JA and Hutchison, MA and Chen, SA and Thorsell, A and Heilig, M and Riley, AL}, title = {Exposure to nicotine during periadolescence or early adulthood alters aversive and physiological effects induced by ethanol.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {99}, number = {1}, pages = {7-16}, pmid = {21420998}, issn = {1873-5177}, support = {Z99 AA999999//Intramural NIH HHS/United States ; }, mesh = {Age Factors ; *Alcohol Drinking/blood/physiopathology ; Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Classical/drug effects/physiology ; Ethanol/*administration & dosage/blood ; Extinction, Psychological/drug effects/physiology ; Hypothermia/blood/chemically induced ; Male ; Motor Activity/*drug effects/physiology ; Nicotine/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The majority of smokers begin their habit during adolescence, which often precedes experimentation with alcohol. Interestingly, very little preclinical work has been done examining how exposure to nicotine during periadolescence impacts the affective properties of alcohol in adulthood. Understanding how periadolescent nicotine exposure influences the aversive effects of alcohol might help to explain why it becomes more acceptable to this preexposed population. Thus, Experiment 1 exposed male Sprague Dawley rats to either saline or nicotine (0.4mg/kg, IP) from postnatal days 34 to 43 (periadolescence) and then examined changes in the aversive effects of alcohol (0, 0.56, 1.0 and 1.8g/kg, IP) in adulthood using the conditioned taste aversion (CTA) design. Changes in blood alcohol concentration (BAC) as well as alcohol-induced hypothermia and locomotor suppression were also assessed. To determine if changes seen were specific to nicotine exposure during periadolescence, the procedures were replicated in adults (Experiment 2). Preexposure to nicotine during periadolescence attenuated the acquisition of the alcohol-induced CTAs (at 1.0g/kg) and the hypothermic effects of alcohol (1.0g/kg). Adult nicotine preexposure produced similar attenuation in alcohol's aversive (at 1.8g/kg) and hypothermic (1.8g/kg) effects. Neither adolescent nor adult nicotine preexposure altered BACs or alcohol-induced locomotor suppression. These results suggest that nicotine may alter the aversive and physiological effects of alcohol, regardless of the age at which exposure occurs, possibly increasing its overall reinforcing value and making it more likely to be consumed.}, } @article {pmid21407164, year = {2011}, author = {Zach, P and Mrzilkova, J and Stuchlik, A and Vales, K and Rezacova, L}, title = {Delayed effect of chronic administration of corticoids on the taste aversion learning.}, journal = {Neuro endocrinology letters}, volume = {32}, number = {1}, pages = {90-95}, pmid = {21407164}, issn = {0172-780X}, mesh = {Adrenal Cortex Hormones/*toxicity ; Amygdala/drug effects/pathology ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Brain/*drug effects/*pathology ; Brain Stem/drug effects/pathology ; Conditioning, Psychological/drug effects ; Hippocampus/drug effects/pathology ; Male ; Prefrontal Cortex/drug effects/pathology ; Rats ; Rats, Long-Evans ; Reaction Time/drug effects ; Taste/*drug effects ; }, abstract = {BACKGROUND: Long term permanent changes of eating behavior and concomitant structural changes in the CNS are matter of debade in literature. Often there is not enough distinction beween acute and chronic exposure to corticoids in evaluating its effect on behavior and/or brain structural changes. For behavioral evaluation we used well established conditioned taste aversion (CTA) paradigm and coronal Nissl-stained brain sections for evaluation of neuroanatomical changes. The CTA is part of complex adaptive behavioral processes controling food intake. It is well established methodological tool for study of biological substrates of learning and memory.

AIM: Our hypothesis was that long term changes in laboratory rat behavior induced by exogenous corticosterone are not accompanyied by neurohistological changes in the rat brain, previously described in literature.

RESULTS: Firstly, our results support CTA paradigm as promising tool for testing chronic influence of stress hormones on eating behavior and memory. The results support fact that previous long term elevated corticosterone levels disrupt normal eating behavior and it could also lead to structural changes, which could be biological substrates of behavioral changes. The fact we have not found significant morphological changes in brain strengthen the notion of possible subcellular impairment taking place instead of simple neuronal loss.}, } @article {pmid21385959, year = {2011}, author = {Kita, S and Hashiba, R and Ueki, S and Kimoto, Y and Abe, Y and Gotoda, Y and Suzuki, R and Uraki, E and Nara, N and Kanazawa, A and Hatakeyama, D and Kawai, R and Fujito, Y and Lukowiak, K and Ito, E}, title = {Does conditioned taste aversion learning in the pond snail Lymnaea stagnalis produce conditioned fear?.}, journal = {The Biological bulletin}, volume = {220}, number = {1}, pages = {71-81}, doi = {10.1086/BBLv220n1p71}, pmid = {21385959}, issn = {1939-8697}, support = {MOP 64339//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; Fear/drug effects ; Feeding Behavior/drug effects ; Lymnaea/drug effects/*physiology ; Taste/drug effects ; United States ; }, abstract = {In conditioned taste aversion (CTA) training performed on the pond snail Lymnaea stagnalis, a stimulus (the conditional stimulus, CS; e.g., sucrose) that elicits a feeding response is paired with an aversive stimulus (the unconditional stimulus, US) that elicits the whole-body withdrawal response and inhibits feeding. After CTA training and memory formation, the CS no longer elicits feeding. We hypothesize that one reason for this result is that after CTA training the CS now elicits a fear response. Consistent with this hypothesis, we predict the CS will cause (1) the heart to skip a beat and (2) a significant change in the heart rate. Such changes are seen in mammalian preparations exposed to fearful stimuli. We found that in snails exhibiting long-term memory for one-trial CTA (i.e., good learners) the CS significantly increased the probability of a skipped heartbeat, but did not significantly change the heart rate. The probability of a skipped heartbeat was unaltered in control snails given backward conditioning (US followed by CS) or in snails that did not acquire associative learning (i.e., poor learners) after the one-trial CTA training. These results suggest that as a consequence of acquiring CTA, the CS evokes conditioned fear in the conditioned snails, as evidenced by a change in the nervous system control of cardiac activity.}, } @article {pmid21373786, year = {2011}, author = {Albaugh, DL and Rinker, JA and Baumann, MH and Sink, JR and Riley, AL}, title = {Rats preexposed to MDMA display attenuated responses to its aversive effects in the absence of persistent monoamine depletions.}, journal = {Psychopharmacology}, volume = {216}, number = {3}, pages = {441-449}, pmid = {21373786}, issn = {1432-2072}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amphetamine-Related Disorders/metabolism/*psychology ; Animals ; Biogenic Monoamines/*metabolism ; Caudate Nucleus/drug effects/metabolism ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Frontal Lobe/drug effects/metabolism ; Male ; N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology ; Putamen/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Reward ; Taste Perception/*drug effects ; }, abstract = {RATIONALE: The abuse potential of a given drug may be mediated by both its rewarding and aversive effects, the latter of which are often far less characterized.

OBJECTIVES: Using the conditioned taste-aversion (CTA) preparation, the present experiments examined changes in the aversive effects of the commonly used recreational drug MDMA following repeated drug exposures.

METHODS: Experiment 1 used three varying doses of MDMA (1.0, 1.8, and 3.2 mg/kg) to determine a dose that produced taste aversions of intermediate strength. Experiments 2 and 3 characterized the effects of repeated preexposures to MDMA (1.8 or 3.2 mg/kg) on taste aversions induced by MDMA (1.8 mg/kg). Additionally, levels of several monoamines and metabolites were analyzed in frontal cortex and caudate-putamen from subjects in Experiment 3 to assess for persistent monoamine depletions.

RESULTS: MDMA induced dose-dependent taste aversions. Preexposure to MDMA (at both doses) resulted in an attenuation of MDMA-induced taste aversions. These effects were not likely due to persistent monoamine depletions, as subjects preexposed to the higher MDMA dose did not differ from controls in levels of monoamines or metabolites in either brain region examined.

CONCLUSIONS: Prior MDMA experience weakened the ability of MDMA to induce taste aversions. This attenuation of MDMA's aversive effects may occur with low doses that do not persistently alter monoamine levels.}, } @article {pmid21352907, year = {2011}, author = {Pascual, M and Baliño, P and Alfonso-Loeches, S and Aragón, CM and Guerri, C}, title = {Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.}, journal = {Brain, behavior, and immunity}, volume = {25 Suppl 1}, number = {}, pages = {S80-91}, doi = {10.1016/j.bbi.2011.02.012}, pmid = {21352907}, issn = {1090-2139}, mesh = {Acetylation ; Alcohol-Related Disorders/*metabolism/physiopathology ; Alcohols/administration & dosage ; Analysis of Variance ; Animals ; Association Learning/drug effects/physiology ; Astrocytes/drug effects/metabolism ; Behavior, Animal/drug effects/*physiology ; Brain/drug effects/*metabolism ; Cognition/drug effects/*physiology ; Ethanol/*administration & dosage ; Histones/metabolism ; Immunohistochemistry ; Male ; Memory/drug effects/physiology ; Mice ; Mice, Knockout ; Microglia/drug effects/metabolism ; Motor Activity/drug effects/physiology ; Toll-Like Receptor 4/genetics/*metabolism ; }, abstract = {Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions.}, } @article {pmid21335984, year = {2011}, author = {Vidal, J}, title = {Mice do not develop conditioned taste aversion because of immunity loss.}, journal = {Neuroimmunomodulation}, volume = {18}, number = {3}, pages = {191-197}, doi = {10.1159/000323772}, pmid = {21335984}, issn = {1423-0216}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Immune Tolerance/physiology ; Immunosuppression Therapy/*methods ; Immunosuppressive Agents/*adverse effects ; Male ; Mice ; Taste/*immunology ; Taste Disorders/*immunology/psychology ; }, abstract = {OBJECTIVES: This study intends to test the generation of conditioned taste aversion and conditioned immunodepression by daily paired administration of saccharin solution with cyclophosphamide, 15 mg/kg, for 4 days.

METHODS: One group of male mice of the outbred CD1 strain drank 0.15% saccharin and received 1 injection of cyclophosphamide, 15 mg/kg, for 4 days (paired group), another group (unpaired group) received the same doses of saccharin and cyclophosphamide noncontingently, the third group (cy60) received saccharin paired with cyclophosphamide, 60 mg/kg, and the fourth group (placebo) received saccharin in the absence of cyclophosphamide. All mice were immunized with keyhole limpet hemocyanin (KLH), 0.2 mg, 1 day before the treatments.

RESULTS: Mice of the paired, unpaired and cy60 groups displayed a similarly decreased antibody response to KLH, but mice of the paired group did not develop an aversion to saccharin while mice of the cy60 group did. Besides, repeat presentation of saccharin to mice of the paired group did not alter their antibody response to ovalbumin compared with mice of the unpaired or placebo group.

CONCLUSIONS: Taste aversion was not elicited in response to impaired immunity and the conditioned stimulus (saccharin) did not impair the antibody response.}, } @article {pmid21309945, year = {2011}, author = {Camp, MC and Feyder, M and Ihne, J and Palachick, B and Hurd, B and Karlsson, RM and Noronha, B and Chen, YC and Coba, MP and Grant, SG and Holmes, A}, title = {A novel role for PSD-95 in mediating ethanol intoxication, drinking and place preference.}, journal = {Addiction biology}, volume = {16}, number = {3}, pages = {428-439}, pmid = {21309945}, issn = {1369-1600}, support = {Z01 AA000411/ImNIH/Intramural NIH HHS/United States ; ZIA AA000411-07/ImNIH/Intramural NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Alcohol Drinking/*genetics ; Alcoholic Intoxication/*genetics/*psychology ; Animals ; Antimanic Agents/pharmacology ; Association Learning/*drug effects ; Choice Behavior/*drug effects ; Conditioning, Classical/*drug effects ; Disks Large Homolog 4 Protein ; Dizocilpine Maleate/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; Guanylate Kinases/*genetics ; Injections, Intraperitoneal ; Lithium Chloride/toxicity ; Male ; Membrane Proteins/*genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Signal Transduction/genetics ; *Social Environment ; Taste/drug effects/genetics ; }, abstract = {The synaptic signaling mechanisms mediating the behavioral effects of ethanol (EtOH) remain poorly understood. Post-synaptic density 95 (PSD-95, SAP-90, Dlg4) is a key orchestrator of N-methyl-D-aspartate receptors (NMDAR) and glutamatergic synapses, which are known to be major sites of EtOH's behavioral actions. However, the potential contribution of PSD-95 to EtOH-related behaviors has not been established. Here, we evaluated knockout (KO) mice lacking PSD-95 for multiple measures of sensitivity to the acute intoxicating effects of EtOH (ataxia, hypothermia, sedation/hypnosis), EtOH drinking under conditions of free access and following deprivation, acquisition and long-term retention of EtOH conditioned place preference (CPP) (and lithium chloride-induced conditioned taste aversion), and intoxication-potentiating responses to NMDAR antagonism. PSD-95 KO exhibited increased sensitivity to the sedative/hypnotic, but not ataxic or hypothermic, effects of acute EtOH relative to wild-type controls (WT). PSD-95 KO consumed less EtOH than WT, particularly at higher EtOH concentrations, although increases in KO drinking could be induced by concentration-fading and deprivation. PSD-95 KO showed normal EtOH CPP 1 day after conditioning, but showed significant aversion 2 weeks later. Lithium chloride-induced taste aversion was impaired in PSD-95 KO at both time points. Finally, the EtOH-potentiating effects of the NMDAR antagonist MK-801 were intact in PSD-95 KO at the dose tested. These data reveal a major, novel role for PSD-95 in mediating EtOH behaviors, and add to growing evidence that PSD-95 is a key mediator of the effects of multiple abused drugs.}, } @article {pmid21307245, year = {2011}, author = {Ma, L and Wang, DD and Zhang, TY and Yu, H and Wang, Y and Huang, SH and Lee, FS and Chen, ZY}, title = {Region-specific involvement of BDNF secretion and synthesis in conditioned taste aversion memory formation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {31}, number = {6}, pages = {2079-2090}, pmid = {21307245}, issn = {1529-2401}, support = {R01 NS052819/NS/NINDS NIH HHS/United States ; R01 NS052819-07/NS/NINDS NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Anxiety/metabolism ; Avoidance Learning/drug effects/*physiology ; Brain/anatomy & histology/*metabolism ; Brain-Derived Neurotrophic Factor/genetics/*metabolism/pharmacology ; Chromatography, High Pressure Liquid/methods ; Conditioning, Classical/drug effects/*physiology ; Enzyme Inhibitors/pharmacology ; Enzyme-Linked Immunosorbent Assay/methods ; Gene Expression Regulation/physiology ; Immunoprecipitation/methods ; Lithium Chloride/adverse effects ; Male ; Memory/drug effects/*physiology ; Microinjections/methods ; Oligodeoxyribonucleotides, Antisense/pharmacology ; RNA, Messenger/metabolism ; Rats ; Rats, Wistar ; Receptor, trkB/metabolism ; Restraint, Physical/methods ; Taste/*physiology ; Time Factors ; }, abstract = {Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in activity-dependent plasticity processes such as long-term potentiation, learning, and memory. It has been shown that BDNF exerts different or even opposite effects on behavior depending on the neural circuit. However, the detailed role of BDNF in memory process on the basis of its location has not been fully understood. Here, we aim to investigate the regional specific involvement of BDNF/TrkB in hippocampal-independent conditioned taste aversion (CTA) memory processes. We found region-specific changes in BDNF expression during CTA learning. CTA conditioning induced increased BDNF levels in the central nuclei of amygdala (CeA) and insular cortex, but not in the basolateral amygdala (BLA) and ventromedial prefrontal cortex. Interestingly, we found that the enhanced TrkB phosphorylation occurred at the time point before the increased BDNF expression, suggesting rapid induction of activity-dependent BDNF secretion by CTA learning. Moreover, targeted infusion of BDNF antibodies or BDNF antisense oligonucleotides revealed that activity-dependent BDNF secretion and synthesis in the CeA, but not the BLA, was respectively involved in the short- and long-term memory formation of CTA. Finally, we found that infusion of exogenous BDNF into the CeA could enhance CTA learning. These data suggest that region-specific BDNF release and synthesis temporally regulate different CTA memory phases through activation of TrkB receptors.}, } @article {pmid21298379, year = {2011}, author = {Rodríguez, G and Alonso, G}, title = {Effect of extended training on generalization of latent inhibition: an instance of perceptual learning.}, journal = {Learning & behavior}, volume = {39}, number = {1}, pages = {79-86}, pmid = {21298379}, issn = {1543-4494}, mesh = {Animals ; Association Learning/*physiology ; Conditioning, Psychological/*physiology ; Generalization, Psychological/*physiology ; *Inhibition, Psychological ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {Four experiments examined generalization of latent inhibition (LI) as a function of the length of preexposure in a conditioned taste aversion procedure with rats. Experiment 1 showed that one or four nonreinforced presentations of a flavor compound (BX) retarded subsequent conditioning to another compound (AX). However, after eight presentations of BX, conditioning to AX occurred at the same rate as with no preexposure. These results indicate that generalization of LI decreased as the length of preexposure to BX increased. Experiment 2 replicated this effect of reducing generalization, as well as demonstrating that LI actually increased as the length of preexposure to AX increased. Experiment 3 extended the generality of the effect to a procedure in which both BX and AX were preexposed. Experiment 4 demonstrated a similar reducing-generalization effect when generalization of LI from BX to X was assessed. All of these data are consistent with the notion that prolonged preexposure to BX enhances its discriminability. Different learning mechanisms that might be responsible for this perceptual learning effect are discussed.}, } @article {pmid21295056, year = {2011}, author = {Mediavilla, C and Cabello, V and Risco, S}, title = {SB-334867-A, a selective orexin-1 receptor antagonist, enhances taste aversion learning and blocks taste preference learning in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {98}, number = {3}, pages = {385-391}, doi = {10.1016/j.pbb.2011.01.021}, pmid = {21295056}, issn = {1873-5177}, mesh = {Animals ; Avoidance Learning/*drug effects ; Benzoxazoles/*pharmacology ; Body Weight/drug effects ; Dose-Response Relationship, Drug ; Feeding Behavior/drug effects ; Male ; Naphthyridines ; Orexin Receptors ; Rats ; Rats, Wistar ; Receptors, G-Protein-Coupled/*antagonists & inhibitors ; Receptors, Neuropeptide/*antagonists & inhibitors ; *Taste ; Urea/*analogs & derivatives/pharmacology ; }, abstract = {Lateral hypothalamus (LH) has been proposed as a possible center for the anatomical convergence of gustatory and postingestive information relevant to taste aversion learning (TAL) and conditioned flavor preference (CFP). Orexin, a neuropeptide that mainly originates in neurons in lateral hypothalamic areas, was recently related to learning and memory processes. The present study was designed to analyze a possible relationship between the orexinergic system and taste learning. We studied the effect of intracerebroventricular administration of three doses (3, 6, and 12 μg/1 μl) of the selective orexin-1 receptor antagonist SB-334867-A on the acquisition of TAL induced by a single administration of LiCl. Infusion of SB-334867-A did not block this learning and appeared to enhance TAL in a two-bottle test. However, SB-334867-A (6 μg/1 μl) blocked taste preference learning when a flavor associated with saccharin (CS+) was offered on alternate days against a different flavor without saccharin (CS-), during three acquisition sessions. These results offer evidence of a relationship between the orexinergic system and taste learning; they tentatively suggest the possibility that endogenous orexin and gustatory and postingestive (visceral and oral) signals converge in brain areas relevant to the acquisition of taste learning.}, } @article {pmid21266194, year = {2011}, author = {Blednov, YA and Benavidez, JM and Geil, C and Perra, S and Morikawa, H and Harris, RA}, title = {Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice.}, journal = {Brain, behavior, and immunity}, volume = {25 Suppl 1}, number = {Suppl 1}, pages = {S92-S105}, pmid = {21266194}, issn = {1090-2139}, support = {AA06399/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA015521-04/AA/NIAAA NIH HHS/United States ; R01 AA015521/AA/NIAAA NIH HHS/United States ; AA015521/AA/NIAAA NIH HHS/United States ; R01 AA015521-03S1/AA/NIAAA NIH HHS/United States ; AA U01 13520/AA/NIAAA NIH HHS/United States ; U01 AA013520-10/AA/NIAAA NIH HHS/United States ; R01 AA015521-03/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*immunology ; Analysis of Variance ; Animals ; Choice Behavior/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Electrophysiology ; Ethanol/*administration & dosage ; Lipopolysaccharides/*pharmacology ; Mice ; Neurons/*drug effects/immunology ; Self Administration ; Species Specificity ; }, abstract = {Previous studies showed that mice with genetic predisposition for high alcohol consumption as well as human alcoholics show changes in brain expression of genes related to immune signaling. In addition, mutant mice lacking genes related to immune function show decreased alcohol consumption (Blednov et al., 2011), suggesting that immune signaling promotes alcohol consumption. To test the possibility that activation of immune signaling will increase alcohol consumption, we treated mice with lipopolysaccaride (LPS; 1mg/kg, i.p.) and tested alcohol consumption in the continuous two-bottle choice test. To take advantage of the long-lasting activation of brain immune signaling by LPS, we measured drinking beginning one week or one month after LPS treatment and continued the studies for several months. LPS produced persistent increases in alcohol consumption in C57BL/6J (B6) inbred mice, FVBxB6F1 and B6xNZBF1 hybrid mice, but not in FVB inbred mice. To determine if this effect of LPS is mediated through binding to TLR4, we tested mice lacking CD14, a key component of TLR4 signaling. These null mutants showed no increase of alcohol intake after treatment with LPS. LPS treatment decreased ethanol-conditioned taste aversion but did not alter ethanol-conditioned place preference (B6xNZBF1 mice). Electrophysiological studies of dopamine neurons in the ventral tegmental area showed that pretreatment of mice with LPS decreased the neuronal firing rate. These results suggest that activation of immune signaling promotes alcohol consumption and alters certain aspects of alcohol reward/aversion.}, } @article {pmid21219975, year = {2011}, author = {Inui, T and Inui-Yamamoto, C and Yoshioka, Y and Ohzawa, I and Shimura, T}, title = {Activation of projective neurons from the nucleus accumbens to ventral pallidum by a learned aversive taste stimulus in rats: a manganese-enhanced magnetic resonance imaging study.}, journal = {Neuroscience}, volume = {177}, number = {}, pages = {66-73}, doi = {10.1016/j.neuroscience.2011.01.006}, pmid = {21219975}, issn = {1873-7544}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Globus Pallidus/drug effects/*physiology ; Magnetic Resonance Imaging/methods ; Male ; Manganese/metabolism ; Neural Pathways/drug effects/physiology ; Neurons/cytology/drug effects/*physiology ; Nucleus Accumbens/anatomy & histology/drug effects/*physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) causes a palatability shift of a taste stimulus (conditioned stimulus, CS) from ingestive to aversive. We previously found that the ventral pallidum (VP) mediates the palatability shift in CTA. Because the VP receives major projections from the nucleus accumbens (NAc), we examined whether the presentation of CS activates the NAc-VP projective neurons after the establishment of CTA, using a manganese-enhanced magnetic resonance imaging technique. Rats were implanted with a guide cannula in the NAc and an intraoral cannula. After the surgery, they received a pairing of 5 mM saccharin solution with an i.p. injection of 0.15 M lithium chloride (CTA group) or saline (sham group). Two days after the conditioning, rats were microinjected with manganese chloride (MnCl2) into the NAc. Thirty minutes later, the rats were presented with saccharin (CTA-CS and sham-CS groups) or water (CTA-DW and sham-DW groups) via the intraoral cannula. Only the CTA-CS group showed a robust aversion to the CS. At 1 and 2 h after the MnCl2 injection, T1-weighted MR images were acquired using an 11.7 T MRI. Imaging analysis showed that significantly more manganese moved toward the VP in the CTA-CS group than in the other groups. These results indicate that the conditioned aversive taste enhanced the activities of the projective NAc-VP neurons and suggest specific involvement of the NAc-VP pathway in the rejection of CS in retrieval of CTA.}, } @article {pmid21208169, year = {2010}, author = {Camarini, R and Pautassi, RM and Méndez, M and Quadros, IM and Souza-Formigoni, ML and Boerngen-Lacerda, R}, title = {Behavioral and neurochemical studies in distinct animal models of ethanol's motivational effects.}, journal = {Current drug abuse reviews}, volume = {3}, number = {4}, pages = {205-221}, doi = {10.2174/1874473711003040205}, pmid = {21208169}, issn = {1874-4745}, support = {AA013098/AA/NIAAA NIH HHS/United States ; AA015992/AA/NIAAA NIH HHS/United States ; AA11960/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholism/*psychology ; Animals ; Brain/drug effects/metabolism ; *Disease Models, Animal ; Enkephalins/metabolism ; Ethanol/administration & dosage/*pharmacology ; Humans ; Motivation/*drug effects ; Reinforcement, Psychology ; Self Administration ; Synaptic Transmission/*drug effects ; }, abstract = {In the last decades, the goal of creating a unique and complete model of alcohol use and alcoholism has been replaced by a myriad of different animal models, each addressing a specific feature of problematic alcohol consumption. This mini-review highlights selected findings in the field of alcohol abuse and dependence, as found through the use of animal models. There are models (e.g., drinking in the dark, drinking after alcohol adulteration or alcohol deprivation) in which animals self-administer alcohol, that are useful to analyze determinants and consequences of binge drinking, progression from casual to problematic alcohol use and relapse or loss of control over alcohol drinking. In other models (e.g., conditioned place preference, conditioned taste aversion, ethanol-induced behavioral sensitization) alcohol dosing is precisely controlled by the experimenter. These models are useful to study motivational (i.e, appetitive, aversive and negative reinforcing) effects of alcohol and neuroadaptive changes that occur after repeated alcohol exposure. The study of age-related differences in reactivity to alcohol provides yet another avenue for analyzing alcohol's acute and chronic consequences. Ethanol interacts with several neurotransmitter (dopaminergic, glutamatergic, opioidergic and cannabinoid) and neuromodulators and these interactions are involved in the development and maintenance of alcohol self-administration. The findings described in the review, however, indicate a key role of the endogenous opioid system, notably in the mediation of alcohol's postitive rewarding effects. The Review also highlights the need to further assess the inter-relationship between different indices of ethanol's motivational effects as well as their association with alcohol intake and preference.}, } @article {pmid21199647, year = {2011}, author = {Irani, BG and Xiang, Z and Yarandi, HN and Holder, JR and Moore, MC and Bauzo, RM and Proneth, B and Shaw, AM and Millard, WJ and Chambers, JB and Benoit, SC and Clegg, DJ and Haskell-Luevano, C}, title = {Implication of the melanocortin-3 receptor in the regulation of food intake.}, journal = {European journal of pharmacology}, volume = {660}, number = {1}, pages = {80-87}, pmid = {21199647}, issn = {1879-0712}, support = {DK57080/DK/NIDDK NIH HHS/United States ; R01 DK064250-07/DK/NIDDK NIH HHS/United States ; R01 DK064250-06S1/DK/NIDDK NIH HHS/United States ; R01 DK064250-08/DK/NIDDK NIH HHS/United States ; R01 DK057080/DK/NIDDK NIH HHS/United States ; R01 DK064250/DK/NIDDK NIH HHS/United States ; R01 DK064250-06/DK/NIDDK NIH HHS/United States ; R56 DK057080-10/DK/NIDDK NIH HHS/United States ; R56 DK057080/DK/NIDDK NIH HHS/United States ; DK6425/DK/NIDDK NIH HHS/United States ; R01 DK064250-05A2/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Eating/*drug effects/genetics ; Gene Knockout Techniques ; Humans ; Ligands ; Mice ; Molecular Sequence Data ; Oligopeptides/chemistry/pharmacology ; Receptor, Melanocortin, Type 3/agonists/antagonists & inhibitors/genetics/*metabolism ; Receptor, Melanocortin, Type 4/agonists/antagonists & inhibitors/genetics/metabolism ; Satiation ; alpha-MSH/analogs & derivatives/chemistry/pharmacology ; }, abstract = {The melanocortin system is well recognized to be involved in the regulation of food intake, body weight, and energy homeostasis. To probe the role of the MC(3) in the regulation of food intake, JRH322-18 a mixed MC(3) partial agonist/antagonist and MC(4) agonist tetrapeptide was examined in wild type (WT) and melanocortin 4 receptor (MC(4)) knockout mice and shown to reduce food intake in both models. In the wild type mice, 2.0 nmol of JRH322-18 statistically reduced food intake 4h post icv treatment into satiated nocturnally feeding wild type mice. The same dose in the MC(4)KO mice significantly reduced cumulative food intake 24h post treatment. Conditioned taste aversion as well as activity studies supports that the decreased food intake was not due to visceral illness. Since these studies resulted in loss-of-function results, the SHU9119 and agouti-related protein (AGRP) melanocortin receptor antagonists were administered to wild type as well as the MC(3) and MC(4) knockout mice in anticipation of gain-of-function results. The SHU9119 ligand produced an increase in food intake in the wild type mice as anticipated, however no effect was observed in the MC(3) and MC(4) knockout mice as compared to the saline control. The AGRP ligand however, produced a significant increase in food intake in the wild type as well as the MC(3) and MC(4) knockout mice and it had a prolonged affect for several days. These data support the hypothesis that the MC(3) plays a subtle role in the regulation of food intake, however the mechanism by which this is occurring remains to be determined.}, } @article {pmid21193052, year = {2011}, author = {Rodriguez-Ortiz, CJ and Balderas, I and Saucedo-Alquicira, F and Cruz-Castañeda, P and Bermudez-Rattoni, F}, title = {Long-term aversive taste memory requires insular and amygdala protein degradation.}, journal = {Neurobiology of learning and memory}, volume = {95}, number = {3}, pages = {311-315}, doi = {10.1016/j.nlm.2010.12.010}, pmid = {21193052}, issn = {1095-9564}, mesh = {Acetylcysteine/*analogs & derivatives/pharmacology ; Amygdala/drug effects/*metabolism ; Animals ; Association Learning/drug effects/physiology ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*metabolism ; Cysteine Proteinase Inhibitors/*pharmacology ; Male ; Memory, Long-Term/drug effects/*physiology ; Nerve Tissue Proteins/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors ; Rats ; Rats, Wistar ; Taste ; Ubiquitin/antagonists & inhibitors/metabolism ; }, abstract = {Some reports have shown that the ubiquitin-proteasome system (UPS) is necessary to degrade repressor factors to produce new proteins essential to memory consolidation. Furthermore, recent evidence suggests that memory updating also relies on protein degradation through the UPS. To evaluate whether degradation of proteins is part of the cellular events needed for long-term storage of taste aversion, we injected lactacystin--an UPS inhibitor--into the amygdala and/or insular cortex 30 min before the first or second training trials. The results revealed that degradation of proteins in either the amygdala or insular cortex suffices for long-term stabilization of first-time encounter taste aversion. On the other hand, lactacystin applied in the insula, but not in the amygdala, before the second training prevented long-term storage of updated information. Our results support that degradation of proteins by means of the UPS is required every time taste aversion is to be stored in long-term memory.}, } @article {pmid21193021, year = {2011}, author = {Quintero, E and Díaz, E and Vargas, JP and Schmajuk, N and López, JC and De la Casa, LG}, title = {Effects of context novelty vs. familiarity on latent inhibition with a conditioned taste aversion procedure.}, journal = {Behavioural processes}, volume = {86}, number = {2}, pages = {242-249}, doi = {10.1016/j.beproc.2010.12.011}, pmid = {21193021}, issn = {1872-8308}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/*physiology ; Drinking Behavior/physiology ; *Environment ; Male ; Rats ; Rats, Wistar ; Recognition, Psychology/*physiology ; Saccharin ; Taste/*physiology ; }, abstract = {The latent inhibition phenomenon is observed when a conditioned stimulus is preexposed without any consequence before conditioning. The result of this manipulation is a reduction in conditioned response intensity to such a stimulus. In this study, we analyse the role of context novelty/familiarity on LI modulation by changing the context using a three-stage conditioned taste aversion procedure. Experiment 1 revealed that, similar to other learning procedures, a context change between preexposure and conditioning/testing (but not between preexposure/conditioning and testing) resulted in LI attenuation when the experimental contexts were novel. Experiment 2, using animals' home cages as one of the contexts, revealed a different pattern of results, with an unexpected increase in LI magnitude when the context change was introduced between conditioning and test stages. The Schmajuk et al. (1996) computational model explains these results in terms of the increased novelty of the conditioned stimulus during preexposure, conditioning, and testing.}, } @article {pmid21187242, year = {2011}, author = {Pautassi, RM and Myers, M and Spear, LP and Molina, JC and Spear, NE}, title = {Ethanol induces second-order aversive conditioning in adolescent and adult rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {45}, number = {1}, pages = {45-55}, pmid = {21187242}, issn = {1873-6823}, support = {R01 AA018036/AA/NIAAA NIH HHS/United States ; R37 MH035219/MH/NIMH NIH HHS/United States ; R01 AA016887-02/AA/NIAAA NIH HHS/United States ; R01 AA016887/AA/NIAAA NIH HHS/United States ; AA011960/AA/NIAAA NIH HHS/United States ; AA018036/AA/NIAAA NIH HHS/United States ; R01 MH035219/MH/NIMH NIH HHS/United States ; R01 AA018026-03/AA/NIAAA NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; R37 AA012525/AA/NIAAA NIH HHS/United States ; R01 AA015992/AA/NIAAA NIH HHS/United States ; R01 AA012525/AA/NIAAA NIH HHS/United States ; R01 AA011960/AA/NIAAA NIH HHS/United States ; AA013098/AA/NIAAA NIH HHS/United States ; AA16887/AA/NIAAA NIH HHS/United States ; R37 AA012525-10/AA/NIAAA NIH HHS/United States ; MH035219/MH/NIMH NIH HHS/United States ; AA015992/AA/NIAAA NIH HHS/United States ; R01 AA018026/AA/NIAAA NIH HHS/United States ; AA012525/AA/NIAAA NIH HHS/United States ; R01 AA013098/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; *Aging ; Animals ; Appetitive Behavior/physiology ; Aversive Therapy ; *Avoidance Learning ; Brain Chemistry ; *Conditioning, Psychological ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage/analysis/blood ; Female ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Alcohol abuse and dependence are considered public health problems, with an etiological onset often occurring during late childhood and adolescence, and understanding age-related differences in ethanol sensitivity is important. Low to moderate ethanol doses (0.5 and 2.0 g/kg, intragastrically [i.g.]) induce single-trial, appetitive second-order place conditioning (SOC) in adolescent, but not adult, rats. Recent studies have demonstrated that adolescents may be less sensitive than adults to the aversive properties of ethanol, reflected by conditioned taste aversion. The present study assessed the aversive motivational effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescents and adults, respectively) using SOC. Experiment 1 revealed similar blood and brain ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol, respectively. In Experiment 2, animals received ethanol or vehicle paired with intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or three conditioning trials, the rats were presented with the CS1 while in a distinctive chamber (CS2). When tested for CS2 preference, ethanol-treated animals exhibited reduced preference for the CS2 compared with controls. This result, indicative of ethanol-mediated aversive place conditioning, was similar for adolescents and adults; for females and males; and after one, two, or three training trials. In conjunction with previous results, the present study showed that, in adolescent rats subjected to SOC, ethanol's hedonic effects vary from appetitive to aversive as the ethanol dose increases. Adolescent and adult animals appear to perceive the postingestive effects of high-dose ethanol as similarly aversive when assessed by SOC.}, } @article {pmid21186921, year = {2010}, author = {Rose, JE and Behm, FM and Murugesan, T and McClernon, FJ}, title = {Silver acetate interactions with nicotine and non-nicotine smoke components.}, journal = {Experimental and clinical psychopharmacology}, volume = {18}, number = {6}, pages = {462-469}, doi = {10.1037/a0021966}, pmid = {21186921}, issn = {1936-2293}, mesh = {Acetates/administration & dosage/*pharmacology ; Adult ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Nicotine/*administration & dosage/chemistry ; Nicotinic Agonists/administration & dosage/chemistry ; Silver Compounds/administration & dosage/*pharmacology ; Smoking Cessation/*methods ; *Smoking Prevention ; Taste ; Tobacco/chemistry ; }, abstract = {Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment.}, } @article {pmid21147152, year = {2011}, author = {Cobuzzi, JL and Riley, AL}, title = {Spontaneous withdrawal in opiate-dependent Fischer 344, Lewis and Sprague-Dawley rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {98}, number = {1}, pages = {28-34}, doi = {10.1016/j.pbb.2010.12.003}, pmid = {21147152}, issn = {1873-5177}, mesh = {Animals ; Behavior, Animal/drug effects/physiology ; Body Weight/drug effects/physiology ; Disease Models, Animal ; Drinking/drug effects/physiology ; Male ; Morphine/administration & dosage/toxicity ; Morphine Dependence/*physiopathology/psychology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Species Specificity ; Substance Withdrawal Syndrome/*physiopathology/psychology ; }, abstract = {The Lewis (LEW) and Fischer 344 (F344) inbred rat strains react differentially to acute morphine administration for a variety of behavioral and neurochemical measures. Investigations into effects of chronic morphine are less common, and investigations assessing dependence have been limited to those utilizing antagonist-precipitated withdrawal. The present experiment extended these assessments by examining spontaneous withdrawal in the LEW and F344 strains. In this preparation, males of the LEW, F344 and the outbred Sprague-Dawley (SD) strain were made dependent on morphine. Following this, opiate administration was terminated and animals were examined for spontaneous withdrawal by the acquisition of a withdrawal-associated taste aversion, changes in body weight loss and the display of several behaviors characteristic of opiate withdrawal. Although all morphine-treated subjects decreased body weight and avoided consumption of the withdrawal-associated solution, indicating successful induction of dependence, no difference between the strains emerged in these indices of withdrawal severity. The only strain difference to appear in the behavioral indicators of withdrawal was with diarrhea (LEW>F344). That the strains differ in acute reactivity to opioids, but not in the overall severity of withdrawal, was discussed in relation to the need to examine the relationship between neurochemical and behavioral data in a variety of neural systems and behavioral endpoints.}, } @article {pmid21118699, year = {2011}, author = {Houpt, TA and Carella, L and Gonzalez, D and Janowitz, I and Mueller, A and Mueller, K and Neth, B and Smith, JC}, title = {Behavioral effects on rats of motion within a high static magnetic field.}, journal = {Physiology & behavior}, volume = {102}, number = {3-4}, pages = {338-346}, pmid = {21118699}, issn = {1873-507X}, support = {R01 DC004607/DC/NIDCD NIH HHS/United States ; R01 DC004607-07/DC/NIDCD NIH HHS/United States ; R01DC4607/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; *Electromagnetic Fields ; Female ; Motor Activity/*physiology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Some human subjects report vestibular disturbances such as vertigo, apparent motion, and nausea around or within high strength MRI systems operating at 4 T to 9.4 T. These vestibular effects have been ascribed to the consequences of movement through the high magnetic field. We have previously found that exposure to magnetic fields above 7 T suppresses rearing, causes locomotor circling, and induces conditioned taste aversion (CTA) in rodents. The present experiments were designed to test the effects on rats of motion through the magnetic field of the 14.1 T superconducting magnet. In Experiment 1, we compared the effects of multiple rapid insertions and removals from the center of the magnet to the effects of continuous exposure. Repeated traversal of the magnetic field gradient with only momentary exposure to 14.1 T was sufficient to suppress rearing and induce a significant CTA. Repeated insertion and removal from the magnet, however, did not have a greater effect than a single 30-min exposure on either acute locomotor behavior or CTA acquisition. Prolonged exposure was required to induce locomotor circling. In the second series of experiments, we controlled the rate of insertion and removal by means of an electric motor. Locomotor circling appeared to be dependent on the speed of insertion and removal, but the suppression of rearing and the acquisition of CTA were independent of speed of insertion and removal. In Experiment 3, we inserted rats into the center of the magnet and then rotated them about their rostral-caudal axis during a 30-min 14.1 T exposure. Rotation within the magnet did not modulate the behavioral effects of exposure. We conclude that, in rats, movement through the steep gradient of a high magnetic field has some behavioral effects, but sustained exposure to the homogenous center of the field is required for the full behavioral consequences.}, } @article {pmid21093598, year = {2011}, author = {Fowler, SW and Ramsey, AK and Walker, JM and Serfozo, P and Olive, MF and Schachtman, TR and Simonyi, A}, title = {Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats.}, journal = {Neurobiology of learning and memory}, volume = {95}, number = {1}, pages = {73-79}, pmid = {21093598}, issn = {1095-9564}, support = {1R01 DA024355/DA/NIDA NIH HHS/United States ; R21 AT003859/AT/NCCIH NIH HHS/United States ; 1R21 AT 003859/AT/NCCIH NIH HHS/United States ; R21 AT003859-01A2/AT/NCCIH NIH HHS/United States ; R01 DA024355/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Benzamides/pharmacology ; Conditioning, Psychological/drug effects/*physiology ; Dizocilpine Maleate/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Male ; Motor Activity/drug effects/physiology ; Pyrazoles/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/*physiology ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology ; }, abstract = {Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 h after training. However, CDPPB (at 3mg/kg) attenuated the MK-801 (0.2mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory.}, } @article {pmid21093482, year = {2011}, author = {West, EA and Forcelli, PA and Murnen, A and Gale, K and Malkova, L}, title = {A visual, position-independent instrumental reinforcer devaluation task for rats.}, journal = {Journal of neuroscience methods}, volume = {194}, number = {2}, pages = {297-304}, pmid = {21093482}, issn = {1872-678X}, support = {T32 NS041231/NS/NINDS NIH HHS/United States ; F31 NS066822-02/NS/NINDS NIH HHS/United States ; T32DA007291/DA/NIDA NIH HHS/United States ; T32NS041231/NS/NINDS NIH HHS/United States ; T32 NS041231-09/NS/NINDS NIH HHS/United States ; T32 DA007291-05/DA/NIDA NIH HHS/United States ; T32 DA007291/DA/NIDA NIH HHS/United States ; F31 NS066822/NS/NINDS NIH HHS/United States ; F31 NS066822-01/NS/NINDS NIH HHS/United States ; F31NS066822/NS/NINDS NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Behavior, Animal ; Choice Behavior/physiology ; Conditioning, Operant/*physiology ; Cues ; Discrimination, Psychological/*physiology ; Extinction, Psychological/*physiology ; Female ; Food Preferences/physiology ; Photic Stimulation/methods ; Rats ; Rats, Sprague-Dawley ; *Reinforcement, Psychology ; Visual Perception/*physiology ; }, abstract = {Flexible goal-directed behavior has been studied across species using reinforcer devaluation tasks, in which subjects form associations between specific stimuli (cues) and specific reinforcer(s). The reinforcer is subsequently devalued by selective satiation or taste aversion. Following devaluation, subjects adjust their responding to the cues reflecting the new value of the reinforcer. Tasks currently used in rats differ in several ways from tasks used in monkeys and this may explain contrasting results between the two species. To address one of the differences, we developed a rat task independent of spatial cues. It employs two visual cues presented simultaneously, changing left and right positions pseudorandomly. Each cue predicts one of two food reinforcers. Rats were trained to lever press in response to the two visual cues. Subsequently, they were satiated on one of the foods followed by an extinction test where in each trial they could choose to respond to one of the two cues, one predicting the devalued reinforcer and the other the non-devalued. This procedure was repeated later with the alternative food devalued. The rats adjusted their responding by choosing the cue predicting the devalued food significantly less (p<0.05) than the alternative cue. These results show that rats can discriminate two visual stimuli presented simultaneously, devalue two different foods by selective satiation, and transfer the new value to the visual cues. Discrimination of the visual cues is not aided by spatial cues, thereby eliminating a major difference between the instrumental tasks used in rats and the task used in monkeys.}, } @article {pmid21088698, year = {2010}, author = {Singh, T and McDannald, MA and Haney, RZ and Cerri, DH and Schoenbaum, G}, title = {Nucleus Accumbens Core and Shell are Necessary for Reinforcer Devaluation Effects on Pavlovian Conditioned Responding.}, journal = {Frontiers in integrative neuroscience}, volume = {4}, number = {}, pages = {126}, pmid = {21088698}, issn = {1662-5145}, support = {R01 AG027097/AG/NIA NIH HHS/United States ; }, abstract = {The nucleus accumbens (NA) has been hypothesized to be part of a circuit in which cue-evoked information about expected outcomes is mobilized to guide behavior. Here we tested this hypothesis using a Pavlovian reinforcer devaluation task, previously applied to assess outcome-guided behavior after damage to regions such as the orbitofrontal cortex and amygdala that send projections to NA. Rats with sham lesions or neurotoxic lesions of either the core or shell subdivision of NA were trained to associate a 10-s CS+ with delivery of three food pellets. After training, half of the rats in each lesion group received food paired with illness induced by LiCl injections; the remaining rats received food and illness unpaired. Subsequently, responding to the CS+ was assessed in an extinction probe test. Both sham and lesioned rats conditioned to the CS+ and formed a conditioned taste aversion. However only sham rats reduced their conditioned responding as a result of reinforcer devaluation; devalued rats with lesions of either core or shell showed levels of responding that were similar to lesioned, non-devalued rats. This impairment was not due to the loss of motivational salience conferred to the CS+ in lesioned rats as both groups responded similarly for the cue in conditioned reinforcement testing. These data suggest that NA core and shell are part of a circuit necessary for the use of cue-evoked information about expected outcomes to guide behavior.}, } @article {pmid21081136, year = {2011}, author = {Washio, Y and Hayes, LJ and Hunter, KW and Pritchard, JK}, title = {Backward conditioning of tumor necrosis factor-α in a single trial: changing intervals between exposures to lipopolysaccharide and saccharin taste.}, journal = {Physiology & behavior}, volume = {102}, number = {2}, pages = {239-244}, doi = {10.1016/j.physbeh.2010.11.010}, pmid = {21081136}, issn = {1873-507X}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Behavior, Animal/drug effects ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Female ; Gene Expression Regulation/*drug effects ; Immunoassay/methods ; Lipopolysaccharides/*adverse effects ; Mice ; Mice, Inbred BALB C ; Saccharin/*administration & dosage ; Taste/drug effects/*physiology ; Time Factors ; Tumor Necrosis Factor-alpha/*blood ; }, abstract = {The current study examined the effect of backward conditioning with three different time intervals between exposures to lipopolysaccharide (LPS) as the unconditioned stimulus (US) and saccharin taste in water as the potential conditioned stimulus (CS). Forty-eight naïve female BALB/c mice at three months of age served as subjects, divided into six groups. Four groups were assigned to Experiment 1 for the tumor necrosis factor alpha (TNF-α) measure, and the remaining two groups were used in Experiment 2 to measure taste aversion behavior. Both experiments employed a single trial. The timing of introduction to the saccharin taste varied between 3 min, 7 h, and 24 h following an LPS injection in Experiment 1. Experiment 2 employed the three-minute interval only. These intervals correspond to distinct immunological, physiological, and behavioral events induced by LPS. On the day after re-exposure to the saccharin taste, the TNF-α groups were challenged with LPS to test the LPS tolerance response. While backward conditioning of taste aversion behavior was not observed, some evidence of conditioned TNF-α response and subsequent development of LPS tolerance was observed with backward conditioning in a single trial. This exploratory study demonstrated that the effect of backward conditioning on conditioned TNF-α response and LPS tolerance response in a single trial depended on the timing of when a CS is presented after LPS exposure.}, } @article {pmid21060877, year = {2010}, author = {Ayestaran, A and Giurfa, M and de Brito Sanchez, MG}, title = {Toxic but drank: gustatory aversive compounds induce post-ingestional malaise in harnessed honeybees.}, journal = {PloS one}, volume = {5}, number = {10}, pages = {e15000}, pmid = {21060877}, issn = {1932-6203}, mesh = {Animals ; Bees/*physiology ; Fatigue/*prevention & control ; *Taste ; }, abstract = {BACKGROUND: Deterrent substances produced by plants are relevant due to their potential toxicity. The fact that most of these substances have an unpalatable taste for humans and other mammals contrasts with the fact that honeybees do not reject them in the range of concentrations in which these compounds are present in flower nectars. Here we asked whether honeybees detect and ingest deterrent substances and whether these substances are really toxic to them.

RESULTS: We show that pairing aversive substances with an odor retards learning of this odor when it is subsequently paired with sucrose. Harnessed honeybees in the laboratory ingest without reluctance a considerable volume (20 µl) of various aversive substances, even if some of them induce significant post-ingestional mortality. These substances do not seem, therefore, to be unpalatable to harnessed bees but induce a malaise-like state that in some cases results in death. Consistently with this finding, bees learning that one odor is associated with sugar, and experiencing in a subsequent phase that the sugar was paired with 20 µl of an aversive substance (devaluation phase), respond less than control bees to the odor and the sugar. Such stimulus devaluation can be accounted for by the malaise-like state induced by the aversive substances.

CONCLUSION: Our results indicate that substances that taste bitter to humans as well as concentrated saline solutions base their aversive effect on the physiological consequences that their ingestion generates in harnessed bees rather than on an unpalatable taste. This conclusion is only valid for harnessed bees in the laboratory as freely-moving bees might react differently to aversive compounds could actively reject aversive substances. Our results open a new possibility to study conditioned taste aversion based on post-ingestional malaise and thus broaden the spectrum of aversive learning protocols available in honeybees.}, } @article {pmid21054690, year = {2012}, author = {McCool, BA and Chappell, AM}, title = {Using monosodium glutamate to initiate ethanol self-administration in inbred mouse strains.}, journal = {Addiction biology}, volume = {17}, number = {1}, pages = {121-131}, pmid = {21054690}, issn = {1369-1600}, support = {U01 AA016671/AA/NIAAA NIH HHS/United States ; P01 AA017056-030003/AA/NIAAA NIH HHS/United States ; U01 AA016671-03/AA/NIAAA NIH HHS/United States ; P01 AA021099/AA/NIAAA NIH HHS/United States ; AA017056/AA/NIAAA NIH HHS/United States ; R01 AA014445-07/AA/NIAAA NIH HHS/United States ; P01 AA017056/AA/NIAAA NIH HHS/United States ; R01 AA014445/AA/NIAAA NIH HHS/United States ; }, mesh = {*Alcohol Drinking ; Animals ; Behavior, Animal ; Central Nervous System Depressants/*administration & dosage ; Choice Behavior ; Ethanol/*administration & dosage ; Food Additives/pharmacology ; Food Preferences ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Inbred Strains ; Self Administration ; Sodium Glutamate/*pharmacology ; Species Specificity ; Sucrose/administration & dosage ; Sweetening Agents/administration & dosage ; }, abstract = {Voluntary oral ethanol consumption in rodents is generally limited by strong taste-aversion in these species. Historically, this has been overcome by combining ethanol with a sweetener, typically sucrose or saccharine, and then slowly 'fading' away the sweetener. While useful in most instances, this approach has not proven as successful for some inbred strains of mice (e.g. DBA/2J) despite consistent evidence in the literature that these same strains express strong conditioned place preference for intraperitoneal- or intragastric-administered ethanol. Importantly, DBA/2J mice express a polymorphism in a 'sweet' taste receptor subunit gene that reduces the potency of sweet substances in these mice. We hypothesized that the presence of this polymorphism might help explain the contrasting behavioral findings of weak voluntary oral ethanol consumption following sucrose-fade yet robust conditioned place preference for ethanol in this strain. To test this, we compared ethanol consumption initiated by either a 'traditional' sucrose-fade or a fade from an alternative tastant, monosodium glutamate (MSG). We found that in both C57BL/6J and DBA/2J mice, the MSG-fade produced robust increases in home cage ethanol consumption relative to the traditional sucrose-fade. This increased ethanol intake following MSG-fade was evident across a range of ethanol concentrations. Our findings suggest the potential utility of the MSG-fade to establish stable voluntary oral ethanol consumption in mice, particularly ethanol 'non-preferring' strains such as DBA/2J and lend additional support to the notion that ethanol consumption in DBA/2J mice is limited by pronounced taste aversion.}, } @article {pmid20974194, year = {2011}, author = {Castillo, DV and Escobar, ML}, title = {A role for MAPK and PI-3K signaling pathways in brain-derived neurotrophic factor modification of conditioned taste aversion retention.}, journal = {Behavioural brain research}, volume = {217}, number = {1}, pages = {248-252}, doi = {10.1016/j.bbr.2010.10.013}, pmid = {20974194}, issn = {1872-7549}, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology ; Conditioning, Classical/drug effects/physiology ; Male ; Microinjections ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Rats ; Rats, Wistar ; Retention, Psychology/*drug effects ; Signal Transduction/drug effects/*physiology ; Taste ; Temporal Lobe/drug effects/*metabolism ; }, abstract = {Brain-derived neurotrophic factor (BDNF) has emerged as an important molecular mediator of synaptic plasticity. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that the intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the projection from the basolateral nucleus of the amygdala (Bla) to the IC of adult rats in vivo. Recently, we have found that intracortical microinfusion of BDNF previous to CTA training modifies the retention of this task. In this work, we present experimental data showing that BDNF effects on CTA retention are dependent on both the activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase (PI-3K) at the insular cortex. Our results are evidence of the crucial role of both pathways in the modification of the CTA trace of memory caused by BDNF at a neocortical area.}, } @article {pmid20971936, year = {2010}, author = {Roitman, MF and Wheeler, RA and Tiesinga, PH and Roitman, JD and Carelli, RM}, title = {Hedonic and nucleus accumbens neural responses to a natural reward are regulated by aversive conditioning.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {17}, number = {11}, pages = {539-546}, pmid = {20971936}, issn = {1549-5485}, support = {R01 DA025634/DA/NIDA NIH HHS/United States ; DA025679/DA/NIDA NIH HHS/United States ; R01 DA014339/DA/NIDA NIH HHS/United States ; DA014339/DA/NIDA NIH HHS/United States ; R00 DA025679/DA/NIDA NIH HHS/United States ; R21 DA027127/DA/NIDA NIH HHS/United States ; DA027127/DA/NIDA NIH HHS/United States ; DA025634/DA/NIDA NIH HHS/United States ; K99 DA025679/DA/NIDA NIH HHS/United States ; }, mesh = {Action Potentials/physiology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Operant/*physiology ; Electromyography/methods ; Food Preferences/*physiology ; Male ; Muscle, Skeletal/physiology ; Neurons/physiology ; Nucleus Accumbens/cytology/*physiology ; Rats ; Rats, Sprague-Dawley ; *Reward ; Sucrose/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/physiology ; }, abstract = {The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA) paradigm. Electrophysiological and electromyographic (EMG) responses to intraoral infusions of a sucrose (0.3 M) solution were made in naïve rats (Day 1). Immediately following the session, half of the rats (n = 6; Paired) received an injection of lithium chloride (0.15 M; i.p.) to induce malaise and establish a CTA while the other half (n = 6; Unpaired) received a saline injection. Days later (Day 5), NAc recordings during infusions of sucrose were again made. Electrophysiological and EMG responses to sucrose did not differ between groups on Day 1. For both groups, the majority of sucrose responsive neurons exhibited a decrease in firing rate (77% and 71% for Paired and Unpaired, respectively). Following conditioning, in Paired rats, EMG responses were indicative of aversion. Moreover, the majority of responsive NAc neurons now exhibited an increase in firing rate (69%). Responses in Unpaired rats were unchanged by the experience. Thus, the NAc differentially encodes the hedonic value of the same stimulus based on learned associations.}, } @article {pmid20955809, year = {2011}, author = {Stehberg, J and Simon, F}, title = {Involvement of the insular cortex in retention of conditioned taste aversion is not time dependent.}, journal = {Neurobiology of learning and memory}, volume = {95}, number = {1}, pages = {14-18}, doi = {10.1016/j.nlm.2010.10.002}, pmid = {20955809}, issn = {1095-9564}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Ibotenic Acid/pharmacology ; Male ; Microinjections ; Rats ; Rats, Wistar ; Retention, Psychology/drug effects/*physiology ; Statistics, Nonparametric ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {In fear-associated learning paradigms, hippocampal lesions induce memory deficits of recent but not remote memories, while amygdala lesions produce retention deficits irrespective of the age of the memory. In conditioned taste aversion (CTA), non-hippocampal mediated learning paradigm, the insular vortex (IC) has shown to have a crucial role in consolidation and storage of CTA memory. Due to the functional and anatomical similarities to the hippocampus, a time dependent role of the IC in CTA retention cannot be ruled out. To test whether the IC shows a time dependent role in CTA memory retention, male Wistar rats were CTA trained on saccharin 0.1% (LiCl 0.15M, 2% b/w, 40 min after drinking) and lesioned with ibotenic acid (200-300 nL, 5mg/mL) unilaterally into the IC 1 week or bilaterally 1 or 6 weeks after CTA. CTA memory was completely disrupted in both bilateral lesion groups but unaffected in the unilateral lesioned group. The resulting preference was comparable to that of the bilaterally IC lesioned animals exposed to the taste for the first time, proving that in these animals a complete amnesic state was achieved. Bilaterally IC lesioned rats showed normal discrimination between preferred (sucrose 5%) and non-preferred (quinone) tastes. Our data indicates that the involvement of the IC in CTA is not time dependent and that CTA memories are stored in each hemisphere separately.}, } @article {pmid20946908, year = {2011}, author = {Liang, NC and Bello, NT and Moran, TH}, title = {Experience with activity based anorexia enhances conditioned taste aversion learning in rats.}, journal = {Physiology & behavior}, volume = {102}, number = {1}, pages = {51-57}, pmid = {20946908}, issn = {1873-507X}, support = {R01 DK019302/DK/NIDDK NIH HHS/United States ; R01 DK019302-34/DK/NIDDK NIH HHS/United States ; R56 DK019302/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anorexia Nervosa/*psychology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Disease Models, Animal ; Extinction, Psychological/physiology ; Female ; Food ; Lithium Chloride ; Motor Activity/*physiology ; Rats ; Rats, Sprague-Dawley ; Sucrose ; }, abstract = {Activity based anorexia (ABA) is a model that mimics the self-starvation and hyperactivity features of anorexia nervosa (AN). This study investigated whether a history of ABA will enhance food avoidance learning and retard its extinction in female rats. We compared the acquisition and extinction of a conditioned taste aversion (CTA) in naive (ad lib with no access to RW), ABA, and pair-fed to the food intake of ABA (with access to a locked RW) female Sprague-Dawley rats. The CTA conditioning was conducted after the ABA and pair-fed rats had recovered to their pre-food restriction body weights. For the CTA learning, 0.3M sucrose consumption was followed by low doses LiCl (0.009M or 0.018M at 1.33ml/100g of body weight, IP) injection. The results revealed that the ABA rats acquired an aversion to sucrose significantly sooner than the naive controls. Furthermore, they completely avoided sucrose while the naive and pair-fed controls still sampled it by the end of 10 conditioning trials. When extinction was assessed by 1-bottle and 2-bottle tests, the ABA rats extinguished more slowly than the controls. However, the differences in sucrose aversion extinction between the ABA and control rats were only significant in the 1-bottle test. These data suggest that experience with AN-like behaviors results in an acquired aversion to a preferred food sooner and a longer retention of the negative food associations. These findings have implications for understanding the persistence of aberrant eating behaviors in eating disorders.}, } @article {pmid20876231, year = {2011}, author = {Blednov, YA and Borghese, CM and McCracken, ML and Benavidez, JM and Geil, CR and Osterndorff-Kahanek, E and Werner, DF and Iyer, S and Swihart, A and Harrison, NL and Homanics, GE and Harris, RA}, title = {Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive α2-containing GABA(A) receptors.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {336}, number = {1}, pages = {145-154}, pmid = {20876231}, issn = {1521-0103}, support = {R37 AA010422/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; P01 GM047818/GM/NIGMS NIH HHS/United States ; GM47818/GM/NIGMS NIH HHS/United States ; R01 AA010422/AA/NIAAA NIH HHS/United States ; AA13520/AA/NIAAA NIH HHS/United States ; AA06399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; AA10422/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/genetics ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Ethanol/*administration & dosage ; Female ; Gene Knock-In Techniques ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Motor Activity/drug effects/*genetics ; Receptors, GABA-A/*genetics/physiology ; Taste/drug effects/*genetics ; Xenopus laevis ; }, abstract = {GABA type A receptors (GABA(A)-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABA(A)-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705-714, 2004; Pharmacol Biochem Behav 90:95-104, 2008; J Psychiatr Res 42:184-191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism.}, } @article {pmid20860618, year = {2010}, author = {Anderson, RI and Varlinskaya, EI and Spear, LP}, title = {Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.}, journal = {Alcoholism, clinical and experimental research}, volume = {34}, number = {12}, pages = {2106-2115}, pmid = {20860618}, issn = {1530-0277}, support = {R01 AA016887/AA/NIAAA NIH HHS/United States ; R01 AA016887-04/AA/NIAAA NIH HHS/United States ; R01 AA16887/AA/NIAAA NIH HHS/United States ; R37 AA12525/AA/NIAAA NIH HHS/United States ; R37 AA012525/AA/NIAAA NIH HHS/United States ; R01 AA018026-02/AA/NIAAA NIH HHS/United States ; R37 AA012525-09/AA/NIAAA NIH HHS/United States ; R01 AA018026/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological/*psychology ; *Taste ; }, abstract = {BACKGROUND: Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed.

METHODS: Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings.

RESULTS: This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment.

CONCLUSIONS: Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption.}, } @article {pmid20860614, year = {2010}, author = {Schramm-Sapyta, NL and DiFeliceantonio, AG and Foscue, E and Glowacz, S and Haseeb, N and Wang, N and Zhou, C and Kuhn, CM}, title = {Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.}, journal = {Alcoholism, clinical and experimental research}, volume = {34}, number = {12}, pages = {2061-2069}, pmid = {20860614}, issn = {1530-0277}, support = {K01 DA020729/DA/NIDA NIH HHS/United States ; K01 DA020729-05/DA/NIDA NIH HHS/United States ; R01 AA017621/AA/NIAAA NIH HHS/United States ; DA020729/DA/NIDA NIH HHS/United States ; }, mesh = {Age Factors ; Alcohol Drinking/blood/*psychology ; Animals ; Avoidance Learning/drug effects ; Body Temperature/drug effects ; Conditioning, Classical/drug effects ; Drug-Seeking Behavior/drug effects ; Ethanol/blood/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Sleep/drug effects ; Taste ; }, abstract = {BACKGROUND: Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects?

METHODS: Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs).

RESULTS: We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs.

CONCLUSIONS: These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol.}, } @article {pmid20837048, year = {2010}, author = {Hutchison, MA and Albaugh, DL and Riley, AL}, title = {Exposure to alcohol during adolescence alters the aversive and locomotor-activating effects of cocaine in adult rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {97}, number = {2}, pages = {370-376}, doi = {10.1016/j.pbb.2010.09.006}, pmid = {20837048}, issn = {1873-5177}, mesh = {Animals ; Avoidance Learning/drug effects ; Central Nervous System Depressants/*pharmacology ; Cocaine/*pharmacology ; Conditioning, Operant/drug effects ; Drug Interactions ; Ethanol/*pharmacology ; Male ; Motivation ; Motor Activity/*drug effects ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; }, abstract = {OBJECTIVES: The present study assessed the effect of adolescent alcohol exposure on the later aversive and locomotor-activating effects of cocaine.

METHODS: Male rats were exposed to alcohol or vehicle for 10days [postnatal day (PND) 30-39; 2g/kg IP]. Taste aversion conditioning began on PND 65. During aversion conditioning, subjects were presented with saccharin followed by cocaine (32mg/kg; 15, 180 or 300min post saccharin) or saline. Following each injection, animals were placed in locomotor chambers for 1h. To determine if any effects seen were specific to the adolescent developmental period, the procedure was replicated in adult animals.

RESULTS: Animals exposed to vehicle during adolescence showed significant aversions at all time delays. Animals exposed to ethanol during adolescence showed a decrease in consumption only at the 15 and 180min delays. Groups exposed to alcohol during adolescence showed a decrease in gross, and an increase in fine, motor activity in response to cocaine. Animals exposed to alcohol during adulthood also showed attenuated taste aversions.

CONCLUSIONS: Exposure to ethanol during adolescence attenuated the aversive effects of cocaine and altered its locomotor-activating effects. Although this effect is not specific to adolescence, this is the time when alcohol use is typically initiated so that such exposure may enhance later abuse liability of cocaine.}, } @article {pmid20826200, year = {2010}, author = {Lin, PY and Wang, SP and Tai, MY and Tsai, YF}, title = {Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning.}, journal = {Neuroscience}, volume = {171}, number = {1}, pages = {125-133}, doi = {10.1016/j.neuroscience.2010.08.066}, pmid = {20826200}, issn = {1873-7544}, mesh = {Adaptation, Physiological ; Amygdala/*physiology ; Analysis of Variance ; Animals ; Conditioning, Operant/*physiology ; Extinction, Psychological/*physiology ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Male ; Phosphorylation ; Prefrontal Cortex/drug effects/*physiology ; Rats ; Rats, Long-Evans ; Reinforcement, Psychology ; Sucrose/administration & dosage ; Taste/*physiology ; Time Factors ; Water Deprivation/physiology ; }, abstract = {Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is differentially involved in these processes.}, } @article {pmid20738016, year = {2010}, author = {Walker, EA}, title = {Animal models.}, journal = {Advances in experimental medicine and biology}, volume = {678}, number = {}, pages = {138-146}, doi = {10.1007/978-1-4419-6306-2_18}, pmid = {20738016}, issn = {0065-2598}, support = {R01 CA129092/CA/NCI NIH HHS/United States ; CA129092/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/adverse effects/pharmacology/therapeutic use ; Memory/drug effects ; *Models, Animal ; Motor Activity/drug effects ; Neoplasms/drug therapy/physiopathology ; Sensation/drug effects ; }, abstract = {As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.}, } @article {pmid20729290, year = {2010}, author = {Bi, AL and Wang, Y and Li, BQ and Wang, QQ and Ma, L and Yu, H and Zhao, L and Chen, ZY}, title = {Region-specific involvement of actin rearrangement-related synaptic structure alterations in conditioned taste aversion memory.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {17}, number = {9}, pages = {420-427}, doi = {10.1101/lm.1772310}, pmid = {20729290}, issn = {1549-5485}, mesh = {Actins/metabolism/*ultrastructure ; Amygdala/metabolism/ultrastructure ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/metabolism/*ultrastructure ; Conditioning, Classical/physiology ; Male ; Mental Recall/physiology ; Rats ; Rats, Wistar ; Retention, Psychology/*physiology ; Statistics, Nonparametric ; Synapses/metabolism/*ultrastructure ; Time Factors ; }, abstract = {Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related synaptic structure alterations in different memory processes. We found that CTA training could induce increased postsynaptic density (PSD) length in insular cortex (IC), but not in basolateral amygdala (BLA) and prelimbic cortex (PrL) during short-term memory (STM) formation, whereas it led to increased PSD length and synapse density in both IC and PrL during long-term memory (LTM) formation. Inhibition of actin rearrangement in the IC, but not in the BLA and PrL, impaired memory acquisition. Furthermore, actin dynamics in the IC or PrL is necessary for memory consolidation. On the contrary, inhibition of actin dynamics in the IC, BLA, or PrL had no effect on CTA memory retrieval. Our results suggest temporal and regional-specific regulation of actin rearrangement-related synaptic structure in different phases of CTA memory.}, } @article {pmid20722718, year = {2010}, author = {Garcia-Delatorre, P and Rodríguez-Ortiz, CJ and Balderas, I and Bermúdez-Rattoni, F}, title = {Differential participation of temporal structures in the consolidation and reconsolidation of taste aversion extinction.}, journal = {The European journal of neuroscience}, volume = {32}, number = {6}, pages = {1018-1023}, doi = {10.1111/j.1460-9568.2010.07365.x}, pmid = {20722718}, issn = {1460-9568}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; Temporal Lobe/*physiology ; }, abstract = {The extinction process has been described as the decline in the frequency or intensity of the conditioned response following the withdrawal of reinforcement. Hence, experimental extinction does not reflect loss of the original memory, but rather reflects new learning, which in turn requires consolidation in order to be maintained in the long term. During extinction of conditioned taste aversion (CTA), a taste previously associated with aversive consequences acquires a safe status through continuous presentations of the flavor with no aversive consequence. In addition, reconsolidation has been defined as the labile state of a consolidated memory after its reactivation by the presentation of relevant information. In this study, we analyzed structures from the temporal lobe that could be involved in consolidation and reconsolidation of extinction of CTA by means of new protein synthesis. Our results showed that protein synthesis in the hippocampus (HC), the perirhinal cortex (PR) and the insular cortex (IC) of rats participate in extinction consolidation, whereas the basolateral amygdala plays no part in this phenomenon. Furthermore, we found that inhibition of protein synthesis in the IC in a third extinction trial had an effect on reconsolidation of extinction. The participation of the HC in taste memory has been described as a downmodulator for CTA consolidation, and has been related to a context-taste association. Altogether, these data suggest that extinction of aversive taste memories are subserved by the IC, HC and PR, and that extinction can undergo reconsolidation, a process depending only on the IC.}, } @article {pmid20655940, year = {2010}, author = {Harrod, SB and Lacy, RT and Ballina, LE}, title = {Persistent expression of methamphetamine-induced CTA in periadolescent rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {96}, number = {4}, pages = {515-520}, pmid = {20655940}, issn = {1873-5177}, support = {R01 DA021287/DA/NIDA NIH HHS/United States ; DA021287/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; *Conditioning, Operant ; Dose-Response Relationship, Drug ; Methamphetamine/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {It is well documented that the transition from periadolescence to adulthood produces profound changes in motivated behavior, and furthermore, attenuates the aversive experience of abused drugs. Little is known, however, about adolescent memory for the conditioned aversive effects of abused drugs following retention intervals that span this developmental transition. The present experiment investigated methamphetamine-induced conditioned taste aversion (CTA) in periadolescent rats to determine if the magnitude of conditioning was altered following retention intervals that extend to adulthood. Rats consumed saccharin (0.1%, w/v) and were immediately injected with saline or methamphetamine (3.0mg/kg) either once (PND 40) or three times (PND 38-40), and memory was assessed one or 50 days later on post natal days 41 or 90, respectively. Rats exhibited robust methamphetamine-induced CTA one and 50 days after conditioning, and the strength of responding did not change as a function of retention interval, regardless if animals were trained with one or three saccharin-methamphetamine pairings. These findings indicate that the expression of memory for the aversive effects of methamphetamine was resistant to degradation throughout the developmental period of periadolescence to adulthood.}, } @article {pmid20631825, year = {2010}, author = {Sadamoto, H and Kitahashi, T and Fujito, Y and Ito, E}, title = {Learning-Dependent Gene Expression of CREB1 Isoforms in the Molluscan Brain.}, journal = {Frontiers in behavioral neuroscience}, volume = {4}, number = {}, pages = {25}, pmid = {20631825}, issn = {1662-5153}, abstract = {Cyclic AMP-responsive element binding protein1 (CREB1) has multiple functions in gene regulation. Various studies have reported that CREB1-dependent gene induction is necessary for memory formation and long-lasting behavioral changes in both vertebrates and invertebrates. In the present study, we characterized Lymnaea CREB1 (LymCREB1) mRNA isoforms of spliced variants in the central nervous system (CNS) of the pond snail Lymnaea stagnalis. Among these spliced variants, the three isoforms that code a whole LymCREB1 protein are considered to be the activators for gene regulation. The other four isoforms, which code truncated LymCREB1 proteins with no kinase inducible domain, are the repressors. For a better understanding of the possible roles of different LymCREB1 isoforms, the expression level of these isoform mRNAs was investigated by a real-time quantitative RT-PCR method. Further, we examined the changes in gene expression for all the isoforms in the CNS after conditioned taste aversion (CTA) learning or backward conditioning as a control. The results showed that CTA learning increased LymCREB1 gene expression, but it did not change the activator/repressor ratio. Our findings showed that the repressor isoforms, as well as the activator ones, are expressed in large amounts in the CNS, and the gene expression of CREB1 isoforms appeared to be specific for the given stimulus. This was the first quantitative analysis of the expression patterns of CREB1 isoforms at the mRNA level and their association with learning behavior.}, } @article {pmid20626247, year = {2010}, author = {Eller, LK and Reimer, RA}, title = {Attenuation in weight gain with high calcium- and dairy-enriched diets is not associated with taste aversion in rats: a comparison with casein, whey, and soy.}, journal = {Journal of medicinal food}, volume = {13}, number = {5}, pages = {1182-1188}, doi = {10.1089/jmf.2009.0223}, pmid = {20626247}, issn = {1557-7600}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Calcium, Dietary/*administration & dosage ; Caseins/administration & dosage ; Dairy Products ; Diet ; Dietary Proteins/*administration & dosage ; Eating ; *Food Preferences ; Male ; Milk Proteins/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Satiation ; Soybean Proteins/administration & dosage ; *Taste ; *Weight Gain ; Whey Proteins ; }, abstract = {A systematic evaluation of the effects of calcium (Ca) and protein source on food intake and taste aversion (TA) in rats is lacking. The purpose of this research was twofold: (1) to determine if Sprague-Dawley rats display TA to standard rat chow supplemented with 2.4% Ca and (2) to determine if short (24-hour) and long-term (weekly) food intake and weight gain are altered when rats are given access to diets containing various protein sources (casein, whey, dairy, or soy). Rats were assigned to one of two diet groups to examine high (2.4%) versus low (0.67%) Ca or to one of four groups to examine taste preference of diets where the sole protein was one of casein, soy, whey, or complete dairy. A crossover design was used to ensure rats consumed all test diets. Food intake and behavioral sequence of satiety were measured. There was no TA to the 2.4% Ca diet or to any protein source. Food intake did not differ between the two Ca diets or between the four protein diets. The dairy diet attenuated weekly weight gain compared to all other diets except whey. Overall, this study suggests that the levels of Ca and types of protein used in previous work addressing changes in body weight in rats do not influence food intake or trigger TA.}, } @article {pmid20605874, year = {2010}, author = {Nelson, TM and Lopezjimenez, ND and Tessarollo, L and Inoue, M and Bachmanov, AA and Sullivan, SL}, title = {Taste function in mice with a targeted mutation of the pkd1l3 gene.}, journal = {Chemical senses}, volume = {35}, number = {7}, pages = {565-577}, pmid = {20605874}, issn = {1464-3553}, support = {R01 DC00882/DC/NIDCD NIH HHS/United States ; R01 AA011028/AA/NIAAA NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; R01 AA11028/AA/NIAAA NIH HHS/United States ; R01 DC000882/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Calcium Channels ; Gene Knockout Techniques ; Gene Targeting ; Male ; Mice ; Mice, Inbred C57BL ; Mutation/*genetics ; TRPP Cation Channels/*genetics ; Taste/*genetics ; }, abstract = {Recent studies, both in vitro and in vivo, have suggested the involvement of the polycystic kidney disease-1 and -2 like genes, Pkd1l3 and Pkd2l1, in acid taste transduction. In mice, disruption of taste cells expressing PKD2L1 eliminates gustatory neural responses to acids. However, no previous data exist on taste responses in the absence of PKD1L3 or on behavioral responses in mice lacking either of these proteins. In order to assess the function of PKD1L3, we genetically engineered mice with a targeted mutation of the Pkd1l3 gene. We then examined taste responsiveness of mutant and wild-type mice using several different approaches. In separate groups of mice, we measured preference scores in 48-h 2-bottle tests, determined NaCl or citric acid taste thresholds using a conditioned taste aversion technique, and conducted electrophysiological recordings of activity in the chorda tympani and glossopharyngeal nerves. Multiple taste compounds representing all major taste qualities were used in the preference tests and nerve-recording experiments. We found no significant reduction in taste responsiveness in Pkd1l3 mutant mice in behavioral or electrophysiological tests when compared with wild-type controls. Therefore, further studies are needed to elucidate the function of PKD1L3 in taste bud cells.}, } @article {pmid20599840, year = {2010}, author = {Oberbeck, DL and McCormack, S and Houpt, TA}, title = {Intra-amygdalar okadaic acid enhances conditioned taste aversion learning and CREB phosphorylation in rats.}, journal = {Brain research}, volume = {1348}, number = {}, pages = {84-94}, pmid = {20599840}, issn = {1872-6240}, support = {R01 DC003198-08/DC/NIDCD NIH HHS/United States ; R01DC03198/DC/NIDCD NIH HHS/United States ; F31DC06129/DC/NIDCD NIH HHS/United States ; T32DC00044/DC/NIDCD NIH HHS/United States ; R01 DC003198/DC/NIDCD NIH HHS/United States ; F31 DC006129/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/*drug effects ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; CREB-Binding Protein/*metabolism ; Conditioning, Classical/drug effects ; Food Preferences/drug effects ; Lithium Chloride/administration & dosage ; Male ; Okadaic Acid/*pharmacology ; Phosphorylation/drug effects ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Statistics, Nonparametric ; Sweetening Agents/administration & dosage ; Taste/*drug effects ; }, abstract = {Protein phosphatases (PPs) regulate many substrates implicated in learning and memory. Conditioned taste aversion (CTA) learning, in which animals associate a novel taste paired with a toxin and subsequently avoid the taste, is dependent on several serine/threonine phosphatase substrates and the PP1-binding protein spinophilin. In order to examine the effects of PP1/2A blockade on CTA acquisition and extinction, rats received bilateral infusions of okadaic acid (OA) (100nM, 1microl/hemisphere) or vehicle (0.15M NaCl) into the amygdala either 5min prior to, or 5min after, a single pairing of sodium saccharin (0.125%, 10-min access) and LiCl or NaCl (0.15M, 3ml/kg i.p.). Two-bottle, 24-h preference tests were conducted for 13days to measure CTA expression and extinction. Rats conditioned with saccharin and LiCl showed a decreased preference for saccharin, and OA administered before (but not after) the pairing of saccharin and LiCl resulted in a significantly stronger CTA that did not extinguish over 13days. The enhancement of the CTA was not due to aversive effects of OA, because rats given OA and a pairing of saccharin and NaCl did not acquire a CTA. Finally, OA administration increased levels of phosphorylated CREB immunoreactivity following a CTA trial. Together, these results suggest a critical role for PP1/2A during normal CTA learning. Because CTA learning was enhanced only when OA was given prior to conditioning, phosphatase activity may be a constraint on learning during the taste-toxin interval but not during acquisition and consolidation processes that occur after toxin administration.}, } @article {pmid20553875, year = {2010}, author = {Cason, AM and Kwon, B and Smith, JC and Houpt, TA}, title = {c-Fos induction by a 14 T magnetic field in visceral and vestibular relays of the female rat brainstem is modulated by estradiol.}, journal = {Brain research}, volume = {1347}, number = {}, pages = {48-57}, pmid = {20553875}, issn = {1872-6240}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; R01 DC003198-08/DC/NIDCD NIH HHS/United States ; R01 DC004607/DC/NIDCD NIH HHS/United States ; R01 DC004607-07/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; *Brain Stem/drug effects/metabolism/radiation effects ; Estradiol/*pharmacology ; Estrogens/*pharmacology ; Female ; *Gene Expression Regulation/drug effects/physiology/radiation effects ; Magnetic Resonance Spectroscopy/methods ; Magnetics/*methods ; Motor Activity/drug effects/radiation effects ; Ovariectomy/methods ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Statistics as Topic ; Vestibular Nuclei/*physiology ; Viscera/*innervation ; }, abstract = {There is increasing evidence that high magnetic fields interact with the vestibular system of humans and rodents. In rats, exposure to high magnetic fields of 7 T or above induces locomotor circling and leads to a conditioned taste aversion if paired with a novel taste. Sex differences in the behavioral responses to magnetic field exposure have been found, such that female rats show more locomotor circling and enhanced conditioned taste aversion compared to male rats. To determine if estrogen modulates the neural response to high magnetic fields, c-Fos expression after 14 T magnetic field exposure was compared in ovariectomized rats and ovariectomized rats with estradiol replacement. Compared to sham exposure, magnetic field exposure induced significantly more c-Fos positive cells in the nucleus of the solitary tract and the parabrachial, medial vestibular, prepositus, and supragenualis nuclei. Furthermore, there was a significant asymmetry in c-Fos induction between sides of the brainstem in several regions. In ovariectomized rats, there was more c-Fos expressed in the right side compared to left side in the locus coeruleus and parabrachial, superior vestibular, and supragenualis nuclei; less expression in the right compared to left side of the medial vestibular; and no asymmetry in the prepositus nucleus and the nucleus of the solitary tract. Chronic estradiol treatment modulated the neural response in some regions: less c-Fos was induced in the superior vestibular nucleus and locus coeruleus after estradiol replacement; estradiol treatment eliminated the asymmetry of c-Fos expression in the locus coeruleus and supragenualis nucleus, created an asymmetry in the prepositus nucleus and reversed the asymmetry in the parabrachial nucleus. These results suggest that ovarian steroids may mediate sex differences in the behavioral responses to magnetic field exposure at the level of visceral and vestibular nuclei of the brainstem.}, } @article {pmid20537986, year = {2010}, author = {Li, S and Gu, Y and Meng, B and Mei, B and Li, F}, title = {The different effects of over-expressing murine NMDA receptor 2B subunit in the forebrain on conditioned taste aversion.}, journal = {Brain research}, volume = {1351}, number = {}, pages = {165-171}, doi = {10.1016/j.brainres.2010.06.004}, pmid = {20537986}, issn = {1872-6240}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/physiology ; Male ; Mice ; Mice, Inbred CBA ; Mice, Transgenic ; Prosencephalon/*metabolism ; Protein Subunits/*biosynthesis/genetics ; Receptors, N-Methyl-D-Aspartate/*biosynthesis/genetics ; Taste/*genetics ; }, abstract = {The glutamate transmission system and the N-methyl-D-aspartate receptor (NMDA-R), in particular its 2B subunit (NR2B), have been reported to be possibly related to taste memory as a result of treatment with NMDA antagonists and agonists. In order to further study the role of the NR2B subunit in gustation memory, we applied four different taste aversive tasks to observe the behavior of a transgenic mice model in which the NR2B subunit was specifically over-expressed in the forebrain. We found that in both short- and long-term conditioned taste aversion (CTA) experiments, mice with forebrain expression of the NR2B transgene (Tg) showed significantly enhanced CTA 2 days after training. However, both the Tg and the wild-type (Wt) mice shared the same level of aversive memory on the 30th day after training. In both fast and slow extinction experiments, Tg mice maintained a higher CTA memory than that of control mice in most extinction trials. The third experiment, which involved testing the memory for familiar taste, demonstrated that NR2B augmentation had no benefit on the latent inhibition (LI) of CTA. In addition, the last experiment (two-taste LI) showed a suppression of enhanced CTA in Tg mice when the mice were exposed to both novel and familiar tastes. These data suggested that forebrain NR2B over-expression had different effects on gustatory learning and memory. The transgenic animals were only sensitive to novel but not familiar tastes, and up-regulation of NR2B resulted in enhanced CTA function for only a short period of time.}, } @article {pmid20457865, year = {2010}, author = {Koyanagi, Y and Yamamoto, K and Oi, Y and Koshikawa, N and Kobayashi, M}, title = {Presynaptic interneuron subtype- and age-dependent modulation of GABAergic synaptic transmission by beta-adrenoceptors in rat insular cortex.}, journal = {Journal of neurophysiology}, volume = {103}, number = {5}, pages = {2876-2888}, doi = {10.1152/jn.00972.2009}, pmid = {20457865}, issn = {1522-1598}, mesh = {Action Potentials/drug effects/physiology ; Adrenergic alpha-Agonists/pharmacology ; Adrenergic beta-Agonists/pharmacology ; Aging/drug effects/*physiology ; Animals ; Cerebral Cortex/drug effects/growth & development/*physiology ; Female ; In Vitro Techniques ; Inhibitory Postsynaptic Potentials/drug effects/physiology ; Interneurons/drug effects/*physiology ; Isoproterenol/pharmacology ; Male ; Patch-Clamp Techniques ; Presynaptic Terminals/drug effects/*physiology ; Propranolol ; Pyramidal Cells/drug effects/growth & development/physiology ; Rats ; Rats, Transgenic ; Receptors, Adrenergic, beta/*metabolism ; Synaptic Transmission/drug effects/*physiology ; gamma-Aminobutyric Acid/*metabolism ; }, abstract = {beta-Adrenoceptors play a crucial role in the regulation of taste aversion learning in the insular cortex (IC). However, beta-adrenergic effects on inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA) remain unknown. To elucidate the mechanisms of beta-adrenergic modulation of inhibitory synaptic transmission, we performed paired whole cell patch-clamp recordings from layer V GABAergic interneurons and pyramidal cells of rat IC aged from postnatal day 17 (PD17) to PD46 and examined the effects of isoproterenol, a beta-adrenoceptor agonist, on unitary inhibitory postsynaptic currents (uIPSCs). Isoproterenol (100 microM) induced facilitating effects on uIPSCs in 33.3% of cell pairs accompanied by decreases in coefficient of variation (CV) of the first uIPSC amplitude and paired-pulse ratio (PPR) of the second to first uIPSC amplitude, whereas 35.9% of pairs showed suppressive effects of isoproterenol on uIPSC amplitude obtained from fast spiking (FS) to pyramidal cell pairs. Facilitatory effects of isoproterenol were frequently observed in FS-pyramidal cell pairs at > or =PD24. On the other hand, isoproterenol suppressed uIPSC amplitude by 52.3 and 39.8% in low-threshold spike (LTS)-pyramidal and late spiking (LS)-pyramidal cell pairs, respectively, with increases in CV and PPR. The isoproterenol-induced suppressive effects were blocked by preapplication of 100 microM propranolol, a beta-adrenoceptor antagonist. There was no significant correlation between age and changes of uIPSCs in LTS-/LS-pyramidal cell pairs. These results suggest the presence of differential mechanisms in presynaptic GABA release and/or postsynaptic GABA(A) receptor-related assemblies among interneuron subtypes. Age- and interneuron subtype-specific beta-adrenergic modulation of IPSCs may contribute to experience-dependent plasticity in the IC.}, } @article {pmid20457177, year = {2010}, author = {Taraschenko, OD and Maisonneuve, IM and Glick, SD}, title = {18-Methoxycoronaridine, a potential anti-obesity agent, does not produce a conditioned taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {96}, number = {3}, pages = {247-250}, pmid = {20457177}, issn = {1873-5177}, support = {R01 DA016283/DA/NIDA NIH HHS/United States ; DA 016283/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Anti-Obesity Agents/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Eating/drug effects ; Female ; Ibogaine/*analogs & derivatives/pharmacology ; Lithium Chloride ; Rats ; Rats, Sprague-Dawley ; Sucrose ; Taste/*drug effects ; }, abstract = {18-Methoxycoronaridine (18-MC), a selective antagonist of alpha3beta4 nicotinic receptors, has been shown to reduce the self-administration of several drugs of abuse. Recently, this agent has also been shown to attenuate sucrose reward, decrease sucrose intake and prevent the development of sucrose-induced obesity in rats. The present experiments were designed to determine whether the latter effect was due to an 18-MC-induced conditioned taste aversion to sucrose. Both 18-MC (20mg/ kg, i.p.) and control agent, lithium chloride (100mg/kg, i.p.), reduced sucrose intake 24h after association with sucrose; however, only lithium chloride reduced sucrose intake 72h later. Consistent with previous data, 18-MC appears to have proactive effect for 24h and it does not induce a conditioned taste aversion.}, } @article {pmid20451634, year = {2010}, author = {Knapman, A and Heinzmann, JM and Holsboer, F and Landgraf, R and Touma, C}, title = {Modeling psychotic and cognitive symptoms of affective disorders: Disrupted latent inhibition and reversal learning deficits in highly stress reactive mice.}, journal = {Neurobiology of learning and memory}, volume = {94}, number = {2}, pages = {145-152}, doi = {10.1016/j.nlm.2010.04.010}, pmid = {20451634}, issn = {1095-9564}, mesh = {Affective Symptoms/etiology/*physiopathology/psychology ; Animals ; Avoidance Learning/physiology ; Brain/metabolism/physiology ; Cognition/physiology ; Corticosterone/blood ; Depressive Disorder, Major/complications/*physiopathology/psychology ; *Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins/genetics/metabolism ; Inhibition, Psychological ; Male ; Mice ; Mice, Inbred Strains ; Psychotic Disorders/etiology/*physiopathology/psychology ; RNA, Messenger/analysis ; Receptors, Dopamine D1/genetics/metabolism ; Receptors, Dopamine D2/genetics/metabolism ; Reversal Learning/physiology ; Schizophrenia/complications/*physiopathology ; Stress, Psychological/complications/*physiopathology/psychology ; }, abstract = {Increased stress reactivity has repeatedly been reported in patients suffering from psychiatric diseases including schizophrenia and major depression. These disorders also have other symptoms in common, such as cognitive deficits and psychotic-like behavior. We have therefore investigated if increased stress reactivity is associated with these phenotypic endpoints in an animal model of affective disorders. The stress reactivity mouse model used in this study consists of three CD-1-derived mouse lines, that have been selectively bred for high (HR), intermediate (IR) or low (LR) stress reactivity. Male mice from these three breeding lines were subjected to a reversal learning task and latent inhibition (Li) was assessed using a conditioned taste aversion paradigm. Furthermore, as the dopaminergic system is involved in both Li and reversal learning, the dopamine 1 receptor (D1R), dopamine 2 receptor (D2R) and dopamine transporter (DAT) mRNA expression levels were assessed in relevant brain areas of these animals. The results demonstrate that HR mice show perseveration in the reversal learning task and have disrupted Li. Furthermore, compared to LR mice, HR mice have decreased D2R mRNA levels in the ventral tegmental area, as well as decreased D1R mRNA levels in the cingulate cortex, and an increased expression of D2R mRNA in the nucleus accumbens. Taken together, these results demonstrate that the HR mice display cognitive deficits associated with psychotic-like behavior, similar to those observed in patients suffering from schizophrenia and major depression and could be utilized in the search for better treatment strategies for these symptoms of psychiatric disorders.}, } @article {pmid20435101, year = {2010}, author = {Reyes-López, J and Nuñez-Jaramillo, L and Morán-Guel, E and Miranda, MI}, title = {Differential effects of beta-adrenergic receptor blockade in the medial prefrontal cortex during aversive and incidental taste memory formation.}, journal = {Neuroscience}, volume = {169}, number = {1}, pages = {195-202}, doi = {10.1016/j.neuroscience.2010.04.054}, pmid = {20435101}, issn = {1873-7544}, mesh = {Adrenergic beta-Antagonists/*pharmacology/toxicity ; Animals ; Appetitive Behavior/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Lithium Chloride/toxicity ; Male ; Memory Disorders/*chemically induced/physiopathology ; Memory, Long-Term/drug effects/*physiology ; Memory, Short-Term/drug effects/*physiology ; Mental Recall/drug effects/physiology ; Prefrontal Cortex/*drug effects/physiology ; Propranolol/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/drug effects/*physiology ; Saccharin ; Taste Perception/drug effects/*physiology ; }, abstract = {The medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. Specifically, the noradrenergic system in this cortex is involved in aversive learning, as well as in the retrieval of these memories. Some evidence suggests that this area has an important role during taste memory, particularly during conditioned taste aversion (CTA), a model of aversive memory. Despite some previous evidence, there is scarce information about the role of adrenergic receptors in the mPFC during formation of aversive taste memory and appetitive/incidental taste memory. The goal of this research was to evaluate the role of mPFC beta-adrenergic receptors during CTA acquisition/consolidation or CTA retrieval, as well as during incidental taste memory formation using the model of latent inhibition of CTA. The results showed that infusions in the mPFC of the beta-adrenergic antagonist propranolol before CTA acquisition impaired both short- and long-term aversive taste memory formation, and also that propranolol infusions before the memory test impaired CTA retrieval. However, propranolol infusions before pre-exposure to the taste during the latent inhibition procedure had no effect on incidental taste memory acquisition or consolidation. These data indicate that beta-adrenergic receptors in the mPFC have different functions during taste memory formation: they have an important role during aversive taste association as well as during aversive retrieval but not during incidental taste memory formation.}, } @article {pmid20427724, year = {2010}, author = {Olszewski, PK and Grace, MK and Fard, SS and Le Grevès, M and Klockars, A and Massi, M and Schiöth, HB and Levine, AS}, title = {Central nociceptin/orphanin FQ system elevates food consumption by both increasing energy intake and reducing aversive responsiveness.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {299}, number = {2}, pages = {R655-63}, pmid = {20427724}, issn = {1522-1490}, support = {P30 DK-50456/DK/NIDDK NIH HHS/United States ; R01 DA-021280/DA/NIDA NIH HHS/United States ; }, mesh = {Amygdala/metabolism ; Animals ; *Behavior, Animal/drug effects ; Brain/drug effects/*metabolism ; Brain Stem/metabolism ; *Conditioning, Psychological/drug effects ; *Eating/drug effects ; *Energy Intake/drug effects ; Extinction, Psychological ; Gene Expression Regulation ; *Hunger/drug effects ; Hypothalamus/metabolism ; Immunohistochemistry ; Injections, Intraventricular ; Lithium Chloride/administration & dosage ; Male ; Narcotic Antagonists ; Opioid Peptides/genetics/*metabolism ; Peptide Fragments/administration & dosage ; Proto-Oncogene Proteins c-fos/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; *Signal Transduction/drug effects ; Time Factors ; }, abstract = {Nociceptin/orphanin FQ (N/OFQ), the nociceptin opioid peptide (NOP) receptor ligand, increases feeding when injected centrally. Initial data suggest that N/OFQ blocks the development of a conditioned taste aversion (CTA). The current project further characterized the involvement of N/OFQ in the regulation of hunger vs. aversive responses in rats by employing behavioral, immunohistochemical, and real-time PCR methodology. We determined that the same low dose of the NOP antagonist [Nphe(1)]N/OFQ(1-13)NH(2) delivered via the lateral ventricle diminishes both N/OFQ- and deprivation-induced feeding. This anorexigenic effect did not stem from aversive consequences, as the antagonist did not cause the development of a CTA. When [Nphe(1)]N/OFQ(1-13)NH(2) was administered with LiCl, it moderately delayed extinction of the LiCl-induced CTA. Injection of LiCl + antagonist compared with LiCl alone generated an increase in c-Fos immunoreactivity in the central nucleus of the amygdala. The antagonist alone elevated Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, and central nucleus of the amygdala. Hypothalamic NOP mRNA levels were decreased during energy intake restriction induced by aversion, as well as in non-CTA rats food-restricted to match CTA-reduced consumption. Brain stem NOP was upregulated only in aversion. Prepro-N/OFQ mRNA showed a trend toward upregulation in restricted rats (P = 0.068). We conclude that the N/OFQ system promotes feeding by affecting the need to replenish lacking calories and by reducing aversive responsiveness. It may belong to mechanisms that shift a balance between the drive to ingest energy and avoidance of potentially tainted food.}, } @article {pmid20412388, year = {2010}, author = {Guzmán-Ramos, K and Osorio-Gómez, D and Moreno-Castilla, P and Bermúdez-Rattoni, F}, title = {Off-line concomitant release of dopamine and glutamate involvement in taste memory consolidation.}, journal = {Journal of neurochemistry}, volume = {114}, number = {1}, pages = {226-236}, doi = {10.1111/j.1471-4159.2010.06758.x}, pmid = {20412388}, issn = {1471-4159}, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning ; Benzazepines/pharmacology ; Cerebral Cortex/metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Dopamine/*metabolism ; Electrophoresis, Capillary ; Glutamic Acid/*metabolism ; Male ; *Memory ; Microdialysis ; Neurotransmitter Agents/*metabolism ; Rats ; Rats, Wistar ; Receptors, Dopamine D1/antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; *Taste ; Valine/analogs & derivatives/pharmacology ; }, abstract = {It has been postulated that memory consolidation process requires post-learning molecular changes that will support long-term experiences. In the present study, we assessed with in vivo microdialysis and capillary electrophoresis whether such changes involve the release of neurotransmitters at post-acquisition stages. Using conditioned taste aversion paradigm we observed spontaneous off-line (i.e. in absence of stimulation) dopamine and glutamate reactivation within the insular cortex about 45 min after the stimuli association. These increments did not appear in control groups that were unable to acquire the task, and it seems to be dependent on amygdala activity since its reversible inactivation by tetrodotoxin impaired cortical off-line release of both neurotransmitters and memory consolidation. In addition, blockade of dopaminergic D1 and/or NMDA receptors before the off-line activity impaired long- but not short-term memory. These results suggest that off-line extracellular increments of glutamate and dopamine have a significant functional role in consolidation of taste memory.}, } @article {pmid20407284, year = {2010}, author = {Vidal, J and Chamizo, VD}, title = {The conditioned stimulus elicits taste aversion but not sickness behavior in conditioned mice.}, journal = {Neuroimmunomodulation}, volume = {17}, number = {5}, pages = {325-332}, doi = {10.1159/000292021}, pmid = {20407284}, issn = {1423-0216}, mesh = {Animals ; Avoidance Learning/*physiology ; Bacterial Infections/immunology/*physiopathology/*psychology ; Conditioning, Psychological/*physiology ; Female ; Illness Behavior/*physiology ; Male ; Mice ; Neuropsychological Tests ; Taste/immunology/*physiology ; }, abstract = {OBJECTIVES: This article extends previous reports on (i) elicitation of taste aversion after pairing a flavored beverage (saccharin solution) with a disease-provoking microbial product (lipopolysaccharide, LPS, or polyinosinic:polycytidylic acid, poly I:C); (ii) elicitation of sickness behavior (assessed as diminished ingestion of water and food) by the conditioned stimulus, and (iii) development of tolerance to those microbial products.

METHODS: Mice of the CD1 strain were conditioned by pairing ingestion of 0.15% saccharin solution with injection of LPS (100 mug/mouse) or poly I:C (6 mg/kg). A few days later, some mice were offered saccharin solution and were injected with saline, whereas other mice were offered saccharin solution and were injected with the microbial product.

RESULTS: Regardless of the nature of the unconditioned stimulus (LPS or poly I:C), (i) taste aversion to saccharin ensued, (ii) tolerance ensued to sickness elicitation by a second administration of the microbial component, and (iii) saccharin taste did not evoke sickness.

CONCLUSIONS: Symptoms of infectious sickness in the absence of infection are hardly explained by exposure to the conditioned stimulus.}, } @article {pmid20400730, year = {2010}, author = {Davis, CM and de Brugada, I and Riley, AL}, title = {The role of injection cues in the production of the morphine preexposure effect in taste aversion learning.}, journal = {Learning & behavior}, volume = {38}, number = {2}, pages = {103-110}, pmid = {20400730}, issn = {1543-4494}, mesh = {Animals ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; *Cues ; Drug Tolerance ; Extinction, Psychological ; *Injections, Subcutaneous ; Morphine/*pharmacology ; Narcotics/*pharmacology ; Taste/*drug effects ; }, abstract = {The attenuation of an LiCl-induced conditioned taste aversion (CTA) by LiCl preexposure is mediated primarily by associative blocking via injection-related cues. Given that preexposure to morphine attenuates morphine-induced CTAs, it was of interest to determine whether injection cues also mediate this effect. Certain morphine-induced behaviors such as analgesic tolerance are controlled associatively, via injection-related cues. Accordingly, animals in the present experiments were preexposed to morphine (or vehicle) every other day for five total exposures, followed by an extinction phase, in which the subjects were given saline injections (or no treatment) for 8 (Experiment 1) or 16 (Experiment 2) consecutive days. All of the animals then received five CTA trials with morphine (or vehicle). The morphine-preexposed animals in Experiment 1 displayed an attenuation of the morphine CTA that was unaffected by extinction saline injections, suggesting that blocking by injection cues during morphine preexposure does not mediate this effect. All of the morphine-preexposed subjects in Experiment 2 displayed a weakened preexposure effect, an effect inconsistent with a selective extinction of drug-associated stimuli. The attenuating effects of morphine preexposure in aversion learning are most likely controlled by nonassociative mechanisms, like drug tolerance.}, } @article {pmid20398692, year = {2010}, author = {Klinkenberg, I and Blokland, A}, title = {The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {34}, number = {8}, pages = {1307-1350}, doi = {10.1016/j.neubiorev.2010.04.001}, pmid = {20398692}, issn = {1873-7528}, mesh = {Animals ; Behavior, Animal/*drug effects ; Brain/drug effects/metabolism/pathology/physiopathology ; Cholinergic Antagonists/*adverse effects/chemistry ; Cognition Disorders/*chemically induced/pathology/physiopathology ; Discrimination, Psychological/drug effects ; *Disease Models, Animal ; Humans ; Learning/drug effects ; Locomotion/drug effects ; Scopolamine/*adverse effects/chemistry ; }, abstract = {Scopolamine is used as a standard/reference drug for inducing cognitive deficits in healthy humans and animals. Effects are often interpreted in terms of a role of acetylcholine in mnemonic and/or attentional processes. In this paper an overview is given of the effects of scopolamine on animal behavior. Examination of the dose-response curve of systemically administered scopolamine indicates that sensory discrimination and attention are most sensitive to disruption. When higher doses (>0.03mg/kg) are used, deficits in other cognitive and non-cognitive functions (e.g., learning and memory, locomotor activity) are reported. Several behavioral processes (taste aversion, anxiety, short-term memory, attention) are found to be affected after intracerebral injections of scopolamine. It is concluded that effects on learning and memory performance which are observed after higher doses of scopolamine are mediated by (1) primary effects on attention and sensory/stimulus discrimination, (2) non-specific effects on behavior (e.g., locomotor activity, anxiety), and (3) peripheral side-effects (e.g., pupil dilation, salivation). Finally, the validity of scopolamine as a pharmacological model for cognitive impairment is discussed. The use of muscarinic M1 antagonists is suggested as a more selective and effective way of inducing cholinergic-induced cognitive deficits.}, } @article {pmid20384402, year = {2010}, author = {Gottlieb, DA and Rescorla, RA}, title = {Within-subject effects of number of trials in rat conditioning procedures.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {36}, number = {2}, pages = {217-231}, doi = {10.1037/a0016425}, pmid = {20384402}, issn = {1939-2184}, mesh = {Acoustic Stimulation/methods ; Animals ; Association Learning/*physiology ; Avoidance Learning/physiology ; Conditioning, Classical/*physiology ; Conditioning, Operant/*physiology ; Extinction, Psychological ; Fear ; Male ; Photic Stimulation/methods ; Rats ; Rats, Sprague-Dawley ; Reinforcement Schedule ; Reinforcement, Psychology ; Time Factors ; }, abstract = {D. A. Gottlieb (2008) reported finding no effects of number of conditioning trials in a series of between-subjects magazine approach experiments, when number of sessions and total training time were held constant. This article reports 7 comparable within-subject experiments that looked for effects of number of trials in a variety of conditioning preparations. Experiments 1-3 detected effects of multiplying the number of trials by factors of 4 and 8 in a conditioned magazine approach procedure in which visual and auditory stimuli were paired with food. Experiments 4A and 4B detected effects of a factor of 4 trials in a conditioned flavor preference procedure in which flavors were paired with polycose. Experiments 5 and 6 detected an effect of a factor of 3 trials in a conditioned taste aversion procedure and in a fear conditioning procedure, respectively. Results suggest that variables other than number of trials might play important roles in determining the acquisition of conditioned responding, but effects of number of trials can be detected with sensitive enough procedures.}, } @article {pmid20373327, year = {2010}, author = {Acevedo, MB and Molina, JC and Nizhnikov, ME and Spear, NE and Pautassi, RM}, title = {High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence.}, journal = {Developmental psychobiology}, volume = {52}, number = {5}, pages = {424-440}, pmid = {20373327}, issn = {1098-2302}, support = {R01 AA013098-08/AA/NIAAA NIH HHS/United States ; AA011960/AA/NIAAA NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; AA01309/AA/NIAAA NIH HHS/United States ; R01 AA011960/AA/NIAAA NIH HHS/United States ; R01 AA015992-05/AA/NIAAA NIH HHS/United States ; R01 AA013098/AA/NIAAA NIH HHS/United States ; R01 AA013098-09/AA/NIAAA NIH HHS/United States ; R01 AA015992/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Alcohol Drinking/*psychology ; Alcoholic Intoxication/*psychology ; Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; *Critical Period, Psychological ; Dose-Response Relationship, Drug ; Ethanol/blood/*toxicity ; Female ; Male ; Motivation ; Motor Activity/*drug effects ; Rats ; Rats, Wistar ; Sex Factors ; Taste/drug effects ; }, abstract = {Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post-administration interval. In Experiment 2, adolescent rats were assessed for ethanol-induced locomotor activation on postnatal Day 28. These animals were then evaluated for ethanol-mediated conditioned taste aversion and underwent a 16-day-long ethanol intake protocol. Ethanol-mediated aversive effects were unrelated to ethanol locomotor stimulation or subsequent ethanol consumption patterns. Ethanol intake during late adolescence was greatest in animals initiated to ethanol earliest at postnatal Day 28. Females that were more sensitive to ethanol's locomotor-activating effects showed a transient increase in ethanol self-administration. Blood ethanol concentrations during initiation were not related to ethanol-induced locomotor activation. Adolescent rats appeared sensitive to the locomotor-stimulatory effects of ethanol. Even brief ethanol exposure during adolescence may promote later ethanol intake.}, } @article {pmid20364436, year = {2010}, author = {Ozburn, AR and Harris, RA and Blednov, YA}, title = {Behavioral differences between C57BL/6J x FVB/NJ and C57BL/6J x NZB/B1NJ F1 hybrid mice: relation to control of ethanol intake.}, journal = {Behavior genetics}, volume = {40}, number = {4}, pages = {551-563}, pmid = {20364436}, issn = {1573-3297}, support = {AA13520/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; AA16424/AA/NIAAA NIH HHS/United States ; R01 AA006399-28/AA/NIAAA NIH HHS/United States ; AA06399-S/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; F31 AA016424/AA/NIAAA NIH HHS/United States ; U01 AA013520-08/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Behavior, Animal/*drug effects ; Conditioning, Operant/*drug effects ; Crosses, Genetic ; Ethanol/administration & dosage ; Female ; Heterozygote ; Maze Learning ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NZB ; Mice, Inbred Strains ; Motor Activity ; Reflex/*drug effects ; Self Administration ; Species Specificity ; }, abstract = {C57BL/6J x FVB/NJ F1 (B6 x FVB) mice consume more alcohol than C57BL/6J x NZB/B1NJ F1 (B6 x NZB) mice and this high alcohol consumption is stable after abstinence whereas B6 x NZB show reduced consumption, thus providing models of Sustained Alcohol Preference (SAP) and Reduced Alcohol Preference (RAP). In female hybrids, we assessed several behavioral responses to define behaviors which might predict SAP and RAP. B6 x FVB exhibited less severe ethanol-induced conditioned taste aversion and were less sensitive to ethanol-induced loss of righting reflex than B6 x NZB. Both hybrids demonstrated ethanol-induced place preference and a low ethanol withdrawal severity. We found that these hybrids differ in their sensitivity to the aversive and sedative, but not rewarding, effects of ethanol. Results of elevated plus maze, mirror chamber, and locomotor tests reveal B6 x FVB mice are less anxious and more active than B6 x NZB mice. Results obtained offer insights about factors that determine SAP and RAP in these new genetic models of alcohol consumption.}, } @article {pmid20363219, year = {2010}, author = {Simonyi, A and Schachtman, TR and Christoffersen, GR}, title = {Metabotropic glutamate receptor subtype 5 antagonism in learning and memory.}, journal = {European journal of pharmacology}, volume = {639}, number = {1-3}, pages = {17-25}, pmid = {20363219}, issn = {1879-0712}, support = {R03 MH064486/MH/NIMH NIH HHS/United States ; R03 MH064486-02/MH/NIMH NIH HHS/United States ; MH64486-01A1/MH/NIMH NIH HHS/United States ; R01 MH59039-01/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists/*pharmacology ; Learning/*drug effects/physiology ; Locomotion/drug effects/physiology ; Memory/*drug effects/physiology ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/*antagonists & inhibitors/metabolism ; }, abstract = {The role of the metabotropic glutamate receptor 5 (mGlu(5) receptor) in learning and memory and other behaviors are reviewed by examining the influence of selective antagonists and genetic knockout on performance. This receptor is involved in spatial learning, contextual fear conditioning, inhibitory avoidance, fear potentiated startle, and conditioned taste aversion. However, mGlu(5) receptor antagonists have proven to be ineffective in other learning tasks, such as the delayed-match-to-position test and a three-hole spatial learning task. Locomotion is often decreased by mGlu(5) receptor antagonists; and other behaviors such as social interaction and consummatory responses can also be affected. In mGlu(5) receptor knockout mice, performance in contextual fear conditioning and spatial water maze tasks is impaired. Although the available evidence is suggestive of an important contribution of mGlu(5) receptors to cognitive functions, further studies are needed, particularly those with in vivo evaluation of the role of mGlu(5) receptors in selective brain regions in different stages of memory formation.}, } @article {pmid20346924, year = {2010}, author = {Kwon, B and Houpt, TA}, title = {Phospho-acetylation of histone H3 in the amygdala after acute lithium chloride.}, journal = {Brain research}, volume = {1333}, number = {}, pages = {36-47}, pmid = {20346924}, issn = {1872-6240}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; R01 DC003198-08/DC/NIDCD NIH HHS/United States ; R01DC03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Acetylation/drug effects ; Amygdala/*drug effects ; Animals ; Antimanic Agents/*pharmacology ; Avoidance Learning/drug effects ; Butyric Acid/pharmacology ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation/drug effects ; Histamine Antagonists/pharmacology ; Histone Deacetylases/*metabolism ; Histones/*metabolism ; Lithium Chloride/*pharmacology ; Male ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors ; }, abstract = {Acute injection of a high dose of lithium chloride (LiCl) increases c-Fos expression in the central nucleus of the amygdala (CeA). We investigated if LiCl-induced c-Fos expression in the CeA is correlated with histone acetylation and phospho-acetylation. Chromatin modifications such as acetylation and phosphorylation are necessary for optimal gene expression, and gene expression may be increased by inhibiting the activity of histone deacetylases. LiCl (0.15 M, 12 ml/kg, i.p.) highly increased the levels of acetylation and phospho-acetylation of histone H3 in the CeA. The time course of these increases closely corresponded to and preceded the time course of c-Fos induction. Moreover, LiCl-induced c-Fos was co-localized with phospho-acetylated histone H3 in a majority of c-Fos-positive cells in the CeA. Systemic administration of a histone deacetylase inhibitor, sodium butyrate (NaB; 0.3 M, 0.4 g/kg, i.p.), significantly increased the levels of LiCl-induced c-Fos and phospho-acetylated histone H3 in the CeA. NaB also enhanced conditioned taste aversion learning induced by pairing saccharin consumption with LiCl injection, by making the conditioned taste aversion more resistant to extinction. These results suggest that LiCl-induced c-Fos expression may be regulated by modification of histone H3, especially phospho-acetylation, in the CeA. Furthermore, the level of phospho-acetylation of histone H3, c-Fos induction, and amygdalar-dependent taste aversion learning is constrained by endogenous histone deacetylase activity.}, } @article {pmid20201857, year = {2010}, author = {Davis, CM and Riley, AL}, title = {Conditioned taste aversion learning: implications for animal models of drug abuse.}, journal = {Annals of the New York Academy of Sciences}, volume = {1187}, number = {}, pages = {247-275}, doi = {10.1111/j.1749-6632.2009.05147.x}, pmid = {20201857}, issn = {1749-6632}, mesh = {Animals ; Behavior, Animal ; *Conditioning, Psychological ; Mice ; Models, Psychological ; Rats ; Reward ; Self Administration/psychology ; Species Specificity ; Substance-Related Disorders/etiology/*psychology ; *Taste ; }, abstract = {Drugs of abuse are typically discussed in terms of their rewarding effects and how these effects mediate drug taking. However, these drugs produce aversive effects that could have an important role in the overall acceptability of a drug and its likelihood of being self-administered. Rewarding and aversive effects, then, could be interpreted as separate behavioral effects, with the balance of the two determining overall drug acceptability. Interestingly, the role of aversive effects on drug acceptability in the self-administration preparation has received limited attention in this context. This chapter examines the aversive effects of drugs and discusses their role in drug taking. If these aversive effects serve a protective function, manipulations that alter or decrease these effects could have implications for drug taking. Several factors have been reported to alter conditioned taste aversion (CTA) learning, a preparation used in the assessment of the aversive effects of drugs in general. Two of these factors, drug history and strain, are reviewed here. By reviewing these, we intend to demonstrate the protective nature of aversive effects in the initiation and escalation of drug taking and to provide evidence that reductions in aversive effects could produce changes in patterns of drug self-administration that could lead to an increased vulnerability to abuse drugs by altering the reward-aversion balance. The aim of this chapter is not to question the importance of rewarding effects in self-administration but rather to provide evidence that aversive effects are an important factor that needs to be considered in discussions of drug-taking behavior.}, } @article {pmid20188481, year = {2010}, author = {Asakawa, A and Fujimiya, M and Niijima, A and Fujino, K and Kodama, N and Sato, Y and Kato, I and Nanba, H and Laviano, A and Meguid, MM and Inui, A}, title = {Parathyroid hormone-related protein has an anorexigenic activity via activation of hypothalamic urocortins 2 and 3.}, journal = {Psychoneuroendocrinology}, volume = {35}, number = {8}, pages = {1178-1186}, doi = {10.1016/j.psyneuen.2010.02.003}, pmid = {20188481}, issn = {1873-3360}, mesh = {Animals ; Anorexia/*chemically induced/metabolism ; Appetite Depressants/*pharmacology ; Drug Evaluation, Preclinical ; Eating/drug effects ; Gastric Emptying/drug effects ; Hypothalamus/*drug effects/metabolism ; Infusions, Intraventricular ; Male ; Mice ; Parathyroid Hormone-Related Protein/administration & dosage/*pharmacology ; Rats ; Rats, Wistar ; Signal Transduction/drug effects ; Time Factors ; Urocortins/agonists/genetics/*metabolism ; Weight Gain/drug effects ; }, abstract = {Cancer cachexia is reported to be a major cause of cancer-related death. Since the pathogenesis is not entirely understood, only few effective therapies have been established. Since myriad tumors produce parathyroid hormone-related protein (PTHrP), plasma concentrations of PTHrP are increased in cancer cachexia. We measured the food intake, gastric emptying, conditioned taste aversion (CTA), and gene expression of hypothalamic neuropeptides in mice after administering PTHrP intraperitoneally. We administered PTHrP intravenously in rats and examined the gastroduodenal motility and vagal nerve activities. We also examined whether chronic administration of PTHrP influenced the food intake and body weight. Peripherally administered PTHrP induced negative energy balance by decreasing the food intake and gastric emptying; however, it did not induce CTA. The mechanism involved the activation of hypothalamic urocortins 2 and 3 through vagal afferent pathways and the suppression of gastroduodenal motor activity. The continuous infusion of PTHrP reduced the food intake and body weight gain with a concomitant decrease in the fat and skeletal muscle. Our findings suggest that PTHrP influences the food intake and body weight; therefore, PTHrP can be considered as a therapeutic target for cancer cachexia.}, } @article {pmid20167260, year = {2010}, author = {Inui-Yamamoto, C and Yoshioka, Y and Inui, T and Sasaki, KS and Ooi, Y and Ueda, K and Seiyama, A and Ohzawa, I}, title = {The brain mapping of the retrieval of conditioned taste aversion memory using manganese-enhanced magnetic resonance imaging in rats.}, journal = {Neuroscience}, volume = {167}, number = {2}, pages = {199-204}, doi = {10.1016/j.neuroscience.2010.02.027}, pmid = {20167260}, issn = {1873-7544}, mesh = {Animals ; *Avoidance Learning ; Brain/*physiology ; Brain Mapping ; Conditioning, Classical ; Image Enhancement ; Magnetic Resonance Imaging ; Male ; *Manganese ; *Memory ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {Manganese-enhanced MRI (MEMRI) is a newly developed noninvasive imaging technique of brain activities. The signal intensity of MEMRI reflects cumulative activities of the neurons. To validate the use of MEMRI technique to investigate the neural mechanisms of learning and memory, we tried to map brain areas involved in the retrieval of conditioned taste aversion (CTA) memory. CTAs were established to saccharin (conditioned stimulus: CS) by pairing its ingestion with an i.p. injection of LiCl (unconditioned stimulus: US). LiCl solutions (as a robust aversion chemical) of 0.15 M were injected i.p. 15 min after drinking the saccharine solution (CS). After the two times conditionings, these rats showed a robust aversion to the saccharine solution (CS). Rats of the control group were injected saline i.p. instead of LiCl solutions. The MRI signal intensities at the gustatory cortex (GC), the core subregion of the nucleus accumbens (NAcC), the shell subregion of the nucleus accumbens (NAcSh), the ventral pallidum (VP), the central nucleus of amygdala (CeA), the lateral hypothalamus (LH), and the basolateral nucleus of amygdala (BLA) of the conditioned group were higher than those of the control group. There were no significant differences between the conditioned and the control groups in the intensities for other regions, such as the striatum area, motor cortex, cingulate cortex, interstitial nucleus of the posterior limb of the anterior commissure and hippocampus. These indicate that the GC, NAcC, NAcSh, VP, CeA, LH and BLA have important roles in the memory retrieval of CTA.}, } @article {pmid20161299, year = {2009}, author = {Mickley, GA and Disorbo, A and Wilson, GN and Huffman, J and Bacik, S and Hoxha, Z and Biada, JM and Kim, YH}, title = {Explicit disassociation of a conditioned stimulus and unconditioned stimulus during extinction training reduces both time to asymptotic extinction and spontaneous recovery of a conditioned taste aversion.}, journal = {Learning and motivation}, volume = {40}, number = {2}, pages = {209-220}, pmid = {20161299}, issn = {0023-9690}, support = {R15 MH063720/MH/NIMH NIH HHS/United States ; R15 MH063720-03/MH/NIMH NIH HHS/United States ; }, abstract = {Conditioned taste aversions (CTAs) may be acquired when an animal consumes a novel taste (CS) and then experiences the symptoms of poisoning (US). This aversion may be extinguished by repeated exposure to the CS alone. However, following a latency period in which the CS is not presented, the CTA will spontaneously recover (SR). In the current study we employed an explicitly unpaired extinction procedure (EU-EXT) to determine if it could thwart SR of a CTA. Sprague-Dawley rats acquired a strong CTA after 3 pairings of saccharin (SAC the CS) and Lithium Chloride (LiCl the US). CTA acquisition was followed by extinction (EXT) training consisting of either (a) CS-only exposure (CSO) or, (b) exposure to saccharin and Lithium Chloride on alternate days (i.e., explicitly unpaired: EU). Both extinction procedures resulted in >/= 90% reacceptance of SAC, although the EU extinction procedure (EU-EXT) significantly decreased the time necessary for rats to reach this criterion (compared to CSO controls). Rats were subsequently tested for SR of the CTA upon re-exposure to SAC following a 30-day latency period of water drinking. Rats that acquired a CTA and then underwent the CSO extinction procedure exhibited a significant suppression of SAC drinking during the SR test (as compared to their SAC drinking at the end of extinction). However, animals in the EU-EXT group did not show such suppression in drinking compared to CSO controls. These data suggest that the EU-EXT procedure may be useful in reducing both time to extinction and the spontaneous recovery of fears.}, } @article {pmid20103704, year = {2010}, author = {Kim, DH and Woods, SC and Seeley, RJ}, title = {Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight.}, journal = {Diabetes}, volume = {59}, number = {4}, pages = {907-915}, pmid = {20103704}, issn = {1939-327X}, support = {DK54080/DK/NIDDK NIH HHS/United States ; R01 DK054080/DK/NIDDK NIH HHS/United States ; DK073505/DK/NIDDK NIH HHS/United States ; DK56863/DK/NIDDK NIH HHS/United States ; P01 DK056863/DK/NIDDK NIH HHS/United States ; R01 DK073505/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue/*blood supply/drug effects ; Agouti-Related Protein/genetics ; Animals ; Apoptosis/drug effects/*physiology ; Body Composition ; Body Weight/drug effects ; Diet, Fat-Restricted ; Dietary Fats/*pharmacology ; Eating/drug effects/genetics ; Endothelial Cells/drug effects/*physiology ; Energy Intake/drug effects/genetics ; Hypothalamus/physiology ; Leptin/blood/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Neovascularization, Physiologic ; Neuropeptide Y/genetics ; Obesity/etiology/genetics/metabolism ; Peptide Fragments/pharmacology ; Peptides/*pharmacology ; Pro-Opiomelanocortin/genetics ; RNA, Messenger/genetics ; Rats ; }, abstract = {OBJECTIVE: Because adipose tissue is highly vascularized, modifying adipose tissue vasculature may provide a novel method for reducing body fat. A peptide sequence that elicits apoptosis of endothelium in white fat potently reduced body weight. We sought to determine how inhibiting adipose tissue vasculature changes key aspects of energy balance regulation and the neuroendocrine system that maintains energy balance.

RESEARCH DESIGN AND METHODS: Lean and obese mice or rats were treated with proapoptotic peptide for 4 or 27 days. Daily energy intake and expenditure were measured in mice on a low- (LFD) or high-fat diet (HFD) and in rats on a HFD. A conditioned taste aversion test was performed to assess whether proapoptotic peptide produces visceral illness. Hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocoritin (POMC) mRNA expression and plasma leptin levels were evaluated.

RESULTS: Proapoptotic peptide completely reversed HFD-induced obesity in mice and reduced body weight in mice and rats on a HFD but not in those on a LFD. Fat loss occurred with no change of energy expenditure but reduced food intake that occurred without signs of illness and despite reduced circulating leptin and reduced hypothalamic POMC gene expression, indicating that the decrease in food intake is independent of the action of leptin.

CONCLUSIONS: These experiments provide compelling evidence for a previously unknown relationship between the status of adipose tissue vasculature and the regulation of food intake.}, } @article {pmid20092558, year = {2010}, author = {Devi, L and Ohno, M}, title = {Genetic reductions of beta-site amyloid precursor protein-cleaving enzyme 1 and amyloid-beta ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice.}, journal = {The European journal of neuroscience}, volume = {31}, number = {1}, pages = {110-118}, pmid = {20092558}, issn = {1460-9568}, support = {R01 MH067251/MH/NIMH NIH HHS/United States ; R01 MH067251-05/MH/NIMH NIH HHS/United States ; }, mesh = {Aging ; Alzheimer Disease/enzymology/genetics/*physiopathology ; Amyloid Precursor Protein Secretases/genetics/*metabolism ; Amyloid beta-Peptides/genetics/*metabolism ; Amyloid beta-Protein Precursor/genetics ; Animals ; Aspartic Acid Endopeptidases/genetics/*metabolism ; Avoidance Learning/physiology ; Brain/enzymology/*physiopathology ; Conditioning, Classical/physiology ; Disease Models, Animal ; Fear/physiology ; Humans ; Memory/physiology ; Memory Disorders/enzymology/*genetics/*physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Presenilin-1/genetics ; Protease Nexins ; Receptors, Cell Surface/genetics ; Space Perception/physiology ; Taste Perception/physiology ; }, abstract = {Although transgenic mouse models of Alzheimer's disease (AD) recapitulate amyloid-beta (Abeta)-related pathologies and cognitive impairments, previous studies have mainly evaluated their hippocampus-dependent memory dysfunctions using behavioral tasks such as the water maze and fear conditioning. However, multiple memory systems become impaired in AD as the disease progresses and it is important to test whether other forms of memory are affected in AD models. This study was designed to use conditioned taste aversion (CTA) and contextual fear conditioning paradigms to compare the phenotypes of hippocampus-independent and -dependent memory functions, respectively, in 5XFAD amyloid precursor protein/presenilin-1 transgenic mice that harbor five familial AD mutations. Although both types of memory were significantly impaired in 5XFAD mice, the onset of CTA memory deficits (approximately 9 months of age) was delayed compared with that of contextual memory deficits (approximately 6 months of age). Furthermore, 5XFAD mice that were genetically engineered to have reduced levels of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) (BACE1(+/-).5XFAD) exhibited improved CTA memory, which was equivalent to the performance of wild-type controls. Importantly, elevated levels of cerebral beta-secretase-cleaved C-terminal fragment (C99) and Abeta peptides in 5XFAD mice were significantly reduced in BACE1(+/-).5XFAD mice. Furthermore, Abeta deposition in the insular cortex and basolateral amygdala, two brain regions that are critically involved in CTA performance, was also reduced in BACE1(+/-).5XFAD compared with 5XFAD mice. Our findings indicate that the CTA paradigm is useful for evaluating a hippocampus-independent form of memory defect in AD model mice, which is sensitive to rescue by partial reductions of the beta-secretase BACE1 and consequently of cerebral Abeta.}, } @article {pmid20045422, year = {2010}, author = {Houpt, TA and Cassell, JA and Hood, A and DenBleyker, M and Janowitz, I and Mueller, K and Ortega, B and Smith, JC}, title = {Repeated exposure attenuates the behavioral response of rats to static high magnetic fields.}, journal = {Physiology & behavior}, volume = {99}, number = {4}, pages = {500-508}, pmid = {20045422}, issn = {1873-507X}, support = {R01 DC004607/DC/NIDCD NIH HHS/United States ; R01 DC004607-07/DC/NIDCD NIH HHS/United States ; R01DC4607/DC/NIDCD NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic/administration & dosage ; Animals ; Avoidance Learning/radiation effects ; Behavior, Animal/*radiation effects ; Conditioning, Psychological/radiation effects ; Dose-Response Relationship, Radiation ; Electromagnetic Fields/*adverse effects ; Female ; Food Preferences/radiation effects ; Lithium Chloride/administration & dosage ; Motor Activity/radiation effects ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Time Factors ; }, abstract = {Exposure of rats to high strength static magnetic fields of 7 T or above has behavioral effects such as the induction of locomotor circling, the suppression of rearing, and the acquisition of conditioned taste aversion (CTA). To determine if habituation occurs across magnetic field exposures, rats were pre-exposed two times to a 14 T static magnetic field for 30 min on two consecutive days; on the third day, rats were given access to a novel 0.125% saccharin prior to a third 30-min exposure to the 14 T magnetic field. Compared to sham-exposed rats, pre-exposed rats showed less locomotor circling and an attenuated CTA. Rearing was suppressed in all magnet-exposed groups regardless of pre-exposure, suggesting that the suppression of rearing is more sensitive than other behavioral responses to magnet exposure. Habituation was also observed when rats underwent pre-exposures at 2-3h intervals on a single day. Components of the habituation were also long-lasting; a diminished circling response was observed when rats were exposed to magnetic field 36 days after 2 pre-exposures. To control for possible effects of unconditioned stimulus pre-exposure, rats were also tested in a similar experimental design with two injections of LiCl prior to the pairing of saccharin with a third injection of LiCl. Pre-exposure to LiCl did not attenuate the LiCl-induced CTA, suggesting that 2 pre-exposures to an unconditioned stimulus are not sufficient to explain the habituation to magnet exposure. Because the effects of magnetic field exposure are dependent on an intact vestibular apparatus, and because the vestibular system can habituate to many forms of perturbation, habituation to magnetic field exposure is consistent with mediation of magnetic field effects by the vestibular system.}, } @article {pmid20039021, year = {2010}, author = {Harkness, JH and Webb, S and Grimm, JW}, title = {Abstinence-dependent transfer of lithium chloride-induced sucrose aversion to a sucrose-paired cue in rats.}, journal = {Psychopharmacology}, volume = {208}, number = {4}, pages = {521-530}, pmid = {20039021}, issn = {1432-2072}, support = {R15 DA016285/DA/NIDA NIH HHS/United States ; R15 DA016285-02/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Operant/*drug effects ; *Cues ; Drug-Seeking Behavior/drug effects ; Extinction, Psychological ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Long-Evans ; Self Administration ; Sucrose/administration & dosage/*pharmacology ; Taste/*drug effects ; Transfer, Psychology/*drug effects ; }, abstract = {RATIONALE: Responding for a drug- or sucrose-paired cue increases over forced abstinence (incubation of craving). If the incentive value of a cue depends on the incentive value of the primary reward, devaluing the primary reward should reduce cue reactivity.

OBJECTIVES: We investigated whether conditioned taste aversion (CTA) to sucrose would transfer to a sucrose-paired cue after 1 or 30 days of forced abstinence and whether CTA after 1 day of forced abstinence would affect incubation of craving.

MATERIALS AND METHODS: Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After 1 (Exp.1) or 30 (Exp.2) days of forced abstinence, rats received two home-cage pairings of sucrose with either LiCl (65 mg/kg, IP) to produce CTA or saline as a control. Two days later, rats responded for the cue alone. The following day, sucrose consumption was assessed in the same operant conditioning chamber. Exp.1 rats were tested again 1 month later to determine if CTA would affect incubation of craving.

RESULTS: Exp.1: CTA after 1 day of forced abstinence did not attenuate cue reactivity when tested immediately after CTA, nor did the treatment affect incubation of craving or incubation of sucrose consumption. Exp.2: CTA after 1 month of forced abstinence resulted in a significant reduction in cue reactivity.

CONCLUSION: The incentive values of sucrose and the conditioned representation of sucrose increase over an extended period of forced abstinence. This incubation appears to facilitate the transfer of an aversion to the primary reward to the conditioned cue.}, } @article {pmid20033312, year = {2010}, author = {Komissarova, NV and Tiunova, AA and Anokhin, KV}, title = {Selective impairments to memory consolidation in chicks produced by 5'-iodo-2'-deoxyuridine.}, journal = {Neuroscience and behavioral physiology}, volume = {40}, number = {2}, pages = {215-223}, pmid = {20033312}, issn = {1573-899X}, mesh = {Amnesia, Retrograde/physiopathology ; Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Brain/physiopathology ; Bromodeoxyuridine/pharmacology ; Chickens ; DNA/*biosynthesis ; Idoxuridine/*analogs & derivatives/pharmacology ; Immunohistochemistry ; Imprinting, Psychological/physiology ; Learning/physiology ; Memory/*physiology ; Memory Disorders/*physiopathology ; Neuropsychological Tests ; Photomicrography ; Space Perception/physiology ; Taste Perception/physiology ; Time Factors ; }, abstract = {The aim of the present work was to study the role of DNA synthesis in the formation of different types of memory in neonatal chicks. The nucleotide analogs 5'-iodo-2'-deoxyuridine (IdU) and 5'-bromo-2'-deoxyuridine (BrdU) were used; these are incorporated into DNA, impairing its function, and have amnestic actions in defined models of learning in mice. We studied the effects of 5'-iodo-2'-deoxyuridine of the formation of long-term memory in chicks during training in different models: passive avoidance, imprinting, taste aversion, and spatial learning in a maze. In the taste aversion model, i.p. administration of IdU (10 mg/kg 5 min before or 50 min after training) had an amnestic effect on testing 1-2 days after training. IdU-induced amnesia developed more than 6 h after training, while administration of IdU 2 h after training had no amnestic effect. 5'-Bromo-2'-deoxyuridine also had a similar amnestic action in the taste aversion model. In the passive avoidance, imprinting, and spatial maze learning models, administration of IdU at the same dose before and after training did not induce amnesia. These data lead to the suggestion that DNA synthesis in the brain may play a critical role in the mechanisms of memory consolidation in chicks in types of learning such as taste aversion.}, } @article {pmid20026412, year = {2010}, author = {Kim, MJ and Mizumori, SJ and Bernstein, IL}, title = {Neuronal representation of conditioned taste in the basolateral amygdala of rats.}, journal = {Neurobiology of learning and memory}, volume = {93}, number = {3}, pages = {406-414}, pmid = {20026412}, issn = {1095-9564}, support = {R01 MH058755/MH/NIMH NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; MH58755/MH/NIMH NIH HHS/United States ; R01 NS037040-07/NS/NINDS NIH HHS/United States ; R01 NS037040/NS/NINDS NIH HHS/United States ; R56 MH058755/MH/NIMH NIH HHS/United States ; }, mesh = {Affect ; Amygdala/*anatomy & histology/*physiology ; Animals ; *Conditioning, Psychological ; Learning/physiology ; Male ; Nerve Net/*physiology ; Rats ; Rats, Long-Evans ; Taste/*physiology ; }, abstract = {Animals develop robust learning and long lasting taste aversion memory once they experience a new taste that is followed by visceral discomfort. A large body of literature has supported the hypothesis that basolateral amygdala (BLA) plays a critical role in the acquisition and extinction of such conditioned taste aversions (CTA). Despite the evidence that BLA is crucially engaged during CTA training, it is unclear how BLA neural activity represents the conditioned tastes. Here, we incorporated a modified behavioral paradigm suitable for single unit study, one which utilizes a sequence of pulsed saccharin and water infusion via intraoral cannulae. After conditioning, we investigated BLA unit activity while animals experience the conditioned taste (saccharin). Behavioral tests of taste reactivity confirmed that the utilized training procedure produced reliable acquisition and expression of the aversion throughout test sessions. When neural activity was compared between saccharin and water trials, half of the recorded BLA units (77/149) showed differential activity according to the types of solution. 76% of those cells (29/38) in the conditioned group showed suppressed activity, while only 44% of taste reactive cells (17/39) in controls showed suppressed activity during saccharin trials (relative to water trials). In addition, the overall excitability of BLA units was increased as shown by altered characteristics of burst activity after conditioning. The changes in BLA activity as a consequence of CTA were maintained throughout test sessions, consistent with the behavioral study. The current study suggests that the neuronal activity evoked by a sweet taste is altered as a consequence of CTA learning, and that the overall change might be related to the learning induced negative affect.}, } @article {pmid20026166, year = {2010}, author = {Wang, YC and Huang, AC and Hsiao, S}, title = {Paradoxical simultaneous occurrence of amphetamine-induced conditioned taste aversion and conditioned place preference with the same single drug injection: a new "pre- and post-association" experimental paradigm.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {95}, number = {1}, pages = {80-87}, doi = {10.1016/j.pbb.2009.12.009}, pmid = {20026166}, issn = {1873-5177}, mesh = {Amphetamines/*administration & dosage ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; Male ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The paradoxical phenomenon of co-existing physically aversive and psychologically rewarding effects of drugs is a crucial issue for drug addiction. The present study employed a new experimental paradigm to test whether the rewarding and aversive properties of amphetamine (AMPH) can exist simultaneously. Rats were given a 15 min period of exposure to saccharin injected with 0.15M NaCl or 1.5mg/kg AMPH and then were confined to one compartment of a test box for 30 min. After three paired and unpaired cycles, the aversive and rewarding effects were assessed. A reduction in consumption of the paired flavored solution provided evidence of avoidance while preference for the AMPH injection context provided evidence of rewarding effects. The present findings demonstrate that the development of AMPH-induced rewarding and aversive effects depends on the particular behavioral conditions and support both the task-dependent drug effects hypothesis and the reward comparison hypothesis. The formation of associations with stimuli that comes before (pre) vs. after (post) the unconditioned stimulus and the role of the dopaminergic system in such associations are discussed.}, } @article {pmid19969013, year = {2010}, author = {Jones, JD and Hall, FS and Uhl, GR and Riley, AL}, title = {Dopamine, norepinephrine and serotonin transporter gene deletions differentially alter cocaine-induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {94}, number = {4}, pages = {580-587}, pmid = {19969013}, issn = {1873-5177}, support = {ZIA DA000165-15/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Dopamine Plasma Membrane Transport Proteins/*genetics ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Norepinephrine Plasma Membrane Transport Proteins/*genetics ; Serotonin Plasma Membrane Transport Proteins/*genetics ; Taste ; }, abstract = {Although cocaine is primarily known for its powerful hedonic effects, there is evidence that its affective experience has a notable aversive component that is less well understood. A variety of pharmacological and molecular approaches have implicated enhanced monoamine (MA) neurotransmission in the aversive effects of cocaine. Although numerous studies have yielded data supportive of the role of the monoamines (indirectly and directly), the specific system suggested to be involved differs across studies and paradigms (Freeman et al., 2005b; Grupp, 1997; Roberts and Fibiger, 1997). Monoamine transporter knockout mice have been useful in the study of many different aspects of cocaine effects relevant to human drug use and addiction, yet an assessment of the effects of deletion of the genes for the dopamine, norepinephrine and serotonin transporters (DAT, NET, and SERT, respectively) on cocaine's aversive properties has yet to be performed (Uhl et al., 2002). In the current investigation, the strength of cocaine-induced aversions was compared among three groups of transgenic mice with deletions of the genes responsible for the production of one of the monoamine transporters. When compared to their respective WT controls, dopamine transporter deletion slightly attenuated cocaine-induced aversion while deletion of SERT or NET resulted in a more significant delay in the onset and strength of cocaine-induced taste aversions. The data lead us to conclude that the action of cocaine to inhibit NET contributes most substantially to its aversive effects, with some involvement of SERT and minimal contribution of DAT.}, } @article {pmid19922355, year = {2009}, author = {Lee, JY and Lee, JH and Moon, YW and Chun, BG and Jahng, JW}, title = {Proteomic analysis of lithium-induced gene expression in the rat hypothalamus.}, journal = {The International journal of neuroscience}, volume = {119}, number = {9}, pages = {1267-1281}, doi = {10.1080/00207450902889201}, pmid = {19922355}, issn = {1563-5279}, mesh = {Animals ; Antimanic Agents/*pharmacology ; Databases, Genetic ; Echocardiography ; Gene Expression/*drug effects ; Hypothalamus/drug effects/*metabolism ; Injections, Intraperitoneal ; Lithium Chloride/*pharmacology ; Male ; Nerve Tissue Proteins/*biosynthesis/genetics ; Proteins/chemistry ; *Proteomics ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {The hypothalamic proteomes were analyzed 1 and 6 hr after an intraperitoneal injection of lithium chloride or sodium chloride (0.15 M, 12 ml/kg). Results showed that expression of 14 and 32 proteomes was increased consistently by 1 hr and 6 hr of lithium treatment, respectively. Among them, tentative implications of glial fibrillary acidic protein, receptor-type protein tyrosine phosphatase, spectrin, and glutamate dehydrogenase in the lithium-induced activation of the hypothalamic-pituitary-adrenal axis, and conditioned taste aversion have been discussed. The proteomes listed in this study will provide, at least, a new insight to understand the molecular mechanism of lithium's action in the brain.}, } @article {pmid19914357, year = {2010}, author = {Nagaishi, T and Nakajima, S}, title = {Overshadowing of running-based taste aversion learning by another taste cue.}, journal = {Behavioural processes}, volume = {83}, number = {1}, pages = {134-136}, doi = {10.1016/j.beproc.2009.11.003}, pmid = {19914357}, issn = {1872-8308}, mesh = {Animals ; *Avoidance Learning ; Behavior, Animal ; Conditioning, Psychological ; Cues ; Male ; Rats ; Rats, Sprague-Dawley ; *Running ; *Taste ; }, abstract = {Training rats with serial presentations of two taste solutions before confinement in an activity wheel (X-->A-->running) resulted in weak aversion to taste X, compared to a training procedure without the presentation of A. Demonstration of the overshadowing effect in the present study provides another parallel feature between running-based taste aversion learning and Pavlovian conditioning preparations including poison-based taste aversion learning. It also indirectly supports the claim that cue competition causes degraded contingency effect and cover-cue effect in rats' running-based taste aversion (Nakajima, 2008).}, } @article {pmid19903834, year = {2010}, author = {Long, DJ and Devantier, HR and Brennan, FX and Bryant, RW and Salemme, FR and Palmer, RK}, title = {Pharmacologic antagonism of the oral aversive taste-directed response to capsaicin in a mouse brief access taste aversion assay.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {332}, number = {2}, pages = {525-530}, doi = {10.1124/jpet.109.155416}, pmid = {19903834}, issn = {1521-0103}, mesh = {Acrylamides/pharmacology ; Administration, Oral ; Alkaloids ; Anilides/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Benzodioxoles ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Capsaicin/administration & dosage/analogs & derivatives/*antagonists & inhibitors/*pharmacology ; Cinnamates/pharmacology ; Diterpenes/pharmacology ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Piperidines ; Polyunsaturated Alkamides ; Pyrazines/pharmacology ; Pyridines/pharmacology ; TRPM Cation Channels/genetics ; TRPV Cation Channels/*agonists/*antagonists & inhibitors ; Taste/*drug effects ; }, abstract = {Chemosensory signaling by the tongue is a primary determinant of ingestive behavior and is mediated by specific interactions between tastant molecules and G protein-coupled and ion channel receptors. The functional relationship between tastant and receptor should be amenable to pharmacologic methods and manipulation. We have performed a pharmacologic characterization of the taste-directed licking of mice presented with solutions of capsaicin and other transient receptor potential vanilloid-1 (TRPV1) agonists using a brief access taste aversion assay. Dose-response functions for lick-rate suppression were established for capsaicin (EC(50) = 0.5 microM), piperine (EC(50) = 2 muM), and resiniferatoxin (EC(50) = 0.02 microM). Little or no effect on lick rate was observed in response to the full TRPV1 agonist olvanil. Capsaicin lick rates of wild-type and transient receptor potential melastatin-5 (TRPM5) knockout mice were equivalent, indicating that TRPM5, a critical component of aversive signaling for many bitter tastants, did not contribute to the capsaicin taste response. The selective TRPV1 antagonists N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (10 microM) and (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (AMG9810) (10 microM) effectively blocked capsaicin- and piperine-mediated lick suppression. However, (E)-3-(4-chlorophenyl)-N-(3-methoxyphenyl)-N-phenylprop-2-enamide (SB 366791) and capsazepine, also TRPV1 antagonists, were without effect at test concentrations of up to 30 and 100 microM, respectively. Our results demonstrate that TRPV1-mediated oral aversiveness presents a pharmacologic profile differing from what has been reported previously for TRPV1 pain signaling and, furthermore, that aversive tastes can be evaluated and controlled pharmacologically.}, } @article {pmid19895565, year = {2009}, author = {Languille, S and Davis, S and Richer, P and Alcacer, C and Laroche, S and Hars, B}, title = {Extracellular signal-regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesis.}, journal = {The European journal of neuroscience}, volume = {30}, number = {10}, pages = {1923-1930}, doi = {10.1111/j.1460-9568.2009.06971.x}, pmid = {19895565}, issn = {1460-9568}, mesh = {*Aging ; Aminoacetonitrile/analogs & derivatives/pharmacology ; Animals ; Animals, Newborn ; Avoidance Learning/drug effects/*physiology ; Brain/anatomy & histology/drug effects/enzymology ; Enzyme Activation/drug effects/physiology ; Enzyme Inhibitors/pharmacology ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Female ; Male ; Memory/drug effects/*physiology ; Phosphorylation/drug effects ; Rats ; Signal Transduction/drug effects/physiology ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {The ability to form long-term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny.}, } @article {pmid19861403, year = {2009}, author = {Akirav, I and Segev, A and Motanis, H and Maroun, M}, title = {D-cycloserine into the BLA reverses the impairing effects of exposure to stress on the extinction of contextual fear, but not conditioned taste aversion.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {16}, number = {11}, pages = {682-686}, doi = {10.1101/lm.1565109}, pmid = {19861403}, issn = {1549-5485}, mesh = {Amygdala/*drug effects/physiology ; Analysis of Variance ; Animals ; Antimetabolites/*pharmacology ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Cycloserine/*pharmacology ; Exploratory Behavior/drug effects ; Extinction, Psychological/*drug effects ; Fear/drug effects ; Learning Disabilities/*drug therapy/etiology ; Lithium Chloride/adverse effects ; Locomotion/drug effects ; Male ; Rats ; Rats, Wistar ; Stress, Psychological/complications ; Taste/drug effects ; }, abstract = {We investigated whether the N-methyl-D-aspartate (NMDA) receptor partial agonist D-cycloserine (DCS, 20 microg/side) microinfused into the basolateral amygdala (BLA) would reverse stress-induced impairment of extinction in two aversive learning paradigms: contextual fear conditioning and conditioned taste aversion (CTA). We found that DCS in the BLA show differential involvement in the extinction of these two paradigms and in its modulation of stress-induced impairment of extinction. This may suggest that the dysfunctional extinction of fear and taste aversion following exposure to a stressful experience may be modulated by different mechanisms.}, } @article {pmid19836034, year = {2010}, author = {Pacífico da Silva, I and Soto-Blanco, B}, title = {Conditioning taste aversion to Mascagnia rigida (Malpighiaceae) in sheep.}, journal = {Research in veterinary science}, volume = {88}, number = {2}, pages = {239-241}, doi = {10.1016/j.rvsc.2009.08.012}, pmid = {19836034}, issn = {1532-2661}, mesh = {Animals ; *Conditioning, Psychological ; Emetics/pharmacology ; Feeding Behavior/drug effects ; Female ; Food Preferences ; Lithium Chloride/pharmacology ; Malpighiaceae/*toxicity ; Plants, Toxic/*toxicity ; *Sheep ; Sheep Diseases/prevention & control ; *Taste ; }, abstract = {The objective of this study was to determine if sheep could be averted to Mascagnia rigida, a toxic plant found in the semiarid region of northeastern Brazil. Twelve female sheep naïve to M. rigida were randomly allocated to two treatment groups: control (treated with 15 mL water orally by a drenching gun) and lithium group (treated with 150 mg LiCl/kg body weight orally by a drenching gun). For conditioning, sheep were allowed to feed on M. rigida leaves for 15 min, followed by LiCl or water administration. The time spent eating M. rigida leaves was measured. The conditioning was repeated daily until the LiCl-treated sheep stopped eating M. rigida, which occurred at days 2 and 3. Persistence trials were conducted on day 10, 24, 40, 55, and 70 of the trial using single-choice tests. There was no difference between the two treatment groups with respect to the consumption of M. rigida on the first day of aversion conditioning. On the second day, three out of the six sheep in the lithium group did not eat the leaves, but on the third day, all the sheep in the lithium group did not ingest M. rigida. This aversion persisted throughout all the persistence trials. This indicates that sheep can be easily conditioned by using lithium chloride to avoid eating M. rigida.}, } @article {pmid19828818, year = {2009}, author = {Foo, H and Mason, P}, title = {Analgesia accompanying food consumption requires ingestion of hedonic foods.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {29}, number = {41}, pages = {13053-13062}, pmid = {19828818}, issn = {1529-2401}, support = {R01 DA022978/DA/NIDA NIH HHS/United States ; R01 DA022978-06A1/DA/NIDA NIH HHS/United States ; R01 DA022978-07/DA/NIDA NIH HHS/United States ; R01 DA022978-08/DA/NIDA NIH HHS/United States ; }, mesh = {*Analgesia ; Analgesics, Non-Narcotic/administration & dosage/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/*physiology ; Cacao ; Conditioning, Classical/drug effects/physiology ; Conditioning, Operant/drug effects/physiology ; Eating/drug effects/*physiology ; Electromyography/methods ; Feeding Behavior/drug effects/*physiology ; Food Preferences/drug effects/*physiology ; Hot Temperature/adverse effects ; Hypnotics and Sedatives/pharmacology ; Lipopolysaccharides/pharmacology ; Male ; Pentobarbital/pharmacology ; Quinine/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Reaction Time/drug effects ; Sweetening Agents/administration & dosage/pharmacology ; }, abstract = {Animals eat rather than react to moderate pain. Here, we examined the behavioral, hedonic, and neural requirements for ingestion analgesia in ad libitum fed rats. Noxious heat-evoked withdrawals were similarly suppressed during self-initiated chocolate eating and ingestion of intraorally infused water, sucrose, or saccharin, demonstrating that ingestion analgesia does not require feeding motivation, self-initiated food procurement, sucrose, or calories. Rather, food hedonics is important because neither salt ingestion nor quinine rejection elicited analgesia. During quinine-induced nausea and lipopolysaccharide (LPS)-induced illness, conditions when chocolate eating was presumably less pleasurable, analgesia accompanying chocolate consumption was attenuated, yet analgesia during water ingestion was preserved in LPS-injected rats who showed enhanced palatability for water within this context. The dependence of ingestion analgesia on the positive hedonics of an ingestate was confirmed in rats with a conditioned taste aversion to sucrose: after paired exposure to sucrose and LPS, rats no longer showed analgesia during sucrose ingestion but continued to show analgesia during chocolate consumption. Eating pauses tended to occur less often and for shorter durations in the presence of ingestion analgesia than in its absence. Therefore, we propose that ingestion analgesia functions to defend eating from ending. Muscimol inactivation of the medullary raphe magnus blocked the analgesia normally observed during water ingestion, showing the involvement of brainstem endogenous pain inhibitory mechanisms in ingestion analgesia. Brainstem-mediated defense of the consumption of palatable foods may explain, at least in part, why overeating tasty foods is so irresistible even in the face of opposing cognitive and motivational forces.}, } @article {pmid19825424, year = {2010}, author = {Purón-Sierra, L and Sabath, E and Nuñez-Jaramillo, L and Miranda, MI}, title = {Blockade of nucleus basalis magnocellularis or activation of insular cortex histamine receptors disrupts formation but not retrieval of aversive taste memory.}, journal = {Neurobiology of learning and memory}, volume = {93}, number = {2}, pages = {216-220}, doi = {10.1016/j.nlm.2009.10.001}, pmid = {19825424}, issn = {1095-9564}, mesh = {Animals ; Basal Nucleus of Meynert/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Histamine Agonists/pharmacology ; Histamine H1 Antagonists/pharmacology ; Male ; Mental Recall/drug effects/*physiology ; Methylhistamines/pharmacology ; Pyrilamine/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine/*metabolism ; Receptors, Histamine H1/metabolism ; Receptors, Histamine H3/metabolism ; Taste Perception/*physiology ; Temporal Lobe/drug effects/*physiology ; Time Factors ; }, abstract = {Recent research, using several experimental models, demonstrated that the histaminergic system is clearly involved in memory formation. This evidence suggested that during different associative learning tasks, histamine receptor subtypes have opposite functions, related to the regulation of cortical cholinergic activity. Given that cortical cholinergic activity and nucleus basalis magnocellularis (NBM) integrity are needed during taste memory formation, the aim of this study was to determine the role of histamine receptors during conditioned taste aversion (CTA). We evaluated the effects of bilateral infusions of 0.5 microl of pyrilamine (100 mM), an H(1) receptor antagonist, into the NBM, or of R-alpha-methylhistamine (RAMH) (10 mM), an H(3) receptor agonist, into the insular cortex of male Sprague-Dawley rats 20 min before acquisition and/or retrieval of conditioned taste aversion. The results showed that blockade of H(1) receptors in NBM or activation of H(3) receptors in the insular cortex impairs formation but not retrieval of aversive taste memory. These results demonstrated differential roles for histamine receptors in two important areas for taste memory formation and suggest that these effects could be related with the cortical cholinergic activity modulation during CTA acquisition.}, } @article {pmid19797341, year = {2009}, author = {Yamamoto, T and Watanabe, U and Fujimoto, M and Sako, N}, title = {Taste preference and nerve response to 5'-inosine monophosphate are enhanced by glutathione in mice.}, journal = {Chemical senses}, volume = {34}, number = {9}, pages = {809-818}, doi = {10.1093/chemse/bjp070}, pmid = {19797341}, issn = {1464-3553}, mesh = {Animals ; Chorda Tympani Nerve/physiology ; Cranial Nerves/*physiology ; Electrophysiology ; Food Preferences ; Glossopharyngeal Nerve/physiology ; Glutathione/*metabolism ; Inosine Monophosphate/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Sodium Glutamate/metabolism ; *Taste ; Time Factors ; }, abstract = {Previous human sensory evaluation studies have shown that glutathione (GSH) enhances deliciousness, accompanied by thickness, mouthfulness, and continuity feeling, which is known as "kokumi" in Japanese, in an umami solution containing monosodium glutamate and 5'-inosine monophosphate (IMP). We conducted behavioral and electrophysiological experiments to explore possible interactions of taste effectiveness between GSH and umami substances in mice. The 2-bottle preference test revealed that the mice preferred GSH at concentrations ranging from 1 to 10 mM. When GSH was added to IMP or a mixture of IMP and monopotassium glutamate (MPG), the mice showed increased preference for these solutions over the individual IMP or the binary mixture of IMP and MPG in both short-term and long-term tests. The addition of GSH to MPG, however, did not increase preference. Neural responses of the chorda tympani and glossopharyngeal nerves to the mixture of IMP and GSH showed synergism, whereas synergism was not observed in the mixture of MPG and GSH in either taste nerve. Another behavioral study with the use of the conditioned taste aversion paradigm showed that aversions to MPG generalized moderately to GSH, but aversions to GSH did not generalize to MPG. The present study suggests that GSH enhances preference for umami solutions containing 5'-ribonucleotide rather than glutamate. On the basis of these results, we discuss possible receptors involved for the action of GSH.}, } @article {pmid19767625, year = {2009}, author = {Vetter-O'Hagen, C and Varlinskaya, E and Spear, L}, title = {Sex differences in ethanol intake and sensitivity to aversive effects during adolescence and adulthood.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {44}, number = {6}, pages = {547-554}, pmid = {19767625}, issn = {1464-3502}, support = {R01 AA012453/AA/NIAAA NIH HHS/United States ; R01 AA016887/AA/NIAAA NIH HHS/United States ; R01 AA07135501/AA/NIAAA NIH HHS/United States ; R01 AA12453/AA/NIAAA NIH HHS/United States ; R01 AA017355/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Alcohol Drinking/blood ; Animals ; Avoidance Learning/*drug effects/physiology ; Ethanol/*administration & dosage/blood ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; *Sex Characteristics ; }, abstract = {AIMS: The present experiments examined sex differences in ethanol intake and in the influence of a social context on aversive properties of ethanol in adolescent and adult Sprague-Dawley rats.

METHODS: Experiment 1 examined ethanol intake, with animals receiving daily 2-h access to ethanol and water for 8 days. Experiment 2 assessed the aversive effects of ethanol using a conditioned taste aversion (CTA) paradigm, with animals placed either alone or with a same-sex, same-age peer during the ethanol intoxication phase of conditioning.

RESULTS: Ethanol intake varied with both age and sex, although the sex differences emerging at each age were opposite in nature. Adolescent males consumed more ethanol relative to their body weights than adolescent females and adults of both sexes, whereas adult females generally consumed more than adult males. The CTA test revealed no sex differences in aversive effects of ethanol in adults, whereas adolescent males were less sensitive to the aversive properties of ethanol than adolescent females when intoxication occurred in the presence of a peer. Ethanol-induced CTA was evident in adults at lower doses than in adolescents.

CONCLUSIONS: These results suggest that age differences in ethanol intake in males and sex differences in intake during adolescence may be associated in part with the relative insensitivity of the male adolescents to ethanol's aversive properties, especially when intoxication occurred in a social context. However, the elevated ethanol intake observed in adult females relative to their male counterparts appears to be unrelated to the aversive properties of ethanol.}, } @article {pmid19706834, year = {2009}, author = {García-DeLaTorre, P and Rodriguez-Ortiz, CJ and Arreguin-Martinez, JL and Cruz-Castañeda, P and Bermúdez-Rattoni, F}, title = {Simultaneous but not independent anisomycin infusions in insular cortex and amygdala hinder stabilization of taste memory when updated.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {16}, number = {9}, pages = {514-519}, doi = {10.1101/lm.1356509}, pmid = {19706834}, issn = {1549-5485}, mesh = {Amygdala/*drug effects/physiology ; Analysis of Variance ; Animals ; Anisomycin/*pharmacology ; Behavior, Animal/drug effects ; Cerebral Cortex/*drug effects/physiology ; Conditioning, Classical/drug effects ; Lithium Chloride/adverse effects ; Male ; Memory/*drug effects ; Protein Synthesis Inhibitors/*pharmacology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/*drug effects/physiology ; }, abstract = {Reconsolidation has been described as a process where a consolidated memory returns to a labile state when retrieved. Growing evidence suggests that reconsolidation is, in fact, a destabilization/stabilization process that incorporates updated information to a previously consolidated memory. We used the conditioned taste aversion (CTA) task in order to test this theory. On the first trial, the conditioned stimulus (CS) (saccharin) was associated to the unconditioned stimulus (US) (LiCl injection), and as a result, aversion to saccharin was obtained. The following day, animals were injected with anisomycin in either the insular cortex (IC), central amygdala (CeA), basolateral amygdala (BLA), or simultaneously in IC and CeA or IC and BLA, and a second CTA trial was carried out in which updated information was acquired. Animals were tested 24 h later. When protein synthesis was inhibited in either the IC or CeA, consolidation was affected and previously consolidated memory was unimpaired. However, when both the IC and CeA were simultaneously anisomycin injected, the previously consolidated memory was affected. After repeated association trials, protein synthesis inhibition in the IC and CeA did not have an effect on taste memory. These results suggest that the IC and the CeA are necessary for taste-aversion consolidation, and that both share the previously consolidated memory trace. In addition, our data demonstrated that protein synthesis in either the IC or the CeA suffices to stabilize previously consolidated taste memory when destabilized by incorporation of updated information.}, } @article {pmid19706547, year = {2009}, author = {Ballarini, F and Moncada, D and Martinez, MC and Alen, N and Viola, H}, title = {Behavioral tagging is a general mechanism of long-term memory formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {34}, pages = {14599-14604}, pmid = {19706547}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Conditioning, Psychological/physiology ; Discrimination Learning/physiology ; Fear/psychology ; Hippocampus/physiology ; Learning/physiology ; Long-Term Potentiation/physiology ; Male ; Memory/*physiology ; Memory, Short-Term/physiology ; Neocortex/physiology ; Neuronal Plasticity/physiology ; Psychomotor Performance/*physiology ; Rats ; Rats, Wistar ; Saccharin/chemistry ; Sodium Chloride/chemistry ; Spatial Behavior/physiology ; Taste ; Time Factors ; }, abstract = {In daily life, memories are intertwined events. Little is known about the mechanisms involved in their interactions. Using two hippocampus-dependent (spatial object recognition and contextual fear conditioning) and one hippocampus-independent (conditioned taste aversion) learning tasks, we show that in rats subjected to weak training protocols that induce solely short term memory (STM), long term memory (LTM) is promoted and formed only if training sessions took place in contingence with a novel, but not familiar, experience occurring during a critical time window around training. This process requires newly synthesized proteins induced by novelty and reveals a general mechanism of LTM formation that begins with the setting of a "learning tag" established by a weak training. These findings represent the first comprehensive set of evidences indicating the existence of a behavioral tagging process that in analogy to the synaptic tagging and capture process, need the creation of a transient, protein synthesis-independent, and input specific tag.}, } @article {pmid19705551, year = {2009}, author = {Blednov, YA and Harris, RA}, title = {Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol.}, journal = {Neuropharmacology}, volume = {56}, number = {4}, pages = {814-820}, pmid = {19705551}, issn = {1873-7064}, support = {R01 AA006399/AA/NIAAA NIH HHS/United States ; A06399//PHS HHS/United States ; R01 AA006399-26/AA/NIAAA NIH HHS/United States ; U01 AA13520/AA/NIAAA NIH HHS/United States ; U01 AA013520-08/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics/*psychology ; Animals ; Capsaicin/analogs & derivatives/pharmacology ; Central Nervous System Depressants/adverse effects/pharmacokinetics/*pharmacology ; Choice Behavior ; Ethanol/adverse effects/pharmacokinetics/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Postural Balance/drug effects ; Substance Withdrawal Syndrome/psychology ; TRPV Cation Channels/agonists/*genetics ; Taste/drug effects ; }, abstract = {The vanilloid receptor TRPV1 is activated by ethanol and this may be important for some of the central and peripheral actions of ethanol. To determine if this receptor has a role in ethanol-mediated behaviors, we studied null mutant mice in which the Trpv1 gene was deleted. Mice lacking this gene showed significantly higher preference for ethanol and consumed more ethanol in a two-bottle choice test as compared with wild type littermates. Null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol (2 g/kg). However, there were no differences between null mutant and wild type mice in severity of ethanol-induced acute withdrawal (4 g/kg) or conditioned taste aversion to ethanol (2.5 g/kg). Two behavioral phenotypes (decreased sensitivity to ethanol-induced sedation and faster recovery from ethanol-induced motor incoordination) seen in null mutant mice were reproduced in wild type mice by injection of a TRPV1 antagonist, capsazepine (10 mg/kg). These two ethanol behaviors were changed in the opposite direction after injection of capsaicin, a selective TRPV1 agonist, in wild type mice. The studies provide the first evidence that TRPV1 is important for specific behavioral actions of ethanol.}, } @article {pmid19703430, year = {2009}, author = {Lin, JY and Roman, C and Reilly, S}, title = {Taste-potentiated odor aversion learning in rats with lesions of the insular cortex.}, journal = {Brain research}, volume = {1297}, number = {}, pages = {135-142}, pmid = {19703430}, issn = {1872-6240}, support = {R01 DC004341/DC/NIDCD NIH HHS/United States ; DC04341/DC/NIDCD NIH HHS/United States ; R01 DC006456-03/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; R01 DC006456/DC/NIDCD NIH HHS/United States ; R01 DC004341-05/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Cortex/anatomy & histology/*physiology ; Denervation ; Male ; Neuronal Plasticity/physiology ; Neuropsychological Tests ; *Odorants ; Olfactory Pathways/physiology ; Physical Stimulation ; Rats ; Rats, Sprague-Dawley ; Smell/*physiology ; Staining and Labeling ; Taste/*physiology ; Water Deprivation/physiology ; }, abstract = {The current study assessed the influence of excitotoxic lesions of the insular cortex (IC) on taste-potentiated odor aversion (TPOA) learning. Water-deprived rats initially received a single odor-toxicosis or odor/taste-toxicosis pairing and were subsequently tested, in separate trials, with the odor and the taste stimulus. Indicating TPOA, neurologically intact rats conditioned with the odor/taste compound stimulus acquired significantly stronger odor aversions than normal rats conditioned with the odor stimulus. IC lesions disrupted TPOA, conditioned taste aversion and taste neophobia. The finding that taste did not potentiate odor aversion learning in the IC-lesioned rats provides support for the "within-compound association" analysis but is inconsistent with the "sensory-and-gate" account of TPOA learning.}, } @article {pmid19689456, year = {2009}, author = {Wheeler, JM and Reed, C and Burkhart-Kasch, S and Li, N and Cunningham, CL and Janowsky, A and Franken, FH and Wiren, KM and Hashimoto, JG and Scibelli, AC and Phillips, TJ}, title = {Genetically correlated effects of selective breeding for high and low methamphetamine consumption.}, journal = {Genes, brain, and behavior}, volume = {8}, number = {8}, pages = {758-771}, pmid = {19689456}, issn = {1601-183X}, support = {T32 DA007262/DA/NIDA NIH HHS/United States ; P50 DA018165-04/DA/NIDA NIH HHS/United States ; P50DA018165/DA/NIDA NIH HHS/United States ; P50 DA018165/DA/NIDA NIH HHS/United States ; T32DA07262/DA/NIDA NIH HHS/United States ; }, mesh = {Administration, Oral ; Amphetamine-Related Disorders/*genetics ; Animals ; Apoptosis/genetics ; Avoidance Learning/drug effects/physiology ; Breeding/*methods ; Central Nervous System Stimulants/metabolism/pharmacology ; Conditioning, Psychological/drug effects/physiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease/*genetics ; Genotype ; Immune System/physiology ; Male ; Methamphetamine/metabolism/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Motivation/drug effects/genetics ; Phenotype ; Proto-Oncogene Proteins c-fos/genetics ; Proto-Oncogene Proteins c-rel/genetics ; Receptors, Serotonin, 5-HT3/genetics ; Self Administration ; Serotonin Plasma Membrane Transport Proteins/genetics ; }, abstract = {Improved prevention and treatment of drug addiction will require deeper understanding of genetic factors contributing to susceptibility to excessive drug use. Intravenous operant self-administration methods have greatly advanced understanding of behavioral traits related to addiction. However, these methods are not suitable for large-scale genetic experiments in mice. Selective breeding of mice can aggregate 'addiction alleles' in a model that has the potential to identify coordinated effects of multiple genes. We produced mouse lines that orally self-administer high (MAHDR) or low (MALDR) amounts of methamphetamine, representing the first demonstration of selective breeding for self-administration of any psychostimulant drug. Conditioned place preference and taste aversion results indicate that MAHDR mice are relatively more sensitive to the rewarding effects and less sensitive to the aversive effects of methamphetamine, compared to MALDR mice. These results validate the oral route of self-administration for investigation of the motivational effects of methamphetamine and provide a viable alternative to intravenous self-administration procedures. Gene expression results for a subset of genes relevant to addiction-related processes suggest differential regulation by methamphetamine of apoptosis and immune pathways in the nucleus accumbens of MAHDR and MALDR mice. In each line, methamphetamine reduced an allostatic state by bringing gene expression back toward 'normal' levels. Genes differentially expressed in the drug-naï ve state, including Slc6a4 (serotonin transporter), Htr3a (serotonin receptor 3A), Rela [nuclear factor kappaB (NFkappaB)] and Fos (cFos), represent candidates whose expression levels may predict methamphetamine consumption and susceptibility to methamphetamine reward and aversion.}, } @article {pmid19686105, year = {2009}, author = {Delay, ER and Eddy, MC and Eschle, BK}, title = {Behavioral studies of umami: tales told by mice and rats.}, journal = {Annals of the New York Academy of Sciences}, volume = {1170}, number = {}, pages = {41-45}, doi = {10.1111/j.1749-6632.2009.03933.x}, pmid = {19686105}, issn = {1749-6632}, support = {R15 DC007617/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Conditioning, Operant ; Mice ; Mice, Knockout ; Psychophysics ; Rats ; Receptors, G-Protein-Coupled/genetics/physiology ; *Taste ; }, abstract = {Psychophysical research with rats and mice has been instrumental in understanding umami taste transduction and perception. Although early studies suggested that an NMDA-like receptor detected substances that elicit an umami taste, studies using behavioral methods with both rats and mice indicate that the picture is much more complex. When the G protein-coupled receptor T1R1+T1R3 was discovered, it was believed to be the umami receptor and a more broadly tuned L-amino acid receptor. However, since then a number of behavioral studies, like molecular and physiological studies, report evidence that other receptors may contribute to umami taste. For example, T1R3 knockout mice (KO) have only slightly elevated detection thresholds for monosodium glutamate (MSG) and L-alanine. In conditioned taste aversion studies, T1R3 KO mice show bidirectional generalization of the aversion between MSG and L-alanine, suggesting that these substances have similar tastes. However, these KO mice can discriminate between the tastes of the two substances, indicating other receptors also respond to these amino acids. (RS)-alpha-cycloprophy-4-phosphonophenylglycine (CPPG), a potent mGluR4 antagonist, decreases an aversion to MSG in rats while increasing the strength of generalization of the aversion to L-arginine or L-serine. These behavioral studies suggest that glutamate can activate several putative receptors, most notably T1R1+T1R3 and taste-mGluR4, and possibly NMDA-like receptors or taste-mGluR1. These receptors generate similar but not identical sensations which, when combined, form a complex perception identified as umami. Further, these studies suggest that afferent signaling from T1R1+T1R3 and taste-mGluR4 likely combine to generate the taste sensations associated with other L-amino acids.}, } @article {pmid19666040, year = {2009}, author = {Murata, Y and Beauchamp, GK and Bachmanov, AA}, title = {Taste perception of monosodium glutamate and inosine monophosphate by 129P3/J and C57BL/6ByJ mice.}, journal = {Physiology & behavior}, volume = {98}, number = {4}, pages = {481-488}, pmid = {19666040}, issn = {1873-507X}, support = {R01 DC000882-25A2/DC/NIDCD NIH HHS/United States ; DC00882/DC/NIDCD NIH HHS/United States ; R01 DC000882/DC/NIDCD NIH HHS/United States ; R01 DC000882-24/DC/NIDCD NIH HHS/United States ; R01 DC000882-26/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Feeding Behavior/drug effects ; Food Additives/*pharmacology ; Food Preferences/*drug effects/physiology ; Generalization, Psychological/drug effects/physiology ; Inosine Monophosphate/*pharmacology ; Mice ; Mice, Inbred C57BL ; Sodium Glutamate/*pharmacology ; Taste/drug effects ; Taste Perception/*drug effects/*genetics ; Taste Threshold/drug effects/physiology ; }, abstract = {Our previous studies have shown that in long-term two-bottle preference tests, mice from the C57BL/6ByJ (B6) inbred strain drink more monosodium glutamate (MSG) and inosine monophosphate (IMP) than mice from the 129P3/J (129) inbred strain. The goal of this study was to examine whether this variation in consumption could be attributed to strain differences in perception of the taste quality of MSG and IMP. We developed a conditioned taste aversion (CTA) in B6 and 129 mice to 100 mM MSG or 10 mM IMP and used a brief-access taste assay to examine CTA generalization. B6 and 129 mice did not differ in the generalization patterns following CTA to MSG: mice from both strains generalized CTA from MSG to NaCl. In contrast, strain differences in the generalization patterns were evident following the CTA to IMP: while mice from both strains generalized CTA from IMP to MSG, 129 mice tended to have stronger CTA generalization to saccharin and d-tryptophan, both of which are perceived as sweet by humans. These data suggest that the strain differences in MSG consumption are not due to variation in perception of the taste quality of MSG. Instead, the differential intake of IMP likely reflects strain differences in the way the taste quality of IMP is perceived. Our data suggest that mice perceive MSG and IMP as complex taste stimuli: some taste components are shared between these two substances, but their relative intensity seems to be different for MSG and IMP. The amiloride-sensitive salt taste component is more prevalent in MSG than in IMP taste, and in B6 compared with 129 mice.}, } @article {pmid19634944, year = {2009}, author = {Kwapis, JL and Jarome, TJ and Lonergan, ME and Helmstetter, FJ}, title = {Protein kinase Mzeta maintains fear memory in the amygdala but not in the hippocampus.}, journal = {Behavioral neuroscience}, volume = {123}, number = {4}, pages = {844-850}, pmid = {19634944}, issn = {1939-0084}, support = {MH069558/MH/NIMH NIH HHS/United States ; MH060668/MH/NIMH NIH HHS/United States ; R01 MH069558-01A2/MH/NIMH NIH HHS/United States ; R01 MH060668-01A2/MH/NIMH NIH HHS/United States ; R01 MH060668/MH/NIMH NIH HHS/United States ; R01 MH069558/MH/NIMH NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Amygdala/*physiology ; Analysis of Variance ; Animals ; Auditory Perception/physiology ; Conditioning, Classical/*physiology ; Electroshock ; *Fear ; Freezing Reaction, Cataleptic ; Heat-Shock Proteins/genetics/metabolism ; Hippocampus/*physiology ; Male ; Memory/*physiology ; Protein Kinase C/antagonists & inhibitors/*metabolism ; Rats ; Rats, Long-Evans ; Sequestosome-1 Protein ; Time Factors ; }, abstract = {Recent work on the long-term stability of memory and synaptic plasticity has identified a potentially critical role for protein kinase Mzeta (PKMzeta). PKMzeta is a constitutively active, atypical isoform of protein kinase C that is believed to maintain long term potentiation at hippocampal synapses in vitro. In behaving animals, local inhibition of PKMzeta disrupts spatial memory in the hippocampus and conditioned taste aversion memory in the insular cortex. The role of PKMzeta in context fear memory is less clear. This study examined the role of PKMzeta in amygdala and hippocampal neurons following a standard fear conditioning protocol. The results indicate that PKMzeta inhibition in the amygdala, but not in the hippocampus, can disrupt fear memory. This suggests that PKMzeta may only maintain select forms of memory in specific brain structures and does not participate in a universal memory storage mechanism.}, } @article {pmid19634934, year = {2009}, author = {Clark, EW and Bernstein, IL}, title = {Boosting cholinergic activity in gustatory cortex enhances the salience of a familiar conditioned stimulus in taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {123}, number = {4}, pages = {764-771}, pmid = {19634934}, issn = {1939-0084}, support = {R01 NS037040/NS/NINDS NIH HHS/United States ; R01 NS037040-02/NS/NINDS NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Analysis of Variance ; Animals ; Carbachol/pharmacology ; Catheterization ; Cholinergic Agonists/pharmacology ; Conditioning, Classical/drug effects/*physiology ; Hippocampus/physiology ; Immunohistochemistry ; Learning/drug effects/*physiology ; Lithium Chloride ; Male ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Long-Evans ; Receptors, Cholinergic/*metabolism ; Recognition, Psychology/drug effects/physiology ; Saccharin/administration & dosage ; Somatosensory Cortex/drug effects/*physiology ; Taste Perception/drug effects/*physiology ; }, abstract = {The cholinergic system is important for learning, memory, and responses to novel stimuli. Exposure to novel, but not familiar, tastes increases extracellular acetylcholine (ACh) levels in insular cortex (IC). To further examine whether cholinergic activation is a critical signal of taste novelty, in these studies carbachol, a direct cholinergic agonist, was infused into IC before conditioned taste aversion (CTA) training with a familiar taste. By mimicking the cholinergic activation generated by novel taste exposure, it was hypothesized that a familiar taste would be treated as novel and therefore a salient target for aversion learning. As predicted, rats infused with the agonist were able to acquire CTAs to familiar saccharin. Effects of carbachol infusion on patterns of neuronal activation during conditioned stimulus-unconditioned stimulus pairing were assessed using Fos-like immunoreactivity (FLI). Familiar taste-illness pairing following carbachol, but not vehicle, induced significant elevations of FLI in amygdala, a region with reciprocal connections to IC that is also important for CTA learning. These results support the view that IC ACh activity provides a critical signal of taste novelty that facilitates CTA acquisition.}, } @article {pmid19631258, year = {2009}, author = {Eschle, BK and Eddy, MC and Delay, ER}, title = {Antagonism of metabotropic glutamate receptor 4 receptors by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine alters the taste of amino acids in rats.}, journal = {Neuroscience}, volume = {163}, number = {4}, pages = {1292-1301}, doi = {10.1016/j.neuroscience.2009.07.035}, pmid = {19631258}, issn = {1873-7544}, mesh = {*Amino Acids ; Animals ; Arginine ; Avoidance Learning ; Conditioning, Classical ; Excitatory Amino Acid Antagonists/*pharmacology ; Glycine/*analogs & derivatives/pharmacology ; Male ; Neuropsychological Tests ; Physical Stimulation ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/*antagonists & inhibitors/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Serine ; Sodium Glutamate ; Taste Perception/*drug effects/physiology ; }, abstract = {T1R1/T1R3, taste-metabotropic glutamate receptor (mGluR) 4 and other taste receptors have been implicated in umami taste perceptionT1R1/T1R3 has also been identified as an L-amino acid receptor. We investigated the possibility that taste-mGluR4 receptors may also play a role in the taste of amino acids in Sprague-Dawley rats using conditioned taste aversion methods. Specifically, we examined whether a taste aversion generalized between L-monosodium glutamate (MSG) and one of three amino acids (glycine, L-serine, and L-arginine), and whether (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG), a group III mGluR selective antagonist with a strong binding affinity for mGluR4 receptors, can impact stimulus generalization. Rats showed cross-generalization between MSG and all three amino acids (all mixed with amiloride to block the taste of sodium), although less so for L-arginine than the other two amino acids, suggesting that all of the amino acids shared at least some taste qualities with MSG. However, when 1 mM CPPG was mixed with these amino acids, the strength of the learned taste aversions and cross-generalization for all but glycine were either decreased or increased. The increase in generalization induced by CPPG indicated that the antagonist did not simply reduce the intensity of the stimulus experience but also changed the qualities of the sensory experience. These findings suggest that multiple receptors are involved in amino acid taste and that taste-mGluR4 receptors contribute to the taste of MSG and at least some l-amino acids.}, } @article {pmid19629920, year = {2009}, author = {Schneider, S and Janssen, M and Röhrig, S and Schüssler, M and Solle, D}, title = {["Why not?"--content analysis of answers from more than 700 pupils about their motives for not smoking].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {134}, number = {31-32}, pages = {1573-1577}, doi = {10.1055/s-0029-1233982}, pmid = {19629920}, issn = {1439-4413}, mesh = {Adolescent ; Child ; Female ; Germany ; Humans ; Male ; *Motivation ; Reproducibility of Results ; Schools/classification ; Smoking/*psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND AND OBJECTIVE: In spite of declining smoking prevalence nothing is known about the motives of adolescents in Germany who abstain from smoking. If one knows what motives prevent youngsters from ever starting to smoke it would make it possible to adjust future preventive strategies that would reach the "hard core" of smoking adolescents. This study investigated the true motives of non-smokers and also focused on possible gender and social background as well as age differences in the structure of their motivation.

METHOD: In the SToP-Study ("Sources of Tobacco for Pupils" Study 2008) 780 pupils, of whom 709 were non-smokers from 32 school classes, grades 7-9, were interviewed about their smoking experience. In anonymized answers to the questions pupils wrote down their motives for being non-smokers. A total of 1,329 free text statements, some of them very elaborate, were categorized and evaluated in a qualitative analysis.

RESULTS: The most important and frequently mentioned motives for not smoking were health related (78,1%). But the most significant health risks of tobacco consumption (cardiac and cerebrovascular disease, chronic obstructive pulmonary disease), except cancer risk, were hardly appreciated. Other important reasons for not smoking were aesthetic aversion (38.6%), lacking perception of a benefit (25.1%) and economic motives (20.9%). It was especially female grammar school pupils who most frequently expressed health and aesthetic reasons (such as disgust, smell and taste aversion, dental and finger discolorations) as motives for not smoking.

CONCLUSION: Extrinsic reasons (legal restrictions, smoking bans imposed by parents and schools, age limits etc.) are not important reasons to abstain for young non-smokers. Specifically, arguments about health, participation in sports and being in good physical condition should be central to any advice given to young smokers within the setting of general medical practice.}, } @article {pmid19626313, year = {2009}, author = {Callaerts-Vegh, Z and Hoyer, D and Kelly, PH}, title = {Selective effects of benzodiazepines on the acquisition of conditioned taste aversion compared to attenuation of neophobia in C57BL/6 mice.}, journal = {Psychopharmacology}, volume = {206}, number = {3}, pages = {389-401}, pmid = {19626313}, issn = {1432-2072}, mesh = {Alprazolam/administration & dosage/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Benzodiazepines/administration & dosage/*pharmacology ; Chlordiazepoxide/administration & dosage/pharmacology ; Dose-Response Relationship, Drug ; Drinking Behavior/*drug effects ; Extinction, Psychological ; Hypnotics and Sedatives/administration & dosage/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Saccharin ; Taste ; }, abstract = {INTRODUCTION: The effects of pre-conditioning administration of anxiolytic benzodiazepines on the acquisition of a conditioned taste aversion (CTA) and on the acquisition of attenuation of neophobia (AN) were investigated in C57BL/6 mice.

MATERIALS AND METHODS: A CTA was induced by injecting lithium chloride (LiCl; 6 mEq x kg(-1)) 30 min after the animal had imbibed a novel 0.5% saccharin solution. In other animals, neophobia was attenuated by a single access to the novel 0.5% saccharin solution, followed only by injection of saline.

RESULTS AND DISCUSSION: Pre-conditioning administration of chlordiazepoxide (CDZ; 6-24 mg x kg(-1), i.p.) and alprazolam (0.3-1 mg x kg(-1), p.o.) resulted in a CTA that did not differ initially from that observed in vehicle-treated controls, but which showed faster extinction. The acquisition of AN was impaired only after the higher doses of CDZ (12-24 mg x kg(-1), i.p.) or alprazolam (1 mg x kg(-1), i.p.). The results show that in this test, altered acquisition of an aversive CTA memory by anxiolytic benzodiazepines is reflected in more rapid extinction. Moreover, at low doses, these drugs showed selectivity for weakening CTA learning compared to AN learning. Evidence is discussed that selective weakening of aversive memory formation is a clinically relevant effect of anxiolytic benzodiazepines.}, } @article {pmid19617910, year = {2009}, author = {Huynh, DP and Maalouf, M and Silva, AJ and Schweizer, FE and Pulst, SM}, title = {Dissociated fear and spatial learning in mice with deficiency of ataxin-2.}, journal = {PloS one}, volume = {4}, number = {7}, pages = {e6235}, pmid = {19617910}, issn = {1932-6203}, support = {K01-NS047548-01A4/NS/NINDS NIH HHS/United States ; R01-AG13622/AG/NIA NIH HHS/United States ; K01 NS047548/NS/NINDS NIH HHS/United States ; R01 AG013622/AG/NIA NIH HHS/United States ; R01 NS033123/NS/NINDS NIH HHS/United States ; P50-MH0779720/MH/NIMH NIH HHS/United States ; R01 NS33123/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Animals ; Ataxins ; Behavior, Animal ; Conditioning, Operant ; *Fear ; Female ; Hippocampus/physiology ; Homozygote ; *Learning ; Long-Term Potentiation ; Male ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics/*physiology ; *Space Perception ; }, abstract = {Mouse models with physiological and behavioral differences attributable to differential plasticity of hippocampal and amygdalar neuronal networks are rare. We previously generated ataxin-2 (Atxn2) knockout mice and demonstrated that these animals lacked obvious anatomical abnormalities of the CNS, but showed marked obesity and reduced fertility. We now report on behavioral changes as a consequence of Atxn2-deficiency. Atxn2-deficiency was associated with impaired long-term potentiation (LTP) in the amygdala, but normal LTP in the hippocampus. Intact hippocampal plasticity was associated behaviorally with normal Morris Water maze testing. Impaired amygdala plasticity was associated with reduced cued and contextual fear conditioning. Conditioned taste aversion, however, was normal. In addition, knockout mice showed decreased innate fear in several tests and motor hyperactivity in open cage testing. Our results suggest that Atxn2-deficiency results in a specific set of behavioral and cellular disturbances that include motor hyperactivity and abnormal fear-related behaviors, but intact hippocampal function. This animal model may be useful for the study of anxiety disorders and should encourage studies of anxiety in patients with spinocerebellar ataxia type 2 (SCA2).}, } @article {pmid19584428, year = {2009}, author = {Ramírez-Lugo, L and Jensen, MS and Søderman, A and West, MJ}, title = {Deficits in aversive but not in safe taste memory in the APPswe/PS1dE9 mice.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {18}, number = {2}, pages = {281-293}, doi = {10.3233/JAD-2009-1141}, pmid = {19584428}, issn = {1875-8908}, mesh = {Age Factors ; Amyloid beta-Peptides/*metabolism ; Amyloid beta-Protein Precursor/genetics ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Body Weight/genetics ; Disease Models, Animal ; Extinction, Psychological/physiology ; Female ; Food Preferences/physiology ; Memory Disorders/*genetics/physiopathology ; Mice ; Mice, Transgenic ; Mutation/drug effects ; Presenilin-1/genetics ; Saccharin/administration & dosage/pharmacology ; Sweetening Agents/administration & dosage/pharmacology ; Taste/*genetics ; Time Factors ; }, abstract = {Age-related changes in taste memory were evaluated in APPswe/PS1dE9 transgenic (Tg) mice and age-matched wild type littermate controls (Wt). These Tg mice produce increasing amounts of amyloid-beta in the brain with age, develop significant amounts of plaques by 9 months of age, and provide an opportunity to study the effects of Alzheimer's disease-like amyloidosis on different aspects of taste memory. In groups of mice ranging from 15-16 months of age, the neophobic response and its attenuation were similar in Tg and Wt mice. However, conditioned taste aversion (CTA), which resulted from the association between a new taste and an artificially induced gastric malaise, was significantly reduced in the 15-16 month old Tg mice compared to the Wt mice, but not in the 3-4 or 7-8 month old mice. The extinction of CTA was normal in 3-4 month old Tg mice, but occurred more rapidly in the 7-8 and 15-16 months old Tg mice than in the age-matched controls. These results provide evidence of differences in the neuronal systems involved in the attenuation of neophobia and CTA and suggest that the progressive amyloidosis that takes place in APPswe/PS1dE9 mice selectively affects the aversion component of taste memory.}, } @article {pmid19576896, year = {2009}, author = {Fudge, MA and Kavaliers, M and Baird, JP and Ossenkopp, KP}, title = {Tamoxifen produces conditioned taste avoidance in male rats: an analysis of microstructural licking patterns and taste reactivity.}, journal = {Hormones and behavior}, volume = {56}, number = {3}, pages = {322-331}, pmid = {19576896}, issn = {1095-6867}, support = {R15 DC007389/DC/NIDCD NIH HHS/United States ; R15 DC007389-02/DC/NIDCD NIH HHS/United States ; DC-07389/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight ; Conditioning, Classical/*drug effects ; Drinking Behavior/*drug effects ; Estradiol/pharmacology ; Estrogens/pharmacology ; Locomotion/drug effects ; Male ; Motor Activity/drug effects ; Rats ; Rats, Long-Evans ; Selective Estrogen Receptor Modulators/administration & dosage/*pharmacology ; Sucrose/administration & dosage ; Tamoxifen/administration & dosage/*pharmacology ; Taste/drug effects ; Time Factors ; }, abstract = {Estrogen receptor activation has been shown to reduce body weight and produce a conditioned reduction in food intake in male rats that is putatively mediated by estradiol's suggested aversive effects. Evidence has shown that the selective estrogen receptor modulator tamoxifen used in the prevention and treatment of breast cancer may also produce changes in food intake and body weight, which are known to impact cancer development and survival. The purpose of the present study was to examine whether tamoxifen produces a conditioned reduction in intake similar to estradiol by producing a conditioned aversion. A one bottle lickometer test was used to examine conditioned changes in sucrose drinking, while the taste reactivity test was used to measure rejection reactions, which serve to index aversion in rats. A backward conditioning procedure that consisted of 3 conditioning days and one vehicle test day was used to examine conditioned changes in 0.3 M sucrose intake and taste reactivity. Our results show that tamoxifen produced a conditioned reduction in sucrose drinking in a one bottle fluid intake test that was similar to the effects produced by estradiol (positive control); however, no active rejection reactions were produced by either tamoxifen (1 and 10 mg/kg) or estradiol. The present results suggest that tamoxifen, at the doses used in the present study, acts as an estrogen receptor agonist to regulate food intake and that the conditioned reduction in intake produced by tamoxifen and estradiol reflects conditioned taste avoidance rather than conditioned taste aversion.}, } @article {pmid19531382, year = {2009}, author = {Daniel, AM and Ortega, LA and Papini, MR}, title = {Role of the opioid system in incentive downshift situations.}, journal = {Neurobiology of learning and memory}, volume = {92}, number = {3}, pages = {439-450}, doi = {10.1016/j.nlm.2009.06.003}, pmid = {19531382}, issn = {1095-9564}, mesh = {Analgesics, Opioid/*pharmacology ; Animals ; Conditioning, Classical/drug effects ; Dietary Sucrose/*administration & dosage ; Drinking Behavior/*drug effects ; Enkephalin, D-Penicillamine (2,5)-/pharmacology ; Extinction, Psychological/drug effects ; Feeding Behavior/drug effects ; Female ; Goals ; Male ; *Motivation ; Naloxone/pharmacology ; Naltrexone/analogs & derivatives/pharmacology ; Narcotic Antagonists/*pharmacology ; Random Allocation ; Rats ; Rats, Long-Evans ; Receptors, Opioid, mu/agonists/antagonists & inhibitors ; Taste Perception/drug effects ; Time Factors ; }, abstract = {Previous research has shown that opioid blockage enhances consummatory successive negative contrast (cSNC)-a suppression of consummatory behavior following a downshift from 32% to 4% sucrose solution. In Experiment 1, administration of the nonselective opioid receptor antagonist naloxone (2 mg/kg, ip) distorted the comparison between expected and received incentives. The results of Experiment 2 discarded the alternative that naloxone enhances cSNC by inducing a conditioned taste aversion. The results of Experiments 3a-3c provided no evidence that opioid administration after the first downshift trial modulated subsequent consummatory performance. The opioids tested included naloxone (2mg/kg, ip), the delta-opioid receptor selective antagonist naltrindole (1 mg/kg, ip), and the delta-opioid receptor selective agonist DPDPE (24 microg/kg, ip). The selected doses have proven in earlier experiments to be effective when administered before training. Experiments 4-5 failed to uncover any effects of posttraining opioid blockage with naloxone in an appetitive extinction task (autoshaping with lever-food pairings). These results add to our previous understanding of opioid function in situations involving incentive downshifts, suggesting a role in the comparison process that triggers cSNC, but no apparent function in memory consolidation related to the downshift event.}, } @article {pmid19531156, year = {2009}, author = {Hanna, A and Horne, P and Yager, D and Eckman, C and Eckman, E and Janus, C}, title = {Amyloid beta and impairment in multiple memory systems in older transgenic APP TgCRND8 mice.}, journal = {Genes, brain, and behavior}, volume = {8}, number = {7}, pages = {676-684}, doi = {10.1111/j.1601-183X.2009.00510.x}, pmid = {19531156}, issn = {1601-183X}, support = {NS048554/NS/NINDS NIH HHS/United States ; }, mesh = {Alzheimer Disease/genetics/*metabolism/physiopathology ; Amyloid beta-Peptides/*metabolism ; Amyloid beta-Protein Precursor/genetics ; Animals ; Avoidance Learning/physiology ; Brain/*metabolism/pathology/physiopathology ; Disease Models, Animal ; Disease Progression ; Female ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; Memory Disorders/genetics/*metabolism/physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Net/metabolism/pathology/physiopathology ; Plaque, Amyloid/genetics/*metabolism/pathology ; }, abstract = {The relationship between amyloid beta and cognitive dysfunction in mouse models of Alzheimer's disease has been evaluated predominantly with the spatial reference memory version of the water maze task. However, as Alzheimer's disease encompasses decline in multiple memory systems, it is important to also utilize non-spatial tasks to fully characterize the role of amyloid on behaviour in animal models. We used the TgCRND8 mouse model of Alzheimer's disease to evaluate the effect of amyloid on spatial reference memory, as well as on the non-spatial task of acquisition of conditioned taste aversion, and on the procedural task of swimming to a visible platform. We demonstrate that 8- to 12-month-old TgCRND8 mice are significantly impaired in all three tasks, and that the levels of soluble amyloid beta are significantly correlated with impairment in spatial reference memory, but not with impairment in conditioned taste aversion or swimming to a visible platform. Insoluble fractions of amyloid, which correspond closely to amyloid plaque burden in the brain, are not associated with any behavioural measure. Our study extends the characterization of the model to stages of advanced amyloid pathology and demonstrates that older TgCRND8 mice are impaired in multiple memory systems, including procedural tasks, which are spared at younger ages. The lack of association between amyloid plaques and memory decline supports clinical findings in Alzheimer's patients.}, } @article {pmid19523097, year = {2009}, author = {Inui, T and Yamamoto, T and Shimura, T}, title = {GABAergic transmission in the rat ventral pallidum mediates a saccharin palatability shift in conditioned taste aversion.}, journal = {The European journal of neuroscience}, volume = {30}, number = {1}, pages = {110-115}, doi = {10.1111/j.1460-9568.2009.06800.x}, pmid = {19523097}, issn = {1460-9568}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Catheterization ; Conditioning, Classical/*physiology ; Feeding Behavior/physiology ; Globus Pallidus/*physiology ; Lithium Chloride ; Male ; Microdialysis ; Quinine ; Rats ; Rats, Wistar ; Saccharin ; Synaptic Transmission/*physiology ; Taste Perception/*physiology ; Time Factors ; gamma-Aminobutyric Acid/*metabolism ; }, abstract = {We previously found that the blockade of gamma-aminobutyric acid (GABA)(A) receptors in the ventral pallidum (VP) alters the taste palatability of a conditioned stimulus (CS) from aversive to ingestive after the establishment of conditioned taste aversion (CTA). Because these results suggest that GABAergic transmission in the VP mediates decreased palatability of the taste in CTA, the present study aimed to examine the effects of taste stimulation on the extracellular release of GABA in the VP using in vivo microdialysis. Initially, rats received a paired presentation of 5 mm saccharin or 0.3 mm quinine solution with an intraperitoneal injection of 0.15 m lithium chloride (S-CTA and Q-CTA groups) or saline (S-control and Q-control groups). After conditioning, microdialysis was carried out before, during and after the presentation of the CS via an intra-oral cannula. We measured the latency of the first aversive orofacial responses to the CS as behavioral indices. In the S-CTA group, which rapidly rejected the CS (within 100 s), the GABA efflux was significantly increased (147%) and was maintained for 2 h. On the other hand, the S-control group expressed no aversive responses and showed no significant alterations in GABA efflux. Although the Q-CTA group immediately expressed aversive responses to the CS (within 30 s), GABA release was not changed by presentation of the CS, which was similar in the Q-control group. These findings suggest that the palatability shift from ingestive to aversive in conditioned aversion to saccharin, but not quinine, is mediated by the change in GABAergic transmission in the VP.}, } @article {pmid19508878, year = {2009}, author = {Davis, CM and Rice, KC and Riley, AL}, title = {Opiate-agonist induced taste aversion learning in the Fischer 344 and Lewis inbred rat strains: evidence for differential mu opioid receptor activation.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {93}, number = {4}, pages = {397-405}, pmid = {19508878}, issn = {1873-5177}, support = {Z01 DA000520-01/ImNIH/Intramural NIH HHS/United States ; }, mesh = {3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Benzamides/pharmacology ; Dose-Response Relationship, Drug ; Heroin/pharmacology ; Narcotics/pharmacology ; Piperazines/pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Receptors, Opioid, delta/agonists/genetics ; Receptors, Opioid, kappa/agonists/genetics ; Receptors, Opioid, mu/*agonists/genetics ; Species Specificity ; Taste/*drug effects ; }, abstract = {The Fischer 344 (F344) and Lewis (LEW) inbred rat strains react differently to morphine in a number of behavioral and physiological preparations, including the acquisition of aversions induced by this compound. The present experiment tested the ability of various compounds with relative selectivity at kappa, delta and mu receptor subtypes to assess the relative roles of these subtypes in mediating the differential aversive effects of morphine in the two strains. In the assessment of the role of the kappa receptor in morphine-induced aversions, animals in both strains were given access to saccharin followed by varying doses of the kappa agonist (-)-U50,488H (0.0, 0.28, 0.90 and 1.60 mg/kg). Although (-)-U50,488H induced aversions in both strains, no strain differences emerged. A separate subset of subjects was trained with the selective delta opioid agonist, SNC80 (0.0, 5.6, 10.0 and 18.0 mg/kg), and again although SNC80 induced aversions, there were no strain differences. Finally, a third subset of subjects was trained with heroin (0.0, 3.2, 5.6 and 10.0 mg/kg), a compound with activity at all three opiate receptor subtypes. Although heroin induced aversions in both strains, the aversions were significantly greater in the F344 strain, suggesting that differential activation of the mu opioid receptor likely mediates the reported strain differences in morphine-induced aversion learning. These data were discussed in terms of strain differences in opioid system functioning and the implications of such differences for other morphine-induced behavioral effects reported in F344 and LEW rats.}, } @article {pmid19485574, year = {2009}, author = {Nielsen, DM and Evans, JJ and Derber, WJ and Johnston, KA and Laudenslager, ML and Crnic, LS and Maclean, KN}, title = {Mouse model of fragile X syndrome: behavioral and hormonal response to stressors.}, journal = {Behavioral neuroscience}, volume = {123}, number = {3}, pages = {677-686}, doi = {10.1037/a0015242}, pmid = {19485574}, issn = {0735-7044}, support = {HD017449/HD/NICHD NIH HHS/United States ; HD04024/HD/NICHD NIH HHS/United States ; HD047029/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/physiology ; Conditioning, Psychological/physiology ; Corticosterone/blood ; Disease Models, Animal ; Electroshock ; Fragile X Mental Retardation Protein/genetics ; Fragile X Syndrome/*physiopathology/*psychology ; Freezing Reaction, Cataleptic ; Male ; Memory/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Restraint, Physical ; Stress, Psychological/*physiopathology ; Swimming ; Taste ; }, abstract = {Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.}, } @article {pmid19439188, year = {2009}, author = {Simonyi, A and Serfozo, P and Parker, KE and Ramsey, AK and Schachtman, TR}, title = {Metabotropic glutamate receptor 5 in conditioned taste aversion learning.}, journal = {Neurobiology of learning and memory}, volume = {92}, number = {3}, pages = {460-463}, pmid = {19439188}, issn = {1095-9564}, support = {R03 MH064486/MH/NIMH NIH HHS/United States ; R03 MH064486-01A1/MH/NIMH NIH HHS/United States ; R03 MH64486-01A1/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/drug effects/physiology ; Animals ; Avoidance Learning/*physiology ; Brain/drug effects/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/drug effects/physiology ; Male ; Parietal Lobe/drug effects/physiology ; Pyridines/administration & dosage/pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/*metabolism ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste Perception/*physiology ; Temporal Lobe/drug effects/physiology ; Thiazoles/administration & dosage/pharmacology ; Time Factors ; }, abstract = {In conditioned taste aversion (CTA), animals learn to avoid a flavored solution (conditioned stimulus, CS) previously paired with internal malaise (unconditioned stimulus, US). Metabotropic glutamate receptor 5 (mGlu5) has been implicated in learning and memory processes and is necessary for CTA. In the present study, local microinjections of a mGlu5-selective antagonist, 3-[2-methyl-1,3-thiazol-4yl)ethynyl]pyridine (MTEP, 0, 1 or 5 microg) into the insular cortex and basolateral amygdala were used in male, Sprague-Dawley rats to examine the role of mGlu5 receptors in the encoding of taste memory. MTEP was infused 20 min before saccharin intake during CTA conditioning. MTEP injection into the basolateral amygdala resulted in robust CTA, similar to the vehicle-treated animals but slowed extinction; that is, MTEP enhanced CTA. MTEP injection into the insular cortex resulted in an increased saccharin intake on the conditioning trial, which potentially influenced the performance on the test trials; MTEP had no effect on CTA learning when controlled access to saccharin was used on the conditioning trial. These results indicate that mGlu5 receptors are involved in taste memories in a region-specific manner.}, } @article {pmid19423656, year = {2009}, author = {St John, SJ and Boughter, JD}, title = {Orosensory responsiveness to and preference for hydroxide-containing salts in mice.}, journal = {Chemical senses}, volume = {34}, number = {6}, pages = {487-498}, pmid = {19423656}, issn = {1464-3553}, support = {DC 000353/DC/NIDCD NIH HHS/United States ; NS 052366/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Calcium Hydroxide/*pharmacology ; Food Preferences/physiology ; Hydroxides/*pharmacology ; Mice ; Mice, Inbred Strains ; Salts/pharmacology ; Sodium Hydroxide/*pharmacology ; Species Specificity ; Taste/*physiology ; Taste Threshold ; }, abstract = {Historically, taste researchers have considered the possibility that the gustatory system detects basic compounds, such as those containing the hydroxide ion, but evidence for an "alkaline taste" has not been strong. We found that, in 48 h, 2-bottle preference tests, C3HeB/FeJ (C3) mice showed a preference for Ca(OH)(2), whereas SWR/J (SW) mice showed avoidance. Strain differences were also apparent to NaOH but not CaCl(2). Follow-up studies showed that the strain difference for Ca(OH)(2) was stable over time (Experiment 2) but that C3 and SW mice did not differ in their responses to Ca(OH)(2) or NaOH in brief-access tests, where both mice avoided high concentrations of these compounds (Experiment 3). In order to assess the perceived quality of Ca(OH)(2), mice were tested in 2 taste aversion generalization experiments (Experiments 4 and 5). Aversions to Ca(OH)(2) generalized to NaOH but not CaCl(2) in both strains, suggesting that the generalization was based on the hydroxide ion. Both strains also generalized aversions to quinine, suggesting the possibility that the hydroxide ion has a bitter taste quality to these mice, despite the preference shown by C3 mice to middle concentrations in long-term tests.}, } @article {pmid19420241, year = {2009}, author = {Saavedra-Rodríguez, L and Vázquez, A and Ortiz-Zuazaga, HG and Chorna, NE and González, FA and Andrés, L and Rodríguez, K and Ramírez, F and Rodríguez, A and Peña de Ortiz, S}, title = {Identification of flap structure-specific endonuclease 1 as a factor involved in long-term memory formation of aversive learning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {29}, number = {18}, pages = {5726-5737}, pmid = {19420241}, issn = {1529-2401}, support = {P20 RR-016470/RR/NCRR NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; T34 GM007821/GM/NIGMS NIH HHS/United States ; 5P20 RR-15565-02/RR/NCRR NIH HHS/United States ; P20 RR016470/RR/NCRR NIH HHS/United States ; SO6GMO8102/SO/PHSPO CDC HHS/United States ; S06 GM008102/GM/NIGMS NIH HHS/United States ; 5T34GM07821/GM/NIGMS NIH HHS/United States ; S06 GM008102-360085/GM/NIGMS NIH HHS/United States ; P20 RR015565/RR/NCRR NIH HHS/United States ; SC1 MH086072/MH/NIMH NIH HHS/United States ; SC1 MH086072-01/MH/NIMH NIH HHS/United States ; 1SC1MH086072-01/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/cytology/metabolism ; Analysis of Variance ; Animals ; Astrocytes/metabolism ; Avoidance Learning/*physiology ; Behavior, Animal ; Cell Line, Transformed ; Flap Endonucleases/genetics/*metabolism ; Gene Expression Regulation, Enzymologic/drug effects/physiology ; Glial Fibrillary Acidic Protein/metabolism ; Male ; Memory/drug effects/*physiology ; Neurons/cytology/drug effects/metabolism ; Oligodeoxyribonucleotides, Antisense/pharmacology ; Phosphopyruvate Hydratase/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Long-Evans ; *Taste ; }, abstract = {We previously proposed that DNA recombination/repair processes play a role in memory formation. Here, we examined the possible role of the fen-1 gene, encoding a flap structure-specific endonuclease, in memory consolidation of conditioned taste aversion (CTA). Quantitative real-time PCR showed that amygdalar fen-1 mRNA induction was associated to the central processing of the illness experience related to CTA and to CTA itself, but not to the central processing resulting from the presentation of a novel flavor. CTA also increased expression of the Fen-1 protein in the amygdala, but not the insular cortex. In addition, double immunofluorescence analyses showed that amygdalar Fen-1 expression is mostly localized within neurons. Importantly, functional studies demonstrated that amygdalar antisense knockdown of fen-1 expression impaired consolidation, but not short-term memory, of CTA. Overall, these studies define the fen-1 endonuclease as a new DNA recombination/repair factor involved in the formation of long-term memories.}, } @article {pmid19419674, year = {2009}, author = {Cason, AM and Kwon, B and Smith, JC and Houpt, TA}, title = {Labyrinthectomy abolishes the behavioral and neural response of rats to a high-strength static magnetic field.}, journal = {Physiology & behavior}, volume = {97}, number = {1}, pages = {36-43}, doi = {10.1016/j.physbeh.2009.01.018}, pmid = {19419674}, issn = {0031-9384}, support = {R01 DC004607/DC/NIDCD NIH HHS/United States ; T32DC0044/DC/NIDCD NIH HHS/United States ; R01DC4607/DC/NIDCD NIH HHS/United States ; F31DC6521/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Arsanilic Acid ; Brain Stem/*metabolism ; Conditioning, Psychological/*physiology ; Ear, Inner/*physiology ; Female ; *Locomotion ; *Magnetics ; Neural Pathways/metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Vertigo is a commonly-reported side effect of exposure to the high magnetic fields found in magnetic resonance imaging machines. Although it has been hypothesized that high magnetic fields interact with the vestibular apparatus of the inner ear, there has been no direct evidence establishing its role in magnet-induced vertigo. Our laboratory has shown that following exposure to high magnetic fields, rats walk in circles, acquire a conditioned taste aversion (CTA), and express c-Fos in vestibular and visceral relays of the brainstem, consistent with vestibular stimulation and vertigo or motion sickness. To determine if the inner ear is required for these effects, rats were chemically labyrinthectomized with sodium arsanilate and tested for locomotor circling, CTA acquisition, and c-Fos induction after exposure within a 14.1 T magnet. Intact rats circled counterclockwise after 30-min exposure to 14.1 T, but labyrinthectomized rats showed no increase in circling after magnetic field exposure. After 3 pairings of 0.125% saccharin with 30-min exposure at 14.1 T, intact rats acquired a profound CTA that persisted for 14 days of extinction testing; labyrinthectomized rats, however, did not acquire a CTA and showed a high preference for saccharin similar to sham-exposed rats. Finally, significant c-Fos was induced in the brainstem of intact rats by 30-min exposure to 14.1 T, but magnetic field exposure did not elevate c-Fos in labyrinthectomized rats above sham-exposed levels. These results demonstrate that an intact inner ear is necessary for all the observed effects of exposure to high magnetic fields in rats.}, } @article {pmid19419428, year = {2009}, author = {Desgranges, B and Sevelinges, Y and Bonnefond, M and Lévy, F and Ravel, N and Ferreira, G}, title = {Critical role of insular cortex in taste but not odour aversion memory.}, journal = {The European journal of neuroscience}, volume = {29}, number = {8}, pages = {1654-1662}, doi = {10.1111/j.1460-9568.2009.06711.x}, pmid = {19419428}, issn = {1460-9568}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Cerebral Cortex/anatomy & histology/*physiology ; Conditioning, Classical/*physiology ; Food ; Male ; Memory/*physiology ; *Odorants ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Conditioned odour aversion (COA) and conditioned taste aversion (CTA) result from the association of a novel odour or a novel taste with delayed visceral illness. The insular cortex (IC) is crucial for CTA memory, and the present experiments sought to determine whether the IC is required for the formation and the retrieval of COA memory as it is for CTA. We first demonstrated that ingested odour is as effective as taste for single-trial aversion learning in rats conditioned in their home cage. COA, like CTA, tolerates long intervals between the ingested stimuli and the illness and is long-lasting. Transient inactivation of the IC during acquisition spared COA whereas it greatly impaired CTA. Similarly, blockade of protein synthesis in IC did not affect COA but prevented CTA consolidation. Moreover, IC inactivation before retrieval tests did not interfere with COA memory expression when performed either 2 days (recent memory) or 36 days after acquisition (remote memory). Similar IC inactivation impaired the retrieval of either recent or remote CTA memory. Altogether these findings indicate that the IC is not necessary for aversive odour memory whereas it is essential for acquisition, consolidation and retrieval of aversive taste memory. We propose that the chemosensory stimulations modulate IC recruitment during the formation and the retrieval of food aversive memory.}, } @article {pmid19394353, year = {2009}, author = {Koh, MT and Wheeler, DS and Gallagher, M}, title = {Hippocampal lesions interfere with long-trace taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {98}, number = {1-2}, pages = {103-107}, pmid = {19394353}, issn = {1873-507X}, support = {P01 AG009973/AG/NIA NIH HHS/United States ; P01 AG009973-16A1/AG/NIA NIH HHS/United States ; P01-AG-09973/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/physiology ; Fear/physiology ; Hippocampus/injuries/*physiology ; Male ; Maze Learning/physiology ; Rats ; Rats, Long-Evans ; Taste/*physiology ; Water Deprivation ; }, abstract = {This series of experiments investigated the effects of dorsal and ventral hippocampal lesions on taste aversion learning. Although damage to the hippocampus did not affect the acquisition of a taste aversion when the conditioning procedure used a relatively standard interval between taste and illness, both types of lesions produced a deficit in taste aversion when a long interval (3 h) was interposed between taste exposure and induction of illness. In the same subjects, trace fear conditioning was selectively impaired by ventral lesions, whereas water maze performance was selectively impaired by dorsal lesions. The results replicate past dissociations of dorsal and ventral hippocampal function, and also suggest that the hippocampus has a less differentiated role in long-trace taste aversion learning.}, } @article {pmid19389389, year = {2009}, author = {Hanamori, T}, title = {Effects of electrical and chemical stimulation of the amygdala on the spontaneous discharge in the insular cortex in rats.}, journal = {Brain research}, volume = {1276}, number = {}, pages = {91-102}, doi = {10.1016/j.brainres.2009.04.024}, pmid = {19389389}, issn = {1872-6240}, mesh = {Action Potentials/drug effects/physiology ; Amygdala/drug effects/*physiology ; Animals ; Electric Stimulation ; Excitatory Amino Acid Agents/administration & dosage ; GABA Agents/administration & dosage ; Glutamic Acid/administration & dosage ; Male ; Microelectrodes ; Microinjections ; Neural Pathways/drug effects/physiology ; Neurons/drug effects/*physiology ; Parietal Lobe/drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Temporal Lobe/drug effects/*physiology ; gamma-Aminobutyric Acid/administration & dosage ; }, abstract = {Both the amygdala (especially, the basolateral nucleus of the amygdala) and the insular cortex are important for conditioned taste aversion. From the anatomical view point, there are reciprocal connections between the insular cortex and the amygdala. In the present study, we investigated the effect of electrical and chemical stimulation of the amygdala on the spontaneous discharge of the insular cortex neurons in anesthetized rats. In most neurons (10 of 14), spontaneous discharge was decreased after a microinjection of glutamate (Glu). In these neurons, the injection site was within the basolateral nucleus of the amygdala (the basolateral/lateral nuclei). On the other hand, when a gamma amino-butyric acid (GABA) was microinjected into the basolateral nucleus of the amygdala, none of the 5 neurons showed any change in spontaneous discharge. Electrical train stimulation of the basolateral nucleus of the amygdala (100 Hz, 2-6 s) depressed the spontaneous discharge of the neurons in the insular cortex, as in the case of a Glu microinjection. These results indicate that activation of the basolateral nucleus of the amygdala could depress the neuronal activity in the insular cortex. Such results may yield data leading to the elucidation of the neuronal mechanisms of conditioned taste aversion.}, } @article {pmid19376154, year = {2009}, author = {Jones, JD and Hall, FS and Uhl, GR and Rice, K and Riley, AL}, title = {Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {93}, number = {1}, pages = {75-81}, pmid = {19376154}, issn = {1873-5177}, support = {Z99 DA999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Cocaine/*toxicity ; Cocaine-Related Disorders/physiopathology/psychology ; Conditioning, Psychological ; Dopamine/*physiology ; Dopamine Uptake Inhibitors/pharmacology ; Fluoxetine/analogs & derivatives/pharmacology ; Male ; Mice ; Norepinephrine/antagonists & inhibitors/*physiology ; Piperazines/pharmacology ; Serotonin/*physiology ; Serotonin Uptake Inhibitors/pharmacology ; Taste/*drug effects/*physiology ; }, abstract = {Despite the impact of cocaine's aversive effects on its abuse potential, the neurochemical basis of these aversive effects remains poorly understood. By blocking the reuptake of the monoamine neurotransmitters dopamine (DA), norepinephrine (NE) and serotonin (5-HT) into the presynaptic terminal, cocaine acts as a potent indirect agonist of each of these systems. The following studies attempted to assess the extent of monoaminergic mediation of cocaine's aversive effects using conditioned taste aversion (CTA) learning [Garcia, J., Kimeldorf, D.J., Koelling, R.A., Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 1955;122:157-158.]. Specifically, Experiment 1 assessed the ability of selective monoamine transporter inhibitors, e.g., DAT (vanoxerine), NET (nisoxetine) and SERT (fluoxetine), to induce taste aversions (relative to cocaine). Only the NET inhibitor approximated the aversive strength of cocaine. Experiment 2 compared the effects of pretreatment of each of these transport inhibitors on the development of a cocaine-induced CTA. Pretreatment with nisoxetine and fluoxetine both attenuated cocaine-induced aversions in a manner comparable to that produced by cocaine itself. The DAT inhibitor was without effect. Combined, the results of these investigations indicate little or no involvement of dopaminergic systems in cocaine's aversive effects while NE appears to contribute most substantially, with a possible modulatory involvement by serotonin.}, } @article {pmid19361543, year = {2009}, author = {Miranda, F and Jiménez, JC and Cedillo, LN and Sandoval-Sánchez, A and Millán-Mejía, P and Sánchez-Castillo, H and Velázquez-Martínez, DN}, title = {The GABA-B antagonist 2-hydroxysaclofen reverses the effects of baclofen on the discriminative stimulus effects of D-amphetamine in the conditioned taste aversion procedure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {93}, number = {1}, pages = {25-30}, doi = {10.1016/j.pbb.2009.04.002}, pmid = {19361543}, issn = {1873-5177}, mesh = {Animals ; Baclofen/*analogs & derivatives/*pharmacology ; Central Nervous System Stimulants/pharmacology ; Conditioning, Psychological/drug effects/physiology ; Dextroamphetamine/*pharmacology ; Discrimination, Psychological/*drug effects/physiology ; Disease Models, Animal ; GABA Antagonists/pharmacology ; *GABA-B Receptor Antagonists ; Male ; Rats ; Rats, Wistar ; Receptors, GABA-B/physiology ; Substance-Related Disorders/etiology/physiopathology/psychology ; Synaptic Transmission/drug effects/physiology ; Taste Perception/drug effects/physiology ; }, abstract = {Some of the behavioral effects of d-amphetamine (d-AMPH) are mediated by an increase in dopamine neurotransmission in the nucleus accumbens. However, there is evidence that gamma-amino-butyric-acid-B (GABA-B) receptors are involved in some behavioral effects of D-AMPH and cocaine. Here, we examined the effects of baclofen on the discriminative stimulus properties of D-AMPH, using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received D-AMPH (1 mg/kg, i.p.) before gaining access to saccharin, which was followed by an injection of LiCl. On alternate days, the subjects received saline before and after the access to saccharin. After the rats learned the D-AMPH-saline discrimination, the standard dose of D-AMPH was replaced by different doses of D-AMPH, baclofen (a GABA-B receptor agonist), 2-hydroxysaclofen (a GABA-B receptor antagonist), a combination of baclofen+D-AMPH, or a combination of 2-hydroxysaclofen+baclofen+D-AMPH. Baclofen did not substitute for D-AMPH, but, when combined with D-AMPH, it produced a small but significant decrease in the discriminative stimulus effects of D-AMPH. This effect was reversed by administration of 2-hydroxysaclofen. These data suggest that GABA-B receptors play a regulatory role in the discriminative stimulus effects of D-AMPH.}, } @article {pmid19341747, year = {2009}, author = {Lu, B and Yan, J and Yang, X}, title = {Effects of sodium depletion on detection thresholds for salty taste in rats.}, journal = {Physiology & behavior}, volume = {97}, number = {3-4}, pages = {463-469}, doi = {10.1016/j.physbeh.2009.03.022}, pmid = {19341747}, issn = {1873-507X}, mesh = {Analysis of Variance ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Avoidance Learning/drug effects ; Captopril/pharmacology ; Choice Behavior/drug effects/physiology ; Conditioning, Operant/drug effects/physiology ; Diet, Sodium-Restricted ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Food Preferences/drug effects/*physiology ; Furosemide/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium/*deficiency ; Sodium Potassium Chloride Symporter Inhibitors/pharmacology ; Sodium, Dietary/administration & dosage/pharmacology ; Taste/drug effects/*physiology ; Taste Threshold/drug effects/*physiology ; }, abstract = {Previous studies, which have mostly focused on concentrated NaCl solution intake, have suggested sodium depletion may be accompanied with salt taste sensory changes. To further investigate whether the function of the salt taste system changes in different patterns for highly concentrated and diluted NaCl taste stimuli, the effects of sodium depletion on NaCl taste detection threshold in rats were examined. After a conditioned taste aversion (CTA) to a suprathreshold concentration of NaCl (0.1 M) was established, rats were given a series of two-bottle choice tests between distilled water and different concentrations of NaCl. Conditioned rats will generalize the aversion to diluted solutions when they are detected. The taste detection threshold for NaCl is defined as the lowest concentration at which there is a reliable difference in the preference scores between conditioned and control subjects. The results showed that detection threshold for NaCl lay between 0.003 M and 0.005 M in sodium-replete rats, whereas in sodium-depleted rats that have an amplified action of angiotensin II in the brain, the threshold significantly decreased to be between 0.0001 M and 0.0003 M. However, in rats with a blocked action of angiotensin II in the brain the decreased NaCl detection threshold was between 0.001 M and 0.003 M. These findings suggest that sodium-depleted rats could decrease the NaCl taste detection threshold to increase the ability to find sodium ions. And the regulation of the salt taste sensitivity may be related to the action of angiotensin II in brain.}, } @article {pmid19339601, year = {2009}, author = {Yu, H and Wang, Y and Pattwell, S and Jing, D and Liu, T and Zhang, Y and Bath, KG and Lee, FS and Chen, ZY}, title = {Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive memory.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {29}, number = {13}, pages = {4056-4064}, pmid = {19339601}, issn = {1529-2401}, support = {MH079513/MH/NIMH NIH HHS/United States ; P50 MH079513-01A10001/MH/NIMH NIH HHS/United States ; P50 MH079513/MH/NIMH NIH HHS/United States ; R01 NS052819-04/NS/NINDS NIH HHS/United States ; R01 NS052819/NS/NINDS NIH HHS/United States ; MH060478/MH/NIMH NIH HHS/United States ; NS052819/NS/NINDS NIH HHS/United States ; R25 MH060478/MH/NIMH NIH HHS/United States ; MH068850/MH/NIMH NIH HHS/United States ; K08 MH068850/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/physiology ; Brain/drug effects/ultrastructure ; Brain-Derived Neurotrophic Factor/*genetics ; Cycloserine/pharmacology ; Extinction, Psychological/drug effects/*physiology ; Food Preferences ; Lithium Chloride/administration & dosage ; Male ; Memory/drug effects/*physiology ; Methionine/*genetics ; Mice ; Mice, Transgenic ; Polymorphism, Genetic/*genetics ; Proto-Oncogene Proteins c-fos/metabolism ; Silver Staining/methods ; Taste/genetics ; Time Factors ; Valine/*genetics ; }, abstract = {Brain-derived neurotrophic factor (BDNF) plays important roles in activity-dependent plasticity processes, such as long-term potentiation, learning, and memory. The recently reported human BDNF Val66Met (BDNF(Met)) polymorphism has been shown to lead to altered hippocampal volume and impaired hippocampal-dependent memory and is associated with a variety of neuropsychiatric disorders. There are few studies, however, that investigate the effect of the BDNF(Met) polymorphism on hippocampal-independent memory processes. A conditioned taste aversion (CTA) task was used for studying the mechanisms of long-term, hippocampal-independent, nondeclarative memory in the mammalian brain. Using the CTA paradigm, we found a novel impairment in extinction learning, but not acquisition or retention, of aversive memories resulting from the variant BDNF(Met). BDNF(Met) mice were slower to extinguish an aversive CTA memory compared with wild-type counterparts. Moreover, the BDNF(Met) was associated with smaller volume and decreased neuronal dendritic complexity in the ventromedial prefrontal cortex (vmPFC), which plays a significant role in extinction of CTA. Finally, this delay in extinction learning could be rescued pharmacologically with a cognitive enhancer, d-cycloserine (DCS). To our knowledge, this is the first evidence that the BDNF(Met) polymorphism contributes to abnormalities in memory extinction. This abnormality in extinction learning may be explained by alterations in neuronal morphology, as well as decreased neural activity in the vmPFC. Importantly, DCS was effective in rescuing this delay in extinction, suggesting that when coupled with behavior therapy, DCS may be an effective treatment option for anxiety disorders in humans with this genetic variant BDNF.}, } @article {pmid19281838, year = {2009}, author = {Arias, C and Molina, JC and Spear, NE}, title = {Ethanol-mediated aversive learning as a function of locomotor activity in a novel environment in infant Sprague-Dawley rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {92}, number = {4}, pages = {621-628}, pmid = {19281838}, issn = {1873-5177}, support = {R37 MH035219/MH/NIMH NIH HHS/United States ; AA11960/AA/NIAAA NIH HHS/United States ; R01 AA015992-01A1/AA/NIAAA NIH HHS/United States ; R01 AA011960/AA/NIAAA NIH HHS/United States ; R01 AA015992-03/AA/NIAAA NIH HHS/United States ; AA013098/AA/NIAAA NIH HHS/United States ; R01 MH035219/MH/NIMH NIH HHS/United States ; MH035219/MH/NIMH NIH HHS/United States ; P50 AA017823/AA/NIAAA NIH HHS/United States ; AA015992/AA/NIAAA NIH HHS/United States ; R01 AA015992/AA/NIAAA NIH HHS/United States ; R01 AA011960-10/AA/NIAAA NIH HHS/United States ; R01 AA013098/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Animals, Suckling ; Conditioning, Psychological ; Environment ; Ethanol/*toxicity ; Female ; Learning/*drug effects/*physiology ; Male ; Motor Activity/*drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; Saccharin/administration & dosage ; }, abstract = {Unlike adult heterogeneous rats, infant rats are sensitive to ethanol's locomotor stimulating effects. Susceptibility to this ethanol effect varies as a function of baseline locomotor activity levels. Infant rats with higher baseline activity levels are more sensitive to ethanol's stimulating effects than those with lower baseline activity levels. The present study was designed to analyze susceptibility to ethanol-induced motivational learning in subpopulations of infant heterogeneous rats that differ in baseline activity in a novel environment. On postnatal day 11 (PD 11) baseline locomotor activity was registered and infants were divided into high and low responders (HR, LR). In Experiment 1, pups were trained in a procedure of conditioned taste aversion employing ethanol (0.0, 0.5 or 2.5 g/kg) as unconditioned stimulus (US) and saccharin as conditioned stimulus. In Experiment 2 the same procedure was employed with LiCl (0.0, 0.25 or 0.5% of body weight of a 0.3 M LiCl solution) as US. HR were more resistant to the aversive effects of ethanol than LR while magnitude of LiCl-induced conditioned taste aversion was similar in HR and LR. These results suggest the possibility of early detection of subpopulations of rats with differential sensitivity to ethanol's effects.}, } @article {pmid19272397, year = {2009}, author = {Dalla, C and Shors, TJ}, title = {Sex differences in learning processes of classical and operant conditioning.}, journal = {Physiology & behavior}, volume = {97}, number = {2}, pages = {229-238}, pmid = {19272397}, issn = {1873-507X}, support = {R01 MH059970-08/MH/NIMH NIH HHS/United States ; R01 MH059970-04/MH/NIMH NIH HHS/United States ; MH59970/MH/NIMH NIH HHS/United States ; R01 MH059970-05/MH/NIMH NIH HHS/United States ; R01 MH059970-07/MH/NIMH NIH HHS/United States ; R01 MH059970-10/MH/NIMH NIH HHS/United States ; R01 MH059970-03/MH/NIMH NIH HHS/United States ; R01 MH059970-06/MH/NIMH NIH HHS/United States ; R01 MH059970-02/MH/NIMH NIH HHS/United States ; R01 MH059970-09/MH/NIMH NIH HHS/United States ; R01 MH059970/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Blinking/physiology ; Conditioning, Classical/*physiology ; Conditioning, Operant/*physiology ; Fear/physiology ; Female ; Humans ; Male ; Memory/physiology ; *Sex Characteristics ; Taste/physiology ; }, abstract = {Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear-conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion, males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent in one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them.}, } @article {pmid19249379, year = {2009}, author = {Pedroza-Llinás, R and Ramírez-Lugo, L and Guzmán-Ramos, K and Zavala-Vega, S and Bermúdez-Rattoni, F}, title = {Safe taste memory consolidation is disrupted by a protein synthesis inhibitor in the nucleus accumbens shell.}, journal = {Neurobiology of learning and memory}, volume = {92}, number = {1}, pages = {45-52}, doi = {10.1016/j.nlm.2009.02.011}, pmid = {19249379}, issn = {1095-9564}, mesh = {Analysis of Variance ; Animals ; Anisomycin/*administration & dosage ; Avoidance Learning/drug effects ; Catheterization ; Conditioning, Classical/drug effects ; Feeding Behavior/*drug effects ; Lithium Chloride/toxicity ; Male ; Memory/*drug effects ; Nucleus Accumbens/*drug effects ; Protein Synthesis Inhibitors/*administration & dosage ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste ; }, abstract = {Consolidation is the process by which a new memory is stabilized over time, and is dependent on de novo protein synthesis. A useful model for studying memory formation is gustatory memory, a type of memory in which a novel taste may become either safe by not being followed by negative consequences (attenuation of neophobia, AN), or aversive by being followed by post-digestive malaise (conditioned taste aversion, CTA). Here we evaluated the effects of the administration of a protein synthesis inhibitor in the nucleus accumbens (NAc) shell for either safe or aversive taste memory trace consolidation. To test the effects on CTA and AN of protein synthesis inhibition, anisomycin (100microg/microl) was bilaterally infused into the NAc shell of Wistar rats' brains. We found that post-trial protein synthesis blockade impaired the long-term safe taste memory. However, protein synthesis inhibition failed to disrupt the long-term memory of CTA. In addition, we infused anisomycin in the NAc shell after the pre-exposure to saccharin in a latent inhibition of aversive taste. We found that the protein synthesis inhibition impaired the consolidation of safe taste memory, allowing the aversive taste memory to form and consolidate. Our results suggest that protein synthesis is required in the NAc shell for consolidation of safe but not aversive taste memories, supporting the notion that consolidation of taste memory is processed in several brain regions in parallel, and implying that inhibitory interactions between both taste memory traces do occur.}, } @article {pmid19200060, year = {2009}, author = {Stehberg, J and Levy, D and Zangen, A}, title = {Impairment of aversive memory reconsolidation by localized intracranial electrical stimulation.}, journal = {The European journal of neuroscience}, volume = {29}, number = {5}, pages = {964-969}, doi = {10.1111/j.1460-9568.2009.06634.x}, pmid = {19200060}, issn = {1460-9568}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Biophysics ; Cerebral Cortex/*physiopathology ; Electric Stimulation/*adverse effects ; Male ; Memory Disorders/*etiology ; Rats ; Rats, Wistar ; Taste/*physiology ; Time Factors ; Transcranial Magnetic Stimulation/*adverse effects ; }, abstract = {Reconsolidation of long-term memory is blocked in animal models by macromolecular synthesis inhibitors, resulting in item-specific post-retrieval amnesia. The induction of such amnesia could ameliorate traumatic memories and phobias. However, this pharmacological approach is of limited value in humans because of toxicity. Here we report that reconsolidation of conditioned taste aversion in the rat is impaired by localized intracranial electrical stimulation. Lasting impairment was obtained only when stimulation was applied during memory reactivation and only to the dysgranular insular cortex bilaterally, which subserves the memory, but not to adjacent brain sites. The ability to learn a new association was not affected. The same method blocked new memory consolidation, but produced anterograde amnesia, reminiscent of the known effect of non-localized electroconvulsive therapy. Our results suggest that localized electrical microstimulation, such as produced by deep-brain stimulation or deep transcranial magnetic stimulation, could be used to impair long-term memory if applied during memory reactivation, and could lead to the development of a novel treatment for intractable post-traumatic stress disorder.}, } @article {pmid19199031, year = {2009}, author = {Mohajeri, MH and Wolfer, DP}, title = {Neprilysin deficiency-dependent impairment of cognitive functions in a mouse model of amyloidosis.}, journal = {Neurochemical research}, volume = {34}, number = {4}, pages = {717-726}, pmid = {19199031}, issn = {1573-6903}, mesh = {Amyloid beta-Peptides/*metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloidosis/*enzymology/pathology/psychology ; Animals ; Avoidance Learning ; Behavior, Animal ; Cognition Disorders/*enzymology/pathology/psychology ; Hippocampus/physiopathology ; Maze Learning ; Mice ; Mice, Transgenic ; Neprilysin/genetics/*metabolism ; Plaque, Amyloid/pathology ; }, abstract = {Alzheimer's disease, responsible for the vast majority of dementia cases in the elderly population, is caused by accumulation of toxic levels of amyloid beta peptide (A beta) in the brain. Neprilysin is a major enzyme responsible for the degradation of A beta in vivo. We have previously shown that elevation of neprilysin levels in the brain delays the deposition of A beta-plaques in a mouse model of amyloidosis and that lack of neprilysin leads to increased A beta generation and to signs of incipient neurodegeneration in mouse brains. This study was designed to test whether low brain levels of neprilysin affect the amyloid pathology or perturb the learning and memory performance of mice. Double-mutated mice carrying a targeted depletion of one allele of Mme, the gene encoding neprilysin, and over-expressing human amyloid precursor protein (APP), exhibited a reinforced amyloid pathology in comparison with their APP transgenic littermates. Moreover, in contrast to their parental lines, these mice were impaired in the Morris water maze learning and memory paradigm and showed facilitated extinction in the conditioned taste aversion test. These data suggest that even a partial neprilysin deficiency, as is found during aging, exacerbates amyloid pathology and may impair cognitive functions.}, } @article {pmid19192851, year = {2009}, author = {Vidal, J and Chamizo, VD}, title = {Taste-aversion conditioning, but not immunosuppression conditioning, occurs under partial water deprivation.}, journal = {The Journal of general psychology}, volume = {136}, number = {1}, pages = {71-89}, doi = {10.3200/GENP.136.1.71-90}, pmid = {19192851}, issn = {0022-1309}, mesh = {Animals ; Antibody Formation/immunology/physiology ; B-Lymphocytes/immunology ; Conditioning, Classical/*physiology ; Cyclophosphamide/toxicity ; Dose-Response Relationship, Drug ; Female ; Hemocyanins/immunology ; Immunoglobulin M/blood ; *Immunosuppression Therapy ; Male ; Mice ; Saccharin ; Sucrose ; Taste/*immunology ; Water Deprivation/*physiology ; }, abstract = {The authors investigated whether conditioned taste aversion and immunosuppression took place when water was available during conditioning and test protocols. The authors elicited taste-aversion conditioning and immunosuppression in outbred CD1-strain mice by pairing a conditioned stimulus (sucrose or saccharin solution) with an unconditioned stimulus (cyclophosphamide) that causes gastrointestinal upset and is immunosuppressive. The authors introduced a new conditioning protocol: 5 pairings of a saccharin solution with a low-dose injection of cyclophosphamide. Under these conditions, the authors generated conditioned aversion to saccharin but did not generate conditioned decrease of the antibody response. The authors conclude that taste-aversion conditioning, but not immunosuppression conditioning, occurred under partial water deprivation.}, } @article {pmid19188279, year = {2009}, author = {Ishiwatari, Y and Bachmanov, AA}, title = {A high-throughput method to measure NaCl and acid taste thresholds in mice.}, journal = {Chemical senses}, volume = {34}, number = {4}, pages = {277-293}, pmid = {19188279}, issn = {1464-3553}, support = {R01 DC000882/DC/NIDCD NIH HHS/United States ; DC00882/DC/NIDCD NIH HHS/United States ; }, mesh = {Aconitic Acid/administration & dosage ; Animals ; Avoidance Learning/physiology ; Behavior, Animal/physiology ; Conditioning, Psychological/*physiology ; Lithium Chloride/administration & dosage/toxicity ; Male ; Mice ; Psychology, Experimental/methods ; Recognition, Psychology/physiology ; Self Administration ; Sodium Chloride/*administration & dosage ; Taste Threshold/*physiology ; }, abstract = {To develop a technique suitable for measuring NaCl taste thresholds in genetic studies, we conducted a series of experiments with outbred CD-1 mice using conditioned taste aversion (CTA) and two-bottle preference tests. In Experiment 1, we compared conditioning procedures involving either oral self-administration of LiCl or pairing NaCl intake with LiCl injections and found that thresholds were the lowest after LiCl self-administration. In Experiment 2, we compared different procedures (30-min and 48-h tests) for testing conditioned mice and found that the 48-h test is more sensitive. In Experiment 3, we examined the effects of varying strength of conditioned (NaCl or LiCl taste intensity) and unconditioned (LiCl toxicity) stimuli and concluded that 75-150 mM LiCl or its mixtures with NaCl are the optimal stimuli for conditioning by oral self-administration. In Experiment 4, we examined whether this technique is applicable for measuring taste thresholds for other taste stimuli. Results of these experiments show that conditioning by oral self-administration of LiCl solutions or its mixtures with other taste stimuli followed by 48-h two-bottle tests of concentration series of a conditioned stimulus is an efficient and sensitive method to measure taste thresholds. Thresholds measured with this technique were 2 mM for NaCl and 1 mM for citric acid. This approach is suitable for simultaneous testing of large numbers of animals, which is required for genetic studies. These data demonstrate that mice, like several other species, generalize CTA from LiCl to NaCl, suggesting that they perceive taste of NaCl and LiCl as qualitatively similar, and they also can generalize CTA of a binary mixture of taste stimuli to mixture components.}, } @article {pmid19181618, year = {2009}, author = {Shema, R and Hazvi, S and Sacktor, TC and Dudai, Y}, title = {Boundary conditions for the maintenance of memory by PKMzeta in neocortex.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {16}, number = {2}, pages = {122-128}, pmid = {19181618}, issn = {1549-5485}, support = {R37 MH057068/MH/NIMH NIH HHS/United States ; R29 MH053576/MH/NIMH NIH HHS/United States ; MH57068/MH/NIMH NIH HHS/United States ; R01 MH053576/MH/NIMH NIH HHS/United States ; R01 MH057068/MH/NIMH NIH HHS/United States ; MH53576/MH/NIMH NIH HHS/United States ; }, mesh = {1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology ; Animals ; Avoidance Learning/drug effects ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/administration & dosage/*pharmacology ; Male ; Memory/*physiology ; Microinjections ; Neocortex/*enzymology/*physiology ; Oligopeptides/*pharmacology ; Protein Kinase C/*antagonists & inhibitors/*physiology ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Rats ; Rats, Wistar ; Taste/drug effects ; }, abstract = {We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKMzeta, abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is relatively ineffective toward PKMzeta, is independent of the intensity of training and the perceptual quality of the taste saccharin (conditioned stimulus, CS), and does not affect the ability of the insular cortex to re-encode the same specific CTA association again. The memory trace is, however, insensitive to ZIP during or immediately after training. This implies that the experience-dependent cellular plasticity mechanism targeted by ZIP is established following a brief time window after encoding, consistent with the standard period of cellular consolidation, but then, once established, does not consolidate further to gain immunity to the amnesic agent. Hence, we conclude that PKMzeta is not involved in short-term CTA memory, but is a critical component of the cortical machinery that stores long- and very long-term CTA memories.}, } @article {pmid19178072, year = {2008}, author = {Komissarova, NV and Tiunova, AA and Anokhin, KV}, title = {[Selective disruption of memory consolidation in chicks produced by 5'-iodo-2'-deoxyuridine].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {58}, number = {6}, pages = {700-710}, pmid = {19178072}, issn = {0044-4677}, mesh = {Animals ; Animals, Newborn ; Avoidance Learning/drug effects ; Brain/metabolism ; Bromodeoxyuridine/pharmacology ; Chickens ; DNA/biosynthesis ; Idoxuridine/*pharmacology ; Imprinting, Psychological/drug effects ; Maze Learning/drug effects ; Memory/*drug effects ; Protein Synthesis Inhibitors/*pharmacology ; Taste Perception/drug effects/physiology ; }, abstract = {We tested the hypothesis that DNA synthesis is involved in molecular mechanisms of memory consolidation. Nucleotide analogs 5'-iodo- and 5'-bromo-2'-deoxyuridine impair DNA functions being incorporated into elongated DNA chain and cause amnesia in a number of training models in mice. We studied possible amnestic effects of 5'-iodo-2'-deoxyuridine (IdU) in different training models in newborn chicks--in passive avoidance, taste aversion, imprinting and spatial learning in a maze. In the taste aversion model injection of IdU (10 mg/kg 5 min before or 50 min after training) produced amnesia at test 1-2 days after training, at the same time it had no effect on memory retention in test 6 h after training. IdU injection 2 h after training produced no amnesia. Similar amnestic effect in taste aversion model was found for 5'-bromo-2'-deoxyuridine (BrdU). In models of imprinting, passive avoidance and spatial learning IdU injection before or after training had no effect on memory retention. These data presuppose that brain DNA synthesis might play a critical role in mechanisms of memory consolidation in taste aversion learning in chicks.}, } @article {pmid19171164, year = {2009}, author = {Disorbo, A and Wilson, GN and Bacik, S and Hoxha, Z and Biada, JM and Mickley, GA}, title = {Time-dependent retrograde amnesic effects of muscimol on conditioned taste aversion extinction.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {92}, number = {2}, pages = {319-326}, pmid = {19171164}, issn = {0091-3057}, support = {R15 MH063720-03/MH/NIMH NIH HHS/United States ; 2-R15-MH063720-03/MH/NIMH NIH HHS/United States ; }, mesh = {Amnesia/*chemically induced ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; GABA Agonists/*pharmacology ; Male ; Muscimol/*pharmacology ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {We explored how stimulation of GABA(A) receptors at different times during conditioned taste aversion (CTA) acquisition or extinction influenced extinction. In Experiment 1, rats acquired a CTA to 0.3% saccharin-flavored water (SAC) when it followed an injection of lithium chloride (LiCl; 81.0 mg/kg, i.p.). Following conditioning, rats received extinction training in which the GABA(A) agonist muscimol (1.0 mg/kg, i.p.), or control (saline) injections, were administered either before or after each extinction trial. Muscimol hindered extinction when administered after extinction trials. Muscimol's inhibitory effects may have impeded extinction learning by disrupting synaptic mechanisms required to consolidate information experienced during extinction training. In Experiment 2, we studied the effects of muscimol on CTA acquisition and subsequent extinction. Rats received muscimol (1.0 mg/kg, i.p.) either before or after CTA conditioning trials. Following CTA acquisition, all rats were given CTA extinction training without muscimol administration. All groups developed CTA, but the group that received muscimol before CTA conditioning trials extinguished rapidly in comparison to other treatment groups. Differences between muscimol's effects on CTA conditioning and CTA extinction indicate that fear conditioning and extinction involve, to some degree, different neuronal mechanisms.}, } @article {pmid19170438, year = {2009}, author = {Ruetti, E and Justel, N and Mustaca, AE and Papini, MR}, title = {Posttrial corticosterone administration enhances the effects of incentive downshift: exploring the boundaries of this effect.}, journal = {Behavioral neuroscience}, volume = {123}, number = {1}, pages = {137-144}, doi = {10.1037/a0013805}, pmid = {19170438}, issn = {0735-7044}, mesh = {Analysis of Variance ; Animals ; Association Learning/drug effects ; Conditioning, Operant/drug effects ; Consummatory Behavior/*drug effects ; Corticosterone/*administration & dosage ; Dose-Response Relationship, Drug ; Extinction, Psychological/*drug effects ; Food Preferences/drug effects ; Goals ; Male ; *Motivation ; Random Allocation ; Rats ; Rats, Wistar ; Sucrose/administration & dosage ; Sweetening Agents/administration & dosage ; }, abstract = {Posttrial administration of corticosterone was previously shown to enhance consummatory successive negative contrast (cSNC) in rats. The present series of experiments provides additional information that helps determine the boundaries of this effect. Posttrial corticosterone administration (1) enhances cSNC when rats experience a large downshift (32% to 4% sucrose), but not after a small downshift (8% to 4% sucrose; Experiment 1); (2) has no effect in an anticipatory negative contrast situation in which 4% sucrose precedes 32% sucrose in daily trials (Experiment 2); (3) does not support the development of a conditioned taste aversion to 4% sucrose, in the absence of an incentive downshift (Experiment 3); and (4) facilitates the extinction of consummatory behavior (Experiment 4). These results suggest that corticosterone facilitates the encoding of an egocentric aversive memory of the incentive downshift experience.}, } @article {pmid19158296, year = {2009}, author = {Johnson, AW and Gallagher, M and Holland, PC}, title = {The basolateral amygdala is critical to the expression of pavlovian and instrumental outcome-specific reinforcer devaluation effects.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {29}, number = {3}, pages = {696-704}, pmid = {19158296}, issn = {1529-2401}, support = {R01 MH060179/MH/NIMH NIH HHS/United States ; R01 MH060179-09/MH/NIMH NIH HHS/United States ; MH60179/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/injuries/*physiology ; Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Choice Behavior ; Conditioning, Classical/*physiology ; Conditioning, Operant/*physiology ; *Extinction, Psychological ; Male ; Rats ; Rats, Long-Evans ; *Reinforcement, Psychology ; }, abstract = {Considerable evidence implicates the basolateral amygdala (BLA) in the formation of outcome representations that link cues to the incentive properties of reinforcers. Animals with BLA damage show impaired performance in reinforcer devaluation tasks, in which the value of the food reinforcer is reduced by satiation or food-toxin pairings after the completion of cue or response training. Although intact animals spontaneously reduce their conditioned responding after such reinforcer devaluation procedures, animals with BLA lesions made before training typically do not, as evidenced across a range of species, training contingencies, and devaluation procedures. In contrast, the role of the BLA in devaluation task performance once such outcome representations are established is unclear. Whereas Pickens et al. (2003) found normal devaluation performance in rats when BLA lesions were made after pavlovian light-food pairings but before devaluation by food-toxin pairings, Ostlund and Balleine (2008) found impaired devaluation performance when BLA lesions were made after instrumental training with multiple instrumental responses and food reinforcers but before devaluation of one reinforcer by selective satiation. Those studies differed in their use of pavlovian or operant training contingencies, single or multiple reinforcers, and associative or motivational devaluation procedures. Here we found that, when multiple reinforcers were used, posttraining BLA lesions disrupted the expression of devaluation performance in rats, using either pavlovian or instrumental training procedures and either conditioned taste aversion or satiation devaluation procedures. Thus, BLA apparently plays a critical role in maintaining or using sensory associations of reinforcer value when multiple outcomes must be coded but not under single-outcome conditions.}, } @article {pmid19150440, year = {2009}, author = {Roman, C and Lin, JY and Reilly, S}, title = {Conditioned taste aversion and latent inhibition following extensive taste preexposure in rats with insular cortex lesions.}, journal = {Brain research}, volume = {1259}, number = {}, pages = {68-73}, pmid = {19150440}, issn = {1872-6240}, support = {R01 DC004341/DC/NIDCD NIH HHS/United States ; DC04341/DC/NIDCD NIH HHS/United States ; R01 DC006456-03/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; R01 DC006456/DC/NIDCD NIH HHS/United States ; R01 DC004341-05/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; *Conditioning, Psychological ; Drinking Behavior/physiology ; *Food Preferences ; Limbic System/physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; Taste/*physiology ; Temporal Lobe/*physiopathology ; }, abstract = {Lesions of the insular cortex (IC) attenuate acquisition of conditioned taste aversions (CTAs). We have suggested that this impairment is the expected consequence of a failure of IC-lesioned (ICX) rats to recognize unfamiliar taste stimuli as novel. That is, ICX rats treat novel taste stimuli as if they are familiar and as a result show a latent inhibition-like retardation of learning. This account anticipates that ICX rats should acquire CTAs at the same slow rate as normal rats that are familiar with the taste stimulus. The present experiment confirmed this hypothesis in a design that compared CTA acquisition in normal and ICX rats following either extensive taste familiarization or no taste familiarization prior to conditioning.}, } @article {pmid19146964, year = {2009}, author = {Smith, AM and Chen, WJ}, title = {Neonatal amphetamine exposure and hippocampus-mediated behaviors.}, journal = {Neurobiology of learning and memory}, volume = {91}, number = {3}, pages = {207-217}, pmid = {19146964}, issn = {1095-9564}, support = {F31 DA018809/DA/NIDA NIH HHS/United States ; F31 DA018809-03/DA/NIDA NIH HHS/United States ; DA018809/DA/NIDA NIH HHS/United States ; }, mesh = {Amphetamine/*toxicity ; Analysis of Variance ; Animals ; Animals, Newborn ; Behavior, Animal/drug effects ; Conditioning, Psychological/*drug effects ; Exploratory Behavior/drug effects ; Female ; Food Preferences ; Hippocampus/*drug effects/physiology ; Male ; Maze Learning/*drug effects ; Memory/*drug effects ; Motor Activity/drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sex Factors ; Task Performance and Analysis ; }, abstract = {Previous studies linking amphetamine use during pregnancy to changes in the behavioral development of affected infants have greatly increased society's level of concern regarding amphetamine use by women of reproductive age. The aim of this study was to investigate whether exposure to d-amphetamine sulfate during the brain growth spurt, the most dynamic period of brain development, alters hippocampus-mediated behaviors during both pre-adolescence and young adulthood. Sprague-Dawley rat pups were intragastrically administered a milk formula containing 0, 5, 15 or 25 mg/kg/day of amphetamine from postnatal day (PD) 4-9. Following weaning, the effects of neonatal amphetamine exposure on hippocampus-mediated behaviors were assessed using the open-field, the water maze, and the conditioned taste aversion behavioral tasks. Results from these behavioral tests revealed that while amphetamine exposure during the brain growth spurt alters behaviors in open-field testing, it does not interfere with performance in either the water maze or the conditioned taste aversion paradigm. These results offer speculation that the effects of neonatal amphetamine exposure on hippocampus-mediated behaviors may be related to interactions between the "temporal" (time of drug exposure) and "regional" (different regions of the hippocampus) vulnerability issues.}, } @article {pmid19100809, year = {2009}, author = {Mierzejewski, P and Korkosz, A and Rogowski, A and Korkosz, I and Kostowski, W and Scinska, A}, title = {Post-session injections of a protein synthesis inhibitor, cycloheximide do not alter saccharin self-administration.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {33}, number = {2}, pages = {286-289}, doi = {10.1016/j.pnpbp.2008.11.015}, pmid = {19100809}, issn = {0278-5846}, mesh = {Analysis of Variance ; Animals ; Conditioning, Operant/drug effects ; Cycloheximide/*pharmacology ; Extinction, Psychological/drug effects ; Food Preferences/*drug effects ; Male ; Protein Synthesis Inhibitors/*pharmacology ; Rats ; Rats, Wistar ; Saccharin/*pharmacology ; Self Administration ; Sweetening Agents/*pharmacology ; }, abstract = {A large body of evidence indicates that reactivation of aversive memories leads to protein synthesis-dependent memory reconsolidation which can be disrupted by cycloheximide (CHX) and other protein synthesis inhibitors. The aim of the present study was to investigate whether CHX would alter maintenance of well-trained instrumental responding for 0.1% saccharin. Male Wistar rats were trained to lever press for saccharin. When lever pressing stabilized, experimental self-administration sessions with CHX (3 mg/kg, s.c.) started. The animals received four experimental sessions, with each session separated by 5 days. The protein synthesis inhibitor was injected immediately after the experimental sessions 1-3. Repeated post-session injections of CHX did not alter saccharin self-administration. A two-bottle choice test conducted after the last experimental session revealed that CHX had not induced any conditioned taste aversion to 0.1% saccharin. The present results suggest that well-consolidated long-term memory of an appetitive instrumental task does not depend on de novo protein synthesis.}, } @article {pmid19097273, year = {2008}, author = {Houchi, H and Warnault, V and Barbier, E and Dubois, C and Pierrefiche, O and Ledent, C and Daoust, M and Naassila, M}, title = {Involvement of A2A receptors in anxiolytic, locomotor and motivational properties of ethanol in mice.}, journal = {Genes, brain, and behavior}, volume = {7}, number = {8}, pages = {887-898}, doi = {10.1111/j.1601-183x.2008.00427.x}, pmid = {19097273}, issn = {1601-183X}, mesh = {Adenosine/*metabolism ; Alcohol-Induced Disorders, Nervous System/*genetics/metabolism/physiopathology ; Animals ; Anti-Anxiety Agents/pharmacology ; Anxiety/drug therapy/genetics/metabolism ; Behavior, Animal/drug effects/physiology ; Brain/*drug effects/metabolism/physiopathology ; Central Nervous System Depressants/pharmacology ; Conditioning, Psychological/drug effects/physiology ; Disease Models, Animal ; Drug Resistance/drug effects/genetics ; Ethanol/*pharmacology ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motivation ; Motor Activity/drug effects/physiology ; Receptor, Adenosine A2A/*drug effects/metabolism ; Species Specificity ; }, abstract = {We have shown previously that mice lacking the adenosine A2A receptor (A2AR) generated on a CD1 background self-administer more ethanol and exhibit hyposensitivity to acute ethanol. We aimed to investigate if the increased propensity of A2A(-/-) mice to consume ethanol is associated with an altered sensitivity in the motivational properties of ethanol in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms and with an altered development of sensitization to the locomotor effects of ethanol. We also tested their sensitivity to the anxiolytic effects of ethanol. Our results show that A2A(-/-) mice produced on a CD1 background displayed a reduced ethanol-induced CPP and an increased sensitivity to the anxiolytic and locomotorstimulant effects of ethanol, but they did not show alteration in ethanol-induced CTA and locomotor sensitization. Ethanol-induced CPP, ethanol consumption and the locomotor effects of ethanol were also tested in A2A(-/-) mice produced on a C57BL/6J background. Our results emphasized the importance of the genetic background because alteration in ethanol consumption and preference, ethanol-induced CPP and locomotor-stimulant effects were not found in knockout mice produced on the alcohol-preferring C57BL/6J genetic background. Finally, the A2AR agonist, 2-p-(2-carboxyethyl)-phenylethylamino-50-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice. In conclusion, A2AR deficiency in mice generated on a CD1 background leads to high ethanol consumption that is associated with an increased sensitivity to the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in ethanol-induced CPP.}, } @article {pmid19095011, year = {2009}, author = {Cabanac, M and Cabanac, AJ and Parent, A}, title = {The emergence of consciousness in phylogeny.}, journal = {Behavioural brain research}, volume = {198}, number = {2}, pages = {267-272}, doi = {10.1016/j.bbr.2008.11.028}, pmid = {19095011}, issn = {1872-7549}, mesh = {Animals ; Brain/*anatomy & histology/*physiology ; Consciousness/*physiology ; Decision Making/physiology ; Dopamine/metabolism ; Emotions/*physiology ; Neurotransmitter Agents/biosynthesis/*metabolism/physiology ; *Phylogeny ; Sleep/physiology ; Species Specificity ; }, abstract = {The brains of animals show chemical, anatomical, and functional differences, such as dopamine production and structure of sleep, between Amniota and older groups. In addition, play behavior, capacity to acquire taste aversion, sensory pleasure in decision making, and expression of emotional tachycardia and fever started also to be displayed by Amniota, suggesting that the brain may have began to work differently in early Amniota than in Lissamphibia and earlier vertebrates. Thus we propose that emotion, and more broadly speaking consciousness, emerged in the evolutionary line among the early Amniota. We also propose that consciousness is characterized by a common mental pathway that uses pleasure, or its counterpart displeasure, as a means to optimize behavior.}, } @article {pmid19091953, year = {2008}, author = {Barot, SK and Kyono, Y and Clark, EW and Bernstein, IL}, title = {Visualizing stimulus convergence in amygdala neurons during associative learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {52}, pages = {20959-20963}, pmid = {19091953}, issn = {1091-6490}, support = {R01 NS037040/NS/NINDS NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/cytology/*metabolism ; Animals ; In Situ Hybridization/methods ; Male ; Memory/*physiology ; Neurons/cytology/*metabolism ; Rats ; Rats, Long-Evans ; Transcription, Genetic/*physiology ; }, abstract = {A central feature of models of associative memory formation is the reliance on information convergence from pathways responsive to the conditioned stimulus (CS) and unconditioned stimulus (US). In particular, cells receiving coincident input are held to be critical for subsequent plasticity. Yet identification of neurons in the mammalian brain that respond to such coincident inputs during a learning event remains elusive. Here we use Arc cellular compartmental analysis of temporal gene transcription by fluorescence in situ hybridization (catFISH) to locate populations of neurons in the mammalian brain that respond to both the CS and US during training in a one-trial learning task, conditioned taste aversion (CTA). Individual neurons in the basolateral nucleus of the amygdala (BLA) responded to both the CS taste and US drug during conditioning. Coincident activation was not evident, however, when stimulus exposure was altered so as to be ineffective in promoting learning (backward conditioning, latent inhibition). Together, these data provide clear visualization of neurons in the mammalian brain receiving convergent information about the CS and US during acquisition of a learned association.}, } @article {pmid19059225, year = {2009}, author = {Lin, JY and Roman, C and St Andre, J and Reilly, S}, title = {Taste, olfactory and trigeminal neophobia in rats with forebrain lesions.}, journal = {Brain research}, volume = {1251}, number = {}, pages = {195-203}, pmid = {19059225}, issn = {1872-6240}, support = {R01 DC004341/DC/NIDCD NIH HHS/United States ; DC04341/DC/NIDCD NIH HHS/United States ; R01 DC006456-03/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; R01 DC006456/DC/NIDCD NIH HHS/United States ; R01 DC004341-05/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/anatomy & histology/physiology ; Animals ; Avoidance Learning/*physiology ; Capsaicin/pharmacology ; Cerebral Cortex/anatomy & histology/physiology ; Denervation ; Disease Models, Animal ; Male ; Neuropsychological Tests ; Pain/*physiopathology/psychology ; Pentanols/pharmacology ; Phobic Disorders/etiology/*physiopathology/psychology ; Physical Stimulation ; Prosencephalon/anatomy & histology/*physiology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Smell/*physiology ; Taste/*physiology ; }, abstract = {The present study was designed to examine whether lesions of the insular cortex (IC; Experiment 1), the basolateral amygdala (BLA) or medial amygdala (MeA; Experiment 2) influence the neophobic reactions to orally consumed liquid stimuli. Three different types of stimuli were used: taste (0.5% saccharin), olfactory (0.1% amyl acetate), and trigeminal (0.01 mM capsaicin). Rats with IC, BLA and MeA lesions showed normal responses to the olfactory and trigeminal stimuli. Each type of lesion, however, disrupted the initial occurrence of neophobia to the taste stimulus. The significance of these findings to conditioned taste aversion is discussed.}, } @article {pmid19047011, year = {2009}, author = {Ishitobi, S and Ayuse, T and Yoshida, H and Oi, K and Toda, K and Miyamoto, T}, title = {Effects of midazolam on acquisition and extinction of conditioned taste aversion memory in rats.}, journal = {Neuroscience letters}, volume = {450}, number = {3}, pages = {270-274}, doi = {10.1016/j.neulet.2008.11.044}, pmid = {19047011}, issn = {0304-3940}, mesh = {Adrenergic alpha-2 Receptor Antagonists ; Adrenergic alpha-Antagonists/pharmacology ; Animals ; Avoidance Learning/*drug effects/physiology ; Brain/drug effects/metabolism ; Conditioning, Psychological/*drug effects/physiology ; Extinction, Psychological/*drug effects/physiology ; GABA Modulators/pharmacology ; Male ; Memory/*drug effects/physiology ; Midazolam/*pharmacology ; Neural Inhibition/drug effects/physiology ; Norepinephrine/metabolism ; Rats ; Rats, Wistar ; Receptors, Adrenergic, alpha-2/metabolism ; Synaptic Transmission/drug effects/physiology ; Yohimbine/pharmacology ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {Some intravenous anesthetic agents such as midazolam are known to induce anterograde and retrograde amnesia. We analyzed the effect of midazolam by the conditioned taste aversion (CTA) acquisition and retention. After the rats were offered 0.1% sodium saccharin (Sac) as conditioned stimulus (CS), an intraperitoneal (i.p.) injection of several concentrations (5-30mg/kg) of midazolam was followed by an i.p. injection of 0.15M LiCl (2% of body weight) as unconditioned stimulus (US). The rats, which acquired CTA by every CS-US paradigm, strongly avoided Sac on the 1st test day after conditioning and maintained the avoidance for 3 days. We have already reported that Sac intake abruptly increased on the 2nd test day and the almost complete extinction occurred on the 3rd test day after conditioning by injection of subhypnotic dose of propofol before LiCl-injection. In contrast, we found that subhypnotic dose of midazolam suppressed not only CTA acquisition, but also CTA retention. On the other hand, an alpha2-adrenergic blocker, yohimbin (1mg/kg) suppressed only the CTA retention. These results suggest that the subhypnotic doses of midazolam firstly affect the acquisition mechanism of the CTA memory (CTAM), resulting the suppression of the retention of CTAM.}, } @article {pmid19045958, year = {2008}, author = {Grigson, PS}, title = {The state of the reward comparison hypothesis: theoretical comment on Huang and Hsiao (2008).}, journal = {Behavioral neuroscience}, volume = {122}, number = {6}, pages = {1383-1390}, pmid = {19045958}, issn = {0735-7044}, support = {DA09815/DA/NIDA NIH HHS/United States ; R37 DA009815/DA/NIDA NIH HHS/United States ; R01 DA009815/DA/NIDA NIH HHS/United States ; R01 DA012473/DA/NIDA NIH HHS/United States ; DA12473/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal ; *Conditioning, Psychological ; Food Preferences ; Humans ; *Psychological Theory ; *Reward ; }, abstract = {Rats avoid intake of a gustatory cue following pairings with a drug of abuse, such as morphine or cocaine. Despite the well-established rewarding properties of these drugs, the reduction in intake of the taste cue has been interpreted as a conditioned taste aversion for decades. In 1997, I proposed the reward comparison hypothesis suggesting that rats avoided intake of the drug-associated taste cue because the value of the taste cue pales in comparison to the highly rewarding drug of abuse expected in the near future. In this issue of Behavioral Neuroscience, A. C. W. Huang and S. Hsiao challenge the reward comparison hypothesis by showing parallels between amphetamine and LiCl-induced suppression of CS intake. This commentary addresses the current state of the reward comparison hypothesis in the context of the experiments completed by Huang and Hsiao and their new task-dependent drug effects hypothesis.}, } @article {pmid19045940, year = {2008}, author = {Huang, AC and Hsiao, S}, title = {Re-examination of amphetamine-induced conditioned suppression of tastant intake in rats: the task-dependent drug effects hypothesis.}, journal = {Behavioral neuroscience}, volume = {122}, number = {6}, pages = {1207-1216}, doi = {10.1037/a0013511}, pmid = {19045940}, issn = {0735-7044}, mesh = {Amphetamine/*pharmacology ; Analysis of Variance ; Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Food Deprivation ; Food Preferences/*drug effects ; *Inhibition, Psychological ; Lithium Chloride/pharmacology ; Male ; *Psychological Theory ; Rats ; Rats, Sprague-Dawley ; Reward ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/*drug effects ; }, abstract = {This study reexamined Grigson's reward comparison hypothesis (1997), which claimed to have resolved the paradox of addictive, rewarding drugs manifesting an aversive effect in the conditioned taste aversion (CTA) paradigm. Here, the authors compared the conditioned suppression effects of lithium chloride (LiCl) and amphetamine in a series of three experiments. In Experiment 1, the concentrations of saccharin solution (conditioned stimulus [CS]) and the doses of amphetamine or LiCl (unconditioned stimulus [US]) were manipulated. In Experiment 2, the effects of employing backward versus forward pairings of the CS and US were compared. Finally, in Experiment 3, the additivity of amphetamine's reward property and LiCl's aversive property was examined. The results of these experiments, respectively, indicated that: (1) manipulating saccharin solution concentrations does not distinguish the suppression effect caused by rewarding or aversive effects when amphetamine or LiCl served as the US; (2) both backward and forward pairings produced suppression of saccharin solution intake regardless of whether amphetamine or LiCl was used as the US; and (3) combining amphetamine and LiCl did not diminish the suppression effect, as would be expected if they had opposing mechanisms for the effects; instead, an additive effect occurred. Taken together, these results suggest that the drug of abuse amphetamine and the emetic drug LiCl both possess aversive properties in the CTA paradigm. No rewarding effects of amphetamine were detected in our experimental data. In all, our results do not support the Grigson's reward comparison hypothesis (1997) and a new "task-dependent drug effects hypothesis" is proposed.}, } @article {pmid19041747, year = {2008}, author = {Gillum, MP and Zhang, D and Zhang, XM and Erion, DM and Jamison, RA and Choi, C and Dong, J and Shanabrough, M and Duenas, HR and Frederick, DW and Hsiao, JJ and Horvath, TL and Lo, CM and Tso, P and Cline, GW and Shulman, GI}, title = {N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake.}, journal = {Cell}, volume = {135}, number = {5}, pages = {813-824}, pmid = {19041747}, issn = {1097-4172}, support = {R01 DK049230/DK/NIDDK NIH HHS/United States ; U24 DK076169/DK/NIDDK NIH HHS/United States ; R01 DK-40936/DK/NIDDK NIH HHS/United States ; R01 DK040936/DK/NIDDK NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; U24 DK-76169/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P30 DK045735-119001/DK/NIDDK NIH HHS/United States ; U24 DK059635/DK/NIDDK NIH HHS/United States ; R01 DK040936-11/DK/NIDDK NIH HHS/United States ; P30 DK-45735/DK/NIDDK NIH HHS/United States ; R24 DK085638/DK/NIDDK NIH HHS/United States ; U24 DK076169-03/DK/NIDDK NIH HHS/United States ; }, mesh = {Amides ; Animals ; *Appetite Regulation ; Body Weight ; Dietary Fats/metabolism ; Endocannabinoids ; Ethanolamines ; Hypothalamus/metabolism ; Intestine, Small/metabolism ; Mice ; Mice, Obese ; Motor Activity ; Obesity/metabolism ; Palmitic Acids/metabolism ; Phosphatidylethanolamines/blood/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Tandem Mass Spectrometry ; }, abstract = {N-acylphosphatidylethanolamines (NAPEs) are a relatively abundant group of plasma lipids of unknown physiological significance. Here, we show that NAPEs are secreted into circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats without causing conditioned taste aversion. Furthermore, (14)C-radiolabeled NAPE enters the brain and is particularly concentrated in the hypothalamus, and intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake, collectively suggesting that its effects may be mediated through direct interactions with the central nervous system. Finally, chronic NAPE infusion results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogs may be novel therapeutic targets for the treatment of obesity.}, } @article {pmid19037784, year = {2008}, author = {St-Pierre, LS and Persinger, MA}, title = {Behavioral changes in adult rats after prenatal exposures to complex, weak magnetic fields.}, journal = {Electromagnetic biology and medicine}, volume = {27}, number = {4}, pages = {355-364}, doi = {10.1080/15368370802493396}, pmid = {19037784}, issn = {1536-8386}, mesh = {Animals ; Behavior, Animal/*radiation effects ; Conditioning, Psychological/radiation effects ; *Electromagnetic Fields ; Fear/radiation effects ; Female ; Male ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; Taste Perception/radiation effects ; Time Factors ; }, abstract = {More than 100 adult male and female albino Wistar rats that had been exposed during their entire prenatal development to one of two patterns of magnetic fields and one of four intensities (reference: 5 to 20 nT; low: 30 to 50 nT; medium: 90 to 580 nT; high: 590 nT to 1.2 microT) were tested for their capacity for two forms of classical conditioning. The rats exposed for 10 sec every 50 sec to a field composed of successive 200 msec sequences of several different patterns known to produce physiological effects exhibited significantly more intense conditioned fear and taste aversion than those exposed continuously to a single frequency-modulated pattern. The behavioral differences, relative to the reference group ("controls"), were greatest for rats exposed to the 30 to 50 nT or 90 to 580 nT (low to medium intensities) for both patterns of fields. These results suggest that prenatal exposure to physiologically-patterned magnetic fields within a specific "window" of intensities that overlap with values found in many human habitats may produce long-term changes in behaviors.}, } @article {pmid19016240, year = {2009}, author = {Manrique, T and Gámiz, F and Morón, I and Ballesteros, MA and Gallo, M}, title = {Peculiar modulation of taste aversion learning by the time of day in developing rats.}, journal = {Developmental psychobiology}, volume = {51}, number = {2}, pages = {147-157}, doi = {10.1002/dev.20354}, pmid = {19016240}, issn = {1098-2302}, mesh = {Affect ; Animals ; *Circadian Rhythm ; Conditioning, Psychological ; Habituation, Psychophysiologic ; *Learning ; Male ; Random Allocation ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {The ontogeny of the temporal context modulation of conditioned taste aversion was studied in male Wistar rats using a palatable 1% NaCl solution. A procedure that included two saline preexposures, a single pairing saline-lithium chloride (0.15 M; 1% b.w.) either at the same or a different time of day of preexposures and a one-bottle test at the same time than preexposure was applied. Four age groups (PN32, PN48, PN64, and PN100) covering the complete range from adolescence to the adult period were tested. The results showed no effect of a temporal context shift in PN32. A peculiar enhancement of temporal context-specific saline aversions was exhibited by PN48 and PN64 rats, while the adult typical temporal context specificity of latent inhibition was only evident in PN100 rats. The results are discussed in terms of the peculiar brain functional organization during a protracted adolescence period.}, } @article {pmid19000706, year = {2009}, author = {Stephens, MK and Riley, AL}, title = {Naloxone-precipitated conditioned taste aversions in morphine-dependent Fischer (F344) and Lewis rat strains.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {92}, number = {1}, pages = {60-67}, doi = {10.1016/j.pbb.2008.10.011}, pmid = {19000706}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Body Weight/drug effects ; Conditioning, Operant/drug effects ; Extinction, Psychological/drug effects ; Morphine Dependence/*psychology ; Naloxone/*pharmacology ; Narcotic Antagonists/*pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Species Specificity ; Taste/*drug effects ; }, abstract = {The Fischer 344 (F344) and Lewis (LEW) rat strains are genetically divergent populations that are used to study the effects of and responses to drugs of abuse. In this context, LEW rats display faster acquisition of drug self-administration than F344 rats. Interestingly, these strains have also been reported to differ in their somatic responses to morphine withdrawal. To address possible strain differences in the affective response to withdrawal, the present study assessed the ability of naloxone-precipitated withdrawal from morphine to induce conditioned taste aversions in male F344 and LEW rats. Specifically, subjects from each of these strains were given chronic morphine to induce dependence and then given access to a novel saccharin solution followed by naloxone. These pairings were given every fourth day for a total of two conditioning trials after which subjects were given access to saccharin but without naloxone administration to assess extinction of the naloxone-induced aversion. Behavioral assays of withdrawal were also performed after each naloxone administration. Both F344 and LEW subjects acquired aversions to the naloxone-associated taste with no significant differences in the rate of acquisition of the aversions. Differences did appear during extinction with LEW animals extinguishing the taste aversion significantly faster than F344 animals. The data were discussed in terms of the relative strength of the affective responses during withdrawal and the role of such responses to drug use and abuse.}, } @article {pmid18973564, year = {2008}, author = {De la Cruz, V and Rodriguez-Ortiz, CJ and Balderas, I and Bermudez-Rattoni, F}, title = {Medial temporal lobe structures participate differentially in consolidation of safe and aversive taste memories.}, journal = {The European journal of neuroscience}, volume = {28}, number = {7}, pages = {1377-1381}, doi = {10.1111/j.1460-9568.2008.06432.x}, pmid = {18973564}, issn = {1460-9568}, mesh = {Amygdala/anatomy & histology/drug effects/*metabolism ; Animals ; Anisomycin/pharmacology ; Avoidance Learning/drug effects/*physiology ; Hippocampus/anatomy & histology/drug effects/*metabolism ; Male ; Memory/drug effects/*physiology ; Nerve Net/drug effects/metabolism ; Nerve Tissue Proteins/antagonists & inhibitors/biosynthesis ; Parahippocampal Gyrus/anatomy & histology/drug effects/metabolism ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Wistar ; Taste/drug effects/*physiology ; }, abstract = {Taste memories are amongst the most important kinds of memories, as adequate identification of safe and toxic edibles will determine the subject's survival. Despite the well-established role that the medial temporal lobe plays in consolidation of memory, specific contributions of the different regions of the temporal lobe to taste memory consolidation remain unknown. In the present report, we assessed the participation of perirhinal cortex (Ph), dorsal hippocampus (Hipp), basolateral (BLA) and central nuclei of the amygdala (CeA) in safe and aversive taste memories by means of local infusions of the protein synthesis inhibitor anisomycin in the rat. The results showed that protein synthesis in the CeA, but not BLA, is required to stabilize taste aversion memory. Surprisingly, the Ph and Hipp seem to be essential to consolidate safe taste memory. These data suggest that different networks within the temporal lobe are recruited to consolidate memory depending on the consequences associated with tastes.}, } @article {pmid18958188, year = {2007}, author = {Poirier, R and Cheval, H and Mailhes, C and Charnay, P and Davis, S and Laroche, S}, title = {Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory.}, journal = {Frontiers in behavioral neuroscience}, volume = {1}, number = {}, pages = {6}, pmid = {18958188}, issn = {1662-5153}, abstract = {It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain.}, } @article {pmid18948144, year = {2009}, author = {Clark, EW and Bernstein, IL}, title = {Establishing aversive, but not safe, taste memories requires lateralized pontine-cortical connections.}, journal = {Behavioural brain research}, volume = {197}, number = {2}, pages = {356-363}, pmid = {18948144}, issn = {1872-7549}, support = {R01 NS037040/NS/NINDS NIH HHS/United States ; R01 NS037040-04A1/NS/NINDS NIH HHS/United States ; R01 NS037040-05/NS/NINDS NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/anatomy & histology/metabolism/physiology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/anatomy & histology/metabolism/*physiology ; Conditioning, Operant/physiology ; Functional Laterality/physiology ; Immunohistochemistry ; Male ; Memory/*physiology ; Pons/anatomy & histology/metabolism/*physiology ; Prosencephalon/anatomy & histology/metabolism/physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Long-Evans ; Signal Transduction/physiology ; Taste/*physiology ; }, abstract = {Aversive and safe taste memory processing is dramatically disrupted by bilateral lesions of the pontine parabrachial nucleus (PBN). To determine how such lesions affect patterns of neuronal activation in forebrain, lesions were combined with assessment of cFos-like immunoreactivity (FLI) in insular cortex (IC) and amygdala after conditioned taste aversion (CTA) training. Increases in FLI in amygdala and IC, which are normally seen following novel (versus familiar) CS-US pairing, were eliminated after PBN lesions. This suggests that PBN lesions prevent transmission of critical CS and US information to forebrain regions for the processing of both aversive and safe taste memories. Unilateral asymmetrical lesions of PBN and IC blocked CTA acquisition as well as normal patterns of FLI in amygdala after novel CS-US pairing, an effect not seen when unilateral lesions were confined to a single hemisphere. The crossed-disconnection experiments provide compelling evidence that functional interactions between PBN and IC are required for CTA acquisition, but not for safe taste memory formation and retrieval. The dissociation between effects of the different types of lesions on safe and aversive taste memories supports emerging evidence that the neural underpinnings of the two types of taste learning differ.}, } @article {pmid18930757, year = {2009}, author = {Davenport, RA and Houpt, TA}, title = {D-cycloserine enhances short-delay, but not long-delay, conditioned taste aversion learning in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {91}, number = {4}, pages = {596-603}, pmid = {18930757}, issn = {0091-3057}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; R01 DC003198-08/DC/NIDCD NIH HHS/United States ; DC03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Operant/*drug effects ; Cycloserine/*pharmacology ; Glycine/pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/drug effects ; Reinforcement Schedule ; Taste/*drug effects ; Time Factors ; }, abstract = {NMDA receptors have been implicated in conditioned taste aversion (CTA), a form of associative learning with the unique temporal characteristic of associating taste and toxic stimuli across very long delays. d-cycloserine (DCS), an NMDA receptor agonist, has been shown to enhance short-delay CTA learning. Here we examined the interaction of DCS with varying temporal parameters of CTA. DCS (15 mg/kg) administered prior to the pairing of 0.125% saccharin and LiCl (38 mM, 12 ml/kg) enhanced CTA when there was a short delay between the taste-toxin pairing (10 min), but not when there was a long delay (45 min). DCS activity remained at effective levels over the long delay, because DCS administered 60 min prior to a short-delay pairing enhanced CTA. The interaction of DCS with the delay between taste stimulus onset and LiCl injection was investigated by administering DCS and then 5 min access to saccharin 45 min prior to a short-delay pairing of saccharin and LiCl. DCS failed to enhance CTA in rats pre-exposed to saccharin, even with a short delay between the second saccharin exposure and LiCl injection. These results suggest that DCS enhancement of CTA is dependent on mechanisms underlying gustatory processing during long-delay taste-toxin associations.}, } @article {pmid18853399, year = {2009}, author = {Haksar, A and Sharma, A and Chawla, R and Kumar, R and Lahiri, SS and Islam, F and Arora, MP and Sharma, RK and Tripathi, RP and Arora, R}, title = {Mint oil (Mentha spicata Linn.) offers behavioral radioprotection: a radiation-induced conditioned taste aversion study.}, journal = {Phytotherapy research : PTR}, volume = {23}, number = {2}, pages = {293-296}, doi = {10.1002/ptr.2604}, pmid = {18853399}, issn = {1099-1573}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Gamma Rays/*adverse effects ; Male ; Mentha/*chemistry ; Plant Oils/*pharmacology ; Radiation-Protective Agents/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Taste/*radiation effects ; }, abstract = {Mentha spicata Linn. (mint), a herb well known for its gastroprotective properties in the traditional system of medicine has been shown to protect against radiation-induced lethality, and recently its constituents have been found to possess calcium channel antagonizing properties. The present study examined the behavioral radioprotective efficacy of mint oil (obtained from Mentha spicata), particularly in mitigating radiation-induced conditioned taste aversion (CTA), which has been proposed as a behavioral endpoint that is mediated by the toxic effects of gamma radiation on peripheral systems, primarily the gastrointestinal system in the Sprague-Dawley rat model. Intraperitoneal administration of Mentha spicata oil 10% (v/v), 1 h before 2 Gy gamma radiation, was found to render significant radioprotection against CTA (p < 0.05), by blocking the saccharin avoidance response within 5 post-treatment observational days, with the highest saccharin intake being observed on day 5. This finding clearly demonstrates that gastroprotective and calcium channel antagonizing properties of Mentha spicata can be effectively utilized in preventing radiation-induced behavioral changes.}, } @article {pmid18835568, year = {2009}, author = {Metzger, MM and Riccio, DC}, title = {The forgetting of stimulus attributes in latent inhibition.}, journal = {Physiology & behavior}, volume = {96}, number = {1}, pages = {194-198}, doi = {10.1016/j.physbeh.2008.09.012}, pmid = {18835568}, issn = {0031-9384}, support = {MH37535/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Association Learning ; Avoidance Learning/*physiology ; Behavior, Animal ; *Inhibition, Psychological ; Male ; Memory Disorders/*physiopathology ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology/physiology ; Sucrose/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/physiology ; }, abstract = {Numerous studies have demonstrated that the forgetting of stimulus attributes is a common occurrence; that is, organisms forget the specific characteristics of training stimuli over long retention intervals, while retaining general information of the training stimuli themselves. However, most studies have examined this effect after a learning episode, and there have been virtually no accounts to test whether the forgetting of attributes occurs for stimuli presented prior to training. Therefore, this experiment was designed to test that possibility, and it examined whether the forgetting of stimulus attributes occurred prior to training for the flavor stimulus in a conditioned taste aversion (CTA) procedure. Specifically, a latent inhibition (LI) procedure was used to measure the extent of forgetting for a pre-exposed flavor over short and long retention intervals. The results indicate that rats forgot the specific characteristics of the flavor stimulus (CS) while retaining memory for pre-exposure sessions over a long retention interval. That is, subjects pre-exposed and conditioned with different concentrations of sucrose showed no LI effect with a 1-day delay between pre-exposure and training, but demonstrated a generalized LI with an 8-day delay between pre-exposure and conditioning. This experiment provides further evidence for the robustness of the forgetting of stimulus attributes, and demonstrates that this specific type of forgetting also occurs prior to the learning of a CTA task.}, } @article {pmid18835436, year = {2009}, author = {Cross-Mellor, SK and Foley, KA and Parker, LA and Ossenkopp, KP}, title = {Lipopolysaccharide dose dependently impairs rapid toxin (LiCl)-induced gustatory conditioning: a taste reactivity examination of the conditioned taste aversion.}, journal = {Brain, behavior, and immunity}, volume = {23}, number = {2}, pages = {204-216}, doi = {10.1016/j.bbi.2008.09.006}, pmid = {18835436}, issn = {1090-2139}, mesh = {Administration, Oral ; Animals ; Association Learning/drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/*drug effects/*physiology ; Conditioning, Operant/*drug effects/physiology ; Dose-Response Relationship, Drug ; Endotoxins/administration & dosage/toxicity ; Habituation, Psychophysiologic/drug effects ; Lipopolysaccharides/administration & dosage/*toxicity ; Lithium Chloride/administration & dosage/*toxicity ; Male ; Rats ; Rats, Long-Evans ; Sodium Chloride/administration & dosage ; Sucrose/administration & dosage ; Taste/drug effects/immunology/*physiology ; }, abstract = {There is much debate on how immune activation affects cognitive processing. Research has shown that stimulation of the immune system can significantly impair, have no adverse effects, or enhance learning and memory processes in animals. The present experiment evaluated the effects of the bacterial endotoxin, lipopolysaccharide (LPS) on the acquisition of a rapidly acquired conditioned taste aversion using a toxin-containing food. Male Long Evans rats were fitted with intraoral cannulae and habituated to the taste reactivity procedure. Rats received two conditioning days, 72 h apart, in which they were injected systemically with LPS (200, 100, or 50 microg/kg) or NaCl (0.9% vehicle) and 90 min later placed in the taste reactivity test chamber. Rats were given 5 brief (1 min) intraoral infusions of either a LiCl-adulterated sucrose solution (0.15M LiCl+0.3M sucrose) or NaCl-sucrose solution (0.15M NaCl+0.3M sucrose) across a 1h period. On the test day (72 h after the last conditioning trial), rats were given a 2 min intraoral infusion of the respective taste in a drug-free state. Individual taste reactivity responses were recorded and analyzed. Results demonstrate that rats treated with LPS dose-dependently increased ingestive responding to the LiCl-sucrose flavor while at the same time showing reduced rejection response frequency on the two conditioning days. LPS treatment did not alter taste reactivity responding to the NaCl-sucrose solution. On the test day, the LPS groups again displayed a dose dependent increase in ingestive responses and a decrease in rejection responses to the LiCl-sucrose taste. The present results suggest that LPS-induced immune system activation, significantly impairs the rapid acquisition of a conditioned taste aversion.}, } @article {pmid18823162, year = {2008}, author = {Dwyer, DM and Boakes, RA and Hayward, AJ}, title = {Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {122}, number = {5}, pages = {1051-1060}, doi = {10.1037/a0012703}, pmid = {18823162}, issn = {0735-7044}, support = {BB/C006380/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amphetamine/*pharmacology ; Analysis of Variance ; Animals ; Antimanic Agents/*pharmacology ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Conditioning, Psychological ; Dopamine Agents/*pharmacology ; Food Preferences/drug effects ; Lithium Chloride/*pharmacology ; Locomotion/drug effects ; Male ; Rats ; Taste/*drug effects ; Water Deprivation/physiology ; }, abstract = {Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea.}, } @article {pmid18823161, year = {2008}, author = {Geddes, RI and Han, L and Baldwin, AE and Norgren, R and Grigson, PS}, title = {Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake.}, journal = {Behavioral neuroscience}, volume = {122}, number = {5}, pages = {1038-1050}, pmid = {18823161}, issn = {0735-7044}, support = {R01 DC000240/DC/NIDCD NIH HHS/United States ; F31 DA017416-01/DA/NIDA NIH HHS/United States ; DC00240/DC/NIDCD NIH HHS/United States ; R01 DA012473/DA/NIDA NIH HHS/United States ; DA12473/DA/NIDA NIH HHS/United States ; R37 DA009815/DA/NIDA NIH HHS/United States ; F31 DA017416-02/DA/NIDA NIH HHS/United States ; R01 DA009815/DA/NIDA NIH HHS/United States ; DA017146/DA/NIDA NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic/pharmacology ; Analgesics/pharmacology ; Analysis of Variance ; Animals ; Behavior, Animal/drug effects ; Brain Injuries/*pathology ; Cerebral Cortex/drug effects/metabolism/pathology/*physiopathology ; Cocaine/pharmacology ; Conditioning, Operant/*physiology ; Dose-Response Relationship, Drug ; Food Preferences/drug effects/*physiology ; *Inhibition, Psychological ; Lithium Chloride/pharmacology ; Male ; Morphine/pharmacology ; Phosphopyruvate Hydratase/metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substance such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15 and a 30 mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS.}, } @article {pmid18797244, year = {2008}, author = {Devantier, HR and Long, DJ and Brennan, FX and Carlucci, SA and Hendrix, C and Bryant, RW and Salemme, FR and Palmer, RK}, title = {Quantitative assessment of TRPM5-dependent oral aversiveness of pharmaceuticals using a mouse brief-access taste aversion assay.}, journal = {Behavioural pharmacology}, volume = {19}, number = {7}, pages = {673-682}, doi = {10.1097/FBP.0b013e3283123cd6}, pmid = {18797244}, issn = {0955-8810}, mesh = {Animals ; Avoidance Learning/*physiology ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drinking Behavior/physiology ; Female ; Gene Expression/physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Nonprescription Drugs ; *Prescription Drugs ; Species Specificity ; TRPM Cation Channels/*genetics ; Taste/*genetics ; Taste Threshold/genetics ; }, abstract = {Many orally administered pharmaceuticals are regarded by humans as aversive, most often described as 'bitter'. Taste aversiveness often leads to patient noncompliance and reduced treatment effectiveness. 'Bitter' taste is mediated by T2R G-protein coupled receptors through a peripheral signaling pathway critically dependent upon function of the TRPM5 ion channel. The brief-access taste aversion (BATA) assay operationally defines aversive taste as suppression of the rate at which a rodent licks from sipper tubes that deliver tastant solutions or suspensions. We have used a mouse BATA assay for rapid quantification of oral aversiveness from a set of 20 active pharmaceutical ingredients (APIs). Robust lick-rate dose-response functions were obtained from both C57BL/6J wild type (WT) and C57BL/6J/TRPM5-/- (TRPM5 knockout) mouse strains, generating reliable determinations of potency and relative maximal oral aversiveness for each API. A subset of APIs was also evaluated in a human bitterness assessment test; effective concentrations for half-maximum responses (EC50s) from both the human test and WT mouse BATA were equivalent. Relative to WT potencies, EC50s from TRPM5 knockout mice were right-shifted more than 10-fold for most APIs. However, APIs were identified for which EC50s were essentially identical in both mouse strains, indicating a TRPM5-independent alternative aversive pathway. Our results suggest the BATA assay will facilitate formulation strategies and taste assessment of late development-phase APIs.}, } @article {pmid18786528, year = {2008}, author = {Kayir, H and Alici, T and Göktalay, G and Yildirim, M and Ulusoy, GK and Ceyhan, M and Celik, T and Uzbay, TI}, title = {Stimulus properties of venlafaxine in a conditioned taste aversion procedure.}, journal = {European journal of pharmacology}, volume = {596}, number = {1-3}, pages = {102-106}, doi = {10.1016/j.ejphar.2008.08.015}, pmid = {18786528}, issn = {0014-2999}, mesh = {Adrenergic Uptake Inhibitors/*pharmacology ; Animals ; Antidepressive Agents/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Cyclohexanols/*pharmacology ; Male ; Mice ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/physiology ; Nitric Oxide Synthase/antagonists & inhibitors ; Serotonin Uptake Inhibitors/*pharmacology ; *Taste ; Venlafaxine Hydrochloride ; }, abstract = {Conditioned stimulus properties of venlafaxine are still unknown. In the present study, the discriminative stimulus properties of venlafaxine by using a conditioned taste aversion procedure were investigated. Swiss Webster mice were allowed to reach water from 2 pipettes for 20 min (09:00-11:30 h), plus 30 min (15:30-16:00 h), daily. During the 4 days, the test drugs [fluoxetine, escitalopram, tianeptine, reboxetine, and Nomega-nitro-L-arginine methyl ester (L-NAME)] were injected to mice at least 1 h after they had first water session. On day 5, they consumed glucose solution (5% w/v) and immediately injected with conditioning drug (venlafaxine 32 mg/kg). On day 8, mice were allowed to make a choice between water and glucose solution. The amount of glucose consumption as a percentage of total fluid intakes was calculated for each animal. Significant reduction in glucose choice was defined as conditioned taste aversion. Venlafaxine (32 mg/kg) induced a robust conditioned taste aversion in mice. Pre-exposure to tianeptine (2.5-10 mg/kg), fluoxetine (10 mg/kg), escitalopram (32 mg/kg), and reboxetine (5 mg/kg) substituted for venlafaxine by preventing the conditioned taste aversion induced by venlafaxine. L-NAME did not substitute for venlafaxine. Substitution of venlafaxine by fluoxetine, tianeptine, escitalopram, and reboxetine provides further evidence that both 5-HT and noradrenaline reuptake inhibition may play an important role in the stimulus effect of venlafaxine.}, } @article {pmid18778149, year = {2008}, author = {Parker, LA and Rana, SA and Limebeer, CL}, title = {Conditioned nausea in rats: assessment by conditioned disgust reactions, rather than conditioned taste avoidance.}, journal = {Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale}, volume = {62}, number = {3}, pages = {198-209}, doi = {10.1037/a0012531}, pmid = {18778149}, issn = {1196-1961}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Psychological ; *Nausea ; Rats ; *Taste ; }, abstract = {The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat drinks in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed using the taste reactivity (TR) test that includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned disgust reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Only treatments that produce nausea produce conditioned disgust reactions, but even rewarding drugs produce conditioned taste avoidance. Furthermore, treatments that alleviate nausea prevent the establishment and the expression of conditioned disgust reactions, but they do not necessarily modify conditioned taste avoidance. Considerable evidence exists indicating that these two measures can be independent of one another. The potential of a compound to produce conditioned disgust reactions is a reflection of its nausea-inducing properties. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but conditioned disgust is motivated by conditioned nausea.}, } @article {pmid18706935, year = {2009}, author = {Gomez-Serrano, MA and Kearns, DN and Riley, AL}, title = {The effects of light cycle phase on morphine-induced conditioned taste aversions in the Lewis, Fischer and Sprague-Dawley rat strains.}, journal = {Behavioural brain research}, volume = {196}, number = {1}, pages = {116-122}, doi = {10.1016/j.bbr.2008.07.023}, pmid = {18706935}, issn = {1872-7549}, mesh = {Analgesics, Opioid/administration & dosage/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Biological Clocks/physiology ; Body Weight/drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Drinking/drug effects/physiology ; Injections, Subcutaneous ; Morphine/administration & dosage/*pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Saccharin/administration & dosage/pharmacology ; Species Specificity ; Sweetening Agents/administration & dosage/pharmacology ; Taste/*drug effects ; Time Factors ; Water Deprivation/physiology ; }, abstract = {The present experiment investigated the effect of light cycle phase on morphine-induced conditioned taste aversions in the Lewis (LEW), Fischer (F344) and Sprague-Dawley (SD) rat strains. Separate groups of rats from each strain were trained during either the light phase or the dark phase on a procedure in which saccharin was paired with one of two doses of morphine (or vehicle). With 3.2mg/kg morphine, strain differences were observed during the light phase, with F344 rats displaying a significantly stronger taste aversion than the LEW rats, who displayed a significantly stronger aversion than the SD rats. In contrast, during the dark phase, 3.2mg/kg morphine produced comparable, moderately strong aversions in all strains. With 10.0mg/kg morphine, F344 rats developed stronger aversions than either the LEW or SD rats in both phases of the light cycle. The effect of light cycle was most clearly seen in the SD rats, where stronger aversions were produced in the dark phase for both morphine doses. For the LEW rats, stronger aversions were produced in the dark as compared to the light only with the low dose of morphine. For the F344 rats, aversions of comparable strength were observed in both phases of the light cycle for both morphine doses. The finding that light cycle differentially affects morphine-induced taste aversions in these strains is consistent with what is known about strain differences in circadian patterns of corticosterone activity and with previous results relating corticosterone to morphine-induced taste aversions.}, } @article {pmid18702705, year = {2008}, author = {Sellings, LH and Baharnouri, G and McQuade, LE and Clarke, PB}, title = {Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens.}, journal = {The European journal of neuroscience}, volume = {28}, number = {2}, pages = {342-352}, doi = {10.1111/j.1460-9568.2008.06341.x}, pmid = {18702705}, issn = {1460-9568}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Choice Behavior/drug effects ; Conditioning, Psychological/drug effects ; Dopamine/*metabolism ; Injections, Intravenous ; Injections, Subcutaneous ; Male ; Nicotine/administration & dosage/*pharmacology ; Nucleus Accumbens/drug effects/metabolism/*physiology ; Oxidopamine/pharmacology ; Rats ; Rats, Long-Evans ; *Reward ; Spatial Behavior/drug effects ; Synaptic Transmission/*physiology ; Taste/physiology ; }, abstract = {Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.}, } @article {pmid18685032, year = {2008}, author = {Hefner, K and Whittle, N and Juhasz, J and Norcross, M and Karlsson, RM and Saksida, LM and Bussey, TJ and Singewald, N and Holmes, A}, title = {Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {28}, number = {32}, pages = {8074-8085}, pmid = {18685032}, issn = {1529-2401}, support = {G0001354/MRC_/Medical Research Council/United Kingdom ; Z01 AA000411/ImNIH/Intramural NIH HHS/United States ; Z01 AA000411-04/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Amygdala/*abnormalities ; Animals ; Avoidance Learning ; Behavior, Animal ; Conditioning, Psychological ; Cycloserine/pharmacology ; Early Growth Response Protein 1/metabolism ; *Extinction, Psychological ; *Fear/drug effects ; Interneurons/metabolism ; *Learning ; Male ; Mental Recall ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Nervous System Malformations/genetics/metabolism/physiopathology/*psychology ; Neural Pathways/abnormalities ; Nociceptors ; Prefrontal Cortex/*abnormalities ; Proto-Oncogene Proteins c-fos/metabolism ; Taste ; Yohimbine/pharmacology ; }, abstract = {Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C57BL/6J for one-trial and multitrial fear conditioning, nociception, and extinction of conditioned taste aversion and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as d-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped after extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor d-cycloserine treatment improved 129S1 extinction. After extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders.}, } @article {pmid18680140, year = {2009}, author = {Manrique, T and Morón, I and Ballesteros, MA and Guerrero, RM and Fenton, AA and Gallo, M}, title = {Hippocampus, aging, and segregating memories.}, journal = {Hippocampus}, volume = {19}, number = {1}, pages = {57-65}, doi = {10.1002/hipo.20481}, pmid = {18680140}, issn = {1098-1063}, mesh = {Aging/*physiology ; Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/physiology ; Conditioning, Psychological/physiology ; Denervation ; Hippocampus/*physiology ; Learning/*physiology ; Lithium Chloride/pharmacology ; Male ; Memory/*physiology ; Memory Disorders/physiopathology ; Parietal Lobe/anatomy & histology/physiology ; Rats ; Rats, Wistar ; Time Perception/*physiology ; }, abstract = {Rats use time-of-day cues to modulate learned taste aversion memories. If adult rats are accustomed to drinking saline in the evening and they receive a lithium chloride injection after drinking saline in the morning, they form a stronger aversion to saline than rats that were conditioned after drinking saline at the familiar time. The difference indicated that the rats formed segregated representations of saline taste and the time of day the saline was consumed. This was inferred because the modulation of learning by time of day was observed when the aversions were tested at the familiar evening drinking time. If the rats had formed a compound representation of saline taste and the time of day it was consumed, the opposite pattern of differences would be expected. We used this modulation of learning by time of day to assay whether aged rats have an impaired ability to form segregated representations of experience. We find that aged rats had similar saline aversions if they were conditioned at either the familiar or the unfamiliar time of day. Furthermore, dorsal hippocampal lesions affecting also the overlying parietal cortex in the aged rats caused greater saline aversions if the rats were conditioned after drinking saline at the familiar time of day. This indicated that aged rats are aware of the time of day but after the lesion, they act as if they do not segregate saline taste from the time of day it was consumed. The results suggest that the ability to form segregated representations of a complex experience is impaired in aging and abolished by hippocampal lesions.}, } @article {pmid18672009, year = {2008}, author = {Takács, G and Lukáts, B and Papp, S and Szalay, C and Karádi, Z}, title = {Taste reactivity alterations after IL-1beta microinjection into the ventromedial hypothalamic nucleus of the rat.}, journal = {Neuroscience research}, volume = {62}, number = {2}, pages = {118-122}, doi = {10.1016/j.neures.2008.06.010}, pmid = {18672009}, issn = {0168-0102}, mesh = {Animals ; Anorexia/physiopathology ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; Dysgeusia/*physiopathology ; Feeding Behavior/drug effects ; Injections, Intraventricular ; Interleukin-1beta/*administration & dosage ; Male ; Microinjections ; Rats ; Rats, Wistar ; Taste/*physiology ; Ventromedial Hypothalamic Nucleus/*drug effects/physiology ; }, abstract = {The ventromedial hypothalamic nucleus (VMH) is a central site of action of interleukin-1beta (IL-1beta) induced feeding disturbances. This study was designed to elucidate taste-related perceptual and motivational processes potentially contributing to the anorexia and adipsia seen after bilateral IL-1beta microinjection into the VMH. A saccharin conditioned taste aversion (CTA) paradigm was tested after the central IL-1beta administration. To further investigate whether gustatory deficits are involved in development of the feeding alterations, IL-1beta induced changes of taste responsiveness were also studied in taste reactivity tests. Administration of the cytokine into the VMH did not cause the development of CTA. During taste reactivity tests, however, IL-1beta treated rats displayed significantly poorer ingestive reactions to pleasant taste stimuli than did animals of the control group. In addition, the aversive responses of IL-1beta injected rats to pleasant tastes were significantly more robust than those of control animals. The cytokine treated animals also showed stronger aversion than ingestion to hedonically positive tastes. The present findings indicate that (1) anorexigenic and adipsogenic consequences of IL-1beta microinjection into the VMH are not due to development of cytokine induced CTA; and (2) hedonic responsiveness to palatable tastes is processed by IL-1beta mediated neural mechanisms in the VMH.}, } @article {pmid18667714, year = {2008}, author = {Mansouri, A and Aja, S and Moran, TH and Ronnett, G and Kuhajda, FP and Arnold, M and Geary, N and Langhans, W and Leonhardt, M}, title = {Intraperitoneal injections of low doses of C75 elicit a behaviorally specific and vagal afferent-independent inhibition of eating in rats.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {295}, number = {3}, pages = {R799-805}, pmid = {18667714}, issn = {0363-6119}, support = {DK-019302/DK/NIDDK NIH HHS/United States ; CA-087850/CA/NCI NIH HHS/United States ; DK-060735/DK/NIDDK NIH HHS/United States ; DK-064000/DK/NIDDK NIH HHS/United States ; DK-068054/DK/NIDDK NIH HHS/United States ; DC-02979/DC/NIDCD NIH HHS/United States ; }, mesh = {4-Butyrolactone/*analogs & derivatives/pharmacology ; Animals ; Carnitine O-Palmitoyltransferase/antagonists & inhibitors/metabolism ; Conditioning, Psychological/drug effects/physiology ; Dose-Response Relationship, Drug ; Eating/drug effects/physiology ; Fatty Acid Synthases/antagonists & inhibitors/metabolism ; Fatty Acids/metabolism ; Feeding Behavior/*drug effects/physiology ; Injections, Intraperitoneal ; Male ; Neurons, Afferent/*drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Vagotomy ; Vagus Nerve/cytology/*drug effects/physiology ; }, abstract = {Central and intraperitoneal C75, an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyl-transferase-1, inhibits eating in mice and rats. Mechanisms involved in feeding inhibition after central C75 have been identified, but little is yet known about how systemic C75 might inhibit eating. One issue is whether intraperitoneal C75 reduces food intake in rats by influencing normal physiological controls of food intake or acts nonselectively, for example by eliciting illness or aversion. Another issue relates to whether intraperitoneal C75 acts centrally or, similar to some other peripheral metabolic controls of eating, activates abdominal vagal afferents to inhibit eating. To further address these questions, we investigated the effects of intraperitoneal C75 on spontaneous meal patterns and the formation of conditioned taste aversion (CTA). We also tested whether the eating inhibitory effect of intraperitoneal C75 is vagally mediated by testing rats after either total subdiaphragmatic vagotomy (TVX) or selective subdiaphragmatic vagal deafferentations (SDA). Intraperitoneal injection of 3.2 and 7.5 mg/kg of C75 significantly reduced food intake 3, 12, and 24 h after injection by reducing the number of meals without affecting meal size, whereas 15 mg/kg of C75 reduced both meal number and meal size. The two smaller doses of C75 failed to induce a CTA, but 15 mg/kg C75 did. The eating inhibitory effect of C75 was not diminished in either TVX or SDA rats. We conclude that intraperitoneal injections of low doses of C75 inhibit eating in a behaviorally specific manner and that this effect does not require abdominal vagal afferents.}, } @article {pmid18664369, year = {2008}, author = {Grobe, CL and Spector, AC}, title = {Constructing quality profiles for taste compounds in rats: a novel paradigm.}, journal = {Physiology & behavior}, volume = {95}, number = {3}, pages = {413-424}, doi = {10.1016/j.physbeh.2008.07.007}, pmid = {18664369}, issn = {0031-9384}, support = {F31-DC007301/DC/NIDCD NIH HHS/United States ; R01-DC01628/DC/NIDCD NIH HHS/United States ; }, mesh = {Analgesics, Non-Narcotic/pharmacology ; Animals ; Behavior, Animal/drug effects ; Citric Acid/pharmacology ; Conditioning, Psychological/drug effects/physiology ; Discrimination Learning/drug effects/physiology ; Dose-Response Relationship, Drug ; Generalization, Stimulus/drug effects/physiology ; Male ; Quinine/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Stimulation, Chemical ; Sucrose/pharmacology ; Sweetening Agents/pharmacology ; Taste/drug effects/*physiology ; Taste Perception/drug effects/*physiology ; Taste Threshold/drug effects/physiology ; }, abstract = {We developed a novel behavioral method, adapted from the work by Morrison (1967), for the assessment of taste quality in rats. Four groups of rats were trained to discriminate a standard stimulus (either NaCl, sucrose, quinine, or citric acid, which are widely thought to represent the four basic human taste qualities of salty, sweet, bitter, and sour, respectively) from the remaining three compounds (each at multiple concentrations). Animals were then tested for generalization to the standard stimuli when test compounds were presented and a quality profile was constructed. Rats generalized novel concentrations of standard stimuli completely to their training concentrations and generalized their responses to mixtures of NaCl and sucrose on the basis of the relative concentrations of the stimulus components. In general, the sugars (at high concentrations), denatonium, tartaric acid, and sodium gluconate generalized to sucrose, quinine, citric acid, and NaCl, respectively. Monosodium glutamate generalized to a mixture of sucrose and NaCl. KCl produced a complex generalization profile with notable quinine and citric acid components. Our procedure supplements the current use of the conditioned taste aversion generalization procedure which has some procedural and interpretive limitations. Although our procedure involves the use of a complex stimulus delivery and response measurement apparatus and requires substantial initial conditioning of animals, once trained, a single cohort of animals can be tested for its response to a substantial number of test stimuli over the course of many months without any ostensible loss of stimulus control.}, } @article {pmid18652377, year = {2008}, author = {Nomura, Y and Hatakeyama, D and Horikoshi, T and Sakakibara, M}, title = {Immunohistological studies on the distribution of learning-related peptides in the central nervous system of conditioned Lymnaea.}, journal = {Acta biologica Hungarica}, volume = {59 Suppl}, number = {}, pages = {81-92}, doi = {10.1556/ABiol.59.2008.Suppl.13}, pmid = {18652377}, issn = {0236-5383}, mesh = {Animals ; Central Nervous System/anatomy & histology/physiology ; Conditioning, Psychological/physiology ; Immunohistochemistry ; Learning/physiology ; Lymnaea/anatomy & histology/*physiology ; Neuropeptides/metabolism ; Taste/physiology ; }, abstract = {Behavioral conditioning in Lymnaea increased the amount of immunolabeling in the central nervous system for the memory-associated protein calexcitin. The staining level of anti-calexcitin positive neurons was always stronger in conditioned animals than in naive animals. In the visuo-vestibular conditioned animals, right-parietal and visceral group neurons as well as withdrawal-related neurons were positively stained with anti-calexcitin antibody. In taste-aversion conditioned animals, right-parietal visceral G-group neurons and withdrawal-related neurons were selectively stained. These neurons are candidate neurons for modulation by these conditioning paradigms.}, } @article {pmid18647616, year = {2008}, author = {Smith, S and Fieser, S and Jones, J and Schachtman, TR}, title = {Effects of swim stress on latent inhibition using a conditioned taste aversion procedure.}, journal = {Physiology & behavior}, volume = {95}, number = {3}, pages = {539-541}, doi = {10.1016/j.physbeh.2008.06.014}, pmid = {18647616}, issn = {0031-9384}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; *Conditioning, Psychological ; Female ; Food Preferences ; *Inhibition, Psychological ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Stress, Psychological/*psychology ; Sweetening Agents/administration & dosage ; *Swimming ; *Taste ; }, abstract = {Rats were used to examine the effects of inescapable swim stress on latent inhibition using a conditioned taste aversion procedure. Subjects were subjected to inescapable swim after each of three saccharin taste preexposures and saccharin was later paired with LiCl. The ability of swim to influence latent inhibition was assessed on subsequent saccharin test trials. Swim stress significantly attenuated latent inhibition. The implications of these results regarding the effects of swim stress on conditioned taste aversion are discussed.}, } @article {pmid18642757, year = {2008}, author = {Yamamoto, T}, title = {Central mechanisms of roles of taste in reward and eating.}, journal = {Acta physiologica Hungarica}, volume = {95}, number = {2}, pages = {165-186}, doi = {10.1556/APhysiol.95.2008.2.2}, pmid = {18642757}, issn = {0231-424X}, mesh = {Animals ; Cerebrum/*physiology ; Eating/physiology/*psychology ; Feeding Behavior/physiology/*psychology ; Humans ; *Reward ; Taste/*physiology ; }, abstract = {Taste is unique among sensory systems in its innate association with mechanisms of reward and aversion in addition to its recognition of quality, e.g., sucrose is sweet and preferable, and quinine is bitter and aversive. Taste information is sent to the reward system and feeding center via the prefrontal cortices such as the mediodorsal and ventrolateral prefrontal cortices in rodents and the orbitofrontal cortex in primates. The amygdala, which receives taste inputs, also influences reward and feeding. In terms of neuroactive substances, palatability is closely related to benzodiazepine derivatives and beta-endorphin, both of which facilitate consumption of food and fluid. The reward system contains the ventral tegmental area, nucleus accumbens and ventral pallidum and finally sends information to the lateral hypothalamic area, the feeding center. The dopaminergic system originating from the ventral tegmental area mediates the motivation to consume palatable food. The actual ingestive behavior is promoted by the orexigenic neuropeptides from the hypothalamus. Even palatable food can become aversive and avoided as a consequence of a postingestional unpleasant experience such as malaise. The neural mechanisms of this conditioned taste aversion will also be elucidated.}, } @article {pmid18639579, year = {2008}, author = {Roma, PG and Rinker, JA and Serafine, KM and Chen, SA and Barr, CS and Cheng, K and Rice, KC and Riley, AL}, title = {Genetic and early environmental contributions to alcohol's aversive and physiological effects.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {91}, number = {1}, pages = {134-139}, pmid = {18639579}, issn = {0091-3057}, support = {Z01 AA000214-06/ImNIH/Intramural NIH HHS/United States ; Z01 DA000520-01/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Central Nervous System Depressants/*antagonists & inhibitors/blood/*pharmacology ; Conditioning, Operant/drug effects ; Data Interpretation, Statistical ; Dynorphins/administration & dosage/pharmacology ; Ethanol/*antagonists & inhibitors/blood/*pharmacology ; Extinction, Psychological/drug effects ; Female ; Hypothermia/chemically induced/physiopathology ; Maternal Behavior/drug effects ; *Motivation ; Naltrexone/administration & dosage/analogs & derivatives/pharmacology ; Rats ; Receptors, Opioid, kappa/drug effects/genetics ; Taste/drug effects ; }, abstract = {Genetic and early environmental factors interact to influence ethanol's motivational effects. To explore these issues, a reciprocal cross-fostering paradigm was applied to Fischer and Lewis rats. The adult female offspring received vehicle or the kappa opioid antagonist nor-BNI (1 mg/kg) followed by assessments of conditioned taste aversion (CTA), blood alcohol concentrations (BACs) and hypothermia induced by 1.25 g/kg intraperitoneal ethanol. CTA acquisition in the in-fostered Fischer and Lewis animals did not differ; however, the Fischer maternal environment produced stronger acquisition in the cross-fostered Lewis rats versus their in-fostered counterparts. CTAs in the Fischer rats were not affected by cross-fostering. In extinction, the in-fostered Lewis animals displayed stronger aversions than the Fischer groups on two trials (of 12) whereas the cross-fostered Lewis differed from the Fischer groups on nine trials. Despite these CTA effects, Lewis rats exhibited higher BACs and stronger hypothermic responses than Fischer with no cross-fostering effects in either strain. No phenotypes were affected by nor-BNI. These data extend previous findings dissociating the aversive and peripheral physiological effects of ethanol in female Fischer and Lewis rats, and highlight the importance of genetic and early environmental factors in shaping subsequent responses to alcohol's motivational effects in adulthood.}, } @article {pmid18626094, year = {2008}, author = {Merhav, M and Rosenblum, K}, title = {Facilitation of taste memory acquisition by experiencing previous novel taste is protein-synthesis dependent.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {15}, number = {7}, pages = {501-507}, pmid = {18626094}, issn = {1549-5485}, mesh = {Analysis of Variance ; Animals ; Anisomycin/pharmacology ; Avoidance Learning/drug effects ; Behavior, Animal ; Brain/*metabolism ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Inhibition, Psychological ; Male ; Memory/drug effects/*physiology ; Microinjections/methods ; Nerve Tissue Proteins/*biosynthesis ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Sodium Chloride/administration & dosage ; Taste/drug effects/*physiology ; Taste Threshold/drug effects ; Time Factors ; }, abstract = {Very little is known about the biological and molecular mechanisms that determine the effect of previous experience on implicit learning tasks. In the present study, we first defined weak and strong taste inputs according to measurements in the behavioral paradigm known as latent inhibition of conditioned taste aversion. We then demonstrated that a strong novel taste input facilitated acquisition of the memory of subsequent weak taste input in inverse correlation with the time interval between the inputs. However, not only was a strong taste input unable to rescue an immediately subsequent strong taste input when the gustatory cortex was under the influence of the protein-synthesis inhibitor, anisomycin, but the effect of the interaction was to reduce the variation among individual taste memories. Taken together, these results demonstrate that taste memory facilitation, induced by previously experiencing a different unimodal taste input, depended on time, novelty, and directionality. Moreover, the results imply that learning is enhanced on the level of acquisition but not of molecular consolidation.}, } @article {pmid18625328, year = {2008}, author = {Moguel-González, M and Gómez-Palacio-Schjetnan, A and Escobar, ML}, title = {BDNF reverses the CTA memory deficits produced by inhibition of protein synthesis.}, journal = {Neurobiology of learning and memory}, volume = {90}, number = {3}, pages = {584-587}, doi = {10.1016/j.nlm.2008.06.003}, pmid = {18625328}, issn = {1095-9564}, mesh = {Animals ; Anisomycin/pharmacology ; Avoidance Learning/drug effects/*physiology ; Brain-Derived Neurotrophic Factor/administration & dosage/*physiology ; Conditioning, Classical/drug effects/*physiology ; Male ; Microinjections ; Nerve Tissue Proteins/biosynthesis/drug effects ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Wistar ; Signal Transduction/drug effects/physiology ; Taste ; Temporal Lobe/drug effects/*physiology ; }, abstract = {Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the projection from the basolateral nucleus of the amygdala (Bla) to the IC of adult rats in vivo. Recently, we found that intracortical microinfusion of BDNF previous to CTA training enhances the retention of this task. In this work, we present experimental data showing that acute intracortical delivery of BDNF (2 microg/2 microl per side) reverses the deficit in CTA memory caused by inhibition of insular cortex protein synthesis due to anisomycin administration (100 microg/microl per side) in male adult Wistar rats. These findings suggest that BDNF is a protein synthesis product essential for neocortical long-term memory storage.}, } @article {pmid18622888, year = {2009}, author = {Dwyer, DM}, title = {Microstructural analysis of ingestive behaviour reveals no contribution of palatability to the incomplete extinction of a conditioned taste aversion.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {62}, number = {1}, pages = {9-17}, doi = {10.1080/17470210802215152}, pmid = {18622888}, issn = {1747-0226}, support = {BB/C006380/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; *Conditioning, Psychological ; Extinction, Psychological/*physiology ; Feeding Behavior/*physiology ; Food Preferences/*physiology ; Fructose/administration & dosage ; Lithium Chloride/administration & dosage ; Male ; Rats ; Taste/*physiology ; }, abstract = {An analysis of the microstructure of licking responses was used to investigate the effects of conditioning and extinguishing a taste aversion. Rats received a single pairing of 8% fructose with lithium chloride (LiCl) while controls received unpaired exposure to fructose and LiCl. Pairing fructose with LiCl produced a reduction both in consumption and in the size of licking clusters. Subsequent exposure to fructose in the absence of LiCl produced some extinction of the taste aversion although at asymptote there was a residual difference in consumption between the taste aversion group and unpaired controls. In contrast the reduction in lick cluster size did completely extinguish. Previous analyses of licking microstructure indicate that lick cluster size is related to the palatability of the ingested solution. Thus these results indicate that although taste aversion learning initially reduces the palatability of the cue solution this reduction is not permanent. These results are discussed with reference to the possibility that preparatory behaviours are more resistant to extinction than are consummatory behaviours.}, } @article {pmid18612067, year = {2008}, author = {Miranda, MI and Quirarte, GL and Rodriguez-Garcia, G and McGaugh, JL and Roozendaal, B}, title = {Glucocorticoids enhance taste aversion memory via actions in the insular cortex and basolateral amygdala.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {15}, number = {7}, pages = {468-476}, pmid = {18612067}, issn = {1549-5485}, support = {R01 MH012526/MH/NIMH NIH HHS/United States ; R56 MH012526/MH/NIMH NIH HHS/United States ; MH12526/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/anatomy & histology/drug effects/*physiology ; Animals ; Avoidance Learning/*drug effects ; Corticosterone/administration & dosage/*pharmacology ; Drinking Behavior ; Habituation, Psychophysiologic ; Hippocampus/drug effects/*physiology ; Infusions, Intravenous ; Lithium Chloride/*pharmacology ; Male ; Memory/drug effects/*physiology ; Pyridines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/*pharmacology ; Taste/drug effects/*physiology ; Water ; }, abstract = {It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function. Corticosterone (1.0 or 3.0 mg/kg) administered subcutaneously to male Sprague-Dawley rats immediately after the pairing of saccharin consumption with the visceral malaise-inducing agent lithium chloride (LiCl) dose-dependently increased aversion to the saccharin taste on a 96-h retention test trial. In a second experiment, rats received corticosterone either immediately after saccharin consumption or after the LiCl injection, when both stimuli were separated by a 3-h time interval, to investigate whether corticosterone enhances memory of the gustatory or visceral stimulus presentation. Consistent with the finding that the LiCl injection, but not saccharin consumption, increases endogenous corticosterone levels, corticosterone selectively enhanced CTA memory when administered after the LiCl injection. Suppression of this training-induced release of corticosterone with the synthesis-inhibitor metyrapone (35 mg/kg) impaired CTA memory, and was dose-dependently reversed by post-training supplementation of corticosterone. Moreover, direct post-training infusions of corticosterone into the insular cortex or basolateral complex of the amygdala, two brain regions that are critically involved in the acquisition and consolidation of CTA, also enhanced CTA retention, whereas post-training infusions into the dorsal hippocampus were ineffective. These findings provide evidence that glucocorticoid effects on memory consolidation are not limited to hippocampus-dependent spatial/contextual information, but that these hormones also modulate memory consolidation of discrete-cue associative learning via actions in other brain regions.}, } @article {pmid18606192, year = {2008}, author = {Macedo, CE and Angst, MJ and Gounot, D and Sandner, G}, title = {Overshadowing in conditioned taste aversion or in conditioned emotional response after neonatal ventral hippocampal lesions in rats.}, journal = {Behavioural brain research}, volume = {194}, number = {1}, pages = {15-20}, doi = {10.1016/j.bbr.2008.06.014}, pmid = {18606192}, issn = {0166-4328}, mesh = {Acoustic Stimulation/methods ; Animals ; Animals, Newborn ; Avoidance Learning/*physiology ; Behavior, Animal ; Brain Injuries/*pathology ; Conditioning, Psychological/*physiology ; Drinking Behavior/physiology ; *Emotions ; Hippocampus/*pathology ; Magnetic Resonance Imaging ; Male ; Rats ; Rats, Sprague-Dawley ; Reaction Time/physiology ; Taste/*physiology ; }, abstract = {The neonatal hippocampus lesion thought to model schizophrenia should show the same modifications in behavioural tests as other models, especially pharmacological models, namely decreased latent inhibition, blocking and overshadowing. The present study is set out to evaluate overshadowing in order to complement our previous studies, which had tested latent inhibition. "Overshadowing" refers to the decreased conditioning that occurs when the to-be-conditioned stimulus is combined with another stimulus at the conditioning stage. We used the same two Pavlovian conditioning paradigms as in our previous works, namely conditioned taste aversion (CTA) and conditioned emotional response (CER). A sweet taste overshadowed a salty conditioned stimulus, and a tone overshadowed a flashing light. Totally different stimuli were used to counter possible sensory biases. The protocols were validated with two groups of Sprague Dawley rats. The same two protocols were then applied to a cohort of rats whose ventral hippocampus had been destroyed when they were 7days old. Only rats with extended ventral hippocampus lesions were included. The overall effect of Pavlovian conditioning was attenuated, significantly so in the conditioned emotional response paradigm, but overshadowing appeared not to be modified in either the conditioned emotional response or the conditioned taste aversion paradigm.}, } @article {pmid18594795, year = {2009}, author = {Davis, CM and Stevenson, GW and Cañadas, F and Ullrich, T and Rice, KC and Riley, AL}, title = {Discriminative stimulus properties of naloxone in Long-Evans rats: assessment with the conditioned taste aversion baseline of drug discrimination learning.}, journal = {Psychopharmacology}, volume = {203}, number = {2}, pages = {421-429}, pmid = {18594795}, issn = {1432-2072}, support = {Z01 DA000520-01/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Discrimination Learning/*drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Naloxone/*pharmacology ; Narcotic Antagonists/*pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Opioid, delta/antagonists & inhibitors ; Receptors, Opioid, kappa/antagonists & inhibitors ; Receptors, Opioid, mu/antagonists & inhibitors ; Saccharin/administration & dosage ; Taste/*drug effects ; }, abstract = {RATIONALE: The characterization of the discriminative stimulus properties of naloxone has focused primarily on its actions at the mu opioid receptor, although naloxone also displays an affinity for delta and kappa receptor subtypes.

OBJECTIVES: The present study extends this characterization of the naloxone cue by investigating if relatively specific antagonists for the mu (naltrexone: 0.10-0.56 mg/kg), delta (naltrindole: 1-18 mg/kg), and kappa (MR2266: 1.8-10 mg/kg) opioid receptor subtypes will substitute for naloxone in animals trained to discriminate naloxone from its vehicle. The temporal nature of the naloxone cue was examined by varying pretreatment time points (15, 30, 45, 60 min). Finally, various doses of naltrexone methobromide (1-18 mg/kg) were assessed to determine peripheral mediation of the cue.

MATERIALS AND METHODS: Female Long-Evans rats (N = 30) received an injection of naloxone (1 mg/kg; i.p.) 15 min prior to a pairing of saccharin (20-min access) and the emetic LiCl (1.8 mEq; i.p.; n = 16, group NL) or vehicle (n = 14, group NW); on other days, they were injected with saline prior to saccharin alone. Substitution tests with compounds with various receptor affinities and selective CNS and PNS actions were then assessed.

RESULTS: Only naloxone and naltrexone produced dose-dependent decreases in saccharin consumption. Naloxone administered at 15 and 30 min before saccharin produced decreases in consumption similar to that displayed on training days. Naltrexone methobromide substituted only at the highest dose tested (18 mg/kg).

CONCLUSIONS: Naloxone's stimulus effects appear to be mediated centrally via activity at the mu opioid receptor.}, } @article {pmid18574458, year = {2008}, author = {Verbaeys, I and León-Tamariz, F and Pottel, H and Decuypere, E and Swennen, Q and Cokelaere, M}, title = {PEGylated cholecystokinin is more potent in inducing anorexia than conditioned taste aversion in rats.}, journal = {British journal of pharmacology}, volume = {155}, number = {3}, pages = {417-423}, pmid = {18574458}, issn = {0007-1188}, mesh = {Animals ; Anorexia/*chemically induced ; Aspartic Acid/analogs & derivatives/pharmacology ; Avoidance Learning/drug effects ; Cholecystokinin/administration & dosage/chemistry/*pharmacology ; Devazepide/pharmacology ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Male ; Naphthalenesulfonates/pharmacology ; Peptide Fragments/administration & dosage/chemistry/*pharmacology ; Polyethylene Glycols/chemistry ; Rats ; Rats, Wistar ; Receptor, Cholecystokinin A/*drug effects/metabolism ; Saccharin ; Satiety Response/*drug effects ; Taste ; }, abstract = {BACKGROUND AND PURPOSE: The physiological involvement of endogenous cholecystokinin (CCK) in the termination of feeding has been challenged by evidence of aversive effects of exogenous CCK8. We previously prolonged the anorectic effect of CCK by conjugation to polyethylene glycol (PEGylation) to produce PEG-CCK9. In this study, we investigated the ability of different doses of PEG-CCK9 to induce conditioned taste aversion (CTA) and satiety and identified the receptors involved in CTA induction.

EXPERIMENTAL APPROACH: Induction of CTA, measured by the saccharin preference ratio determined in a two-bottle CTA procedure, and of satiety in adult male Wistar rats after intraperitoneal (i.p.) injection of different doses of PEG-CCK9 (1, 2, 4, 8, 16 or 32 microg kg(-1)) was compared. Devazepide (100 microg kg(-1)) and 2-NAP (3 mg kg(-1)), two selective CCK1-receptor antagonists, were co-administered i.p. with PEG-CCK9 (8 microg kg(-1)) and the CTA effects monitored.

KEY RESULTS: PEG-CCK9 dose-dependently induced CTA, with a minimal effective dose of 8 microg kg(-1), whereas the minimal effective dose to induce satiety was 1 microg kg(-1). The CTA effects of PEG-CCK9 were completely abolished by i.p. administration of devazepide prior to PEG-CCK9 treatment and only partially abolished by administration of 2-NAP.

CONCLUSIONS AND IMPLICATIONS: Although PEG-CCK9-induced satiety and PEG-CCK9-induced CTA both increased with dose, the conjugate was more potent in inducing satiety, suggesting that the anorexia could not be completely attributed to the aversiveness of the drug. As observed with induction of satiety, PEG-CCK9-induced CTA was mediated by CCK1-receptors.}, } @article {pmid18562069, year = {2008}, author = {Curry, LL and Roberts, A}, title = {Subchronic toxicity of rebaudioside A.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {46 Suppl 7}, number = {}, pages = {S11-20}, doi = {10.1016/j.fct.2008.04.042}, pmid = {18562069}, issn = {0278-6915}, mesh = {Animals ; Bile Acids and Salts/blood/metabolism ; Cholesterol/blood ; Diet ; Diterpenes, Kaurane/administration & dosage/*toxicity ; Dose-Response Relationship, Drug ; Eating/drug effects ; Energy Intake ; Female ; Liver/metabolism ; Male ; Rats ; Rats, Wistar ; Sex Characteristics ; Sweetening Agents/administration & dosage/*toxicity ; Time Factors ; Weight Gain/drug effects ; }, abstract = {The safety of the stevia-derived sweetener, rebaudioside A (CAS No. 58543-16-1), was evaluated in two oral toxicity studies. In a 4-week study, Wistar rats were administered rebaudioside A at dietary concentrations of 0, 25,000, 50,000, 75,000 and 100,000ppm. The NOAEL, including an evaluation of testes histopathology, was determined to be 100,000 ppm. In the 13-week study, Wistar rats were administered rebaudioside A at dietary concentrations of 0, 12,500, 25,000 and 50,000ppm. Reductions in body weight gain attributable to initial taste aversion and lower caloric density of the diet were observed in high-dose male and females groups. Inconsistent reductions in serum bile acids and cholesterol were attributed to physiological changes in bile acid metabolism due to excretion of high levels of rebaudioside A via the liver. All other hepatic function test results and liver histopathology were within normal limits. Significant changes in other clinical pathology results, organ weights and functional observational battery test results were not observed. Macroscopic and microscopic examinations of all organs, including testes and kidneys, were unremarkable with respect to treatment-related findings. The NOAEL in the 13-week toxicity study was considered to be 50,000ppm or approximately 4161 and 4645mg/kg body weight/day in male and female rats, respectively.}, } @article {pmid18558472, year = {2008}, author = {Hutchison, MA and Riley, AL}, title = {Adolescent exposure to nicotine alters the aversive effects of cocaine in adult rats.}, journal = {Neurotoxicology and teratology}, volume = {30}, number = {5}, pages = {404-411}, doi = {10.1016/j.ntt.2008.04.004}, pmid = {18558472}, issn = {0892-0362}, mesh = {Age Factors ; Animals ; Avoidance Learning/drug effects/physiology ; Brain/*drug effects/metabolism/physiopathology ; Brain Chemistry/*drug effects/physiology ; Cocaine/*adverse effects ; Cocaine-Related Disorders/*physiopathology ; Dopamine Uptake Inhibitors/adverse effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Extinction, Psychological/drug effects/physiology ; Male ; Nicotine/*pharmacology ; Nicotinic Agonists/pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; }, abstract = {Nicotine is one of the most commonly used drugs in adolescence and has been shown to alter the rewarding effects of cocaine when administered in adulthood. Although the abuse potential of a drug has been suggested to be a balance between its rewarding and aversive effects, the long-term effects of nicotine on the aversive properties of other drugs had not been studied. To that end, in the present study rats exposed to nicotine (0.4 mg/kg) during adolescence (postnatal days 35-44) were tested for the acquisition and extinction of a cocaine-induced conditioned taste aversion (10, 18 or 32 mg/kg) in adulthood. Conditioning consisted of four saccharin-drug pairings followed by six extinction trials. Although cocaine-induced aversions at all doses, no effect of nicotine preexposure was seen during acquisition. During extinction, the nicotine-preexposed groups conditioned with 10 and 18 mg/kg cocaine displayed a decreased rate of extinction compared to their respective controls. These results suggest that while adolescent nicotine exposure does not appear to directly alter the aversive properties of cocaine it may affect other processes related to the response to drugs given in adulthood.}, } @article {pmid18556053, year = {2008}, author = {Rauhut, AS and Hawrylak, M and Mardekian, SK}, title = {Bupropion differentially alters the aversive, locomotor and rewarding properties of nicotine in CD-1 mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {90}, number = {4}, pages = {598-607}, pmid = {18556053}, issn = {0091-3057}, support = {R15 DA019866/DA/NIDA NIH HHS/United States ; R15 DA019866-01/DA/NIDA NIH HHS/United States ; DA019866/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Antidepressive Agents, Second-Generation/*pharmacology ; Bupropion/*pharmacology ; Conditioning, Operant/*drug effects ; Data Interpretation, Statistical ; Dose-Response Relationship, Drug ; Male ; Mice ; Motor Activity/*drug effects ; Nicotine/*antagonists & inhibitors/*pharmacology ; Nicotinic Agonists/*pharmacology ; Reinforcement, Psychology ; Taste/drug effects ; }, abstract = {The present experiments determined the effects of bupropion on the motivational (aversive and rewarding) and locomotor properties of nicotine in CD-1 mice. Preliminary experiments determined effective nicotine doses (0.1-2.0 mg/kg) to produce a conditioned taste aversion (CTA) or conditioned place preference (CPP; Experiments 1a and 2a, respectively). Mice were administered vehicle or bupropion (1-20 mg/kg) followed by vehicle or nicotine after drinking saccharin during CTA training (Experiment 1b). Mice were administered vehicle or bupropion (1-20 mg/kg) 15 (Experiment 2b) or 30 (Experiment 2c) minutes (min) prior to vehicle or nicotine during CPP training. The two highest nicotine doses produced CTAs and a moderate nicotine dose (0.4 mg/kg) produced a CPP. Bupropion dose-dependently blocked nicotine CTA. For the 15-min pretreatment interval, bupropion dose-dependently increased locomotor activity and produced CPPs when administered alone; whereas for the 30-min pretreatment interval, only the highest bupropion dose increased locomotor activity and produced a CPP. However, bupropion failed to alter nicotine CPP and the co-administration of bupropion and nicotine did not increase locomotor activity more so than when bupropion was administered alone regardless as to the pretreatment interval. Thus, bupropion selectively altered the aversive properties of nicotine in CD-1 mice.}, } @article {pmid18514923, year = {2008}, author = {Wood, MD and Norris, JN and Daniel, AM and Papini, MR}, title = {Trial-selective effects of U50,488H, a kappa-opioid receptor agonist, on consummatory successive negative contrast.}, journal = {Behavioural brain research}, volume = {193}, number = {1}, pages = {28-36}, doi = {10.1016/j.bbr.2008.04.016}, pmid = {18514923}, issn = {0166-4328}, mesh = {3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/administration & dosage/*pharmacology ; Analgesics, Non-Narcotic/administration & dosage/pharmacology ; Animals ; Behavior, Animal/drug effects/physiology ; Consummatory Behavior/*drug effects/physiology ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Male ; Rats ; Rats, Long-Evans ; Receptors, Opioid, kappa/*agonists ; }, abstract = {A series of experiments studied the effects of the kappa-opioid receptor agonist U50,488H on consummatory successive negative contrast (cSNC) in rats. In cSNC, previous experience with a 32% sucrose solution leads to greater rejection of 4% sucrose than exclusive experience with 4% sucrose. Experiments 1 and 2 revealed that U50,488H failed to influence cSNC when administered before the first downshifted trial, but either attenuated (1mg/kg) or enhanced (3 and 10mg/kg) cSNC when administered before the second downshift trial. Experiment 3 showed that U50,488H administered immediately after the first downshift trial had no effect on cSNC at the 1mg/kg dose, but tended to increase cSNC at the 3mg/kg dose. However, Experiment 4 suggested that the apparent enhancement of cSNC after 3mg/kg U50 administered posttrial 11 may have reflected the development of a conditioned taste aversion. The trial-selective attenuating effect of the low dose may reflect an anxiolytic-like property of U50,488H.}, } @article {pmid18479764, year = {2008}, author = {Guitton, MJ and Klin, Y and Dudai, Y}, title = {Taste-dependent sociophobia: when food and company do not mix.}, journal = {Behavioural brain research}, volume = {191}, number = {2}, pages = {148-152}, doi = {10.1016/j.bbr.2008.03.022}, pmid = {18479764}, issn = {0166-4328}, mesh = {Animals ; Antimanic Agents/administration & dosage ; Avoidance Learning/physiology ; Behavior, Animal/drug effects ; Conditioning, Classical/drug effects/physiology ; *Food ; *Interpersonal Relations ; Linear Models ; Lithium Chloride/administration & dosage ; Phobic Disorders/*etiology ; Piperazines/adverse effects ; Rats ; Serotonin Receptor Agonists/adverse effects ; *Taste ; }, abstract = {Using a combination of the paradigm of conditioned taste aversion (CTA) and of the paradigm of social interactions, we report here that in the rat, eating while anxious may result in long-term alterations in social behavior. In the conventional CTA, the subject learns to associate a tastant (the conditioned stimulus, CS) with delayed toxicosis (an unconditioned stimulus, UCS) to yield taste aversion (the conditioned response, CR). However, the association of taste with delayed negative internal states that could generate CRs that are different from taste aversion should not be neglected. Such associations may contribute to the ontogenesis, reinforcement and symptoms of some types of taste- and food-related disorders. We have recently reported that a delayed anxiety-like state, induced by the anxiogenic drug meta-chlorophenylpiperazine (mCPP), can specifically associate with taste to produce CTA. We now show that a similar protocol results in a marked lingering impairment in social interactions in response to the conditioned taste. This is hence a learned situation in which food and company do not mix well.}, } @article {pmid18452819, year = {2008}, author = {Perrotti, M and Doyle, T and Kumar, P and McLeod, D and Badger, W and Prater, S and Moran, M and Rosenberg, S and Bonatsos, C and Kreitner, C and Kiehl, R and Chang, T and Kolodziej, M}, title = {Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10).}, journal = {Urologic oncology}, volume = {26}, number = {3}, pages = {276-280}, doi = {10.1016/j.urolonc.2007.04.003}, pmid = {18452819}, issn = {1078-1439}, mesh = {Aged ; Combined Modality Therapy/adverse effects ; Docetaxel ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prostatic Neoplasms/*drug therapy/pathology/*radiotherapy ; Risk Factors ; Taxoids/adverse effects/*therapeutic use ; }, abstract = {PURPOSE: A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer.

PATIENTS AND METHODS: Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded.

RESULTS: Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive.

CONCLUSION: The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.}, } @article {pmid18450070, year = {2003}, author = {Brooks, DC and Bowker, JL and Anderson, JE and Palmatier, MI}, title = {Impact of brief or extended extinction of a taste aversion on inhibitory associations: evidence from summation, retardation, and preference tests.}, journal = {Learning & behavior}, volume = {31}, number = {1}, pages = {69-84}, pmid = {18450070}, issn = {1543-4494}, mesh = {Animals ; *Choice Behavior ; Conditioning, Psychological ; *Extinction, Psychological ; *Inhibition, Psychological ; Male ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Time Factors ; }, abstract = {In five conditioned taste aversion experiments with rats, summation, retardation, and preference tests were used to assess the effects of extinguishing a conditioned saccharin aversion for three or nine trials. In Experiment 1, a summation test showed that saccharin aversion extinguished over nine trials reduced the aversion to a merely conditioned flavor (vinegar), whereas three saccharin extinction trials did not subsequently influence the vinegar aversion. Experiment 2 clarified that result, with unpaired controls equated on flavor exposure prior to testing; the results with those controls suggested that the flavor extinguished for nine trials produced generalization decrement during testing. In Experiment 3, the saccharin aversion reconditioned slowly after nine extinction trials, but not after three. Those results suggested the development of latent inhibition after more than three extinction trials. Preference tests comparing saccharin consumption with a concurrently available fluid (water in Experiment 4, saline in Experiment 5) showed that the preference for saccharin was greater after nine extinction trials than after three. However, saccharin preference after nine extinction trials was not greater, as compared with that for either latent inhibition controls (Experiments 4 and 5) or a control given equated exposures to saccharin and trained to drink saline at a high rate prior to testing (Experiment 5). Concerns about whether conditioned inhibition has been demonstrated in any flavor aversion procedure are discussed. Our findings help explain both successes and failures in demonstrating post-extinction conditioned response recovery effects reported in the conditioned taste aversion literature, and they can be explained using a memory interference account.}, } @article {pmid18441286, year = {2008}, author = {Ding, HK and Teixeira, CM and Frankland, PW}, title = {Inactivation of the anterior cingulate cortex blocks expression of remote, but not recent, conditioned taste aversion memory.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {15}, number = {5}, pages = {290-293}, doi = {10.1101/lm.905008}, pmid = {18441286}, issn = {1549-5485}, mesh = {Anesthetics, Local/administration & dosage/pharmacology ; Animals ; *Avoidance Learning/drug effects ; *Conditioning, Psychological/drug effects ; Gyrus Cinguli/*drug effects ; Hippocampus/drug effects ; Lidocaine/administration & dosage/pharmacology ; *Memory ; Mice ; *Taste ; }, abstract = {Previous studies have shown that medial prefrontal cortical regions, such as the anterior cingulate cortex (ACC), play a key role in the expression of remote spatial and contextual memory. To evaluate whether this role is conserved in hippocampal-independent tasks we trained mice in the conditioned taste aversion (CTA) paradigm. Lidocaine-induced inactivation of the ACC blocked the expression of CTA tested one month (remote), but not one day (recent), after conditioning with either a weak or strong unconditioned stimulus (US). These data suggest that the ACC may play a conserved role in remote memory, regardless of memory strength or content.}, } @article {pmid18439577, year = {2008}, author = {Brand, L and Groenewald, I and Stein, DJ and Wegener, G and Harvey, BH}, title = {Stress and re-stress increases conditioned taste aversion learning in rats: possible frontal cortical and hippocampal muscarinic receptor involvement.}, journal = {European journal of pharmacology}, volume = {586}, number = {1-3}, pages = {205-211}, doi = {10.1016/j.ejphar.2008.03.004}, pmid = {18439577}, issn = {0014-2999}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Hippocampus/*physiology ; Lithium Chloride/pharmacology ; Male ; Mental Recall/drug effects ; Muscarinic Antagonists/pharmacology ; Prefrontal Cortex/drug effects/*physiology ; Quinuclidinyl Benzilate/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M1/drug effects/metabolism ; Receptors, Muscarinic/drug effects/*physiology ; Stress Disorders, Post-Traumatic/psychology ; Stress, Psychological/*psychology ; Taste/drug effects/*physiology ; }, abstract = {Symptoms of posttraumatic stress disorder are often precipitated by sensory cues in the form of visual, auditory, olfactory and gustatory "flashbacks" resulting in enhanced fear-memory consolidation and the characteristic symptoms of re-experiencing, avoidance and hyper-arousal. Single prolonged stress with and without re-stress have been used to explore the neurobiology of this disorder, particularly with respect to contextual conditioning and spatial memory impairment. However, less work has been done regarding associative sensory-related memories linked to aversive events. Although growing evidence supports a role for cholinergic pathways in stress, this has not been studied in the above animal models. We studied the effects of single prolonged stress with and without re-stress on conditioned taste aversion learning in rats, together with differential analysis of frontal cortical and hippocampal [3H]-quinuclidinyl benzylate ([3H]-QNB) muscarinic receptor binding. Single prolonged stress with and without re-stress both enhanced associative sensory aversion learning 7 days after stressor-taste pairing, although re-stress did not strengthen this response. Increased cortical and hippocampal muscarinic receptor density (Bmax) was found 7 days after single prolonged stress with re-stress, although receptor affinity remained unaltered. Frontal cortical and hippocampal muscarinic receptor changes may thus underlie conditioned taste aversion learning in rats exposed to stress and re-stress. These data suggest that it may be useful to study the role of cholinergic pathways in mediating associative memory in psychiatric disorders such as posttraumatic stress disorder.}, } @article {pmid18433849, year = {2008}, author = {Traverso, LM and Ruiz, G and Camino, G and De la Casa, LG}, title = {Ketamine blocks the formation of a gustatory memory trace in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {90}, number = {3}, pages = {305-311}, doi = {10.1016/j.pbb.2008.03.002}, pmid = {18433849}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Classical/drug effects ; Excitatory Amino Acid Antagonists/*pharmacology ; Ketamine/*pharmacology ; Male ; Memory/*drug effects ; Motivation ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/drug effects ; Taste/*drug effects ; }, abstract = {N-methyl-D-aspartate (NMDA) receptors appear to play a central role in learning and memory processes, as the administration of antagonistic substances of these receptors hinders learning acquisition by using different behavioral paradigms (e.g., Riedel G, Platt B, Micheau J. Glutamate receptor function in learning and memory. Behavioural Brain Research, 2003;140 (1-2):1-47.). In the specific case of conditioned taste aversion, the administration of ketamine seems to affect the acquisition of conditioning when the drugs are administered before the experimental treatment. In this paper we present three experiments designed to analyze the effect of different ketamine doses (25 mg/kg, 50 mg/kg, 75 mg/kg and 120 mg/kg), administered between exposure to a taste (the conditioned stimulus) and the administration of the unconditioned stimulus, on the acquisition of a taste aversion association. The results reveal that higher ketamine doses (75 mg/kg and 120 mg/kg) have a disruptive effect on conditioned taste aversion by impeding the formation of the gustatory trace.}, } @article {pmid18394466, year = {2008}, author = {Sacktor, TC}, title = {PKMzeta, LTP maintenance, and the dynamic molecular biology of memory storage.}, journal = {Progress in brain research}, volume = {169}, number = {}, pages = {27-40}, doi = {10.1016/S0079-6123(07)00002-7}, pmid = {18394466}, issn = {0079-6123}, mesh = {Animals ; Excitatory Postsynaptic Potentials/physiology ; Hippocampus/physiology ; Humans ; Long-Term Potentiation/*physiology ; Memory/*physiology ; *Molecular Biology ; Protein Kinase C/*genetics/*metabolism ; Rats ; }, abstract = {How memories persist is a fundamental neurobiological question. The most commonly studied physiological model of memory is long-term potentiation (LTP). The molecular mechanisms of LTP can be divided into two phases: induction, triggering the potentiation; and maintenance, sustaining the potentiation over time. Although many molecules participate in induction, very few have been implicated in the mechanism of maintenance. Understanding maintenance, however, is critical for testing the hypothesis that LTP sustains memory storage in the brain. Only a single molecule has been found both necessary and sufficient for maintaining LTP--the brain-specific, atypical PKC isoform, protein kinase Mzeta (PKMzeta). Although full-length PKC isoforms respond to transient second messengers, and are involved in LTP induction, PKMzeta is a second messenger-independent kinase, consisting of the independent catalytic domain of PKCzeta, and is persistently active to sustain LTP maintenance. PKMzeta is produced by a unique PKMzeta mRNA, which is generated by an internal promoter within the PKCzeta gene and transported to the dendrites of neurons. LTP induction increases new PKMzeta synthesis, and the increased level of PKMzeta then enhances synaptic transmission by doubling the number of postsynaptic AMPA receptors (AMPAR) through GluR2 subunit-mediated trafficking of the receptors to the synapse. PKMzeta mediates synaptic potentiation specifically during the late-phase of LTP, as PKMzeta inhibitors can reverse established LTP when applied several hours after tetanization in hippocampal slices or 1 day after tetanization in vivo. These studies set the stage for testing the hypothesis that the mechanism of LTP maintenance sustains memory storage. PKMzeta inhibition in the hippocampus after learning eliminates the retention of spatial memory. Once the PKMzeta inhibitor has been eliminated, the memory is still erased, but new spatial memories can be learned and stored. Similar results are found for conditioned taste aversion when the inhibitor is injected in the insular neocortex. Thus PKMzeta is the first molecule found to be a component of the long-term memory trace.}, } @article {pmid18393275, year = {2008}, author = {Pautassi, RM and Arias, C and Molina, JC and Spear, N}, title = {Domperidone interferes with conditioned disgust reactions but not taste avoidance evoked by a LiCl-paired taste in infant rats.}, journal = {Developmental psychobiology}, volume = {50}, number = {4}, pages = {343-352}, doi = {10.1002/dev.20288}, pmid = {18393275}, issn = {1098-2302}, support = {AA013098/AA/NIAAA NIH HHS/United States ; AA11960/AA/NIAAA NIH HHS/United States ; MH035219/MH/NIMH NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic/administration & dosage/*pharmacology ; Animals ; Animals, Newborn ; Antiemetics/administration & dosage/*pharmacology ; Avoidance Learning/*drug effects ; Blood-Brain Barrier/drug effects ; Conditioning, Psychological/*drug effects ; Domperidone/administration & dosage/*pharmacology ; Female ; Lithium Chloride/administration & dosage/*pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Rats exhibit taste avoidance and conditioned disgust reactions when stimulated with a tastant paired with lithium chloride (LiCl). Lithium-mediated activation of chemoreceptor nuclei at the brainstem appears to determine the acquisition of conditioned taste aversion (CTA) in adult rodents. Domperidone (DOM), an anti-emetic drug that does not cross the blood-brain barrier, was employed to analyze mechanisms underlying LiCl-mediated CTA in infant rats. On postnatal day 13 animals were given DOM followed by a pairing between intraoral saccharin and LiCl. Saccharin consumption at testing was lower in lithium-treated pups than in controls. DOM did not interfere with this LiCl-mediated taste avoidance but significantly decreased LiCl-mediated disgust reactions (head-shaking and wall climbing). Activation of the emetic system of the brainstem does not seem necessary for the acquisition of LiCl-mediated conditioned taste avoidance. Yet, these centers seem to be involved in the palatability shift resulting from taste-LiCl pairings. These results indicate an early dissociation between conditioned disgust reactions and conditioned taste avoidance.}, } @article {pmid18380122, year = {2007}, author = {Minnier, E and Misanin, JR and Hinderliter, CF}, title = {Age and interstimulus interval in forward and backward long-trace taste-aversion conditioning.}, journal = {Perceptual and motor skills}, volume = {105}, number = {3 Pt 2}, pages = {1223-1226}, doi = {10.2466/pms.105.4.1223-1226}, pmid = {18380122}, issn = {0031-5125}, mesh = {Age Factors ; Aging/physiology ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/physiology ; Conditioning, Classical/drug effects/*physiology ; Drinking/drug effects/*physiology ; Female ; Injections, Intraperitoneal ; Lithium Chloride/pharmacology ; Rats ; Reinforcement Schedule ; Saccharin ; Taste/drug effects/*physiology ; }, abstract = {Rats, 70-79 days old and 477-557 days old, experienced either a forward or backward taste-aversion conditioning trial with a 15-min. or 45-min. interstimulus interval. Forward conditioning was evident in both age groups at both interstimulus intervals. Backward conditioning was evident in both age groups only at the 15-min. interstimulus interval. The failure to obtain backward conditioning at the 45-min. interval was attributed to the effect of stress, produced by injection of the US, on long-trace conditioning. As reported with forward conditioning, stress may alter metabolic rate such that the intervals at which associations can be formed are shortened.}, } @article {pmid18374904, year = {2008}, author = {Kwon, B and Goltz, M and Houpt, TA}, title = {Expression of AP-1 family transcription factors in the amygdala during conditioned taste aversion learning: role for Fra-2.}, journal = {Brain research}, volume = {1207}, number = {}, pages = {128-141}, pmid = {18374904}, issn = {0006-8993}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; R01 DC003198-08/DC/NIDCD NIH HHS/United States ; R01DC03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Food Preferences ; Fos-Related Antigen-2/*physiology ; Gene Expression/drug effects/physiology ; Gene Expression Regulation/drug effects/*physiology ; Lithium Chloride/pharmacology ; Male ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {Conditioned taste aversion (CTA) learning occurs after the pairing of a novel taste with a toxin (e.g. sucrose with LiCl). The immediate early gene c-Fos is necessary for CTA learning, but c-Fos alone cannot be sufficient for consolidation. The expression of other AP-1 proteins from the Fos- and Jun-families may also be required shortly after conditioning for CTA consolidation. To screen for the expression of AP-1 transcription factors within small subregions, RT-PCR analysis was used after laser capture microdissection of the amygdala. Rats were infused intraorally with 5% sucrose (6 ml/6 min) or injected with LiCl (12 ml/kg, 0.15 M, i.p.) or given sucrose paired with LiCl (sucrose/LiCl), or not treated; 1 h later their brains were dissected. The lateral (LA), basolateral (BLA), and central (CeA) subnuclei of the amgydala of single 5 microm sections from individual rats were dissected using the Arcturus PixCell II system. Semi-quantitative RT-PCR showed the consistent presence of c-Fos, Fra-2, c-Jun, and JunD in the amygdala. In situ hybridization confirmed that c-Fos and Fra-2 mRNA expression was increased in the CeA after LiCl and sucrose/LiCl treatment. Immunohistochemistry for Fra-2 revealed high baseline levels of Fra-2 protein in the BLA and CeA, but also an increase in Fra-2 in the BLA and CeA after LiCl and sucrose/LiCl treatment. The similarity of response in LiCl and sucrose/LiCl treated groups might reflect activation by LiCl in both groups. To control for the effects of LiCl, rats were tested in a learned safety experiment. Fra-2 and c-Fos were examined in response to sucrose/LiCl in rats with prior familiarity with sucrose compared to rats without prior exposure to sucrose. The familiar (pre-exposure) group showed a significantly decreased number of Fra-2-positive cells compared with the novel group in the BLA, but not in the CeA. Because pre-exposure to sucrose attenuates CTA learning, a decreased cellular response in pre-exposed rats suggests a specific correlation with CTA learning. Changes in Fra-2 and c-Fos expression in the BLA and CeA at the time of conditioning, together with constitutive expression of c-Jun and JunD, may contribute to CTA learning.}, } @article {pmid18372387, year = {2008}, author = {Pittman, DW and Smith, KR and Crawley, ME and Corbin, CH and Hansen, DR and Watson, KJ and Gilbertson, TA}, title = {Orosensory detection of fatty acids by obesity-prone and obesity-resistant rats: strain and sex differences.}, journal = {Chemical senses}, volume = {33}, number = {5}, pages = {449-460}, doi = {10.1093/chemse/bjn012}, pmid = {18372387}, issn = {1464-3553}, support = {DK59611/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Fatty Acids/*pharmacology ; Female ; Lithium Chloride/pharmacology ; Male ; *Obesity/genetics ; Rats ; Rats, Inbred Strains ; *Sex Characteristics ; Sodium Chloride/pharmacology ; Species Specificity ; Stimulation, Chemical ; Taste/drug effects/*physiology ; }, abstract = {A series of brief-access (15s) behavioral assays following the formation of a conditioned taste aversion (CTA) to linoleic acid were performed in order to follow up on observations showing differences in the chemosensory responses to dietary fat in obesity-prone (Osborne-Mendel [O-M]) and obesity-resistant (S5B/Pl) rat strains. Strong aversions to linoleic acid (conditioned stimulus 100 microM) were generated in both O-M and S5B/Pl rats to concentrations as low as 2.5 microM. Observed strain differences were in contrast to expectations based upon electrophysiological studies previously showing greater fatty acid-induced inhibition of delayed rectifying K+ channels in S5B/Pl rats. In the CTA assays, the O-M rats showed aversions at lower fatty acid concentrations with more resistance to extinction in brief-access orosensory tests, suggesting that the obesity-prone strain may be more sensitive in the detection and subsequent avoidance of linoleic acid than the obesity-resistant strain. The independent variable of sex produced even greater differences in the avoidance of linoleic acid following conditioning than the effects of strain. Female rats of both strains were significantly more sensitive to fatty acids, showed greater cross-generalization from linoleic to oleic acid, and showed greater avoidance of linoleic acid than male counterparts. These findings suggest genetic influences on yet to be identified mechanisms potentially within the gustatory system that affect the sensitivity to detect the fatty acid chemicals found in dietary fat during brief-access orosensory testing.}, } @article {pmid18337417, year = {2008}, author = {Grossman, SE and Fontanini, A and Wieskopf, JS and Katz, DB}, title = {Learning-related plasticity of temporal coding in simultaneously recorded amygdala-cortical ensembles.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {28}, number = {11}, pages = {2864-2873}, pmid = {18337417}, issn = {1529-2401}, support = {DC-008720/DC/NIDCD NIH HHS/United States ; R03 DC008885/DC/NIDCD NIH HHS/United States ; R01 DC006666/DC/NIDCD NIH HHS/United States ; F31 DC008720/DC/NIDCD NIH HHS/United States ; DC-006666/DC/NIDCD NIH HHS/United States ; DC-008885/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Cerebral Cortex/*physiology ; Female ; Learning/*physiology ; Male ; Neural Pathways/physiology ; Neuronal Plasticity/*physiology ; Rats ; Rats, Long-Evans ; Time Factors ; }, abstract = {Emotional learning requires the coordinated action of neural populations in limbic and cortical networks. Here, we performed simultaneous extracellular recordings from gustatory cortical (GC) and basolateral amygdalar (BLA) neural ensembles as awake, behaving rats learned to dislike the taste of saccharin [via conditioned taste aversion (CTA)]. Learning-related changes in single-neuron sensory responses were observed in both regions, but the nature of the changes was region specific. In GC, most changes were restricted to relatively late aspects of the response (starting approximately 1.0 s after stimulus administration), supporting our hypothesis that in this paradigm palatability-related information resides exclusively in later cortical responses. In contrast, and consistent with data suggesting the amygdala's primary role in judging stimulus palatability, CTA altered all components of BLA taste responses, including the earliest. Finally, learning caused dramatic increases in the functional connectivity (measured in terms of cross-correlation peak heights) between pairs of simultaneously recorded BLA and GC neurons, increases that were evident only during taste processing. Our simultaneous assays of the activity of single neurons in multiple relevant brain regions across learning suggest that the transmission of taste information through amygdala-cortical circuits plays a vital role in CTA memory formation.}, } @article {pmid18337024, year = {2008}, author = {Nakajima, S}, title = {Effect of extra running on running-based taste aversion in rats.}, journal = {Behavioural processes}, volume = {78}, number = {3}, pages = {470-472}, doi = {10.1016/j.beproc.2008.01.018}, pmid = {18337024}, issn = {0376-6357}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Conditioning, Classical/*physiology ; Cues ; Male ; Motor Activity/physiology ; Physical Conditioning, Animal/physiology/psychology ; Rats ; Rats, Wistar ; Running/*physiology/psychology ; Taste/*physiology ; Thirst/physiology ; Time Factors ; }, abstract = {Voluntary running in an activity wheel endowed rats with aversion to a taste solution consumed before the running. This running-based taste aversion was attenuated by extra running opportunities interspersed among the taste-running pairings, but the attenuating effect was reduced by signaling the extra running by another taste cue. These results correspond to the so-called degraded contingency effect and cover-cue effect in the traditional preparations of Pavlovian conditioning.}, } @article {pmid18325609, year = {2008}, author = {Lukong, KE and Richard, S}, title = {Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.}, journal = {Behavioural brain research}, volume = {189}, number = {2}, pages = {357-363}, doi = {10.1016/j.bbr.2008.01.010}, pmid = {18325609}, issn = {0166-4328}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Animals ; Avoidance Learning/physiology ; Cerebellum/*metabolism ; Conditioning, Classical/physiology ; Gait/genetics/*physiology ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Skills/*physiology ; Muscle Strength/genetics/physiology ; Pattern Recognition, Visual/*physiology ; Postural Balance/physiology ; RNA-Binding Proteins/genetics/*metabolism ; Recognition, Psychology/physiology ; Rotarod Performance Test ; Spatial Behavior/physiology ; }, abstract = {The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.}, } @article {pmid18305172, year = {2008}, author = {Accolla, R and Carleton, A}, title = {Internal body state influences topographical plasticity of sensory representations in the rat gustatory cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {10}, pages = {4010-4015}, pmid = {18305172}, issn = {1091-6490}, mesh = {Animals ; Conditioning, Psychological/drug effects ; Extinction, Psychological/drug effects ; *Homeostasis/drug effects ; Models, Neurological ; Rats ; Rats, Wistar ; Saccharin/administration & dosage/pharmacology ; Somatosensory Cortex/cytology/drug effects/*physiology ; Taste/drug effects/*physiology ; }, abstract = {Primary sensory cortices are remarkably organized in spatial maps according to specific sensory features of the stimuli. These cortical maps can undergo plastic rearrangements after changes in afferent ("bottom-up") sensory inputs such as peripheral lesions or passive sensory experience. However, much less is known about the influence of "top-down" factors on cortical plasticity. Here, we studied the effect of a visceral malaise on taste representations in the gustatory cortex (GC). Using in vivo optical imaging, we showed that inducing conditioned taste aversion (CTA) to a sweet and pleasant stimulus induced plastic rearrangement of its cortical representation, becoming more similar to a bitter and unpleasant taste representation. Using a behavior task, we showed that changes in hedonic perception are directly related to the maps plasticity in the GC. Indeed imaging the animals after CTA extinction indicated that sweet and bitter representations were dissimilar. In conclusion, we showed that an internal state of malaise induces plastic reshaping in the GC associated to behavioral shift of the stimulus hedonic value. We propose that the GC not only encodes taste modality, intensity, and memory but extends its integrative properties to process also the stimulus hedonic value.}, } @article {pmid18304749, year = {2008}, author = {Pistell, PJ and Zhu, M and Ingram, DK}, title = {Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease.}, journal = {Neuroscience}, volume = {152}, number = {3}, pages = {594-600}, pmid = {18304749}, issn = {0306-4522}, support = {P20 RR021945/RR/NCRR NIH HHS/United States ; P30 DK072476/DK/NIDDK NIH HHS/United States ; 1P30 DK072476/DK/NIDDK NIH HHS/United States ; 1P20RR02-1945/RR/NCRR NIH HHS/United States ; P30 DK072476-01/DK/NIDDK NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; P20 RR021945-01/RR/NCRR NIH HHS/United States ; }, mesh = {Alzheimer Disease/complications/genetics/*metabolism ; Amyloid beta-Protein Precursor/genetics/*metabolism ; Animals ; Avoidance Learning/physiology ; Brain/*metabolism/pathology/physiopathology ; Conditioning, Psychological/physiology ; Disease Models, Animal ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Learning Disabilities/genetics/*metabolism/physiopathology ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Mutation/genetics ; Plaque, Amyloid/genetics/metabolism/pathology ; Presenilin-1/genetics/*metabolism ; Sex Characteristics ; Taste Disorders/genetics/metabolism/physiopathology ; }, abstract = {Research into the underlying mechanisms of cognitive dysfunction in Alzheimer's disease (AD) has relied traditionally on tasks such as the water maze which evaluate spatial learning and memory. Since non-spatial forms of memory are also disrupted by AD, it is critical to establish other paradigms capable of investigating these deficits. Utilizing a non-spatial learning task, acquisition of conditioned taste aversion (CTA) was evaluated in a mouse model of AD. This line of transgenic mice encode a mutated allele of the human amyloid precursor protein (APP) and presenilin 1 (PS1) genes and exhibit extensive amyloid plaque deposition in the brain by 6-7 mo of age. Compared with wild-type mice, 10-17 month old APP/PS1 mice failed to acquire CTA to saccharin. Mice that only possessed one of the two mutations were able to acquire CTA to the saccharin. In 2-5 month old APP/PS1 mice acquisition of CTA was disrupted despite the lack of extensive plaque deposition. However, further analysis indicated a potential gender difference in both the CTA deficit and onset of plaque deposition with females showing greater conditioned aversion.}, } @article {pmid18276171, year = {2008}, author = {Miranda, MI and Rodríguez-García, G and Reyes-López, JV and Ferry, B and Ferreira, G}, title = {Differential effects of beta-adrenergic receptor blockade in basolateral amygdala or insular cortex on incidental and associative taste learning.}, journal = {Neurobiology of learning and memory}, volume = {90}, number = {1}, pages = {54-61}, doi = {10.1016/j.nlm.2008.01.004}, pmid = {18276171}, issn = {1095-9564}, mesh = {Adrenergic beta-Antagonists/*pharmacology ; Amygdala/drug effects/*physiology ; Animals ; Association Learning/*drug effects/physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Habituation, Psychophysiologic/drug effects/physiology ; Male ; Microinjections ; Norepinephrine/physiology ; Propranolol/*pharmacology ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta/*physiology ; Taste ; }, abstract = {The importance of central beta-adrenergic system has been essentially investigated in aversive/emotional learning tasks. However, recent data suggest that the beta-adrenergic system is also required for incidental taste learning. In the present study we evaluated in rats whether beta-adrenergic receptor activity is required for taste habituation, an incidental taste learning, and also for conditioned taste aversion (CTA) learning, an associative learning. To address this issue, a low dose of the beta-adrenergic antagonist propranolol was infused before learning in either the basolateral amygdala (BLA) or the insular cortex (IC), two forebrain areas reported to play a key role in taste memory formation. Incidental taste learning was assessed using a single presentation of the sweet taste saccharin 0.1%, which is sufficient to increase saccharin consumption (relative to water baseline) during a second presentation. CTA was assessed by pairing the first saccharin 0.1% presentation with a delayed gastric malaise, thus causing a decrease in saccharin consumption (relative to water baseline) during a second presentation. Propranolol infusion in BLA (1microg/0.2microl) or IC (2.5microg/0.5microl) before the first taste exposure impaired incidental taste learning but did not affect CTA. These results highlight the important role played by the beta-adrenergic receptor activation in cortical and amygdaloid structures during taste learning. Moreover, they are the first to suggest that incidental learning is more sensitive to blockade of noradrenergic system than associative learning.}, } @article {pmid18264696, year = {2008}, author = {Järbe, TU and Li, C and Vadivel, SK and Makriyannis, A}, title = {Discriminative stimulus effects of the cannabinoid CB1 receptor antagonist rimonabant in rats.}, journal = {Psychopharmacology}, volume = {198}, number = {4}, pages = {467-478}, pmid = {18264696}, issn = {0033-3158}, support = {DA 9158/DA/NIDA NIH HHS/United States ; K02 DA000253/DA/NIDA NIH HHS/United States ; K05 DA000493/DA/NIDA NIH HHS/United States ; DA 13429/DA/NIDA NIH HHS/United States ; DA 7215/DA/NIDA NIH HHS/United States ; DA 03801/DA/NIDA NIH HHS/United States ; R01 DA007215/DA/NIDA NIH HHS/United States ; P01 DA009158/DA/NIDA NIH HHS/United States ; R01 DA009064/DA/NIDA NIH HHS/United States ; DA 09064/DA/NIDA NIH HHS/United States ; DA 00253/DA/NIDA NIH HHS/United States ; DA 00493/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Arachidonic Acids/pharmacology ; Avoidance Learning/drug effects ; Camphanes/pharmacology ; Discrimination Learning/drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Dronabinol/pharmacology ; Hallucinogens/pharmacology ; Indoles/pharmacology ; Injections, Intraperitoneal ; Lithium Chloride/pharmacology ; Male ; Piperidines/administration & dosage/*pharmacology ; Pyrazoles/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/*antagonists & inhibitors ; Receptor, Cannabinoid, CB2/antagonists & inhibitors ; Rimonabant ; Taste/drug effects ; }, abstract = {OBJECTIVE: To examine the discriminative stimulus effects of the cannabinoid CB(1) receptor (CB(1)R) antagonist/inverse agonist rimonabant (SR141716A) using a discriminated taste aversion (DTA) procedure.

MATERIALS AND METHODS: Groups of rats were trained to discriminate between drug (5.6 or 3 mg/kg) and vehicle in DTA (t' = 20 min). The 30-min drinking opportunity after rimonabant pretreatment was followed by injection of lithium chloride (120 mg/kg) in the experimental (EXP) animals. When offered fluid after vehicle pretreatment, EXP animals subsequently were given intraperitoneal saline (NaCl, 10 ml/kg). Post-drinking treatment for controls (CONT) was NaCl irrespective of the pretreatment condition (rimonabant or vehicle). Tests examined other doses and drugs (t' = 20 min).

RESULTS: The rimonabant analog AM251 (1 to 5.6 mg/kg) substituted for rimonabant. AM281 also appeared to substitute, but interpretation is complicated by unconditioned effects (drinking suppressed also in the CONT group). The CB(2)R antagonists SR144528 (18 and 30 mg/kg), AM630 (1 to 10 mg/kg), and the CB(1)R agonist methanandamide (mAEA, 3 and 10 mg/kg) did not substitute. There was a dose-related attenuation of the rimonabant-induced suppression of saccharin drinking when Delta9-tetrahydrocannabinol (Delta9-THC; 0.3 to 5.6 mg/kg), but not mAEA (1 to 10 mg/kg), was given together with rimonabant (3 mg/kg). Unconditioned effects occurred with the mAEA-rimonabant combination, not evident for combinations of rimonabant and Delta9-THC. mAEA (10 mg/kg) plus AM251 (5.6 mg/kg) resulted in strong unconditioned effects.

CONCLUSION: Rimonabant induces a discriminative stimulus in DTA that continues to show potential for further examination of cannabinoid receptor antagonism.}, } @article {pmid18207023, year = {2008}, author = {Teixeira, G and Paschoal, PO and de Oliveira, VL and Pedruzzi, MM and Campos, SM and Andrade, L and Nóbrega, A}, title = {Diet selection in immunologically manipulated mice.}, journal = {Immunobiology}, volume = {213}, number = {1}, pages = {1-12}, doi = {10.1016/j.imbio.2007.08.001}, pmid = {18207023}, issn = {0171-2985}, mesh = {Anacardium/adverse effects/chemistry/*immunology ; Animals ; Antibodies/blood ; Arachis/adverse effects/chemistry/*immunology ; Behavior, Animal ; *Diet ; *Feeding Behavior ; Female ; Food Hypersensitivity/immunology ; *Food Preferences ; Immune Tolerance ; Male ; Mice ; Mice, Inbred Strains ; }, abstract = {Diet selection is a complex problem that animals in wildlife have to deal with daily. In their natural environment, these animals meet a great variety of foods some of which they are able and prepared to eat, yet, not all of it is eaten. In addition to the biological factors, some of which we shall discuss deeper in this paper, an important factor in food preference is social contact. Alterations in the physiology of mammals can have profound effects on the choice or preference for certain foods. On the other hand the decline of taste and smell perception in the elderly, the degree of food restriction, the sensorial properties of foods (such as presentation, taste, and smell) can be considered factors that influence feeding behavior leading to aversion. Many species, including man, learn to associate nausea with taste, and as a consequence avoid its specific intake, which has been shown to be persistent. Conditioned taste aversion is a form of associative learning in which animals display an aversion to the taste of a food that has previously been paired with illness. Our group has investigated the pattern of ingestion of foods that are frequently eaten by mice in wildlife and are potentially allergenic to humans in order to study the immunological consequences to these foods such as oral tolerance and inflammatory processes of the gut. We have chosen two seeds, peanuts (Arachis hypogea) and cashew nuts (Anacardium occidentale), as our source of antigens as the first is considered to be one of the most potent food allergens and for the second there seems to be very little allergy in the human setting. We used male and female, normal, adult CBA/J, A/J, C57BL/6 and Balb/c mice 2-3 months old and hybrid (C57Bl/6xBalb/c) F1, (Balb/cxC57Bl/6) F1), (C57Bl/6xDBA2) F1 mice. Food preference appeared to be strain-specific. Animals tolerized to a determined seed, then immunized with its protein extract and re-exposed to the seed in natura alter their feeding pattern. We suggest that diet selection, a multi-factorial event, is influenced by genetic factors such as the MHC and the immunological status of the animal.}, } @article {pmid18204997, year = {2008}, author = {Rinker, JA and Busse, GD and Roma, PG and Chen, SA and Barr, CS and Riley, AL}, title = {The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.}, journal = {Psychopharmacology}, volume = {197}, number = {3}, pages = {409-419}, pmid = {18204997}, issn = {0033-3158}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Body Temperature Regulation/drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drug Interactions ; Ethanol/blood/*toxicity ; Female ; Injections, Intravenous ; Nicotine/*pharmacology/toxicity ; Rats ; Rats, Long-Evans ; Taste/*drug effects ; }, abstract = {RATIONALE: Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use.

OBJECTIVES: Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design.

MATERIALS AND METHODS: Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined.

RESULTS: Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination.

CONCLUSIONS: These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.}, } @article {pmid18193413, year = {2008}, author = {De la Torre Vacas, ML and Agüero Zapata, A}, title = {The role of the dorsal-most part of the lateral parabrachial nucleus in the processing of hypertonic NaCl using different conditioned flavor avoidance paradigms.}, journal = {Experimental brain research}, volume = {186}, number = {3}, pages = {481-491}, pmid = {18193413}, issn = {1432-1106}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Brain Injuries/physiopathology ; Drinking Behavior/physiology ; Gastric Fistula/physiopathology ; Habituation, Psychophysiologic ; Humans ; Male ; Pons/*physiology ; Rats ; Rats, Wistar ; *Sodium Chloride ; *Taste ; Water Deprivation/physiology ; }, abstract = {The parabrachial nucleus (PBN) has been strongly associated with taste aversion learning (TAL) acquisition. Independent of its suggested associative functions, this brain stem centre plays a key role in the sensorial processing of both gustatory and visceral information. The sensory visceral functions have been attributed to the lateral area of the PBN (PBNl) but, recently, it has been proposed that within this area a form of anatomical and functional segregation may also exist, determined by factors such as, the learning paradigm used, the nature of aversive agent used, or the route chosen for the administration of this agent. This study used a lesion approach in rats to address the question of whether the dorsal most portion of the PBNl plays a key role in the acquisition of a conditioned avoidance to flavored stimuli induced by hypertonic sodium chloride (intra gastric), and whether this role is dependent on the flavor avoidance learning (FAL) paradigm used, concurrent (experiment 1) or delayed-sequential FAL (experiment 2). Results showed a clear disruptive effect of the PBNl electrolytic lesion on the acquisition of the concurrent FAL, but hardly any attenuation of the delayed-sequential FAL. This finding is discussed in the context of the hypothesis that two separate and apparently non-redundant routes exist for the processing of the visceral information.}, } @article {pmid18174371, year = {2008}, author = {Antion, MD and Merhav, M and Hoeffer, CA and Reis, G and Kozma, SC and Thomas, G and Schuman, EM and Rosenblum, K and Klann, E}, title = {Removal of S6K1 and S6K2 leads to divergent alterations in learning, memory, and synaptic plasticity.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {15}, number = {1}, pages = {29-38}, pmid = {18174371}, issn = {1549-5485}, support = {R01 NS034007/NS/NINDS NIH HHS/United States ; R01 NS047384/NS/NINDS NIH HHS/United States ; NS047384/NS/NINDS NIH HHS/United States ; R37 NS034007/NS/NINDS NIH HHS/United States ; R29 NS034007/NS/NINDS NIH HHS/United States ; NS34007/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Classical ; Fear ; Learning/*physiology ; Memory/*physiology ; Mice ; Mice, Knockout ; Models, Animal ; Neuronal Plasticity/*physiology ; Ribosomal Protein S6 Kinases, 70-kDa/*deficiency/*genetics ; Space Perception/*physiology ; Synapses/physiology ; Taste/physiology ; }, abstract = {Protein synthesis is required for the expression of enduring memories and long-lasting synaptic plasticity. During cellular proliferation and growth, S6 kinases (S6Ks) are activated and coordinate the synthesis of de novo proteins. We hypothesized that protein synthesis mediated by S6Ks is critical for the manifestation of learning, memory, and synaptic plasticity. We have tested this hypothesis with genetically engineered mice deficient for either S6K1 or S6K2. We have found that S6K1-deficient mice express an early-onset contextual fear memory deficit within one hour of training, a deficit in conditioned taste aversion (CTA), impaired Morris water maze acquisition, and hypoactive exploratory behavior. In contrast, S6K2-deficient mice exhibit decreased contextual fear memory seven days after training, a reduction in latent inhibition of CTA, and normal spatial learning in the Morris water maze. Surprisingly, neither S6K1- nor S6K2-deficient mice exhibited alterations in protein synthesis-dependent late-phase long-term potentiation (L-LTP). However, removal of S6K1, but not S6K2, compromised early-phase LTP expression. Furthermore, we observed that S6K1-deficient mice have elevated basal levels of Akt phosphorylation, which is further elevated following induction of L-LTP. Taken together, our findings demonstrate that removal of S6K1 leads to a distinct array of behavioral and synaptic plasticity phenotypes that are not mirrored by the removal of S6K2. Our observations suggest that neither gene by itself is required for L-LTP but instead may be required for other types of synaptic plasticity required for cognitive processing.}, } @article {pmid18164576, year = {2008}, author = {Green, AS and Grahame, NJ}, title = {Ethanol drinking in rodents: is free-choice drinking related to the reinforcing effects of ethanol?.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {42}, number = {1}, pages = {1-11}, pmid = {18164576}, issn = {0741-8329}, support = {U01 AA 13483/AA/NIAAA NIH HHS/United States ; T32 AA007462/AA/NIAAA NIH HHS/United States ; T32 AA007462-21/AA/NIAAA NIH HHS/United States ; U01 AA013483-06/AA/NIAAA NIH HHS/United States ; AA07462/AA/NIAAA NIH HHS/United States ; U01 AA013483-05/AA/NIAAA NIH HHS/United States ; U01 AA013483/AA/NIAAA NIH HHS/United States ; T32 AA007462-20/AA/NIAAA NIH HHS/United States ; }, mesh = {*Alcohol Drinking ; Animals ; Conditioning, Classical/drug effects ; Conditioning, Operant/drug effects ; Mice ; Models, Animal ; Rats ; *Reinforcement, Psychology ; Self Administration ; }, abstract = {Many studies have used voluntary ethanol consumption by animals to assess the influence of genetic and environmental manipulations on ethanol drinking. However, the relationship between home cage ethanol consumption and more formal assessments of ethanol-reinforced behavior using operant and instrumental conditioning procedures is not always clear. The present review attempted to evaluate whether there are consistent correlations between mouse and rat home cage ethanol drinking on the one hand, and either operant oral self-administration (OSA), conditioned taste aversion (CTA), or conditioned place preference (CPP) with ethanol on the other. We also review literature on intravenous ethanol self-administration (IVSA). To collect data, we evaluated a range of genetic manipulations that can change both genes and ethanol drinking behavior including selective breeding, transgenic and knockout models, and inbred and recombinant inbred strain panels. For a genetic model to be included in the analysis, there had to be published data resulting in differences on home cage drinking and data for at least one of the other behavioral measures. A consistent, positive correlation was observed between ethanol drinking and OSA, suggesting that instrumental behavior is closely genetically related to consummatory and ingestive behavior directed at ethanol. A negative correlation was observed between CTA and drinking, suggesting that ethanol's aversive actions may limit oral consumption of ethanol. A more modest, positive relationship was observed between drinking and CPP, and there were not enough studies available to determine a relationship with IVSA. That some consistent outcomes were observed between widely disparate behavioral procedures and genetic populations may increase confidence in the validity of findings from these assays. These findings may also have important implications when researchers decide which phenotypes to use in measuring alcohol-reward relevant behaviors in novel animal models.}, } @article {pmid18159430, year = {2003}, author = {Allen, UD and Lapointe, N and Read, SE and Forbes, JC and King, SM and Wasfy, S and , }, title = {Response to a protease-inhibitor (ritonavir)-containing combination antiretroviral regimen in HIV-infected children.}, journal = {The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses}, volume = {14}, number = {2}, pages = {89-93}, pmid = {18159430}, issn = {1180-2332}, abstract = {INTRODUCTION: The number of antiretroviral agents available for children who are failing existing therapy is limited. Data are lacking on the use of various combination regimens and the resulting viral load dynamics in such children.

METHODS: Between March 1998 and March 2000, HIV-infected children younger than 18 years of age were studied in an open trial. The study regimen included ritonavir, with at least two drugs to which the virus was known or presumed to be sensitive. Subjects were ritonavir-naive and were included if they had high viral loads while receiving antiretroviral therapy. Patients had clinical assessments, CD4 counts and viral load monitoring.

RESULTS: Fifteen antiretroviral-experienced HIV-infected children were enrolled. Approximately 87% (13 of 15) had perinatally-acquired HIV; median age was 7.9 years (range 1.6 to 14.8). At enrolment, the median CD4 count was 557 cells/mm(3) (range 57 to 1702) and the median viral load was 72,600 copies/mL (range 3626 to 796,440). The majority of children (73.3%) had increases in CD4 counts within 12 weeks. During this period, the median increase in CD4 counts over baseline was 30.0%. Approximately 73% (eight of 11) of subjects with initial improvements in CD4 counts had sustained increases at 32 to 48 weeks. Over the first 12 weeks, 60% (nine of 15) had greater than 0.5 log(10) decreases in viral load. The improvement was sustained in 88.9% (eight of nine) of these patients at 32 to 48 weeks. Three patients discontinued therapy due to taste aversion.

CONCLUSIONS: Among pediatric patients with high viral loads while on existing therapy, the ritonavir-containing regimen was generally well tolerated. In a significant proportion of patients, modification of therapy was associated with sustained improvements in viral loads and CD4 counts over 32 to 48 weeks.}, } @article {pmid18069020, year = {2008}, author = {Ciamei, A and Morton, AJ}, title = {Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's disease.}, journal = {Neurobiology of learning and memory}, volume = {89}, number = {4}, pages = {533-544}, doi = {10.1016/j.nlm.2007.10.009}, pmid = {18069020}, issn = {1095-9564}, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning/physiology ; Disease Models, Animal ; Emotions/*physiology ; Extinction, Psychological/physiology ; Female ; Food Preferences/physiology ; Huntington Disease/*physiopathology ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Neurologic Mutants ; Mice, Transgenic ; Prefrontal Cortex/physiology ; *Social Behavior ; Taste ; }, abstract = {Four experiments were conducted to examine social and emotional memory in the R6/2 transgenic mouse model of Huntington's disease. First, R6/2 mice were tested in a social transmission of food preference task where they had to acquire a preference for a flavoured food (acquisition) and subsequently to learn a preference for a different flavour (shifted reinforcement). R6/2 mice performed well in the acquisition trial. However, they were impaired in the shifted reinforcement trial and perseverated on the first preference learned. Second, mice were trained in an inhibitory avoidance paradigm, with either one or two footshocks delivered during the training. WT mice given one footshock showed retention levels lower than those of mice trained with two footshocks. By contrast, there was no difference in retention levels of R6/2 mice given either one or two footshocks. Third, mice were tested in an active avoidance task that paired a mild footshock with a warning light. R6/2 mice had a strong age-dependent deficit in this task. Finally, mice were tested in a conditioned taste aversion task that paired a saccharine solution with a nausea-inducing agent (LiCl). R6/2 mice displayed normal aversion, however this was not extinguished following repeated exposure to saccharine solution alone. Our data show that while R6/2 mice have functional hippocampus-based memory, they have deficits in striatum-based memory skills. Further, social and emotional memories appear to be encoded in a rigid way that is not influenced by subsequent learning or by arousal levels.}, } @article {pmid18064349, year = {2007}, author = {Vogel, EH and Soto, FA and Castro, ME and Solar, PA}, title = {Stimulus specificity in the acquisition and extinction of conditioned taste aversion.}, journal = {Biological research}, volume = {40}, number = {2}, pages = {123-129}, doi = {10.4067/s0716-97602007000200003}, pmid = {18064349}, issn = {0716-9760}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/drug effects/*physiology ; Cyclophosphamide/pharmacology ; Extinction, Psychological/drug effects/*physiology ; Male ; Rats ; Taste/*physiology ; }, abstract = {An experiment evaluated whether the acquisition and extinction of conditioned taste aversion in the rat is stimulus-specific by testing the degree of response transfer between sweet and salty tastes. Animals in the paired-same and paired-different groups received a presentation of a gustatory CS and a cyclophosphamide injection US. Nonconditioned control groups received unpaired CS /US presentations or the CS followed by a vehicle injection. Taste avoidance was evaluated in three nonreinforced test sessions. In the paired-same, unpaired and vehicle groups, all test sessions were conducted with the same flavor as originally used in training, whereas the paired-different group was tested with a novel flavor on the first and second sessions and with the originally trained flavor in last session. Stimulus specific acquisition was apparent in the first test session, when the animals in the group paired-same exhibited lower fluid intake than the other three groups. Evidence of specificity of extinction was apparent in the last test session, when animals in the group paired-different exhibited lower fluid intake than the other three groups. These results provide further evidence of stimulus specificity in acquisition and extinction of conditioned taste aversion, supporting the associative interpretation of these phenomena.}, } @article {pmid18056987, year = {2008}, author = {Aja, S and Landree, LE and Kleman, AM and Medghalchi, SM and Vadlamudi, A and McFadden, JM and Aplasca, A and Hyun, J and Plummer, E and Daniels, K and Kemm, M and Townsend, CA and Thupari, JN and Kuhajda, FP and Moran, TH and Ronnett, GV}, title = {Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {294}, number = {2}, pages = {R352-61}, doi = {10.1152/ajpregu.00862.2006}, pmid = {18056987}, issn = {0363-6119}, support = {CA 087850/CA/NCI NIH HHS/United States ; CA 091634/CA/NCI NIH HHS/United States ; DK 019302/DK/NIDDK NIH HHS/United States ; DK 064000/DK/NIDDK NIH HHS/United States ; DK 068054/DK/NIDDK NIH HHS/United States ; }, mesh = {4-Butyrolactone/analogs & derivatives/pharmacology ; Animals ; Body Weight/drug effects/*physiology ; Carnitine O-Palmitoyltransferase/*metabolism ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Eating/drug effects/*physiology ; Energy Metabolism/drug effects/physiology ; Enzyme Activation/drug effects/physiology ; Enzyme Inhibitors/pharmacology ; Epoxy Compounds/pharmacology ; Fatty Acid Synthesis Inhibitors/metabolism ; Fatty Acids/metabolism ; Female ; Hypothalamus/cytology/drug effects/*enzymology ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neurons/cytology/drug effects/enzymology ; Pregnancy ; Rats ; }, abstract = {Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1-56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.}, } @article {pmid18048951, year = {2007}, author = {Miranda, F and Sandoval-Sánchez, A and Cedillo, LN and Jiménez, JC and Millán-Mejía, P and Velázquez-Martínez, DN}, title = {Modulatory role of 5-HT1B receptors in the discriminative signal of amphetamine in the conditioned taste aversion paradigm.}, journal = {Pharmacological reports : PR}, volume = {59}, number = {5}, pages = {517-524}, pmid = {18048951}, issn = {1734-1140}, mesh = {Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Psychological/drug effects ; Discrimination, Psychological/*drug effects ; Drinking Behavior/*drug effects ; Generalization, Psychological/drug effects ; Ligands ; Male ; Rats ; Rats, Wistar ; Receptor, Serotonin, 5-HT1B/*physiology ; Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT1 Receptor Antagonists ; Taste/*drug effects ; }, abstract = {Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine (DA) system. The behavioral effects of AMPH are largely mediated by increased DA neurotransmission in the nucleus accumbens. However, there is evidence that serotonin (5-hydroxytryptamine - 5-HT) systems may regulate forebrain DA function. We examined the role of 5-HT1B receptors on the discriminative stimulus properties of AMPH using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received the administration of AMPH (1.0 mg/kg) before a 10 min period of access to saccharin solution and followed by an injection of LiCl; on alternate days, rats received saline before and after the access to saccharin solution. In generalization and combination tests, the training dose of AMPH was substituted by 5-HT1B receptor ligands RU24969 (5-HT1B agonist: 0.1, 0.3 and 1.0 mg/kg), CP94253 (5-HT1B agonist: 1.0, 3.0 and 5.6 mg/kg) and GR127935 (5-HT1B antagonist: 0.3, 1.0 and 3.0 mg/kg) or a combination of RU24969 (0.1, 0.3 and 1.0 mg/kg), CP94253 (1.0, 3.0 and 5.6 mg/kg) or GR127935 (0.3, 1.0 and 3.0 mg/kg) with AMPH (0.3 mg/kg) or GR127935 (0.3, 1.0 and 3.0 mg/kg) and CP94253 (5.6 mg/kg) with AMPH (0.3 mg/kg). The results showed that 5-HT1B agonists RU24969 and CP94253 produced partial generalization of 48% and 60%, respectively, and the 5-HT1B antagonist GR127935 neither substituted for AMPH nor affected the discriminative cue of AMPH; however, when RU24969 or CP94253 were administrated in combination with AMPH, they increased the discriminative cue of AMPH. This effect was reversed by the administration of 5-HT1B antagonist GR127935. These data suggest that 5-HT1B receptors play a modulatory role in the discriminative cue of AMPH.}, } @article {pmid18045672, year = {2008}, author = {Freeman, KB and Verendeev, A and Riley, AL}, title = {Noradrenergic antagonism enhances the conditioned aversive effects of cocaine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {88}, number = {4}, pages = {523-532}, doi = {10.1016/j.pbb.2007.10.011}, pmid = {18045672}, issn = {0091-3057}, mesh = {Adrenergic alpha-Antagonists/pharmacology ; Adrenergic beta-Antagonists/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Conditioning, Operant/drug effects ; Dopamine Uptake Inhibitors/*pharmacology ; Dose-Response Relationship, Drug ; Male ; Norepinephrine/*antagonists & inhibitors ; Prazosin/pharmacology ; Propranolol/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sympathetic Nervous System/*drug effects ; Taste/drug effects ; }, abstract = {The propensity to self-administer cocaine may be a function of both its positively reinforcing and aversive effects, with the latter acting as a limiting factor on overall drug taking. However, relative to what is known about the physiological underpinnings of cocaine's positively reinforcing effects, little is known about its aversive effects. There is some evidence that cocaine's aversive effects, as indexed in the conditioned taste aversion (CTA) preparation, are catecholaminergically mediated, i.e., through cocaine's actions on the dopaminergic and noradrenergic neurotransmitter systems. Although limited evidence suggests a role for dopamine, there has yet to be a direct assessment of noradrenergic involvement. To better characterize a role for this system, cocaine-induced CTAs (10, 18 and 32 mg/kg) were conducted under conditions of antagonism at the norepinephrine alpha(1) and beta receptors using prazosin (0.3 mg/kg; Experiment 2) and propranolol (10 mg/kg; Experiment 3), respectively, at doses that were determined to be non-aversive (Experiment 1). In each case of noradrenergic antagonism, CTAs with cocaine were not attenuated, suggesting that this drug's conditioned aversive effects are mediated by non-noradrenergic NT activity. Furthermore, prazosin and propranolol administration appeared to facilitate the conditioned aversive effects of cocaine. The implications of these findings in regards to other neurochemical processes are discussed.}, } @article {pmid18034694, year = {2007}, author = {Diaz-Granados, JL and Graham, DL}, title = {The effects of continuous and intermittent ethanol exposure in adolesence on the aversive properties of ethanol during adulthood.}, journal = {Alcoholism, clinical and experimental research}, volume = {31}, number = {12}, pages = {2020-2027}, doi = {10.1111/j.1530-0277.2007.00534.x}, pmid = {18034694}, issn = {1530-0277}, support = {F31 AA05594/AA/NIAAA NIH HHS/United States ; R01 AA12438/AA/NIAAA NIH HHS/United States ; }, mesh = {Administration, Inhalation ; Age Factors ; Alcohol Drinking/psychology ; Alcoholism/psychology ; Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Drug Administration Schedule ; Ethanol/administration & dosage/blood/*toxicity ; Habituation, Psychophysiologic ; Male ; Mice ; Mice, Inbred C3H ; Saccharin ; *Taste ; }, abstract = {BACKGROUND: Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol. The present study was designed to examine whether ethanol exposure, continuous versus intermittent, during the adolescent developmental period would alter the aversive properties of ethanol in adult C3H mice.

METHODS: Periadolescent (PD28) male C3H mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion conditioning was carried out on both ethanol pre-exposed and ethanol-naive animals using a 1-trial, 1-flavor taste-conditioning procedure.

RESULTS: Ethanol exposure during the periadolescent period significantly attenuated a subsequent ethanol-induced conditioned taste aversion, as compared with control animals. Adult animals exposed to chronic ethanol vapor during adolescence showed less of an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent exposure to ethanol vapor during periadolescence produced a greater attenuation.

CONCLUSION: It is suggested that ethanol exposure during the periadolescent period results in long-term neurobehavioral changes, which lessen a conditioned aversion to ethanol in adulthood. It is suggested that this age-related effect may underlie the increased susceptibility to alcohol-related problems which is negatively correlated with the age of onset for alcohol abuse.}, } @article {pmid18031736, year = {2008}, author = {Patel, JD and Ebenezer, IS}, title = {The effect of intraperitoneal administration of leptin on short-term food intake in rats.}, journal = {European journal of pharmacology}, volume = {580}, number = {1-2}, pages = {143-152}, doi = {10.1016/j.ejphar.2007.10.046}, pmid = {18031736}, issn = {0014-2999}, mesh = {Animals ; Avoidance Learning/drug effects ; Cholecystokinin/metabolism ; Dose-Response Relationship, Drug ; Drinking/*drug effects ; Eating/*drug effects ; Food Deprivation ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Leptin/administration & dosage/*pharmacology ; Male ; Rats ; Rats, Wistar ; Time Factors ; Vagotomy ; }, abstract = {The effects of intraperitoneal (i.p.) injection of leptin (1, 5, and 10 mug/kg) were investigated on the food consumption during a 60 min test meal in 21 h fasted rats. All doses of leptin produced significant reductions in cumulative food intake during the first 15 min and 30 min (at least, P<0.05) after administration. Similarly, i.p., but not subcutaneous (s.c.), administration of leptin (25 microg/kg) reduced food intake in 21 h fasted rats. Leptin (10 and 25 microg/kg, i.p.) did not reduce water intake in 16 h water-deprived rats, nor did leptin (25 microg/kg) produce aversion in a two-bottle conditioned taste aversion test indicating that the hypophagic effect of leptin is (i) behaviourally specific for food and not water intake, and (ii) not due to drug-induced malaise. Moreover, leptin (10 and 25 microg/kg, i.p.) did not significantly alter food intake in non-deprived rats when measured at 30 min intervals over a period of 24 h. Chemical vagotomy with capsaicin abolished the inhibitory effects of leptin (25 microg/kg, i.p) on food intake in fasted rats and suggest that the hypophagic effect is dependent on intact vagal afferent nerves. Furthermore, the hypophagia induced by leptin (10 microg/kg, i.p.) in fasted rats was not attenuated by systemic administration of the peripherally acting cholecystokinin(1) receptor antagonist, 2-naphthalenesulphanyl-L-aspartyl-2-(phenethyl) amide (2-NAP; 2 mg/kg, i.p.), indicating that the suppressant effects of leptin on food consumption are not secondary to the release of endogenous peripheral cholecystokinin.}, } @article {pmid18023617, year = {2007}, author = {Hoebel, BG and Avena, NM and Rada, P}, title = {Accumbens dopamine-acetylcholine balance in approach and avoidance.}, journal = {Current opinion in pharmacology}, volume = {7}, number = {6}, pages = {617-627}, pmid = {18023617}, issn = {1471-4892}, support = {R01 DA010608/DA/NIDA NIH HHS/United States ; R21 MH065024/MH/NIMH NIH HHS/United States ; R01 DA010608-05/DA/NIDA NIH HHS/United States ; MH 65024/MH/NIMH NIH HHS/United States ; R21 MH065024-05/MH/NIMH NIH HHS/United States ; R01 AA012882-06/AA/NIAAA NIH HHS/United States ; AA 12882/AA/NIAAA NIH HHS/United States ; DA 10608/DA/NIDA NIH HHS/United States ; }, mesh = {Acetylcholine/metabolism/*physiology ; Animals ; Avoidance Learning/physiology ; Basal Ganglia/physiology ; Behavior/*physiology ; Behavior, Animal/physiology ; Dopamine/metabolism/*physiology ; Eating/*physiology ; Humans ; Hypothalamus/physiology ; Nucleus Accumbens/*metabolism/*physiology ; Satiety Response ; Self Stimulation ; Substance Withdrawal Syndrome/metabolism/physiopathology ; Taste/physiology ; }, abstract = {Understanding systems for approach and avoidance is basic for behavioral neuroscience. Research on the neural organization and functions of the dorsal striatum in movement disorders, such as Huntington's and Parkinson's Disease, can inform the study of the nucleus accumbens (NAc) in motivational disorders, such as addiction and depression. We propose opposing roles for dopamine (DA) and acetylcholine (ACh) in the NAc in the control of GABA output systems for approach and avoidance. Contrary to DA, which fosters approach, ACh release is a correlate or cause of meal satiation, conditioned taste aversion and aversive brain stimulation. ACh may also counteract excessive DA-mediated approach behavior as revealed during withdrawal from drugs of abuse or sugar when the animal enters an ACh-mediated state of anxiety and behavioral depression. This review summarizes evidence that ACh is important in the inhibition of behavior when extracellular DA is high and the generation of an anxious or depressed state when DA is relatively low.}, } @article {pmid17970726, year = {2007}, author = {Roman, C and Reilly, S}, title = {Effects of insular cortex lesions on conditioned taste aversion and latent inhibition in the rat.}, journal = {The European journal of neuroscience}, volume = {26}, number = {9}, pages = {2627-2632}, doi = {10.1111/j.1460-9568.2007.05872.x}, pmid = {17970726}, issn = {0953-816X}, support = {R01 DC004341/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC04341/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/injuries/*physiopathology ; Conditioning, Psychological/*physiology ; Denervation ; Learning/physiology ; Male ; Neural Inhibition/*physiology ; Phobic Disorders/physiopathology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Taste/*physiology ; Taste Disorders/*physiopathology ; }, abstract = {The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be interpreted as disruptions of taste detection or stimulus intensity, but is consistent with the view that insular cortex lesions disrupt taste neophobia, a dysfunction that consequently retards CTA acquisition because of a latent inhibition-like effect.}, } @article {pmid17945339, year = {2008}, author = {Rinker, JA and Busse, GD and Riley, AL}, title = {An assessment of sex differences in nicotine-induced conditioned taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {88}, number = {4}, pages = {427-431}, doi = {10.1016/j.pbb.2007.09.016}, pmid = {17945339}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Female ; Male ; Nicotine/*pharmacology ; Nicotinic Agonists/*pharmacology ; Rats ; Rats, Long-Evans ; Saccharin/pharmacology ; Self Administration ; Sex Characteristics ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {Sex differences in taste aversion learning have been reported for a number of different compounds. It is unknown, however, to what degree, if any, such differences exist when nicotine is the aversion-inducing agent. To address this issue, in the present experiment male and female rats were given limited access to saccharin followed by an intraperitoneal (i.p.) injection of either vehicle or nicotine (0.4, 0.8 or 1.2 mg/kg). Although nicotine induced significant taste aversions in both males and females, the aversions were generally weak at all doses tested. There were no sex differences in the acquisition or strength of the aversions induced by nicotine. The vulnerability to drug abuse has been suggested to be a function of the balance of the rewarding and aversive effects of a drug. Given the relatively weak aversions induced in both sexes and the absence of differences between males and females, it is unlikely that the reported sex difference in the self-administration of nicotine is a function of differences in nicotine's aversive effects. The reported difference in the self-administration of nicotine by males and females is more likely a function of differences in the sensitivity to the rewarding effects of the drug.}, } @article {pmid17942718, year = {2007}, author = {Dotson, CD and Spector, AC}, title = {Behavioral discrimination between sucrose and other natural sweeteners in mice: implications for the neural coding of T1R ligands.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {27}, number = {42}, pages = {11242-11253}, pmid = {17942718}, issn = {1529-2401}, support = {F31 DC007358/DC/NIDCD NIH HHS/United States ; R01 DC004574/DC/NIDCD NIH HHS/United States ; F31-DC007358/DC/NIDCD NIH HHS/United States ; R01-DC04574/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Discrimination, Psychological/drug effects/*physiology ; Ligands ; Mice ; Nerve Net/drug effects/*metabolism ; Receptors, G-Protein-Coupled/*metabolism/physiology ; Sucrose/*administration & dosage/metabolism ; Sweetening Agents/*administration & dosage/metabolism ; Taste/drug effects/physiology ; }, abstract = {In taste bud cells, two different T1R heteromeric taste receptors mediate signal transduction of sugars (the canonical "sweet" taste receptor, T1R2 + T1R3) and L-amino acids (the T1R1 + T1R3 receptor). The T1R1 + T1R3 receptor is thought to mediate what is considered the fifth basic taste quality "umami." However, a subset of L-amino acids is "sweet tasting" to humans and appears to possess a "sucrose-like" taste quality to nonhuman mammals. This suggests, to varying degrees, that all of these compounds activate a single neural channel that leads to the perception of sweetness. The experiments detailed here were designed to test the ability of mice to distinguish between sucrose and various others sugars and L-amino acids in operant taste discrimination tasks. Mice had at least some difficulty discriminating sucrose from L-serine, L-threonine, maltose, fructose, and glucose. For example, when concentration effects are taken into consideration, mice discriminated poorly, if at all, sucrose from glucose or fructose and, to a lesser extent maltose, suggesting that sugars generate a unitary perceptual quality. However, mice were able to reliably discriminate sucrose from L-serine and L-threonine. Data gathered using a conditioned taste aversion assay also suggest that, although qualitatively similar to the taste of sucrose, L-serine and L-threonine generate distinctive percepts. In conclusion, it appears that some signals from taste receptor proteins binding with sugars and some L-amino acids converge somewhere along the gustatory neuraxis. However, the results of these experiments also imply that sweet-tasting L-amino acids may possess qualitative taste characteristics that are distinguishable from the prototypical sweetener sucrose.}, } @article {pmid17942491, year = {2007}, author = {Santollo, J and Wiley, MD and Eckel, LA}, title = {Acute activation of ER alpha decreases food intake, meal size, and body weight in ovariectomized rats.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {293}, number = {6}, pages = {R2194-201}, doi = {10.1152/ajpregu.00385.2007}, pmid = {17942491}, issn = {0363-6119}, support = {DK-073936/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/drug effects/*physiology ; Body Weight/drug effects/*physiology ; Eating/drug effects/*physiology ; Estrogen Receptor alpha/drug effects/*metabolism ; Estrogen Receptor beta/drug effects/*metabolism ; Feeding Behavior/drug effects/physiology ; Female ; Nitriles/administration & dosage ; *Ovariectomy ; Phenols ; Pyrazoles/administration & dosage ; Rats ; Rats, Inbred LEC ; Weight Loss/drug effects/*physiology ; }, abstract = {Estradiol exerts many of its actions by coupling with two nuclear estrogen receptor (ER) proteins, ER alpha, and ER beta. While the acute, anorexigenic effect of estradiol appears to involve such a mechanism, the relative contributions of ERalpha and ERbeta are equivocal. To address this problem, food intake was monitored in ovariectomized (OVX) rats following acute administration of a selective ER alpha agonist (4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT; dose range = 0-200 microg), a selective ER beta agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN; dose range = 0-600 microg), and a physiological (4 microg) dose of estradiol benzoate (EB). While PPT-treated rats displayed dose-dependent decreases in daily food intake and body weight, neither of these measures was influenced by any dose of DPN. In addition, DPN failed to modulate the anorexigenic effect of PPT when the two ER agonists were coadministered. Meal pattern analysis revealed that the anorexigenic effect of 75 microg PPT (a dose of PPT that produced a similar decrease in daily food intake as 4 microg EB) was mediated by a decrease in meal size, not meal number. Thus, PPT, like EB and endogenous estradiol, decreases food intake by selectively affecting the controls of meal size. The finding that acute administration of 75 microg PPT failed to induce a conditioned taste aversion suggests that the anorexigenic effect of this dose of PPT is not secondary to malaise. Taken together, our findings demonstrate that selective activation of ER alpha decreases food intake, body weight, and meal size in the ovariectomized rat.}, } @article {pmid19424832, year = {2007}, author = {Carrihill-Knoll, KL and Rabin, BM and Shukitt-Hale, B and Joseph, JA and Carey, A}, title = {Amphetamine-induced taste aversion learning in young and old F-344 rats following exposure to 56Fe particles.}, journal = {Age (Dordrecht, Netherlands)}, volume = {29}, number = {2-3}, pages = {69-76}, pmid = {19424832}, issn = {1574-4647}, abstract = {Exposure to (56)Fe particles produces changes in dopaminergic function and in dopamine-dependent behaviors, including amphetamine-induced conditioned taste aversion (CTA) learning. Because many of these changes are characteristic of the changes that accompany the aging process, the present study was designed to determine whether or not there would be an interaction between age and exposure to (56)Fe particles in the disruption of an amphetamine-induced CTA. One hundred and forty F-344 male rats 2-, 7-, 12-, and 16-months old, were radiated with (56)Fe particles (0.25-2.00 Gy, 1 GeV/n) at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of radiation on the acquisition of a CTA produced by injection of amphetamine (3 mg/kg, i.p.). The main effect of age was to produce a significant decrease in conditioning day sucrose intake; there was no affect of age on the acquisition of the amphetamine-induced CTA. Exposing rats to (56)Fe particles disrupted the acquisition of the CTA produced by injection of amphetamine only in the 2-month-old rats. These results do not support the hypothesis of an interaction between age and exposure to (56)Fe particles in producing a disruption of amphetamine-induced CTA learning. As such, these results suggest that the aging produced by exposure to (56)Fe particles may be endpoint specific.}, } @article {pmid17640625, year = {2007}, author = {Inui, T and Shimura, T and Yamamoto, T}, title = {The role of the ventral pallidum GABAergic system in conditioned taste aversion: effects of microinjections of a GABAA receptor antagonist on taste palatability of a conditioned stimulus.}, journal = {Brain research}, volume = {1164}, number = {}, pages = {117-124}, doi = {10.1016/j.brainres.2007.06.031}, pmid = {17640625}, issn = {0006-8993}, mesh = {Animals ; Appetite/drug effects/physiology ; Avoidance Learning/drug effects/*physiology ; Basal Ganglia/drug effects/*metabolism ; Bicuculline/pharmacology ; Conditioning, Psychological ; GABA Antagonists/pharmacology ; GABA-A Receptor Antagonists ; Globus Pallidus/drug effects/*metabolism ; Male ; Microinjections ; Neural Pathways/drug effects/metabolism ; Rats ; Rats, Wistar ; Receptors, GABA-A/*metabolism ; Reward ; Saccharin/pharmacology ; Taste/drug effects/*physiology ; gamma-Aminobutyric Acid/*metabolism ; }, abstract = {When subjects receive a taste stimulus (conditioned stimulus, CS) that is paired with malaise, they acquire conditioned taste aversion (CTA). It is thought that the taste CS changes from appetitive to aversive after acquisition of CTA. Previous studies have suggested that the ventral pallidum (VP) is involved in the hedonics of taste stimuli, therefore the present study investigated whether the VP is a neural substrate for the shift in preference of the CS after CTA acquisition. In the first experiment, CTA-learned rats received microinjections of the GABA(A) receptor antagonist bicuculline into the VP just before presentation of the CS (saccharin or quinine) in a single-bottle test. The bicuculline-injected rats showed higher intake of the saccharin CS than the vehicle-injected rats. To test whether these results were due to a change in taste preference for the CS, in the second experiment, we examined the effects of bicuculline on the affective aspects of the saccharin CS using a taste reactivity test, which is a useful tool for evaluating taste palatability. The bicuculline-injected rats showed higher appetitive and lower aversive responses to the saccharin CS than the vehicle-injected group. These results suggest that the higher saccharin intake observed in the first experiment was at least partly due to the bicuculline injection, which changed the perceived palatability of the taste CS (saccharin) from aversive to appetitive. The GABAergic system in the VP may play an important role in hedonic-based ingestive behaviors after CTA.}, } @article {pmid17638581, year = {2007}, author = {Mediavilla, C and Bernal, A and Puerto, A}, title = {Taste aversion learning induced c-fos expression in the nucleus of the solitary tract after spontaneous flavor intake: role of the inter-stimulus interval.}, journal = {Neurobiology of learning and memory}, volume = {88}, number = {2}, pages = {264-268}, doi = {10.1016/j.nlm.2007.05.008}, pmid = {17638581}, issn = {1074-7427}, mesh = {Animals ; *Avoidance Learning ; Flavoring Agents/*administration & dosage ; Physical Stimulation/*methods ; Proto-Oncogene Proteins c-fos/*metabolism ; Solitary Nucleus/*metabolism ; *Taste ; Time Factors ; }, abstract = {Taste aversion learning (TAL) can be induced by associating a flavor intake with the immediate or delayed (30 min) intragastric administration of a noxious substance, e.g., hypertonic NaCl. The objective of this study was to analyze the induction of c-Fos immunoreactivity in the intermediate nucleus of the solitary nucleus (iNST) after acquisition of a contiguous or delayed TAL, offering the flavor for voluntary consumption in both cases. The behavioral results obtained indicate that, although the learning was established under both experimental conditions, an increase in c-Fos induction was only produced in the group that learned by means of a non-delayed TAL. Immunohistochemical analyses revealed the participation of different brain structures in these two TAL modalities. Thus, the nucleus of the solitary tract may be involved in the TAL procedure in which voluntary flavor intake and intragastric administration of the noxious visceral stimulus are contiguous but not in delayed TAL, which would depend on other anatomical circuits that do not include the iNST.}, } @article {pmid17629624, year = {2007}, author = {Delay, ER and Mitzelfelt, JD and Westburg, AM and Gross, N and Duran, BL and Eschle, BK}, title = {Comparison of L-monosodium glutamate and L-amino acid taste in rats.}, journal = {Neuroscience}, volume = {148}, number = {1}, pages = {266-278}, doi = {10.1016/j.neuroscience.2007.05.045}, pmid = {17629624}, issn = {0306-4522}, mesh = {Amino Acids/*pharmacology ; Animals ; Arginine/pharmacology ; Avoidance Learning/drug effects/physiology ; Dose-Response Relationship, Drug ; Glycine/pharmacology ; Isomerism ; Male ; Perception/drug effects/physiology ; Proline/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled/drug effects/*physiology ; Serine/pharmacology ; Signal Transduction/drug effects ; Sodium Glutamate/*pharmacology ; Taste/drug effects/*physiology ; Taste Buds/drug effects/*physiology ; Taste Threshold/drug effects/physiology ; Visceral Afferents/drug effects/*physiology ; }, abstract = {T1R2/T1R3 heterodimers are selectively responsive to sweet substances whereas T1R1/T1R3 receptors are selective for umami substances, represented by monosodium glutamate (MSG), and for L-amino acids. If a single receptor is responsible for detection of umami and L-amino acids, then it would be predicted that MSG and L-amino acids elicit similar tastes in rats. The present study compared the taste profile of MSG with four amino acids (glycine, L-proline, L-serine and L-arginine) using conditioned taste aversion, detection threshold, and taste discrimination methods. These experiments were designed to either reduce or neutralize the taste of sodium associated with MSG and the other amino acids. Detection threshold studies showed that rats were most sensitive to L-arginine and least sensitive to L-proline. Glycine and L-serine thresholds were similar to those previously reported for MSG. Like MSG, a conditioned taste aversion to each of the four amino acids generalized to sucrose in the presence of amiloride, a sodium channel blocker. Rats showed moderate generalization of aversion between MSG and L-arginine, suggesting that these two amino acids taste only moderately alike. However, the taste aversion experiments indicated that glycine, L-serine, and L-proline elicit taste sensations similar to MSG when amiloride is present. Discrimination experiments further compared the tastes of these three amino acids with MSG. When the sodium taste associated with MSG was reduced or neutralized, glycine and L-proline elicited tastes very similar but not identical to the taste of MSG. Low (but not higher) concentrations of L-serine were also difficult for rats to discriminate from MSG. While there are taste qualities common to all of these amino acids, the perceptual differences found in this study, combined with previous reports, suggest either multiple taste receptors and/or multiple signaling pathways may be involved in umami and amino acid taste perception in rats.}, } @article {pmid17581841, year = {2007}, author = {Wang, C and Bomberg, E and Billington, C and Levine, A and Kotz, CM}, title = {Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reduces energy intake.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {293}, number = {3}, pages = {R1003-12}, doi = {10.1152/ajpregu.00011.2007}, pmid = {17581841}, issn = {0363-6119}, mesh = {Animals ; Appetite Stimulants/pharmacology ; Arcuate Nucleus of Hypothalamus/physiology ; Body Weight/drug effects ; Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology ; Catheterization ; DNA Primers ; Eating/drug effects ; Energy Intake/*drug effects ; Food Deprivation/physiology ; Gliosis/chemically induced/pathology ; Male ; Neuropeptide Y/pharmacology ; Paraventricular Hypothalamic Nucleus/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; }, abstract = {Recent studies show that brain-derived neurotrophic factor (BDNF) decreases feeding and body weight after peripheral and ventricular administration. BDNF mRNA and protein, and its receptor tyrosine kinase B (TrkB) are widely distributed in the hypothalamus and other brain regions. However, there are few reports on specific brain sites of actions for BDNF. We evaluated the effect of BDNF in the hypothalamic paraventricular nucleus (PVN) on feeding. BDNF injected unilaterally or bilaterally into the PVN of food-deprived and nondeprived rats significantly decreased feeding and body weight gain within the 0- to 24-h and 24- to 48-h postinjection intervals. Effective doses producing inhibition of feeding behavior did not establish a conditioned taste aversion. PVN BDNF significantly decreased PVN neuropeptide Y (NPY)-induced feeding at 1, 2, and 4 h following injection. BDNF administration in the PVN abolished food-restriction-induced NPY gene expression in the hypothalamic arcuate nucleus. In conclusion, BDNF in the PVN significantly decreases food intake and body weight gain, suggesting that the PVN is an important site of action for BDNF in its effects on energy metabolism. Furthermore, BDNF appears to interact with NPY in its anorectic actions, although a direct effect on NPY remains to be established.}, } @article {pmid17578927, year = {2007}, author = {Zorrilla, EP and Sanchez-Alavez, M and Sugama, S and Brennan, M and Fernandez, R and Bartfai, T and Conti, B}, title = {Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {26}, pages = {11097-11102}, pmid = {17578927}, issn = {1091-6490}, support = {P30N5057096//PHS HHS/United States ; AG28040/AG/NIA NIH HHS/United States ; R21 DK077616/DK/NIDDK NIH HHS/United States ; NS43501/NS/NINDS NIH HHS/United States ; DK077616/DK/NIDDK NIH HHS/United States ; R01 NS043501/NS/NINDS NIH HHS/United States ; R01 AG028040/AG/NIA NIH HHS/United States ; DK07118/DK/NIDDK NIH HHS/United States ; }, mesh = {Adiposity/drug effects ; Age Factors ; Animals ; Appetite/*drug effects ; Appetite Depressants ; Eating/*drug effects ; Energy Intake/*drug effects ; Female ; Homeostasis ; Interleukin-18/genetics/*pharmacology/*physiology ; Male ; Metabolism/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Overweight ; Pulmonary Gas Exchange ; Sex Factors ; }, abstract = {Circulating levels of the cytokine interleukin 18 (IL-18) are elevated in obesity. Here, we show that administration of IL-18 suppresses appetite, feed efficiency, and weight regain in food-deprived male and female C57BL/6J mice. Intraperitoneal vs. intracerebroventricular routes of IL-18 administration had similar potency and did not promote formation of a conditioned taste aversion (malaise-like behavior). Mice partially (Il18(+/-)) or totally (Il18(-/-)) deficient in IL-18 were hyperphagic by young adulthood, with null mutants then becoming overweight by the fifth month of life. Adult Il18(-/-) mice gained 2- to 3-fold more weight than WT mice per unit energy consumed of low- or high-fat diet. Indirect calorimetry revealed reduced energy expenditure in female Il18(-/-) mice and increased respiratory exchange ratios [volume of carbon dioxide production (VCO(2))/volume of oxygen consumption (VO(2))] in mutants of both sexes. Hyperphagia continued in maturity, with overeating greatest during the mid- to late-dark cycle. Relative white fat-pad mass of Il18(-/-) mice was approximately 2- to 3-fold greater than that of WT, with gonadal, mesenteric, and inguinal depots growing most. The data suggest that endogenous IL-18 signaling modulates food intake, metabolism, and adiposity during adulthood and might be a central or peripheral pharmacological target for controlling energy homeostasis.}, } @article {pmid17568635, year = {2007}, author = {Houpt, TA and Cassell, JA and Cason, AM and Riedell, A and Golden, GJ and Riccardi, C and Smith, JC}, title = {Evidence for a cephalic site of action of high magnetic fields on the behavioral responses of rats.}, journal = {Physiology & behavior}, volume = {92}, number = {4}, pages = {665-674}, doi = {10.1016/j.physbeh.2007.05.011}, pmid = {17568635}, issn = {0031-9384}, support = {R01 DC004607/DC/NIDCD NIH HHS/United States ; F31DC6521/DC/NIDCD NIH HHS/United States ; R01DC4607/DC/NIDCD NIH HHS/United States ; T32DC0044/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology/radiation effects ; Brain/*physiology/radiation effects ; Dose-Response Relationship, Radiation ; Electric Stimulation/*instrumentation ; *Electromagnetic Fields ; Female ; Male ; Motor Activity/*physiology/radiation effects ; Rats ; Rats, Sprague-Dawley ; Sex Factors ; Statistics, Nonparametric ; Taste ; }, abstract = {Static high magnetic fields (MFs) from 7 T to 9 T can elicit behavioral responses in rodents such as suppression of rearing, locomotor circling, and acquisition of a conditioned taste aversion (CTA). MF exposure also induces c-Fos expression in the visceral and vestibular nuclei of the brainstem, suggesting the stimulation of some sensory pathways. It is not clear, however, if the effects of the MF are caused by exposure to the uniform maximal field at the center of the magnet, or by exposure to the steep field gradients along the bore of the magnet during the rat's placement. In addition, the site of action within the rat is unknown. In an attempt to limit MF exposure to rostral or caudal portions of the rats' body, we exposed male and female rats at different positions within the bore of a 14.1-T superconducting magnet ranging from 2 cm (1.6 T at the head) to 155 cm (0.05 T at the head), with the center of the bore at 65 cm (14.1 T across the whole body). This approach also allowed us to expose rats to the maximal field strength (14.1 T) vs. the maximal field gradients (54 T/m). To assess both immediate and delayed behavioral effects, locomotor and CTA responses were recorded. A small but significant CTA was seen after exposure of the head to the lowest MF tested (0.05 T at 155 cm). Graded effects were seen, however, with greater circling and CTA acquisition as the MF strength increased at the rostral end of the rat. This suggests a cephalic site of action. Furthermore, maximal circling and CTA were induced after exposure to the uniform center field, and not after exposure to high field gradients on either side of the center. This suggests that the behavioral responses seen after MF exposure are a consequence of the uniform static field at the center of the magnet, and are not caused by passage through, or exposure to, the vertical field gradients. Female rats responded similarly to male rats, although magnet-induced CTA appeared resistant to extinction in female rats.}, } @article {pmid17561237, year = {2007}, author = {Nunnink, M and Davenport, RA and Ortega, B and Houpt, TA}, title = {D-Cycloserine enhances conditioned taste aversion learning in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {87}, number = {3}, pages = {321-330}, pmid = {17561237}, issn = {0091-3057}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; R01 DC003198-08/DC/NIDCD NIH HHS/United States ; DC03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Cycloserine/*pharmacology ; Drinking/drug effects ; Excitatory Amino Acid Agonists/pharmacology ; Gene Expression/drug effects ; Genes, fos/drug effects ; Lithium Chloride/pharmacology ; Male ; Pyrrolidinones/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/agonists ; Stimulation, Chemical ; Taste/*drug effects ; }, abstract = {Conditioned taste aversion (CTA) is a form of associative learning in which the pairing of a taste with a toxin causes an animal to avoid the taste. NMDA receptor mediated neurotransmission has been implicated in CTA, but the role of the NMDA receptor glycine-binding site has not been examined. To examine the effects on CTA of the glycinergic NMDA receptor agonist D-cycloserine, rats received D-cycloserine (15 mg/kg, i.p.) or vehicle 15 min before 10-min access to 0.125% saccharin, followed by a low dose of LiCl (19 mg/kg, i.p.). CTA was measured with 24-h, 2-bottle preference tests between water and saccharin. Vehicle-treated rats formed a mild CTA that rapidly extinguished, while d-cycloserine-treated rats formed a stronger CTA that extinguished slowly. The effect of d-cycloserine was specific to the NMDA receptor glycine-binding site, because pretreatment with HA-966 (6 mg/kg), a partial glycinergic agonist, blocked enhancement by D-cycloserine. Three follow-up experiments suggest that the enhancement of CTA was not due to an aversive effect of D-cycloserine. First, saccharin paired with D-cycloserine (15 mg/kg) alone did not induce a CTA, although a higher dose (30 mg/kg) did significantly lower saccharin preference. Second, pretreatment with D-cycloserine did not increase the duration of "lying-on-belly" behavior induced by LiCl. Third, pretreatment with D-cycloserine did not increase c-Fos induction by either LiCl or vehicle injection in central visceral relays (the nucleus of the solitary tract, the parabrachial nucleus, the central nucleus of the amygdala, the supraoptic nucleus, and the paraventricular nucleus). These results confirm the participation of NMDA receptor, and specifically the glycine-binding site of NMDA receptor, in CTA learning.}, } @article {pmid17553842, year = {2007}, author = {Wang, C and Bomberg, E and Levine, A and Billington, C and Kotz, CM}, title = {Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {293}, number = {3}, pages = {R1037-45}, doi = {10.1152/ajpregu.00125.2007}, pmid = {17553842}, issn = {0363-6119}, mesh = {Animals ; Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology ; Dose-Response Relationship, Drug ; Eating/drug effects ; Energy Intake/*drug effects ; Feeding Behavior/drug effects ; Food Deprivation/physiology ; Food Preferences/drug effects ; Male ; Neuropeptide Y/antagonists & inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB/drug effects ; Saccharin/pharmacology ; Taste/drug effects ; Ventromedial Hypothalamic Nucleus/*physiology ; Weight Gain/drug effects ; }, abstract = {Recent studies show that brain-derived neurotrophic factor (BDNF) decreases feeding and body weight after peripheral and ventricular administration. BDNF mRNA and protein, and its receptor TrkB, are widely distributed in the hypothalamus and other brain regions. However, there are few reports on specific brain sites of actions for BDNF. We evaluated the effect of BDNF, given into the ventromedial nucleus of the hypothalamus (VMH), on normal and deprivation- and neuropeptide Y (NPY)-induced feeding behavior and body weight. BDNF injected unilaterally or bilaterally into the VMH of food-deprived and nondeprived rats significantly decreased feeding and body weight gain within the 0- to 24-h and the 24- to 48-h postinjection intervals. Doses effectively producing inhibition of feeding behavior did not establish a conditioned taste aversion. BDNF-induced feeding inhibition was attenuated by pretreatment of the TrkB-Fc fusion protein that blocks binding between BDNF and its receptor TrkB. VMH-injected BDNF significantly decreased VMH NPY-induced feeding at 1, 2, and 4 h after injection. In summary, BDNF in the VMH significantly decreases food intake and body weight gain, by TrkB receptor-mediated actions. Furthermore, the anorectic effects of BDNF in this site appear to be mediated by NPY. These data suggest that the VMH is an important site of action for BDNF in its effects on energy metabolism.}, } @article {pmid17553010, year = {2007}, author = {Kobilo, T and Hazvi, S and Dudai, Y}, title = {Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memory.}, journal = {The European journal of neuroscience}, volume = {25}, number = {11}, pages = {3417-3421}, doi = {10.1111/j.1460-9568.2007.05561.x}, pmid = {17553010}, issn = {0953-816X}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects ; Benzoxazines/pharmacology ; Cerebral Cortex/*metabolism ; Conditioning, Classical/drug effects/*physiology ; Male ; Memory/drug effects/*physiology ; Morpholines/pharmacology ; Naphthalenes/pharmacology ; Rats ; Rats, Wistar ; Receptor, Cannabinoid, CB1/agonists/*physiology ; *Taste/drug effects ; }, abstract = {The brain endocannabinoid system has been shown to play a role in memory, though the extent to which this role generalizes over different types and processes of memory is not yet determined. Here we show that the cannabinoid receptor 1 (CB1) plays differential roles in acquisition, extinction and reconsolidation of conditioned taste aversion (CTA) memory in the rat insular cortex, which contains the taste cortex. Activation of the CB1 receptor in the insular cortex inhibits acquisition and reconsolidation but not extinction, whereas blockade of the CB1 receptor promotes memory and blocks extinction of CTA, while having no apparent effect on reconsolidation. The CB1 ligands used in this study were incapable of substituting the unconditioned stimulus in CTA training. All in all, the data raise the possibility that the state of activity of the CB1 receptor in the insular cortex contributes to the encoding of hedonic valence that enters into association with taste items.}, } @article {pmid17532044, year = {2007}, author = {O'Donnell, KC and Gould, TD}, title = {The behavioral actions of lithium in rodent models: leads to develop novel therapeutics.}, journal = {Neuroscience and biobehavioral reviews}, volume = {31}, number = {6}, pages = {932-962}, pmid = {17532044}, issn = {0149-7634}, support = {NIH0010875152//Intramural NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*drug effects ; Bipolar Disorder/drug therapy ; Depressive Disorder/drug therapy ; Disease Models, Animal ; Humans ; Lithium Compounds/*pharmacology/therapeutic use ; Mice ; Mice, Inbred Strains ; Rats ; Rats, Inbred Strains ; Species Specificity ; }, abstract = {For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium.}, } @article {pmid17524460, year = {2007}, author = {Davis, CM and Riley, AL}, title = {The effects of cocaine preexposure on cocaine-induced taste aversion learning in Fischer and Lewis rat strains.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {87}, number = {1}, pages = {198-202}, doi = {10.1016/j.pbb.2007.04.016}, pmid = {17524460}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Cocaine-Related Disorders/*genetics/*psychology ; Genotype ; Male ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Saccharin ; Taste/drug effects ; }, abstract = {The Fischer (F344) and Lewis (LEW) inbred rat strains differ on a number of behaviors, including those induced by a variety of drugs of abuse. Although a number of physiological and biochemical differences between the strains have been reported following both single and repeated drug administration, studies assessing changes in the affective properties of drugs after repeated exposure are limited. To that end, using the F344 and LEW strains, the present study examined the effects of repeated exposure to cocaine on the subsequent acquisition of cocaine-induced conditioned taste aversions, a preparation often used in assessing the development of tolerance to the drug's aversive effects. Specifically, separate groups of male F344 and LEW rats received five injections of 32 mg/kg cocaine (or vehicle) prior to taste aversion conditioning with 32 mg/kg cocaine (or vehicle). Vehicle-preexposed subjects of both strains acquired aversions to the cocaine-associated taste with no differences in the strength of the aversions. Further, cocaine-preexposed subjects displayed significantly attenuated aversions, an effect consistent with prior work with outbred animals. There was no difference between the two strains in this attenuation, suggesting that there were no genotype-specific differences in tolerance to cocaine's aversive effects. The data were discussed in relation to genetic/environmental interactions in the vulnerability to drugs of abuse.}, } @article {pmid17474323, year = {2007}, author = {Vogel, EH and Castro, ME and Solar, PA and Soto, FA}, title = {Enhancement of Pavlovian conditioned immunosuppression in rats.}, journal = {Acta neurobiologiae experimentalis}, volume = {67}, number = {1}, pages = {71-81}, pmid = {17474323}, issn = {0065-1400}, mesh = {Animals ; Behavior, Animal/drug effects ; Conditioning, Classical/*drug effects/physiology ; Cyclophosphamide/*pharmacology ; Drug Administration Schedule ; *Immunosuppression Therapy ; Immunosuppressive Agents/*pharmacology ; Male ; Rats ; Time Factors ; }, abstract = {The goal of this study was to define conditions under which conditioned immunosuppression may be observed reliably. In three experiments, rats were exposed to a gustatory conditioned stimulus (CS) paired with cyclophosphamide (US), which induces immunosuppression and malaise. In Experiment 1, a single pairing of the CS with low, medium, or high doses of cyclophosphamide in separate groups produced no reliable conditioned immunosuppression even though conditioned taste aversion was observed in groups trained with high and medium doses of CY. Experiment 2 replicated the lack of effect following a single pairing of the CS with the medium dose of cyclophosphamide but demonstrated that three pairings are sufficient to induce conditioned immunosuppression. Experiment 3 demonstrated that significant immunosuppression is observable following a single CS-US pairing if the CS is presented in compound with a previously nonreinforced CS during training, an effect reminiscent of supernormal conditioning. These findings indicate that conditioned immunosuppression effects can be enhanced in magnitude through the use of certain procedural techniques.}, } @article {pmid17469933, year = {2007}, author = {Flint, RW and Marino, CL}, title = {Cycloheximide impairs reconsolidation of a contextually reactivated memory in a conditioned taste aversion paradigm.}, journal = {Behavioral neuroscience}, volume = {121}, number = {2}, pages = {433-438}, doi = {10.1037/0735-7044.121.2.433}, pmid = {17469933}, issn = {0735-7044}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Cycloheximide/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Memory/*drug effects ; Protein Synthesis Inhibitors/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Sucrose/pharmacology ; Taste/*drug effects ; }, abstract = {Rats were used to examine the impact of systemic protein synthesis inhibition (PSI) on the reconsolidation of a contextually reactivated memory of conditioned taste aversion (CTA). Rats were administered intraperitoneal injections of saline or lithium chloride (LiCl; .15 M) following exposure to a novel sucrose solution in a unique context. Seven days later, rats were injected subcutaneously with saline or cycloheximide (CXM; 1 mg/kg) and returned to their home cage or placed into the CTA training context in the absence of the target conditioned stimulus to reactivate the training memory. At testing, LiCl-trained rats that had been given CXM at reactivation had significantly greater difference scores (sucrose-water) in comparison with LiCl/CXM rats that had not been given a reactivation treatment and LiCl/saline memory-reactivated rats. These results suggest that context re-exposure effectively reactivates memory of CTA training that may be weakened through PSI. Extinction tests revealed rapid attenuation of taste aversions in all of the LiCl-injected groups. The involvement of taste-potentiated aversions and the role of the context in taste aversion conditioning are discussed.}, } @article {pmid17446235, year = {2007}, author = {Kim, YM and An, JJ and Jin, YJ and Rhee, Y and Cha, BS and Lee, HC and Lim, SK}, title = {Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732.}, journal = {Journal of molecular endocrinology}, volume = {38}, number = {4}, pages = {455-465}, doi = {10.1677/jme.1.02165}, pmid = {17446235}, issn = {1479-6813}, mesh = {Adipocytes/drug effects/pathology ; Adipose Tissue/drug effects ; Animals ; Anti-Obesity Agents/administration & dosage/*pharmacology/therapeutic use ; Arcuate Nucleus of Hypothalamus/pathology ; Body Weight/drug effects ; Cell Size/drug effects ; Cinnamates/administration & dosage/*pharmacology/therapeutic use ; Cyclohexanes/administration & dosage/chemistry/*pharmacology/therapeutic use ; Eating/drug effects ; Epoxy Compounds/administration & dosage/*pharmacology/therapeutic use ; Hypothalamus/metabolism ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Obese ; Neuropeptides/metabolism ; O-(Chloroacetylcarbamoyl)fumagillol ; Obesity/*drug therapy ; Rats ; Rats, Inbred OLETF ; Sesquiterpenes/administration & dosage/chemistry/*pharmacology/therapeutic use ; Taste/drug effects ; }, abstract = {The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114.8 +/- 13.4 g vs 170.7 +/- 20.6 g, 7.9 +/- 0.5% decrease vs 0.3 +/- 2.2% decrease; in treated OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.}, } @article {pmid17442279, year = {2007}, author = {Mickley, GA and Hoxha, Z and Bacik, S and Kenmuir, CL and Wellman, JA and Biada, JM and DiSorbo, A}, title = {Spontaneous recovery of a conditioned taste aversion differentially alters extinction-induced changes in c-Fos protein expression in rat amygdala and neocortex.}, journal = {Brain research}, volume = {1152}, number = {}, pages = {139-157}, doi = {10.1016/j.brainres.2007.03.050}, pmid = {17442279}, issn = {0006-8993}, support = {1-R15-MH63720-02/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*metabolism ; Animals ; *Avoidance Learning ; Conditioning, Classical ; *Extinction, Psychological ; Fear ; Immunohistochemistry ; Male ; Neocortex/*metabolism ; Proto-Oncogene Proteins c-fos/*biosynthesis ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {Conditioned taste aversions (CTAs) may be acquired when an animal consumes a novel taste (conditioned stimulus; CS) and then experiences the symptoms of poisoning (unconditioned stimulus; US). Animals will later avoid the taste that was previously associated with malaise. Extinction of a CTA is observed following repeated, non-reinforced exposures to the CS and represents itself as a resumption of eating/drinking the once-avoided tastant. Spontaneous recovery (SR) of a CTA (a revival of the taste avoidance) occurs when the CS is offered after a latency period in which the CS was not presented. An initial study explored the experimental parameters required to produce a reliable SR following acquisition and extinction of a robust CTA in rats. A CTA was formed through 3 pairings of 0.3% oral saccharin (SAC) and 81 mg/kg i.p. lithium chloride (LiCl) followed by extinction training resulting in 90% reacceptance of SAC. After extinction training, some of the animals were also tested for SR of the CTA upon exposure to SAC following a 15-, 30-, or 60-day latency period of water drinking. We report here that latencies of 15, 30, or 60 days produced small, but reliable, SRs of the CTA--with longer latencies producing progressively more suppression of SAC consumption. A second study investigated changes in the amygdala (AMY), gustatory neocortex (GNC), and medial prefrontal cortex (mPFC) functioning during SR of a CTA. Using immunohistochemical methods, brain c-Fos protein expression was analyzed in rats that extinguished the CTA as well as those that exhibited SR of the CTA after a 30-day latency. Our previous studies indicated that the numbers of c-Fos-labeled neurons in GNC and mPFC is low following CTA acquisition and increase dramatically as rats fully extinguished the aversion. Here we report that cortical c-Fos protein expression declines significantly following SR of the CTA. Expression of c-Fos in basolateral AMY decreased significantly from EXT to SR, but control animals with an intact CTA also decreased significantly from a short-term CTA test to a long-term CTA test. Low levels of c-Fos expression in the central nucleus of the amygdala (CE) were observed throughout EXT with little change in expression detectable following SR. These measurements reflect the dynamic nature of brain activity during acquisition and extinction of a CTA and highlight an important role for cortical neurons in the brain reorganization that occurs during SR of a CTA. The data also suggest that certain sub-nuclei of the AMY may play a relatively minor role in SR of this defensive reaction to a learned fear.}, } @article {pmid17434542, year = {2007}, author = {Geerse, GJ and van Gurp, LC and van Wijk, DC and Wiegant, VM and Stam, R}, title = {Duodenal pain and spinal morphine induce conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {91}, number = {2-3}, pages = {310-317}, doi = {10.1016/j.physbeh.2007.03.007}, pmid = {17434542}, issn = {0031-9384}, mesh = {Animals ; Association Learning/*drug effects/physiology ; Avoidance Learning/*drug effects/physiology ; Blood Pressure/drug effects/physiology ; Conditioning, Classical/*drug effects/physiology ; Dilatation/adverse effects ; Duodenum/physiopathology ; Heart Rate/drug effects/physiology ; Injections, Spinal ; Male ; Morphine/administration & dosage/*adverse effects ; Narcotics/administration & dosage/*adverse effects ; Pain/drug therapy/etiology/*physiopathology ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {Conditioned taste aversion (CTA) is a behavioural response essential to the survival of an individual. The combination of taste and odour of most foods provides a strong conditioned stimulus (CS) for an animal to respond in an appropriate way to any harmful unconditioned stimuli (US) that follow. The most widely used conditioned stimuli are drinkable sweet solutions, such as saccharin and sucrose. CTA-like responses are also found for environmental unconditioned stimuli, but these usually take longer training. In the present study, the aversive nature of a duodenal distention with an implanted balloon catheter was studied in freely moving rats using either CTA against a sucrose solution, or a light-dark passive avoidance (PA) paradigm. In addition, the effect of spinal morphine on CTA and the cardiovascular response to duodenal distention were studied. CTA could be induced by a single, but long-lasting 20-minute duodenal distention, which did not induce PA behaviour in a light-dark box. Spinal infusion of morphine alone induced CTA, suggesting that the model is unsuitable to investigate spinal pharmacological modulation of visceral pain. Spinal morphine did reduce the cardiovascular response to duodenal distention, strengthening its validity as a visceral pain model. Since CTA is a complicating factor in the field of chemotherapy in cancer patients and spinal morphine causes nausea and vomiting in humans, CTA may also complicate spinal drug treatment or anaesthesia.}, } @article {pmid17433569, year = {2007}, author = {Houpt, KA}, title = {Imprinting training and conditioned taste aversion.}, journal = {Behavioural processes}, volume = {76}, number = {1}, pages = {14-6; discussion 57-60}, doi = {10.1016/j.beproc.2006.09.016}, pmid = {17433569}, issn = {0376-6357}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical ; Conditioning, Psychological/*physiology ; Horses/*physiology/*psychology ; Mental Processes ; Rejection, Psychology ; Taste/*physiology ; }, } @article {pmid17428454, year = {2007}, author = {Pittman, D and Crawley, ME and Corbin, CH and Smith, KR}, title = {Chorda tympani nerve transection impairs the gustatory detection of free fatty acids in male and female rats.}, journal = {Brain research}, volume = {1151}, number = {}, pages = {74-83}, doi = {10.1016/j.brainres.2007.03.027}, pmid = {17428454}, issn = {0006-8993}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning ; Behavior, Animal ; Chorda Tympani Nerve/*physiology/surgery ; Conditioning, Operant/drug effects/*physiology ; Fatty Acids, Nonesterified/*metabolism ; Female ; Linoleic Acid/administration & dosage ; Male ; Oleic Acid/administration & dosage ; Rats ; Rats, Sprague-Dawley ; *Sex Characteristics ; Taste/*physiology ; }, abstract = {Sprague-Dawley rats with intact (SHAM) and bilaterally transected chorda tympani nerves (CTX) received conditioned taste aversions (CTAs) to the free fatty acids (FFAs), linoleic and oleic acid, at micromolar quantities. Two-bottle preference tests showed that CTX eliminated avoidance of 88 muM linoleic acid but did not affect CTA avoidance of corn oil or 250 mM sucrose. Short-duration stimulus tests following single-pairing CTAs revealed that 8-s stimulus durations resulted in higher detection thresholds for linoleic acid than 30-s trials. In these short-duration tests, CTX rats showed 2-fold elevations in threshold for linoleic acid compared to the SHAM rats. A single-pairing CTA did not produce avoidance of oleic acid during the short-duration tests; however, 3 consecutive days of CTA pairings did produce avoidance of oleic acid in both male and female rats. Finally, both male and female rats received SHAM or CTX surgery after demonstrating successful CTAs to either 100 microM linoleic or oleic acid. The ability to detect and avoid linoleic and oleic acid was eliminated by CTX for both sexes. Differences in the ability of rats to form CTAs to linoleic and oleic acid suggest that linoleic acid is a more salient stimulus than oleic acid. Our results suggest that FFAs stimulate afferent taste signals in the chorda tympani nerve of male and female rats and that these signals play an important role in the gustatory behavior of accepting or avoiding taste stimuli following a conditioned taste aversion.}, } @article {pmid17412515, year = {2007}, author = {Yasoshima, Y and Scott, TR and Yamamoto, T}, title = {Differential activation of anterior and midline thalamic nuclei following retrieval of aversively motivated learning tasks.}, journal = {Neuroscience}, volume = {146}, number = {3}, pages = {922-930}, doi = {10.1016/j.neuroscience.2007.02.044}, pmid = {17412515}, issn = {0306-4522}, mesh = {Animals ; Anterior Thalamic Nuclei/cytology/physiology ; Avoidance Learning/physiology ; Data Interpretation, Statistical ; Electroshock ; Genes, fos/genetics ; Immunohistochemistry ; Intralaminar Thalamic Nuclei/cytology/physiology ; Learning/*physiology ; Male ; Midline Thalamic Nuclei/cytology/physiology ; *Motivation ; Rats ; Rats, Wistar ; Reinforcement, Psychology ; Taste/physiology ; Thalamic Nuclei/cytology/*physiology ; }, abstract = {Two thalamic nuclear groups, the anterior thalamic nuclei (ATN) and midline and intralaminar thalamic complex (MITC) have connections to the prefrontal cortex, amygdala, hippocampus and accumbens that are important for learning and memory. However, the anatomical proximity between the ATN and MITC makes it difficult to reveal their roles in memory retrieval of aversive conditioned behavior. To address the issue, we explored the activation of the ATN and MITC, as represented by the expression of the immediate early gene c-fos, following either the retrieval of a conditioned taste aversion (CTA) induced by taste-LiCl pairing (visceral aversion) or of inhibitory avoidance (IA) induced by context-foot shock pairing (somatic aversion) in rats. The anterodorsal (AD) nucleus in the ATN was activated by foot shock and the recall of IA, but not by i.p. injection of LiCl or the recall of CTA. No significant elevation was observed in the other ATN following these treatments. Among nuclei of the MITC, the paraventricular thalamic nucleus (PVT) was activated by the delivery of shock or LiCl and by the recall of both CTA and IA, while the mediodorsal thalamus (MD) and central medial and intermediate thalamus (CM/IMD) were not. The innately aversive taste of quinine did not elevate c-fos expression in either the ATN or MITC. These results suggest that the PVT in the MITC is involved in the processing and retrieval of both taste-malaise and context-shock association tasks, while the AD in the ATN is involved in those of context-shock association only. The difference of the activity between the ATN and MITC demonstrates their functional and anatomical heterogeneity in neural substrates for aversive learning tasks.}, } @article {pmid17382305, year = {2007}, author = {Uchida, S and Umeeda, H and Kitamoto, A and Masushige, S and Kida, S}, title = {Chronic reduction in dietary tryptophan leads to a selective impairment of contextual fear memory in mice.}, journal = {Brain research}, volume = {1149}, number = {}, pages = {149-156}, doi = {10.1016/j.brainres.2007.02.049}, pmid = {17382305}, issn = {0006-8993}, mesh = {Animals ; Brain/*physiopathology ; Conditioning, Classical ; *Diet ; Fear/*physiology ; Learning/*physiology ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Tryptophan/*deficiency ; }, abstract = {The depletion of systemic tryptophan is an important tool to study the effects of reduced 5-HT on cognition. Indeed, previous reports indicated that acute depletion of TRP leads to a memory impairment in human subjects and rodents. From the view of nutrition, it is important to investigate the effects of chronic limitation of L-tryptophan (TRP) on learning and memory formation. In this study, we examined the effects of chronic consumption of a low TRP diet on memory formation in mice. Specifically, we assessed the ability to form contextual fear, cued fear, conditioned taste aversion, and spatial memories in mice fed a TRP-limited diet for at least 1 month. TRP-limited mice showed impaired formation of contextual fear memory that is hippocampus-dependent. In contrast, these mice showed normal hippocampus-dependent spatial memory in the Morris water maze test, as well as in cued fear and conditioned taste aversion memories, which are amygdala-dependent memory processes. Thus, dietary TRP restriction appears to result in selective impairments in hippocampus-dependent contextual fear memory formation in mice.}, } @article {pmid17382303, year = {2007}, author = {Núñez-Jaramillo, L and Delint-Ramirez, I and Bermúdez-Rattoni, F}, title = {PKC blockade differentially affects aversive but not appetitive gustatory memories.}, journal = {Brain research}, volume = {1148}, number = {}, pages = {177-182}, doi = {10.1016/j.brainres.2007.02.032}, pmid = {17382303}, issn = {0006-8993}, mesh = {Alkaloids/adverse effects ; Animals ; Appetite/drug effects/physiology ; Appetitive Behavior/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Benzophenanthridines/adverse effects ; Brain/drug effects/*enzymology ; Cerebral Cortex/drug effects/enzymology ; Enzyme Inhibitors/adverse effects ; Feeding Behavior/drug effects/physiology ; Memory/drug effects/*physiology ; Parietal Lobe/drug effects/enzymology ; Protein Kinase C/antagonists & inhibitors/*metabolism ; Rats ; Rats, Wistar ; Taste/drug effects/*physiology ; }, abstract = {After consumption of a new taste, there are mainly two possible outcomes for the establishment of a taste memory, either it will be aversive or safe depending on the consequences of taste consumption. It has been proposed that both types of learning share a common initial taste memory trace, which will lead to two different memory traces, safe or aversive. To study the role of PKC activity in aversive or safe taste memory formation, we administered chelerythrine, a PKC inhibitor, into the insular cortex or parietal cortex 20 min before conditioned taste aversion or attenuation of neophobia training. The results suggest that PKC activity is needed in the insular cortex for the establishment of aversive taste memory, but not for safe taste memory.}, } @article {pmid17376151, year = {2008}, author = {Blednov, YA and Walker, D and Martinez, M and Levine, M and Damak, S and Margolskee, RF}, title = {Perception of sweet taste is important for voluntary alcohol consumption in mice.}, journal = {Genes, brain, and behavior}, volume = {7}, number = {1}, pages = {1-13}, pmid = {17376151}, issn = {1601-183X}, support = {R01 DC003155/DC/NIDCD NIH HHS/United States ; A06399//PHS HHS/United States ; DC03155/DC/NIDCD NIH HHS/United States ; AA U01 13520-INIA/AA/NIAAA NIH HHS/United States ; U01 AA013520-07/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics/psychology ; Animals ; Avoidance Learning ; Conditioning, Classical ; Crosses, Genetic ; Female ; Heterotrimeric GTP-Binding Proteins/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Mutant Strains ; Quinine ; Receptors, G-Protein-Coupled/*genetics ; Saccharin ; TRPM Cation Channels/*genetics ; Taste/*genetics ; }, abstract = {To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.}, } @article {pmid17371921, year = {2007}, author = {Sugai, R and Azami, S and Shiga, H and Watanabe, T and Sadamoto, H and Kobayashi, S and Hatakeyama, D and Fujito, Y and Lukowiak, K and Ito, E}, title = {One-trial conditioned taste aversion in Lymnaea: good and poor performers in long-term memory acquisition.}, journal = {The Journal of experimental biology}, volume = {210}, number = {Pt 7}, pages = {1225-1237}, doi = {10.1242/jeb.02735}, pmid = {17371921}, issn = {0022-0949}, mesh = {Analysis of Variance ; Animals ; Conditioning, Psychological ; Food Deprivation/physiology ; Lymnaea/*physiology ; Memory/*physiology ; Potassium Chloride ; Sucrose ; Taste/*physiology ; Temperature ; }, abstract = {In the majority of studies designed to elucidate the causal mechanisms of memory formation, certain members of the experimental cohort, even though subjected to exactly the same conditioning procedures, remember significantly better than others, whereas others show little or no long-term memory (LTM) formation. To begin to address the question of why this phenomenon occurs and thereby help clarify the causal mechanism of LTM formation, we used a conditioned taste aversion (CTA) procedure on individuals of the pond snail Lymnaea stagnalis and analyzed their subsequent behavior. Using sucrose as an appetitive stimulus and KCl as an aversive stimulus, we obtained a constant ratio of ;poor' to ;good' performers for CTA-LTM. We found that approximately 40% of trained snails possessed LTM following a one-trial conditioning procedure. When we examined the time-window necessary for the memory consolidation, we found that if we cooled snails to 4 degrees C for 30 min within 10 min after the one-trial conditioning, LTM was blocked. However, with delayed cooling (i.e. longer than 10 min), LTM was present. We could further interfere with LTM formation by inducing inhibitory learning (i.e. backward conditioning) after the one-trial conditioning. Finally, we examined whether we could motivate snails to acquire LTM by depriving them of food for 5 days before the one-trial conditioning. Food-deprived snails, however, failed to exhibit LTM following the one-trial conditioning. These results will help us begin to clarify why some individuals are better at learning and forming memory for specific tasks at the neuronal level.}, } @article {pmid17350084, year = {2007}, author = {Golden, GJ and Houpt, TA}, title = {NMDA receptor in conditioned flavor-taste preference learning: blockade by MK-801 and enhancement by D-cycloserine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {86}, number = {3}, pages = {587-596}, pmid = {17350084}, issn = {0091-3057}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; T32 DC000044/DC/NIDCD NIH HHS/United States ; DC03198/DC/NIDCD NIH HHS/United States ; T32 DC00044/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/*drug effects/*physiology ; Cycloserine/*pharmacology ; Dizocilpine Maleate/*pharmacology ; Glycine/agonists ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/*agonists/*antagonists & inhibitors/physiology ; Taste ; }, abstract = {Conditioned flavor-taste preference (CFTP) is a robust form of learning in which animals acquire a preference for a flavor (e.g. Kool-Aid) previously mixed with a highly preferred tastant (e.g. fructose) over a flavor previously mixed with a less-preferred tastant (e.g. saccharin). Here, the role of the N-methyl-D-aspartate (NMDA) glutamate-glycine receptor (NR) was probed using systemic MK-801, a non-competitive antagonist, and D-cycloserine (DCS), a glycine agonist. Rats were injected with MK-801 (100 microg/kg) or vehicle 30 min prior to a daily 2-h conditioning session with 1-bottle access to a Kool-Aid flavor (grape or cherry) mixed with either 8% fructose (CS+/F) or 0.2% saccharin (CS-/S). CFTP expression was measured in 2-bottle preference tests between the Kool-Aid flavors mixed with 0.2% saccharin (CS+/S vs. CS-/S). While vehicle-treated rats acquired a preference for CS+/S over CS-/S, MK-801 prior to conditioning completely blocked CFTP learning. The effect of MK-801 was specific to CFTP acquisition, because follow-up experiments demonstrated that MK-801 did not induce a conditioned taste aversion, cause state-dependent learning, or affect CFTP expression. In a second approach, rats were injected with DCS (15 mg/kg) 60 min prior to daily conditioning. In contrast to MK-801, administration of DCS prior to conditioning enhanced CFTP learning (but not reversal conditioning). These results demonstrate that NR neurotransmission is critical for CFTP learning. Furthermore, enhancement of CFTP learning by DCS suggests that endogenous levels of glycine or D-serine may be a limiting factor in CFTP learning.}, } @article {pmid17342776, year = {2007}, author = {Faber, WD and Deyo, JA and Stump, DG and Ruble, K}, title = {Two-generation reproduction study of di-2-ethylhexyl terephthalate in Crl:CD rats.}, journal = {Birth defects research. Part B, Developmental and reproductive toxicology}, volume = {80}, number = {2}, pages = {69-81}, doi = {10.1002/bdrb.20108}, pmid = {17342776}, issn = {1542-9733}, mesh = {Animals ; Animals, Newborn ; Breeding ; Diethylhexyl Phthalate/*toxicity ; Female ; Follow-Up Studies ; Lactation/drug effects ; Male ; Models, Biological ; Pregnancy ; *Pregnancy, Animal ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Inbred Strains ; Reproduction/*drug effects ; Sexual Behavior, Animal/drug effects ; }, abstract = {BACKGROUND: This study was conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) on reproductive capability from exposure of F(0) and F(1) parental animals.

METHODS: Four groups of male and female Crl:CD (SD)IGS BR rats (30/gender/group) were exposed to 0, 0.3%, 0.6%, and 1.0% DEHT in the feed for at least 70 consecutive days before mating for the F(0) and F(1) generations. Exposure for the F(0) and F(1) males continued throughout the mating period until euthanasia. Exposure for the F(0) and F(1) females continued throughout mating, gestation, and lactation. The F(1) and F(2) pups were weaned on postnatal day (PND) 21. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F(0) and F(1) generations, and F(1) generation offspring growth and development.

RESULTS: DEHT exposure did not affect clinical observations. However, lethality was observed in F(0) and F(1) dams consuming the 1.0% diet during the post-weaning period. No treatment-related mortality occurred in any of the male groups exposed to DEHT or in the female groups exposed to 0.3% or 0.6% DEHT. Male rats consuming the 1.0% diet in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F(0) or F(1) generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size, developmental landmarks, and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts for the F(1) females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F(0) and F(1) generations.

CONCLUSIONS: Increases in liver weights were found in the male and female animals exposed to 0.6% or 1.0% DEHT in the diet. Because there were no accompanying histopathologic changes, this effect was not considered adverse. Significant decreases in feed consumption in the female animals from the groups consuming 1.0% DEHT in the diet during lactation accompanied reduced postnatal pup body weights and rate of weight gain. Reductions in pup body weights later in lactation may also have been due to direct consumption of the treated feed by the pups or taste aversion to the same. Reduced relative spleen weight was found in male weanling pups from the 1.0% group in both generations and reduced relative spleen and thymus weights were found in female pups from the 1.0% group in the F(2) generation at necropsy on PND 21. Therefore, for parental and pup systemic toxicity, 0.3% DEHT in the diet (182 mg/kg/day) was considered no-observed-effect level (NOEL). The 1.0% DEHT (614 mg/kg/day) in the diet exposure concentration was considered a NOEL for F(0) and F(1) reproductive toxicity endpoints.}, } @article {pmid17328870, year = {2007}, author = {Angst, MJ and Macedo, CE and Guiberteau, T and Sandner, G}, title = {Alteration of conditioned emotional response and conditioned taste aversion after neonatal ventral hippocampus lesions in rats.}, journal = {Brain research}, volume = {1143}, number = {}, pages = {183-192}, doi = {10.1016/j.brainres.2007.01.093}, pmid = {17328870}, issn = {0006-8993}, mesh = {Amphetamine/pharmacology ; Animals ; Animals, Newborn ; Avoidance Learning/*physiology ; Behavior, Animal/drug effects ; Brain Injuries/*pathology ; Central Nervous System Stimulants/pharmacology ; Conditioning, Psychological/*physiology ; *Emotions ; Hippocampus/*physiopathology ; Inhibition, Psychological ; Locomotion/drug effects ; Rats ; Rats, Sprague-Dawley ; Reaction Time/drug effects/physiology ; Reflex, Startle/drug effects ; *Taste ; }, abstract = {Sprague-Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth according to the Lipska and Weinberger's procedure for modeling schizophrenia. The aim of the present work was to better characterize their learning capacity. A double latent inhibition study was conducted using respectively conditioned taste aversion and conditioned emotional response. In the background of this evaluation, locomotion under apomorphine and startle reactions, inhibited or not by prepulses, was also evaluated. Our experimental methods were the same as those used in previous studies from the laboratory which were found to be sensitive to pharmacological manipulations and shown by others to be unaffected by lesions of the ventral hippocampus carried out in adult rats. In contrast, neonatally lesioned rats, once adults (over 60 days old), were hyper-responsive to noise--i.e., the startle response to a 105 db(A) noise pulse was enhanced--and hyperactive under apomorphine (0.7 mg/kg). The prepulse inhibition properties of the startle remained unchanged. Lesioned rats showed a deficit but not a suppression of conditioning, similar in both tests, but latent inhibition was preserved. Such observations complement the already known memory deficit produced in this neurodevelopmental model of schizophrenia.}, } @article {pmid17324053, year = {2007}, author = {St Andre, J and Reilly, S}, title = {Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition.}, journal = {Behavioral neuroscience}, volume = {121}, number = {1}, pages = {90-99}, doi = {10.1037/0735-7044.121.1.90}, pmid = {17324053}, issn = {0735-7044}, support = {DC04341/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {*Amygdala/injuries/pathology/physiopathology ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Conditioning, Psychological/*physiology ; Excitatory Amino Acid Agonists/adverse effects ; Ibotenic Acid/adverse effects ; *Inhibition, Psychological ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; *Taste ; }, abstract = {The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty.}, } @article {pmid17320310, year = {2007}, author = {Pineño, O}, title = {An examination of the effectiveness of inflation and deflation treatments in detecting within-compound learning of a taste aversion.}, journal = {Behavioural processes}, volume = {75}, number = {1}, pages = {33-39}, doi = {10.1016/j.beproc.2007.01.004}, pmid = {17320310}, issn = {0376-6357}, mesh = {Analysis of Variance ; Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Two conditioned taste aversion experiments with rats assessed the relative effectiveness in providing evidence of within-compound learning of different procedures that involve the initial compound presentation of two stimuli, A and X, with the unconditioned stimulus (i.e., AX+). In Experiment 1, following a single AX+ trial, groups A+ and B+ received an additional conditioning trial (i.e., inflation treatment) with A and B, respectively, whereas group A- received an extinction trial (i.e., deflation treatment) with A. The results showed a reduction in the aversion elicited by the target stimulus, X, in group A- relative to both groups A+ and B+, which did not differ. Experiment 2 further investigated the failure of group A+ to increase the aversion to X relative to control group B+ by pairing A or B with either the same unconditioned stimulus that was previously paired with AX (groups A+ and B+) or with a stronger unconditioned stimulus (groups A* and B*). The results showed increased aversion to X in group A* relative to group B*, but not in group A+ relative to group B+. These results are interpreted as indicative of extinction of the within-compound association during the treatment with A, which could likely impair the detection of within-compound learning following an inflation, but not a deflation treatment.}, } @article {pmid17307643, year = {2006}, author = {Blednov, YA and Walker, D and Martinez, M and Harris, RA}, title = {Reduced alcohol consumption in mice lacking preprodynorphin.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {40}, number = {2}, pages = {73-86}, pmid = {17307643}, issn = {0741-8329}, support = {AA13520/AA/NIAAA NIH HHS/United States ; AA06399/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013520/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics/*psychology ; Animals ; Central Nervous System Depressants/metabolism/pharmacology ; Conditioning, Operant/drug effects ; Dynorphins/*genetics/*physiology ; Ethanol/metabolism/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Postural Balance/drug effects ; Protein Precursors/*genetics/*physiology ; Receptors, Opioid, kappa/physiology ; Reflex/drug effects ; Reward ; Saccharin/pharmacology ; Substance Withdrawal Syndrome/psychology ; Sucrose/pharmacology ; Taste/drug effects ; }, abstract = {Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).}, } @article {pmid17299789, year = {2007}, author = {Roma, PG and Davis, CM and Riley, AL}, title = {Effects of cross-fostering on cocaine-induced conditioned taste aversions in Fischer and Lewis rats.}, journal = {Developmental psychobiology}, volume = {49}, number = {2}, pages = {172-179}, doi = {10.1002/dev.20168}, pmid = {17299789}, issn = {0012-1630}, mesh = {Animals ; Cocaine/administration & dosage/*pharmacology ; Conditioning, Psychological/*drug effects ; Dopamine Uptake Inhibitors/administration & dosage/*pharmacology ; Escape Reaction/*drug effects ; Female ; Locomotion/drug effects ; Male ; Pregnancy ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Taste/*drug effects ; }, abstract = {The systematic comparison between Fischer and Lewis rats is a popular animal model of genetic factors in drug abuse. Although genetic and environmental factors interact to affect drug abuse in humans, analogous effects have not yet been reported within the Fischer-Lewis model. In order to assess the contributions and interaction of genotype and early maternal environment on responses to a drug of abuse, the present study employed a cross-fostering design, where male and female Fischer and Lewis pups were reared by unrelated dams of their own strain (in-fostered) or of the other strain (cross-fostered). As adults, rats from both strains were tested for their ability to acquire a conditioned taste aversion to a novel saccharin solution that had been repeatedly paired with an injection of cocaine (32 mg/kg, subcutaneous). In-fostered Fischer females acquired significantly weaker aversions than in-fostered Lewis females across the multiple saccharin-cocaine pairings. However, cross-fostered Fischer females exhibited aversions that were not only significantly stronger than their in-fostered Fischer counterparts, but identical to all groups of the Lewis genotype. No strain differences or cross-fostering effects were observed in the males. The data with the female subjects cannot be accounted for simply by the genetic strain of the subjects and demonstrate a clear gene-environment interaction effect on responses to the aversive effects of cocaine in Fischer and Lewis rats. Implications for studying maternal behavior as a source of epigenetic modulation of drug abuse vulnerability were discussed.}, } @article {pmid17283607, year = {2006}, author = {Giovannini, MG}, title = {The role of the extracellular signal-regulated kinase pathway in memory encoding.}, journal = {Reviews in the neurosciences}, volume = {17}, number = {6}, pages = {619-634}, doi = {10.1515/revneuro.2006.17.6.619}, pmid = {17283607}, issn = {0334-1763}, mesh = {Acetylcholine/physiology ; Animals ; Avoidance Learning/physiology ; Enzyme Activation/physiology ; Extracellular Signal-Regulated MAP Kinases/metabolism/*physiology ; Humans ; Long-Term Potentiation/physiology ; Memory/*physiology ; Neurotransmitter Agents/*physiology ; }, abstract = {All types of memory depend on the integrated activity of various brain structures and neurotransmitter systems and involve more than one receptor, signal transduction pathway and postsynaptic mechanism. The components of the extracellular signal regulated kinases-1 and -2 (ERK1/2) signal transduction pathways are ubiquitous and well conserved protein kinases involved in relaying extracellular signals into intracellular responses, and are involved in the mechanisms of synaptic plasticity, learning and memory. ERK activation is required for the full expression of long-term potentiation (LTP), the principal cellular mechanism thought to underlie neuronal plasticity. Furthermore, ERK is activated in and is necessary for the development of several forms of memory, such as fear conditioning, conditioned taste aversion memory, spatial memory, step-down inhibitory avoidance and object recognition memory. ERK activation is secondary to neurotransmitter release and activation of the forebrain cholinergic neurons during and immediately after acquisition of an inhibitory avoidance response, revealed by increased release of acetylcholine (ACh), which in turn activates ERK in neurons located in the medial prefrontal cortex and ventral hippocampus. Increased release of ACh and ERK activation are events mechanistically related to each other, as demonstrated by the use of scopolamine, a muscarinic receptor antagonist, and by inhibitors of ERK activation, which blocked memory encoding and ERK activation. A critical function of activated ERK downstream of the increased ACh release occurring during learning is to promote cellular integration of divergent downstream effectors which may trigger different responses, depending upon which subsets of scaffolding anchors, target proteins and regulatory phosphatases are involved. The hope is that by studying how ERK is activated by different neurotransmitter systems and the ensuing downstream cellular modifications, the molecular basis of memory will be ultimately understood.}, } @article {pmid17277925, year = {2007}, author = {Jager-Wittenaar, H and Dijkstra, PU and Vissink, A and van der Laan, BF and van Oort, RP and Roodenburg, JL}, title = {Critical weight loss in head and neck cancer--prevalence and risk factors at diagnosis: an explorative study.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {15}, number = {9}, pages = {1045-1050}, pmid = {17277925}, issn = {0941-4355}, mesh = {Aged ; Female ; Head and Neck Neoplasms/*complications/diagnosis ; Humans ; Male ; Middle Aged ; Nutrition Disorders/*epidemiology/etiology ; Prevalence ; Risk Factors ; *Weight Loss ; }, abstract = {GOALS OF WORK: Critical weight loss (> or =5% in 1 month or > or =10% in 6 months) is a common phenomenon in head and neck cancer patients. It is unknown which complaints are most strongly related to critical weight loss in head and neck cancer patients at the time of diagnosis. The aim of this explorative study was to assess the prevalence of critical weight loss and to analyze risk factors for critical weight loss in head and neck cancer patients before treatment.

MATERIALS AND METHODS: Critical weight loss and factors reducing dietary intake were assessed in 447 patients referred to an ear, nose and throat clinic at the time of diagnosis.

MAIN RESULTS: In total, data of 407 patients were analyzed. Critical weight loss was present in 19% of the patients. Patients with cancer in the hypopharynx, oropharynx/oral cavity and supraglottic larynx had the highest risk for critical weight loss. Loss of appetite, dysphagia/passage difficulties and loss of taste/aversion were significantly (p < 0.05) associated with critical weight loss.

CONCLUSIONS: Already before treatment, critical weight loss is a considerable problem in head and neck cancer patients. Critical weight loss is frequently observed in patients with cancer in the hypopharynx, oropharynx/oral cavity and supraglottic larynx.}, } @article {pmid17276421, year = {2007}, author = {Tokita, K and Shimura, T and Nakamura, S and Inoue, T and Yamamoto, T}, title = {Involvement of forebrain in parabrachial neuronal activation induced by aversively conditioned taste stimuli in the rat.}, journal = {Brain research}, volume = {1141}, number = {}, pages = {188-196}, doi = {10.1016/j.brainres.2007.01.023}, pmid = {17276421}, issn = {0006-8993}, mesh = {Amiloride/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Conditioning, Classical/*physiology ; Decerebrate State/metabolism ; Dose-Response Relationship, Drug ; Drug Interactions ; Electric Stimulation/methods ; Immunohistochemistry ; Male ; Neurons/drug effects/*physiology ; Oncogene Proteins v-fos/metabolism ; Pons/*cytology ; Prosencephalon/*physiology ; Rats ; Rats, Wistar ; Sodium Channel Blockers/pharmacology ; Sodium Chloride/pharmacology ; Taste/*physiology ; }, abstract = {We previously have shown that forebrain inputs increase responses of amiloride-sensitive NaCl-best neurons to the conditioned stimulus (CS) in the rat parabrachial nucleus (PBN) after the establishment of conditioned taste aversion (CTA) to NaCl. In the present study, we examined the effects of aversively-conditioned NaCl taste stimulation on Fos-like immunoreactivity (FLI) in the PBN using awake intact and decerebrate rats. In Experiment 1, the CTA-trained and sham-conditioned control rats were intraorally infused with 0.1 M NaCl or 0.1 M NaCl mixed with 10(-4) M amiloride, a sodium-channel blocker. Significantly more NaCl-stimulated FLI was observed in the central medial (cms) and external lateral subnuclei (els) of PBN in the CTA-trained group than in the control group. In both groups, amiloride markedly reduced NaCl-stimulated FLI in the cms but not in the els. In Experiment 2, we found that after decerebration, there was no significant difference in FLI between the CTA-trained and sham-conditioned groups. These results suggest that (1) amirolide-sensitive taste information of NaCl projects mainly to the cms; (2) sensory information of aversive taste stimuli is likely to be represented in the els; and (3) forebrain inputs are required for elevated FLI in the PBN after CTA.}, } @article {pmid21171363, year = {2007}, author = {Li, X and Jiang, ZL and Wang, GH and Shen, HM}, title = {[Relationship among sexual differences of susceptibility to motion sickness, AVP levels of plasma and pituitary and V1b receptor expression of pituitary in rats].}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {23}, number = {1}, pages = {35-40}, pmid = {21171363}, issn = {1000-6834}, mesh = {Animals ; Arginine Vasopressin/*blood ; Female ; Male ; Motion Sickness/*metabolism ; Pituitary Gland/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Vasopressin/*metabolism ; Sensitivity and Specificity ; Sex Characteristics ; }, abstract = {AIM: To investigate the relationship among sexual differences of motion sickness (MS), AVP levels of plasma and pituitary and the expression of pituitary V1b receptors for further understanding of the MS mechanisms.

METHODS: The conditioned taste aversion (CTA) of 0.15% saccharin sodium solution (SSS) was served as MS model. 98 (49 male and 49 female) rats were used in this experiment, 50 for the detection of the AVP level in plasma and pituitary with radioimmunoassay (RIA), 12 for the observation of the number of V1b receptor-positive neurons in the pituitary with the fluorescence immunohistochemistry method, the rest for the evaluation of the expression of V1b receptor in the pituitary by Western blot.

RESULTS: With regard to male rats, decrease of the drinking volume of 0.15% SSS was greater in female rats after rotatory stimulation. The plasma AVP concentration of female rats was significantly higher than that of males under normal conditions, but reduced significantly after rotatory stimulation. However, no significant change was found in male rats. In addition, the pituitary AVP level of the female rats was significantly higher than that of the male rats under normal conditions, but decreased at 8 h and significantly at 24 h after rotation. Similarly, the pituitary AVP level of male rats also decreased significantly at 8 h after rotation, but this decrease was not comparable to that of the females. At 24 h after rotation the pituitary AVP level almost recovered in male rats. In the pituitary, which was related to the stress response, the V1b receptor-positive neurons and the expression level of V1b receptor in female rats were significantly higher than those of the male rats, but they decreased significantly after rotation, while no apparent change was detected in the male rats.

CONCLUSION: The changes of plasma and pituitary AVP and V1b receptor level of the pituitary after rotatory stimulation are different between male and female rats and the AVP secretion of the pituitary may be involved in the sexual difference in susceptibility to motion sickness.}, } @article {pmid17258476, year = {2007}, author = {Blaiss, CA and Janak, PH}, title = {Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach.}, journal = {Neurobiology of learning and memory}, volume = {87}, number = {4}, pages = {644-658}, pmid = {17258476}, issn = {1074-7427}, support = {F31 DA016881/DA/NIDA NIH HHS/United States ; F31 DA016881-03/DA/NIDA NIH HHS/United States ; 1 F31 DA016881/DA/NIDA NIH HHS/United States ; }, mesh = {Amphetamine/*pharmacology ; Analysis of Variance ; Animals ; Anisomycin/*pharmacology ; Appetitive Behavior/drug effects ; Association Learning/drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Classical/*drug effects ; Drug Administration Schedule ; Exploratory Behavior/drug effects ; Male ; Memory/drug effects ; Protein Synthesis Inhibitors/*pharmacology ; Rats ; Rats, Long-Evans ; Time Factors ; }, abstract = {The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.}, } @article {pmid17233637, year = {2007}, author = {Rhodes, JS and Ford, MM and Yu, CH and Brown, LL and Finn, DA and Garland, T and Crabbe, JC}, title = {Mouse inbred strain differences in ethanol drinking to intoxication.}, journal = {Genes, brain, and behavior}, volume = {6}, number = {1}, pages = {1-18}, doi = {10.1111/j.1601-183X.2006.00210.x}, pmid = {17233637}, issn = {1601-1848}, support = {AA13519/AA/NIAAA NIH HHS/United States ; AA13478/AA/NIAAA NIH HHS/United States ; AA15234/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; AA12714/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/blood/*genetics/psychology ; Alcoholic Intoxication/blood/*genetics/psychology ; Animals ; Choice Behavior/physiology ; Darkness ; Disease Models, Animal ; Drinking Behavior/*physiology ; Ethanol/blood ; Female ; *Genetic Variation ; Genetics, Behavioral/methods ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; *Phylogeny ; Rotarod Performance Test ; Self Administration ; Sex Factors ; Species Specificity ; }, abstract = {Recently, we described a simple procedure, Drinking in the Dark (DID), in which C57BL/6J mice self-administer ethanol to a blood ethanol concentration (BEC) above 1 mg/ml. The test consists of replacing the water with 20% ethanol in the home cage for 4 h early during the dark phase of the light/dark cycle. Three experiments were conducted to explore this high ethanol drinking model further. In experiment 1, a microanalysis of C57BL/6J behavior showed that the pattern of ethanol drinking was different from routine water intake. In experiment 2, drinking impaired performance of C57BL/6J on the accelerating rotarod and balance beam. In experiment 3, 12 inbred strains were screened to estimate genetic influences on DID and correlations with other traits. Large, reliable differences in intake and BEC were detected among the strains, with C57BL/6J showing the highest values. Strain means were positively correlated with intake and BEC in the standard (24 h) and a limited (4 h) two-bottle ethanol vs. water test, but BECs reached higher levels for DID. Strain mean correlations with other traits in the Mouse Phenome Project database supported previously reported genetic relationships of high ethanol drinking with low chronic ethanol withdrawal severity and low ethanol-conditioned taste aversion. We extend these findings by showing that the correlation estimates remain relatively unchanged even after correcting for phylogenetic relatedness among the strains, thus relaxing the assumption that the strain means are statistically independent. We discuss applications of the model for finding genes that predispose pharmacologically significant drinking in mice.}, } @article {pmid17229530, year = {2007}, author = {Forristall, JR and Hookey, BL and Grant, VL}, title = {Conditioned taste avoidance induced by forced and voluntary wheel running in rats.}, journal = {Behavioural processes}, volume = {74}, number = {3}, pages = {326-333}, doi = {10.1016/j.beproc.2006.12.002}, pmid = {17229530}, issn = {0376-6357}, mesh = {Animals ; Avoidance Learning/*physiology ; Choice Behavior/*physiology ; Conditioning, Classical/*physiology ; Energy Metabolism/physiology ; Male ; Physical Conditioning, Animal/*physiology/psychology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {Voluntary exercise by rats running in a freely rotating wheel (free wheel) produces conditioned taste avoidance (CTA) of a flavored solution consumed before running [e.g., Lett, B.T., Grant, V.L., 1996. Wheel running induces conditioned taste aversion in rats trained while hungry and thirsty. Physiol. Behav. 59, 699-702]. Forced exercise, swimming or running, also produces CTA in rats [e.g., Masaki, T., Nakajima, S., 2006. Taste aversion induced by forced swimming, voluntary running, forced running, and lithium chloride injection treatments. Physiol. Behav. 88, 411-416]. Energy expenditure may be the critical factor in producing such CTA. If so, forced running in a motorized running wheel should produce CTA equivalent to that produced by a similar amount of voluntary running. In two experiments, we compared forced running in a motorized wheel with voluntary running in a free wheel. Mean distance run over 30 min was equated as closely as possible in the two apparatuses. Both types of exercise produced CTA relative to sedentary, locked-wheel controls. However, voluntary running produced greater CTA than forced running. We consider differences between running in the free and motorized wheels that may account for the differences in strength of CTA.}, } @article {pmid17211649, year = {2007}, author = {Schramm-Sapyta, NL and Cha, YM and Chaudhry, S and Wilson, WA and Swartzwelder, HS and Kuhn, CM}, title = {Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and adult rats.}, journal = {Psychopharmacology}, volume = {191}, number = {4}, pages = {867-877}, pmid = {17211649}, issn = {0033-3158}, support = {K01 DA020729/DA/NIDA NIH HHS/United States ; K01 DA020729-01A1/DA/NIDA NIH HHS/United States ; DA019346/DA/NIDA NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/blood ; Age Factors ; *Aging ; Animals ; *Anxiety ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Conditioning, Psychological/drug effects ; Corticosterone/blood ; Dose-Response Relationship, Drug ; Dronabinol/*pharmacology ; Hallucinogens/*pharmacology ; Male ; Motor Activity/*drug effects ; Psychotropic Drugs/*pharmacology ; Rats ; Taste ; Time Factors ; }, abstract = {RATIONALE: Unpleasant side effects of drugs of abuse often limit their repeated use; however, such effects may be attenuated in adolescents compared to adults.

OBJECTIVES: We investigated whether the anxiogenic, aversive, or locomotor effects of delta-9-tetrahydrocannabinol (THC) differ between adolescent and adult rats.

METHODS: We used the elevated plus maze (EPM) and light-dark tests of anxiety, the conditioned taste aversion and conditioned place aversion (CPA) tests of generalized aversion, and measures of stress hormone levels in serum to examine effects of THC in adolescent and adult rats. Locomotor activity was also recorded in the EPM, light-dark task, and CPA association sessions.

RESULTS: In the EPM and light-dark tasks, THC was anxiogenic in both age groups, but the drug was more anxiogenic in adults than in adolescents. In the place and taste aversion tasks, THC was aversive in both ages, and at 1.25 and 5 mg/kg, was more aversive in adults than in adolescents. The locomotor response to THC, as measured in the anxiety tasks and CPA, affected adults more than adolescents. Multiple measures revealed a locomotor-decreasing effect in adults, whereas some measures suggested a small locomotor-increasing effect in adolescent rats.

CONCLUSIONS: These results suggest that THC can have greater anxiogenic, aversive, and locomotor-reducing effects in adult rats than in adolescent rats. These findings suggest an explanation for reduced marijuana use in adult humans compared to teenagers.}, } @article {pmid17204251, year = {2007}, author = {St Andre, J and Albanos, K and Reilly, S}, title = {C-fos expression in the rat brain following lithium chloride-induced illness.}, journal = {Brain research}, volume = {1135}, number = {1}, pages = {122-128}, pmid = {17204251}, issn = {0006-8993}, support = {R01 DC004341/DC/NIDCD NIH HHS/United States ; R01 DC006456/DC/NIDCD NIH HHS/United States ; R56 DC006456/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/*pharmacology ; Brain/*drug effects ; Gene Expression/*drug effects ; Immunohistochemistry/methods ; Lithium Chloride/*pharmacology ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The present study examined c-Fos expression in selected brain areas consequent to administration of lithium chloride, the typical illness-inducing agent used in laboratory studies of conditioned taste aversion. The results replicated previous findings of significant c-Fos expression in the parabrachial nucleus, the central nucleus of the amygdala and the basolateral amygdala. New findings indicate significant lithium-induced c-Fos in the gustatory region of the thalamus and the bed nucleus of the stria terminalis but not in the insular cortex. The results are discussed with respect to the neural substrates of conditioned taste aversion.}, } @article {pmid17201472, year = {2006}, author = {Tracy, AL and Davidson, TL}, title = {Comparison of nutritive and nonnutritive stimuli in intestinal and oral conditioned taste aversion paradigms.}, journal = {Behavioral neuroscience}, volume = {120}, number = {6}, pages = {1268-1278}, doi = {10.1037/0735-7044.120.6.1268}, pmid = {17201472}, issn = {0735-7044}, support = {R01HD29792/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal ; Conditioning, Psychological/drug effects/*physiology ; Eating/drug effects ; Flavoring Agents/administration & dosage ; *Food ; Intestines/drug effects/*physiology ; Intubation, Gastrointestinal/methods ; Lithium Chloride/administration & dosage ; Male ; Polysaccharides/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/*physiology ; }, abstract = {The intestinal taste aversion paradigm has previously demonstrated that animals could orally discriminate between carbohydrate and fat subsequent to pairing a gastrointestinal (GI) infusion of 1 nutrient with lithium chloride (LiCl), whereas they could not discriminate between 2 nonnutritive flavors (A. L. Tracy, R. J. Phillips, M. M. Chi, T. L. Powley, & T. L. Davidson, 2004). The present experiments assessed the relative salience of nutritive and nonnutritive stimuli when presented either intestinally or orally. Two compound stimuli, each comprising 1 nutrient and 1 nonnutritive flavor, were presented in training and were paired with LiCl or saline. Subsequent oral intake of the nutrients alone, the flavors alone, or the compounds was measured. Results showed that rats discriminated both nutrients and flavors independently after GI or oral training, whereas the compounds were discriminated only after oral training, indicating substantive differences in the processing of these stimuli. This suggests that nutrient activation of the GI tract may potentiate learning about nonnutritive flavors analogously to taste-potentiated odor conditioning. The ability to learn about the oral properties of stimuli in the GI tract suggests a new account of delayed taste aversion learning as well as learning about the positive nutritive consequences of food consumption.}, } @article {pmid17201470, year = {2006}, author = {Roman, C and Nebieridze, N and Sastre, A and Reilly, S}, title = {Effects of lesions of the bed nucleus of the stria terminalis, lateral hypothalamus, or insular cortex on conditioned taste aversion and conditioned odor aversion.}, journal = {Behavioral neuroscience}, volume = {120}, number = {6}, pages = {1257-1267}, doi = {10.1037/0735-7044.120.6.1257}, pmid = {17201470}, issn = {0735-7044}, support = {R01 DC004341/DC/NIDCD NIH HHS/United States ; DC04341/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Cerebral Cortex/*injuries/physiopathology ; *Conditioning, Classical ; Hypothalamic Area, Lateral/*injuries/physiopathology ; Male ; *Odorants ; Rats ; Rats, Sprague-Dawley ; Septal Nuclei/*injuries/physiopathology ; *Taste ; }, abstract = {The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition.}, } @article {pmid17188369, year = {2007}, author = {Fresquet, N and Angst, MJ and Schleef, C and Gobaille, S and Sandner, G}, title = {Adrenergic drugs modify the level of noradrenaline in the insular cortex and alter extinction of conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {178}, number = {1}, pages = {39-46}, doi = {10.1016/j.bbr.2006.11.047}, pmid = {17188369}, issn = {0166-4328}, mesh = {Adrenergic Agents/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Blood Glucose/physiology ; Cerebral Cortex/*metabolism ; Conditioning, Classical/drug effects/*physiology ; Drinking Behavior/drug effects/physiology ; Extinction, Psychological/drug effects/*physiology ; Guanfacine/pharmacology ; Idazoxan/analogs & derivatives/pharmacology ; Male ; Microdialysis ; Norepinephrine/*metabolism ; Rats ; Rats, Long-Evans ; Receptors, Adrenergic, alpha-2/drug effects/metabolism ; Taste ; }, abstract = {We compared the effect of conditioned taste aversion in rats by measuring the amount of sucrose that they drunk after conditioning, which differed according to whether rats had drunk the sucrose freely (SD: self drinking) during the conditioning session, or had been forced to drink it (IO: intra-oral administration through a chronically implanted cannula). The SD procedure delayed the extinction of conditioned taste aversion. Enhanced arousal, alertness, awareness or attention in the SD condition may have strengthened the memory of the taste. Brain noradrenergic networks are involved in such processes. We administered two noradrenergic drugs that produce opposite effects on noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.), and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that is an essential factor of taste learning and (iii) on the comparative SD versus IO conditioned taste aversion protocol mentioned above. Injecting RX821001 increased the level of noradrenaline in the gustatory cortex up to two-fold of the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any alteration of glycaemia. It enhanced extinction of conditioned taste aversion in the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite effect. The noradrenaline level of the gustatory cortex decreased, but only down to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia. Extinction of conditioned taste aversion was only marginally decreased by guanfacine in the SD group of rats. These results fit with Aston-Jones' point of view that the role of the noradrenergic coeruleo-cortical system may be to enhance arousal, alertness, awareness or attention to an event by a transient increase of cortical noradrenaline.}, } @article {pmid17180617, year = {2007}, author = {Chang, T and Meyer, U and Feldon, J and Yee, BK}, title = {Disruption of the US pre-exposure effect and latent inhibition in two-way active avoidance by systemic amphetamine in C57BL/6 mice.}, journal = {Psychopharmacology}, volume = {191}, number = {2}, pages = {211-221}, pmid = {17180617}, issn = {0033-3158}, mesh = {Amphetamine/*pharmacology ; Analysis of Variance ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Classical/drug effects ; Dopamine/metabolism ; Dopamine Agents/*pharmacology ; *Inhibition, Psychological ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {RATIONALE: Pre-exposure to either one of the two to-be-associated stimuli alone is known to reduce the efficiency of the learning of their association when they are subsequently paired explicitly. In classical conditioning, pre-exposure to the conditioned stimulus (CS) gives rise to latent inhibition (LI); and pre-exposure to the unconditioned stimulus (US) results in the US pre-exposure effect (USPEE). Considerable evidence supports an important role of central dopamine in the regulation and modulation of LI; it has been suggested that the USPEE may be similarly controlled by dopamine, but this parallelism has only been directly demonstrated in the conditioned taste aversion paradigm.

OBJECTIVE: The present study tested this hypothesis by comparing the efficacy of systemic amphetamine treatment to affect the expression of LI and the USPEE in a two-way active avoidance paradigm.

METHODS: C57BL/6 male mice were tested in active avoidance using a tone CS and a foot-shock US. Twenty-four hours before, they were pre-exposed to 100 presentations of the CS or the US, or to the test apparatus only. Amphetamine (2.5 mg/kg) or saline was administered before stimulus pre-exposure and conditioned avoidance test, in which the mice learned to avoid the shock by shuttling in response to the tone.

RESULTS: Amphetamine disrupted both stimulus pre-exposure effects, thus, lending further support to the hypothesis that the USPEE is similar to LI in its sensitivity to dopamine receptor agonist. Hence, the USPEE paradigm may represent a valuable addition to the study of dopamine-sensitive processes of selective learning currently implicated in LI and Kamin blocking.}, } @article {pmid17164820, year = {2007}, author = {Blednov, YA and Cravatt, BF and Boehm, SL and Walker, D and Harris, RA}, title = {Role of endocannabinoids in alcohol consumption and intoxication: studies of mice lacking fatty acid amide hydrolase.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {32}, number = {7}, pages = {1570-1582}, doi = {10.1038/sj.npp.1301274}, pmid = {17164820}, issn = {0893-133X}, support = {AA06399/AA/NIAAA NIH HHS/United States ; AA13520/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol-Induced Disorders, Nervous System/*enzymology/genetics/physiopathology ; Amidohydrolases/*genetics ; Animals ; Avoidance Learning/drug effects/physiology ; Brain/*drug effects/*enzymology/physiopathology ; Brain Chemistry/drug effects/genetics ; Cannabinoid Receptor Modulators/*metabolism ; *Endocannabinoids ; Enzyme Inhibitors/pharmacology ; Ethanol/*pharmacology ; Fatty Acids/metabolism ; Female ; Genetic Predisposition to Disease/genetics ; Male ; Metabolic Clearance Rate/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Movement Disorders/enzymology/genetics ; Recovery of Function/drug effects/physiology ; Sex Characteristics ; Substance Withdrawal Syndrome/enzymology/genetics/physiopathology ; }, abstract = {Endocannabinoid signaling plays the important role in regulation of ethanol intake. Fatty acid amide hydrolase (FAAH) is a key membrane protein for metabolism of endocannabinoids, including anandamide, and blockade of FAAH increases the level of anandamide in the brain. To determine if FAAH regulates ethanol consumption, we studied mutant mice with deletion of the FAAH gene. Null mutant mice showed higher preference for alcohol and voluntarily consumed more alcohol than wild-type littermates. There was no significant difference in consumption of sweet or bitter solutions. To determine the specificity of FAAH for ethanol intake, we studied additional ethanol-related behaviors. There were no differences between null mutant and wild-type mice in severity of ethanol-induced acute withdrawal, conditioned taste aversion to alcohol, conditioned place preference, or sensitivity to hypnotic effect of ethanol. However, null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol. All three behavioral phenotypes (increased preference for ethanol, decreased sensitivity to ethanol-induced sedation, and faster recovery from ethanol-induced motor incoordination) seen in mutant mice were reproduced in wild-type mice by injection of a specific inhibitor of FAAH activity--URB597. These data suggest that increased endocannabinoid signaling increased ethanol consumption owing to decreased acute ethanol intoxication.}, } @article {pmid17162504, year = {2007}, author = {Rosas, JM and Callejas-Aguilera, JE}, title = {Acquisition of a conditioned taste aversion becomes context dependent when it is learned after extinction.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {60}, number = {1}, pages = {9-15}, doi = {10.1080/17470210600971519}, pmid = {17162504}, issn = {1747-0218}, mesh = {Analysis of Variance ; Animals ; Attention/physiology ; Behavior, Animal/*physiology ; Conditioning, Psychological/*physiology ; Cues ; Extinction, Psychological/*physiology ; Female ; Learning/*physiology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Sodium Chloride/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/*physiology ; Water/administration & dosage ; }, abstract = {A conditioned taste aversion experiment tested context-switch effects on retrieval of conditioned stimulus (CS)-unconditioned stimulus (US) acquisition performance in rats. A context switch impaired performance when the target flavour was trained in a context where a different flavour underwent extinction. Conditioned taste aversion in the absence of previous extinction of the alternate flavour was not context dependent. It is suggested that the ambiguity in the meaning of the extinguished cue leads animals to pay attention to the context, so that the information learned in that context becomes context dependent.}, } @article {pmid17160932, year = {2006}, author = {Abdala-Sepúlveda, P}, title = {[The neural bases of taste aversion learning: the precision of neuroscientific vocabulary].}, journal = {Revista de neurologia}, volume = {43}, number = {12}, pages = {766}, pmid = {17160932}, issn = {0210-0010}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/anatomy & histology ; *Neuroanatomy ; Rats ; Taste/*physiology ; *Terminology as Topic ; }, } @article {pmid17142307, year = {2006}, author = {Wang, Y and Fontanini, A and Katz, DB}, title = {Temporary basolateral amygdala lesions disrupt acquisition of socially transmitted food preferences in rats.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {13}, number = {6}, pages = {794-800}, pmid = {17142307}, issn = {1072-0502}, support = {R01 DC006666/DC/NIDCD NIH HHS/United States ; DC006666/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Analysis of Variance ; Animals ; Association Learning/*physiology ; Feeding Behavior/*physiology ; Female ; Food Preferences/*physiology ; Imitative Behavior/physiology ; Rats ; Rats, Long-Evans ; Smell/physiology ; Social Environment ; Taste/physiology ; }, abstract = {Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in chemosensory learning remains somewhat controversial. In particular, it has been suggested that the amygdala may not be involved in a form of chemosensory learning that has recently received a substantial amount of study-socially transmitted food preference (STFP). Here, we provide evidence for this involvement by pharmacologically inactivating the basolateral amygdala bilaterally during STFP training. The same inactivation sites that impaired taste aversion learning eliminated the normally conditioned preference for a food smelled on a conspecific's breath. Impairments of learned preference persisted even in testing sessions in which BLA was not inactivated, and learning was normal when the BLA was inactivated only during testing sessions; thus, the impairment was a true acquisition deficit. In conjunction with previous results from other paradigms, therefore, our data suggest that the amygdala is vital for learning procedures involving pairings of potent and arbitrary chemosensory stimuli.}, } @article {pmid17140739, year = {2007}, author = {López-Velázquez, L and Aguirre, E and Paredes, RG}, title = {Kindling increases aversion to saccharin in taste aversion learning.}, journal = {Neuroscience}, volume = {144}, number = {3}, pages = {808-814}, doi = {10.1016/j.neuroscience.2006.09.063}, pmid = {17140739}, issn = {0306-4522}, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Cerebral Cortex/physiology ; Electric Stimulation ; Electrodes, Implanted ; Kindling, Neurologic/*physiology ; Male ; Memory/physiology ; Neuronal Plasticity/*physiology ; Rats ; Saccharin/adverse effects ; Taste/*physiology ; Time ; }, abstract = {Kindling is a model in which an initially subconvulsive electrical stimulation of certain brain areas eventually develops a generalized seizure that produces behavioral and long term neuronal changes. In the present study we evaluated if kindling can modify conditioning taste aversion (CTA). In this paradigm animals acquire aversion to saccharin when it is presented as the conditioned stimulus (CS) followed by an injection of lithium chloride (LiCl) that induces a gastric irritation as the unconditioned stimulus (US). Male Wistar rats were implanted with bipolar electrodes aimed at the right amygdala (AMG) or at the right insular cortex (IC). The animals were stimulated daily until they reached stages 2-4 (intermediate) or until kindling was fully established (three consecutive stage 5 seizures). At least two weeks after kindling stimulation had ceased the animals were deprived of water for 24 h and given 10-min drinking sessions twice a day for 4 days. On day 5 (morning session) tap water was replaced by saccharin solution (0.1%), 20 min later the animals were injected with LiCl (7.5 ml/kg i.p., 0.2 M) to induce gastric malaise or taste aversion. After three more days of baseline consumption, water was substituted by a fresh 0.1% saccharin solution to test the aversion. AMG-kindling delayed the extinction of CTA. Animals with kindling in the IC had a higher retention than the sham kindling group; that is, they drank significantly less saccharin solution than the other groups. The results of the present experiment show that local modification of brain function induced by kindling stimulation can prolong the aversive effects of CTA.}, } @article {pmid17132826, year = {2007}, author = {Sun, HD and Malabunga, M and Tonra, JR and DiRenzo, R and Carrick, FE and Zheng, H and Berthoud, HR and McGuinness, OP and Shen, J and Bohlen, P and Leibel, RL and Kussie, P}, title = {Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {292}, number = {3}, pages = {E964-76}, doi = {10.1152/ajpendo.00089.2006}, pmid = {17132826}, issn = {0193-1849}, support = {DK-071082/DK/NIDDK NIH HHS/United States ; U24-DK-59637/DK/NIDDK NIH HHS/United States ; DK-52431-14/DK/NIDDK NIH HHS/United States ; DK-47384/DK/NIDDK NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30-DK-26687-27/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/adverse effects/*pharmacology ; Antibody Specificity ; Body Composition/drug effects ; Central Nervous System/drug effects ; Eating/*drug effects ; Energy Metabolism/drug effects ; Female ; Macaca fascicularis ; Male ; Mice ; Mice, Inbred C57BL ; Protein Isoforms/immunology ; Rats ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1/*antagonists & inhibitors/*immunology ; Weight Loss/*drug effects ; }, abstract = {We generated three fully human monoclonal antibody antagonists against fibroblast growth factor receptor-1 (FGFR1) that potently block FGF signaling. We found that antibodies targeting the c-splice form of the receptor (FGFR1c) were anorexigenic when administered intraperitoneally three times weekly to mice, resulting in rapid, dose-dependent weight loss that plateaued (for doses>4 mg/kg) at 35-40% in 2 wk. Animals appeared healthy during treatment and regained their normal body weights and growth trajectories upon clearance of the antibodies from the bloodstream. Measurements of food consumption and energy expenditure indicated that the rapid weight loss was induced primarily by decreased energy intake and not by increased energy expenditure or cachexia and was accompanied by a greater reduction in fat than lean body mass. Hypophagia was not caused through malaise or illness, as indicated by absence of conditioned taste aversion, pica behavior, and decreased need-induced salt intake in rats. In support of a hypothalamic site of action, we found that, after intraperitoneal injections, anti-FGFR1c (IMC-A1), but not a control antibody, accumulated in the median eminence and adjacent mediobasal hypothalamus and that FGFR1c is enriched in the hypothalamus of mice. Furthermore, a single intracerebroventricular administration of 3 microg of IMC-A1 via the 3rd ventricle to mice caused an approximately 36% reduction in food intake and an approximately 6% weight loss within the ensuing 24 h. Our data suggest that FGF signaling through FGFR1c may play a physiological role in hypothalamic feeding circuit and that blocking it leads to hypophagia and weight loss.}, } @article {pmid17110527, year = {2007}, author = {Bernstein, IL and Koh, MT}, title = {Molecular signaling during taste aversion learning.}, journal = {Chemical senses}, volume = {32}, number = {1}, pages = {99-103}, doi = {10.1093/chemse/bjj032}, pmid = {17110527}, issn = {0379-864X}, mesh = {Animals ; *Avoidance Learning ; Humans ; *Signal Transduction ; *Taste ; }, abstract = {Behavioral and neural assessment tools have been used to identify cellular and molecular events that occur during taste aversion acquisition. Studies described here include an assessment of taste information processing and taste-illness association using fos-like immunoreactivity (FLI) to mark populations of cells that react strongly to the taste conditioned stimulus (CS), the illness unconditioned stimulus (US), or the pairing of CS and US. Exposure to a novel, but not a familiar, CS taste (saccharin) was found to induce robust increases in FLI in some, but not all, brain regions previously implicated in taste processing or taste aversion learning. Striking effects of taste novelty on FLI were found in central amygdala (CNA) and insular cortex (IC) but not in basolateral amygdala (BLA), pontine parabrachial nucleus (PBN), or nucleus of the solitary tract (NTS). Of those regions responding to taste novelty, only CNA showed significant elevations in FLI in response to the US, LiCl. In additional studies, FLI was examined after an effective training experience, novel CS-US pairing, and compared with an ineffective one, familiar CS-US pairing. After CS-US pairing, taste novelty modulated FLI in virtually all the regions previously implicated in conditioned taste aversion (CTA) learning, including PBN, CNA, BLA, IC, as well as NTS. Thus, a distributed and interdependent neural CTA circuit is mapped using this method, and the use of localized lesion and inactivation studies promises to further define the functional role of structures within this circuit.}, } @article {pmid17110526, year = {2007}, author = {Yamamoto, T}, title = {Brain regions responsible for the expression of conditioned taste aversion in rats.}, journal = {Chemical senses}, volume = {32}, number = {1}, pages = {105-109}, doi = {10.1093/chemse/bjj045}, pmid = {17110526}, issn = {0379-864X}, mesh = {Animals ; *Avoidance Learning ; Brain/*physiology ; *Conditioning, Classical ; Rats ; *Taste ; }, abstract = {Conditioned taste aversion (CTA) is acquired when the ingestion of a food is followed by malaise. CTA is a kind of fear learning making animals avoid subsequent intake of the food and show aversive behavior to the taste of the food. To elucidate the brain regions responsible for the expression of CTA, our previous electrophysiological and recent c-fos immunohistochemical studies have been reviewed. Among a variety of brain regions including the parabrachial nucleus, amygdala, insular cortex, supramammillary nucleus, nucleus accumbens, and ventral pallidum that are involved in different phases of CTA expression, the enhanced taste sensitivity to facilitate detection of the conditioned stimulus may originate in the central nucleus of the amygdala and the hedonic shift, from positive to negative, may originate in the basolateral nucleus of the amygdala.}, } @article {pmid17110525, year = {2007}, author = {Manrique, T and Morón, I and Ballesteros, MA and Guerrero, RM and Gallo, M}, title = {Hippocampus, ageing, and taste memories.}, journal = {Chemical senses}, volume = {32}, number = {1}, pages = {111-117}, doi = {10.1093/chemse/bjl042}, pmid = {17110525}, issn = {0379-864X}, mesh = {Aging/*physiology ; Animals ; Hippocampus/*physiology ; Humans ; *Memory ; *Taste ; }, abstract = {Previous studies have shown that ageing may induce deficits in hippocampal-dependent learning and memory tasks, the spatial task being most extensively applied in rats. It is proposed that taste learning and memory tasks may assist in understanding the ageing of memory systems, giving access to a more complete picture. Taste learning tasks allow us to explore a variety of learning phenomena in safe and aversive memories using similar behavioral procedures. In demanding the same sensory, response, and motivational requirements, this approach provides reliable comparisons between the performance of hippocampal lesioned and aged rats in different types of memory. Present knowledge on the effect of both ageing and hippocampal damage in complex taste learning phenomena is reviewed. Besides inducing deficits in hippocampal-dependent phenomena, such as blocking of conditioned taste aversion, while at the same time leaving intact nonhippocampal-dependent effects, such as latent inhibition, ageing is also associated with an increased neophobia by previous aversive taste memories and enhanced taste aversion conditioning which cannot be explained by age-related changes in taste or visceral distress sensitivity. In all, the results indicate a peculiar organization of the memory systems during aging that cannot be explained by a general cognitive decline or exclusively by the decay of the hippocampal function.}, } @article {pmid17108183, year = {2007}, author = {Wifall, TC and Faes, TM and Taylor-Burds, CC and Mitzelfelt, JD and Delay, ER}, title = {An analysis of 5'-inosine and 5'-guanosine monophosphate taste in rats.}, journal = {Chemical senses}, volume = {32}, number = {2}, pages = {161-172}, doi = {10.1093/chemse/bjl043}, pmid = {17108183}, issn = {0379-864X}, support = {R15 DC005962-01/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/drug effects ; Conditioning, Psychological/drug effects ; Drug Synergism ; Guanosine Monophosphate/administration & dosage/*pharmacology ; Inosine Monophosphate/administration & dosage/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Glutamate/administration & dosage/pharmacology ; Taste/*drug effects ; Taste Threshold/drug effects ; }, abstract = {Inosine monophosphate (IMP) and guanosine monophosphate (GMP) elicit an umami taste in humans and synergistically increase the intensity of the umami taste of monosodium glutamate (MSG). Conditioned taste aversion (CTA) studies in rodents indicate that these nucleotides and MSG elicit quite similar tastes, but recent physiological evidence suggests that these nucleotides and MSG may not activate the same population of taste receptors and therefore may not elicit identical taste qualities. This study reports the findings of several behavioral experiments with rats that compared the taste properties of IMP and GMP with each other and with those of MSG. Well-trained rats were able to detect both nucleotides at nanomolar concentrations, but they did not respond to either nucleotide in two-bottle preference tests or brief-access CTA tests at concentrations less than 0.5 mM. Discrimination experiments found that the tastes of these nucleotides could not be discriminated from each other, but both could be discriminated from MSG, even when the taste of Na(+) was controlled. Overall, these experiments indicate the taste properties of the two 5'-ribonucleotides are quite similar to each other, and even though they may elicit an umami sensation, these sensations are not identical to the taste of MSG.}, } @article {pmid17108179, year = {2006}, author = {Moechars, D and Weston, MC and Leo, S and Callaerts-Vegh, Z and Goris, I and Daneels, G and Buist, A and Cik, M and van der Spek, P and Kass, S and Meert, T and D'Hooge, R and Rosenmund, C and Hampson, RM}, title = {Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {26}, number = {46}, pages = {12055-12066}, pmid = {17108179}, issn = {1529-2401}, support = {R01 NS051262/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Chronic Disease ; Disease Models, Animal ; Excitatory Postsynaptic Potentials/genetics ; Genes, Lethal/genetics ; Glutamic Acid/*metabolism ; Hippocampus/metabolism/physiopathology/ultrastructure ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neuralgia/genetics/*metabolism/physiopathology ; Pain Measurement/methods ; Peripheral Nervous System Diseases/genetics/*metabolism/physiopathology ; Presynaptic Terminals/*metabolism ; Synaptic Transmission/genetics ; Synaptic Vesicles/*metabolism ; Thalamus/metabolism/physiopathology/ultrastructure ; Vesicular Glutamate Transport Protein 2/genetics/*metabolism ; }, abstract = {Uptake of L-glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Three transporters (VGLUT1-VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 is the most abundantly expressed paralog in the thalamus, midbrain, and brainstem. Previous studies have shown that VGLUT1 is necessary for glutamatergic transmission in the hippocampus, but the role of VGLUT2 in excitatory transmission is unexplored in glutamatergic neurons and in vivo. We examined the electrophysiological and behavioral consequences of loss of either one or both alleles of VGLUT2. We show that targeted deletion of VGLUT2 in mice causes perinatal lethality and a 95% reduction in evoked glutamatergic responses in thalamic neurons, although hippocampal synapses function normally. Behavioral analysis of heterozygous VGLUT2 mice showed unchanged motor function, learning and memory, acute nociception, and inflammatory pain, but acquisition of neuropathic pain, maintenance of conditioned taste aversion, and defensive marble burying were all impaired. Reduction or loss of VGLUT2 in heterozygous and homozygous VGLUT2 knock-outs led to a graded reduction in the amplitude of the postsynaptic response to single-vesicle fusion in thalamic neurons, indicating that the vesicular VGLUT content is critically important for quantal size and demonstrating that VGLUT2-mediated reduction of excitatory drive affects specific forms of sensory processing.}, } @article {pmid17096193, year = {2007}, author = {Blizard, DA}, title = {Sweet and bitter taste of ethanol in C57BL/6J and DBA2/J mouse strains.}, journal = {Behavior genetics}, volume = {37}, number = {1}, pages = {146-159}, doi = {10.1007/s10519-006-9121-4}, pmid = {17096193}, issn = {0001-8244}, support = {AA-08454/AA/NIAAA NIH HHS/United States ; AA-14711/AA/NIAAA NIH HHS/United States ; DC-004099/DC/NIDCD NIH HHS/United States ; DC-02230/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Ethanol/metabolism/*pharmacology ; Food Preferences ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Quinine/metabolism/pharmacology ; Species Specificity ; Stimulation, Chemical ; Sucrose/metabolism/pharmacology ; *Taste/genetics ; }, abstract = {Studies of inbred strains of rats and mice have suggested a positive association between strain variations in sweet taste and ethanol intake. However, strain associations by themselves are insufficient to support a functional link between taste and ethanol intake. We used conditioned taste aversion (CTA) to explore the sweet and bitter taste of ethanol and ability to detect sucrose, quinine and ethanol in C57BL/6J (B6) and DBA/2J (D2) mouse strains that are frequently used in alcohol research. The present study showed that C57BL/6J mice generalized taste aversions from sucrose and quinine solutions to 10% ethanol and, reciprocally, aversions to 10% ethanol generalized to each of these solutions presented separately. Only conditioned aversions to quinine generalized to ethanol in the DBA/2J strain but an aversion conditioned to ethanol did not generalize reciprocally to quinine. Thus, considering these two gustatory qualities, 10% ethanol tastes both sweet and bitter to B6 mice but only bitter to D2. Both strains were able to generalize taste aversions across different concentrations of the same compound. B6 were able to detect lower concentrations of quinine than D2 but both strains were able to detect sucrose and (in contrast to previous findings) ethanol at similar concentrations. The strain-dependent gustatory profiles for ethanol may make an important contribution to the understanding of the undoubtedly complex mechanisms influencing high ethanol preference of B6 and pronounced ethanol avoidance of D2 mice.}, } @article {pmid17029989, year = {2007}, author = {Banko, JL and Merhav, M and Stern, E and Sonenberg, N and Rosenblum, K and Klann, E}, title = {Behavioral alterations in mice lacking the translation repressor 4E-BP2.}, journal = {Neurobiology of learning and memory}, volume = {87}, number = {2}, pages = {248-256}, doi = {10.1016/j.nlm.2006.08.012}, pmid = {17029989}, issn = {1074-7427}, mesh = {Animals ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Eukaryotic Initiation Factors/*deficiency ; Exploratory Behavior/physiology ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/genetics ; Psychomotor Performance/physiology ; Reaction Time/genetics ; Rotarod Performance Test/methods ; Taste ; Time Factors ; }, abstract = {The requirement for de novo protein synthesis during multiple forms of learning, memory and behavior is well-established; however, we are only beginning to uncover the regulatory mechanisms that govern this process. In order to determine how translation initiation is regulated during neuroplasticity we engineered mutant C57Bl/6J mice that lack the translation repressor eukaryotic initiation factor 4E-binding protein 2 (4E-BP2) and have previously demonstrated that 4E-BP2 plays a critical role in hippocampus-dependent synaptic plasticity and memory. Herein, we examined the 4E-BP2 knockout mice in a battery of paradigms to address motor activity and motor skill learning, anxiety and social dominance behaviors, working memory and conditioned taste aversion. We found that the 4E-BP2 knockout mice demonstrated altered activity in the rotating rod test, light/dark exploration test, spontaneous alternation T-maze and conditioned taste aversion test. The information gained from these studies builds a solid foundation for future studies on the specific role of 4E-BP2 in various types of behavior, and for a broader, more detailed examination of the mechanisms of translational control in the brain.}, } @article {pmid17023060, year = {2006}, author = {Scott-Railton, J and Arnold, G and Vezina, P}, title = {Appetitive sensitization by amphetamine does not reduce its ability to produce conditioned taste aversion to saccharin.}, journal = {Behavioural brain research}, volume = {175}, number = {2}, pages = {305-314}, pmid = {17023060}, issn = {0166-4328}, support = {R01 DA009397/DA/NIDA NIH HHS/United States ; DA09397/DA/NIDA NIH HHS/United States ; }, mesh = {Amphetamine/*pharmacology ; Animals ; Appetitive Behavior/drug effects ; Association Learning/*drug effects/physiology ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal/*drug effects ; Central Nervous System Stimulants/*pharmacology ; Drug Administration Schedule ; Male ; Microinjections ; Motivation ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Taste/drug effects/physiology ; Time Factors ; Ventral Tegmental Area/*drug effects/physiology ; }, abstract = {Previous exposure to amphetamine attenuates its ability to induce conditioned taste aversion (CTA). Because amphetamine, unlike emetic agents like LiCl, possesses appetitive properties that sensitize when it is administered repeatedly, the present study assessed the contribution of sensitization to this US-pre-exposure effect (US-PEE). It was found that not all sensitizing regimens of systemic amphetamine injections produce a US-PEE. In addition, previous exposure to amphetamine in the VTA, where it acts to induce sensitization but not CTA, did not produce a US-PEE. It is concluded that amphetamine sensitization alone does not modulate this drug's ability to produce CTA. Implications of these findings for anatomically based associative and non-associative models of CTA and the US-PEE are discussed.}, } @article {pmid17019404, year = {2007}, author = {Fekete, EM and Inoue, K and Zhao, Y and Rivier, JE and Vale, WW and Szücs, A and Koob, GF and Zorrilla, EP}, title = {Delayed satiety-like actions and altered feeding microstructure by a selective type 2 corticotropin-releasing factor agonist in rats: intra-hypothalamic urocortin 3 administration reduces food intake by prolonging the post-meal interval.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {32}, number = {5}, pages = {1052-1068}, pmid = {17019404}, issn = {0893-133X}, support = {DK26741/DK/NIDDK NIH HHS/United States ; P01 DK026741-280004/DK/NIDDK NIH HHS/United States ; DK70118/DK/NIDDK NIH HHS/United States ; R03 DK064871-01/DK/NIDDK NIH HHS/United States ; P01 DK026741/DK/NIDDK NIH HHS/United States ; DK64871/DK/NIDDK NIH HHS/United States ; R01 DK070118/DK/NIDDK NIH HHS/United States ; R03 DK064871/DK/NIDDK NIH HHS/United States ; }, mesh = {Amygdala/drug effects/metabolism ; Animals ; Appetite Regulation/drug effects/*physiology ; Corticotropin-Releasing Hormone/agonists/*metabolism/pharmacology ; Feeding Behavior/drug effects/*physiology ; Hypothalamus/drug effects/*metabolism ; Injections, Intraventricular ; Male ; Neural Pathways/drug effects/metabolism ; Paraventricular Hypothalamic Nucleus/drug effects/metabolism ; Peptide Fragments/pharmacology ; Rats ; Rats, Wistar ; Reaction Time/drug effects/physiology ; Receptors, Corticotropin-Releasing Hormone/agonists/*metabolism ; Satiety Response/drug effects/*physiology ; Time Factors ; Urocortins ; Ventromedial Hypothalamic Nucleus/drug effects/metabolism ; }, abstract = {Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized to control feeding, with central administration of 'type 2' urocortins producing delayed anorexia. The present study sought to identify the receptor subtype, brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal food intake in rats. Non-food-deprived male Wistar rats (n=176) were administered Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala (MeA), regions in which Ucn 3 is expressed in proximity to CRF(2) receptors. LV Ucn 3 suppressed ingestion during the third-fourth post-injection hours. LV Ucn 3 anorexia was reversed by cotreatment with astressin(2)-B, a selective CRF(2) antagonist and not observed following equimole subcutaneous or fourth ventricle administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV infusion, reduced the quantity (57-73%) and duration of ingestion (32-68%) during the third-fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn 3 slowed the eating rate and reduced intake by prolonging the post-meal interval. Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally specific, because minimal effective anorectic Ucn 3 doses did not alter drinking rate or promote a conditioned taste aversion, and site-specific, because intra-MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering total intake. The results implicate the VMN and PVN of the hypothalamus as sites for Ucn 3-CRF(2) control of food intake.}, } @article {pmid17013639, year = {2006}, author = {Roma, PG and Flint, WW and Higley, JD and Riley, AL}, title = {Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats.}, journal = {Psychopharmacology}, volume = {189}, number = {2}, pages = {187-199}, pmid = {17013639}, issn = {0033-3158}, support = {//Intramural NIH HHS/United States ; }, mesh = {Alcohol Drinking/genetics/psychology ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Body Temperature/drug effects ; Central Nervous System Depressants/administration & dosage/blood/pharmacology ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/administration & dosage/blood/*pharmacology ; Genotype ; Male ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Saccharin/administration & dosage ; Substance-Related Disorders/genetics/psychology ; Taste/drug effects ; }, abstract = {RATIONALE: Application of the Fischer-Lewis genetic model of drug abuse to the study of alcohol's motivational properties has been limited.

OBJECTIVES: To assess the aversive and rewarding effects of ethanol in Fischer and Lewis rats.

MATERIALS AND METHODS: Fischer and Lewis rats underwent a four-trial combined conditioned taste aversion/conditioned place preference procedure (CTA/CPP; 0, 1, 1.25, or 1.5 g/kg IP ethanol). Others received 0, 1, or 1.5 g/kg followed by tail blood sampling at 15-, 60- and 180-min post-injection. In additional groups, hypothermia to 0, 1.5, and 3 g/kg was assessed before and 30- and 60-min post-injection.

RESULTS: All alcohol-treated groups except low-dose Lewis acquired CTA after one trial. Fischer rats developed stronger CTAs than Lewis at 1.25 and 1.5 g/kg. Ethanol-induced reward in taste or place conditioning was not evident in either strain. Lewis animals showed overall higher peak blood alcohol concentrations, but hypothermia did not vary by strain.

CONCLUSION: Compared to Fischer, Lewis rats are less sensitive to alcohol's aversive effects as assessed in the CTA paradigm. The behavioral differences observed are not due to hypothermia, but pharmacokinetic differences may contribute. These data underscore the importance of genetic factors and the aversive effects of initial drug exposures in modeling vulnerability to abuse. In addition to its application with other drugs, the Fischer-Lewis model may be useful for investigating the biobehavioral bases of alcohol abuse.}, } @article {pmid16998901, year = {2006}, author = {Madani, R and Poirier, R and Wolfer, DP and Welzl, H and Groscurth, P and Lipp, HP and Lu, B and El Mouedden, M and Mercken, M and Nitsch, RM and Mohajeri, MH}, title = {Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo.}, journal = {Journal of neuroscience research}, volume = {84}, number = {8}, pages = {1871-1878}, doi = {10.1002/jnr.21074}, pmid = {16998901}, issn = {0360-4012}, mesh = {Age Factors ; Amyloid/*metabolism/ultrastructure ; Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Brain/*pathology/ultrastructure ; Conditioning, Operant/physiology ; Enzyme-Linked Immunosorbent Assay/methods ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron, Transmission/methods ; Neprilysin/*deficiency ; Water Deprivation/physiology ; }, abstract = {Accumulation of the beta-amyloid peptide (Abeta) in the brain is a major pathological hallmark of Alzheimer's disease (AD), leading to synaptic dysfunction, neuronal death, and memory impairment. The levels of neprilysin, a major Abeta-degrading enzyme, are decreased in AD brains and during aging. Because neprilysin cleaves Abeta in vivo, its down-regulation may contribute to the pathophysiology of AD. The aim of this study was to assess the consequences of neprilysin deficiency on accumulation of murine Abeta in brains and associated pathologies in vivo by investigating neprilysin-deficient mice on biochemical, morphological, and behavioral levels. Aged neprilysin-deficient mice expressed physiological amyloid precursor protein (APP) levels and exhibited elevated brain Abeta concentrations and amyloid-like deposits in addition to signs of neuronal degeneration in their brains. Behaviorally, neprilysin-deficient mice acquired a significantly weaker conditioned taste aversion that extinguished faster than the aversion of age-matched controls. Our data establish that, under physiological APP expression levels, neprilysin deficiency is associated with increased Abeta accumulation in the brain and leads to deposition of amyloid-like structures in vivo as well as with signs of AD-like pathology and with behavioral deficits.}, } @article {pmid16963089, year = {2006}, author = {Stratford, JM and Curtis, KS and Contreras, RJ}, title = {Chorda tympani nerve transection alters linoleic acid taste discrimination by male and female rats.}, journal = {Physiology & behavior}, volume = {89}, number = {3}, pages = {311-319}, doi = {10.1016/j.physbeh.2006.06.009}, pmid = {16963089}, issn = {0031-9384}, support = {DC 04785/DC/NIDCD NIH HHS/United States ; DC 06360/DC/NIDCD NIH HHS/United States ; T32 DC 00044/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Behavior, Animal ; Body Weight/physiology ; Central Nervous System Depressants/pharmacology ; *Chorda Tympani Nerve ; Discrimination, Psychological/drug effects/*physiology ; Dose-Response Relationship, Drug ; Drinking Behavior/physiology ; Drug Interactions ; Ethanol/pharmacology ; Facial Nerve Diseases/*physiopathology ; Female ; Food Preferences/drug effects/physiology ; *Linoleic Acid ; Male ; Ovariectomy/methods ; Rats ; Rats, Sprague-Dawley ; Sex Factors ; Sucrose/pharmacology ; Sweetening Agents ; Taste/drug effects/*physiology ; Taste Threshold/drug effects/physiology ; }, abstract = {Taste is intimately associated with food choice, yet little is known about the role of taste in preferences for dietary fat, a major component of many foods. We measured the taste threshold for linoleic acid (LA), an essential free fatty acid found in dietary fat, before and after bilateral transections of the chorda tympani nerve (CTX) in adult male and female rats. We conditioned a taste aversion to 88 microM LA and assessed the generalization of the aversion to lower LA concentrations to determine LA discrimination thresholds. We discovered that female rats had a lower LA discrimination threshold (approximately 2.75 microM LA) than did male rats (approximately 11 microM LA). In another set of animals, we performed CTX and found that CTX elevated LA threshold to the same level (approximately 22 microM LA) in male and female rats. Finally, we evaluated licking responses to 11, 22, 44 and 88 microM LA mixed in sucrose by male rats and ovariectomized (OVX) female rats treated with estradiol benzoate or oil vehicle. All rats increased licking to increasing LA concentrations, but OVX rats responded to a lower LA concentration (22 microM) than did males (44 microM) in 10-s trials. However, estradiol did not affect this outcome. Collectively, these experiments show that male and female rats use taste to discriminate LA and that the chorda tympani nerve, which innervates taste buds on the anterior tongue, plays a role in this discrimination. Furthermore, sex differences in fat preferences may depend on differences in fatty acid taste thresholds as well as on the taste stimuli with which fat is combined.}, } @article {pmid16962209, year = {2006}, author = {Chelikani, PK and Haver, AC and Reidelberger, RD}, title = {Dose-dependent effects of peptide YY(3-36) on conditioned taste aversion in rats.}, journal = {Peptides}, volume = {27}, number = {12}, pages = {3193-3201}, doi = {10.1016/j.peptides.2006.08.001}, pmid = {16962209}, issn = {0196-9781}, support = {DK55830/DK/NIDDK NIH HHS/United States ; DK73152/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant ; Dose-Response Relationship, Drug ; Infusions, Intravenous ; Male ; Peptide Fragments/administration & dosage/*physiology ; Peptide YY/administration & dosage/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {We used a conditioned taste aversion test to assess whether PYY(3-36) reduces food intake by producing malaise. Two-hour IV infusion of PYY(3-36) (8, 15, and 30 pmol/kg/min) at dark onset in non-food-deprived rats produced a dose-dependent inhibition of feeding and a conditioned aversion to the flavored chow paired with PYY(3-36) infusion. In food-deprived rats, PYY(3-36) at 2 and 4 pmol/kg/min inhibited intake of a flavored saccharin solution without producing conditioned taste aversion, whereas higher doses (8 and 15 pmol/kg/min) inhibited saccharin intake and produced taste aversion. These results suggest that anorexic doses of PYY(3-36) may produce a dose-dependent malaise in rats, which is similar to that reported for PYY(3-36) infusion in humans. Previous studies have shown that PYY(3-36) potently inhibits gastric emptying, and that gut distention can produce a conditioned taste aversion. Thus, PYY(3-36) may produce conditioned taste aversion in part by slowing gastric emptying.}, } @article {pmid16941636, year = {2006}, author = {Azami, S and Wagatsuma, A and Sadamoto, H and Hatakeyama, D and Usami, T and Fujie, M and Koyanagi, R and Azumi, K and Fujito, Y and Lukowiak, K and Ito, E}, title = {Altered gene activity correlated with long-term memory formation of conditioned taste aversion in Lymnaea.}, journal = {Journal of neuroscience research}, volume = {84}, number = {7}, pages = {1610-1620}, doi = {10.1002/jnr.21045}, pmid = {16941636}, issn = {0360-4012}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; CREB-Binding Protein/genetics/metabolism ; Conditioning, Classical/*physiology ; Gene Expression Regulation/*physiology ; Lymnaea/*physiology ; Memory/*physiology ; Neuropeptides/genetics/metabolism ; Oligonucleotide Array Sequence Analysis/methods ; RNA Interference/physiology ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; *Taste ; }, abstract = {The pond snail Lymnaea stagnalis is capable of learning conditioned taste aversion (CTA) and then consolidating that learning into long-term memory (LTM) that persists for at least 1 month. LTM requires de novo protein synthesis and altered gene activity. Changes in gene activity in Lymnaea that are correlated with, much less causative, memory formation have not yet been identified. As a first step toward rectifying this situation, we constructed a cDNA microarray with mRNAs extracted from the central nervous system (CNS) of Lymnaea. We then, using this microarray assay, identified genes whose activity either increased or decreased following CTA memory consolidation. We also identified genes whose expression levels were altered after inhibition of the cyclic AMP response element-binding protein (CREB) that is hypothesized to be a key transcription factor for CTA memory. We found that the molluscan insulin-related peptide II (MIP II) was up-regulated during CTA-LTM, whereas the gene encoding pedal peptide preprohormone (Pep) was down-regulated by CREB2 RNA interference. We next examined mRNAs of MIP II and Pep using real-time RT-PCR with SYBR Green. The MIP II mRNA level in the CNS of snails exhibiting "good" memory for CTA was confirmed to be significantly higher than that from the CNS of snails exhibiting "poor" memory. In contrast, there was no significant difference in expression levels of the Pep mRNA between "good" and "poor" performers. These data suggest that in Lymnaea MIP II may play a role in the consolidation process that forms LTM following CTA training.}, } @article {pmid16931062, year = {2006}, author = {Zafra, MA and Prados, M and Molina, F and Puerto, A}, title = {Capsaicin-sensitive afferent vagal fibers are involved in concurrent taste aversion learning.}, journal = {Neurobiology of learning and memory}, volume = {86}, number = {3}, pages = {349-352}, doi = {10.1016/j.nlm.2006.07.004}, pmid = {16931062}, issn = {1074-7427}, mesh = {Afferent Pathways/drug effects/*physiology ; Analgesics, Non-Narcotic/pharmacology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Capsaicin/pharmacology ; Male ; Rats ; Rats, Wistar ; Serial Learning/*physiology ; Statistics, Nonparametric ; Taste/*physiology ; Vagotomy/methods ; Vagus Nerve/drug effects/*physiology ; }, abstract = {Taste aversion learning (TAL) is a type of learning characterized by rejection of a gustatory/flavor stimulus as a consequence of its pairing with visceral discomfort and malaise. TAL can be established in the laboratory by two different behavioral procedures, concurrent or sequential. Neural mechanisms of these learning modalities remain to be elucidated, but several studies have discussed the implication of various anatomical structures, including the vagus nerve. The aim of this study was to examine the role of capsaicin-sensitive vagal afferent fibers in concurrent (Experiment 1) and sequential (Experiment 2) TAL in Wistar rats. Results showed that perivagal administration of capsaicin (1mg of capsaicin dissolved in 1ml of vehicle (10% Tween 80 in oil)) blocked acquisition of concurrent but not sequential TAL. These data support the hypothesis of two different modalities of TAL mediated by distinct neurobiological systems, with vagal nerve participation only being essential in concurrent TAL.}, } @article {pmid16930592, year = {2006}, author = {Vollmer, RR and Li, X and Karam, JR and Amico, JA}, title = {Sodium ingestion in oxytocin knockout mice.}, journal = {Experimental neurology}, volume = {202}, number = {2}, pages = {441-448}, doi = {10.1016/j.expneurol.2006.07.006}, pmid = {16930592}, issn = {0014-4886}, support = {HD 44898/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Behavior, Animal/drug effects ; Body Weight/drug effects ; Drinking/drug effects ; Drinking Behavior/*drug effects ; Eating/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxytocin/*deficiency/genetics ; Sodium/*administration & dosage/metabolism ; Sodium, Dietary/administration & dosage ; Time Factors ; }, abstract = {Under certain circumstances, central oxytocin (OT) pathways inhibit dietary intake of NaCl in rats and mice. C57BL/6 OT knockout (OT KO) mice were reported to consume greater amounts of saline solution than wild type (WT) cohorts when both were water deprived overnight. In this study, we determined that OT KO and WT mice of C57BL/6 strain demonstrate an equivalent taste aversion for continuously available 0.2 M, 0.3 M or 0.5 M NaCl. The aversion was proportional to the concentration of NaCl, similar to what has been reported in rats. Furthermore, OT KO and WT animals ingested the same daily amounts of a low, 0.01%, regular, 1.0%, and a high, 8.0%, NaCl diet that was provided ad libitum as a single choice. While consuming these diets, mice were given the choice to drink water or saline (0.5 M NaCl). As the amount of NaCl in the diet increased, mice of both genotypes significantly decreased the consumption of saline solution to an equal degree. Additionally, in an experimental model of sustained dehydration previously developed in rats, 0.5 M NaCl was the only available drinking fluid. Like rats subjected to this paradigm, OT KO and WT mice decreased food intake, decreased body weight and increased fluid ingestion with no genotypic differences. These findings suggest that oxytocinergic neuronal pathways cannot be the only regulator of ad libitum intake of NaCl in drinking solutions or diet. It appears that OT pathways may be more critical in controlling NaCl intake over brief intervals when an animal is quickly compensating for a dehydrating stimulus.}, } @article {pmid16928868, year = {2006}, author = {Jacobson, LH and Kelly, PH and Bettler, B and Kaupmann, K and Cryan, JF}, title = {GABA(B(1)) receptor isoforms differentially mediate the acquisition and extinction of aversive taste memories.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {26}, number = {34}, pages = {8800-8803}, pmid = {16928868}, issn = {1529-2401}, support = {U01 MH069062/MH/NIMH NIH HHS/United States ; U01 MH69062/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/physiology ; Extinction, Psychological/physiology ; Male ; Memory/*physiology ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Point Mutation ; Protein Isoforms/physiology ; Receptors, GABA-B/genetics/*physiology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is a form of aversive memory in which an association is made between a consumed substance and a subsequent malaise. CTA is a critical mechanism for the successful survival, and hence evolution, of most animal species. The role of excitatory neurotransmitters in the neurochemical mechanisms of CTA is well recognized; however, less is known about the involvement of inhibitory receptor systems. In particular, the potential functions of metabotropic GABA(B) receptors in CTA have not yet been fully explored. GABA(B) receptors are metabotropic GABA receptors that are comprised of two subunits, GABA(B(1)) and GABA(B(2)), which form heterodimers. The Gabbr1 gene is transcribed into two predominant isoforms, GABA(B(1a)) and GABA(B(1b)), which differ in sequence primarily by the inclusion of a pair of sushi domains (also known as short consensus repeats) in the GABA(B(1a)) N terminus. The behavioral function of mammalian GABA(B(1)) receptor isoforms is currently unknown. Here, using a point mutation strategy in mice, we demonstrate that these two GABA(B(1)) receptor isoforms are differentially involved in critical components of CTA. In contrast to GABA(B(1b))-/- and wild-type mice, GABA(B(1a))-/- mice failed to acquire CTA. In contrast, GABA(B(1b))-/- mice robustly acquired CTA but failed to show any extinction of this aversion. The data demonstrate that GABA(B) receptors are involved in both the acquisition and extinction of CTA; however, receptors containing the GABA(B(1a)) or the GABA(B(1b)) isoform differentially contribute to the mechanisms used to learn and remember the salience of aversive stimuli.}, } @article {pmid16923777, year = {2006}, author = {Pittman, DW and Labban, CE and Anderson, AA and O'Connor, HE}, title = {Linoleic and oleic acids alter the licking responses to sweet, salt, sour, and bitter tastants in rats.}, journal = {Chemical senses}, volume = {31}, number = {9}, pages = {835-843}, doi = {10.1093/chemse/bjl026}, pmid = {16923777}, issn = {0379-864X}, mesh = {Animals ; Drinking Behavior/*drug effects ; Linoleic Acid/*pharmacology ; Male ; Oleic Acid/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Stimulation, Chemical ; Taste/*drug effects/*physiology ; Taste Threshold/drug effects ; }, abstract = {The free fatty acids (FFAs), linoleic and oleic acids, commonly found in dietary fats can be detected by rats on the basis of gustatory cues following conditioned taste aversion pairings. FFAs depolarize the membrane potential of isolated rat taste receptor cells by inhibiting delayed rectifying potassium channels. This study examined the licking response of rats to sweet, salt, sour, and bitter taste solutions when 88 muM linoleic acid, 88 muM oleic acid, or an 88 muM linoleic-oleic acid mixture was added to the solutions. The presence of linoleic, oleic, and the linoleic-oleic acid mixture in sweet solutions produced increases in the licking responses, whereas adding linoleic, oleic, and the linoleic-oleic acid mixture to salt, sour, or bitter taste solutions produced decreases in licking responses when compared with the licking responses to the solutions in the absence of the FFAs. We conclude that FFAs may act in the oral cavity to depolarize taste receptor cells and therefore to increase the perceived intensity of concomitant tastants, thus contributing to the enhanced palatability associated with foods containing high dietary fat.}, } @article {pmid16914504, year = {2007}, author = {Ramírez-Lugo, L and Núñez-Jaramillo, L and Bermúdez-Rattoni, F}, title = {Taste memory formation: role of nucleus accumbens.}, journal = {Chemical senses}, volume = {32}, number = {1}, pages = {93-97}, doi = {10.1093/chemse/bjl023}, pmid = {16914504}, issn = {0379-864X}, mesh = {Animals ; Humans ; *Memory ; Nucleus Accumbens/*physiology ; Taste/*physiology ; }, abstract = {When a novel taste has been associated with postingestive malaise, animals recognize this taste as aversive. This associative learning is known as conditioned taste aversion. However, when an animal consumes a novel taste and no aversive consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent presentations. In this review, we will discuss the results related to the taste memory formation focusing particularly on the nucleus accumbens (NAcc). The NAcc keeps projections with amygdala, insular cortex, parabrachial nucleus, and nucleus of the solitary tract areas important for taste memory formation. We will review the evidence relating to how the NAcc could be involved in taste memory formation, due to its role in the taste memory trace formation and its role in the association of the conditioned stimulus-unconditioned stimulus, and finally the retrieval of taste memory. In this context, we will review the participation of the cholinergic, dopaminergic, and glutamatergic systems in the NAcc during taste memory formation.}, } @article {pmid16914421, year = {2006}, author = {Vrang, N and Madsen, AN and Tang-Christensen, M and Hansen, G and Larsen, PJ}, title = {PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {291}, number = {2}, pages = {R367-75}, doi = {10.1152/ajpregu.00726.2005}, pmid = {16914421}, issn = {0363-6119}, mesh = {Animals ; Blood Glucose/metabolism ; Body Weight/*drug effects ; Disease Models, Animal ; Drug Administration Routes ; Eating/*drug effects ; Feeding Behavior ; Insulin/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Obesity/*drug therapy/etiology ; Peptide Fragments ; Peptide YY/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Rodentia ; Taste/drug effects ; }, abstract = {The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3-36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 microg.kg-1.day-1) of PYY(3-36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 microg.kg-1.day-1) of PYY(3-36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 microg.kg-1.day-1 PYY(3-36) weighed approximately 10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3-36) (250 and 1,000 microg.kg-1.day-1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 microg/kg PYY(3-36) elicited a conditioned taste aversion in male rats.}, } @article {pmid16901953, year = {2006}, author = {Manita, S and Bachmanov, AA and Li, X and Beauchamp, GK and Inoue, M}, title = {Is glycine "sweet" to mice? Mouse strain differences in perception of glycine taste.}, journal = {Chemical senses}, volume = {31}, number = {9}, pages = {785-793}, pmid = {16901953}, issn = {0379-864X}, support = {R01 DC000882/DC/NIDCD NIH HHS/United States ; R01 DC000882-24/DC/NIDCD NIH HHS/United States ; R01 DC 00882/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Drinking Behavior/*drug effects ; Genotype ; Glycine/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains/*genetics ; Receptors, G-Protein-Coupled/genetics ; Species Specificity ; Taste/*drug effects/*genetics ; }, abstract = {Glycine is an amino acid tasting sweet to humans. In 2-bottle tests, C57BL/6ByJ (B6) mice strongly prefer glycine solutions, whereas 129P3/J (129) mice do not, suggesting that they differ in perception of glycine taste. We examined this question using the conditioned taste aversion (CTA) generalization technique. CTA was achieved by injecting LiCl after drinking glycine, and next its generalization to 10 taste solutions (glycine, sucrose, saccharin, D-tryptophan, L-tryptophan, L-alanine, L-proline, L-glutamine, NaCl, and HCl) was examined by video recording licking behavior. Both B6 and 129 mice generalized the aversion to sucrose, saccharin, L-alanine, and L-proline and did not generalize it to NaCl, HCl, and L-tryptophan. This indicates that both B6 and 129 mice perceive the sweetness (i.e., a sucrose-like taste) of glycine. Thus, the lack of a glycine preference by 129 mice cannot be explained by their inability to perceive its sweetness. Strain differences were observed for CTA generalization to 2 amino acids: 129 mice generalized aversion to L-glutamine but not D-tryptophan, whereas B6 mice generalized it to D-tryptophan but not L-glutamine. 129.B6-Tas1r3 congenic mice with 2 genotypes of the Tas1r3 locus (B6/129 heterozygotes and 129/129 homozygotes) did not differ in aversion generalization, suggesting that the differences between 129 and B6 strains are not attributed to the Tas1r3 allelic variants and that other, yet unknown, genes are involved in taste perception of amino acids.}, } @article {pmid16893301, year = {2006}, author = {Limebeer, CL and Parker, LA}, title = {Effect of conditioning method and testing method on strength of lithium-induced taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {120}, number = {4}, pages = {963-969}, doi = {10.1037/0735-7044.120.4.963}, pmid = {16893301}, issn = {0735-7044}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Conditioning, Psychological/drug effects/*physiology ; Dose-Response Relationship, Drug ; Drug Administration Routes ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Here the authors evaluated the effect of the method of conditioning (bottle or intraoral [IO] infusion) on the strength of a flavor-drug association when measured in a standard 1-bottle consumption test or when measured by IO infusion in a taste reactivity test. When tested with the bottle test in Experiment 1, rats conditioned by bottle displayed stronger taste avoidance than those conditioned by IO infusion. When tested for rejection reactions with the taste reactivity test in Experiment 2, rats conditioned by infusion displayed a stronger aversion than did rats conditioned by bottle. The results suggest that when the contextual cues of conditioning are similar at conditioning and testing, a stronger association is evident regardless of the individual specifics of each method. These results may shed light on recent reports that different neural mechanisms are involved in conditioning by active consumption and passive infusion.}, } @article {pmid16893300, year = {2006}, author = {Ferreira, G and Ferry, B and Meurisse, M and Lévy, F}, title = {Forebrain structures specifically activated by conditioned taste aversion.}, journal = {Behavioral neuroscience}, volume = {120}, number = {4}, pages = {952-962}, doi = {10.1037/0735-7044.120.4.952}, pmid = {16893300}, issn = {0735-7044}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Brain Mapping ; *Conditioning, Psychological ; Lithium Chloride/administration & dosage ; Male ; Prosencephalon/anatomy & histology/*physiology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; *Taste ; }, abstract = {This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste-malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste-malaise convergence during CTA acquisition depending on the strength of the aversion.}, } @article {pmid16893297, year = {2006}, author = {Curtis, KS and Contreras, RJ}, title = {Sex differences in electrophysiological and behavioral responses to NaCl taste.}, journal = {Behavioral neuroscience}, volume = {120}, number = {4}, pages = {917-924}, doi = {10.1037/0735-7044.120.4.917}, pmid = {16893297}, issn = {0735-7044}, support = {DC04785/DC/NIDCD NIH HHS/United States ; DC06360/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Area Under Curve ; Behavior, Animal/drug effects/*physiology ; Chorda Tympani Nerve/*drug effects/physiology ; Dose-Response Relationship, Drug ; Electrophysiology ; Estradiol/analogs & derivatives/pharmacology ; Female ; Male ; Ovariectomy/methods ; Rats ; Rats, Sprague-Dawley ; *Sex Characteristics ; Sodium Chloride/*pharmacology ; Taste/drug effects/*physiology ; }, abstract = {We tested the hypothesis that sex differences in preference for NaCl are attributable to estrogen-mediated alterations in gustatory processing. Electrophysiological responses of the chorda tympani nerve to NaCl were blunted by estrogen treatment in ovariectomized female rats, suggesting that females are less sensitive to concentrated NaCl solutions during high estrogen conditions. In contrast, after a taste aversion was conditioned to 150-mM NaCl, estrogen- and oil-treated ovariectomized rats generalized the aversion to a lower concentration of NaCl than did males, suggesting that females are more sensitive to the taste of dilute NaCl solutions regardless of estrogen. Thus, sex differences in NaCl preferences may be attributable to differences in NaCl taste processing that involve both acute and developmental effects of estrogen.}, } @article {pmid16879631, year = {2006}, author = {Pennanen, L and Wolfer, DP and Nitsch, RM and Götz, J}, title = {Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice.}, journal = {Genes, brain, and behavior}, volume = {5}, number = {5}, pages = {369-379}, doi = {10.1111/j.1601-183X.2005.00165.x}, pmid = {16879631}, issn = {1601-1848}, mesh = {Aging/*physiology ; Analysis of Variance ; Animals ; Exploratory Behavior/*physiology ; Hippocampus/*metabolism ; Humans ; Immunohistochemistry ; Male ; Maze Learning/*physiology ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurofibrillary Tangles/metabolism ; tau Proteins/genetics/*metabolism ; }, abstract = {The neuropathological hallmark shared between Alzheimer's disease (AD) and familial frontotemporal dementia (FTDP-17) are neurofibrillary tangles (NFT) which are composed of filamentous aggregates of the microtubule-associated protein tau. Their formation has been reproduced in transgenic mice, which express the FTDP-17-associated mutation P301L of tau. In these mice, tau aggregates are found in many brain areas including the hippocampus and the amygdala, both of which are characterized by NFT formation in AD. Previous studies using an amygdala-specific test battery revealed an increase in exploratory behavior and an accelerated extinction of conditioned taste aversion in these mice. Here, we assessed P301L mice in behavioral tests known to depend on an intact hippocampus. Morris water maze and Y-maze revealed intact spatial working memory but impairment in spatial reference memory at 6 and 11 months of age. In addition, a modest disinhibition of exploratory behavior at 6 months of age was confirmed in the open field and the elevated O-maze and was more pronounced during aging.}, } @article {pmid16872643, year = {2006}, author = {Brandt, K and Geary, N and Langhans, W and Leonhardt, M}, title = {Mercaptoacetate fails to block the feeding-inhibitory effect of the beta3-adrenergic receptor agonist CGP 12177A.}, journal = {Physiology & behavior}, volume = {89}, number = {2}, pages = {128-132}, doi = {10.1016/j.physbeh.2006.06.015}, pmid = {16872643}, issn = {0031-9384}, mesh = {3-Hydroxybutyric Acid/blood ; Adrenergic beta-Agonists/*administration & dosage ; Analysis of Variance ; Animals ; Appetite Regulation/*drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Drug Interactions ; Eating/*drug effects ; Fatty Acids/*blood ; Feeding Behavior/drug effects/physiology ; Insulin/blood ; Ketone Bodies/metabolism ; Lipolysis/drug effects ; Liver/drug effects/metabolism ; Male ; Oxidation-Reduction/drug effects ; Propanolamines/*administration & dosage ; Rats ; Receptors, Adrenergic, beta-3/drug effects/physiology ; Statistics, Nonparametric ; Taste ; Thioglycolates/*administration & dosage ; }, abstract = {Peripherally administered beta3-adrenergic receptor (beta3-AR) agonists stimulate lipolysis and inhibit food intake. To test the hypothesis that this inhibition of feeding is due to a substrate-driven increase in hepatic fatty acid oxidation (FAO), we assessed the ability of the FAO inhibitor mercaptoacetate (MA) to reverse the feeding-inhibitory effect of the beta3-AR agonist CGP 12177A (CGP). Adult male Sprague-Dawley rats received intraperitoneal injections of 1 mg/kg CGP, of 45.6 mg/kg MA, or of both drugs, and the effects on food intake, plasma free fatty acids (FFA), and plasma beta-hydroxybutyrate (BHB), an indicator for hepatic FAO, were assessed. Control rats received saline injections. CGP significantly reduced food intake after 0.5 and 6 h and increased plasma FFA and BHB at 0.5 h, suggesting increased lipolysis and hepatic FAO. MA completely reversed the increase in plasma BHB and thus appeared to effectively abolish CGP's effect on hepatic FAO, but MA failed to affect CGP's feeding-inhibitory action. These findings do not support the hypothesis that the beta3-AR agonist CGP inhibits feeding by enhancing hepatic FAO or ketogenesis. Although the beta3-AR agonist CGP reduced saccharin intake in a one-bottle condition taste aversion test, it seems unlikely that the hypophagic effect of CGP is elicited by malaise.}, } @article {pmid16844209, year = {2006}, author = {Graham, DL and Diaz-Granados, JL}, title = {Periadolescent exposure to ethanol and diazepam alters the aversive properties of ethanol in adult mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {84}, number = {3}, pages = {406-414}, doi = {10.1016/j.pbb.2006.05.024}, pmid = {16844209}, issn = {0091-3057}, support = {AA005594/AA/NIAAA NIH HHS/United States ; AA12438/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Anti-Anxiety Agents/pharmacology ; *Avoidance Learning ; Body Weight ; Brain/pathology ; Central Nervous System Depressants/pharmacology ; Conditioning, Classical ; Conditioning, Psychological ; Diazepam/*pharmacology ; Ethanol/*pharmacology ; Male ; Mice ; Mice, Inbred C3H ; Time Factors ; }, abstract = {Evidence suggests that the developing adolescent brain may be especially vulnerable to long-term neurobehavioral consequences following ethanol exposure and withdrawal. In the present study, we examined the long-term effect of adolescent ethanol withdrawal on a subsequent EtOH-induced conditioned taste aversion (CTA). Periadolescent and adult C3H mice were exposed to 64 h of continuous (single withdrawal) or intermittent (multiple withdrawal) ethanol vapor. Following each ethanol exposure, animals received either 0, 1, 2, or 3 mg/kg diazepam (DZP) in an attempt to counteract the possible effect of ethanol withdrawal. About 6 weeks following ethanol and DZP treatment, animals were tested for an EtOH-induced CTA. As expected, exposure to EtOH during adolescence attenuated the EtOH-induced CTA as compared to controls. Unexpectedly, administration of DZP during withdrawal did not spare but rather mimicked the attenuation of the EtOH-induced CTA seen in animals exposed to ethanol in adolescence. This attenuation was not evident when EtOH and/or DZP was administered in adulthood. Given the similar mode of action of EtOH and DZP on the GABA system, the principal implication of the present findings is that the intoxicating effect of ethanol on the developing brain can result in long-term changes in the aversive properties of EtOH.}, } @article {pmid16844150, year = {2006}, author = {Mosher, TM and Smith, JG and Greenshaw, AJ}, title = {Aversive stimulus properties of the 5-HT2C receptor agonist WAY 161503 in rats.}, journal = {Neuropharmacology}, volume = {51}, number = {3}, pages = {641-650}, doi = {10.1016/j.neuropharm.2006.05.006}, pmid = {16844150}, issn = {0028-3908}, mesh = {Amphetamine/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Conditioning, Psychological/*drug effects ; Dopamine Uptake Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Food Preferences/drug effects ; Male ; Pyrazines/*pharmacology ; Quinoxalines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology/drug effects ; Saccharin/pharmacology ; *Serotonin 5-HT2 Receptor Agonists ; Sweetening Agents/pharmacology ; Time Factors ; }, abstract = {Serotonin2C (5-HT2C) receptors may influence motivation and reward through effects on the mesocorticolimbic dopamine (DA) system. Previous work from this laboratory indicated that 5-HT2C receptor stimulation does not induce place conditioning when animals are tested in a drug-free state, but does result in decreased locomotor activity and increased frequency thresholds for electrical self-stimulation of the ventral tegmental area (VTA). The present study was conducted to determine whether the 5-HT2C receptor agonist WAY 161503 may induce place conditioning in a state-dependent manner and also whether this compound will induce gustatory avoidance conditioning in the conditioned taste aversion (CTA) paradigm. The effects of the 5-HT2C receptor agonist WAY 161503 in the place conditioning and CTA (two-bottle choice test) paradigms were assessed in male Sprague-Dawley rats. Administration of WAY 161503 (3.0 mg/kg) induced a state-dependent conditioned place aversion and a CTA to saccharin. The differential state dependency of 5-HT2C receptor agonists' effects in place conditioning (state dependent) and CTA (non-state dependent) is consistent with the activation of different brain systems in these two paradigms. The state-dependent effects in place conditioning underscore the need to include controls for state dependency in studies of 5-HT receptor related compounds.}, } @article {pmid16824919, year = {2006}, author = {Babb, SJ and Crystal, JD}, title = {Episodic-like memory in the rat.}, journal = {Current biology : CB}, volume = {16}, number = {13}, pages = {1317-1321}, doi = {10.1016/j.cub.2006.05.025}, pmid = {16824919}, issn = {0960-9822}, support = {R01 MH064799/MH/NIMH NIH HHS/United States ; MH64799/MH/NIMH NIH HHS/United States ; MH64799-S1/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Feeding Behavior/*psychology ; Rats ; Rats, Long-Evans ; Retention, Psychology/*physiology ; Taste ; }, abstract = {A fundamental question in comparative cognition is whether animals remember unique, personal past experiences. It has long been argued that memories for specific events (referred to as episodic memory) are unique to humans. Recently, considerable evidence has accumulated to show that food-storing birds possess critical behavioral elements of episodic memory, referred to as episodic-like memory in acknowledgment of the fact that behavioral criteria do not assess subjective experiences. Here we show that rats have a detailed representation of remembered events and meet behavioral criteria for episodic-like memory. We provided rats with access to locations baited with distinctive (e.g., grape and raspberry) or nondistinctive (regular chow) flavors. Locations with a distinctive flavor replenished after a long but not a short delay, and locations with the nondistinctive flavor never replenished. One distinctive flavor was devalued after encoding its location by prefeeding that flavor (satiation) or by pairing it with lithium chloride (acquired taste aversion), while the other distinctive flavor was not devalued. The rats selectively decreased revisits to the devalued distinctive flavor but not to the nondevalued distinctive flavor. The present studies demonstrate that rats selectively encode the content of episodic-like memories.}, } @article {pmid16815539, year = {2006}, author = {Schramm-Sapyta, NL and Morris, RW and Kuhn, CM}, title = {Adolescent rats are protected from the conditioned aversive properties of cocaine and lithium chloride.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {84}, number = {2}, pages = {344-352}, pmid = {16815539}, issn = {0091-3057}, support = {R01 DA014931/DA/NIDA NIH HHS/United States ; R01 DA019114/DA/NIDA NIH HHS/United States ; R01 DA019114-05/DA/NIDA NIH HHS/United States ; DA14931/DA/NIDA NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Cocaine/*pharmacology ; Conditioning, Psychological/*drug effects ; Lithium Chloride/*pharmacology ; Male ; Motor Activity ; Rats ; Rats, Sprague-Dawley ; Substance-Related Disorders/etiology ; Taste/*drug effects ; }, abstract = {In humans, most drug use is initiated during adolescence and adolescent users are more likely to become drug-dependent than adult users. Repeated, high levels of use are required for the transition from use to addiction. Individual levels of drug use are thought to result from a balance between the pleasant or rewarding and the unpleasant or aversive properties of the drug. Repeated high levels of drug use are required for the transition from drug use to dependence. We hypothesized that diminished aversive effects of drugs of abuse during adolescence might be one reason for higher rates of use and addiction during this phase. We therefore tested adolescent and adult CD rats in single-dose cocaine conditioned taste aversion (CTA) at a range of doses (10-40 mg/kg), and examined whether various behavioral markers of addiction vulnerability were correlated to outcome in cocaine CTA. We found that adolescents are indeed less susceptible to cocaine CTA. In fact, age was the predominant predictor of CTA outcome, predominating over measures of novelty-seeking, anxiety, and stress hormone levels, which are all known to be related to drug intake in other models. Furthermore, we found that adolescent rats are also less susceptible to conditioned taste aversion to a low dose of a non-addictive substance, lithium chloride. These results suggest that one explanation for elevated drug use and addiction among adolescents is reduced aversive or use-limiting effects of the drugs. This contributes to our understanding of why adolescence is a particularly vulnerable period for development of drug abuse.}, } @article {pmid16807869, year = {2006}, author = {de la Torre-Vacas, L and Agüero-Zapata, A}, title = {[The neural bases of taste aversion learning: the formation of acquired hedonic taste representations].}, journal = {Revista de neurologia}, volume = {43}, number = {1}, pages = {25-31}, pmid = {16807869}, issn = {0210-0010}, mesh = {Amygdala/anatomy & histology/physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Humans ; Neural Pathways/physiology ; Pons/anatomy & histology/physiology ; Solitary Nucleus/anatomy & histology/physiology ; *Taste ; }, abstract = {INTRODUCTION: Taste aversion conditioning is a form of associative learning in which certain qualities of a food (mainly its taste) are associated to specific negative visceral consequences that derive from eating it. Establishing this learning depends on gustatory-visceral integration processes carried out in the central nervous system.

DEVELOPMENT: In this manuscript our aim is to offer a global view of the centres and connections that play the most significant roles in the formation of taste aversion learning (TAL).

CONCLUSIONS: Many researchers consider that the initial level of integration is situated within the parabrachial nuclei. A priori and given the basic vital nature of TAL, its formation and completion could be thought to take place at this brain stem level, without requiring the intervention of the higher processing structures. Nevertheless, in the literature on TAL there is a large body of both neuroanatomical and neurobehavioural evidence that seems to indicate that the formation of TAL requires complex interactions between the parabrachial nuclei and certain prosencephalic structures, such as the insular cortex or the amygdala, among others.}, } @article {pmid16797061, year = {2006}, author = {Haksar, A and Sharma, A and Chawla, R and Kumar, R and Arora, R and Singh, S and Prasad, J and Gupta, M and Tripathi, RP and Arora, MP and Islam, F and Sharma, RK}, title = {Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {84}, number = {2}, pages = {179-188}, doi = {10.1016/j.pbb.2006.04.008}, pmid = {16797061}, issn = {0091-3057}, mesh = {Animals ; Antiemetics/pharmacology ; Conditioning, Psychological/drug effects/*radiation effects ; Dexamethasone/pharmacology ; Drinking Behavior/drug effects/*radiation effects ; Female ; Free Radical Scavengers/pharmacology ; Gamma Rays ; *Ginger ; Male ; Ondansetron/pharmacology ; Plant Extracts/pharmacology ; Radiation-Protective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Taste/drug effects/*radiation effects ; Whole-Body Irradiation/adverse effects ; }, abstract = {At the organismic level, exposure to radiation can produce taste aversion (CTA) learning and emesis, which have been proposed as behavioral endpoints that are mediated by harmful effects of radiations on peripheral systems, primarily the gastrointestinal system. Thus, the aim of the present investigation was to study the gastroprotective action of hydroalcoholic extract of zingiber rhizome (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion (CTA) in both male and female species of animals, for testing its potential as a behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy gamma-radiation was significantly effective in blocking the saccharin avoidance response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for male and female rats, respectively. A comparison of the efficacy of zingiber extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that the extract rendered comparable protection against radiation-induced CTA. Our experiments also confirmed the existence of sex dichotomy (i.e., the sex of animal greatly influenced response towards radiation exposure) in relation to behavioral responses (CTA) or differential metabolism. The observed gender variations were hypothesized to be a result of hormonal fluctuations and differences in pharmacological parameters in male and female rats. To correlate the mechanism of action, the free-radical-scavenging potential of zingiber extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free system and a concentration of 1000 microg/ml, was found to be the most potent, which has been proposed as one the many activities assisting in its overall ability to modulate radiation-induced taste aversion. The results demonstrate that Z. officinale possesses antioxidant, radioprotective and neuromodulatory properties that can be effectively utilized for behavioral radioprotection and for efficiently mitigating radiation-induced CTA in both males and females species.}, } @article {pmid16793068, year = {2006}, author = {Castañé, A and Soria, G and Ledent, C and Maldonado, R and Valverde, O}, title = {Attenuation of nicotine-induced rewarding effects in A2A knockout mice.}, journal = {Neuropharmacology}, volume = {51}, number = {3}, pages = {631-640}, doi = {10.1016/j.neuropharm.2006.05.005}, pmid = {16793068}, issn = {0028-3908}, support = {DA016768/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Conditioning, Psychological/*drug effects ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Mice ; Mice, Knockout ; Microdialysis/methods ; Motor Activity/drug effects ; Nicotine/*pharmacology ; Nicotinic Agonists/*pharmacology ; Nucleus Accumbens/drug effects/metabolism ; Receptor, Adenosine A2A/*deficiency ; *Reward ; Substance Withdrawal Syndrome/etiology ; Taste/drug effects ; }, abstract = {The non-selective A2A antagonist caffeine has been reported to modify nicotine-induced locomotor and reinforcing effects. In the present study, we have investigated the specific role of A2A adenosine receptors in the behavioural responses induced by nicotine by using genetically modified mice lacking A2A adenosine receptors. Acute nicotine administration induced a similar decrease of locomotor activity in A2A knockout mice and wild-type littermates. Acute antinociceptive responses elicited by nicotine in the tail-immersion and hot-plate tests were unaffected in these mutant mice. The rewarding properties of nicotine were then investigated using the place-conditioning paradigm. Nicotine-induced conditioned place preference was suppressed in A2A knockout mice. Accordingly, in vivo microdialysis studies revealed that the extracellular levels of dopamine in the nucleus accumbens were not increased after nicotine administration in mutant mice. Wild-type and A2A knockout mice were trained in conditioned taste aversion procedure in which drinking a saccharin or saline solution was paired with nicotine or saline injections. A similar reduction in the intake of nicotine-paired solution in this paradigm was obtained in both genotypes. Finally, the administration of the nicotinic antagonist mecamylamine in nicotine-dependent mice precipitated a similar withdrawal syndrome in both genotypes. Together, the present results identify A2A adenosine receptors as an important factor that contributes to the rewarding properties of nicotine.}, } @article {pmid16777201, year = {2006}, author = {Fox, MA and Stevenson, GW and Rice, KC and Riley, AL}, title = {Naloxone, not proglumide or MK-801, alters effects of morphine preexposure on morphine-induced taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {84}, number = {1}, pages = {169-177}, doi = {10.1016/j.pbb.2006.05.003}, pmid = {16777201}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical ; Dizocilpine Maleate/*pharmacology ; Male ; Morphine/*pharmacology ; Naloxone/*pharmacology ; Proglumide/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Both cholecystokinin (CCK) antagonists and N-methyl-D-aspartate (NMDA) antagonists block or reduce the development of morphine tolerance in several analgesic assays. The present experiments were performed to assess the ability of the CCK antagonist proglumide and the NMDA antagonist MK-801 to affect tolerance to the aversive properties of morphine as indexed by conditioned taste aversion (CTA) learning. Specifically, male Sprague-Dawley rats were exposed to either vehicle or morphine (5 mg/kg) in combination with either proglumide (5 mg/kg; Experiment 1), MK-801 (0.1 mg/kg; Experiment 2) or naloxone (1, 3.2 mg/kg; Experiment 3). Saccharin was then presented and was followed by an injection of either vehicle or morphine (10 mg/kg). Animals preexposed to and conditioned with morphine acquired an attenuated morphine-induced aversion to saccharin. While neither proglumide nor MK-801 had an effect on this attenuation, naloxone blocked the effects of morphine preexposure, suggesting that neither CCK nor NMDA may be involved in the aversive effects of morphine (or their modulation by drug exposure). That the attenuating effects of morphine preexposure on a morphine-induced CTA can be blocked suggests that the weakening of the aversive effects of morphine with chronic use can be prevented, an effect that may have implications for overall drug acceptability.}, } @article {pmid16777150, year = {2006}, author = {Masaki, T and Nakajima, S}, title = {Taste aversion in rats induced by forced swimming, voluntary running, forced running, and lithium chloride injection treatments.}, journal = {Physiology & behavior}, volume = {88}, number = {4-5}, pages = {411-416}, doi = {10.1016/j.physbeh.2006.04.013}, pmid = {16777150}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Wistar ; Running/*physiology ; Swimming/*physiology ; Taste/*drug effects ; }, abstract = {The present experiment compared the strengths of taste aversion learning in rats induced by forced swimming in a water pool (5, 15, 30, or 60 min), voluntary running in an activity wheel (15, 30, 60, or 120 min), forced running in a motorized wheel (60 min at the speed of 8 m/min), optional running in the apparatus consisting of an activity wheel and a side room (120 min), and a lithium chloride (LiCl, 0.15 M LiCl at 2% of body weight) injection. The rats were given an access to saccharin solution immediately followed by one of the above treatments or simply returned back to the home cages for the control group. On the next 2 days, aversion to the saccharin solution was assessed by two-bottle choice testing between it and tap water. The following results were obtained. (1) The saccharin aversion was a positive function of exercise durations in the forced swimming and voluntary running rats, and the exercise of more than 30 min induced statistically significant saccharin aversion, compared with the control rats. (2) The forced running caused relatively strong saccharin aversion. The group of forced running rats acquired the numerically strongest saccharin aversion on average among all exercised rats. (3) The optional running treatment had little effect. (4) The LiCl injection resulted in the strongest aversion among the all treatments explored here.}, } @article {pmid16768622, year = {2006}, author = {Arias, C and Chotro, MG}, title = {Ethanol-induced preferences or aversions as a function of age in preweanling rats.}, journal = {Behavioral neuroscience}, volume = {120}, number = {3}, pages = {710-718}, doi = {10.1037/0735-7044.120.3.710}, pmid = {16768622}, issn = {1939-0084}, mesh = {Age Factors ; Alcohol Drinking/*physiopathology ; Analysis of Variance ; Animals ; Animals, Newborn ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Body Weight/drug effects ; Central Nervous System Depressants/*administration & dosage ; Ethanol/*administration & dosage ; Female ; Food Preferences/*drug effects ; Male ; Motor Activity/drug effects ; Psychomotor Performance/drug effects ; Rats ; Rats, Wistar ; Taste/drug effects ; }, abstract = {The reinforcing value of a relatively high ethanol dose (3 g/kg) administered intragastrically was investigated in preweanling rats. Ethanol intoxication on Postnatal Days 7-8 increased ethanol intake and enhanced the drug's palatability when tested 3 days later. In contrast, intoxication on Days 10-11 decreased ethanol intake and increased aversive responses to the drug. When reducing the delay between intoxication and test to 24 hr, the taste aversion was enhanced, whereas the preference was unaffected. Results suggest an ontogenetic change in pups' perception of the reinforcing value of ethanol that coincides with the end of a sensitive period for learning preferences in rats younger than 9 days old (T. L. Roth & R. M. Sullivan, 2003; R. M. Sullivan, M. Landers, B. Yeaman, & D. A. Wilson, 2000).}, } @article {pmid16768611, year = {2006}, author = {Inui, T and Shimura, T and Yamamoto, T}, title = {Effects of brain lesions on taste-potentiated odor aversion in rats.}, journal = {Behavioral neuroscience}, volume = {120}, number = {3}, pages = {590-599}, doi = {10.1037/0735-7044.120.3.590}, pmid = {16768611}, issn = {1939-0084}, mesh = {Amygdala/physiopathology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Brain Injuries/pathology/*physiopathology ; Conditioning, Classical/physiology ; Drinking/physiology ; Drinking Behavior ; Male ; *Odorants ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Smell/*physiology ; Taste/*physiology ; }, abstract = {Rats failed to acquire aversions to odor stimulus, which was followed 30 min later by an unconditioned stimulus (US). However, when the odor stimulus was accompanied by a taste stimulus, they acquired odor aversions as well as taste aversions. In this phenomenon, referred to as a taste-potentiated odor aversion, lesions of the amygdala disrupted both taste and odor aversions, whereas lesions of the parvicellular part of ventroposteromedial thalamic nucleus (VPMpc) or insular cortex (IC) disrupted taste aversion but attenuated only odor aversion. These results suggest that both taste and odor stimuli are associated with US in the amygdala and that taste inputs delivered to the amygdala through the IC and/or VPMpc play an important role in potentiation of odor aversion.}, } @article {pmid16768607, year = {2006}, author = {Bethus, I and Muscat, R and Goodall, G}, title = {Dopamine manipulations limited to preexposure are sufficient to modulate latent inhibition.}, journal = {Behavioral neuroscience}, volume = {120}, number = {3}, pages = {554-562}, doi = {10.1037/0735-7044.120.3.554}, pmid = {16768607}, issn = {1939-0084}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/*physiology ; Central Nervous System Stimulants/pharmacology ; Conditioning, Classical/drug effects/physiology ; Conditioning, Operant/drug effects/physiology ; Dopamine/*metabolism ; Dopamine Antagonists/pharmacology ; Drinking Behavior/drug effects/physiology ; Drug Administration Schedule ; Haloperidol/pharmacology ; *Inhibition, Psychological ; Male ; Rats ; }, abstract = {Four experiments are reported that demonstrated that dopamine (DA) transmission is involved in the acquisition of latent inhibition (LI) of a conditioned taste aversion. LI refers to weaker conditioning as a consequence of nonreinforced preexposure (PE) of the future conditioned stimulus. Although it is known to depend on DA transmission during the conditioning phase, it is usually thought that the cognitive processes involved in the establishment of LI (during the PE phase) are DA independent. Either amphetamine (AMPH; 0.5 or 1.0 mg/kg) or haloperidol (HAL; 0.1 mg/kg) were injected before 1 or all of the 3 PE sessions. AMPH blocked the acquisition of LI if it was injected before each or before only the last PE session and HAL potentiated LI.}, } @article {pmid16764948, year = {2006}, author = {de Bruin, N and Mahieu, M and Patel, T and Willems, R and Lesage, A and Megens, A}, title = {Performance of F2 B6x129 hybrid mice in the Morris water maze, latent inhibition and prepulse inhibition paradigms: Comparison with C57Bl/6J and 129sv inbred mice.}, journal = {Behavioural brain research}, volume = {172}, number = {1}, pages = {122-134}, doi = {10.1016/j.bbr.2006.05.002}, pmid = {16764948}, issn = {0166-4328}, mesh = {Animals ; Antimanic Agents/pharmacology ; Body Weight/drug effects/physiology ; Conditioning, Psychological/physiology ; Genotype ; Lithium Chloride/pharmacology ; Male ; Maze Learning/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Motor Activity/physiology ; Muscarinic Antagonists/pharmacology ; Reflex, Startle/*physiology ; Reward ; Scopolamine/pharmacology ; Space Perception/physiology ; Species Specificity ; Sucrose ; Taste ; }, abstract = {Assessment of cognition and information processing in mice is an important tool in preclinical research that focuses on the development of cognitive enhancing drugs. Analysis of transgenic (TG) and knockout (KO) mice is usually performed on a F2 B6x 129 background. In the present study, we have compared performance of F2 B6x 129 hybrid mice (F2 mice) with that of the two parental inbred strains (C57Bl/6J and 129sv mice), and a wild-type (WT) strain (with a combined B6x 129 background) in three cognitive/information processing paradigms. It was found that the F2 mice outperformed either of the parental strains and provide a control sample with good baseline performance in the Morris water maze (MWM). Reliable deficits could be obtained in learning and memory in this paradigm following injections with scopolamine (0.16 mg/kg) in the F2 mice, which can potentially be used to test effects of reference and novel compounds in order to develop cognitive enhancing drugs. Furthermore, it was shown that the four genotypes showed normal latent inhibition (LI) using the conditioned taste aversion (CTA) paradigm and exhibited no differences in prepulse inhibition (PPI) levels. Following the setup of these procedures in mice, we are now able to compare the effects of gene knockout/mutations used for target validation with results in the present study as a frame of reference.}, } @article {pmid16750261, year = {2006}, author = {Young, R and Rothman, RB and Rangisetty, JB and Partilla, JS and Dukat, M and Glennon, RA}, title = {TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) inhibits the consumption of "snacks" in mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {84}, number = {1}, pages = {74-83}, doi = {10.1016/j.pbb.2006.04.007}, pmid = {16750261}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Dopamine/metabolism ; Feeding Behavior/*drug effects ; Male ; Mice ; Mice, Inbred ICR ; Norepinephrine/metabolism ; Serotonin/metabolism ; Tetrahydroisoquinolines/*pharmacology ; }, abstract = {There is considerable evidence that alpha2-adrenergic receptor activity exerts a pivotal role in initiation of feeding behavior. The appetite suppressant and monoamine release effects of TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline), a putative selective alpha2-adrenergic compound, were compared to those of fenfluramine, a reference drug that produces an anorectic effect via presynaptic release and reuptake inhibition of serotonin. The drugs were administered to two groups of mice that had learned to consume either sweet milk or chocolate pellets (i.e. "snacks") during the low-activity/reduced-feeding "light" portion of their light/dark cycle. The selectivity of the drugs to suppress the consumption of snacks was determined by comparing doses of each drug that inhibited the animals' consumption of snacks to doses of each drug that have been shown, or were shown, to impact the motor (i.e. locomotor, rotarod, and inclined-screen side effect-like tests) or conditioned taste aversion (CTA) behavior of mice. An evaluation of TDIQ as a releaser of monoamines was determined in rodent brain synaptosomes. The administration of TDIQ or fenfluramine inhibited the consumption of the snacks, and a comparison of their ED50 doses indicated that TDIQ is about 3 times more potent than fenfluramine (1.3 mg/kg vs. 4.2 mg/kg, respectively) in the sweet milk test and almost equipotent to fenfluramine (19.4 mg/kg vs. 18.4 mg/kg, respectively) in the chocolate pellet assay. The selectivity of the appetite suppressant effect of TDIQ was differentiated from that of fenfluramine on the basis that TDIQ exhibited a wide separation between its dose-response effects that suppressed snack consumption and its minimal effects in tests that measured behavioral impairment. Moreover, TDIQ was distinguished from fenfluramine in that it displayed very low potencies as a presynaptic releaser of monoamines. Finally, TDIQ (0.3 mg/kg-30.0 mg/kg) did not induce a conditioned taste aversion. TDIQ may represent a novel chemical entity that exhibits a significantly favorable therapeutic-like (i.e. appetite suppressant) effect to side effect-like ratio.}, } @article {pmid16741279, year = {2006}, author = {Akirav, I and Khatsrinov, V and Vouimba, RM and Merhav, M and Ferreira, G and Rosenblum, K and Maroun, M}, title = {Extinction of conditioned taste aversion depends on functional protein synthesis but not on NMDA receptor activation in the ventromedial prefrontal cortex.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {13}, number = {3}, pages = {254-258}, doi = {10.1101/lm.191706}, pmid = {16741279}, issn = {1072-0502}, mesh = {2-Amino-5-phosphonovalerate/administration & dosage/pharmacology ; Animals ; Anisomycin/administration & dosage/pharmacology ; Association Learning/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/physiology ; Dose-Response Relationship, Drug ; Extinction, Psychological/drug effects/*physiology ; Male ; Microinjections ; Prefrontal Cortex/drug effects/*metabolism ; Protein Biosynthesis/drug effects/*physiology ; Protein Synthesis Inhibitors/administration & dosage/pharmacology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism ; Taste/physiology ; }, abstract = {We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin, but not the NMDA receptors antagonist D,L-2-amino-5-phosphonovaleric acid, impaired CTA extinction in the vmPFC. Anisomycin microinfusion into vmPFC had no effect on CTA acquisition and by itself did not induce CTA. These findings show the necessary role functional protein synthesis is playing in the vmPFC during the learning of CTA extinction.}, } @article {pmid16730913, year = {2006}, author = {Paues, J and Mackerlova, L and Blomqvist, A}, title = {Expression of melanocortin-4 receptor by rat parabrachial neurons responsive to immune and aversive stimuli.}, journal = {Neuroscience}, volume = {141}, number = {1}, pages = {287-297}, doi = {10.1016/j.neuroscience.2006.03.041}, pmid = {16730913}, issn = {0306-4522}, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal ; Calcitonin Gene-Related Peptide/genetics/metabolism ; Gene Expression/*drug effects/*physiology ; In Situ Hybridization/methods ; Lipopolysaccharides/*administration & dosage ; Lithium Chloride/pharmacology ; Male ; Neurons/*metabolism ; Pons/*cytology ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Melanocortin, Type 4/genetics/*metabolism ; Taste/drug effects/physiology ; }, abstract = {The pontine parabrachial nucleus is a major relay area for visceral and other interoceptive information, and has been implicated in mechanisms underlying anorexia and food aversion during disease. Thus, physiological studies have shown that peripheral immune stimuli, as well as the administration of aversive substances such as lithium chloride, evoke a prominent Fos-expression in the lateral parabrachial nucleus and behavioral experiments have demonstrated that this structure is critical for the acquisition of conditioned taste aversion. The present study examined in rats the relationship between parabrachial neurons activated by systemic administration of bacterial cell-wall lipopolysaccharide or lithium chloride and the melanocortin system, a major regulator of feeding and energy homeostasis that also has been implicated in aversive behavior. Dual-labeling in situ hybridization showed melanocortin-4 receptor expression on neurons in the external lateral parabrachial subnucleus that displayed lipopolysaccharide- or lithium chloride-induced expression of c-fos mRNA. Melanocortin-4 receptor mRNA was also co-expressed with mRNA for calcitonin gene-related peptide in this subnucleus. Taken together with previous observations showing that calcitonin gene-related peptide expressing neurons in the external lateral parabrachial subnucleus are activated by peripheral immune challenge, that lipopolysaccharide-activated external lateral parabrachial subnucleus neurons project to the amygdala, and that the amygdala-projecting neurons in the external lateral parabrachial subnucleus are calcitonin gene-related peptide-positive, the present findings suggest the presence of a melanocortin-regulated calcitonin gene-related peptide-positive pathway from the external lateral parabrachial subnucleus to the amygdala that relays information of importance to forebrain responses to certain aspects of sickness behavior. These observations may thus help explain how melanocortins can reduce feeding and influence conditioned taste aversion during inflammation and other disease conditions.}, } @article {pmid16707804, year = {2006}, author = {Colón-Cesario, M and Wang, J and Ramos, X and García, HG and Dávila, JJ and Laguna, J and Rosado, C and Peña de Ortiz, S}, title = {An inhibitor of DNA recombination blocks memory consolidation, but not reconsolidation, in context fear conditioning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {26}, number = {20}, pages = {5524-5533}, pmid = {16707804}, issn = {1529-2401}, support = {5R25GM061151/GM/NIGMS NIH HHS/United States ; T34 GM007821/GM/NIGMS NIH HHS/United States ; SO6GMO8102/SO/PHSPO CDC HHS/United States ; 5P20 RR 15565-02/RR/NCRR NIH HHS/United States ; U54 NS39405/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Arabinofuranosylcytosine Triphosphate/pharmacology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; DNA/biosynthesis/genetics ; DNA Ligases/antagonists & inhibitors/metabolism ; Fear/drug effects/*physiology ; Hippocampus/drug effects/metabolism/physiopathology ; Learning/drug effects/physiology ; Long-Term Potentiation/drug effects/genetics ; Male ; Memory/drug effects/*physiology ; Memory Disorders/chemically induced/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Nucleic Acid Synthesis Inhibitors/*pharmacology ; Recombination, Genetic/drug effects/*physiology ; }, abstract = {Genomic recombination requires cutting, processing, and rejoining of DNA by endonucleases, polymerases, and ligases, among other factors. We have proposed that DNA recombination mechanisms may contribute to long-term memory (LTM) formation in the brain. Our previous studies with the nucleoside analog 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM). However, because polymerases and ligases are also essential for DNA replication, it remained unclear whether the effects of this drug on consolidation were attributable to interference with DNA recombination or neurogenesis. Here we show, using C57BL/6 mice, that ara-CTP specifically blocks consolidation but not STM of context fear conditioning, a task previously shown not to require neurogenesis. The effects of a single systemic dose of cytosine arabinoside (ara-C) on LTM were evident as early as 6 h after training. In addition, although ara-C impaired LTM, it did not impair general locomotor activity nor induce brain neurotoxicity. Importantly, hippocampal, but not insular cortex, infusions of ara-C also blocked consolidation of context fear conditioning. Separate studies revealed that context fear conditioning training significantly induced nonhomologous DNA end joining activity indicative of DNA ligase-dependent recombination in hippocampal, but not cortex, protein extracts. Finally, unlike inhibition of protein synthesis, systemic ara-C did not block reconsolidation of context fear conditioning. Our results support the idea that DNA recombination is a process specific to consolidation that is not involved in the postreactivation editing of memories.}, } @article {pmid16683252, year = {2006}, author = {Cai, YQ and Cai, GQ and Liu, GX and Cai, Q and Shi, JH and Shi, J and Ma, SK and Sun, X and Sheng, ZJ and Mei, ZT and Cui, D and Guo, L and Wang, Z and Fei, J}, title = {Mice with genetically altered GABA transporter subtype I (GAT1) expression show altered behavioral responses to ethanol.}, journal = {Journal of neuroscience research}, volume = {84}, number = {2}, pages = {255-267}, doi = {10.1002/jnr.20884}, pmid = {16683252}, issn = {0360-4012}, mesh = {Analgesics, Non-Narcotic/pharmacology ; Animals ; Behavior, Animal/*drug effects ; Blotting, Northern ; Blotting, Southern ; Brain/*drug effects/metabolism ; Central Nervous System Depressants/metabolism/*pharmacology ; Conditioning, Classical/drug effects ; Ethanol/metabolism/*pharmacology ; GABA Plasma Membrane Transport Proteins/biosynthesis/*genetics ; Mice ; Mice, Knockout ; Quinine/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Synaptosomes/drug effects/physiology ; }, abstract = {It is widely accepted that the GABAergic system plays an important role in the action of ethanol in vivo. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites in the CNS and regulates GABAergic transmissions. In this study, mice lacking the GAT1 were developed by homologous recombination. Both hetero- and homozygous GAT1 mutant mice were tested for ethanol, saccharin or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and ethanol-induced sedation/hypnosis. The GAT1(-/-) mice showed decreased ethanol aversion and ethanol reward, and insensitivity to both the sedative/hypnotic and the motor stimulant effects of ethanol, along with increased avoidance of quinine preference and consumption. GAT1(+/-) mice showed significantly increased consumption of ethanol and saccharin, however, enhanced the rewarding and preference effect of ethanol, increased avoidance of quinine, and higher sensitivity to the motor stimulant effect of ethanol. These results demonstrate that GAT1, perhaps in a bi-directional way, modulates some behavioral effects of ethanol. The GAT1 mutant mice provided us a very useful model to investigate the mechanisms of ethanol action in vivo.}, } @article {pmid16650612, year = {2006}, author = {Yasoshima, Y and Scott, TR and Yamamoto, T}, title = {Memory-dependent c-Fos expression in the nucleus accumbens and extended amygdala following the expression of a conditioned taste aversive in the rat.}, journal = {Neuroscience}, volume = {141}, number = {1}, pages = {35-45}, doi = {10.1016/j.neuroscience.2006.03.019}, pmid = {16650612}, issn = {0306-4522}, mesh = {Amygdala/drug effects/*metabolism ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects ; Cell Count/methods ; *Conditioning, Psychological ; Gene Expression/drug effects/physiology ; Immunohistochemistry/methods ; Lithium Chloride/pharmacology ; Male ; Memory/*physiology ; Nucleus Accumbens/drug effects/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Quinine/administration & dosage ; Rats ; Rats, Wistar ; Reaction Time/physiology ; Sucrose/administration & dosage ; Sweetening Agents ; Taste/drug effects/*physiology ; }, abstract = {Retrieving the memory of a conditioned taste aversion involves multiple forebrain areas. Although the amygdala clearly plays a role in the expression of a conditioned taste aversion, critical regions, downstream from the amygdala remain to be defined. To this end, Fos immunoreactivity was used in the rat to explore forebrain structures associated with retrieval that have an anatomical relationship with the amygdala. The results showed that expression of a conditioned taste aversion to 0.5 M sucrose elicited neuronal activation in the nucleus accumbens and in a complex of structures collectively referred to as the extended amygdala. The posterior hypothalamus and parasubthalamic nucleus, which receive inputs from the extended amygdala, were also activated upon re-exposure to the sucrose conditioned stimulus. Fos immunoreactivity did not increase in these regions in response to an innately aversive tastant, quinine hydrochloride (conditioned stimulus control), nor to LiCl-induced visceral stimulation in unconditioned animals (unconditioned stimulus control). In addition, these regions did not respond to the sucrose conditioned stimulus in sham-conditioned animals. These results suggest that conditioned and innately aversive tastes are differentially processed in the forebrain circuitry that includes the nucleus accumbens and extended amygdala.}, } @article {pmid16650466, year = {2006}, author = {Jones, JD and Busse, GD and Riley, AL}, title = {Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {83}, number = {4}, pages = {554-560}, doi = {10.1016/j.pbb.2006.03.017}, pmid = {16650466}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Conditioning, Psychological/*drug effects ; Drug Interactions ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Sex Characteristics ; Species Specificity ; Taste/*drug effects ; }, abstract = {Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.}, } @article {pmid16636292, year = {2006}, author = {Yasoshima, Y and Sako, N and Senba, E and Yamamoto, T}, title = {Acute suppression, but not chronic genetic deficiency, of c-fos gene expression impairs long-term memory in aversive taste learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {18}, pages = {7106-7111}, pmid = {16636292}, issn = {0027-8424}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Early Growth Response Protein 1/genetics/metabolism ; *Gene Expression Regulation ; *Genes, fos ; Male ; Memory/*physiology ; Mice ; Mice, Knockout ; Neurons/cytology/metabolism ; Oligonucleotides, Antisense/genetics/metabolism ; Rats ; Rats, Wistar ; *Taste ; Transcription, Genetic ; }, abstract = {Several lines of evidence have indicated that the establishment of long-term memory requires protein synthesis, including the synthesis of immediate-early gene products. Although the anatomical expression patterns of the c-fos gene, a transcription factor-encoding immediate-early gene, in conditioned taste aversion (CTA) are well documented, the functional roles of c-fos gene expression and Fos-mediated transcription remain to be clarified. Using the antisense oligodeoxynucleotide (AS-ODN) method in rats and gene-targeting knockout techniques in mice (c-fos(-/-) mice), we examined the roles of c-fos gene expression in the acquisition, retrieval, and retention of CTA. Preconditioning microinfusion of AS-ODN directed against c-fos mRNA (c-fos AS-ODN) into the parabrachial nucleus (PBN) impaired the acquisition, whereas infusion of control ODNs consisting of a randomized or inverted base order had no effect. Microinfusion of c-fos AS-ODN into either the amygdala or insular cortex did not impair the acquisition, whereas it attenuated the retention. Retrieval and subsequent retention of an acquired CTA were not disrupted by c-fos AS-ODN infusion into the PBN or amygdala. Microinfusion of another AS-ODN directed against zif268 (egr-1, krox-24, NGFI-A) mRNA into the PBN or amygdala did not affect the acquisition and retention. The genetic deficiency in c-fos(-/-) mice caused normal acquisition and retention. The present results suggest that the Fos-mediated gene transcription in the PBN, amygdala, or insular cortex plays critical roles in the acquisition and/or consolidation, but not the retrieval, of long-term taste memory; nevertheless, some other factors could compensate CTA mechanism when Fos-mediated transcription is not available.}, } @article {pmid16626692, year = {2006}, author = {Korkosz, A and Scinska, A and Taracha, E and Plaznik, A and Kukwa, A and Kostowski, W and Bienkowski, P}, title = {Nicotine-induced conditioned taste aversion in the rat: effects of ethanol.}, journal = {European journal of pharmacology}, volume = {537}, number = {1-3}, pages = {99-105}, doi = {10.1016/j.ejphar.2006.03.023}, pmid = {16626692}, issn = {0014-2999}, mesh = {Animals ; Avoidance Learning/*drug effects ; *Conditioning, Psychological ; Ethanol/blood/pharmacokinetics/*pharmacology ; Male ; Nicotine/*pharmacology ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Self Administration ; Sweetening Agents/administration & dosage ; *Taste ; }, abstract = {It has been shown that small doses of ethanol antagonise the discriminative stimulus properties of nicotine in the rat. The aim of the present study was to evaluate whether ethanol could antagonise the aversive stimulus effects of nicotine. Wistar rats were trained to associate nicotine injections with a novel tasting fluid (0.1% saccharin) in the conditioned taste aversion procedure. Nicotine (0.3 mg/kg, s.c.) was injected 5 min after the end of a 20-min exposure to the saccharin solution. Ethanol (0.25-0.5 g/kg, i.p.) was administered 5 or 50 min before nicotine. In general, ethanol did not inhibit nicotine-induced conditioned taste aversion. Contrary to the findings in drug discrimination studies, a slight but significant enhancement of nicotine-induced taste aversion conditioning was observed after ethanol pre-treatment. Blood ethanol levels were measured in a separate group of rats. Maximal blood ethanol levels after i.p. administration of 0.25 or 0.5 g/kg ethanol exceeded 20 and 80 mg%, respectively. Concluding, the present results may indicate that ethanol does not attenuate nicotine-induced conditioned taste aversion in the rat.}, } @article {pmid16624349, year = {2006}, author = {Nakajima, S and Urata, T and Ogawa, Y}, title = {Familiarization and cross-familiarization of wheel running and LiCl in conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {88}, number = {1-2}, pages = {1-11}, doi = {10.1016/j.physbeh.2006.02.006}, pmid = {16624349}, issn = {0031-9384}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal ; Conditioning, Classical/*drug effects/physiology ; Food Preferences ; *Generalization, Stimulus ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Wistar ; *Running ; Saccharin ; Taste/*physiology ; }, abstract = {Familiarization with an unconditioned stimulus (US) interferes with the learning of subsequent Pavlovian conditioned associations. We conducted a series of experiments exploiting this US preexposure effect to elucidate the underlying mechanism of conditioned taste aversion in rats induced by voluntary wheel running. Experiment 1 demonstrated that running-induced taste aversion was alleviated if rats had sufficient experience of running in advance. In Experiments 2A and 2B, preexposure to wheel running had no effect on subsequent taste aversion conditioning by lithium chloride (LiCl) injection. In Experiment 3, however, we observed a weak partial interference from the LiCl injection pretreatment to the subsequent conditioning by wheel running US. This US crossover effect suggests the possibility that wheel running and LiCl injection share a common or similar physiological mechanism in inducing taste aversion.}, } @article {pmid16603254, year = {2006}, author = {Zach, P and Krivanek, J and Vales, K}, title = {Serotonin and dopamine in the parabrachial nucleus of rats during conditioned taste aversion learning.}, journal = {Behavioural brain research}, volume = {170}, number = {2}, pages = {271-276}, doi = {10.1016/j.bbr.2006.03.001}, pmid = {16603254}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Chromatography, High Pressure Liquid/methods ; Conditioning, Operant/*physiology ; Dopamine/*metabolism ; Food Preferences/physiology ; Hydroxyindoleacetic Acid/metabolism ; Male ; Microdialysis/methods ; Pons/*physiology ; Rats ; Rats, Long-Evans ; Serotonin/*metabolism ; *Taste ; }, abstract = {A microdialysis technique was used to monitor changes in serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and dopamine (DA) in the extracellular space of the parabrachial nucleus (PBN) of rats to estimate the contribution of these neurotransmitter systems to the acquisition of conditioned taste aversion (CTA). A significant (280%) enhancement of 5-HT was found immediately after saccharin drinking (CS). I.p. injection of unconditioned stimulus LiCl alone (after water drinking) also increased level of 5-HT (200%). However, when saccharin intake was followed by injection of LiCl (CS-US pairing), no change in 5-HT was observed. 5-HIAA and DA were unaffected by any of the above treatments. Thus in spite of elevation of 5-HT in PBN following saccharin consumption alone (CS) or LiCl administration alone (US) no changes in 5-HT occurred after pairing of both stimuli (CS-US). Our work demonstrates that participation of 5-HT in acquisition of CTA appears to be unlikely, and also DA appears not to be engaged in this acquisition at all. At the level of the PBN 5-HT participates mainly in CS and/or US stimuli processing, where this phenomenon has close relationship to other important physiological mechanisms, involved in behavioral control. Such as anxiety, alimentation intake.}, } @article {pmid16600311, year = {2006}, author = {Tenk, CM and Kavaliers, M and Ossenkopp, KP}, title = {The effects of acute corticosterone on lithium chloride-induced conditioned place aversion and locomotor activity in rats.}, journal = {Life sciences}, volume = {79}, number = {11}, pages = {1069-1080}, doi = {10.1016/j.lfs.2006.03.008}, pmid = {16600311}, issn = {0024-3205}, mesh = {Animals ; Conditioning, Classical/*drug effects ; Corticosterone/*administration & dosage ; Extinction, Psychological ; Lithium Chloride/*antagonists & inhibitors/pharmacology ; Male ; Motor Activity/*drug effects ; Rats ; Rats, Inbred Strains ; }, abstract = {Acute administration of corticosterone (CORT) facilitates learning in a number of associative paradigms including lithium chloride (LiCl)-induced conditioned taste aversion learning. The present study examined the effects of acute CORT on LiCl-induced conditioned place aversions in male rats. Automated open-fields were partitioned into two chambers distinct in tactile and visual cues. Animals received either LiCl (64 mg/kg, 0.15 M) or saline (NaCl, 0.15 M) followed 10 min later by either CORT (5 mg/kg) or beta-cyclodextrin vehicle (45%) prior to placement in one of the chambers. Control rats received NaCl-Vehicle paired with both chambers. Three experimental groups received either NaCl-CORT, LiCl-Vehicle or LiCl-CORT paired with the preferred chamber and NaCl-Vehicle (control) paired with the non-preferred chamber. During extinction trials, animals were allowed to choose between the two chambers. Locomotor activity and its distribution within the chambers were assessed during both conditioning and extinction trials. CORT administration produced significant increases in a variety of measures of locomotor activity during conditioning trials. During extinction trials both LiCl groups displayed a conditioned place aversion while the NaCl-CORT group did not. In addition, significant increases in vertical activity were recorded in both LiCl groups in the LiCl-paired chamber. Moreover, CORT administration had no effect on LiCl-induced conditioned place aversion as time spent in the LiCl-paired chamber did not significantly differ between LiCl-Vehicle and LiCl-CORT groups. Significant increases in a number of measures of horizontal activity were also observed in both CORT groups. The present study shows that acute CORT administration does not significantly influence LiCl-induced conditioned place aversions and suggests that the facilitatory effects of acute CORT administration on learning are highly context-dependent.}, } @article {pmid16554468, year = {2006}, author = {Yee, BK and Balic, E and Singer, P and Schwerdel, C and Grampp, T and Gabernet, L and Knuesel, I and Benke, D and Feldon, J and Mohler, H and Boison, D}, title = {Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {26}, number = {12}, pages = {3169-3181}, pmid = {16554468}, issn = {1529-2401}, mesh = {Animals ; Anxiety Disorders/genetics ; Attention/physiology ; Avoidance Learning/physiology ; Cognition/physiology ; Disease Models, Animal ; Excitatory Postsynaptic Potentials/genetics ; Female ; Glycine/*metabolism ; Glycine Plasma Membrane Transport Proteins/*genetics ; Learning/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Neurologic Mutants ; Mutation/genetics ; Neurons/*metabolism ; Organ Culture Techniques ; Phenotype ; Prosencephalon/*growth & development/metabolism ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Schizophrenia/genetics/metabolism/*prevention & control ; Synaptic Transmission/genetics ; Up-Regulation/genetics ; }, abstract = {The NMDA receptor is thought to play a central role in some forms of neuronal plasticity, including the induction of long-term potentiation. NMDA receptor hypofunction can result in mnemonic impairment and has been implicated in the cognitive symptoms of schizophrenia. The activity of NMDA receptors is controlled by its endogenous coagonist glycine, and a local elevation of glycine levels is expected to enhance NMDA receptor function. Here, we achieved this by the generation of a novel mouse line (CamKIIalphaCre;Glyt1tm1.2fl/fl) with a neuron and forebrain selective disruption of glycine transporter 1 (GlyT1). The mutation led to a significant reduction of GlyT1 and a corresponding reduction of glycine reuptake in forebrain samples, without affecting NMDA receptor expression. NMDA (but not AMPA) receptor-evoked EPSCs recorded in hippocampal slices of mutant mice were 2.5 times of those recorded in littermate controls, suggesting that neuronal GlyT1 normally assumes a specific role in the regulation of NMDA receptor responses. Concomitantly, the mutants were less responsive to phencyclidine than controls. The mutation enhanced aversive Pavlovian conditioning without affecting spontaneous anxiety-like behavior in the elevated plus maze and augmented a form of attentional learning called latent inhibition in three different experimental paradigms: conditioned freezing, conditioned active avoidance, conditioned taste aversion. The CamKIIalphaCre;Glyt1tm1.2fl/fl mouse model thus suggests that augmentation of forebrain neuronal glycine transmission is promnesic and may also offer an effective therapeutic intervention against the cognitive and attentional impairments characteristic of schizophrenia.}, } @article {pmid16541088, year = {2007}, author = {Akirav, I}, title = {NMDA Partial agonist reverses blocking of extinction of aversive memory by GABA(A) agonist in the amygdala.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {32}, number = {3}, pages = {542-550}, doi = {10.1038/sj.npp.1301050}, pmid = {16541088}, issn = {0893-133X}, mesh = {Amygdala/*drug effects/physiology ; Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Cycloserine/pharmacology ; Drug Interactions ; Excitatory Amino Acid Agonists/*pharmacology ; Extinction, Psychological/*drug effects ; GABA Agonists/*pharmacology ; Male ; Muscimol/pharmacology ; Rats ; Rats, Wistar ; }, abstract = {The ability to extinguish aversive memories is of significant clinical interest. The amygdala plays an important role in emotional conditioning and its experimental extinction. It has been suggested that gamma-aminobutyric acid (GABA) agonists retard extinction and that consolidation of extinction involves N-methyl-D-aspartate receptor (NMDAR)-mediated plasticity. The aim was to further explore the interaction between GABA and NMDA in the amygdala in consolidation of experimental extinction in the rat. To that end conditioned taste aversion (CTA) was used. In CTA, the amygdala has been reported to subserve both acquisition and extinction. The GABA(A) receptor agonist, muscimol, administered into the amygdala immediately after the first extinction session, caused lasting disruption of extinction of CTA for at least 2 weeks. However, the administration of GABA(A) receptor antagonists had no effect on extinction kinetics. Microinfusing the partial NMDA agonist D-cycloserine together with or after muscimol infusion reversed the blocking effects of muscimol. These findings could bear relevance to the potential involvement of extinction abnormalities in behavioral disorders, and their amelioration.}, } @article {pmid16523999, year = {2005}, author = {Lubow, RE and De la Casa, LG}, title = {There is a time and a place for everything: bidirectional modulations of latent inhibition by time-induced context differentiation.}, journal = {Psychonomic bulletin & review}, volume = {12}, number = {5}, pages = {806-821}, pmid = {16523999}, issn = {1069-9384}, mesh = {Humans ; *Inhibition, Psychological ; Learning ; Memory ; *Time Perception ; }, abstract = {Latent inhibition (LI) is defined as poorer evidence of learning with a stimulus that previously was presented without consequence, as compared with a novel or previously attended stimulus. The present article reviews the evidence, mostly from three-stage conditioned taste aversion studies (preexposure, conditioning, and test), that LI can be either attenuated or enhanced depending on the length of the retention interval between conditioning and test and where that interval was spent. Time-induced reduction in LI is observed when the interval context is the same as that of the preexposure, conditioning, and test stages. Super-LI is obtained when a long retention interval is spent in a context that is different from that of the other stages. The differential modulations of LI appear to be the result of the strengthening of primacy effects (i.e., first training disproportionately stronger than subsequent training) by long-interval different contexts, thereby producing super-LI, and the reversal of this effect by long-interval same contexts, thereby producing attenuated LI. The bidirectional effects of time/ context modulations on LI, unaccounted for by current learning theories, are explained, in part, by a time-induced context differentiation process. Implications for theories of LI, learning, and, memory are discussed.}, } @article {pmid16499482, year = {2006}, author = {Fidler, TL and Clews, TW and Cunningham, CL}, title = {Reestablishing an intragastric ethanol self-infusion model in rats.}, journal = {Alcoholism, clinical and experimental research}, volume = {30}, number = {3}, pages = {414-428}, doi = {10.1111/j.1530-0277.2006.00046.x}, pmid = {16499482}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; U01-AA13479/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholic Intoxication/psychology ; Alcoholism/*psychology ; Animals ; Central Nervous System Depressants/administration & dosage/*pharmacology ; Ethanol/administration & dosage/*pharmacology ; Habituation, Psychophysiologic/drug effects ; Intubation, Gastrointestinal ; Male ; Rats ; Rats, Sprague-Dawley ; Recurrence ; Reinforcement Schedule ; Reinforcement, Psychology ; Self Administration ; Substance Withdrawal Syndrome/physiopathology ; Time Factors ; }, abstract = {BACKGROUND: There is a scarcity of behavioral models that will reliably produce ethanol intakes in rodents at levels that induce or maintain dependence. The present experiments were designed to reestablish a model that uses passive intragastric (IG) infusion of ethanol to induce tolerance/dependence/withdrawal before allowing rats to self-infuse ethanol intragastrically.

METHODS: Sprague-Dawley rats were surgically implanted with IG catheters and allowed to recover. During the passive infusion phase (3-6 days), rats in the experimental group were passively infused with 10% (v/v) ethanol (3.3-12.2 g/kg/d). Rats in the control group were not infused. During the self-infusion phase (5-6 days), all rats had access to 2 flavored solutions. Licks on 1 solution were paired with ethanol infusions (20%, v/v) whereas licks on the other solution were unpaired. Experiments differed in the specific passive infusion parameters and in the ethanol intake limit during self-infusion.

RESULTS: Rats in the experimental groups self-infused more ethanol per day (means of 4-7 g/kg/d) than did rats in the control group (means of 0-2.6 g/kg/d). Across all 3 studies, individual total daily intakes exceeded 5 g/kg on 35% of the self-infusion days in ethanol-preexposed rats compared with <1% of the self-infusion days in the control rats. Ethanol-exposed rats also infused a substantially higher percentage (42%) of their total ethanol intake in relatively large bouts (>1.5 g/kg) compared with control rats (<10%). The addition of a daily 6-hour ethanol-free period during the passive infusion phase (in Experiments 2 and 3) led to higher ethanol intakes than in Experiment 1. Results of a control experiment showed that differences between experimental and control groups in Experiments 1 to 3 were a result of ethanol experience and not a general effect of differential infusion experience.

CONCLUSIONS: Relatively short periods of passive IG infusion of ethanol induced levels of ethanol self-infusion in genetically heterogeneous rats that were comparable with drinking intakes previously reported in rats selectively bred for ethanol intake/preference. Although the induction of dependence/withdrawal may have played a role in this outcome, an alternative interpretation is that experimental rats self-infused more ethanol because passive exposure produced tolerance to aversive pharmacological effects that would otherwise limit intake of the paired flavor because of development of conditioned taste aversion. The current findings provide a strong basis for future work designed to identify parametric determinants of this form of self-administration, its sensitivity to genetic influences, and its neurobiological substrates.}, } @article {pmid16481572, year = {2006}, author = {Sugai, R and Shiga, H and Azami, S and Watanabe, T and Sadamoto, H and Fujito, Y and Lukowiak, K and Ito, E}, title = {Taste discrimination in conditioned taste aversion of the pond snail Lymnaea stagnalis.}, journal = {The Journal of experimental biology}, volume = {209}, number = {Pt 5}, pages = {826-833}, doi = {10.1242/jeb.02069}, pmid = {16481572}, issn = {0022-0949}, mesh = {Animals ; Conditioning, Psychological/*physiology ; Lymnaea/*physiology ; Taste/*physiology ; Time Factors ; }, abstract = {Conditioned taste aversion (CTA) in the pond snail Lymnaea stagnalis has been widely used as a model for gaining an understanding of the molecular and behavioral mechanisms underlying learning and memory. At the behavioral level, however, it is still unclear how taste discrimination and CTA interact. We thus examined how CTA to one taste affected the feeding response induced by another appetitive food stimulus. We first demonstrated that snails have the capacity to recognize sucrose and carrot juice as distinct appetitive stimuli. We then found that snails can become conditioned (i.e. CTA) to avoid one of the stimuli and not the other. These results show that snails can distinguish between appetitive stimuli during CTA, suggesting that taste discrimination is processed upstream of the site where memory consolidation in the snail brain occurs. Moreover, we examined second-order conditioning with two appetitive stimuli and one aversive stimulus. Snails acquired second-order conditioning and were still able to distinguish between the different stimuli. Finally, we repeatedly presented the conditional stimulus alone to the conditioned snails, but this procedure did not extinguish the long-term memory of CTA in the snails. Taken together, our data suggest that CTA causes specific, irreversible and rigid changes from appetitive stimuli to aversive ones in the conditioning procedure.}, } @article {pmid16458940, year = {2006}, author = {Mungarndee, SS and Lundy, RF and Norgren, R}, title = {Central gustatory lesions and learned taste aversions: unconditioned stimuli.}, journal = {Physiology & behavior}, volume = {87}, number = {3}, pages = {542-551}, pmid = {16458940}, issn = {0031-9384}, support = {R01 DC000240/DC/NIDCD NIH HHS/United States ; R01 DC005435/DC/NIDCD NIH HHS/United States ; DC 00240/DC/NIDCD NIH HHS/United States ; DC 05435/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Stem/anatomy & histology/physiology ; Conditioning, Operant/drug effects ; Cues ; Cyclophosphamide/pharmacology ; Extinction, Psychological ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/*physiology ; Thalamic Nuclei/anatomy & histology/physiology ; }, abstract = {The efficacy of two different unconditioned stimuli (US) in producing conditioned taste aversion (CTA) was tested in rats after bilateral ibotenic acid (IBO) lesions of the gustatory nucleus of thalamus (TTAx) and the medial and lateral parabrachial nuclei (mPBNx, lPBNx). An initial study determined an equivalent dose for the two USs, LiCl and cyclophosphamide (CY), using non-lesioned rats. Subsequently, using a separate set of lesioned animals and their sham controls (SHAM), injections of CY were paired 3 times with one of two taste stimuli (CSs), 0.1 M NaCl for half the rats in each group, 0.2 M sucrose for the other half. After these conditioning trials, the CS was presented twice more without the US, first in a 1-bottle test, then in a 2-bottle choice with water. The acquisition and test trials had 2 intervening water-only days to assure complete rehydration. Two weeks later, the same rats were tested again for acquisition of a CTA using LiCl as the US and the opposite CS as that used during the CY trials. The SHAM and TTAx groups learned to avoid consuming the taste associated with either CY or LiCl treatment. The two PBNx groups failed to learn an aversion regardless of the US.}, } @article {pmid16457968, year = {2006}, author = {Bills, CH and Dopheide, M and Pineño, O and Schachtman, TR}, title = {Effects of an extinguished CS on competition with another CS.}, journal = {Behavioural processes}, volume = {72}, number = {1}, pages = {14-22}, doi = {10.1016/j.beproc.2005.11.009}, pmid = {16457968}, issn = {0376-6357}, support = {R01 MH59039-01/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Association Learning ; *Attention ; *Avoidance Learning ; *Conditioning, Classical ; *Extinction, Psychological ; Female ; Lithium Chloride/toxicity ; Male ; Mental Recall ; Rats ; Rats, Sprague-Dawley ; Reinforcement Schedule ; *Taste ; }, abstract = {Three experiments were conducted using a conditioned taste aversion procedure with rats to examine the effect of nonreinforced presentations of a conditioned stimulus (CS) on its ability to compete with a target stimulus for manifest conditioned responding. Two CSs (A and B) were presented in a serial compound and then paired with the unconditioned stimulus. CS A was first paired with the US and then presented without the US (i.e., extinction) prior to reinforced presentation of the AB compound. Experiment 1 showed that A was poor at competing with B for conditioned responding when given conditioning and extinction prior to reinforcement of AB relative to a group that received both A and B for the first time during compound conditioning. That is, an extinguished A stimulus allowed greater manifest acquisition to B. Experiment 2 found that extinction treatment produced a poor CR to the pretrained and extinguished CS itself following compound conditioning. Experiment 3 found that interposing a retention interval after extinction of A and prior to compound conditioning enhanced A's ability to compete with B. The results of these experiments are discussed with regard to different theories of extinction and associative competition.}, } @article {pmid16452653, year = {2006}, author = {Ramírez-Lugo, L and Zavala-Vega, S and Bermúdez-Rattoni, F}, title = {NMDA and muscarinic receptors of the nucleus accumbens have differential effects on taste memory formation.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {13}, number = {1}, pages = {45-51}, pmid = {16452653}, issn = {1072-0502}, mesh = {2-Amino-5-phosphonovalerate/administration & dosage ; Animals ; Association Learning/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Excitatory Amino Acid Antagonists/administration & dosage ; Male ; Memory/drug effects/physiology ; Microinjections ; Muscarinic Antagonists/administration & dosage ; Neurons/drug effects/physiology ; Nucleus Accumbens/cytology/drug effects/*physiology ; Rats ; Rats, Wistar ; Receptors, Muscarinic/drug effects/*physiology ; Receptors, N-Methyl-D-Aspartate/drug effects/*physiology ; Scopolamine/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {Animals recognize a taste cue as aversive when it has been associated with post-ingestive malaise; this associative learning is known as conditioned taste aversion (CTA). When an animal consumes a new taste and no negative consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent presentations (attenuation of neophobia, AN). It has been shown that the nucleus accumbens (NAcc) has an important role in taste learning. To elucidate the involvement of N-methyl-D-aspartate (NMDA) and muscarinic receptors in the NAcc during safe and aversive taste memory formation, we administrated bilateral infusions of DL-2-amino-5-phosphonopentanoic acid (APV) or scopolamine in the NAcc shell or core respectively. Our results showed that pre-training injections of APV in the NAcc core and shell disrupted aversive but not safe taste memory formation, whereas pre-training injections of scopolamine in the NAcc shell, but not core, disrupted both CTA and AN. These results suggest that muscarinic receptors seem to be necessary for processing taste stimuli for either safe or aversive taste memory, whereas NMDA receptors are only involved in the aversive taste memory trace formation.}, } @article {pmid16448678, year = {2006}, author = {McCormack, DN and Clyburn, VL and Pittman, DW}, title = {Detection of free fatty acids following a conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {87}, number = {3}, pages = {582-594}, doi = {10.1016/j.physbeh.2005.12.004}, pmid = {16448678}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Central Nervous System Depressants/pharmacology ; Cues ; Ethanol/pharmacology ; Fatty Acids, Nonesterified/*pharmacology ; Generalization, Stimulus ; Linoleic Acid/pharmacology ; Male ; Oleic Acid/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Stimulation, Chemical ; Taste/drug effects/*physiology ; Taste Threshold/drug effects ; }, abstract = {A gustatory transduction mechanism for free fatty acids (FFAs) has been described in isolated rat taste receptor cells; however, the ability of behaving rats to detect FFAs has not been characterized. Through conditioned taste aversion (CTA) methodology, this study defines the ability of rats to detect and avoid the two principal FFA components of corn oil, linoleic and oleic acid. Following taste aversion conditioning, rats avoided both linoleic and oleic acid at greater than or equal to 66 muM and failed to avoid either 44 muM linoleic or oleic acid. Rats demonstrated generalized avoidances between 88 muM linoleic and oleic acid irrespective of presenting the FFAs as either unesterified acids dissolved in 5 mM ethanol or aqueous sodium salts, sodium linoleate and sodium oleate. Following a CTA to linoleic acid, rats did not show generalized avoidance of NaCl or ethanol, two potentially concomitant tastants in the oral cavity. A CTA to linoleic or oleic acid did produce a generalized avoidance to the other FFA. These results support the ability of rats to detect linoleic and oleic acid (>44 muM) and suggest that the two FFAs share common orosensory properties. Furthermore, it is unlikely that the detection of the FFAs is due to an enhancement of other concomitant tastants such as saliva or the delivery solution.}, } @article {pmid16420166, year = {2005}, author = {Barot, SK and Bernstein, IL}, title = {Polycose taste pre-exposure fails to influence behavioral and neural indices of taste novelty.}, journal = {Behavioral neuroscience}, volume = {119}, number = {6}, pages = {1640-1647}, pmid = {16420166}, issn = {0735-7044}, support = {R01 NS037040/NS/NINDS NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; R01 NS037040-05/NS/NINDS NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Antimanic Agents/pharmacology ; Behavior, Animal/*drug effects/physiology ; Brain/cytology ; *Brain Mapping ; Conditioning, Psychological ; Drinking Behavior/drug effects ; Exploratory Behavior/*drug effects/physiology ; Food Preferences/drug effects/physiology ; Gene Expression Regulation/drug effects ; Glucans/*pharmacology ; Immunohistochemistry/methods ; Lithium Chloride/pharmacology ; Male ; Neurons ; Oncogene Proteins v-fos/metabolism ; Rats ; Rats, Long-Evans ; Sweetening Agents/*pharmacology ; Taste/*drug effects/physiology ; }, abstract = {Taste novelty can strongly modulate the speed and efficacy of taste aversion learning. Novel sweet tastes enhance c-Fos-like immunoreactivity (FLI) in the central amygdala and insular cortex. The present studies examined whether this neural correlate of novelty extends to different taste types by measuring FLI signals after exposure to novel and familiar polysaccharide (Polycose) and salt (NaCl) tastes. Novel Polycose not only failed to elevate FLI expression in central amygdala and insular cortex, but also failed to induce stronger taste aversion learning than familiar Polycose. Novel NaCl, on the other hand, showed patterns of FLI activation and aversion learning similar to that of novel sweet tastes. Possible reasons for the resistance of Polycose to typical pre-exposure effects are discussed.}, } @article {pmid16412500, year = {2005}, author = {Pescatore, KA and Glowa, JR and Riley, AL}, title = {Strain differences in the acquisition of nicotine-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {82}, number = {4}, pages = {751-757}, doi = {10.1016/j.pbb.2005.12.002}, pmid = {16412500}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Nicotine/*pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Species Specificity ; Taste/*drug effects ; }, abstract = {Lewis (LEW) and Fischer (F344) rat strains differ on a variety of physiological and behavioral endpoints, including reactivity to drugs of abuse. Although they differ in drug reactivity, such assessments are generally limited to morphine and cocaine. To determine if these differences generalize to other drugs, the present study examined these strains for their reactivity to the affective properties of nicotine, specifically their sensitivity to nicotine in the conditioned taste aversion preparation. For four or five conditioning cycles given every other day, rats from both strains were allowed access to saccharin and injected with nicotine (0.1, 0.4, 0.8 mg/kg) or vehicle. On intervening days, all rats were given access to water and injected with vehicle. Under this one-bottle training and testing procedure, neither strain displayed aversions at the lowest dose of nicotine (0.1 mg/kg). Aversions were evident for both strains at 0.4 and 0.8 mg/kg, although the F344 rats acquired the aversions at 0.4 mg/kg faster and displayed a significantly greater aversion at 0.8 mg/kg than subjects from the LEW strain. For both strains, aversions were evident at all doses (and in a dose-dependent manner) when subjects were given access to saccharin and water in a two-bottle test. There were, however, no strain differences on this test. Differences between the two strains in their acquisition of nicotine-induced taste aversions were discussed in the context of aversion assessments with other compounds as well as in relation to differences in the self-administration of nicotine in the two strains.}, } @article {pmid16403525, year = {2006}, author = {Hatakeyama, D and Sadamoto, H and Watanabe, T and Wagatsuma, A and Kobayashi, S and Fujito, Y and Yamashita, M and Sakakibara, M and Kemenes, G and Ito, E}, title = {Requirement of new protein synthesis of a transcription factor for memory consolidation: paradoxical changes in mRNA and protein levels of C/EBP.}, journal = {Journal of molecular biology}, volume = {356}, number = {3}, pages = {569-577}, doi = {10.1016/j.jmb.2005.12.009}, pmid = {16403525}, issn = {0022-2836}, support = {G0400551/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Aplysia ; Avoidance Learning/*physiology ; CCAAT-Enhancer-Binding Proteins/*biosynthesis/*genetics/metabolism ; Conditioning, Psychological/physiology ; Feeding Behavior/physiology ; Lymnaea ; Memory/*physiology ; Molecular Sequence Data ; Nerve Net/physiology ; Phosphorylation ; RNA, Messenger/*biosynthesis/metabolism ; Sequence Homology, Amino Acid ; Species Specificity ; Taste/genetics/physiology ; }, abstract = {Some specific transcription factors are essential for memory consolidation across species. However, it is still unclear whether only the activation of constitutively expressed forms of these conserved transcription factors is involved in memory consolidation or their de novo synthesis also occurs after learning. This question has remained unanswered partly because of the lack of an efficient method for the determination of copy numbers of particular mRNAs in single neurons, which allows the detection of new transcription at the cellular level. Here we applied a newly developed protocol of single-cell quantitative real-time polymerase chain reaction (qRT-PCR) to single neurons playing an important role in associative learning. Specifically, we examined the changes in the mRNA and protein expression levels of a highly conserved transcription factor, CCAAT/enhancer binding protein (C/EBP), in the paired B2 motoneurons of the pond snail Lymnaea stagnalis. These buccal neurons are involved in the motor control of feeding behavior, with a potentially important role in conditioned taste aversion (CTA). Single-cell qRT-PCR revealed a significant decrease in LymC/EBP mRNA copy numbers in the B2 motoneurons during memory consolidation after CTA training. By contrast, isoelectric focusing and immunoblotting of extracts of the buccal ganglia showed that translation and phosphorylation levels of LymC/EBP significantly increased during memory consolidation. The C/EBP-like immunoreactivity in the B2 motoneurons, which are the major immunopositive component in the buccal ganglia, also significantly increased during memory consolidation, suggesting that the main source of increase in the level of protein in the buccal ganglia are the B2 motoneurons. Thus, early memory consolidation after CTA learning in L.stagnalis involves both the rapid synthesis and phosphorylation of LymC/EBP as well as the rapid breakdown of LymC/EBP mRNA in the neural network controlling feeding, suggesting that all of these processes play a role in the function of C/EBP in memory consolidation.}, } @article {pmid16364259, year = {2006}, author = {Castillo, DV and Figueroa-Guzmán, Y and Escobar, ML}, title = {Brain-derived neurotrophic factor enhances conditioned taste aversion retention.}, journal = {Brain research}, volume = {1067}, number = {1}, pages = {250-255}, doi = {10.1016/j.brainres.2005.10.085}, pmid = {16364259}, issn = {0006-8993}, mesh = {Animals ; Brain-Derived Neurotrophic Factor/administration & dosage/pharmacokinetics/*pharmacology ; Conditioning, Psychological ; Drinking Behavior/drug effects/physiology ; Infusions, Parenteral ; Memory/drug effects/*physiology ; Models, Animal ; Rats ; Synapses/drug effects/physiology ; Taste/drug effects/*physiology ; Tissue Distribution ; }, abstract = {Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the IC, previous to CTA training, enhances the retention of this task. Recently, we found that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the Bla-IC projection of adult rats in vivo. In this work, we present experimental data showing that intracortical microinfusion of BDNF previous to CTA training enhances the retention of this task. These findings support the concept that BDNF may contribute to memory-related functions performed by a neocortical area, playing a critical role in long-term synaptic plasticity.}, } @article {pmid16360711, year = {2006}, author = {Jambor de Sousa, UL and Arnold, M and Langhans, W and Geary, N and Leonhardt, M}, title = {Caprylic acid infusion acts in the liver to decrease food intake in rats.}, journal = {Physiology & behavior}, volume = {87}, number = {2}, pages = {388-395}, doi = {10.1016/j.physbeh.2005.11.004}, pmid = {16360711}, issn = {0031-9384}, support = {DK 060735/DK/NIDDK NIH HHS/United States ; }, mesh = {3-Hydroxybutyric Acid/blood ; Animals ; *Appetite Depressants ; Caprylates/administration & dosage/*pharmacology ; Catheterization, Peripheral ; Corticosterone/blood ; Data Interpretation, Statistical ; Eating/*drug effects ; Fatty Acids/metabolism ; Gastric Emptying/drug effects ; Inflammation/blood/metabolism ; Infusions, Intravenous ; Interleukin-6/blood ; Jugular Veins ; Ketones/metabolism ; Liver/*drug effects ; Male ; Oxidation-Reduction ; Portal Vein ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological/metabolism ; Taste/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Venae Cavae ; }, abstract = {Hepatic portal vein (HPV) infusion of the medium chain fatty acid caprylic acid (CA; 2.3 mg/min, 40 microl/min) for 90 min beginning at dark onset in 18-h food-deprived male rats reduced the size of the first nocturnal meal about 40% (P < 0.01) and reduced 24-h food intake by about 15% (P < 0.001). Identical infusions into the vena cava affected neither initial meal size nor food intake. HPV CA infusion attenuated the postprandial decreases in plasma free fatty acids (P < 0.01) and beta-hydroxybutyrate (P < 0.01). HPV CA infusions did not significantly reduce nocturnal saccharine intake in a two-bottle conditioned taste aversion test, and there was no association between the saccharine intake on the test day and the feeding-inhibitory effect of CA on the conditioning day. HPV CA infusion did not affect plasma concentrations of corticosterone or of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. HPV CA infusion did not increase plasma concentration of the liver enzyme alanine aminotransferase, but did increase plasma concentration of gamma-glutamyl transferase, although not into the pathophysiological range. These data indicate that CA acts in the liver to produce a signal that inhibits feeding and that this inhibitory effect may be related to increases in hepatic fatty acid oxidation rather than be the result of aversion or toxicity.}, } @article {pmid16351881, year = {2002}, author = {Healy, SD and Jones, CM}, title = {Animal learning and memory: an integration of cognition and ecology.}, journal = {Zoology (Jena, Germany)}, volume = {105}, number = {4}, pages = {321-327}, doi = {10.1078/0944-2006-00071}, pmid = {16351881}, issn = {0944-2006}, abstract = {A wonderfully lucid framework for the ways to understand animal behaviour is that represented by the four 'whys' proposed by Tinbergen (1963). For much of the past three decades, however, these four avenues have been pursued more or less in parallel. Functional questions, for example, have been addressed by behavioural ecologists, mechanistic questions by psychologists and ethologists, ontogenetic questions by developmental biologists and neuroscientists and phylogenetic questions by evolutionary biologists. More recently, the value of integration between these differing views has become apparent. In this brief review, we concentrate especially on current attempts to integrate mechanistic and functional approaches. Most of our understanding of learning and memory in animals comes from the psychological literature, which tends to use only rats or pigeons, and more occasionally primates, as subjects. The underlying psychological assumption is of general processes that are similar across species and contexts rather than a range of specific abilities. However, this does not seem to be entirely true as several learned behaviours have been described that are specific to particular species or contexts. The first conspicuous exception to the generalist assumption was the demonstration of long delay taste aversion learning in rats (Garcia et al., 1955), in which it was shown that a stimulus need not be temporally contiguous with a response for the animal to make an association between food and illness. Subsequently, a number of other examples, such as imprinting and song learning in birds (e.g., Bolhuis and Honey, 1998; Catchpole and Slater, 1995; Horn, 1998), have been thoroughly researched. Even in these cases, however, it has been typical for only a few species to be studied (domestic chicks provide the 'model' imprinting species and canaries and zebra finches the song learning 'models'). As a result, a great deal is understood about the neural underpinnings and development of the behaviour, but substantially less is understood about interspecific variation and whether variation in behaviour is correlated with variation in neural processing (see review by Tramontin and Brenowitz, 2000 but see ten Cate and Vos, 1999).}, } @article {pmid16343780, year = {2006}, author = {Pothuizen, HH and Jongen-Rêlo, AL and Feldon, J and Yee, BK}, title = {Latent inhibition of conditioned taste aversion is not disrupted, but can be enhanced, by selective nucleus accumbens shell lesions in rats.}, journal = {Neuroscience}, volume = {137}, number = {4}, pages = {1119-1130}, doi = {10.1016/j.neuroscience.2005.10.032}, pmid = {16343780}, issn = {0306-4522}, mesh = {Animals ; Brain Mapping ; *Conditioning, Psychological ; Nucleus Accumbens/anatomy & histology/pathology/*physiology ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {Latent inhibition is a form of negative priming in which repeated non-reinforced pre-exposures to a stimulus retard subsequent learning about the predictive significance of that stimulus. The nucleus accumbens shell and the anatomical projection it receives from the hippocampal formation have been attributed a pivotal role in the control or regulation of latent inhibition expression. A number of studies in rats have demonstrated the efficacy of selective shell lesions to disrupt latent inhibition in different associative learning paradigms, including conditioned active avoidance and conditioned emotional response. Here, we extended the test to the conditioned taste aversion paradigm, in which the effect of direct hippocampal damage on latent inhibition remains controversial. We demonstrated the expected effect of selective shell lesions on latent inhibition of conditioned emotional response and of conditioned active avoidance, before evaluating in a separate cohort of rats the effect of comparable selective lesions on latent inhibition of conditioned taste aversion: a null effect of the lesions was first obtained using parameters known to be sensitive to amphetamine treatment, then an enhancement of latent inhibition was revealed with a modified conditioned taste aversion procedure. Our results show that depending on the associative learning paradigm chosen, shell lesions can disrupt or enhance the expression of latent inhibition; and the pattern is reminiscent of that seen following hippocampal damage.}, } @article {pmid16342120, year = {2006}, author = {Chen, AP and Ohno, M and Giese, KP and Kühn, R and Chen, RL and Silva, AJ}, title = {Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory.}, journal = {Journal of neuroscience research}, volume = {83}, number = {1}, pages = {28-38}, doi = {10.1002/jnr.20703}, pmid = {16342120}, issn = {0360-4012}, support = {R01NS38480/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Behavior, Animal/physiology ; Blotting, Western ; Discrimination, Psychological/physiology ; Down-Regulation/physiology ; Electrophysiology ; Fear/physiology ; Hippocampus/*physiology ; Immunohistochemistry ; Learning/*physiology ; Long-Term Potentiation/*physiology ; Maze Learning/physiology ; Memory/*physiology ; Mice ; Mice, Knockout ; Proto-Oncogene Proteins B-raf/*genetics/*physiology ; Taste/physiology ; }, abstract = {Raf kinases are downstream effectors of Ras and upstream activators of the MEK-ERK cascade. Ras and MEK-ERK signaling play roles in learning and memory (L&M) and neural plasticity, but the roles of Raf kinases in L&M and plasticity are unclear. Among Raf isoforms, B-raf is preferentially expressed in the brain. To determine whether B-raf has a role in synaptic plasticity and L&M, we used the Cre-LoxP gene targeting system to derive forebrain excitatory neuron B-raf knockout mice. This conditional knockout resulted in deficits in ERK activation and hippocampal long-term potentiation (LTP) and impairments in hippocampus-dependent L&M, including spatial learning and contextual discrimination. Despite the widespread expression of B-raf, this mutation did not disrupt other forms of L&M, such as cued fear conditioning and conditioned taste aversion. Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M.}, } @article {pmid16337262, year = {2005}, author = {Freeman, KB and Rice, KC and Riley, AL}, title = {Assessment of monoamine transporter inhibition in the mediation of cocaine-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {82}, number = {3}, pages = {583-589}, doi = {10.1016/j.pbb.2005.10.014}, pmid = {16337262}, issn = {0091-3057}, mesh = {Analysis of Variance ; Animals ; *Avoidance Learning ; Cocaine/*pharmacology ; *Conditioning, Operant ; Male ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {Although the mechanisms of cocaine reward have been well characterized, the pharmacological basis of cocaine's aversive effects is less understood. Using the conditioned taste aversion (CTA) preparation, the present study examined the role of monoamine uptake inhibition in cocaine's aversive effects by comparing cocaine to three reuptake inhibitors with relative specificity for the transporters of dopamine (DAT; GBR 12909), norepinephrine (NET; desipramine) and serotonin (SERT; clomipramine). Specifically, 104 male Sprague-Dawley rats were given 20-min access to a novel saccharin solution followed immediately by a subcutaneous injection of cocaine, GBR 12909, desipramine, clomipramine (each at 18, 32 or 50 mg/kg; 12 groups) or drug vehicle (equivolume to the highest cocaine dose). Over trials, cocaine and desipramine each dose-dependently suppressed saccharin consumption and did so in an equivalent manner when matched by dose. However, both GBR 12909 and clomipramine conditioned weaker aversions than cocaine at the two lowest doses (18 and 32 mg/kg). At the highest dose (50 mg/kg), GBR 12909 produced equivalent suppression of saccharin consumption to cocaine while clomipramine's conditioned suppression remained relatively weak at this dose. These results suggest that cocaine's adrenergic actions resulting from NET inhibition may play a more significant role in the mediation of its aversive effects than its actions at DAT and SERT.}, } @article {pmid16322360, year = {2005}, author = {Stone, ME and Grimes, BS and Katz, DB}, title = {Hippocampal inactivation enhances taste learning.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {12}, number = {6}, pages = {579-586}, pmid = {16322360}, issn = {1072-0502}, support = {R01 DC007703/DC/NIDCD NIH HHS/United States ; R03 DC005312/DC/NIDCD NIH HHS/United States ; 5R03-DC005312/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Female ; GABA Agonists/administration & dosage ; Hippocampus/drug effects/*physiology ; Maze Learning/drug effects/physiology ; Memory/drug effects/*physiology ; Mental Processes/drug effects/*physiology ; Microinjections ; Models, Neurological ; Muscimol/administration & dosage ; Rats ; Rats, Long-Evans ; Taste/drug effects/*physiology ; }, abstract = {Learning tasks are typically thought to be either hippocampal-dependent (impaired by hippocampal lesions) or hippocampal-independent (indifferent to hippocampal lesions). Here, we show that conditioned taste aversion (CTA) learning fits into neither of these categories. Rats were trained to avoid two taste stimuli, one novel and one familiar. Muscimol infused through surgically implanted intracranial cannulae temporarily inactivated the dorsal hippocampus during familiarization, subsequent CTA training, or both. As shown previously, hippocampal inactivation during familiarization enhanced the effect of that familiarization on learning (i.e., hippocampal inactivation enhanced latent inhibition of CTA); more novel and surprising, however, was the finding that hippocampal inactivation during training sessions strongly enhanced CTA learning itself. These phenomena were not caused by specific aspects of our infusion technique--muscimol infusions into the hippocampus during familiarization sessions did not cause CTAs, muscimol infusions into gustatory cortex caused the expected attenuation of CTA, and hippocampal inactivation caused the expected attenuation of spatial learning. Thus, we suggest that hippocampal memory processes interfere with the specific learning mechanisms underlying CTA, and more generally that multiple memory systems do not operate independently.}, } @article {pmid16321549, year = {2006}, author = {Anderson, MJ and Hinderliter, CF and Misanin, JR}, title = {The effects of chronic water deprivation on metabolic rate and long-trace taste-aversion conditioning in rats.}, journal = {Neurobiology of learning and memory}, volume = {85}, number = {3}, pages = {199-205}, doi = {10.1016/j.nlm.2005.10.004}, pmid = {16321549}, issn = {1074-7427}, mesh = {Animals ; Basal Metabolism/*physiology ; Behavior, Animal/physiology ; Chronic Disease ; *Conditioning, Classical ; Dehydration/*metabolism ; Female ; Male ; Oxygen Consumption ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {The effect of chronic water deprivation on metabolic rate and long-trace taste-aversion conditioning was examined in Wistar-derived rats. Subjects were either maintained on a water deprivation regimen or allowed free access to water for a seven-week period prior to conditioning. At conditioning, rats were presented a saccharin CS followed 0-, 45-, 90-, or 180-min later by an i.p. injection of LiCl. Additionally, pseudo-conditioned groups were presented the CS followed immediately by an injection of physiological saline. Heightened oxygen consumption in deprived subjects suggested that chronic water deprivation increased metabolic rate. While no differences in the amount of saccharin intake were observed at conditioning, percent preference for saccharin scores during a 24-h two-bottle water/saccharin test revealed that non-chronically deprived rats supported conditioning at longer CS-US intervals than did chronically water-deprived rats. Results are interpreted in terms of a time-contraction effect stemming from an alteration of an internal metabolic count-down timer.}, } @article {pmid16307602, year = {2005}, author = {Ferreira, G and Miranda, MI and De la Cruz, V and Rodríguez-Ortiz, CJ and Bermúdez-Rattoni, F}, title = {Basolateral amygdala glutamatergic activation enhances taste aversion through NMDA receptor activation in the insular cortex.}, journal = {The European journal of neuroscience}, volume = {22}, number = {10}, pages = {2596-2604}, doi = {10.1111/j.1460-9568.2005.04440.x}, pmid = {16307602}, issn = {0953-816X}, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Amygdala/*physiology ; Animals ; Avoidance Learning/*drug effects ; Cerebral Cortex/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Functional Laterality/physiology ; Glutamates/administration & dosage/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Memory/physiology ; Microinjections ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*agonists ; Taste/*drug effects ; }, abstract = {In conditioned taste aversion (CTA), a subject learns to associate a novel taste with visceral malaise. Brainstem, limbic and neocortical structures have been implicated in CTA memory formation. Nevertheless, the role of interactions between forebrain structures during these processes is still unknown. The present experiment was aimed at investigating the possible interaction between the basolateral nucleus of the amygdala (BLA) and the insular cortex (IC) during CTA memory formation. Injection of a low dose of lithium chloride (30 mg/kg, i.p.) 30 min after novel taste consumption (saccharin 0.1%) induces a weak CTA. Unilateral BLA injection of glutamate (2 microg in 0.5 microL) just before low lithium induces a stronger CTA. Unilateral injection of an N-methyl-d-aspartate (NMDA) receptor antagonist (AP5, 5 microg in 0.5 microL) in IC has no effect. However, AP5 treatment in IC at the same time or 1 h after the ipsilateral BLA injection reverses the glutamate-induced CTA enhancement. Injection of AP5 in IC 3 h after BLA injection does not interfere with the glutamate effect. Moreover, the CTA-enhancing effect of glutamate was also blocked by contralateral IC injection of AP5 at the same time. These results provide strong evidence that NMDA receptor activation in the IC is essential to enable CTA enhancement induced by glutamate infusion in the BLA during a limited time period that extends to 1 but not to 3 hours. These findings indicate that BLA-IC interactions regulate the strength of CTA. The bilateral nature of these amygdalo-cortical interactions is discussed.}, } @article {pmid16273405, year = {2006}, author = {Vales, K and Zach, P and Bielavska, E}, title = {Metabotropic glutamate receptor antagonists but not NMDA antagonists affect conditioned taste aversion acquisition in the parabrachial nucleus of rats.}, journal = {Experimental brain research}, volume = {169}, number = {1}, pages = {50-57}, pmid = {16273405}, issn = {0014-4819}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal/drug effects ; Brain Stem/*drug effects ; Conditioning, Classical/*drug effects/physiology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Amino Acid Antagonists/*pharmacology ; Lithium Chloride/adverse effects ; Male ; Rats ; Saccharin/pharmacology ; Taste/*drug effects/physiology ; }, abstract = {The effect of glutamate receptor antagonists on conditioned taste aversion (CTA) was studied in rats. The association of the short-term memory of a gustatory conditioned stimulus (CS) with visceral malaise (unconditioned stimulus, US) in the CTA paradigm takes place in the parabrachial nuclei (PBN) of the brainstem. The first direct evidence of participation of glutamatergic neurotransmission in the PBN during CTA demonstrated that the extracellular level of glutamate rises during saccharin drinking (Bielavska et al. in Brain Res 887:413-417, 2000). Our results show an effect of microdialysis administration of selective GluR antagonists into the PBN on the formation of CTA engram. We used four glutamate receptor (GluR) antagonists of different types (D-AP5, MK-801 as antagonists of ionotropic GluR and L-AP3, MSPG as antagonists of metabotropic GluR). The disruptive effect of MK-801 on CTA formation in the PBN is concentration-dependent, with the greatest inhibition under the higher concentrations eliciting significant disruption. The application of D-AP5 (0.1, 1, 5 mM) did not elicit a statistically significant blockade of CTA acquisition. This indicates that the association of the US-CS in the PBN is not dependent on NMDA receptors. On the contrary, application of L-AP3 (0.1, 1, 5 mM) blocked the CS-US association.}, } @article {pmid16258524, year = {2006}, author = {Chambers, AP and Koopmans, HS and Pittman, QJ and Sharkey, KA}, title = {AM 251 produces sustained reductions in food intake and body weight that are resistant to tolerance and conditioned taste aversion.}, journal = {British journal of pharmacology}, volume = {147}, number = {1}, pages = {109-116}, pmid = {16258524}, issn = {0007-1188}, support = {R01 DK059359/DK/NIDDK NIH HHS/United States ; DK 59359/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Body Weight/*drug effects ; Central Nervous System/drug effects ; Drug Tolerance ; Eating/*drug effects ; Male ; Piperidines/*pharmacology ; Pyrazoles/*pharmacology ; Rats ; Rats, Inbred Lew ; Receptor, Cannabinoid, CB1/*antagonists & inhibitors ; Taste ; }, abstract = {The cannabinoid 1 (CB(1)) receptor has been implicated in the regulation of food intake. Here, we examine the effect of the CB(1) receptor antagonist AM 251 on food intake and body weight over a prolonged period. Further, we examine whether AM 251 produces conditioned taste aversion (CTA) and if sustained antagonism at central receptors contributes to its anorectic effect. The effect of AM 251 of food intake and body weight was examined in daily (1 mg kg(-1)) and 5-day (5 mg kg(-1)) dosing schedules. Matching reductions in food intake and body weight were observed in both paradigms. A single administration of AM 251 (5 mg kg(-1)) significantly reduced food intake for 4 days. Tolerance to the anorectic effects of AM 251 did not develop in either dosing strategy. Active avoidance of AM 251 (3; 5 mg kg(-1), i.p.) was examined using a CTA assay. Rats showed no evidence of CTA associated with AM 251. We investigated the sustained effect of AM 251 (5 mg kg(-1), i.p.) on CB(1) receptors in the hypothalamus using Delta(9)-tetrahydrocannabinol (8 mg kg(-1), i.p.) induced hypothermia. AM 251 initially blocked hypothermia, but this effect was not seen 2 or 4 days later. The results demonstrate that smaller, or infrequent, administrations of AM 251 can produce sustained reductions in food intake and body weight in rat. Reductions in food intake were sustained longer than AM 251 antagonized the effects of a CB(1) receptor agonist in the hypothalamus, and occurred independently of CTA.}, } @article {pmid16253440, year = {2006}, author = {Misanin, JR and Kaufhold, SE and Paul, RL and Hinderliter, CF and Anderson, MJ}, title = {A time contraction effect of acute tail-pinch stress on the associative learning of rats.}, journal = {Behavioural processes}, volume = {71}, number = {1}, pages = {16-20}, doi = {10.1016/j.beproc.2005.09.001}, pmid = {16253440}, issn = {0376-6357}, mesh = {Animals ; Association Learning/*physiology ; Behavior, Animal/physiology ; Conditioning, Classical/physiology ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Stress, Psychological/*psychology ; Tail/*physiology ; Time Factors ; }, abstract = {The effect of tail-pinch stress interpolated between the saccharin conditioned stimulus (CS) and the illness-inducing unconditioned stimulus (US) during long-trace taste-aversion conditioning was examined in young- and old adult rats with a two-cylinder (saccharin versus water) test. A 2 x 2 x 4 factorial ANOVA was performed on percent-preference-for-saccharin data, with age (young, old), stress condition (stressed, non-stressed), and CS-US interval (22.5-, 45-, 90-, and 180-min) being the factors under consideration. The ANOVA yielded only significant main effects of stress condition and CS-US interval. These findings indicate that stress weakens the CS-US association as evidenced by a higher percent preference for saccharin in the stressed rats than in non-stressed rats at all CS-US intervals. A comparison of the stressed and non-stressed conditioned rats with pseudo-conditioned controls showed that the non-stressed rats formed strong aversions up to the 45-min CS-US interval whereas the stressed rats showed no conditioning beyond the 22.5 min CS-US interval, indicating that stress decreases the effective CS-US interval. Results were interpreted in terms of time-contraction and an internal biological countdown timer hypothesized to govern processes involved in associative learning over long delays.}, } @article {pmid16242859, year = {2006}, author = {Sanjuan, Mdel C and Alonso, G and Nelson, JB}, title = {The contribution of latent inhibition to reduced generalization after pre-exposure to the test stimulus.}, journal = {Behavioural processes}, volume = {71}, number = {1}, pages = {21-28}, doi = {10.1016/j.beproc.2005.09.002}, pmid = {16242859}, issn = {0376-6357}, mesh = {Animals ; Behavior, Animal/physiology ; Conditioning, Psychological ; *Generalization, Psychological ; *Inhibition, Psychological ; Male ; Phobic Disorders/psychology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Two experiments assessed the contribution of latent inhibition to the generalization-reducing effects of pre-exposure to the test stimulus using a taste aversion procedure in rats. In both experiments, lithium chloride induced illness was paired with a flavor compound (AX) of either salt or sugar (A or B) and hydrochloric acid (X). Generalization of the resulting aversion to a test compound (BX), was assessed after varying pre-exposure to BX, X, and B. Experiment 1 showed that generalization to BX was less when BX itself had been exposed than equivalent pre-exposure to either B and X separately or to B and a new compound (CX). Experiment 2 showed that levels of generalization varied directly as a function of the amount of pre-exposure to BX. The findings show that latent inhibition alone cannot account for the generalization-reducing effect of pre-exposure to BX.}, } @article {pmid16217732, year = {2006}, author = {Cotterill, JV and Massei, G and Cowan, DP}, title = {Masking the taste of the conditioned taste aversion agent levamisole using an ion-exchange resin, for practical application in wildlife management.}, journal = {Pest management science}, volume = {62}, number = {2}, pages = {120-125}, doi = {10.1002/ps.1129}, pmid = {16217732}, issn = {1526-498X}, mesh = {Animals ; Animals, Wild ; Avoidance Learning ; Cation Exchange Resins ; Conditioning, Classical ; Food Preferences ; *Levamisole/administration & dosage ; Male ; Pest Control ; Rats ; Rats, Wistar ; Resins, Synthetic ; *Taste ; }, abstract = {For a conditioned taste aversion (CTA) agent to be successful in wildlife management applications, the compound must not be detectable by the animal. Levamisole is an effective CTA agent when administered by oral intubation, but it is readily detected by a number of species when mixed directly in food. This paper describes the development of an ion-exchange resin complex (resinate) to mask the taste of levamisole. Two different resins were evaluated, Amberlite IRP-64 and Amberlite IRP-69, and release studies indicated that the resinate formed using IRP-64 resin would be most suitable for use in wildlife management. Although it contained a relatively low loading of levamisole (77 g kg(-1)), the results indicated that the IRP-64 resinate should be stable in the mouth and release the levamisole quickly in the acid environment of the stomach (93% of levamisole was released into 0.1 M HCl in 5 min). In a bioassay using laboratory rats (Rattus norvegicus Berk), we showed that the taste of levamisole was successfully masked in a biscuit bait using the IRP-64 resinate and that a CTA was generated to untreated bait. The use of ion-exchange resins is a new approach in the taste-masking of CTA agents and could be applied to other wildlife management applications.}, } @article {pmid16214208, year = {2005}, author = {Amer, A and Maher, TJ}, title = {Nasal administration of the calcium channel blocker diltiazem decreases food intake and attenuates weight gain in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {82}, number = {2}, pages = {379-387}, doi = {10.1016/j.pbb.2005.09.008}, pmid = {16214208}, issn = {0091-3057}, mesh = {Administration, Intranasal ; Animals ; Avoidance Learning/drug effects ; Calcium Channel Blockers/administration & dosage/*pharmacology ; Depression, Chemical ; Diet ; Diltiazem/administration & dosage/*pharmacology ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Food Deprivation/physiology ; Injections, Intraperitoneal ; Injections, Intraventricular ; Male ; Psychomotor Performance/drug effects ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; Weight Gain/*drug effects ; }, abstract = {Food intake is normally influenced by a multitude of complex endogenous neurochemical systems, in addition to numerous external environmental stimuli, including olfaction. Since most olfactory neurons process odorant exposures through Ca2+-mediated mechanisms via Ca2+ channels, a novel approach at influencing the ingestive behaviors of animals might therefore involve altering olfactory acuity via Ca2+ channel blockade. We tested the ability of a Ca2+ channel blocker, diltiazem, to alter food intake in hyperphagic rats when administered using the intranasal (i.n.), intraperitoneal (i.p.), oral (p.o.) or intracerebroventricular (i.c.v.) routes of administration. Male Sprague Dawley rats, which had been food-deprived for 4 h at the beginning of the dark cycle, were administered different doses of diltiazem (0-8 mg/animal or 0-40 mg/kg) and the amounts of food consumed were measured. While food intake at 1, 2 and 4 h post drug administration was significantly decreased in a dose-dependent manner after i.n. administration, the i.p., p.o., and i.c.v. routes did not affect food intake. In another experiment, rats trained to eat their daily meal during the first 4 h at the onset of the dark cycle and treated daily with i.n. diltiazem (0-8 mg/animal) prior to food introduction exhibited a significantly decreased rate of weight gain in a dose-dependent manner over a 14-day period. Both i.n. and i.p. diltiazem significantly increased the plasma drug concentration at 1 h, however there was no significant difference between these routes of administration. Additional studies failed to demonstrate any detrimental effects of i.n. diltiazem (0-8 mg/animal) on conditioned taste aversion, locomotion or gross neurological/behavioral competence using the rota-rod test. While a local action on the nasal odorant receptors is most likely the site of diltiazem's action, further studies are needed to determine the exact mechanism of action of i.n. diltiazem.}, } @article {pmid16205360, year = {2005}, author = {Sharpe, AL and Coste, SC and Burkhart-Kasch, S and Li, N and Stenzel-Poore, MP and Phillips, TJ}, title = {Mice deficient in corticotropin-releasing factor receptor type 2 exhibit normal ethanol-associated behaviors.}, journal = {Alcoholism, clinical and experimental research}, volume = {29}, number = {9}, pages = {1601-1609}, doi = {10.1097/01.alc.0000179371.46716.5e}, pmid = {16205360}, issn = {0145-6008}, support = {MH065689/MH/NIMH NIH HHS/United States ; AA013331/AA/NIAAA NIH HHS/United States ; AA007468/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; AA010760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*drug effects ; Body Temperature/drug effects ; Conditioning, Psychological/drug effects ; Corticotropin-Releasing Hormone/physiology ; Ethanol/pharmacokinetics/*pharmacology ; Metabolic Clearance Rate ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Corticotropin-Releasing Hormone/deficiency/*physiology ; Reflex/drug effects ; Taste ; }, abstract = {BACKGROUND: Stress is believed to influence alcohol use and relapse in alcoholics. Animal studies suggest an interaction between corticotropin-releasing factor (CRF) and its receptors and the behavioral effects and consumption of alcohol. The objective of these studies was to examine the effect of corticotropin-releasing factor receptor type 2 (CRF2) on ethanol consumption, conditioned taste aversion, sedation, and hypothermia.

METHODS: CRF2-null mutant or knock-out (KO), and wild-type (WT) mice were used to assess consumption of increasing concentrations of ethanol in a two-bottle, 24-hr test and during daily limited-access sessions. Ethanol-induced conditioned taste aversion (CTA), loss of righting reflex (LORR), hypothermia, and ethanol metabolism kinetics were also examined in the CRF2 KO and WT mice.

RESULTS: CRF2 KO mice did not differ from WT mice in sensitivity to ethanol-induced CTA, LORR, hypothermia, or ethanol metabolism kinetics. There was no genotypic difference in ethanol intake or preference in the 24-hr, two-bottle choice procedure, and only modestly increased [corrected] consumption of the 7.5 and 10% ethanol solutions in KO versus WT mice in the limited-access procedure.

CONCLUSIONS: CRF2 deficiency had little effect on several ethanol-associated behaviors in CRF2-null mutant compared with WT mice, suggesting that this receptor does not have a primary role in modulating these behaviors. Evidence of a role for this receptor in neural circuits subserving stress-coping behaviors suggest that future studies should focus on the role of endogenous CRF2 in ethanol-associated behaviors in mice that are stressed or withdrawing from dependence on ethanol.}, } @article {pmid16187827, year = {2005}, author = {Baird, JP and St John, SJ and Nguyen, EA}, title = {Temporal and qualitative dynamics of conditioned taste aversion processing: combined generalization testing and licking microstructure analysis.}, journal = {Behavioral neuroscience}, volume = {119}, number = {4}, pages = {983-1003}, doi = {10.1037/0735-7044.119.4.983}, pmid = {16187827}, issn = {0735-7044}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/physiology ; Conditioning, Psychological/drug effects/*physiology ; Dose-Response Relationship, Drug ; Drinking/drug effects/physiology ; Drinking Behavior/drug effects/*physiology ; Generalization, Psychological/drug effects/*physiology ; Lithium Chloride/administration & dosage ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/administration & dosage ; Sucrose/administration & dosage ; *Taste ; Time Factors ; }, abstract = {The pattern of licking microstructure during various phases of a conditioned taste aversion (CTA) was evaluated. In Experiment 1, rats ingested lithium chloride (LiCl) for 3 trials and were then offered sodium chloride (NaCl) or sucrose on 3 trials. A CTA to LiCl developed and generalized to NaCl but not to sucrose. CTA intake suppression was characterized by reductions in burst size, average ingestion rate, and intraburst lick rate, and increases in brief pauses and burst counts. Compared with previous studies, LiCl licking shifted from a pattern initially matching that for normally accepted NaCl to one matching licking for normally avoided quinine hydrochloride by the end of the 1st acquisition trial. In Experiment 2, a novel paradigm was developed to show that rats expressed CTA generalization within 9 min of their first LiCl access. These results suggest that licking microstructure analysis can be used to assay changes in hedonic evaluation caused by treatments that produce aversive states.}, } @article {pmid16187819, year = {2005}, author = {Metten, P and Crabbe, JC}, title = {Alcohol withdrawal severity in inbred mouse (Mus musculus) strains.}, journal = {Behavioral neuroscience}, volume = {119}, number = {4}, pages = {911-925}, doi = {10.1037/0735-7044.119.4.911}, pmid = {16187819}, issn = {0735-7044}, support = {AA13519/AA/NIAAA NIH HHS/United States ; P50 AA010760/AA/NIAAA NIH HHS/United States ; AA06243/AA/NIAAA NIH HHS/United States ; U01 AA013519/AA/NIAAA NIH HHS/United States ; R01 AA012714/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; AA12714/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Withdrawal Delirium/blood/genetics/*physiopathology ; Alcohol-Induced Disorders/etiology/genetics/*physiopathology ; Analysis of Variance ; Animals ; Central Nervous System Depressants/*toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Ethanol/blood/*toxicity ; Male ; Mice ; Mice, Inbred Strains/*physiology ; Severity of Illness Index ; Species Specificity ; Statistics as Topic ; Time Factors ; }, abstract = {Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 +/- 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal.}, } @article {pmid16187818, year = {2005}, author = {Phillips, TJ and Broadbent, J and Burkhart-Kasch, S and Henderson, C and Wenger, CD and McMullin, C and McKinnon, CS and Cunningham, CL}, title = {Genetic correlational analyses of ethanol reward and aversion phenotypes in short-term selected mouse lines bred for ethanol drinking or ethanol-induced conditioned taste aversion.}, journal = {Behavioral neuroscience}, volume = {119}, number = {4}, pages = {892-910}, doi = {10.1037/0735-7044.119.4.892}, pmid = {16187818}, issn = {0735-7044}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Analysis of Variance ; Animals ; Association Learning/drug effects/physiology ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal ; Central Nervous System Depressants/*administration & dosage ; Conditioning, Classical/drug effects/physiology ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; *Phenotype ; Quinine/administration & dosage ; *Reward ; Saccharin/administration & dosage ; Selection, Genetic ; Sex Factors ; Statistics as Topic ; Sweetening Agents/administration & dosage ; Time Factors ; }, abstract = {Short-term selective breeding created mouse lines divergent for ethanol drinking (high drinking short-term selected line [STDRHI], low drinking [STDRLO]) or ethanol-induced conditioned taste aversion (CTA; high [HTA], low [LTA]). Compared with STDRLO, STDRHI mice consumed more saccharin and less quinine, exhibited greater ethanol-induced conditioned place preference (CPP), and showed reduced ethanol stimulation and sensitization under some conditions; a line difference in ethanol-induced CTA was not consistently found. Compared with LTA, HTA mice consumed less ethanol but were similar in saccharin consumption, sensitivity to ethanol-induced CPP, and ethanol-induced locomotor stimulation and sensitization. These data suggest that ethanol drinking is genetically associated with several reward-and aversion-related traits. The interpretation of ethanol-induced CTA as more genetically distinct must be tempered by the inability to test the CTA lines beyond Selection Generation 2.}, } @article {pmid16176822, year = {2005}, author = {Houpt, TA and Pittman, DW and Riccardi, C and Cassell, JA and Lockwood, DR and Barranco, JM and Kwon, B and Smith, JC}, title = {Behavioral effects on rats of high strength magnetic fields generated by a resistive electromagnet.}, journal = {Physiology & behavior}, volume = {86}, number = {3}, pages = {379-389}, doi = {10.1016/j.physbeh.2005.08.008}, pmid = {16176822}, issn = {0031-9384}, support = {DC 04607/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/radiation effects ; Behavior, Animal/*radiation effects ; Conditioning, Psychological/radiation effects ; Dose-Response Relationship, Radiation ; *Electromagnetic Fields ; Electromagnetic Phenomena/instrumentation/*methods ; Male ; Motor Activity/radiation effects ; Rats ; Rats, Sprague-Dawley ; Taste/radiation effects ; Time Factors ; }, abstract = {It has been reported previously that exposure to static high magnetic fields of 7 T or above in superconducting magnets has behavioral effects on rats. In particular, magnetic field exposure acutely but transiently suppressed rearing and induced walking in tight circles; the direction of circular locomotion was dependent on the rats' orientation within the magnet. Furthermore, when magnet exposure was paired with consumption of a palatable, novel solution, rats acquired a persistent taste aversion. In order to confirm these results under more controlled conditions, we exposed rats to static magnetic fields of 4 to 19.4 T in a 189 mm bore, 20 T resistive magnet. By using a resistive magnet, field strengths could be arbitrary varied from -19.4 to 19.4 T within the same bore. Rearing was suppressed after exposure to 4 T and above; circling was observed after 7 T and above. Conditioned taste aversion was acquired after 14 T and above. The effects of the magnetic fields were dependent on orientation. Exposure to +14 T induced counter-clockwise circling, while exposure to -14 T induced clockwise circling. Exposure with the rostral-caudal axis of the rat perpendicular to the magnetic field produced an attenuated behavioral response compared to exposure with the rostral-caudal axis parallel to the field. These results in a single resistive magnet confirm and extend our earlier findings using multiple superconducting magnets. They demonstrate that the behavioral effects of exposure within large magnets are dependent on the magnetic field, and not on non-magnetic properties of the machinery. Finally, the effects of exposure to 4 T are clinically relevant, as 4 T magnetic fields are commonly used in functional MRI assays.}, } @article {pmid16175568, year = {2005}, author = {Spencer, CM and Jahng, JW and Ryu, V and Houpt, TA}, title = {Lithium-induced gene expression of inducible cyclic adenosine monophosphate early repressor in the rat adrenal gland.}, journal = {Journal of neuroscience research}, volume = {82}, number = {2}, pages = {273-282}, doi = {10.1002/jnr.20617}, pmid = {16175568}, issn = {0360-4012}, support = {CD-00044/CD/ODCDC CDC HHS/United States ; CD-03198/CD/ODCDC CDC HHS/United States ; }, mesh = {Adrenal Cortex/*metabolism ; Animals ; Antimanic Agents/pharmacology ; Biomarkers ; Brain/*drug effects/metabolism ; Corticosterone/metabolism ; Cyclic AMP/metabolism ; Cyclic AMP Response Element Modulator/*genetics ; Dexamethasone/pharmacology ; Dose-Response Relationship, Drug ; Gene Expression Regulation/drug effects/physiology ; Genes, Immediate-Early/genetics ; Hypothalamo-Hypophyseal System/*drug effects/metabolism ; Lithium Chloride/*pharmacology ; Male ; Pituitary-Adrenal System/*drug effects/metabolism ; Proto-Oncogene Proteins c-fos/genetics ; RNA, Messenger/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Up-Regulation/drug effects/physiology ; }, abstract = {Lithium has acute and chronic effects on the hypothalamic-pituitary-adrenal gland (HPA) axis that are important for both therapeutic (e.g., treatment of mood disorders) and experimental (e.g., as the toxin in conditioned taste aversion studies) applications. We visualized lithium-induced activation of the HPA axis in rats by the adrenal expression of inducible cAMP early repressor (ICER), which is activated by elevated intracellular cAMP. We have shown that 1) intraperitoneal lithium chloride (LiCl) induces transient expression of ICER and c-fos mRNAs in the rat adrenal cortex and increases plasma level of corticosterone; 2) the cortical expression of ICER mRNA by LiCl occurs in a dose-dependent manner; 3) adrenal induction of ICER expression is delayed compared with c-fos expression; 4) dexamethasone pretreatment (4 mg/kg) blocks corticosterone release and adrenocortical ICER induction either by systemic LiCl (76 mg/kg) or by restraint stress; and 5) intracerebroventricular LiCl (127 microg/5 microl) is sufficient for adrenocortical, but not medullary, ICER induction. These results suggest that adrenocortical ICER expression could serve as a reliable marker for lithium-induced activation of the HPA axis. Understanding the activation of immediate-early genes such as c-fos or ICER in response to a single LiCl injection is an important first step in understanding the long-term changes in gene expression elicited by lithium that are involved in its therapeutic and toxic effect. The pattern and mechanism by which lithium stimulates ICER transcription in the adrenal gland would serve as a useful model system in future studies of lithium.}, } @article {pmid16165167, year = {2005}, author = {Walker, EA and Kohut, SJ and Hass, RW and Brown, EK and Prabandham, A and Lefever, T}, title = {Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice.}, journal = {Neuropharmacology}, volume = {49}, number = {8}, pages = {1210-1219}, doi = {10.1016/j.neuropharm.2005.07.015}, pmid = {16165167}, issn = {0028-3908}, support = {DA14673/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Operant/*drug effects ; Cues ; Dose-Response Relationship, Drug ; Lithium Chloride/pharmacology ; Lysergic Acid Diethylamide/analogs & derivatives/pharmacology ; Male ; Mianserin/pharmacology ; Mice ; Piperazines/administration & dosage/*pharmacology ; Pyrazines/administration & dosage/*pharmacology ; Receptor, Serotonin, 5-HT2C/drug effects ; Reinforcement, Psychology ; Serotonin Antagonists/*pharmacology ; Taste/drug effects ; }, abstract = {Serotonin(2C) (5-HT(2C)) receptors have been implicated to treat mood disorders such as depression and anxiety. In the present study, the capacities of two 5-HT(2C) agonists, MK212 and mCPP, to produce conditioned taste aversions in mice were evaluated. On two training days, Swiss-Webster male mice (19-34g) were trained to associate the flavor of a novel solution with the injection of various doses of MK212 or mCPP. On two alternate training days, mice were trained to associate a different flavored solution with an injection of saline. For testing, both flavored solutions were presented simultaneously and an avoidance of the MK212 or mCPP-paired solution indicated conditioned taste aversion. Robust conditioned taste aversions were observed to solutions paired with 1.0 or 10mg/kg MK212 or mCPP. Acquisition of conditioned taste aversions was blocked by nonselective serotonin antagonists cyproheptadine, bromo-LSD, metergoline, methysergide and mianserin. Selective 5-HT(2B/2C) antagonist SB206,553 blocked both MK212- and mCPP-induced conditioned taste aversion although selective 5-HT(2B/2C) antagonist SB200,646 only blocked mCPP-induced conditioned taste aversion. In a single-bottle procedure, MK212, bromo-LSD, and mianserin failed to alter acquisition rate of a LiCl-induced conditioned taste aversion. Taken together, these data indicate that the serotonin agonists MK212 and mCPP produce conditioned taste aversion and that these effects are mediated predominantly through 5-HT(2C) receptors.}, } @article {pmid16158677, year = {2005}, author = {Christianson, JP and Anderson, MJ and Misanin, JR and Hinderliter, CF}, title = {Effect of low body temperature on associative interference in conditioned taste aversion.}, journal = {Perceptual and motor skills}, volume = {100}, number = {3 Pt 2}, pages = {913-919}, doi = {10.2466/pms.100.3c.913-919}, pmid = {16158677}, issn = {0031-5125}, mesh = {Animals ; *Association Learning ; *Attention ; *Avoidance Learning ; *Body Temperature ; *Conditioning, Classical ; *Hypothermia, Induced ; Immersion ; Lithium Chloride/toxicity ; Male ; Rats ; Rats, Wistar ; Reaction Time ; Retention, Psychology ; *Taste ; }, abstract = {When two novel conditioned stimuli precede an unconditioned stimulus (US), the interval between the two conditioned stimuli (CS1 and CS2) influences the magnitude of the CS-US associability of each CS. As the interval between CS1 and CS2 increases, the associability of CS1 with the US decreases due to interference by CS2 and the associability of CS2 increases, given its temporal proximity to the US. Because hypothermia has been reported to increase the interval at which conditioned taste aversions can be formed, its influence was examined on the above relationship, i.e., how interference from CS2 affects the associability of CS1 with the US. Rats received a conditioned taste aversion procedure where CS1 and CS2 were presented either one after the other or separated by an 80-min. delay. For all subjects, the US or pseudo-US was presented immediately after CS2. When hypothermia was interpolated between the two flavor stimuli that were spaced 80 min. apart, CS2-interference with the CS1-US association was greatly attenuated. We propose that hypothermia modifies internal timing mechanisms such that the externally timed 80-min. CS1-CS2 interval was perceived as much shorter for rats made hypothermic. As a result of this perceived shortened inter-CS interval, CS2 produced less interference for the CS1-US association than would be expected for such a relatively long delay between CS1 and CS2.}, } @article {pmid16154625, year = {2005}, author = {Busse, GD and Verendeev, A and Jones, J and Riley, AL}, title = {The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {82}, number = {1}, pages = {207-214}, doi = {10.1016/j.pbb.2005.08.013}, pmid = {16154625}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/administration & dosage/*pharmacology ; Ethanol/administration & dosage/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.}, } @article {pmid16151415, year = {2005}, author = {Malmlöf, K and Zaragoza, F and Golozoubova, V and Refsgaard, HH and Cremers, T and Raun, K and Wulff, BS and Johansen, PB and Westerink, B and Rimvall, K}, title = {Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight.}, journal = {International journal of obesity (2005)}, volume = {29}, number = {12}, pages = {1402-1412}, doi = {10.1038/sj.ijo.0803036}, pmid = {16151415}, issn = {0307-0565}, mesh = {Administration, Oral ; Animals ; Body Weight/drug effects ; Drinking/drug effects ; Eating/drug effects ; Histamine Antagonists/administration & dosage/*pharmacology ; Hypothalamus/*drug effects/metabolism ; Male ; Mice ; Mice, Obese ; Motor Activity/drug effects ; Piperazines/administration & dosage/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H3/blood/*drug effects ; }, abstract = {OBJECTIVE: This study was conducted to elucidate whether antagonistic targeting of the histamine H3 receptor increases hypothalamic histamine levels, in parallel with decreases in food intake and body weight.

METHODS: The competitive antagonist potency of a recently synthesized histamine H3 receptor antagonist, NNC 38-1049, was studied in intact HEK293 cells expressing human or rat histamine H3 receptor, in which NNC 38-1049 was allowed to antagonize the effect of the H3 receptor agonist R-alpha-methylhistamine on isoprenaline-induced accumulation of cAMP. The affinity of NNC 38-1049 for a number of variants of the histamine receptor was also determined. Following single dosing of normal rats with NNC 38-1049, hypothalamic histamine levels were assessed by means of microdialysis. Plasma and brain levels of NNC 38-1049 and acute effects on food intake and energy expenditure were followed after oral doses of 3-60 mg/kg. Potential side effects were examined with rat models of behaviour satiety sequence (BSS), pica behaviour and conditioned taste aversion (CTA). Intakes of food and water together with body weight were recorded for 15 days during daily dosing of dietary obese rats.

RESULTS: NNC 38-1049 was found to be a highly specific and competitive antagonist towards both human and rat histamine H3 receptors, and measurable amounts of NNC 38-1049 were found in the plasma of rats following single oral doses of 3-60 mg/kg and in the brain after 15-60 mg/kg. Following single intraperitoneal injections of NNC 38-1049 (20 mg/kg), significant increases in extracellular histamine concentrations were observed. The same dose did not change BSS or pica behaviour acutely, nor did it induce CTA following repeated administration for 7 days. Reductions in food intake were seen very soon after administration, and occurred in a dose-dependent fashion. Energy expenditure was unchanged, but the respiratory quotient (RQ) tended to decrease at higher doses, indicating an increase in lipid oxidation. Twice daily administration of 20 mg/kg of NNC 38-1049 in old and dietary obese rats resulted in sustained reduction of food intake throughout a 2-week study, and was associated with a highly significant (P<0.01) decrease in body weight compared with controls (-18.4+/-3.4 vs +0.4+/-2.7 g). The same dose of NNC 38-1049 produced an acute decrease of water intake, but 24 h intakes were not significantly changed.

CONCLUSIONS: The results of this study strongly support the idea that an increase in the hypothalamic concentration of histamine produces a specific reduction of food intake and that this effect can be translated into a decrease in body weight.}, } @article {pmid16148441, year = {2005}, author = {Järbe, TU and DiPatrizio, NV}, title = {Delta9-THC induced hyperphagia and tolerance assessment: interactions between the CB1 receptor agonist delta9-THC and the CB1 receptor antagonist SR-141716 (rimonabant) in rats.}, journal = {Behavioural pharmacology}, volume = {16}, number = {5-6}, pages = {373-380}, doi = {10.1097/00008877-200509000-00009}, pmid = {16148441}, issn = {0955-8810}, support = {DA 00253/DA/NIDA NIH HHS/United States ; DA 09064/DA/NIDA NIH HHS/United States ; DA 13429/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Body Weight/drug effects ; Dose-Response Relationship, Drug ; Dronabinol/*pharmacology ; Drug Interactions ; Drug Tolerance ; Eating/drug effects ; Feeding Behavior/drug effects ; Hyperphagia/*chemically induced/physiopathology ; Male ; Piperidines/*pharmacology ; Pyrazoles/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/agonists/antagonists & inhibitors/*physiology ; Rimonabant ; Time Factors ; }, abstract = {This study examined effects of the CB1 receptor antagonist/inverse agonist SR-141716 and the CB1 receptor agonist delta9-tetrahydrocannabinol (delta9-THC) on feeding behavior in male Sprague-Dawley rats. Rats were housed individually with free access to regular pelletized laboratory chow [after a 2 weeks handling phase, animals had access to regular chow for 21 h (Study 1) or 22 h (Study 2); high-fat powder food for 3 h in Study 1 and 2 h in Study 2, respectively], and free access to water. Animals were maintained on a reversed 12-h light/dark cycle (dark beginning at noon). Rats were habituated to this type of feeding and light/dark schedule for 3 weeks until a stable baseline for food intake was achieved. In Study 1, animals were examined after administration of delta9-THC alone (dose range 0.1-1.8 mg/kg), SR-141716 alone (dose range 0.03-0.3 mg/kg), and the two drugs combined; injections were given i.p. at the beginning of the second hour after presenting the high-fat diet and drugs were given twice weekly. There was a dose-related increase in high-fat diet intake, peaking at 0.56-1 mg/kg delta9-THC. SR-141716 alone suppressed the high-fat diet intake below control levels. A combination of 0.3 mg/kg SR-141716 and 0.56 mg/kg delta9-THC counteracted the effects on consumption of either drug alone. In Study 2, experimental rats were treated initially with 0.56 mg/kg delta9-THC for six consecutive days; controls received vehicle. Attenuation of the hyperphagia (high-fat diet) was evident after the second injection. Increasing doses of delta9-THC (1 and 1.8 mg/kg, for two and three consecutive days, respectively) did not reinstate the initial hyperphagia. In conclusion, low-to-moderate doses of delta9-THC produced hyperphagia (to a high-fat food source), which was antagonized by SR-141716. SR-141716 singly suppressed intake of the high-fat diet. Delta9-THC-induced hyperphagia dissipated rapidly upon chronic treatment; however, it is unclear whether this reflects pharmacological tolerance or the emergence of a conditioned taste aversion in Study 2.}, } @article {pmid16131594, year = {2005}, author = {Tovar, S and Nogueiras, R and Tung, LY and Castañeda, TR and Vázquez, MJ and Morris, A and Williams, LM and Dickson, SL and Diéguez, C}, title = {Central administration of resistin promotes short-term satiety in rats.}, journal = {European journal of endocrinology}, volume = {153}, number = {3}, pages = {R1-5}, doi = {10.1530/eje.1.01999}, pmid = {16131594}, issn = {0804-4643}, mesh = {Adiponectin ; Animals ; Body Weight/drug effects ; Eating/*drug effects/physiology ; Hormones, Ectopic/*pharmacology ; Hypothalamus/*drug effects/metabolism ; Immunohistochemistry ; In Situ Hybridization ; Injections, Intraventricular ; Insulin/blood ; Intercellular Signaling Peptides and Proteins/blood ; Leptin/blood ; Male ; Proto-Oncogene Proteins c-fos/metabolism ; RNA, Messenger/genetics ; Rats ; Resistin ; Satiety Response/*drug effects/physiology ; Statistics, Nonparametric ; Taste/physiology ; }, abstract = {OBJECTIVE: Several hormones expressed in white adipose tissue influence food intake at the central level. We sought to determine whether resistin, a circulating adipose-derived hormone in rodents, has actions on the hypothalamus by determining the effects of central resistin injection on food intake and on hypothalamic Fos protein expression.

DESIGN: As resistin expression in adipose tissue is influenced by altered nutritional status, we studied the effect of central resistin in both fed and pre-fasted rats.

RESULTS: In fasted rats, central injection of resistin decreased food intake acutely and increased the number of cells that express Fos protein in the arcuate nucleus but not in any other hypothalamic structure. The effect on food intake was dose-dependent and did not result in the formation of a conditioned taste aversion.

CONCLUSIONS: Taken together, these results provide the first evidence documenting a central action of resistin, which could be involved in a feedback loop targeting the hypothalamus. On the other hand, since we observed resistin mRNA in the arcuate and ventromedial nuclei of the hypothalamus, it is also possible that brain-derived resistin serves as a neuropeptide involved in the regulation of energy homeostasis. However, since resistin-induced satiety was modest and transient, as central administration for several days did not affect body weight, the physiological relevance and therapeutic potential of the observed principal phenomenon may be limited.}, } @article {pmid16125209, year = {2005}, author = {Curtis, KS and Stratford, JM and Contreras, RJ}, title = {Estrogen increases the taste threshold for sucrose in rats.}, journal = {Physiology & behavior}, volume = {86}, number = {3}, pages = {281-286}, doi = {10.1016/j.physbeh.2005.08.002}, pmid = {16125209}, issn = {0031-9384}, support = {DC04785/DC/NIDCD NIH HHS/United States ; DC06360/DC/NIDCD NIH HHS/United States ; T-32 DC00044/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Behavior, Animal ; Dose-Response Relationship, Drug ; Drug Interactions ; Estrogens/*pharmacology ; Female ; Food Preferences/*drug effects ; Generalization, Psychological/drug effects ; Lithium Chloride/pharmacology ; Ovariectomy/methods ; Rats ; Rats, Sprague-Dawley ; Sucrose/*pharmacology ; Sweetening Agents/*pharmacology ; Taste Threshold/*drug effects ; }, abstract = {Anecdotal and empirical evidence suggests that females' preferences for sweet foods are affected by hormonal fluctuations across the reproductive cycle. In rats, the preference for sweet foods may involve estrogen-mediated changes in response to the taste of sweets. Our recent work showed that ovariectomized female rats lick less to dilute sucrose solutions when given estrogen than when given the oil vehicle. These findings suggest that estrogen decreases the preference for less concentrated sucrose solutions; however, an alternative explanation is that estrogen interferes with the ability to detect dilute sucrose solutions. To distinguish between these possibilities, we conditioned a taste aversion to 0.2 M sucrose in ovariectomized rats by pairing it with injection of LiCl and then examined the generalization of that taste aversion to 0.075 and 0.025 M sucrose solutions during estrogen or oil treatment. Oil-treated rats generalized the LiCl-induced aversion conditioned to 0.2 M sucrose to both 0.075 and 0.025 M sucrose. Estrogen-treated rats generalized the LiCl-induced taste aversion to 0.075 M sucrose but not to 0.025 M sucrose. Moreover, two weeks later, when estrogen had cleared the system, both groups generalized the aversion to both 0.075 and 0.025 M sucrose. These results show that estrogen affects the ability to discriminate dilute sucrose from water and suggest that estrogen may have short-term effects on the detection threshold for sucrose taste in rats.}, } @article {pmid16105698, year = {2005}, author = {Blednov, YA and Bergeson, SE and Walker, D and Ferreira, VM and Kuziel, WA and Harris, RA}, title = {Perturbation of chemokine networks by gene deletion alters the reinforcing actions of ethanol.}, journal = {Behavioural brain research}, volume = {165}, number = {1}, pages = {110-125}, pmid = {16105698}, issn = {0166-4328}, support = {AA06399/AA/NIAAA NIH HHS/United States ; R37 AA006399/AA/NIAAA NIH HHS/United States ; R01 AA006399/AA/NIAAA NIH HHS/United States ; U01 AA013475/AA/NIAAA NIH HHS/United States ; U01 AA013475-02/AA/NIAAA NIH HHS/United States ; AA U01 13520/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics/immunology ; Alcoholism/genetics/immunology ; Animals ; Association Learning/physiology ; Chemokine CCL2/deficiency/*genetics ; Chemokine CCL3 ; Chemokine CCL4 ; Chemokines, CC/deficiency/*genetics ; Conditioning, Classical/*physiology ; Disease Models, Animal ; Ethanol ; Female ; Gene Deletion ; Macrophage Inflammatory Proteins/deficiency/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, CCR2 ; Receptors, CCR5/deficiency/genetics ; Receptors, Chemokine/deficiency/genetics ; *Reinforcement, Psychology ; Severity of Illness Index ; Sex Factors ; Signal Transduction/genetics ; Substance Withdrawal Syndrome/genetics/immunology ; Taste/genetics ; }, abstract = {Microarray analysis of human alcoholic brain and cultured cells exposed to ethanol showed significant changes in expression of genes related to immune or inflammatory responses, including chemokines and chemokine receptors. To test the hypothesis that chemokines exhibit previously undiscovered pleiotropic effects important for the behavioral actions of ethanol, we studied mutant mice with deletion of the Ccr2, Ccr5, Ccl2 or Ccl3 genes. Deletion of Ccr2, Ccl2 (females) or Ccl3 in mice resulted in lower preference for alcohol and consumption of lower amounts of alcohol in a two-bottle choice test as compared with wild-type mice. Ethanol treatment (2.5 g/kg, i.p.) induced stronger conditioned taste aversion in Ccr2, Ccl2 or Ccl3 null mutant mice than in controls. Ccr2 and Ccr5 null mutant mice did not differ from wild-type mice in ethanol-induced loss of righting reflex (LORR), but mice lacking Ccl2 or Ccl3 showed longer LORR than wild-type mice. There were no differences between mutant strains and wild-type mice in severity of ethanol-induced withdrawal. Genetic mapping of chromosome 11 for the Ccl2 and Ccl3 genes (46.5 and 47.6 cM, respectively) revealed that an alcohol-induced LORR QTL region was contained within the introgressed region derived from 129/SvJ, which may cause some behavioral phenotypes observed in the null mice. On the contrary, known QTLs on Chr 9 are outside of 129/SvJ region in Ccr2 and Ccr5 (71.9 and 72.0 cM, respectively) null mutant mice. These data show that disruption of the chemokine network interferes with motivational effects of alcohol.}, } @article {pmid16101757, year = {2005}, author = {Cui, Z and Lindl, KA and Mei, B and Zhang, S and Tsien, JZ}, title = {Requirement of NMDA receptor reactivation for consolidation and storage of nondeclarative taste memory revealed by inducible NR1 knockout.}, journal = {The European journal of neuroscience}, volume = {22}, number = {3}, pages = {755-763}, doi = {10.1111/j.1460-9568.2005.04257.x}, pmid = {16101757}, issn = {0953-816X}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/physiology ; Cerebral Cortex/anatomy & histology/*physiology ; Conditioning, Psychological ; Extracellular Matrix Proteins/genetics/metabolism ; Gene Expression Regulation/physiology ; Green Fluorescent Proteins/biosynthesis ; Integrases/genetics ; Lithium Chloride/pharmacology ; Long-Term Potentiation/drug effects/physiology ; Memory/drug effects/*physiology ; Mice ; Mice, Transgenic ; Protein-Lysine 6-Oxidase/genetics/metabolism ; Receptors, N-Methyl-D-Aspartate/deficiency/genetics/*physiology ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {We employed an inducible, reversible and region-specific gene knockout technique to investigate the requirements for cortical NMDA receptors (NMDAR) during the various stages (acquisition, consolidation and storage, and retrieval) of nondeclarative, hippocampal-independent memory in mice using a conditioned taste aversion memory paradigm. Here we show that temporary knockout of the cortical NMDAR during either the learning or postlearning consolidation stage, but not during the retrieval stage, causes severe performance deficits in the 1-month taste memory retention tests. More importantly, we found that the consolidation and storage of the long-term nondeclarative taste memories requires cortical NMDAR reactivation. Thus, the dynamic engagement of the NMDAR during the postlearning stage leads us to postulate that NMDAR reactivation-mediated synaptic re-entry reinforcement is crucial for overcoming the destabilizing effects intrinsic to synaptic protein turnover and for achieving consolidation and storage of nondeclarative memories in the brain.}, } @article {pmid16084590, year = {2005}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {Concurrent conditioned taste aversion: a learning mechanism based on rapid neural versus flexible humoral processing of visceral noxious substances.}, journal = {Neuroscience and biobehavioral reviews}, volume = {29}, number = {7}, pages = {1107-1118}, doi = {10.1016/j.neubiorev.2005.06.002}, pmid = {16084590}, issn = {0149-7634}, mesh = {Adaptation, Physiological/physiology ; Animals ; Avoidance Learning/*physiology ; Central Nervous System/physiology ; Conditioning, Classical/*physiology ; Enteric Nervous System/physiology ; Nausea/*physiopathology ; Neural Pathways/*physiology ; Rats ; Taste/*physiology ; Visceral Afferents/physiology ; Vomiting/*physiopathology ; }, abstract = {Taste aversion learning (TAL) consists of the avoidance of a taste previously associated with a noxious visceral stimulus. Clinical and experimental studies suggest that this adaptive process can be established by different procedures that imply distinct forms of learning and memory, although the final result is analogous, i.e. avoidance of the gustatory stimulus associated with gastrointestinal discomfort. In fact, a double neurobiological system has been anatomically dissociated and, functionally, may be implicated in nausea and emesis, in food selection, and in neuroimmune interactions. Actually, a dual, parallel, and non-redundant gut-brain system has been proposed that sustain two different TAL modalities, concurrent and sequential. Concurrent TAL requires several trials and is inflexible, requiring simultaneity of the stimuli and the participation of the vagus nerve. In contrast, sequential TAL can be acquired in one trial and is flexible, permits long inter-stimulus delays, and is independent of vagal pathways. These two TAL modalities are analyzed in the light of the recent proposal that different acquisition processes are sustained by distinct cerebral systems.}, } @article {pmid16054059, year = {2005}, author = {Halatchev, IG and Cone, RD}, title = {Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice.}, journal = {Cell metabolism}, volume = {1}, number = {3}, pages = {159-168}, doi = {10.1016/j.cmet.2005.02.003}, pmid = {16054059}, issn = {1550-4131}, support = {DK070332/DK/NIDDK NIH HHS/United States ; F31-NS048773-01/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Area Postrema/cytology ; *Aversive Therapy ; Brain Stem/cytology ; Feeding Behavior/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/physiology ; Peptide Fragments/administration & dosage/pharmacology ; Peptide YY/administration & dosage/*pharmacology ; Solitary Nucleus/cytology ; Taste/*drug effects ; Vagus Nerve/physiology ; }, abstract = {Peptide YY (PYY) is a postprandially released gut hormone. Peripheral administration of one form of the peptide PYY3-36 produces a short-term reduction in food intake in rodents. Initial reports suggested that effects of PYY3-36 on food intake are mediated by increasing the anorexigenic drive from melanocortin neurons in the hypothalamic arcuate nucleus. However, more recent data have demonstrated that the anorexigenic activity of PYY3-36 is not dependent on melanocortin ligands or their receptors in the CNS. We demonstrate here that the anorexigenic actions of PYY3-36 are also not dependent on the vagus nerve, a common pathway of satiety signaling. Peripherally administered PYY3-36 activates neurons in the area postrema and nucleus tractus solitarius, brainstem areas known to mediate effects of certain aversive stimuli. Furthermore, peripheral administration of PYY3-36 causes conditioned taste aversion in mice. Thus, inhibition of food intake by PYY3-36 may result in part from induction of an aversive response.}, } @article {pmid16049395, year = {2005}, author = {Bojanowska, E}, title = {Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): the role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {11}, number = {8}, pages = {RA271-8}, pmid = {16049395}, issn = {1234-1010}, mesh = {Animals ; Diabetes Mellitus/*metabolism ; Glucagon/*metabolism ; Glucagon-Like Peptide 1 ; Humans ; Obesity/*metabolism ; Pancreas/metabolism ; Peptide Fragments/*metabolism ; Protein Precursors/*metabolism ; Stress, Physiological/*metabolism ; }, abstract = {Glucagon-like peptide-1 (GLP-1) is produced both in the human and rat intestine and brain. The release of GLP-1 into the blood is mediated by factors of neural and hormonal origin and is stimulated by the presence of nutrients in the digestive tract, while the enzyme dipeptidyl peptidase IV and the kidneys are responsible for, respectively, the rapid degradation and excretion of the hormone. Peripherally secreted GLP-1 enhances insulin synthesis and release and maintains the normal anatomical status of pancreatic islets. Diminished GLP-1 response to ingested food, associated with attenuated insulin release and glucose intolerance, was found in non-insulin-dependent diabetes mellitus. GLP-1 replacement in diabetic subjects normalized these parameters, thus indicating a role for this peptide in the pathogenesis of type 2 diabetes. GLP-1 might also be involved in the pathophysiology of obesity and stress to some extent. Both peripheral and central GLP-1 are probably involved in the control of feeding centers as an anorexic agent. GLP-1 affects the activity of the hypothalamo-pituitary-adrenal axis both under basal and stress conditions, including taste aversion learning. Hence, GLP-1-dependent pathophysiological mechanisms may participate in the pathogenesis of the most common metabolic and behavioral disorders.}, } @article {pmid16038094, year = {2005}, author = {Rabin, BM and Shukitt-Hale, B and Joseph, J and Todd, P}, title = {Diet as a factor in behavioral radiation protection following exposure to heavy particles.}, journal = {Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology}, volume = {18}, number = {2}, pages = {71-77}, pmid = {16038094}, issn = {1089-988X}, mesh = {Aging/radiation effects ; Animals ; Antioxidants/therapeutic use ; Behavior, Animal/drug effects/radiation effects ; Blueberry Plants ; Central Nervous System/radiation effects ; Cognition/radiation effects ; Cosmic Radiation/*adverse effects ; Diet ; Fragaria ; Heavy Ions/*adverse effects ; Immunity/radiation effects ; Neoplasms, Radiation-Induced/*drug therapy/etiology/prevention & control ; Oxidative Stress/radiation effects ; Plant Extracts/*therapeutic use ; Protons/adverse effects ; Radiation Protection/*methods ; Rats ; Reactive Oxygen Species ; Solar Activity ; Space Flight ; }, abstract = {Major risks associated with radiation exposures on deep space missions include carcinogenesis due to heavy-particle exposure of cancer-prone tissues and performance decrements due to neurological damage produced by heavy particles. Because exposure to heavy particles can cause oxidative stress, it is possible that antioxidants can be used to mitigate these risks (and possibly some health risks of microgravity). To assess the capacity of antioxidant diets to mitigate the effects of exposure to heavy particles, rats were maintained on antioxidant diets containing 2% blueberry or strawberry extract or a control diet for 8 weeks prior to exposure to 1.5 or 2.0 Gy of accelerated iron particles at Brookhaven National Laboratory. Following irradiation rats were tested on a series of behavioral tasks: amphetamine-induced taste aversion learning, operant responding and spatial learning and memory. The results indicated that the performance of the irradiated rats maintained on the antioxidant diets was, in general, significantly better than that of the control animals, although the effectiveness of the diets ameliorating the radiation-induced deterioration in performance varied as a function of both the specific diet and the specific endpoint. In addition, animals fed antioxidant diets prior to exposure showed reduced heavy particle-induced tumorigenesis one year after exposure compared to the animals fed the control diet. These results suggest that antioxidant diets have the potential to serve as part of a system designed to provide protection to astronauts against the effects of heavy particles on exploratory missions outside the magnetic field of the earth.}, } @article {pmid16029900, year = {2005}, author = {Treesukosol, Y and Ishizuka, T and Yamamoto, C and Senda, K and Tsutsumi, S and Yamatodani, A and Yamamoto, T}, title = {Hypothalamic histamine release by taste stimuli in freely moving rats: possible implication of palatability.}, journal = {Behavioural brain research}, volume = {164}, number = {1}, pages = {67-72}, doi = {10.1016/j.bbr.2005.06.004}, pmid = {16029900}, issn = {0166-4328}, mesh = {Animals ; Appetite Regulation/physiology ; Avoidance Learning/*physiology ; Chorda Tympani Nerve/physiology ; Conditioning, Classical/physiology ; Facial Nerve/*physiology ; Food Preferences/physiology ; Glossopharyngeal Nerve/*physiology ; Histamine/*metabolism ; Hypothalamic Area, Lateral/physiology ; Hypothalamus/*metabolism ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; Taste Buds/physiology ; Tongue/innervation/physiology ; }, abstract = {Our previous study indicated that taste information via the chorda tympani (CT) activates the central histaminergic system in anesthetized rats. However, the physiological roles of taste-induced histamine release remain unknown, thus to further investigate the relationship between histamine release and gustatory information, in the present study we investigated the effect of taste stimuli infused intraorally on histamine release using in vivo microdialysis in free moving rats. Consistent with findings from our previous study, application of NaCl and HCl caused significant increases in histamine levels further supporting the suggestion that this phenomenon is attributed to the excitation of the CT. When rats were intraorally infused with quinine HCl (QHCl) solution, a significant increase in hypothalamic histamine release was observed. On the other hand, histamine release was decreased by sucrose and saccharin solutions. When rats were conditioned to acquire taste aversion to sucrose solution or saccharin solution, instead of the histamine decrease seen by the palatable solutions, the pattern of histamine release was similar to that seen by QHCl solution. From these observations, it is concluded that the histamine release by the infusion of these tastants may be explained by two mechanisms-by causing a transient increase after taste stimulation and by causing a decrease relative to the tastant's palatability.}, } @article {pmid16023187, year = {2005}, author = {Sharma, A and Haksar, A and Chawla, R and Kumar, R and Arora, R and Singh, S and Prasad, J and Islam, F and Arora, MP and Kumar Sharma, R}, title = {Zingiber officinale Rosc. modulates gamma radiation-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {81}, number = {4}, pages = {864-870}, doi = {10.1016/j.pbb.2005.06.012}, pmid = {16023187}, issn = {0091-3057}, mesh = {Animals ; Body Weight/drug effects/radiation effects ; Brain/drug effects/metabolism/radiation effects ; Conditioning, Psychological/*drug effects/radiation effects ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects/radiation effects ; Free Radical Scavengers/pharmacology ; Gamma Rays ; *Ginger ; Lipid Peroxidation/drug effects/radiation effects ; Male ; Malondialdehyde/metabolism ; Plant Extracts/isolation & purification/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Taste/*drug effects/radiation effects ; Thiobarbituric Acid Reactive Substances/metabolism ; Time Factors ; }, abstract = {The aim of the present study was to investigate the neurobehavioral protective efficacy of a hydroalcoholic extract of ginger (Zingiber officinale Rosc.) in mitigating gamma radiation-induced conditioned taste aversion in Sprague-Dawley rats. Administration of Zingiber extract 1 h before 2-Gy gamma irradiation was effective in blocking the saccharin avoidance response for 5 post-treatment observational days, both in a dose- and time-dependent manner, with 200 mg/kg b.w. i.p. being the most effective dose. Highest saccharin intake in all the groups was observed on the fifth post-treatment day. The potential of ginger extract to inhibit lipid peroxidation induced by radiation (2 Gy) and ascorbate-ion stress in brain homogenate and its ability to scavenge highly reactive superoxide anions were evaluated. The 1000-microg/ml and 2000-microg/ml concentration of ginger extract showed the highest efficiency in scavenging free radicals and in inhibiting lipid peroxidation. The lipid peroxidation and superoxide-anion scavenging ability of the extract further supports its radioprotective properties. The results clearly establish the neurobehavioral efficacy of ginger extract and the antioxidant properties appear to be a contributing factor in its overall ability to modulate radiation-induced conditioned taste aversion. Ginger extract has tremendous potential for clinical applications in mitigation of radiation-induced emesis in humans.}, } @article {pmid16005058, year = {2005}, author = {Busse, GD and Freeman, KB and Riley, AL}, title = {The interaction of sex and route of drug administration in cocaine-induced conditioned taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {81}, number = {4}, pages = {814-820}, doi = {10.1016/j.pbb.2005.06.004}, pmid = {16005058}, issn = {0091-3057}, mesh = {Animals ; Cocaine/administration & dosage/*pharmacology ; Conditioning, Operant/*physiology ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Female ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Sex Factors ; Taste/*drug effects ; }, abstract = {Although taste aversion learning has been reported to be a function of a variety of factors, one that has received considerable attention is the subject's sex, wherein males generally display stronger taste aversions than females. An exception to these findings is with cocaine for which females have been shown to display greater aversions than males. Although suggestive of a Sex x Drug interaction, cocaine was administered subcutaneously (s.c.) in this report while others administered drug intraperitoneally (i.p.). Thus, there may be a Sex x Route interaction. To address the contributions of sex and route in cocaine aversions, the present study examined aversions in male and female Sprague-Dawley rats administered a range of doses of cocaine either s.c. or i.p. At the two higher doses of cocaine tested (20 and 32 mg/kg), aversions were a function of route with animals injected s.c. with cocaine displaying greater aversions than those injected i.p. Although there was no main effect of sex at either dose there was an interaction between sex and route at the 20 mg/kg dose. Specifically, s.c.-injected males displayed stronger aversions than i.p.-injected males. There were no differences between the two routes for females. Further, males displayed stronger aversions than females when injected s.c. There was no sex difference when both groups were injected i.p. This interaction was no longer evident at the highest does of cocaine (32 mg/kg). These data indicate that sex differences in aversion learning with cocaine are a function of the route of cocaine administration (and are dose specific).}, } @article {pmid15977386, year = {2005}, author = {Cai, YL and Ma, WL and Li, M and Ouyang, RY and Hu, L and Sun, YL}, title = {[Behavioral changes of rats under rotation stimulation].}, journal = {Hang tian yi xue yu yi xue gong cheng = Space medicine & medical engineering}, volume = {18}, number = {2}, pages = {98-101}, pmid = {15977386}, issn = {1002-0837}, mesh = {Animals ; Aversive Therapy ; *Behavior, Animal ; Disease Models, Animal ; *Eating ; Kaolin ; Motion Sickness/physiopathology/*prevention & control ; Pica ; Rats ; Rats, Sprague-Dawley ; *Rotation ; Saccharin ; Taste ; Time Factors ; Water ; *Weightlessness Simulation ; }, abstract = {OBJECTIVE: To assess the specification and efficiency of rotation sickness indices by monitoring changes of behaviors in rats under rotation stimulation.

METHOD: SD rats were stimulated by Crampton model with different time courses. Pica or kaolin consumption (KC), conditioned taste aversion (CTA) or saccharine water ingestion (SWI), 2 h food ingestion (2hFI), and open-field test (OFT) scores were observed.

RESULT: Apparent changes of the four indices were observed after rotation stimulation. SWI, OFT scores and 2hFI decreased exponentially with increase of duration of the motion stimulation. KC increased linearly with the increase of time within 12 h stimulation. After 18 h stimulation, KC decreased to a level even lower than that after 6 or 12 h stimulation. The adjusted correlation between changes of the indices and duration of stimulation within 12 h are: 0.94 for KC, 0.54 for SWI, 0.44 for 2hFI and 0.34 for OFT. The maximum efficiency of the four indices appeared at 6-hour stimulation: 70% for KC, 90% for SWI, 80% for 2hFI and 95% for OFT.

CONCLUSION: It is found that pica and CTA were more specific than the other indices. They may serve as primary indices and can be combined with the secondary indices such as 2hFI or OFT. Six hours is the optimal duration of stimulation by Crampton model for rotation sickness studies.}, } @article {pmid15961067, year = {2005}, author = {Mickley, GA and Kenmuir, CL and Yocom, AM and Wellman, JA and Biada, JM}, title = {A role for prefrontal cortex in the extinction of a conditioned taste aversion.}, journal = {Brain research}, volume = {1051}, number = {1-2}, pages = {176-182}, doi = {10.1016/j.brainres.2005.05.033}, pmid = {15961067}, issn = {0006-8993}, support = {1-R15-MH63720-01/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Male ; Prefrontal Cortex/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {This study used immunohistochemical methods to determine if the medial prefrontal cortex (mPFC) is involved in the extinction of a conditioned taste aversion (CTA). As rats reached 90% reacceptance of a tastant (saccharin: SAC) that had previously been associated with lithium chloride-induced malaise, c-Fos protein expression increased dramatically as compared to animals with active CTAs, animals without CTAs (i.e., explicitly unpaired CS-US exposures) or animals drinking SAC for the first time. These data indicate a role for mPFC (prelimbic and infralimbic cortex) in the formation of a CTA extinction memory.}, } @article {pmid15932924, year = {2005}, author = {Talsania, T and Anini, Y and Siu, S and Drucker, DJ and Brubaker, PL}, title = {Peripheral exendin-4 and peptide YY(3-36) synergistically reduce food intake through different mechanisms in mice.}, journal = {Endocrinology}, volume = {146}, number = {9}, pages = {3748-3756}, doi = {10.1210/en.2005-0473}, pmid = {15932924}, issn = {0013-7227}, mesh = {Animals ; Dose-Response Relationship, Drug ; Drug Synergism ; Eating/*drug effects/physiology ; Exenatide ; Gastric Emptying/drug effects/physiology ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy/physiopathology ; Peptide Fragments ; Peptide YY/*pharmacology ; Peptides/*pharmacology ; Satiety Response/drug effects/physiology ; Venoms/*pharmacology ; }, abstract = {Glucagon-like peptide-1(7-36NH2) (GLP-1) and peptide YY(3-36NH2) (PYY(3-36NH2)) are cosecreted from the intestine in response to nutrient ingestion. Peripheral administration of GLP-1 or PYY(3-36NH2) decreases food intake (FI) in rodents and humans; however, the exact mechanisms by which these peptides regulate FI remain unclear. Male C57BL/6 mice were injected (ip) with exendin-4(1-39) (Ex4, a GLP-1 receptor agonist) and/or PYY(3-36NH2) (0.03-3 microg), and FI was determined for up to 24 h. Ex4 and PYY(3-36NH2) alone decreased FI by up to 83 and 26%, respectively (P < 0.05-0.001), whereas a combination of the two peptides (0.06 microg Ex4 plus 3 microg PYY(3-36NH2)) further reduced FI for up to 8 h in a synergistic manner (P < 0.05-0.001). Ex4 and/or PYY(3-36NH2) delayed gastric emptying by a maximum of 19% (P < 0.01-0.001); however, there was no significant effect on locomotor activity nor was there induction of taste aversion. Capsaicin pretreatment prevented the inhibitory effect of Ex4 on FI (P < 0.05), but had no effect on the anorexigenic actions of PYY(3-36NH2). Similarly, exendin-4(9-39) (a GLP-1 receptor antagonist) partially abolished Ex4-induced anorexia (P < 0.05), but did not affect the satiation produced by PYY(3-36NH2). Conversely, BIIE0246 (a Y2 receptor antagonist) completely blocked the anorexigenic effects of PYY(3-36NH2) (P < 0.001), but had no effect on Ex4-induced satiety. Thus, Ex4 and PYY(3-36NH2) suppress FI via independent mechanisms involving a GLP-1 receptor-dependent, sensory afferent pathway (Ex4) and a Y2-receptor mediated pathway (PYY(3-36NH2)). These findings suggest that administration of low doses of Ex4 together with PYY(3-36NH2) may increase the suppression of FI without inducing significant side effects.}, } @article {pmid15932618, year = {2005}, author = {Cannon, CM and Scannell, CA and Palmiter, RD}, title = {Mice lacking dopamine D1 receptors express normal lithium chloride-induced conditioned taste aversion for salt but not sucrose.}, journal = {The European journal of neuroscience}, volume = {21}, number = {9}, pages = {2600-2604}, doi = {10.1111/j.1460-9568.2005.04077.x}, pmid = {15932618}, issn = {0953-816X}, support = {5 T32 NS 07332/NS/NINDS NIH HHS/United States ; T32 DA 07278/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/*pharmacology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Food Preferences/drug effects/*physiology ; Lithium Chloride/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Receptors, Dopamine D1/*genetics ; Salts ; Sucrose ; *Taste ; }, abstract = {Conditioned taste aversion (CTA), is a form of Pavlovian learning wherein a novel flavour is powerfully associated with subsequent feelings of illness, and is afterwards avoided. In rats, pharmacological blockade of dopamine D1 receptors has been reported to prevent the expression of a CTA to the sweet taste of sucrose or saccharine. We used genetically modified mice to determine whether dopamine D1 receptors are necessary for the expression of a CTA. Food-deprived mice lacking the dopamine D1 receptor (D1r-/-) did not express a LiCl-induced (125 or 254 mg/kg) CTA to the sweet taste of 0.5 m sucrose, in agreement with previous pharmacological studies. However, water-deprived D1r-/- mice did express normal LiCl-induced (40, 150 and 254 mg/kg) CTA to a salty taste (0.2 m NaCl). Our results suggest that activation of D1 receptors might contribute to the strength of an aversive gustatory association, but might not be required for the formation of a CTA in general.}, } @article {pmid15927732, year = {2005}, author = {Eccles, S and Kim, EM and O'Hare, E}, title = {Granisetron attenuates exercise-induced conditioned taste aversion in the rat.}, journal = {Appetite}, volume = {44}, number = {3}, pages = {325-328}, doi = {10.1016/j.appet.2005.02.001}, pmid = {15927732}, issn = {0195-6663}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Granisetron/*pharmacology ; Male ; Physical Conditioning, Animal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin Antagonists/*pharmacology ; Taste/*drug effects ; }, abstract = {A conditioned taste aversion (CTA) paradigm was used in the present study to investigate whether CTA produced by exercise could be attenuated by the 5-HT(3) receptor antagonist granisetron. Male Sprague-Dawley rats were randomly allocated to one of four groups (Ns=6) and were exposed to salty (0.128 M sodium chloride) or sour (0.00138M citric acid) solutions. Subjects were injected with either saline solution (1.0 ml, 0.9%) or granisetron (0.5mg/kg, IP) and were exposed to 30 min of forced wheel running exercise (70 revolutions/30min) 10 min after injection. Exercise induced CTA to both the salty (3.7 ml intake) and sour-flaroured (3.1ml intake) solutions as compared with no exercise (intake 14.0 and 13.7 ml), and administration of granisetron significantly attenuated the exercise-induced CTA to the salty- and sour-flavoured solutions.}, } @article {pmid15904710, year = {2005}, author = {Klamer, D and Pålsson, E and Wass, C and Archer, T and Engel, JA and Svensson, L}, title = {Antagonism of the nitric oxide synthase inhibitor, L-NAME, of the effects of phencyclidine on latent inhibition in taste aversion conditioning.}, journal = {Behavioural brain research}, volume = {161}, number = {1}, pages = {60-68}, doi = {10.1016/j.bbr.2005.01.008}, pmid = {15904710}, issn = {0166-4328}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal ; Central Nervous System Stimulants/pharmacology ; Conditioning, Operant/drug effects ; Dextroamphetamine/pharmacology ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Drug Interactions ; Enzyme Inhibitors/*pharmacology ; *Inhibition, Psychological ; Male ; NG-Nitroarginine Methyl Ester/*pharmacology ; Phencyclidine/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Latent inhibition (LI) is a behavioural procedure used to evaluate the potential propsychotic and antipsychotic properties of psychoactive drugs. In the present study, a conditioned taste aversion (CTA) procedure was used to investigate the effects of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), and the psychotomimetic drugs, phencyclidine (PCP) and d-amphetamine (d-AMP) on LI. PCP (2 mg/kg) and d-AMP (0.5 mg/kg) were both found to enhance LI in this procedure. The effect of d-AMP on LI was less pronounced and this drug also caused a weak disruption of taste aversion conditioning. Pretreatment with L-NAME (10 mg/kg) blocked the LI enhancing effect of PCP on LI but not that of d-AMP. L-NAME by itself caused an attenuation of LI. L-NAME has been shown to block also other behavioural and biochemical effects of PCP in previous studies and these results and the present findings suggest that at least some of the effects PCP are dependent on NO and possibly also that some NOS inhibitors may exert antipsychotic properties.}, } @article {pmid15897714, year = {2005}, author = {Fehr, C and Shirley, RL and Crabbe, JC and Belknap, JK and Buck, KJ and Phillips, TJ}, title = {The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2.}, journal = {Alcoholism, clinical and experimental research}, volume = {29}, number = {5}, pages = {708-720}, doi = {10.1097/01.alc.0000164366.18376.ef}, pmid = {15897714}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA06243/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; AA11114/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics/*psychology ; Animals ; Avoidance Learning/drug effects ; Central Nervous System Depressants/pharmacology ; Chromosomes/*genetics ; Ethanol/pharmacology ; Female ; Gene Expression ; Genotype ; Male ; Mice ; Mice, Inbred Strains ; Munc18 Proteins ; Nerve Tissue Proteins/*genetics ; Polymorphism, Genetic/genetics ; RNA, Messenger/biosynthesis/genetics ; Substance Withdrawal Syndrome/psychology ; Taste/drug effects ; Vesicular Transport Proteins/*genetics ; }, abstract = {BACKGROUND: We previously mapped a quantitative trait locus (QTL) for ethanol preference drinking to mouse chromosome 2 (mapped with high confidence, LOD = 15.5, p = 3 x 10(-16)). The specific gene(s) in the QTL interval responsible for phenotypic variation in ethanol preference drinking has not been identified.

METHODS: In the current study, we investigated the association of the syntaxin binding protein 1 gene (Stxbp1) with ethanol preference drinking and other ethanol traits using a panel of B6 x D2 (BXD) recombinant inbred (RI) strains derived from the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. Confirmation analyses for ethanol consumption and withdrawal were performed using a large B6D2 F2 cross, short-term selected lines derived from the B6 and D2 progenitor strains, and standard inbred strains.

RESULTS: BXD RI strain analysis detected provisional associations between Stxbp1 molecular variants and ethanol consumption, as well as severity of acute ethanol withdrawal, ethanol-conditioned taste aversion, and ethanol-induced hypothermia. Confirmation analyses using three independent genetic models supported the involvement of Stxbp1 in ethanol preference drinking but not in ethanol withdrawal.

CONCLUSIONS: Stxbp1 encodes a Sec1/Munc18-type protein essential for vesicular neurotransmitter release. The present study provides supporting evidence for the involvement of Stxbp1 in ethanol preference drinking.}, } @article {pmid15896535, year = {2005}, author = {Nakajima, S and Nagaishi, T}, title = {Summation of latent inhibition and overshadowing in a generalized bait shyness paradigm of rats.}, journal = {Behavioural processes}, volume = {69}, number = {3}, pages = {369-377}, doi = {10.1016/j.beproc.2005.02.022}, pmid = {15896535}, issn = {0376-6357}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*physiology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Wistar ; Sodium Chloride/pharmacology ; Solutions ; Sucrose/pharmacology ; Taste/drug effects ; Water Deprivation ; }, abstract = {This paper reports a single experiment using four groups of rats. A group of thirsty rats showed aversion to sodium chloride (NaCl) solution in testing after drinking lithium chloride (LiCl) solution, demonstrating generalized bait shyness due to the common "salty" taste. The other two groups of rats were treated identically except that the rats were either exposed to NaCl solution prior to drinking the LiCl solution or allowed to drink LiCl-sucrose solution instead of the LiCl solution. The weaker salt aversion observed in these groups indicates latent inhibition and overshadowing, respectively. The rats in the fourth group were preexposed to NaCl and allowed to drink the LiCl-sucrose solution. The weakest salt aversion in this group suggests summation of latent inhibition and overshadowing effects.}, } @article {pmid15893375, year = {2005}, author = {Reilly, S and Bornovalova, MA}, title = {Conditioned taste aversion and amygdala lesions in the rat: a critical review.}, journal = {Neuroscience and biobehavioral reviews}, volume = {29}, number = {7}, pages = {1067-1088}, doi = {10.1016/j.neubiorev.2005.03.025}, pmid = {15893375}, issn = {0149-7634}, support = {DC04341/DC/NIDCD NIH HHS/United States ; DC06456/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; Neural Pathways/physiology ; Rats ; Taste/*physiology ; }, abstract = {Studies using permanent lesions implicate the amygdala, a recipient of gustatory and viscerosensory information, in taste aversion learning. Reviewing this literature with respect to the location of the lesions and the quality of the behavioral methodology reveals little, if any, involvement of the medial amygdala or central nucleus in conditioned taste aversion. Although a disruption is found following damage to the basolateral region, the attenuated conditioned taste aversion appears to be a consequence of a lesion-induced impairment of neophobia rather than an association formation deficit. The key to understanding the functional significance of the basolateral amygdala in conditioned taste aversion reduces, we believe, to determining the role of this structure in gustatory neophobia.}, } @article {pmid15879057, year = {2005}, author = {Proulx, K and Cota, D and Castañeda, TR and Tschöp, MH and D'Alessio, DA and Tso, P and Woods, SC and Seeley, RJ}, title = {Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {289}, number = {3}, pages = {R729-37}, doi = {10.1152/ajpregu.00029.2005}, pmid = {15879057}, issn = {0363-6119}, support = {DK 17844/DK/NIDDK NIH HHS/United States ; DK 54080/DK/NIDDK NIH HHS/United States ; DK 54890/DK/NIDDK NIH HHS/United States ; DK 59630/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/drug effects ; Avoidance Learning/drug effects ; Capsaicin/pharmacology ; Conditioning, Psychological/drug effects ; Energy Metabolism/drug effects ; Feeding Behavior/*drug effects ; Hormone Antagonists/pharmacology ; Hot Temperature ; Housing, Animal ; Imidazoles/administration & dosage/*pharmacology ; Injections, Intraperitoneal ; Male ; Motor Activity/*drug effects ; Proglumide/analogs & derivatives/pharmacology ; Pyrimidines/pharmacology ; Rats ; Rats, Long-Evans ; Sodium ; Space Perception ; Taste ; }, abstract = {Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-alpha. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Because the anorexigenic effect of OEA is associated with delayed feeding onset and reduced locomotion, we examined whether intraperitoneal administration of OEA results in nonspecific behavioral effects that contribute to the anorexia in rats. Moreover, we determined whether circulating levels of other gut hormones are modulated by OEA and whether CCK is involved in OEA-induced anorexia. Our results indicate that OEA reduces food intake without causing a conditioned taste aversion or reducing sodium appetite. It also failed to induce a conditioned place aversion. However, OEA induced changes in posture and reduced spontaneous activity in the open field. This likely underlies the reduced heat expenditure and sodium consumption observed after OEA injection, which disappeared within 1 h. The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-alpha agonist Wy-14643. Plasma levels of ghrelin, peptide YY, glucagon-like peptide 1, and apolipoprotein A-IV were not changed by OEA. Finally, antagonism of CCK-1 receptors did not affect OEA-induced anorexia. These results suggest that OEA suppresses feeding without causing visceral illness and that neither ghrelin, peptide YY, glucagon-like peptide 1, apolipoprotein A-IV, nor CCK plays a critical role in this effect. Despite that OEA-induced anorexia is unlikely to be due to impaired motor activity, our data raise a cautionary note in how specific behavioral and metabolic effects of OEA should be interpreted.}, } @article {pmid15862524, year = {2005}, author = {Yasoshima, Y and Yamamoto, T}, title = {Effects of midazolam on the expression of conditioned taste aversion in rats.}, journal = {Brain research}, volume = {1043}, number = {1-2}, pages = {115-123}, doi = {10.1016/j.brainres.2005.02.070}, pmid = {15862524}, issn = {0006-8993}, mesh = {Amygdala/drug effects/physiology ; Animals ; Anti-Anxiety Agents/*pharmacology ; Anxiety/drug therapy/physiopathology ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Male ; Microinjections ; Midazolam/*pharmacology ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {In conditioned taste aversion (CTA), the animals learn to avoid a taste substance (conditioned stimulus, CS) which was previously associated with visceral distress (unconditioned stimulus, US). The present study examined the effects of administration of midazolam (MDZ), a benzodiazepine agonist, after the acquisition of CTA on the expression of CTA. After ingestion of 0.5 M sucrose (CS) was paired with an intraperitoneal (i.p.) injection of 0.15 M LiCl (US), control rats showed strong CTA to the CS. However, a systemic injection of MDZ (1.5 mg/kg, i.p.) before the retention test prevented conditioned animals from rejecting the CS, but in the subsequent retention tests where the drug was not administrated, those animals again showed strong aversions to the CS. Aversive taste reactivity patterns to the intraorally infused sucrose and 0.3 M dl-alanine in the conditioned animals were also diminished by the similar injection of MDZ, but not by a serotonergic anxiolytic agent, buspirone (2.5 or 5.0 mg/kg, i.p.). General taste sensory deficit might not be induced by MDZ because the drug injection did not impair conditioned aversions to 0.2 M NaCl and 0.01 M HCl. Infusion of MDZ into the basolateral nucleus of the amygdala (BLA) also attenuated conditioned aversions to sucrose. These results suggest that systemic or intra-BLA administrations of MDZ impair the expression of CTA selectively to sweet-tasting substances, implying that a transient MDZ-induced CTA expression deficit is due to the enhancement of palatability of CSs with preferable tastes rather than general anxiolytic or amnesic effects of MDZ.}, } @article {pmid15844374, year = {2005}, author = {De la Casa, LG and Lubow, RE}, title = {Delay-induced super-latent inhibition as a function of order of exposure to two flavours prior to compound conditioning.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {58}, number = {1}, pages = {1-18}, doi = {10.1080/02724990444000014}, pmid = {15844374}, issn = {0272-4995}, mesh = {Animals ; *Conditioning, Psychological ; Escape Reaction ; *Inhibition, Psychological ; Male ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {A number of recent conditioned taste aversion (CTA) experiments have demonstrated a super-latent inhibition (LI) effect--namely, a time-induced increase in the effects of stimulus preexposure when the interval between acquisition and test is spent in a context that is different from the other experimental contexts. Two CTA experiments with rats were conducted to examine the role of primacy in producing super-LI. In Experiment 1, one of two flavours was pre-exposed, following which a second flavour was preexposed. After the second preexposure, animals were conditioned by pairing a compound of the two preexposed flavours with LiCl. The test stage was conducted 1 or 21 days after conditioning, with the interval being spent in either the same or different contexts. In the test, animals were confronted with two bottles, each with one of the two preexposed flavours. Super-LI was obtained only for the first preexposed flavour in the 21-day delay group that spent the interval in a different context. Experiment 2 was designed to ensure that the effects in Experiment 1 represented LI, and to control for order of presentation of the flavours and time between preexposure and acquisition. The results replicated those of Experiment 1. The two experiments support the importance of primacy in the general super-LI experiment where CS-alone preexposure precedes CS-US.}, } @article {pmid15839785, year = {2005}, author = {Koh, MT and Bernstein, IL}, title = {Mapping conditioned taste aversion associations using c-Fos reveals a dynamic role for insular cortex.}, journal = {Behavioral neuroscience}, volume = {119}, number = {2}, pages = {388-398}, doi = {10.1037/0735-7044.119.2.388}, pmid = {15839785}, issn = {0735-7044}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; *Avoidance Learning ; Brain Stem/*physiology ; Cerebral Cortex/physiology ; Conditioning, Operant ; Male ; Proto-Oncogene Proteins c-fos/*analysis ; Rats ; Rats, Long-Evans ; *Taste ; }, abstract = {Novel tastes are more effective than familiar tastes as conditioned stimuli (CSs) in taste aversion learning. Parallel to this, a novel CS-unconditioned stimulus (US) pairing induced stronger Fos-like immunoreactivity (FLI) in insular cortex (IC), amygdala, and brainstem than familiar CS-US pairing, suggesting a large circuit is recruited for acquisition. To better define the role of IC, the authors combined immunostaining with lesion or reversible inactivation of IC. Lesions abolished FLI increases to novel taste pairing in amygdala, suggesting a role in novelty detection. Reversible inactivation during taste preexposure increased FLI to familiar taste pairing in amygdala and brainstem. The difference between temporary inactivation, which blocked establishment of "safe" taste memory, and lesions points to a dual role for IC in taste learning.}, } @article {pmid27415802, year = {1999}, author = {Gallo, M and Ballesteros, MA and Molero, A and Morón, I}, title = {Taste Aversion Learning as a Tool for the Study of Hippocampal and Non-Hippocampal Brain Memory Circuits Regulating Diet Selection.}, journal = {Nutritional neuroscience}, volume = {2}, number = {5}, pages = {277-302}, doi = {10.1080/1028415X.1999.11747284}, pmid = {27415802}, issn = {1028-415X}, abstract = {Diet selection is the result of different learning experiences that accumulate throughout the life of the organism. The acquisition of aversions to the taste of food followed by mild or severe visceral negative effects plays an important role in food selection. Current knowledge on the role of the critical brain areas (parabrachial area, insular cortex and amygdala) involved in the basic associative neural circuit of taste aversion learning is reviewed. In turn, as shown by a variety of learning phenomena, the development of new aversions to the taste of different types of food is profoundly modulated by the memory of previous learning experiences with the same or different tastes. Some of these phenomena may depend on memory brain systems independent of the basic circuit for taste aversion learning. This seems to be the case for contextual effects and conditioned blocking that depend on the hippocampal integrity. Experimental evidence on the neural basis of complex learning phenomena in taste aversion learning is reviewed. Thus, understanding the way in which taste aversion learning regulates diet selection in daily life requires the study of interactions between hippocampal and non-hippocampal dependent memory systems. Taste aversion learning is proposed as a useful behavioral tool in the investigation of different brain circuits that are critical for food selection.}, } @article {pmid24897156, year = {1996}, author = {Roll, JM}, title = {The effect of olfactory and auditory stimuli on drinking suppressed with a conditioned taste aversion.}, journal = {Behavioural processes}, volume = {37}, number = {1}, pages = {31-38}, doi = {10.1016/0376-6357(95)00069-0}, pmid = {24897156}, issn = {0376-6357}, abstract = {Two studies were conducted to assess the effect of auditory and olfactory stimuli on drinking that had been suppressed with a conditioned taste aversion procedure. Each study used a different conditioned stimulus. The first used an 8% saccharin solution which was readily consumed by rats, while the second used a 1% anise solution that was not as readily consumed by rats. The use of a relatively palatable conditioned stimulus and an unpalatable conditioned stimulus allows for an examination of any effect amount of consumption prior to conditioning might have. The results indicated that the stimuli increased drinking suppressed with a conditioned taste aversion in both studies and drinking by control rats in Experiment 2. In Experiment 1 the stimuli either had no effect or suppressed drinking in the control rats. These results indicate that low levels of drinking can under some circumstances, be increased via the presentation of olfactory or auditory stimuli. They further suggest that deflation of drinking from a high to a low rate is not necessary to observe this effect.}, } @article {pmid22302947, year = {1996}, author = {Shoaib, M and Stolerman, IP}, title = {The NMDA antagonist dizocilpine (M K801) attenuates tolerance to nicotine in rats.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {10}, number = {3}, pages = {214-218}, doi = {10.1177/026988119601000306}, pmid = {22302947}, issn = {0269-8811}, abstract = {The N-methyl-D-aspartate antagonist dizocilpine (MK801) has been shown to attenuate neuroadaptations of the locomotor activity responses seen after chronic nicotine administration in rats. The aim of the present study was primarily to examine the effects of dizocilpine on tolerance to the aversive stimulus effect of nicotine, as measured in a conditioned taste aversion (CTA) paradigm. A second aim was to determine whether the previously reported effect of dizocilpine on tolerance to the locomotor depressant effect of nicotine could be confirmed. CTA was assessed from changes in the consumption of saccharin and salt solutions and locomotor activity was measured during 30 min sessions in photocell cages. In control rats, the administration of nicotine (0.4 mg/kg s.c.) produced strong CTA and a biphasic effect on locomotor activity (depression followed by facilitation). Daily treatment for 7 days with nicotine (0.4 mg/kg s.c.) produced tolerance to the CTA and motor effects. This tolerance was not detectable in rats that had received dizocilpine (0.3 mg/kg s.c.) 30 min before each daily injection of nicotine during the period of chronic treatment. The chronic administration of dizocilpine alone did not prevent locomotor effects and CTA when nicotine was administered subsequently. These results suggest that the NMDA receptor may be involved in adaptation to both unconditioned and conditioned behavioural responses to nicotine.}, } @article {pmid27759267, year = {1992}, author = {Semel, B and Nicolaus, LK}, title = {Estrogen-Based Aversion to Eggs Among Free-Ranging Raccoons.}, journal = {Ecological applications : a publication of the Ecological Society of America}, volume = {2}, number = {4}, pages = {439-449}, doi = {10.2307/1941879}, pmid = {27759267}, issn = {1051-0761}, abstract = {Nightly video records of uniquely marked free-ranging raccoons (Procyon lotor) established the events leading to and resulting from estrogen-induced conditioned taste aversion (CTA) to eggs. Observations of animals voluntarily consuming eggs indicated that: (1) some raccoons in the population were more active egg predators than were others and so were the most likely to be treated; (2) a few eggs injected with 30 mg of estrogen were less effective in inducing egg avoidance than were larger numbers of eggs treated with only 10 mg of estrogen; (3) CTA to eggs became well established even though raccoons had become familiar with eggs at the feeding site; (4) treated males tended to abandon egg consumption abruptly, but females tended to sample eggs for a short time before they, too, avoided them at a distance; (5) CTA was not location specific, persisted when surrounding scent cues changed, and failed to extinguish among treated raccoons that were present while untreated individuals consumed untreated eggs freely during the lengthy post-test period; and (6) treated females that avoid eggs may deny their offspring the opportunity to become familiar with egg prey. Observations of egg consumption in the second year of study provided evidence of a prolonged CTA effect in treated animals. Our results enable us to more fully describe a potential non-lethal technology for controlling predation on the eggs of waterfowl or endangered and threatened species.}, } @article {pmid18265490, year = {1991}, author = {Schwarzberg, H and Roth, N and Hiller, K}, title = {Effect of perinatal dexamethasone treatment on conditioned taste aversion in rats.}, journal = {Homeostasis in health and disease : international journal devoted to integrative brain functions and homeostatic systems}, volume = {33}, number = {5-6}, pages = {251-255}, pmid = {18265490}, issn = {0960-7560}, mesh = {Animals ; Animals, Newborn/*physiology ; Anti-Inflammatory Agents/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Cues ; Dexamethasone/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Effect of perinatal dex Rats received a single subcutaneous injection of 1 mg/kg dexamethasone at the age of seven days. One hundred days after the treatment, conditioned taste aversion was determined in the adult animals. Perinatally applied dexamethasone did not affect water consumption but caused a significant attenuation of conditioned taste aversion. These findings may be explained by dexamethasone effects upon brain development which cause impairment of memory functions or, alternatively, decreased responsiveness to aversive stimuli.}, } @article {pmid24263838, year = {1990}, author = {Pfister, JA and Provenza, FD and Manners, GD}, title = {Ingestion of tall larkspur by cattle : Separating effects of flavor from postingestive consequences.}, journal = {Journal of chemical ecology}, volume = {16}, number = {5}, pages = {1697-1705}, pmid = {24263838}, issn = {0098-0331}, abstract = {Tall larkspur (Delphinium spp.) is a palatable but toxic poisonous plant in the western United States. The toxins in tall larkspur are diterpenoid alkaloids. We examined the influences of food flavor and postingestive consequences on consumption of a 33% larkspur pellet during 30-min feeding periods for five days using esophageally fistulated cattle that were sham-fed larkspur pellets. Consumption by the sham-fed group was compared to a control group fed alfalfa pellets, and a larkspur group fed only larkspur pellets. Sham-fed cattle did not decrease (P > 0.1) feed consumption compared to controls, indicating no significant difference in food flavor. The larkspur group decreased (P < 0.05) feed consumption by 41% relative to controls and by 31% relative to sham-fed animals (P = 0.08). This reduction in feed consumption indicates the adverse postingestive consequences of tall larkspur ingestion, as the larkspur group apparently developed a conditioned taste aversion to the larkspur pellet. Even though these animals were averted to the pellets, they showed none of the classical signs of intoxication from ingestion of tall larkspur.}, } @article {pmid24924361, year = {1985}, author = {Kronenberger, JP and Médioni, J}, title = {Food neophobia in wild and laboratory mice (Mus musculus domesticus).}, journal = {Behavioural processes}, volume = {11}, number = {1}, pages = {53-59}, doi = {10.1016/0376-6357(85)90102-0}, pmid = {24924361}, issn = {0376-6357}, abstract = {In a conditioned taste aversion procedure we were specifically interested in the topic of food neophobia. Wild and laboratory mice were individually presented with a novel drink (0.1 % saccharin solution). Compared with the daily water consumption, the intake of this was lower. This decrease was greater: (1) in wild than in tame populations ; (2) in random-bred (Swiss-albinos) than in inbred (C57 B1/6, BALB/c) strains ; (3) in F1-hybrids (either wild x tame or inbred x inbred) than in the parental strains. These results are discussed: (1) in terms of a selective pressure linked to man's fight against rodents, leading to increased neophobia in wild mice ; and (2) by stressing the heterosis an inbreeding depression effects, which suggest that food neophobia is a component of Darwinian fitness.}, } @article {pmid24924359, year = {1985}, author = {Marcant, P and Schmaltz, G and Roy, JC and Leconte, P}, title = {Long-term retention of a poorly learned saccharin aversion : Evidence for an incubation effect.}, journal = {Behavioural processes}, volume = {11}, number = {1}, pages = {15-20}, doi = {10.1016/0376-6357(85)90098-1}, pmid = {24924359}, issn = {0376-6357}, abstract = {The retention of a weak conditioned saccharin aversion was tested using independent groups over a 14-day period. The delay between CS (saccharin 0.1 %) and US (LiCl 0.15 M) was 6 hours. Significant variations in the retention function were observed, in particular an improvement of memory - i.e. an incubation effect - over the 14-day period. This result suggests that retention of conditioned taste aversion may share common features with the retention of more classical aversive conditioning.}, } @article {pmid24896988, year = {1985}, author = {Schneider, K and Loebell, F}, title = {The role of new flavors in the aquisition of odor aversion.}, journal = {Behavioural processes}, volume = {10}, number = {1-2}, pages = {111-121}, doi = {10.1016/0376-6357(85)90122-6}, pmid = {24896988}, issn = {0376-6357}, abstract = {In two experiments rats received either an odor together with a flavor (experiment I) or with tap water (experiment II) prior to lithium chloride-induced illness. The rats were then tested for the aversion of tap water in compound with the illness-paired odor offered together with an alternative new odor not paired with toxicosis. The two-odor-box-choice tests revealed that rats easily acquire an odor aversion even when the odor is not presented in a simultaneous compound with a new flavor and reject the drinking box, where the conditioned odor is presented, purely on the basis of that odor. Food Aversion Learning, Taste Aversion, Odor Aversion, Odor Potentiation.}, } @article {pmid17795833, year = {1983}, author = {Nicolaus, LK and Cassel, JF and Carlson, RB and Gustavson, CR}, title = {Taste-aversion conditioning of crows to control predation on eggs.}, journal = {Science (New York, N.Y.)}, volume = {220}, number = {4593}, pages = {212-214}, doi = {10.1126/science.220.4593.212}, pmid = {17795833}, issn = {0036-8075}, abstract = {Free-ranging crows (Corvus brachyrhynchos) that ate chicken eggs that were painted green and contained a nonlethal toxin subsequently avoided green eggs at various locations, whether or not they contained toxin. The crows also continued to eat unpainted and nontoxic chicken eggs. Illness-induced aversions among predators in nature may be a powerful determiner of the evolution of Batesian mimicry and, in human hands, serve as a practical tool for wildlife ecologists.}, } @article {pmid28310778, year = {1983}, author = {Sorensen, AE}, title = {Taste aversion and frugivore preference.}, journal = {Oecologia}, volume = {56}, number = {1}, pages = {117-120}, pmid = {28310778}, issn = {1432-1939}, abstract = {I tested the hypothesis that thrushes avoid certain species of fruits because of their taste. It was found that thrushes had significant preferences and aversions for the flavours of certain species of fruit. Several species of fruit which thrushes avoided contained identified toxins. It is speculated that some species of plants have evolved fruit toxins to prevent thrushes from consuming fruits and dispersing seeds to unfavourable habitats.}, } @article {pmid27942819, year = {1981}, author = {Novin, D and Rogers, RC and Hermann, G}, title = {Visceral afferent and efferent connections in the brain.}, journal = {Diabetologia}, volume = {20}, number = {Suppl 1}, pages = {331-336}, pmid = {27942819}, issn = {1432-0428}, abstract = {Behavioral and physiological studies have revealed increasing evidence in thirst, hunger, energy and water metabolism for the importance of visceral input to the brain as well as central modulation of visceral events. Recent work in our laboratory has now revealed some new information about the central course of these afferent and efferent systems. From our work and others there is now good evidence that the bed of the hepatic-portal system contains sodium and osmoreceptors. Our electrophysiological and histochemical studies show that one branch overlaps the gustatory pathway. That is, involves the vagus nerve, nucleus tractus solitarius, parabrachial nucleus and ventro-basal thalamus (VBC). Another branch goes not to VBC but to the supra-optic nucleus. At the one level so far investigated clear evidence was obtained for convergence on single cells of visceral and gustatory inputs. It may well occur at other levels. A parallel and perhaps interacting efferent system more related to energy regulation has also been explored. The major parasympathetic output to the viscera are the axons of the brain stem dorsal-motor nucleus (DMV) forming the vagus nerves. We have shown that the paraventricular nucleus, which was known to project to DMV, is the only structure above the brain stem that has a direct input to DMV. However, since the nucleus of the solitary tract and reticular formation send fibers to the DMV the neural substrate exists for considerable indirect input. The significance of these results is that it provides a central neural substrate of the 2-way pathways linking brain and viscera. Thus, we now know more about neural control mechanisms involved in several motivational and metabolic systems. The close contiguity and even convergence of gustatory and visceral afferents may help to explain taste-aversion learning and alterations in the hedonics of taste under different nutritional states. The unique place of the paraventricular nucleus in relation to parasympathetic efferents will doubtless lead to new knowledge of the role of the brain in control of energy metabolism.}, } @article {pmid16812198, year = {1981}, author = {Poling, A and Cleary, J and Monaghan, M}, title = {Burying by rats in response to aversive and nonaversive stimuli.}, journal = {Journal of the experimental analysis of behavior}, volume = {35}, number = {1}, pages = {31-44}, pmid = {16812198}, issn = {0022-5002}, abstract = {Previous investigations have shown that rats bury a variety of conditioned and unconditioned aversive stimuli. Such burying has been considered as a species-typical defensive reaction. In the present studies, rats buried spouts filled with Tabasco sauce, or condensed milk to which a taste aversion was conditioned, but did not bury water-filled spouts or spouts filled with a palatable novel food (apple juice) to which a taste aversion was not conditioned. However, in other experiments rats consistently and repeatedly buried Purina Rat Chow, Purina Rat Chow coated with quinine, and glass marbles. This indicates that a variety of stimuli, not all aversive or novel, evoke burying by rats. Whereas the behavior may reasonably be considered as a species-typical defensive behavior in some situations, the wide range of conditions that occasion burying suggests that the behavior has no single biological function.}, } @article {pmid24925507, year = {1980}, author = {Martin, JR and Baettig, K}, title = {Acquisition and extinction of gustatory aversion in two lines of rats selectively bred for differential shuttlebox avoidance performance.}, journal = {Behavioural processes}, volume = {5}, number = {4}, pages = {303-310}, doi = {10.1016/0376-6357(80)90014-5}, pmid = {24925507}, issn = {0376-6357}, abstract = {Consumption of a palatable saccharin-glucose (SG) solution was compared in Roman High Avoidance (RHA/Verh) and Roman Low Avoidance (RLA/Verh) lines of rats in a taste aversion acquisition and extinction paradigm. Prior to treatment, SG-intake in a 1 -h drinking test by RHA/Verh rats was much greater than that by RLA/Verh rats. Both psychogenetic lines increased SG-intake over a series of exposures when each presentation was followed by saline injection, but decreased SG-intake when each presentation was followed by apomorphine injection. At the end of the acquisition phase, RHA/Verh rats treated with a toxic dose of apomorphine drank 36% less SG than RHA/Verh rats that were injected with saline, whereas RLA/Verh rats treated with apomorphine consumed 54% less SG than RLA/Verh rats injected with saline. Following 16 daily presentations of SG but no injections, extinction of the conditioned gustatory aversion was complete in the RHA/Verh group previously treated with apomorphine, but it remained incomplete in the RLA/Verh rats previously treated with apomorphine. This stronger taste aversion exhibited by RLA/Verh rats is in marked contrast to their extremely inferior performance in a shuttlebox active avoidance task. The basis of the behavioral differences in these two psychogenetically selected lines of rats is discussed.}, } @article {pmid24897363, year = {1979}, author = {Burešová, O and Bureš, J}, title = {Extinction of a newly acquired conditioned taste aversion: Effect of gustatory CS administered under anaesthesia.}, journal = {Behavioural processes}, volume = {4}, number = {4}, pages = {329-339}, doi = {10.1016/0376-6357(79)90017-2}, pmid = {24897363}, issn = {0376-6357}, abstract = {Gustatory stimuli administered by intraperitoneal injection of concentrated flavour to anaesthetized rats cannot be associated with subsequent poisoning, but can extinguish an earlier established conditioned taste aversion (CTA). The differential sensitivity of CTA acquisition and extinction processes to anaesthesia was used to examine their interaction in the early stages of CTA learning. Male, hooded rats maintained on a 24-h water deprivation schedule were offered 15-min access to 0.1% saccharin (CS), were immediately afterwards anaesthetized with sodium pentobarbital and poisoned 30 min later by intraperitoneal injection of LiCl (US, 0.15 M, 2% body weight). Saccharin intake during a second presentation of the CS on the following day served as a measure of retention. Intraperitoneal injection of 2% saccharin (1% body weight) applied in the middle of the CS-US interval or 1 h after US administration did not decrease the CTA strength. Saccharin administered 2, 3, 4, and 5 h after US caused a gradually increasing CTA extinction which was almost complete with the 5-h interval and slightly decreased with the 24-h delay. The failure of the saccharin injection applied 1 h after US to extinguish the newly acquired CTA is not due to coincidence of the gustatory stimulus with the continuing symptoms of poisoning, since LiCl administration preceding saccharin injection does not prevent CTA extinction in rats with well established CTA. It is concluded that the post-acquisition gradient of extinction reflects the decay of the short-term gustatory trace established during the initial saccharin drinking.}, } @article {pmid24896436, year = {1977}, author = {Banerjee, U and Das, P}, title = {Amnesic effects of electroshock and anoxia on conditioned taste aversion learning in rats.}, journal = {Behavioural processes}, volume = {2}, number = {2}, pages = {175-186}, doi = {10.1016/0376-6357(77)90019-5}, pmid = {24896436}, issn = {0376-6357}, abstract = {Albino Wistar rats of both sexes were given a conditioned taste aversion training (CTA). Saccharin was used as the conditional stimulus (CS) and apomorphine-induced illness as the unconditional stimulus (US) on day 4. Amnestic treatment with electroconvulsive shock (ECS) or nitrogen anoxia were given to the rats at various points within the 180-min long CS-US interval as well as after the US. They were reexposed to the CS on days 5 and 6 in order to evaluate CTA and its extinction respectively. Apomorphine injection alone produced significant CTA as long as the CS-US interval was less than 120 min but not beyond it. Saline injections, with or without amnestic treatments, produced only an adaptation to and preference for saccharin. ECS could prevent CTA when delivered within 85 min before or 110 min after the US. Anoxia was effective at a much shorter range of time than ECS. The results are discussed in the perspectives of neophobia, saccharin aversion, amnestic agents and the character as well as gradients of amnesia produced.}, } @article {pmid19604856, year = {1976}, author = {Roberts, DC and Fibiger, HC}, title = {Conditioned taste aversion induced by diethyldithiocarbamate (DDC).}, journal = {Neuroscience letters}, volume = {2}, number = {6}, pages = {339-342}, doi = {10.1016/0304-3940(76)90171-3}, pmid = {19604856}, issn = {0304-3940}, abstract = {Subcutaneous injections of 150, 300, or 600 mg/kg diethyldithiocarbamate (DDC) immediately following a 0.5 h exposure to a novel saccharin solution caused a pronounced aversion to saccharin in rats when tested four days later. No statistical difference was observed between the effects of these dosages. These results suggest that DDC possesses punishing properties and that the previously reported amnesic properties of DDC are not apparent in all passive avoidance tasks.}, } @article {pmid19604802, year = {1975}, author = {Roberts, DC and Fibiger, HC}, title = {Attenuation of amphetamine-induced conditioned taste aversion following intraventricular 6-hydroxydopamine.}, journal = {Neuroscience letters}, volume = {1}, number = {6}, pages = {343-347}, doi = {10.1016/0304-3940(75)90024-5}, pmid = {19604802}, issn = {0304-3940}, abstract = {Intraventricular administration of 6-hydroxydopamine, which depleted central norepinephrine and dopamine contents to 17 and 10% of control levels, respectively, was shown to severely attenuate a conditioned taste aversion induced by repeated exposure to 1.0 mg/kg d-amphetamine. This attenuation was not the result of a general learning deficit because animals with identical treatments acquired a conditioned taste aversion when lithium chloride was used as the punishing stimulus. These and other [5,6] results suggest that the punishing, as well as the rewarding properties of amphetamine are mediated via central catecholaminergic neurons.}, } @article {pmid15839775, year = {2005}, author = {Urushihara, K and Wheeler, DS and Pineño, O and Miller, RR}, title = {An extended comparator hypothesis account of superconditioning.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {31}, number = {2}, pages = {184-198}, doi = {10.1037/0097-7403.31.2.184}, pmid = {15839775}, issn = {0097-7403}, support = {33881//PHS HHS/United States ; }, mesh = {Adjuvants, Immunologic/administration & dosage/pharmacology ; Animals ; *Conditioning, Classical ; Cues ; Female ; Learning ; Lithium Chloride/administration & dosage/pharmacology ; Male ; Neural Inhibition/*physiology ; *Psychological Theory ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Three conditioned taste aversion experiments with rats investigated superconditioning. In each experiment, alternate exposures of 2 flavor compounds with a common element (i.e., AB/AS) were administered to establish an inhibitory relationship between the 2 unique elements, B and S, and prior to testing, S was paired with lithium chloride (LiCl). In Experiment 1, pairings of a neutral cue (X) with S in compound with B after the AB/AS exposures resulted in superconditioning between X and S. Extinction of the common element (A) just before the S-LiCl pairing attenuated both the inhibitory relationship between B and S (Experiment 2) and superconditioning between X and S (Experiment 3). These observations suggest that superconditioning consists of enhanced performance rather than enhanced associative acquisition.}, } @article {pmid15825886, year = {2004}, author = {Smith, ME and Norgren, R and Grigson, PS}, title = {A mixed design reveals that glucose moieties facilitate extinction of a conditioned taste aversion in rats.}, journal = {Learning & behavior}, volume = {32}, number = {4}, pages = {454-462}, pmid = {15825886}, issn = {1543-4494}, support = {DA-09815/DA/NIDA NIH HHS/United States ; DA-12473/DA/NIDA NIH HHS/United States ; DC-00240/DC/NIDCD NIH HHS/United States ; DK-09926/DK/NIDDK NIH HHS/United States ; }, mesh = {Alanine ; Animals ; *Association Learning ; Choice Behavior ; *Conditioning, Classical ; Discrimination Learning ; Dose-Response Relationship, Drug ; Drinking/drug effects ; *Extinction, Psychological ; Fructose ; Glucans ; *Glucose Solution, Hypertonic ; Lithium Chloride/toxicity ; Male ; Maltose ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Sucrose ; *Taste ; }, abstract = {Separate groups of water-deprived rats had four trials with 15-min access to 0.0073 M saccharin, 0.3 M alanine, 0.3 M glucose, 0.1 M maltose, 0.3 M fructose, 0.06 M sucrose, or 0.03 M Polycose. Trials 1-3 were followed by injections of either 0.15 M LiCl (1.33 ml/100 g b.w., i.p.) or saline; Trial 4 (Test) was CS only. Extinction included either 48-h access to water alone or to the appropriate CS, both followed by a 24-h, two-bottle choice of CS and water. This 3-day cycle was repeated five to six times. All rats acquired comparable conditioned taste aversions (CTAs), but extinction rates varied with the test and the taste CS. No CTA extinguished during the two-bottle choices following 2 water days. During one-bottle CS exposure, all CTAs extinguished, but the aversion continued longer in the probe two-bottle tests. Intake of glucose moieties recovered rapidly, often in two cycles; the other CSs took four to six cycles. Thus, CTA extinction varies with the nature of the taste CS.}, } @article {pmid15803624, year = {2004}, author = {Shukitt-Hale, B and Szprengiel, A and Pluhar, J and Rabin, BM and Joseph, JA}, title = {The effects of proton exposure on neurochemistry and behavior.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {33}, number = {8}, pages = {1334-1339}, doi = {10.1016/j.asr.2003.10.038}, pmid = {15803624}, issn = {0273-1177}, mesh = {Animals ; Avoidance Learning/radiation effects ; Behavior, Animal/*radiation effects ; Conditioning, Psychological/*radiation effects ; Dopamine/metabolism/radiation effects ; Dose-Response Relationship, Radiation ; Iron ; Iron Radioisotopes ; Learning/*radiation effects ; Male ; Maze Learning/radiation effects ; Nervous System Physiological Phenomena/radiation effects ; Neurochemistry ; Particle Accelerators ; *Protons ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior/*radiation effects ; Taste/radiation effects ; Time Factors ; Water ; }, abstract = {Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.}, } @article {pmid15803623, year = {2004}, author = {Rabin, BM and Joseph, JA and Shukitt-Hale, B}, title = {Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {33}, number = {8}, pages = {1330-1333}, doi = {10.1016/j.asr.2003.09.051}, pmid = {15803623}, issn = {0273-1177}, mesh = {Amphetamine/radiation effects ; Animals ; Avoidance Learning/radiation effects ; Behavior, Animal/*radiation effects ; Central Nervous System/*radiation effects ; Central Nervous System Stimulants/radiation effects ; Conditioning, Psychological/radiation effects ; Dose-Response Relationship, Radiation ; *Heavy Ions ; Motor Activity/radiation effects ; Nervous System Physiological Phenomena/*radiation effects ; Neurochemistry ; Rats ; Recovery of Function/radiation effects ; Relative Biological Effectiveness ; Taste/radiation effects ; }, abstract = {Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.}, } @article {pmid15800216, year = {2005}, author = {St John, SJ and Pour, L and Boughter, JD}, title = {Phenylthiocarbamide produces conditioned taste aversions in mice.}, journal = {Chemical senses}, volume = {30}, number = {5}, pages = {377-382}, doi = {10.1093/chemse/bji032}, pmid = {15800216}, issn = {0379-864X}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior ; Female ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Phenylthiourea/*pharmacology ; Sucrose ; Taste/*drug effects ; }, abstract = {Previous work has demonstrated that SWR/J (SW) mice avoid phenylthiocarbamide (PTC) to a greater degree than C3HeB/FeJ mice in 48 h, two-bottle preference tests given in ascending series. The authors hypothesized, based also on previous work, that SW mice might form a conditioned taste aversion over time due to the toxic properties of PTC. We directly tested this hypothesis by attempting to condition a taste aversion to sucrose by injections of PTC. In experiment 1, PTC was nearly as effective as a strong dose of LiCl in reducing sucrose drinking. In experiment 2, the sucrose aversions were parametrically modified by both sucrose concentration and PTC dose, a hallmark of conditioned taste aversion. We conclude that PTC can cause a conditioned taste aversion and discuss the importance of considering toxic effects of aversive tastants when analyzing behavioral strain differences.}, } @article {pmid15789863, year = {2005}, author = {McBride, WJ and Bell, RL and Rodd, ZA and Strother, WN and Murphy, JM}, title = {Adolescent alcohol drinking and its long-range consequences. Studies with animal models.}, journal = {Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism}, volume = {17}, number = {}, pages = {123-142}, doi = {10.1007/0-306-48626-1_6}, pmid = {15789863}, issn = {0738-422X}, support = {AA007611/AA/NIAAA NIH HHS/United States ; AA10256/AA/NIAAA NIH HHS/United States ; AA10717/AA/NIAAA NIH HHS/United States ; AA10721/AA/NIAAA NIH HHS/United States ; AA11261/AA/NIAAA NIH HHS/United States ; }, mesh = {Adolescent ; Alcohol Drinking/*epidemiology ; Animals ; Behavior, Animal ; Choice Behavior ; Disease Models, Animal ; Ethanol/administration & dosage/*pharmacology ; Humans ; Rats ; Self Administration ; Serotonin/*metabolism ; }, abstract = {This chapter reviews findings, mainly obtained from the selectively bred alcohol-preferring (P) line of rats, on (a) the development of alcohol drinking during the peri-adolescent period, (b) neurobiological factors that may contribute to adolescent drinking, (c) interventions to prevent alcohol drinking during adolescence, and (d) some long-lasting consequences of adolescent alcohol drinking. The findings indicate that P rats readily initiate alcohol drinking during the early post-weaning, adolescent and peri-adolescent periods of development. The early age-of-onset of alcohol drinking in the P compared to the NP line is associated with (a) higher densities of serotonin-1A (5-HT1A) receptors in cerebral cortical and hippocampal regions; (b) lower densities of dopamine (DA) D2 receptors in the ventral tegmental area (VTA); (c) higher functional activity in several limbic, cortical and hippocampal regions; and (d) sensitivity to the low-dose stimulating effect of ethanol. Conditioned taste aversion (CTA) training during adolescence produces long-term effects on preventing high alcohol drinking behavior of P rats. Alcohol drinking during peri-adolescence by P rats produces long-lasting effects that increase the acquisition of ethanol self-administration in adulthood, and, in addition, increase craving-like behavior and the potential for alcohol relapse. With suitable animal models, a better understanding of the mechanisms underlying adolescent alcohol drinking and its long-range consequences can be attained.}, } @article {pmid15770113, year = {2005}, author = {Pelloux, Y and Hagues, G and Costentin, J and Duterte-Boucher, D}, title = {Helplessness in the tail suspension test is associated with an increase in ethanol intake and its rewarding effect in female mice.}, journal = {Alcoholism, clinical and experimental research}, volume = {29}, number = {3}, pages = {378-388}, doi = {10.1097/01.alc.0000156123.10298.fa}, pmid = {15770113}, issn = {0145-6008}, mesh = {Alcohol Drinking/*psychology ; Animals ; Central Nervous System Depressants/blood/*pharmacology ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/blood/*pharmacology ; Female ; *Helplessness, Learned ; Hindlimb Suspension/*physiology ; Hypothermia/chemically induced ; Mice ; Motor Activity/physiology ; Reward ; Taste/drug effects ; }, abstract = {BACKGROUND: Depression is frequently observed in drug abusers. However, depression may be a primary factor of predisposition to drug abuse or a consequence of drug abuse. The aim of this study was to analyze the influence of a preexisting depressive-like state/helplessness on subsequent alcohol responsiveness in mice.

METHODS: Male and female CD1 mice were selected according to their immobility time in the tail suspension test, and only mice with "high immobility" and "low immobility" time were retained. Using a two-bottle free-choice paradigm, these mice were given continuous access to tap water or solutions of ethanol (3-20% v/v), quinine (12.5-50 mg/liter), or sucrose (1-4% w/v). In female mice, rewarding and aversive effects of ethanol (1.5 and 3 g/kg, intraperitoneally) were also investigated using the conditioned place preference and the conditioned taste aversion paradigms.

RESULTS: Female mice were more immobile and drank more ethanol than male mice. No striking sex difference was observed in quinine consumption. Sucrose intake was higher in female than in male mice, whatever the solution concentration. At the 4% concentrated solution, a sucrose-induced increase in daily fluid intake was observed only in female mice. Female mice with high immobility time (HI) consumed more ethanol at the highest concentration than female mice with low immobility time (LI), whereas no difference was observed between HI and LI male mice. Moreover, whereas LI female mice failed to express place conditioning induced by the 3-g/kg dose of ethanol, HI female mice were strongly responsive to the rewarding effect of this high ethanol dose. Ethanol dose-dependently induced a conditioned taste aversion with a similar magnitude in both LI and HI female mice.

CONCLUSIONS: The findings indicate that female CD1 mice tend to drink greater amounts of ethanol or sucrose solutions than male CD1 mice, suggesting that female mice may be a better model of excessive alcohol intake. Furthermore, no relationship was found between immobility scores and ethanol consumption in male mice. On the contrary, within female mice, HI mice consumed higher amounts of ethanol than LI mice probably because they experienced greater rewarding effects of ethanol. The present results support the hypothesis that depressive-like responses may predispose to ethanol abuse in female mice.}, } @article {pmid15745959, year = {2005}, author = {Pacheco-López, G and Niemi, MB and Kou, W and Härting, M and Fandrey, J and Schedlowski, M}, title = {Neural substrates for behaviorally conditioned immunosuppression in the rat.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {25}, number = {9}, pages = {2330-2337}, pmid = {15745959}, issn = {1529-2401}, mesh = {Amygdala/physiology ; Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Behavior, Animal/drug effects/physiology ; Brain Injuries/chemically induced/physiopathology ; *Brain Mapping ; Cell Proliferation ; Cerebral Cortex/anatomy & histology/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Cyclosporine/pharmacology ; Cytokines/metabolism ; Flow Cytometry/methods ; Hypothalamus, Middle/immunology/physiology ; Immunity, Cellular/drug effects/*physiology ; *Immunosuppression Therapy ; Immunosuppressive Agents/pharmacology ; Leukocyte Count/methods ; Lymphocytes/drug effects/physiology ; Male ; N-Methylaspartate ; Neurons/drug effects/physiology ; Rats ; Time Factors ; }, abstract = {We have previously demonstrated behaviorally conditioned immunosuppression using cyclosporin A as an unconditioned stimulus and saccharin as a conditioned stimulus. In the current study, we examined the central processing of this phenomenon generating excitotoxic lesions before and after acquisition to discriminate between learning and memory processes. Three different brain areas were analyzed: insular cortex (IC), amygdala (Am), and ventromedial nucleus of the hypothalamus (VMH). The results demonstrate that IC lesions performed before and after acquisition disrupted the behavioral component of the conditioned response (taste aversion). In contrast, Am and VMH lesions did not affect conditioned taste aversion. The behaviorally conditioned suppression of splenocyte proliferation and cytokine production (interleukin-2 and interferon-gamma) was differentially affected by the excitotoxic lesions, showing that the IC is essential to acquire and evoke this conditioned response of the immune system. In contrast, the Am seems to mediate the input of visceral information necessary at the acquisition time, whereas the VMH appears to participate within the output pathway to the immune system necessary to evoke the behavioral conditioned immune response. The present data reveal relevant neural mechanisms underlying the learning and memory processes of behaviorally conditioned immunosuppression.}, } @article {pmid15740790, year = {2005}, author = {Simpson, GR and Riley, AL}, title = {Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {80}, number = {3}, pages = {471-479}, doi = {10.1016/j.pbb.2005.01.003}, pmid = {15740790}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Male ; Morphine/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; Time Factors ; }, abstract = {Repeated morphine preexposure has been reported to enhance measures of morphine reward (conditioned place preference; CPP) and attenuate measures of morphine aversion (conditioned taste aversion; CTA). These effects are generally independently assessed, limiting the ability to determine if the enhancing and attenuating effects of morphine exposure are mediated by a common factor. To assess any potential relationship between these two effects, the present study examined the impact of morphine preexposure on these motivational properties of morphine using a combined CTA/CPP procedure in which the same animals receive concurrent taste and place conditioning. Specifically, male Sprague-Dawley rats were preexposed to morphine [5 mg/kg; subcutaneously (sc)] or equivolume drug vehicle. Following preexposure, animals were given saccharin to drink and injected with morphine sulfate (1 or 5 mg/kg sc) or drug vehicle (CTA). Immediately thereafter, they were placed on one side of a two-compartment chamber (CPP). On the next day, they were given water followed by injections of the drug's vehicle and then placed in the other compartment. There were four such conditioning cycles after each of which a CTA and CPP test were given. While preexposure to morphine attenuated morphine-induced CTAs, morphine-induced CPPs were enhanced within the same animals. These effects of morphine preexposure were dose- and time-dependent and parallel. These data indicate that the attenuating and sensitizing effects of morphine preexposure on taste aversions and place preferences, respectively, could be mediated by a common mechanism, although other possibilities for these effects of morphine preexposure remain.}, } @article {pmid15738089, year = {2005}, author = {Yasoshima, Y and Yamamoto, T and Kobayashi, K}, title = {Amygdala-dependent mechanisms underlying memory retrieval of conditioned taste aversion.}, journal = {Chemical senses}, volume = {30 Suppl 1}, number = {}, pages = {i158-9}, doi = {10.1093/chemse/bjh162}, pmid = {15738089}, issn = {1464-3553}, mesh = {Amygdala/*physiology ; Animals ; Benzodiazepines/pharmacology ; Conditioning, Classical ; Desipramine/pharmacology ; Dopamine/metabolism ; Glutamine/metabolism ; *Memory ; Midazolam/pharmacology ; Models, Biological ; Norepinephrine/metabolism ; Rats ; Receptors, AMPA/*metabolism ; *Taste ; gamma-Aminobutyric Acid/metabolism ; }, } @article {pmid15698900, year = {2005}, author = {Bethus, I and Lemaire, V and Lhomme, M and Goodall, G}, title = {Does prenatal stress affect latent inhibition? It depends on the gender.}, journal = {Behavioural brain research}, volume = {158}, number = {2}, pages = {331-338}, doi = {10.1016/j.bbr.2004.09.013}, pmid = {15698900}, issn = {0166-4328}, mesh = {Animals ; Conditioning, Operant/drug effects ; Drinking Behavior/drug effects ; Eating/drug effects/psychology ; Female ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; Reflex, Startle/*physiology ; Sex Characteristics ; Stress, Psychological/*physiopathology ; Taste/drug effects ; }, abstract = {The present experiment was designed to examine the effects of prenatal stress and gender in latent inhibition. Prenatal stress has been proposed as a risk factor both for depression and for schizophrenia, and both of these syndromes are associated with alterations in the functional state of the dopamine system. There is also some evidence that prenatal stress can produce changes in dopamine activity, although the details of the stress-induced changes are a matter of debate. Latent inhibition (LI), which is strongly dependent on dopaminergic activity, consists in delayed Pavlovian conditioning about a stimulus that previously signalled no consequence. We induced prenatal stress by exposing gestating dams to a daily constraint stress during the last week of pregnancy. We tested the rats for LI of conditioned taste aversion by exposing them to sucrose for 3 days prior to conditioning. Irrespective of stress or gender, latent inhibition was observed but the degree of LI varied as a function of both prenatal stress and gender. Unstressed males showed less LI than unstressed females, but prenatal stress increased the amount of LI only in the males. These results are inconsistent with the use of prenatal stress as an animal model for schizophrenia. A model is proposed that accounts for the relationships between gender, dopamine function, cognitive changes and psychiatric pathology.}, } @article {pmid15680181, year = {2005}, author = {Freeman, KB and Konaklieva, MI and Riley, AL}, title = {Assessment of the contributions of Na+ channel inhibition and general peripheral action in cocaine-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {80}, number = {2}, pages = {281-288}, doi = {10.1016/j.pbb.2004.11.009}, pmid = {15680181}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Cocaine/*pharmacology ; Conditioning, Psychological/*drug effects/physiology ; Male ; Peripheral Nervous System/*drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Sodium Channel Blockers/*pharmacology ; Sodium Channels/*physiology ; Taste/*drug effects/physiology ; }, abstract = {While the rewarding properties of cocaine appear to be mediated by its blockade of central monoamine uptake, the mechanisms and sites of action for cocaine's aversive effects have yet to be determined. Using the conditioned taste aversion (CTA) preparation, the present study examined the role of Na(+) channel blockade in cocaine's aversive effects by comparing cocaine to the local anesthetic procaine at three doses (18, 32 and 50 mg/kg). Furthermore, the role of cocaine's peripheral actions in its aversive effects was examined by comparing cocaine to the quaternary analog cocaine methiodide (equimolar to the three doses of cocaine) in establishing CTAs. Procaine and cocaine methiodide each dose-dependently suppressed saccharin consumption, indicating that the aversive effects of cocaine are, in part, mediated by its inhibition of Na(+) channels and via its activity in the PNS. However, the fact that the aversions induced by procaine and cocaine methiodide were weaker than those induced by cocaine at each dose tested suggests other factors are involved in its aversive effects. Possible reasons for the weaker aversions induced by procaine and cocaine methiodide relative to cocaine were discussed.}, } @article {pmid15642601, year = {2005}, author = {Masaki, T and Nakajima, S}, title = {Further evidence for conditioned taste aversion induced by forced swimming.}, journal = {Physiology & behavior}, volume = {84}, number = {1}, pages = {9-15}, doi = {10.1016/j.physbeh.2004.09.022}, pmid = {15642601}, issn = {0031-9384}, mesh = {Analysis of Variance ; Animals ; *Association Learning ; Avoidance Learning/*physiology ; Behavior, Animal ; Conditioning, Classical/*physiology ; Drinking/physiology ; Male ; Rats ; Rats, Wistar ; Saccharin/metabolism ; Swimming/*psychology ; *Taste ; }, abstract = {A series of experiments with rats reported that aversion to a taste solution can be established by forced swimming in a water pool. Experiment 1 demonstrated that correlation of taste and swimming is a critical factor for this phenomenon, indicating associative (i.e., Pavlovian) nature of this learning. Experiment 2 showed that this learning obeys the Pavlovian law of strength, by displaying a positive relationship between the duration of water immersion in training and the taste aversion observed in subsequent testing. Experiment 3 revealed that swimming rather than being wet is the critical agent, because a water shower did not endow rats with taste aversion. Experiment 4 found that taste aversion was a positive function of water level of the pools in training (0, 12 or 32 cm). These results, taken together, suggest that energy expenditure caused by physical exercise might be involved in the development of taste aversion.}, } @article {pmid15617780, year = {2005}, author = {Pålsson, E and Klamer, D and Wass, C and Archer, T and Engel, JA and Svensson, L}, title = {The effects of phencyclidine on latent inhibition in taste aversion conditioning: differential effects of preexposure and conditioning.}, journal = {Behavioural brain research}, volume = {157}, number = {1}, pages = {139-146}, doi = {10.1016/j.bbr.2004.06.018}, pmid = {15617780}, issn = {0166-4328}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dextroamphetamine/pharmacology ; Drug Administration Schedule ; Enzyme Inhibitors/pharmacology ; Hallucinogens/*administration & dosage ; *Inhibition, Psychological ; Injections, Subcutaneous ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Phencyclidine/*administration & dosage ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; }, abstract = {Latent inhibition (LI) is a behavioural procedure in which preexposure to a stimulus not followed by reinforcement retards subsequent conditioning to this stimulus when it is paired with reinforcement. Changes in LI thus reflect greater or lesser retardation of learning which essentially implies a potentiation or an attenuation of the LI effect. LI has proved sensitive to psychotomimetic and antipsychotic treatment, which has encouraged its use to model learning and attention deficits in schizophrenia. In the present study, experiments were conducted to evaluate the effects of the psychotomimetic drug, phencyclidine (PCP, 2 mg/kg), and compare it with D-amphetamine (D-AMP, 0.33 and 1 mg/kg), on LI using a conditioned taste aversion procedure. PCP was found to potentiate LI when administered acutely prior to the conditioning trails, while no such effect was observed when administered prior to the preexposure trials. D-AMP, on the other hand, disrupted LI possibly due to a failure to induce a persistent taste aversion conditioning.}, } @article {pmid15617773, year = {2005}, author = {Bills, C and Schachtman, TR and Serfozo, P and Spooren, WP and Gasparini, F and Simonyi, A}, title = {Effects of metabotropic glutamate receptor 5 on latent inhibition in conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {157}, number = {1}, pages = {71-78}, doi = {10.1016/j.bbr.2004.06.011}, pmid = {15617773}, issn = {0166-4328}, support = {R01 MH59039-01/MH/NIMH NIH HHS/United States ; R03 MH64486-01A1/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists/pharmacology ; *Inhibition, Psychological ; Male ; Pyridines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/drug effects/*physiology ; Taste/drug effects/*physiology ; }, abstract = {Latent inhibition (LI) is a phenomenon by which pre-exposure of a conditioned stimulus (CS) prior to the CS-unconditioned stimulus (US) pairings retards conditioned responding (CR). LI has been demonstrated in a variety of learning tasks including conditioned taste aversion (CTA). Earlier work has shown that systemic administration of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective metabotropic glutamate receptor 5 (mGlu5) antagonist, is able to disrupt classical conditioning in CTA. The present study investigated the involvement of mGlu5 receptors in LI using a CTA procedure. In the first experiment, rats received either water (non-pre-exposed, NPE) or a saccharin solution (pre-exposed, PE) on 2 consecutive days. The animals then received conditioning in which a fixed amount of saccharin was paired with lithium chloride and then the CR to the taste was tested. Either MPEP (3, 6, 12 mg/kg) or vehicle was injected intraperitoneally prior to taste pre-exposure or testing. Animals in the vehicle control groups displayed LI. MPEP injections before pre-exposure trials attenuated LI but also reduced consumption during pre-exposure, which obscured interpretation of the LI effect. The second experiment used four pre-exposure trials and controlled access to fixed amount of the solutions during the pre-exposure as well as the conditioning trials. Rats were injected before pre-exposure trials but not before the test trial. The results found that MPEP attenuates latent inhibition suggesting that the mGlu5 receptor exerts an influence on the processes that underlie the effects of taste pre-exposure on conditioning.}, } @article {pmid15598148, year = {2004}, author = {Capaldi, ED and Hunter, MJ and Privitera, GJ}, title = {Odor of taste stimuli in conditioned "taste" aversion learning.}, journal = {Behavioral neuroscience}, volume = {118}, number = {6}, pages = {1400-1408}, doi = {10.1037/0735-7044.118.6.1400}, pmid = {15598148}, issn = {0735-7044}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal ; Conditioning, Classical/drug effects/*physiology ; Drinking Behavior/drug effects ; Generalization, Stimulus ; Lithium Chloride/pharmacology ; Male ; *Odorants ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; Saccharin/administration & dosage ; Taste/*physiology ; }, abstract = {The present research addresses whether rats can express odor aversions to the odor of taste stimuli. In Experiment 1, saccharin or salt were either mixed in distilled water, so the rats could taste and smell them, or presented on disks attached to the tubes' metal spouts so the rats could only smell them. Aversions were established to taste stimuli under both conditions. The results of Experiment 2 indicate that conditioning was to the odor of the tastes when they were presented on disks in Experiment 1, hence both taste and odor aversions were established by means of "taste" stimuli. Taste aversion learning thus may more properly be termed flavor aversion learning, with flavor referring to both taste and odor components.}, } @article {pmid15582988, year = {2005}, author = {Gessa, GL and Serra, S and Vacca, G and Carai, MA and Colombo, G}, title = {Suppressing effect of the cannabinoid CB1 receptor antagonist, SR147778, on alcohol intake and motivational properties of alcohol in alcohol-preferring sP rats.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {40}, number = {1}, pages = {46-53}, doi = {10.1093/alcalc/agh114}, pmid = {15582988}, issn = {0735-0414}, mesh = {Alcohol Drinking/*prevention & control ; Analysis of Variance ; Animals ; Ethanol/administration & dosage ; Male ; Motivation ; Piperidines/administration & dosage/*pharmacology ; Pyrazoles/administration & dosage/*pharmacology ; Rats ; Receptor, Cannabinoid, CB1/*antagonists & inhibitors ; Rimonabant ; Secondary Prevention ; Self Administration ; Temperance ; Time Factors ; }, abstract = {AIMS: The present study investigated the effect of the newly synthesized cannabinoid CB(1) receptor antagonist, SR147778, on alcohol intake and the motivational properties of alcohol in selectively bred Sardinian alcohol-preferring (sP) rats.

METHODS AND RESULTS: In Experiment 1, the repeated administration of SR147778 (0.3-3 mg/kg twice daily, i.p.) specifically suppressed the acquisition of alcohol drinking behaviour in alcohol-naive rats exposed to the two-bottle "alcohol vs water" choice regimen for 24 h/day. In Experiment 2, an acute administration of SR147778 (2.5-10 mg/kg, i.p.) specifically reduced alcohol intake in alcohol-experienced rats that were given alcohol and water under the two-bottle choice regimen in daily sessions of 4 h. In Experiment 3, an acute administration of SR147778 (0.3-3 mg/kg, i.p.) suppressed the "alcohol deprivation effect", i.e. the extra-intake of alcohol occurring after a period of alcohol abstinence. In Experiment 4, an acute administration of SR147778 (0.3-3 mg/kg, i.p.) specifically suppressed the extinction responding for alcohol, i.e. the maximal number of lever responses reached in the absence of alcohol in rats trained to lever-press for alcohol (measure of the motivational properties of alcohol). In Experiment 5, the combination of 3 mg/kg of SR147778 (i.p.) and 0.5 g/kg of alcohol (i.p.), a dose comparable with those usually consumed by sP rats in each drinking binge, failed to induce any conditioned taste aversion.

CONCLUSION: Taken together, these results extend to SR147778 the anti-alcohol profile of the prototype cannabinoid CB(1) receptor antagonist, rimonabant (SR141716), and strengthen the hypothesis that the cannabinoid CB(1) receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol.}, } @article {pmid15576070, year = {2004}, author = {Guitton, MJ and Dudai, Y}, title = {Anxiety-like state associates with taste to produce conditioned taste aversion.}, journal = {Biological psychiatry}, volume = {56}, number = {11}, pages = {901-904}, doi = {10.1016/j.biopsych.2004.08.024}, pmid = {15576070}, issn = {0006-3223}, mesh = {Animals ; Anxiety/chemically induced/*physiopathology ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal ; Central Nervous System Depressants/pharmacology ; Conditioning, Psychological/drug effects/*physiology ; Disease Models, Animal ; Drug Interactions ; Ethanol/pharmacology ; Glycine/administration & dosage ; Lithium Chloride/toxicity ; Male ; Piperazines/toxicity ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {BACKGROUND: The interactions among experience, emotion, and memory are considered to be instrumental in the ontogeny and maintenance of acquired emotional and behavioral disorders (e.g., phobias). Here we address the question whether an anxiety-like state can associate with taste to produce conditioned taste aversion (CTA).

METHODS: We have used an anxiogenic agent, the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP), to induce an anxiety-like emotional state in rats after consumption of an unfamiliar tastant.

RESULTS: The anxiogenic agent induced CTA. The mCPP-induced CTA could be prevented by concomitant administration of ethanol, which is known to reverse mCPP-induced anxiety-like behavior, at a concentration that had no effect on CTA memory. In contrast, ethanol did not prevent LiCl-induced CTA. Administration of mCPP before the consumption of the tastant had no effect on the preference for that tastant.

CONCLUSIONS: Taken together, these results indicate that anxiety-like state can serve as the unconditioned stimulus in CTA training. This finding may be relevant to the ontogeny of pathologies involving food aversion.}, } @article {pmid15574816, year = {2004}, author = {Taylor-Burds, CC and Westburg, AM and Wifall, TC and Delay, ER}, title = {Behavioral comparisons of the tastes of L-alanine and monosodium glutamate in rats.}, journal = {Chemical senses}, volume = {29}, number = {9}, pages = {807-814}, doi = {10.1093/chemse/bjh246}, pmid = {15574816}, issn = {0379-864X}, support = {DC005962/DC/NIDCD NIH HHS/United States ; }, mesh = {Alanine/*pharmacology ; Amiloride/pharmacology ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Discrimination, Psychological/drug effects ; Diuretics/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Sensory Thresholds/drug effects ; Sodium Glutamate/*pharmacology ; Taste/*drug effects ; }, abstract = {Recent research has implicated T1R1/T1R3 as the primary taste receptor in mammals for detecting L-amino acids, including L-monosodium glutamate (MSG) and L-alanine. Previous behavioral studies with rodents found only minimal evidence that these two substances share perceptual qualities, but those studies did not control for the taste of sodium associated with MSG. This study used several behavioral methods to compare the perceptual qualities of MSG and L-alanine in rats, using amiloride (a sodium channel blocker) to reduce the sodium component of MSG taste. Detection thresholds of L-alanine in rats ranged between 0.4 and 2.5 mM, with or without amiloride added, which are similar to threshold estimates for MSG. Conditioned taste aversion (CTA) found that rats showed strong cross-generalization of CTA between MSG and L-alanine when mixed with amiloride, indicating the two substances have similar perceptual qualities. Discrimination methods showed that rats easily discriminated between L-alanine and MSG unless the cue function of sodium was reduced. The discrimination became significantly more difficult at concentrations < 100 mM when amiloride was added to all stimuli and became even more difficult when NaCl was also added to L-alanine solutions to match the sodium concentrations of MSG. These results indicate that, perceptually, MSG and L-alanine have quite similar taste qualities and support the hypothesis that these two L-amino acids activate a common taste receptor. The differences in perceptual qualities also suggest separate afferent processing of one or both substances may also be involved.}, } @article {pmid15567487, year = {2004}, author = {Jahng, JW and Lee, JH and Lee, S and Lee, JY and Kim, GT and Houpt, TA and Kim, DG}, title = {N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in rats.}, journal = {Neuroscience research}, volume = {50}, number = {4}, pages = {485-492}, doi = {10.1016/j.neures.2004.08.016}, pmid = {15567487}, issn = {0168-0102}, mesh = {Amygdala/drug effects/metabolism ; Animals ; Avoidance Learning/*drug effects/physiology ; Brain/*drug effects/metabolism ; Conditioning, Psychological/*drug effects/physiology ; Corticosterone/blood ; Down-Regulation/drug effects/physiology ; Enzyme Inhibitors/pharmacology ; Hypothalamo-Hypophyseal System/drug effects/metabolism ; Injections, Intraperitoneal ; Lithium/*antagonists & inhibitors ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitrergic Neurons/*drug effects/metabolism ; Nitric Oxide/*metabolism ; Paraventricular Hypothalamic Nucleus/drug effects/metabolism ; Proto-Oncogene Proteins c-fos/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/drug effects/metabolism ; Taste/*drug effects/physiology ; }, abstract = {Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the relevant brain regions and activates the hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric oxide (NO) in the central nervous system may play a role not only in the activation of HPA axis but also in CTA learning, and that LiCl may activate the brain NO system. To determine the role of NO in lithium-induced CTA, we examined the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium-induced c-Fos expression in the brain regions implicated in CTA learning, such as the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA acquisition or the increase in plasma corticosterone was not attenuated by l-NAME pretreatment. These results suggest that NO may be involved in lithium-induced neuronal activation of the brain regions, but not in the CTA acquisition or the HPA axis activation.}, } @article {pmid15544578, year = {2004}, author = {Ponomarev, I and Schafer, GL and Blednov, YA and Williams, RW and Iyer, VR and Harris, RA}, title = {Convergent analysis of cDNA and short oligomer microarrays, mouse null mutants and bioinformatics resources to study complex traits.}, journal = {Genes, brain, and behavior}, volume = {3}, number = {6}, pages = {360-368}, doi = {10.1111/j.1601-183x.2004.00088.x}, pmid = {15544578}, issn = {1601-1848}, support = {AA06399/AA/NIAAA NIH HHS/United States ; AA13518/AA/NIAAA NIH HHS/United States ; AA13520/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Computational Biology ; DNA, Complementary/*analysis ; Databases, Genetic ; Enkephalins/deficiency/genetics ; Ethanol/pharmacology ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; *Gene Expression Profiling ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout/*genetics ; Models, Genetic ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Potassium Channels, Inwardly Rectifying/deficiency/*genetics ; Protein Precursors/deficiency/genetics ; RNA, Messenger/analysis ; Taste/drug effects/*genetics ; }, abstract = {Gene expression data sets have recently been exploited to study genetic factors that modulate complex traits. However, it has been challenging to establish a direct link between variation in patterns of gene expression and variation in higher order traits such as neuropharmacological responses and patterns of behavior. Here we illustrate an approach that combines gene expression data with new bioinformatics resources to discover genes that potentially modulate behavior. We have exploited three complementary genetic models to obtain convergent evidence that differential expression of a subset of genes and molecular pathways influences ethanol-induced conditioned taste aversion (CTA). As a first step, cDNA microarrays were used to compare gene expression profiles of two null mutant mouse lines with difference in ethanol-induced aversion. Mice lacking a functional copy of G protein-gated potassium channel subunit 2 (Girk2) show a decrease in the aversive effects of ethanol, whereas preproenkephalin (Penk) null mutant mice show the opposite response. We hypothesize that these behavioral differences are generated in part by alterations in expression downstream of the null alleles. We then exploited the WebQTL databases to examine the genetic covariance between mRNA expression levels and measurements of ethanol-induced CTA in BXD recombinant inbred (RI) strains. Finally, we identified a subset of genes and functional groups associated with ethanol-induced CTA in both null mutant lines and BXD RI strains. Collectively, these approaches highlight the phosphatidylinositol signaling pathway and identify several genes including protein kinase C beta isoform and preproenkephalin in regulation of ethanol- induced conditioned taste aversion. Our results point to the increasing potential of the convergent approach and biological databases to investigate genetic mechanisms of complex traits.}, } @article {pmid15537740, year = {2004}, author = {Hernandez, PJ and Kelley, AE}, title = {Long-term memory for instrumental responses does not undergo protein synthesis-dependent reconsolidation upon retrieval.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {11}, number = {6}, pages = {748-754}, pmid = {15537740}, issn = {1072-0502}, support = {R01 DA004788/DA/NIDA NIH HHS/United States ; R37 DA004788/DA/NIDA NIH HHS/United States ; DA04788/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Anisomycin/administration & dosage ; Appetitive Behavior/drug effects/physiology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Operant/drug effects/*physiology ; Dose-Response Relationship, Drug ; Feeding Behavior/drug effects/physiology ; Injections, Intraperitoneal ; Male ; Mental Recall/drug effects/*physiology ; Protein Biosynthesis/drug effects/*physiology ; Protein Synthesis Inhibitors/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology/drug effects/*physiology ; Sweetening Agents ; Taste ; Time Factors ; }, abstract = {Recent evidence indicates that certain forms of memory, upon recall, may return to a labile state requiring the synthesis of new proteins in order to preserve or reconsolidate the original memory trace. While the initial consolidation of "instrumental memories" has been shown to require de novo protein synthesis in the nucleus accumbens, it is not known whether memories of this type undergo protein synthesis-dependent reconsolidation. Here we show that low doses of the protein synthesis inhibitor anisomycin (ANI; 5 or 20 mg/kg) administered systemically in rats immediately after recall of a lever-pressing task potently impaired performance on the following daily test sessions. We determined that the nature of this impairment was attributable to conditioned taste aversion (CTA) to the sugar reinforcer used in the task rather than to mnemonic or motoric impairments. However, by substituting a novel flavored reinforcer (chocolate pellets) prior to the administration of doses of ANI (150 or 210 mg/kg) previously shown to cause amnesia, a strong CTA to chocolate was induced sparing any aversion to sugar. Importantly, when sugar was reintroduced on the following session, we found that memory for the task was not significantly affected by ANI. Thus, these data suggest that memory for a well-learned instrumental response does not require protein synthesis-dependent reconsolidation as a means of long-term maintenance.}, } @article {pmid15518986, year = {2004}, author = {Masaki, T and Nakajima, S}, title = {Taste aversion learning induced by delayed swimming activity.}, journal = {Behavioural processes}, volume = {67}, number = {3}, pages = {357-362}, doi = {10.1016/j.beproc.2004.06.005}, pmid = {15518986}, issn = {0376-6357}, mesh = {Animals ; Behavior, Animal ; Choice Behavior ; *Discrimination Learning ; Drinking Behavior ; Male ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Swimming/*physiology ; Taste/*physiology ; Time Factors ; Water ; }, abstract = {The experiment reported here demonstrated that forced swimming endows rats with aversion to a taste solution consumed 30 min before the swimming. The experimental rats were allowed to drink 0.2% sodium saccharin solution, which was followed by a 30-min empty interval, and then a 20-min swimming opportunity in water. Compared with the control rats, which were returned to their home cages after drinking the saccharin, the experimental rats drank a small amount of saccharin solution both in the later sessions of one-bottle training and in the subsequent two-bottle choice (saccharin versus tap water) testing. The delayed swimming procedure was as effective as an immediate swimming procedure, extending the generality of the swimming-induced taste aversion, which we recently discovered with the immediate swimming procedure.}, } @article {pmid15509306, year = {2004}, author = {Mickley, GA and Kenmuir, CL and McMullen, CA and Snyder, A and Yocom, AM and Likins-Fowler, D and Valentine, EL and Weber, B and Biada, JM}, title = {Long-term age-dependent behavioral changes following a single episode of fetal N-methyl-D-Aspartate (NMDA) receptor blockade.}, journal = {BMC pharmacology}, volume = {4}, number = {}, pages = {28}, pmid = {15509306}, issn = {1471-2210}, mesh = {3',5'-Cyclic-GMP Phosphodiesterases/*metabolism ; Animals ; Cyclic GMP-Dependent Protein Kinases/*metabolism ; Excitatory Amino Acid Antagonists/*pharmacology ; Guanylate Cyclase/*metabolism ; Humans ; Hyperammonemia/*physiopathology ; Long-Term Potentiation/*drug effects ; Memory/drug effects ; Rats ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; }, abstract = {BACKGROUND: Administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine during the perinatal period can produce a variety of behavioral and neuroanatomical changes. Our laboratory has reported reliable changes in learning and memory following a single dose of ketamine administered late in gestation. However, the nature of the drug-induced changes depends on the point during embryonic development when ketamine is administered. Embryonic day 18 (E18) rat fetuses pre-treated with ketamine (100 mg/kg, i.p. through the maternal circulation) and taught a conditioned taste aversion (CTA) learn and remember the CTA, whereas E19 fetuses do not. The current study sought to determine if long-term behavioral effects could be detected in animals that received ketamine or a saline control injection on either E18 or E19. Rat behavior was evaluated on two different measures: spontaneous locomotion and water maze learning. Measurements were collected during 2 periods: Juvenile test period [pre-pubertal locomotor test: Postnatal Day 11 (P11); pre-pubertal water maze test: P18] or Young-adult test period [post-pubertal locomotor test: P60; post-pubertal water maze test: P81].

RESULTS: Water maze performance of ketamine-treated rats was similar to that of controls when tested on P18. Likewise, the age of the animal at the time of ketamine/saline treatment did not influence learning of the maze. However, the young-adult water maze test (P81) revealed reliable benefits of prenatal ketamine exposure - especially during the initial re-training trial. On the first trial of the young adult test, rats treated with ketamine on E18 reached the hidden platform faster than any other group - including rats treated with ketamine on E19. Swim speeds of experimental and control rats were not significantly different. Spontaneous horizontal locomotion measured during juvenile testing indicated that ketamine-treated rats were less active than controls. However, later in development, rats treated with ketamine on E18 were more active than rats that received the drug on E19.

CONCLUSION: These data suggest that both the day in fetal development when ketamine is administered and the timing of post-natal behavioral testing interact to influence behavioral outcomes. The data also indicate that the paradoxical age-dependent effects of early ketamine treatment on learning, previously described in fetuses and neonates, may also be detected later in young adult rats.}, } @article {pmid15466818, year = {2004}, author = {Heyer, BR and Taylor-Burds, CC and Mitzelfelt, JD and Delay, ER}, title = {Monosodium glutamate and sweet taste: discrimination between the tastes of sweet stimuli and glutamate in rats.}, journal = {Chemical senses}, volume = {29}, number = {8}, pages = {721-729}, doi = {10.1093/chemse/bjh081}, pmid = {15466818}, issn = {0379-864X}, mesh = {Animals ; Choice Behavior/physiology ; Glucose/pharmacology ; Guanidines/pharmacology ; Male ; Rats ; Saccharin/pharmacology ; Sodium Glutamate/*pharmacology ; Sucrose/pharmacology ; Sweetening Agents/*pharmacology ; Taste/*physiology ; }, abstract = {Generalization of a conditioned taste aversion (CTA) is based on similarities in taste qualities shared by the aversive substance and another taste substance. CTA experiments with rats have found that an aversion to a variety of sweet stimuli will cross-generalize with monosodium glutamate (MSG) when amiloride, a sodium channel blocker, is added to all solutions to reduce the taste of sodium. These findings suggest that the glutamate anion elicits a sweet taste sensation in rats. CTA experiments, however, generally do not indicate whether two substances have different taste qualities. In this study, discrimination methods in which rats focused on perceptual differences were used to determine if they could distinguish between the tastes of MSG and four sweet substances. As expected, rats readily discriminated between two natural sugars (sucrose, glucose) and two artificial sweeteners (saccharin, SC45647). Rats also easily discriminated between MSG and glucose, saccharin and, to a lesser extent, SC45647 when the taste of the sodium ion of MSG was reduced by the addition of amiloride to all solutions, or the addition of amiloride to all solutions and NaCl to each sweet stimulus to match the concentration of Na+ in the MSG solutions. In contrast, reducing the cue function of the Na+ ion significantly decreased their ability to discriminate between sucrose and MSG. These results suggest that the sweet qualities of glutamate taste is not as dominate a component of glutamate taste as CTA experiments suggest and these qualities are most closely related to the taste qualities of sucrose. The findings of this study, in conjunction with other research, suggest that sweet and umami afferent signaling may converge through a taste receptor with a high affinity for glutamate and sucrose or a downstream transduction mechanism. These data also suggest that rats do not necessarily perceive the tastes of these sweet stimuli as similar and that these sweet stimuli are detected by multiple sweet receptors.}, } @article {pmid15459118, year = {2005}, author = {Lachey, JL and D'Alessio, DA and Rinaman, L and Elmquist, JK and Drucker, DJ and Seeley, RJ}, title = {The role of central glucagon-like peptide-1 in mediating the effects of visceral illness: differential effects in rats and mice.}, journal = {Endocrinology}, volume = {146}, number = {1}, pages = {458-462}, doi = {10.1210/en.2004-0419}, pmid = {15459118}, issn = {0013-7227}, support = {DK062656/DK/NIDDK NIH HHS/United States ; DK54890/DK/NIDDK NIH HHS/United States ; DK59751/DK/NIDDK NIH HHS/United States ; MH59911/MH/NIMH NIH HHS/United States ; MH61583/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Anorexia/*chemically induced/metabolism ; *Avoidance Learning ; Brain Diseases/*chemically induced ; Glucagon/antagonists & inhibitors/*metabolism/pharmacology ; Glucagon-Like Peptide 1 ; Lithium Chloride/*poisoning ; Male ; *Mice ; Mice, Inbred Strains ; Mice, Knockout ; Neurons/drug effects/metabolism ; Peptide Fragments/antagonists & inhibitors/*metabolism/pharmacology ; Proglucagon ; Protein Precursors/antagonists & inhibitors/*metabolism/pharmacology ; Rats ; Species Specificity ; Taste/*drug effects ; }, abstract = {In rats, central administration of glucagon-like peptide-1 (GLP-1) elicits symptoms of visceral illness like those caused by the toxin lithium chloride (LiCl), including anorexia, conditioned taste aversion (CTA) formation, and neural activation in the hypothalamus and hindbrain including activation of brainstem preproglucagon cells. Most compellingly, pharmacological antagonists of the GLP-1 receptor (GLP-1R) block several effects of LiCl in rat. The major goal of these experiments was to further test the hypothesis that the central nervous system GLP-1 system is critical to the visceral illness actions of LiCl by using mice with a targeted disruption of the only described GLP-1R. First, we observed that, like the rat, LiCl activates preproglucagon neurons in wild-type mice. Second, GLP-1R -/- mice demonstrated normal anorexic and CTA responses to LiCl. To test the possibility that alternate GLP-1Rs mediate aversive effects, we examined the ability of GLP-1 to produce a CTA in GLP1R -/- mice. Although lateral ventricular GLP-1 produced a CTA in wild-type mice, it did not produce a CTA in GLP-1R -/- mice. Furthermore, the same GLP-1R antagonist that can block the aversive effects of LiCl in the rat failed to do so in the mouse. These results support the conclusion that in mouse, unlike in rat, GLP-1R signaling is not required for the visceral illness response to LiCl. Such species differences are an important consideration when comparing results from rat and mouse studies.}, } @article {pmid15450684, year = {2004}, author = {Hinderliter, CF and Musci, JA and Pollack, CA and Misanin, JR and Anderson, MJ}, title = {Hypothermia modifies the effective CS-US interval in conditioned taste aversion in rats.}, journal = {Neuroscience letters}, volume = {369}, number = {2}, pages = {142-144}, doi = {10.1016/j.neulet.2004.07.077}, pmid = {15450684}, issn = {0304-3940}, mesh = {Age Factors ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Conditioning, Classical/*physiology ; Hypothermia/*physiopathology ; Male ; Rats ; Rats, Wistar ; Reaction Time/physiology ; Time Factors ; }, abstract = {Conditioned taste aversion can be acquired when rats experience an unconditioned stimulus (US) while anesthetized. In contrast to anesthetics, a hypothermia-induced comatose state immediately after presentation of a taste conditioned stimulus (CS) prevented a taste-illness association at relatively short CS-US intervals and potentiated the aversion at longer intervals. Results at shorter CS-US intervals were explained on the basis of hypothermia's temporally graded amnesitc properties. Evidence for conditioning at the longer intervals was discussed in relation to slowing down metabolism allowing for associations to be formed at CS-US intervals that normally do not result in evidence of conditioning. Manipulating body temperature during the CS-US interval was demonstrated to alter rats' ability to bridge temporal gaps in associative learning.}, } @article {pmid15371751, year = {2004}, author = {Cross-Mellor, SK and Hoshooley, JS and Kavaliers, M and Ossenkopp, KP}, title = {Immune activation paired with intraoral sucrose conditions oral rejection.}, journal = {Neuroreport}, volume = {15}, number = {14}, pages = {2287-2291}, doi = {10.1097/00001756-200410050-00029}, pmid = {15371751}, issn = {0959-4965}, mesh = {Administration, Oral ; Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Lipopolysaccharides/pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Long-Evans ; Sucrose/*administration & dosage ; Taste/*drug effects/immunology ; }, abstract = {The effects of lipopolysaccharide (LPS) and LiCl on conditioned taste aversion acquisition using intraoral infusions as the method of taste delivery was examined. Rats received two pairings of an intraorally delivered sucrose (5 ml) taste with the effects of a systemic injection of LPS, LiCl or NaCl. The magnitude of conditioning was quantified by scoring taste reactivity responses to a brief intraoral infusion of sucrose in the absence of any drug injection. Rats previously conditioned with LiCl or LPS displayed clear evidence of conditioned aversion with increased oral rejection responses relative to saline controls. Our results suggest activation of the immune system with LPS can condition consummatory aspects of ingestion when this conditioning involves intraoral fluid presentation.}, } @article {pmid15353168, year = {2004}, author = {Orr, TE and Whitford-Stoddard, JL and Elkins, RL}, title = {Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {33}, number = {1}, pages = {1-7}, doi = {10.1016/j.alcohol.2004.03.002}, pmid = {15353168}, issn = {0741-8329}, mesh = {Alcohol Drinking/*blood/genetics ; Animals ; Avoidance Learning/*drug effects/physiology ; Ethanol/*administration & dosage/*blood ; Female ; Male ; Metabolic Clearance Rate/drug effects/physiology ; Rats ; Self Administration/methods ; Species Specificity ; Taste/*drug effects/genetics ; }, abstract = {Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.}, } @article {pmid15351506, year = {2004}, author = {Sandner, G and Silva, RC and Angst, MJ and Knobloch, J and Danion, JM}, title = {Prenatal exposure of Long-Evans rats to 17alpha-ethinylestradiol modifies neither latent inhibition nor prepulse inhibition of the startle reflex but elicits minor deficits in exploratory behavior.}, journal = {Brain research. Developmental brain research}, volume = {152}, number = {2}, pages = {177-187}, doi = {10.1016/j.devbrainres.2004.06.013}, pmid = {15351506}, issn = {0165-3806}, mesh = {Amphetamine/adverse effects ; Animals ; Animals, Newborn ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/*drug effects/physiology ; Brain/*drug effects/pathology/physiopathology ; Conditioning, Psychological/drug effects/physiology ; Disease Models, Animal ; Exploratory Behavior/drug effects/physiology ; Female ; Hippocampus/drug effects/pathology ; Hyperkinesis/chemically induced/physiopathology ; Male ; Neural Inhibition/drug effects/physiology ; Norethynodrel/adverse effects/*analogs & derivatives ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Long-Evans ; Reflex, Startle/drug effects/physiology ; Schizophrenia/etiology/pathology/physiopathology ; }, abstract = {Prenatal administration of synthetic estrogens in humans as well as lower mammals was reported to alter behavior in adulthood. The alterations remain to be characterized according to specific pathophysiological hypotheses. In this study, three common behavioral models of schizophrenia were tested, i.e., latent inhibition (LI), prepulse inhibition of the startle response (PPI) and hyperlocomotion under amphetamine. Female Long-Evans rats were injected i.p. with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) everyday from day 9 to 14 of pregnancy, and behavioral characteristics of their offspring, raised by Wistar foster mothers, were compared to those of rats born from dams injected with the vehicle only, over the same gestation period. LI was tested in a conditioned taste aversion and a conditioned passive avoidance paradigm followed by a parametric study of PPI and an evaluation of locomotion in an open field under saline or amphetamine (1.5 mg kg(-1)). Histological brain measurements were also carried out in a subset of the same rats. Neither LI nor PPI was altered using methods that had proven sensitive in previous pharmacological studies. Treated rats' locomotion was impaired, but amphetamine did not elicit a differential enhancement. A thinner Amon's horn layer was observed in their hippocampus. This indicates that standard models of schizophrenia did not fit to the behavioral abnormalities found by others and confirmed in this study. They were not due to the abnormal maternal care to pups elicited by the treatment.}, } @article {pmid15341802, year = {2004}, author = {Kawai, R and Sunada, H and Horikoshi, T and Sakakibara, M}, title = {Conditioned taste aversion with sucrose and tactile stimuli in the pond snail Lymnaea stagnalis.}, journal = {Neurobiology of learning and memory}, volume = {82}, number = {2}, pages = {164-168}, doi = {10.1016/j.nlm.2004.06.003}, pmid = {15341802}, issn = {1074-7427}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Cues ; Snails/*physiology ; Sucrose ; Sweetening Agents ; Taste/*physiology ; Touch/*physiology ; }, abstract = {A new form of taste aversion conditioning was established in the pond snail Lymnaea stagnalis. An associative memory, lasting 24h, was produced in the pond snail with 20 pairings of 100 mM sucrose as the conditioned stimulus (CS) and mechanical stimulation to the head as the unconditioned stimulus (UCS). Animals exposed to reverse pairings of the CS and UCS failed to learn the association. The learning was characterized by a shift in the response to the UCS from a whole-body withdrawal response to the cessation of feeding behavior.}, } @article {pmid15341801, year = {2004}, author = {Josselyn, SA and Kida, S and Silva, AJ}, title = {Inducible repression of CREB function disrupts amygdala-dependent memory.}, journal = {Neurobiology of learning and memory}, volume = {82}, number = {2}, pages = {159-163}, doi = {10.1016/j.nlm.2004.05.008}, pmid = {15341801}, issn = {1074-7427}, mesh = {Amygdala/*metabolism ; Animals ; Avoidance Learning/*physiology ; Cyclic AMP Response Element-Binding Protein ; Down-Regulation ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Species Specificity ; *Taste ; Transcription Factors/genetics/*metabolism ; }, abstract = {Evidence from Aplysia, Drosophila, mice, and rats indicates that the CREB (cAMP/Ca2+ responsive element binding protein) family of transcription factors is critical for long-term memory. Recent findings, however, suggest that performance abnormalities may contribute to the memory deficits attributed to CREB manipulations in mammals. To clarify the role of CREB in memory, we used a paradigm, conditioned taste avoidance, that places few performance demands on the subject. We show that lesioning or blocking protein synthesis in the basolateral amygdala of mice disrupts conditioned taste aversion. Furthermore, either chronically or acutely disrupting CREB function in two different types of genetically modified mice blocks memory for conditioned taste aversion measured 24 h following training. Together, these findings indicate that CREB-mediated transcription and protein synthesis are required for conditioned taste aversion memory.}, } @article {pmid15341792, year = {2004}, author = {Manrique, T and Molero, A and Ballesteros, MA and Morón, I and Gallo, M and Fenton, AA}, title = {Time of day-dependent latent inhibition of conditioned taste aversions in rats.}, journal = {Neurobiology of learning and memory}, volume = {82}, number = {2}, pages = {77-80}, doi = {10.1016/j.nlm.2004.04.003}, pmid = {15341792}, issn = {1074-7427}, mesh = {Animals ; Attention/*physiology ; Avoidance Learning/*physiology ; Circadian Rhythm/*physiology ; Cues ; Drinking Behavior/physiology ; Field Dependence-Independence ; Habituation, Psychophysiologic/*physiology ; Male ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {We have determined that the temporal context of drinking can modulate latent inhibition of learned saline aversions in Wistar rats by changing the time of day of drinking of the preexposure and conditioning phases. Latent inhibition was absent in the group preexposed and conditioned to saline at different times of the day, but not in the group that was preexposed and conditioned at the same time of day. The results confirm a previous report that the time of day can modulate taste aversion learning independently of other environmental cues. It is proposed that the features and duration of the habituation training to the temporal contexts used may be critical for time-dependent latent inhibition to appear.}, } @article {pmid15312967, year = {2004}, author = {Janus, C and Welzl, H and Hanna, A and Lovasic, L and Lane, N and St George-Hyslop, P and Westaway, D}, title = {Impaired conditioned taste aversion learning in APP transgenic mice.}, journal = {Neurobiology of aging}, volume = {25}, number = {9}, pages = {1213-1219}, doi = {10.1016/j.neurobiolaging.2003.11.007}, pmid = {15312967}, issn = {0197-4580}, mesh = {Alzheimer Disease/genetics/*physiopathology/psychology ; Amyloid beta-Protein Precursor/genetics/*metabolism ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/metabolism/pathology/physiopathology ; Conditioning, Psychological/physiology ; Disease Models, Animal ; Hippocampus/metabolism/pathology/physiopathology ; Learning Disabilities/genetics/*physiopathology/psychology ; Memory Disorders/genetics/physiopathology/psychology ; Mice ; Mice, Transgenic ; Mutation/genetics ; Plaque, Amyloid/genetics/metabolism/pathology ; Taste/*genetics ; Transgenes/genetics ; }, abstract = {Cognition in transgenic mouse models of Alzheimer's disease (AD) has been predominantly characterized in explicit spatial orientation tasks. However, dementia in AD encompasses also implicit memory systems. In the present study a line of transgenic mice (TgCRND8) encoding a double mutated allele of the human amyloid precursor protein (APP) genes was evaluated in an implicit associative learning task of conditioned taste aversion (CTA). CTA is a form of Pavlovian classical conditioning, in which a mouse learns to avoid a novel taste of saccharine (conditioned stimulus) paired with an experimentally induced (systemic injection of lithium chloride) nausea (unconditioned stimulus). In contrast to conditioned non-Tg mice, TgCRND8 APP mice developed weaker aversion against saccharine and quickly increased its consumption in repeated tests. These results indicate that TgCRND8 mice show a significant impairment not only in explicit spatial memory, as has been previously shown [Nature 408 (2000) 979], but also in implicit memory. Control experiments confirmed that TgCRND8 and non-Tg mice had comparable taste sensitivities in response to appetitive as well as aversive tastes. The study suggests that the CTA paradigm can be a sensitive tool to evaluate deficits in implicit associative learning in APP transgenic mouse models of AD.}, } @article {pmid15302114, year = {2004}, author = {Spray, KJ and Bernstein, IL}, title = {Afferent and efferent connections of the parvicellular subdivision of iNTS: defining a circuit involved in taste aversion learning.}, journal = {Behavioural brain research}, volume = {154}, number = {1}, pages = {85-97}, doi = {10.1016/j.bbr.2004.01.027}, pmid = {15302114}, issn = {0166-4328}, support = {R01 NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/cytology/*physiology ; Amygdala/cytology/physiology ; Animals ; Avoidance Learning/*physiology ; *Brain Mapping ; Conditioning, Operant/physiology ; Efferent Pathways/cytology/*physiology ; Neurons/metabolism ; Paraventricular Hypothalamic Nucleus/cytology/physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Long-Evans ; Solitary Nucleus/cytology/*physiology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) expression is associated with strong increases in Fos-like immunoreactivity (FLI) in a region of the brainstem identified as the parvicellular subdivision of the intermediate nucleus of the solitary tract (iNTSpc). To identify the projections to and from cells in iNTSpc which display strong FLI in response to expression of a CTA, anterograde and retrograde tract tracing was used. When appropriate, tract tracing was combined with double labeling for FLI in animals which received CTA training as well as tracer injections and were re-exposed to the CS taste. With respect to afferent projections, iNTSpc receives a strong, direct, ipsilateral projection from amygdala and the distribution of the fiber terminals yields a striking match to that of cells expressing FLI after CTA expression. As for efferent projections, these cells in iNTSpc are characterized by a mixed, rather than homogeneous, projection pattern. Targets of these cells include pons and forebrain as well as local medullary sites, all of which are known to be involved in gastrointestinal function. Thus, activation of these cells may provide a circuit through which gastrointestinal/visceral responses are coordinated as a component of the conditioned aversion.}, } @article {pmid15301923, year = {2004}, author = {Clark, JJ and Bernstein, IL}, title = {Reciprocal cross-sensitization between amphetamine and salt appetite.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {78}, number = {4}, pages = {691-698}, doi = {10.1016/j.pbb.2004.05.002}, pmid = {15301923}, issn = {0091-3057}, support = {DA014609/DA/NIDA NIH HHS/United States ; }, mesh = {Amphetamine/*pharmacology ; Animals ; Appetite/*drug effects ; Central Nervous System Stimulants/*pharmacology ; Male ; Motor Activity/drug effects ; Rats ; Rats, Long-Evans ; Reward ; Sodium/deficiency ; *Sodium Chloride, Dietary ; }, abstract = {Previous work in our laboratory has demonstrated a potentiation of the psychomotor effects of amphetamine in animals with a history of sodium depletion, a process referred to as cross-sensitization. The present studies were done to further develop this finding by assessing multiple effects of amphetamine in rats with and without a history of sodium depletion. For Experiments 1-3, rats were depleted of sodium twice then subjected to one of three experimental procedures [open-field activity, conditioned place preference (CPP) and conditioned taste aversion (CTA)]. A history of depletion produced an elevation in the psychomotor effects of amphetamine. CPP, used to assess the rewarding properties of amphetamine, developed in rats with a history of depletion but not in controls. The aversive component of amphetamine as measured by CTA was unaffected by previous experience with sodium depletion. Finally, acute salt appetite after depletion was assessed in rats exposed to a sensitizing regimen of amphetamine. Animals with a drug history demonstrated a significant elevation in NaCl solution intake after depletion in comparison to controls. Together, the data provide strong evidence for the reciprocal cross-sensitization of salt appetite and response to amphetamine.}, } @article {pmid15276806, year = {2004}, author = {Scalera, G}, title = {Acid taste thresholds assessed by conditioned taste aversion and two-bottle preference in rats.}, journal = {Physiology & behavior}, volume = {82}, number = {2-3}, pages = {411-423}, doi = {10.1016/j.physbeh.2004.04.052}, pmid = {15276806}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Choice Behavior/*physiology ; Citric Acid ; Conditioning, Operant/*physiology ; Food Preferences/physiology ; Hydrochloric Acid ; Male ; Rats ; Rats, Sprague-Dawley ; Recognition, Psychology/*physiology ; Taste Threshold/*physiology ; }, abstract = {The conditioned taste aversion (CTA) threshold for either citric acid (CA) or HCl solutions and the two-bottle taste preference (TBP) threshold were determined in rats that are familiarized to the odor of conditioning solutions or that are naive. The CTA method appeared to be more sensitive than the TBP test, particularly when rats were not familiarized to the odor of the conditioning solution. The CTA threshold for HCl-conditioned rats and familiarized to the odor of conditioning solution lies between 1.00 and 2.00 mmol; in unconditioned rats, it lies between 4.00 and 5.00 mmol. In CA-conditioned and odor-familiarized rats, the threshold lies between 0.09 and 0.20 mmol; in unconditioned rats, it lies between 7.00 and 10.00 mmol. In rats not familiarized to the odor of the conditioning solution, the threshold for HCl-conditioned rats lies between 0.90 and 1.00 mmol; in unconditioned rats, it lies between 2.00 and 3.00 mmol. In CA-conditioned rats, the CTA threshold lies between 0.03 and 0.05 mmol; in unconditioned rats, it lies between 4.00 and 7.00 mmol. The two-bottle test is less sensitive than the CTA method. The TBP threshold lies between HCl 4.00 and 5.00 mmol, and between CA 4.00 and 7.00 mmol. The odor of a solution may potentiate the ability of rats to detect the concentration of CA and HCl solutions.}, } @article {pmid15276792, year = {2004}, author = {Salvy, SJ and Pierce, WD and Heth, DC and Russell, JC}, title = {Taste avoidance induced by wheel running: effects of backward pairings and robustness of conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {82}, number = {2-3}, pages = {303-308}, doi = {10.1016/j.physbeh.2004.03.017}, pmid = {15276792}, issn = {0031-9384}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; *Cues ; Male ; Motor Activity/*physiology ; Rats ; *Taste ; Time Factors ; }, abstract = {Rats repeatedly exposed to a distinctive novel solution (conditioned stimulus, CS) followed by the opportunity to run in a wheel subsequently drink less of this solution. Investigations on this phenomenon indicate that wheel running is an effective unconditioned stimulus (US) for establishing conditioned taste aversion (CTA) when using a forward conditioning procedure (i.e., the US-wheel running follows the CS-taste). However, other studies show that wheel running produces reliable preference for a distinctive place when pairings are backward (i.e., the CS-location follows the US-wheel running). One possibility to account for these results is that rewarding aftereffects of wheel running conditioned preference to the CS. The main objective of the present study was to assess the effects of backward conditioning using wheel running as the US and a distinctive taste as the CS. In a between-groups design, two experimental groups [i.e., forward (FC) and backward conditioning (BC)] and two control groups [CS-taste alone (TA) and CS-US unpaired (UNP)] were compared. Results from this experiment indicated that there is less suppression of drinking when a CS-taste followed a bout of wheel running. In fact, rats in the BC group drank more of the paired solution than all the other groups.}, } @article {pmid15270229, year = {2004}, author = {Wagatsuma, A and Sugai, R and Chono, K and Azami, S and Hatakeyama, D and Sadamoto, H and Itoi, E}, title = {The early snail acquires the learning. Comparison of scores for conditioned taste aversion between morning and afternoon.}, journal = {Acta biologica Hungarica}, volume = {55}, number = {1-4}, pages = {149-155}, doi = {10.1556/ABiol.55.2004.1-4.18}, pmid = {15270229}, issn = {0236-5383}, mesh = {Afferent Pathways/metabolism ; Animals ; Avoidance Learning/*physiology ; *Behavior, Animal ; Central Nervous System/physiology ; Circadian Rhythm ; Conditioning, Classical/physiology ; Feeding Behavior/*drug effects ; Ganglia, Invertebrate/*physiology ; Interneurons/metabolism ; Learning ; Memory ; Movement ; Snails ; *Taste ; Time Factors ; }, abstract = {The pond snail Lymnaea stagnalis acquires conditioned taste aversion (CTA) and maintains its memory for more than a month. Snails in our laboratory were cultured at 20 degrees C on a 12:12 light-dark cycle (light from 7 am to 7 pm). To examine the hours during which snails acquire CTA effectively, we trained some snails in the morning and others in the afternoon, and then compared their scores. CTA developed in both cases, but scores were significantly better in the morning than in the afternoon. To elucidate the cause of this difference in scores, we observed the voluntary activity of snails and found the circadian rhythm reflected in the snails' free-movement distances; distances at the circadian time 0-12 (daytime) were significantly longer than those at the circadian time 12-24 (nighttime). This rhythm was kept up for at least 3 days, even in constant darkness. In conclusion, L. stagnalis should be trained in the morning to acquire associative learning, possibly because of its greater propensity to roam about at that time as opposed to the afternoon.}, } @article {pmid15256365, year = {2004}, author = {Tracy, AL and Phillips, RJ and Chi, MM and Powley, TL and Davidson, TL}, title = {The gastrointestinal tract "tastes" nutrients: evidence from the intestinal taste aversion paradigm.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {287}, number = {5}, pages = {R1086-100}, doi = {10.1152/ajpregu.00047.2004}, pmid = {15256365}, issn = {0363-6119}, support = {R01-DK-27627/DK/NIDDK NIH HHS/United States ; R01-DK-61317/DK/NIDDK NIH HHS/United States ; R01-HD-29792/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Body Weight/physiology ; Chemoreceptor Cells/physiology ; Conditioning, Operant/drug effects/physiology ; Corn Oil/pharmacology ; Dietary Carbohydrates/administration & dosage/pharmacology ; Dietary Fats/administration & dosage/pharmacology ; Duodenum/physiology ; Esophagogastric Junction/physiology ; Intestines/*physiology ; Intubation, Gastrointestinal ; Lithium Chloride/pharmacology ; Male ; Polysaccharides/pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/*physiology ; }, abstract = {To develop and use a behavioral paradigm for assessments of what nutrient properties are detected by intestinal chemoreceptors, we combined features of the "electronic esophagus" preparation (Elizalde G and Sclafani A. Physiol Behav 47: 63-77, 1990) and the conditioned taste aversion protocol (Garcia J and Koelling RA. Psychon Sci 4: 123-124, 1966). In four experiments, separate groups of food-deprived rats with gastric (experiments 1-4) or duodenal (experiment 4) catheters were infused with either carbohydrates (maltodextrin) or fats (corn oil) into their stomachs or small intestines, either while they consumed nonnutritive flavored solutions (experiments 1 and 2) or in the absence of any intake (experiments 3 and 4). For some animals, one of the macronutrient infusions was paired with lithium chloride injections shown to support conventional conditioned aversions. After training, in various oral preference test trials, animals were given opportunities to taste and consume the nonnutritive solutions that had served as oropharyngeal conditioned stimuli as well as the nutrients that had been infused intragastrically, with or without poisoning, but never sampled by mouth. As previously established, preferences for the nonnutritive flavors were enhanced by association with intragastric infusions of macronutrients, with carbohydrates producing the greater preference. On first exposure to the two macronutrients for oral consumption, animals reduced their intake of the nutrient that had been previously poisoned when it was infused into the gastrointestinal tract. These results, along with additional controls, suggest that nutrient tastes detected in the intestines can be recognized centrally based on oropharyngeal gustatory stimulation.}, } @article {pmid15245503, year = {2004}, author = {Võikar, V and Rossi, J and Rauvala, H and Airaksinen, MS}, title = {Impaired behavioural flexibility and memory in mice lacking GDNF family receptor alpha2.}, journal = {The European journal of neuroscience}, volume = {20}, number = {1}, pages = {308-312}, doi = {10.1111/j.1460-9568.2004.03475.x}, pmid = {15245503}, issn = {0953-816X}, mesh = {Animals ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Brain/metabolism ; Conditioning, Psychological/*physiology ; Exploratory Behavior/physiology ; Fear/physiology ; Glial Cell Line-Derived Neurotrophic Factor Receptors ; Immunohistochemistry ; Maze Learning/physiology ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Neurological ; Motor Activity/genetics/physiology ; Proto-Oncogene Proteins/*deficiency/genetics/physiology ; Proto-Oncogene Proteins c-ret ; Receptor Protein-Tyrosine Kinases/*deficiency/genetics/physiology ; }, abstract = {The glial cell line-derived neurotrophic factor (GDNF) family receptor GFRalpha2 is the binding receptor for neurturin (NRTN). The main biological responses of GFRalpha2 are mediated via the Ret receptor tyrosine kinase, although it may also signal independently of Ret via the neural cell adhesion molecule NCAM. GFRalpha2 is expressed in many neurons of both the central and peripheral nervous system. Mice lacking GFRalpha2 receptors do not exhibit any gross defects in the central nervous system structure. However, they display profound deficits in the parasympathetic and enteric nervous system, accompanied by significant reduction in body weight after weaning. Here we present the results of behavioural analysis of the GFRalpha2-knockout mice. The knockout mice did not differ from wild-type mice in basic tests of motor and exploratory activity. However, differences were established in several memory tasks. The knockout mice were not impaired in the acquisition of spatial escape strategy. However, the deficit in flexibility in establishing a new strategy was revealed during reversal learning with the platform in the opposite quadrant of the pool. Furthermore, the knockout mice displayed significant impairment in contextual fear conditioning and conditioned taste aversion tests of memory. The results suggest that GFRalpha2 signalling plays a role in the development or maintenance of cognitive abilities that help in solving complex learning tasks.}, } @article {pmid15238994, year = {2004}, author = {Meyer, U and Chang, DL and Feldon, J and Yee, BK}, title = {Expression of the CS- and US-pre-exposure effects in the conditioned taste aversion paradigm and their abolition following systemic amphetamine treatment in C57BL6/J mice.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {29}, number = {12}, pages = {2140-2148}, doi = {10.1038/sj.npp.1300522}, pmid = {15238994}, issn = {0893-133X}, mesh = {Amphetamine/*pharmacology ; Analysis of Variance ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Behavior, Animal ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Classical/*drug effects ; In Vitro Techniques ; *Inhibition, Psychological ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Taste/drug effects/physiology ; }, abstract = {In classical conditioning, pre-exposures to either the to-be-conditioned stimulus (CS) or unconditioned stimulus (US) can retard subsequent conditioning between the CS and US. The present experiment evaluated the expression of these two pre-exposure effects in mice of the C57BL6/J strain, one of the most common background strains for genetically altered mice. We tested whether their expression would be disrupted by amphetamine treatment (2.5 mg/kg, i.p.) in a conditioned taste aversion paradigm with sucrose as the CS and lithium chloride-induced gastric malaise as the US. We found that one pre-exposure (PE) to either the CS or the US reduced aversion to sucrose solution in the controls following conditioning, but no such tendency was evident in the amphetamine-treated mice. The present study represents the first report of amphetamine-induced disruption of the CS-PE effect (ie latent inhibition) in mice, and the first attempt to compare it directly with the US-PE effect in any species. It extended previous reports in rats and humans, suggesting that the sensitivity of latent inhibition to amphetamine is largely comparable across species, thereby lending credence to the use of the latent inhibition effect as a behavioral assay for psychotic-like phenotype in transgenic mice. The parallel observation in the US-PE effect further indicates that its expression, at least in the present conditioned taste aversion paradigm, may also be under similar influence of the dopaminergic system.}, } @article {pmid15234610, year = {2004}, author = {Smith, JC}, title = {Gustation as a factor in the ingestion of sweet and fat emulsions by the rat.}, journal = {Physiology & behavior}, volume = {82}, number = {1}, pages = {181-185}, doi = {10.1016/j.physbeh.2004.04.049}, pmid = {15234610}, issn = {0031-9384}, mesh = {Animals ; Body Weight/drug effects ; Corn Oil/*pharmacology ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Drug Interactions ; Emulsions/pharmacology ; Feeding Behavior/*drug effects/physiology ; Glucose/*pharmacology ; Lithium Chloride/pharmacology ; Rats ; Saccharin/*pharmacology ; Time Factors ; }, abstract = {This paper was written to pay honor to Professor Gerard P. Smith because of his strong influence on me to study the ingestion of sweet and fat mixtures. Three experiments are reported here, in which the laboratory rat was given an emulsion of a glucose+saccharin mixture with corn oil. In the first experiment, a two-bottle, 24-h test was given comparing the emulsion with water. Over 6 weeks, the concentration of the corn oil was gradually increased. When given only food and water, or the glucose/saccharin solution, the rats regulated their caloric intake and grew at a normal rate. In contrast, when the corn oil was present, the rats significantly increased their caloric intake, resulting in a marked increase in body weight. In the second experiment, a detailed analysis of the ingestion revealed that the rate of licking the emulsion during drinking bouts increased in a linear manner as the concentration of the corn oil was increased. In the third experiment, a conditioned taste aversion to the sweet/fat emulsion generalized to the fat more than to the sweet solutions. The implications for a gustatory input are discussed.}, } @article {pmid15234255, year = {2004}, author = {Mickley, GA and Kenmuir, CL and McMullen, CA and Yocom, AM and Valentine, EL and Dengler-Crish, CM and Weber, B and Wellman, JA and Remmers-Roeber, DR}, title = {Dynamic processing of taste aversion extinction in the brain.}, journal = {Brain research}, volume = {1016}, number = {1}, pages = {79-89}, doi = {10.1016/j.brainres.2004.04.071}, pmid = {15234255}, issn = {0006-8993}, support = {1-R15-MH63720-01/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Brain/anatomy & histology/*metabolism ; Cell Count/methods ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Gene Expression Regulation/physiology ; Immunohistochemistry/methods ; Lithium Chloride/metabolism ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Saccharin/metabolism ; Taste/*physiology ; }, abstract = {While substantial advances have been made in discovering how the brain learns and remembers, less is known about how the brain discards information, reorganizes information, or both. These topics are not only relevant to normal brain functioning but also speak to pathologies in which painful memories do not wane but are evoked time and again (e.g., post-traumatic stress disorder; PTSD). Here, we measured brain activity (as indicated by the regional expression of c-Fos protein) in rats during acquisition and throughout extinction of a conditioned taste aversion (CTA). We compared that brain activity with animals that had intact CTA memories or those that experienced an explicitly unpaired (EU) conditioned stimulus (CS; saccharin, SAC) and unconditioned stimulus (US; lithium chloride, LiCl). The data show a dynamic and nonuniform pattern of c-Fos protein expression in brain nuclei known to mediate gustation and CTAs. In particular, brainstem nuclei (e.g., nucleus of the solitary tract; NTS) and the basolateral nucleus of the amygdala (BLA) are active early as CTAs are formed and as extinction of the learned response begins. Later in the extinction process, the BLA reduces c-Fos expression relative to nonextinguished controls. Finally, as almost full reacceptance of the taste is achieved, the gustatory neocortex (GNC) expresses enhanced levels of c-Fos protein. Thus, extinction of a CTA is not represented by a simple reversal of the c-Fos activity evoked by CTA conditioning. Rather, the data demonstrate that extinction of conditioned responses is a dynamic process in which the activity levels of particular nuclei along the brain's taste pathway change depending on the extent to which the conditioned response has been extinguished.}, } @article {pmid15222960, year = {2004}, author = {Misanin, JR and Christianson, JP and Anderson, MJ and Giovanni, LM and Hinderliter, CF}, title = {Ketaset-Rompun extends the effective interstimulus interval in long-trace taste-aversion conditioning in rats.}, journal = {Behavioural processes}, volume = {65}, number = {2}, pages = {111-121}, doi = {10.1016/j.beproc.2003.09.001}, pmid = {15222960}, issn = {0376-6357}, mesh = {Adrenergic alpha-Agonists/pharmacology ; Anesthetics, Combined/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Female ; Ketamine/*pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Taste/*drug effects ; Time Perception/drug effects ; Xylazine/*pharmacology ; }, abstract = {The effect of anesthesia (Ketaset-Rompun) interpolated between the conditioned stimulus (CS) and unconditioned stimulus (US) during long-trace taste-aversion conditioning in rats was examined in three experiments. In Experiment 1, rats that were anesthetized immediately after experiencing a saccharin solution formed a taste aversion at a 3-h interval that typically does not support conditioning, a prolongation effect. Prior experience with the anesthetic eliminated the associability of the aversive consequences of the anesthetic but did not eliminate the anesthetic's prolongation effect. Some evidence was also obtained indicating that LiCl produced an aversion at the 3-h interval in unanesthetized rats if they had experience with the anesthetic prior to conditioning. In Experiment 1a, the interval between prior experience and conditioning was extended from 24 to 96 h. Results demonstrated that the evidence for conditioning at 3 h for unanesthetized subjects in Experiment 1 was not a robust finding. By reversing the role of Ketaset-Rompun (KR) and LiCl as prior experience manipulation and US treatment in Experiment 2, the prolongation effect was shown not to be due to the summation of the aversive properties of the anesthetic and the LiCl. Results were interpreted in terms of a hypothesized metabolic pacemaker.}, } @article {pmid15219768, year = {2004}, author = {Sindelar, DK and Shepperd, ML and Pickard, RT and Alexander-Chacko, J and Dill, MJ and Cramer, JW and Smith, DP and Gadski, R}, title = {Central H3R activation by thioperamide does not affect energy balance.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {78}, number = {2}, pages = {275-283}, doi = {10.1016/j.pbb.2004.03.019}, pmid = {15219768}, issn = {0091-3057}, mesh = {Animals ; Darkness ; Dose-Response Relationship, Drug ; Eating/*drug effects/physiology ; Energy Metabolism/*drug effects/physiology ; Male ; Photoperiod ; Piperidines/metabolism/*pharmacology ; Protein Binding/physiology ; Rats ; Rats, Long-Evans ; Receptors, Histamine H3/*metabolism/physiology ; }, abstract = {The central histamine 3 receptor (H3R) is a presynaptic autoreceptor that regulates neuronal release and synthesis of histamine, and is thought to play a key role in controlling numerous central nervous system (CNS)-mediated parameters, including energy homeostasis. Thioperamide, the prototypical selective H3R antagonist, was used to examine the role that H3R plays in regulating energy balance in vivo. Thioperamide was administered either intraperitoneally or orally to rats and the pharmacokinetic parameters were examined along with central H3R binding and histaminergic system activation. Food intake and metabolic parameters of either route of thioperamide administration were likewise examined. In a dose-dependent manner, both the intraperitoneal and oral route of administration resulted in similar ex vivo binding curves and tele-methylhistamine dose-response curves despite the route of administration. However, only intraperitoneal administration of 30 mg/kg thioperamide resulted in a significant decrease in 24-h food intake (60% lower than control) and respiratory quotient (RQ), while the oral route of delivery did not. Moreover, the decrease in RQ with the 30 mg/kg ip administration also decreased energy expenditure (EE) thus resulting in an unchanged energy balance. The decrease in food intake and EE was coupled with a conditioned taste aversion with the 30-mg/kg ip administration. These data indicate that the activation of the central H3R system by thioperamide does not play a direct role in decreasing food intake or altering energy homeostasis.}, } @article {pmid15173421, year = {2004}, author = {L'Heureux-Bouron, D and Tomé, D and Bensaid, A and Morens, C and Gaudichon, C and Fromentin, G}, title = {A very high 70%-protein diet does not induce conditioned taste aversion in rats.}, journal = {The Journal of nutrition}, volume = {134}, number = {6}, pages = {1512-1515}, doi = {10.1093/jn/134.6.1512}, pmid = {15173421}, issn = {0022-3166}, mesh = {Adipose Tissue/anatomy & histology ; Animals ; *Avoidance Learning ; Behavior, Animal ; Body Weight/drug effects ; *Conditioning, Psychological ; Dietary Proteins/*administration & dosage ; Dose-Response Relationship, Drug ; Energy Intake ; Intestines/anatomy & histology ; Kidney/anatomy & histology ; Male ; Organ Size/drug effects ; Rats ; Rats, Wistar ; Satiety Response ; *Taste ; }, abstract = {This study was designed to assess the effects of transition and adaptation to a very high protein diet on behavioral food responses, energy intake, body weight gain, and body composition in rats. For this purpose, adult male Wistar rats were fed either a diet with 70% of energy as protein (P70 group) or a diet with 14% of energy as protein (P14 group) for 16 d. These two groups were compared with a P14 pair-fed (P14-pf) group. A behavioral satiety sequence was also examined. The P70 group ate 21% less than the P14 rats (P < 0.001) and gained less body weight (P < 0.01). The P70 group gained more carcass weight than either P14 or P14-pf rats (P < 0.05). Behavior and food intake data were affected in P70 rats on d 1 of eating the very high protein diet and then returned to baseline values as early as d 2 of consuming the P70 diet. Rats that adapted to the very high protein diet did not acquire a conditioned taste aversion but rather exhibited satiety and a normal behavioral satiety sequence.}, } @article {pmid15169861, year = {2004}, author = {Miranda, MI and McGaugh, JL}, title = {Enhancement of inhibitory avoidance and conditioned taste aversion memory with insular cortex infusions of 8-Br-cAMP: involvement of the basolateral amygdala.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {11}, number = {3}, pages = {312-317}, pmid = {15169861}, issn = {1072-0502}, support = {MH12526/MH/NIMH NIH HHS/United States ; }, mesh = {8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Adrenergic beta-Antagonists/pharmacology ; Amygdala/drug effects/*enzymology ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*enzymology ; Conditioning, Classical/drug effects/*physiology ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Enzyme Activation ; Male ; Memory/drug effects/*physiology ; Muscarinic Agonists/pharmacology ; Neural Inhibition/drug effects/physiology ; Neural Pathways/metabolism ; Oxotremorine/pharmacology ; Propranolol/pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/physiology ; }, abstract = {There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 microg oxotremorine and 1.25 microg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of beta-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation.}, } @article {pmid15167981, year = {2004}, author = {Järbe, TU and Harris, MY and Li, C and Liu, Q and Makriyannis, A}, title = {Discriminative stimulus effects in rats of SR-141716 (rimonabant), a cannabinoid CB1 receptor antagonist.}, journal = {Psychopharmacology}, volume = {177}, number = {1-2}, pages = {35-45}, pmid = {15167981}, issn = {0033-3158}, support = {DA 00253/DA/NIDA NIH HHS/United States ; DA 00493/DA/NIDA NIH HHS/United States ; DA 03801/DA/NIDA NIH HHS/United States ; DA 09064/DA/NIDA NIH HHS/United States ; DA 13429/DA/NIDA NIH HHS/United States ; DA 7215/DA/NIDA NIH HHS/United States ; DA 9158/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Discrimination Learning/*drug effects/physiology ; Dose-Response Relationship, Drug ; Drinking/drug effects/physiology ; Male ; Piperidines/*pharmacology ; Pyrazoles/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/*antagonists & inhibitors/physiology ; Rimonabant ; }, abstract = {OBJECTIVE: To examine the discriminative stimulus effects of (i) the cannabinoid CB(1) receptor antagonist SR-141716 (SR, 5.6 mg/kg) and vehicle, and (ii) the cannabinoid receptor agonist Delta(9)-THC (THC, 1.8 mg/kg) and vehicle using a discriminated taste aversion (DTA) procedure.

METHODS: Two groups of rats (n=6) were trained to discriminate between these drugs and vehicle in DTA (t'=20 min). The 30-min drinking bout of tap water following drug (SR or THC) treatment was followed by an injection of lithium chloride (LiCl, 120 mg/kg) in the experimental animals. When offered water after vehicle pretreatment, experimental animals subsequently were given IP saline (NaCl, 10 ml/kg). Post-drinking treatment for controls (n=6) was NaCl, irrespective of the pretreatment condition (SR, THC or vehicle). Additional water was provided during the afternoon (30 min) with no other manipulations. Food was available ad lib at all times. When the discriminations were established other doses and drugs were examined (t'=20 min). In testing there were no post-drinking treatments.

RESULTS: The SR-related analog AM-251 (dose range: 1-5.6 mg/kg) substituted for SR, whereas other drugs such as the cannabinoid CB(2) receptor antagonist SR-144528 (3 and 10 mg/kg), THC (1-10 mg/kg), flumazenil (1-10 mg/kg), naloxone (1-10 mg/kg), morphine (10 and 18 mg/kg) and d-amphetamine (1 and 3 mg/kg) did not. There was a dose-related attenuation of SR-induced suppression of drinking when THC (1.8-10 mg/kg) was given together with SR (5.6 mg/kg). In the THC trained rats, SR (1-10 mg/kg), morphine (10 and 18 mg/kg) and d-amphetamine (1 and 3 mg/kg) did not substitute for THC. SR (1 mg/kg) attenuated the THC (1.8 mg/kg) induced suppression of drinking. Together with 3 mg/kg SR and 1.8 mg/kg THC, drinking was roughly equally suppressed in both the experimental group and the controls.

CONCLUSION: SR-141716 induces a discriminative stimulus complex in DTA that shows potential for further examination of cannabinoid receptor antagonism.}, } @article {pmid15158074, year = {2004}, author = {Hellemans, KG and Benge, LC and Olmstead, MC}, title = {Adolescent enrichment partially reverses the social isolation syndrome.}, journal = {Brain research. Developmental brain research}, volume = {150}, number = {2}, pages = {103-115}, doi = {10.1016/j.devbrainres.2004.03.003}, pmid = {15158074}, issn = {0165-3806}, mesh = {Adolescent ; Adolescent Development/*physiology ; Analysis of Variance ; Animals ; Animals, Newborn ; Anxiety/physiopathology ; Association Learning/physiology ; Behavior, Animal/*physiology ; Body Weight/physiology ; Cerebral Cortex/pathology ; Habituation, Psychophysiologic ; Humans ; Male ; Maze Learning/physiology ; Models, Animal ; Motivation ; Motor Activity/physiology ; Pain Measurement/methods ; Pain Threshold/physiology ; Rats ; Rats, Long-Evans ; *Social Environment ; *Social Isolation ; Spatial Behavior/physiology ; Time Factors ; }, abstract = {Early environmental experience produces profound neural and behavioural effects. For example, animals reared in isolation show increased anxiety, neophobia, and poorer performance in learning and spatial memory tasks. We investigated whether later enrichment reverses some or all of the deficits induced by isolation rearing. Eighty-four male Long-Evans rats (21 days old) were reared under different conditions: enriched (group housed with toys), isolated (one rat/cage), standard (two rats/cage), isolated-enriched, enriched-isolated, isolated-standard, or enriched-standard. In the latter four conditions, animals were housed in the first environment until adolescence (66 days). Following the 90-day rearing period, all animals were assessed in a battery of behavioural tests and cortical thickness was measured postmortem. Isolation rearing led to significant differences in behavioural tests measuring anxiety, spatial learning, and locomotor activity; switching the rearing condition partially reversed these changes. Rearing condition did not affect pain thresholds in the tail flick test or aversive associative learning in the conditioned taste aversion test. Enriched rats had the thickest cortex; isolated rats the thinnest. None of the switch groups differed significantly from standard-reared rats in this measure. Taken together, these results provide novel and interesting information regarding the effects of pre- or post-adolescent enrichment experience on behavioural and neural expression of the social isolation syndrome.}, } @article {pmid15155275, year = {2004}, author = {Cho, YK and Smith, ME and Norgren, R}, title = {Low-dose furosemide modulates taste responses in the nucleus of the solitary tract of the rat.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {287}, number = {4}, pages = {R706-14}, doi = {10.1152/ajpregu.00090.2004}, pmid = {15155275}, issn = {0363-6119}, mesh = {Animals ; Appetite/drug effects ; Cluster Analysis ; Data Interpretation, Statistical ; Diuretics/*pharmacology ; Electrophysiology ; Entropy ; Extracellular Space/physiology ; Furosemide/*pharmacology ; Male ; Microelectrodes ; Natriuresis/drug effects ; Neurons/drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Sodium, Dietary/pharmacology ; Solitary Nucleus/cytology/*drug effects ; Sucrose/pharmacology ; Taste/*drug effects ; }, abstract = {Taste-evoked neural responses in the nucleus of the solitary tract (NST) are subject to both excitatory and inhibitory modulation by physiological conditions that influence ingestion. Treatments that induce sodium appetite predominantly reduce NST gustatory responsiveness to sapid stimuli. When sodium appetite is aroused with 10 mg of the diuretic furosemide (Furo), however, NST gustatory neurons exhibit an enhanced responsiveness to NaCl. In addition to inducing a sodium appetite, 10 mg Furo supports a conditioned taste aversion (CTA). A lower, 2-mg dose of Furo induces an equivalent sodium appetite, but not a CTA. To determine whether the anomalous electrophysiological results reflected the adverse effects of the 10-mg dose, we replicated the original experiment but instead used 2 mg of Furo. In chronically prepared, lightly anesthetized rats, the responses of 49 single NST neurons to 12 taste stimuli were recorded after subcutaneous injections of either 2 mg Furo or saline. There was no effect of treatment on NST neural responses to the four standard taste stimuli. In the NaCl concentration series, however, 2 mg Furo evoked significantly higher responses to the two highest concentrations of NaCl. There was no effect of treatment in the sucrose concentration series. Thus, unlike other methods that induce a sodium appetite, Furo increases NST neural responsiveness to NaCl. At least as far as the first central relay, sodium appetite apparently does not depend on specific changes in the sensory neural code for taste.}, } @article {pmid15150142, year = {2004}, author = {Delay, ER and Sewczak, GM and Stapleton, JR and Roper, SD}, title = {Glutamate taste: Discrimination between the tastes of glutamate agonists and monosodium glutamate in rats.}, journal = {Chemical senses}, volume = {29}, number = {4}, pages = {291-299}, doi = {10.1093/chemse/bjh031}, pmid = {15150142}, issn = {0379-864X}, support = {DC005962/DC/NIDCD NIH HHS/United States ; DC03013/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/pharmacology ; Aminobutyrates/pharmacology ; Animals ; Aspartic Acid/pharmacology ; Avoidance Learning ; Discrimination, Psychological/*physiology ; Excitatory Amino Acid Agonists/*pharmacology ; Male ; N-Methylaspartate/pharmacology ; Rats ; Sodium Glutamate/*pharmacology ; Taste/*physiology ; Taste Threshold ; }, abstract = {Taste aversion studies have demonstrated that rats conditioned to avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of the sodium component of MSG taste, generalize this aversion to aspartic acid and to L-AP4, but not to ionotropic glutamate receptor agonists. That is, MSG, L-AP4 and aspartate have similar tastes to rats. However, conditioned taste aversion methods are unable to show to what extent the tastes of two substances are different. If two substances activate the same afferent processes (e.g. taste receptors), they are likely to produce the same tastes, but if they activate different afferent processes, the subject may detect differences between the tastes of the substances. In this study, rats were tested to determine if they could discriminate between the tastes of these agonists and MSG. We also established the detection thresholds for NMDA, aspartic acid and L-AP4, with and without amiloride (a sodium channel antagonist). Taste threshold values were 1-4 mM for NMDA and aspartic acid and 0.5-2.5 microM for L-AP4. None were affected by 30 micro M amiloride. Rats could readily distinguish between the tastes of MSG and NMDA but they had difficulty discriminating between the tastes of aspartic acid and MSG. Rats could also easily distinguish between 10-100 mM MSG and 0.01-5 mM L-AP4. However, in two separate experiments error rates increased significantly when L-AP4 concentrations were between 10-100 mM, indicating that the tastes of L-AP4 and MSG were similar at these concentrations.}, } @article {pmid15138758, year = {2004}, author = {Palmer, AA and Sharpe, AL and Burkhart-Kasch, S and McKinnon, CS and Coste, SC and Stenzel-Poore, MP and Phillips, TJ}, title = {Corticotropin-releasing factor overexpression decreases ethanol drinking and increases sensitivity to the sedative effects of ethanol.}, journal = {Psychopharmacology}, volume = {176}, number = {3-4}, pages = {386-397}, pmid = {15138758}, issn = {0033-3158}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA013331/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; MH65689/MH/NIMH NIH HHS/United States ; }, mesh = {Aging/psychology ; Alcohol Drinking/*genetics/*psychology ; Animals ; Avoidance Learning/drug effects ; Central Nervous System Depressants/pharmacokinetics/*pharmacology ; Corticotropin-Releasing Hormone/biosynthesis/*genetics/*physiology ; Ethanol/pharmacokinetics/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Postural Balance/drug effects ; Quinine/pharmacology ; Reflex/drug effects ; Saccharin/pharmacology ; Taste/drug effects ; }, abstract = {RATIONALE: Corticotropin-releasing factor (CRF) may play a significant role in drug and alcohol abuse.

OBJECTIVE: To evaluate the role of CRF in these processes, we examined several ethanol (EtOH) related behaviors in mice that carry a transgene that causes overexpression of CRF.

METHODS: We examined voluntary EtOH drinking, loss of the righting reflex (LORR), EtOH-induced conditioned taste aversion (CTA), and EtOH clearance in littermate transgenic (TG) and non-transgenic (non-TG) mice. In addition, because preliminary results indicated that age exacerbated differences in EtOH consumption between the two genotypes, we performed a cross-sectional and longitudinal evaluation of this trait at two ages (approximately 100 and 200 days old).

RESULTS: We found that TG mice consumed significantly less EtOH and had a lower preference for EtOH-containing solutions compared with their non-TG littermates. We also found that the older drug-naive TG mice drank less EtOH as compared with the younger mice of the same genotype; however, the same relationship did not exist for drug-naive non-TG mice. Prior experience in drinking EtOH when 100 days old led to decreased EtOH drinking when 200 days old in both genotypes. Duration of LORR was longer in the TG mice, EtOH-induced CTA was marginally greater in non-TG mice at the highest dose tested, and there were significant but small differences in EtOH clearance parameters.

CONCLUSIONS: These data show that CRF overexpressing mice voluntarily consume less EtOH. This difference is associated with greater sensitivity to the sedative-hypnotic effects of EtOH, but not with increased sensitivity to the aversive effects of EtOH.}, } @article {pmid15135011, year = {2004}, author = {Lundy, RF and Caloiero, V and Bradley, C and Liang, NC and Norgren, R}, title = {Furosemide-induced food avoidance: evidence for a conditioned response.}, journal = {Physiology & behavior}, volume = {81}, number = {3}, pages = {397-408}, doi = {10.1016/j.physbeh.2004.01.016}, pmid = {15135011}, issn = {0031-9384}, support = {DC 00240/DC/NIDCD NIH HHS/United States ; DC 05156/DC/NIDCD NIH HHS/United States ; MH 43787/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Appetite/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Cues ; Diuretics/*pharmacology ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Extinction, Psychological/drug effects ; Feeding Behavior/*drug effects ; Food ; Furosemide/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium/urine ; Sodium Chloride, Dietary/pharmacology ; Sucrose/pharmacology ; Taste/drug effects ; Water-Electrolyte Balance/drug effects ; Weight Gain/drug effects ; }, abstract = {Furosemide (Furo) is a potent natriuretic drug that is often used experimentally to investigate the brain mechanisms underlying salt appetite. Within this experimental paradigm, however, Furo also has anorectic activity that has received only modest attention. In Experiment 1 we varied two things-administering a 10-mg dose of Furo in a single or a divided dose and preinjection exposure to a Na-free diet. In the 24 h after Furo, all four groups of rats reduced ingestion of Na-free diet. Both the division of the Furo dose and the preexposure to Na-free diet reduced the amount of food consumed even more than a single dose or continuous access to normal chow did. The fact that preexposure to Na-free diet increased the post-Furo anorexia implied an associative component to the phenomenon. Experiments 2 and 3 investigated the ability of Furo (2 and 10 mg) to serve as an unconditioned stimulus in taste aversion learning using 0.2 M sucrose as the conditioned stimulus. A saline (Sal) injection group served as control in both experiments. The results show that animals avoided sucrose when its ingestion was immediately followed by 10 mg Furo but not with 2 mg Furo or Sal. An aversion to sucrose did not develop when 10 mg Furo was administered the day prior to sucrose access. Thus, the suppressive effects of high-dose Furo on food intake might be due to a conditioned response.}, } @article {pmid15121188, year = {2004}, author = {Koponen, E and Võikar, V and Riekki, R and Saarelainen, T and Rauramaa, T and Rauvala, H and Taira, T and Castrén, E}, title = {Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB-PLCgamma pathway, reduced anxiety, and facilitated learning.}, journal = {Molecular and cellular neurosciences}, volume = {26}, number = {1}, pages = {166-181}, doi = {10.1016/j.mcn.2004.01.006}, pmid = {15121188}, issn = {1044-7431}, mesh = {Animals ; Anxiety/genetics/*metabolism ; Avoidance Learning/physiology ; Brain Chemistry/genetics ; Brain-Derived Neurotrophic Factor/*metabolism ; Cerebral Cortex/cytology/metabolism ; Exploratory Behavior/physiology ; Female ; Hippocampus/cytology/metabolism ; Learning/*physiology ; Long-Term Potentiation/genetics ; Male ; Maze Learning/physiology ; Mice ; Mice, Transgenic ; Phospholipase C gamma ; Phosphorylation ; RNA, Messenger/metabolism ; Receptor, trkB/biosynthesis/*genetics ; Signal Transduction/genetics/*physiology ; Synaptic Transmission/genetics ; Type C Phospholipases/*metabolism ; Up-Regulation/genetics ; }, abstract = {We have investigated the biochemical, physiological, and behavioral properties of transgenic mice overexpressing the full-length neurotrophin receptor trkB (trkB.TK+). The highest trkB.TK+ mRNA overexpression was achieved in the cerebral cortex and hippocampal subfields, both areas also showing strongly increased trkB.TK+ receptor protein expression and phosphorylation. Furthermore, as a result of trkB.TK+ overexpression, partial activation of trkB downstream signaling was observed. Phosphorylation of phospholipaseCgamma-1 was increased but unexpectedly, the expression and phosphorylation levels of signaling molecules Shc and mitogen-activated protein kinase (MAPK) were unaltered. Behavioral studies revealed improved learning and memory in the water maze, contextual fear conditioning, and conditioned taste aversion tests, and reduced anxiety in the elevated plus maze (EPM) and light-dark exploration tests in trkB.TK+ transgenic mice. Electrophysiological studies revealed a reduced long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse in trkB.TK+ mice. Altogether, overexpression of the trkB.TK+ receptor postnatally leads to selective activation of trkB signaling pathways and enhanced learning and memory.}, } @article {pmid15119948, year = {2004}, author = {Bures, J and Lánský, P}, title = {From spreading depression to spatial cognition.}, journal = {Physiological research}, volume = {53 Suppl 1}, number = {}, pages = {S177-85}, pmid = {15119948}, issn = {0862-8408}, mesh = {Animals ; Avoidance Learning ; *Behavior, Animal ; Cortical Spreading Depression/*physiology ; Electroencephalography ; Locomotion/*physiology ; Memory ; Mice ; Rats ; Space Perception/*physiology ; Spatial Behavior ; }, abstract = {The Laboratory of Neurophysiology of Memory started its existence in 1954 by systematic research into spreading depression of EEG activity of laboratory rodents and by the use of this remarkable phenomenon as a functional ablation method in behavioral research. Its main contributions were in the study of memory formation and consolidation, interhemispheric transfer, motor learning, conditioned taste aversion and spatial orientation and navigation. In the last five years it concentrated on navigation of rats in multiple reference frames, on electrophysiological evidence for the role of hippocampal place cells support of behavior in such dissociated frames, on the analysis of idiothetic and allothetic forms of navigation and on the mathematical methods allowing assessment of the contribution of goal directed locomotion to place cell activity. The methods used in spatial memory research in rats were used for examination of human subjects in a laboratory equipped with a tracking system for humans in the hospital Homolka. Animal models of Alzheimer disease were studied in transgenic mice with the human gene for the beta amyloid precursor protein.}, } @article {pmid15114433, year = {2004}, author = {Stevenson, CW and Gratton, A}, title = {Role of basolateral amygdala dopamine in modulating prepulse inhibition and latent inhibition in the rat.}, journal = {Psychopharmacology}, volume = {176}, number = {2}, pages = {139-145}, pmid = {15114433}, issn = {0033-3158}, mesh = {Amygdala/drug effects/*physiology ; Animals ; Dopamine/physiology ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Drug ; Male ; Neural Inhibition/drug effects/*physiology ; Rats ; Rats, Long-Evans ; Receptors, Dopamine/*physiology ; Reflex, Startle/drug effects/*physiology ; }, abstract = {RATIONALE: The dopamine (DA) projection to the basolateral amygdala (BLA) modulates nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) DA transmission. Given the involvement of the BLA, and of NAc and mPFC DA, in select forms of information processing, we sought to determine the role of BLA DA in modulating prepulse inhibition (PPI) and latent inhibition (LI).

OBJECTIVE: The effects of BLA D1 (SCH 23390) and D2/D3 (raclopride) receptor blockade on PPI and LI were examined.

METHODS: Separate groups of male Long-Evans rats received bilateral intra-BLA infusions of SCH 23390 (3.2 or 6.4 microg/0.5 microl per side), raclopride (2.5 or 5.0 microg/0.5 microl per side) or saline prior to testing. In two experiments, the effects of BLA DA receptor antagonism on PPI of the acoustic startle response (ASR) and LI of conditioned taste aversion were determined. A control group received bilateral intra-striatal infusions of SCH 23390 or raclopride prior to PPI testing.

RESULTS: Intra-BLA SCH 23390 or raclopride had no effect on the ASR. Intra-BLA SCH 23390 enhanced and raclopride disrupted PPI, both in a dose-related manner. Intra-striatal SCH 23390 or raclopride had no effect on PPI or ASR magnitude. Finally, BLA DA receptor blockade had no effect on LI.

CONCLUSIONS: These results indicate that PPI is modulated by BLA DA and suggest that this modulation occurs independently of changes in NAc and/or mPFC DA transmission. They also suggest that BLA DA is not involved in modulating LI and add to evidence indicating that PPI and LI are mediated by different neural substrates.}, } @article {pmid15110912, year = {2004}, author = {Salvy, SJ and Heth, DC and Pierce, WD and Russell, JC}, title = {Conditioned taste aversion induced by wheel running: further evidence on wheel running duration.}, journal = {Behavioural processes}, volume = {66}, number = {2}, pages = {101-106}, doi = {10.1016/j.beproc.2004.01.006}, pmid = {15110912}, issn = {0376-6357}, mesh = {Animals ; *Avoidance Learning ; Behavior, Animal ; *Conditioning, Psychological ; Environment ; Male ; Random Allocation ; Rats ; *Running ; *Taste ; Time Factors ; }, abstract = {Rats given access to a running wheel after drinking a flavored solution subsequently drink less of that liquid. It has been suggested that suppression of intake is the result of conditioned taste aversion (CTA). This study explored whether the magnitude of CTA is related to time in the wheel (i.e., amount of wheel running). During 4 days of conditioning, rats drank an orange liquid for 60 min. Immediately after drinking, experimental rats were transferred to running wheels for either 20 or 60 min. Control animals remained in their home cages. Following the conditioning phase, all rats received a preference test composed of the paired flavored liquid (i.e., orange solution) and water. Rats in both experimental groups (20 and 60 min) decreased their consumption of the orange flavored liquid, but no difference in CTA was found between these groups. Wheel running, whether for 20 or 60 min, suppresses the consumption of a liquid consumed immediately before wheel access. These findings are discussed in terms of discrepancies between CTA induced by wheel running and CTA induced by emetic agents.}, } @article {pmid15078563, year = {2004}, author = {D'Adamo, P and Wolfer, DP and Kopp, C and Tobler, I and Toniolo, D and Lipp, HP}, title = {Mice deficient for the synaptic vesicle protein Rab3a show impaired spatial reversal learning and increased explorative activity but none of the behavioral changes shown by mice deficient for the Rab3a regulator Gdi1.}, journal = {The European journal of neuroscience}, volume = {19}, number = {7}, pages = {1895-1905}, doi = {10.1111/j.1460-9568.2004.03270.x}, pmid = {15078563}, issn = {0953-816X}, support = {GGP030192/TI_/Telethon/Italy ; }, mesh = {Animals ; Behavior, Animal ; Conditioning, Classical/physiology ; Exploratory Behavior/*physiology ; Fear/physiology ; Guanine Nucleotide Dissociation Inhibitors/*deficiency/genetics/metabolism ; Learning Disabilities/genetics/*physiopathology ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/physiology ; Reaction Time/physiology ; Reversal Learning/*physiology ; Spatial Behavior/*physiology ; Taste/genetics/physiology ; Time Factors ; rab3A GTP-Binding Protein/*deficiency/genetics/metabolism ; }, abstract = {Rab proteins are small GTPases involved in intracellular trafficking. Among the 60 different Rab proteins described in mammals, Rab3a is the most abundant in brain, where it is involved in synaptic vesicle fusion and neurotransmitter release. Rab3a constitutive knockout mice (Rab3a(-/-)) are characterized by deficient short- and long-term synaptic plasticity in the mossy fiber pathway and altered circadian motor activity, while no effects on spatial learning have been reported so far for these mice. The goals of this study were to analyse possible behavioral consequences of the lack of synaptic plasticity in the mossy fiber pathway using a broad battery of sensitive behavioral measures that has been used previously to analyse the behavior of Gdi1 mice lacking a protein thought to regulate Rab3a. Rab3a(-/-) mice showed normal acquisition but moderately impaired platform reversal learning in the water maze including reference memory and episodic-like memory tasks. A mild deficit in spatial working memory was also observed when tested in the radial maze. Analysis of explorative behavior revealed increased locomotor activity and enhanced exploratory activity in open field, O-maze, dark/light box and novel object tests. Spontaneous activity in normal home cage settings was unaffected but Rab3a(-/-) mice showed increased motor activity when the home cage was equipped with a wheel. No differences were found for delayed and trace fear conditioning or for conditioned taste aversion learning. Congruent with earlier data, these results suggest that Rab3a-dependent synaptic plasticity might play a specific role in the reactivity to novel stimuli and behavioral stability rather than being involved in memory processing. On the other hand, the phenotypic changes in the Rab3a(-/-) mice bore no relation to the behavioral changes as observed in the Gdi1 mice. Such divergence in phenotypes implies that the putative synaptic interaction between Gdi1 and Rab3a should be reconsidered and re-analysed.}, } @article {pmid15071088, year = {2004}, author = {Danilova, V and Hellekant, G}, title = {Sense of taste in a New World monkey, the common marmoset. II. Link between behavior and nerve activity.}, journal = {Journal of neurophysiology}, volume = {92}, number = {2}, pages = {1067-1076}, doi = {10.1152/jn.01183.2003}, pmid = {15071088}, issn = {0022-3077}, support = {RR 00167/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Behavior, Animal/*physiology ; Callithrix/*physiology ; Choice Behavior/physiology ; Chorda Tympani Nerve/*physiology ; Conditioning, Psychological ; Female ; Glossopharyngeal Nerve/*physiology ; Male ; Nerve Fibers/physiology ; Pleasure-Pain Principle ; Taste/*physiology ; }, abstract = {In a previous study, we characterized the gustatory system of a New World monkey the common marmoset, Callithrix jacchus jacchus, with electrophysiological techniques by recording from taste fibers of the chorda tympani proper (CT) and glossopharyngeal (NG) nerves. Hierarchical cluster analysis identified three clusters of taste fibers: S fibers, responding predominantly to sweeteners, Q fibers, responding predominantly to bitter stimuli, and H fibers, responding predominantly to acids. In this study, we employed two behavioral techniques, the two-bottle preference (TBP) and conditioned taste aversion (CTA), to study the taste of the compounds used in the previous electrophysiological study. The results showed that compounds that did not stimulate any taste fibers were neither preferred nor rejected. Compounds that activated only S fibers were always preferred over water. When aversion to sucrose was created by the CTA method, these compounds were rejected. Compounds that activated Q fibers were rejected and consumed less than water. We studied the relationship between intake and net response from S and Q fibers in the CT and NG nerves. Intake was measured as a preference ratio in TBP test. The net response was defined as: (S(CT) + S(NG)) - (Q(CT) + Q(NG)), where S(CT) + S(NG) denotes the sum of the responses in S fibers of the CT and NG nerves. Similarly, Q(CT) + Q(NG) represents the sum of the responses in Q fibers of the CT and NG nerves. The relationship between intake and the Net response was linear with a Pearson correlation coefficient 0.85. This study supports our hypothesis that intake is influenced by S and Q fibers, where S fibers serve as a hedonically positive input and Q fibers as a hedonically negative input.}, } @article {pmid15070083, year = {2003}, author = {Foy, MR and Foy, JG}, title = {Reversal of long-delay conditioned taste aversion learning in rats by sex hormone manipulation.}, journal = {Integrative physiological and behavioral science : the official journal of the Pavlovian Society}, volume = {38}, number = {3}, pages = {203-213}, pmid = {15070083}, issn = {1053-881X}, support = {AG 14751/AG/NIA NIH HHS/United States ; }, mesh = {Androgens/pharmacology ; Animals ; Association Learning/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Dihydrotestosterone/pharmacology ; Estradiol/pharmacology ; Female ; Gonadal Steroid Hormones/*physiology ; Lithium Chloride/toxicity ; Male ; Rats ; Taste/drug effects/*physiology ; }, abstract = {Conditioned taste aversion (CTA) learning is an adaptive, robust, well-established learning and memory paradigm. Strong taste aversions develop to the conditioned stimulus (CS = saccharin) despite long delays between exposure to the CS and unconditioned stimulus (US = LiCl). Rats display a sexually dimorphic pattern of long-delay CTA learning (Foy et al., 1996). The present study examines whether this sex difference is a result of activational or organizational hormone action, because here we implanted gonadectomized rats with their normal hormone replacements, or with opposing hormones prior to testing in a 4-hr delayed CTA learning task. We found that gonadally intact male rats displayed a more robust CTA response than intact female rats. Gonadectomy essentially eliminated this sex difference; gonadectomized males and gonadectomized females displayed similar CTA responses. In gonadectomized rats, when their normal sex hormones were replaced with implanted hormone pellets, the sex difference in CTA learning was reinstated. In contrast, when gonadectomized rats were implanted with opposing hormones, the sex difference was reversed. Gonadectomized female rats implanted with 5alpha-DHT pellets (metabolite of testosterone) displayed a stronger CTA response compared to gonadectomized males implanted with 17beta-estradiol pellets. Regardless of the original developmental hormonal environment, our study suggests that an activational manipulation of circulating hormones serves to significantly influence long-delay CTA learning in rats.}, } @article {pmid15056457, year = {2004}, author = {Pennanen, L and Welzl, H and D'Adamo, P and Nitsch, RM and Götz, J}, title = {Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice.}, journal = {Neurobiology of disease}, volume = {15}, number = {3}, pages = {500-509}, doi = {10.1016/j.nbd.2003.11.020}, pmid = {15056457}, issn = {0969-9961}, mesh = {Animals ; Anxiety ; Behavior, Animal/*physiology ; Brain/*pathology/physiology ; Conditioning, Classical/physiology ; Disease Models, Animal ; Extinction, Psychological/*physiology ; Humans ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Microtubule-Associated Proteins/*genetics ; Neurodegenerative Diseases/genetics ; Neurofibrillary Tangles/pathology ; Taste/physiology ; tau Proteins/biosynthesis/*genetics ; }, abstract = {Neurofibrillary tangles, insoluble protein deposits composed of filamentous tau aggregates, are neuropathological hallmarks of Alzheimer's disease and familial frontotemporal dementia (FTDP-17). Transgenic mice expressing the FTDP-17 mutation P301L of tau recapitulate key features of the human pathology, that is, tau proteins aggregate and neurofibrillary tangles begin to appear in the amygdala at 6 months of age. To detect early signs of tau aggregate-associated changes, we investigated behavioral alterations and cognitive deficits in such mice using an amygdala-specific test battery for anxiety-related and cognitive behavior. P301L mice had anxiety levels not different from wild-types, but their exploratory behavior was significantly increased. Acquisition of a fear response to tone and context as well as taste aversion was comparable to wild-types. However, extinction of a conditioned taste aversion was significantly accelerated. We conclude that already aggregation of tau proteins not yet accompanied by massive formation of neurofibrillary tangles causes selective behavioral deficits.}, } @article {pmid15049508, year = {2004}, author = {Bermúdez-Rattoni, F and Ramírez-Lugo, L and Gutiérrez, R and Miranda, MI}, title = {Molecular signals into the insular cortex and amygdala during aversive gustatory memory formation.}, journal = {Cellular and molecular neurobiology}, volume = {24}, number = {1}, pages = {25-36}, pmid = {15049508}, issn = {0272-4340}, mesh = {Amygdala/cytology/*metabolism ; Animals ; Avoidance Learning/physiology ; Cerebral Cortex/cytology/*metabolism ; Humans ; Memory/*physiology ; Neural Pathways/cytology/*metabolism ; Neuronal Plasticity/physiology ; Receptors, Muscarinic/metabolism ; Signal Transduction/physiology ; Taste/*physiology ; }, abstract = {In this paper, we will provide evidence of the putative molecular signals and biochemical events that mediate the formation of long-lasting gustatory memory trace. When an animal drinks a novel taste (the conditioned stimulus; CS) and it is later associated with malaise (unconditioned stimulus; US), the animal will reject it in the next presentation, developing a long-lasting taste aversion, i.e., the taste cue becomes an aversive signal, and this is referred to as conditioning taste aversion. Different evidence indicates that the novel stimulus (taste) induces a rapid and strong cortical acetylcholine activity that decreases when the stimulus becomes familiar after several presentations. Cholinergic activation via muscarinic receptors initiates a series of intracellular events leading to plastic changes that could be related to short- and/or long-term memory gustatory trace. Such plastic changes facilitate the incoming US signals carried out by, in part, the glutamate release induced by the US. Altogether, these events could produce the cellular changes related to the switch from safe to aversive taste memory trace. A proposed working model to explain the biochemical sequence of signals during taste memory formation will be discussed.}, } @article {pmid15009160, year = {2004}, author = {Bahar, A and Dorfman, N and Dudai, Y}, title = {Amygdalar circuits required for either consolidation or extinction of taste aversion memory are not required for reconsolidation.}, journal = {The European journal of neuroscience}, volume = {19}, number = {4}, pages = {1115-1118}, doi = {10.1111/j.0953-816x.2004.03215.x}, pmid = {15009160}, issn = {0953-816X}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Extinction, Psychological/*physiology ; Male ; Memory/physiology ; Nerve Net/*physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Recent reports have revitalized the debate on whether, for each item in memory, consolidation occurs just once, or whether, upon their activation in retrieval, items in memory undergo reconsolidation. Further, it has been recently reported that following retrieval in the absence of reinforcer, the activated memory can either reconsolidate or extinguish, depending on the training history. This raises the question whether consolidation, extinction and reconsolidation share neuronal mechanisms, and moreover, whether reconsolidation recapitulates consolidation. In conditioned taste aversion (CTA), consolidation depends on protein synthesis in the central nucleus of the amygdala, whereas extinction depends on protein synthesis in the basolateral nuclei of the amygdala. Here we show that inhibition of protein synthesis in either of these nuclei has no effect on CTA memory under conditions that initiate reconsolidation. This implies that reconsolidation does not recapitulate consolidation, and that consolidation, reconsolidation and extinction are different processes.}, } @article {pmid15006479, year = {2004}, author = {Riley, AL and Freeman, KB}, title = {Conditioned taste aversion: a database.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {77}, number = {3}, pages = {655-656}, doi = {10.1016/j.pbb.2004.01.002}, pmid = {15006479}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; *Databases, Factual ; Humans ; Taste/*physiology ; }, abstract = {The present commentary describes the availability of a database on conditioned taste aversion learning, the avoidance of fluids and foods previously associated with the aversive effects of a variety of drugs. The database includes articles as early as 1955 by Garcia and his colleagues [Science 122 (1955) 127] (reporting such avoidance in rats) and papers just published given that the database is ongoing and constantly updated. At the printing of this announcement, approximately 2600 papers are included in the database. The database allows the user to search for articles by author(s), key word(s), date, title and journal. These terms can be used as single entries or multiple combinations. Finally, the full database can be viewed by performing the search function without entering any terms in the query window. The database can be accessed at http://www.CTALearning.com.}, } @article {pmid15002878, year = {2003}, author = {McKay, BE and Persinger, MA}, title = {Conditioned taste aversion is not disrupted in rats exposed to weak, complex magnetic fields during the CS-UCS interval.}, journal = {Perceptual and motor skills}, volume = {97}, number = {3 Pt 2}, pages = {1335-1338}, doi = {10.2466/pms.2003.97.3f.1335}, pmid = {15002878}, issn = {0031-5125}, mesh = {Animals ; Behavior, Animal/physiology ; *Conditioning, Psychological ; Electromagnetic Fields/*adverse effects ; Hippocampus/*physiology ; Male ; Neurons/physiology ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {40 normal male Wistar rats were trained for 8 successive days to consume water ad libitum during once-daily 20-min. sessions. On the following day (training day) the rats were presented with a novel solution of 10% sucrose for 20 min. followed by a single exposure for 2 hr. to one of two weak (200 to 500 nanoTesla) complex magnetic fields or to sham-field conditions. The patterns of the two magnetic fields and the durations of their repeated presentations (interstimulus interval) were designed to be resonant with the intrinsic firing of hippocampal pyramidal and solitary neurons, respectively. Immediately after the applications of the fields one-half the number of rats were injected with lithium to evoke gastrointestinal malaise. Although on the test day, three days later, rats previously injected with the lithium exhibited the usual robust reduction in the consumption of sucrose compared to the training day, there were no statistically significant differences between field-exposed and sham-field groups for these ratios. We conclude that a 2-hr. exposure to weak magnetic fields designed to simulate the pattern of two structures likely involved with conditioned taste aversion between the conditioned stimulus and the unconditioned stimulus did not affect this behavior.}, } @article {pmid14992275, year = {2004}, author = {Jiménez, B and Tapia, R}, title = {Biochemical modulation of NMDA receptors: role in conditioned taste aversion.}, journal = {Neurochemical research}, volume = {29}, number = {1}, pages = {161-168}, pmid = {14992275}, issn = {0364-3190}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Operant ; Humans ; Phosphorylation ; Receptors, N-Methyl-D-Aspartate/metabolism/*physiology ; Taste/*physiology ; }, abstract = {Glutamate neurotransmission plays a crucial role in a variety of functions in the central nervous system, including learning and memory. However, little is known about the mechanisms underlying this process in mammals because of the scarceness of experimental models that permit correlation of behavioral and biochemical changes occurring during the different stages of learning and the retrieval of the acquired information. One model that has been useful to study these mechanisms is conditioned taste aversion (CTA), a paradigm in which animals learn to avoid new tastes when they are associated with gastrointestinal malaise. Glutamate receptors of the N-methyl-D-aspartate (NMDA) type appear to be necessary in this process, because blockade of this receptor prevents CTA. Phosphorylation of the main subunits of the NMDA receptor is a well-established biochemical mechanism for the modulation of the receptor response. Such modulation seems to be involved in CTA, because inhibitors of protein kinase C (PKC) block CTA acquisition and because the exposure to an unfamiliar taste results in an increased phosphorylation of tyrosine and serine residues of the NR2B subunit of the receptor in the insular cortex, the cerebral region where gustatory and visceral information converge. In this work we review these mechanisms of NMDA receptor modulation in CTA.}, } @article {pmid14984795, year = {2004}, author = {Nakajima, S and Masaki, T}, title = {Taste aversion learning induced by forced swimming in rats.}, journal = {Physiology & behavior}, volume = {80}, number = {5}, pages = {623-628}, doi = {10.1016/j.physbeh.2003.11.006}, pmid = {14984795}, issn = {0031-9384}, mesh = {Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Male ; Rats ; Rats, Wistar ; *Swimming/psychology ; *Taste ; }, abstract = {Two experiments demonstrated that forced swimming endowed rats with aversion to the taste solution consumed before the swimming. In Experiment 1, the rats given a trial of taste-swimming sequence drank less of the taste solution in a later test than did the rats given a taste-alone trial. The rats given a trial of taste-poisoning-swimming sequence, however, drank more of the taste solution in the testing than did the rats given a trial of taste-poisoning sequence. These results suggest that some effects of swimming (e.g., energy expenditure caused by physical exercise) induce conditioned taste aversion although they attenuate taste aversion conditioned by poisoning. The attenuation of poison-induced taste aversion by swimming has been reported in the literature, but the swimming-induced taste aversion is novel. Experiment 2, accordingly, was planned to confirm this phenomenon with a differential conditioning procedure, where one of two taste solutions was paired with swimming while the other was not. After a few repetitions of these two types of trials, the rats' intakes of these two solutions were differentiated to show that swimming has the ability to cause taste aversion.}, } @article {pmid14973323, year = {2004}, author = {Tokita, K and Karádi, Z and Shimura, T and Yamamoto, T}, title = {Centrifugal inputs modulate taste aversion learning associated parabrachial neuronal activities.}, journal = {Journal of neurophysiology}, volume = {92}, number = {1}, pages = {265-279}, doi = {10.1152/jn.01090.2003}, pmid = {14973323}, issn = {0022-3077}, mesh = {Action Potentials/drug effects/*physiology ; Amygdala/drug effects/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Electric Stimulation/methods ; Male ; Neurons/drug effects/physiology ; Rats ; Rats, Wistar ; Sodium Chloride/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Our previous studies have demonstrated that gustatory neurons in the parabrachial nucleus (PBN) show altered responses after the acquisition of conditioned taste aversion (CTA) to NaCl. The present study was conducted 1) to examine centrifugal influences on the altered gustatory activity of CTA-trained rats, and 2) to evaluate the role of amiloride-sensitive (ASN) and -insensitive NaCl (AIN) best units in coding the taste of NaCl. Animals were separated into 2 groups: a CTA group that had acquired taste aversion to 0.1 M NaCl and a control group that underwent pseudoconditioning before the recording experiment. Single-neuron activity, in 2 separate series of experiments, was extracellularly recorded in anesthetized rats. In the stimulation studies, the effects of electrical stimulation of the gustatory cortex (GC) or the central nucleus of amygdala (CeA) were examined on firing of PBN taste units. CeA stimulation produced excitatory effect in significantly more neurons in the CTA group (n = 8) than in the control group (n = 1). Furthermore, ASN-best units in the CTA group showed larger responses to NaCl than similar units in the control group. In the decerebration experiment, there was no statistical difference among the taste responses between the 2 groups in any best-stimulus category. These results suggest that CTA conditioning uses an effective central amygdaloid input to modulate activity of gustatory neurons in the PBN. Data also substantiate that amiloride-sensitive components of NaCl-best neurons play a critical role in the recognition of distinctive taste of NaCl.}, } @article {pmid14960013, year = {2004}, author = {Võikar, V and Vasar, E and Rauvala, H}, title = {Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: implications for phenotyping screens.}, journal = {Genes, brain, and behavior}, volume = {3}, number = {1}, pages = {27-38}, doi = {10.1046/j.1601-183x.2003.0044.x}, pmid = {14960013}, issn = {1601-1848}, mesh = {Animals ; Behavior, Animal/*physiology ; Conditioning, Psychological/physiology ; Exploratory Behavior/physiology ; *Genetics, Behavioral ; Habituation, Psychophysiologic/genetics/physiology ; Learning/physiology ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Motor Activity/physiology ; *Phenotype ; *Practice, Psychological ; }, abstract = {The C57BL/6JOlaHsd and 129S2/SvHsd mice were tested in a battery designed for behavioral phenotyping of genetically modified mice. The study was performed in order to reveal the effect of training history on the behavior by comparison with the experimentally naive mice in the same tests. Significant strain differences were obtained in all experiments. Previous handling and testing reduced exploratory activity and emotionality significantly in the mice. The coordination ability was better and nociceptive sensitivity was increased in the trained mice. The contextual fear was reduced whereas the cued fear was enhanced in the experienced mice. The training history did not alter initial learning in the water maze. However, after reversal learning the naive mice displayed significant preference for both old and new platform locations, whereas the battery animals did not exhibit preference to the old location. The experienced mice appeared to be less active in the forced swimming test and exhibited decreased conditioned taste aversion. The influence of test history was strain-dependent in certain cases. Therefore, the experience has substantial consequences on the behavior, mainly by reducing exploratory activity, and the previous experience of the animals has always to be considered in the analysis of genetically modified mice.}, } @article {pmid14758341, year = {2004}, author = {Della-Zuana, O and Revereault, L and Beck-Sickinger, A and Monge, A and Caignard, DH and Fauchère, JL and Henlin, JM and Audinot, V and Boutin, JA and Chamorro, S and Félétou, M and Levens, N}, title = {A potent and selective NPY Y5 antagonist reduces food intake but not through blockade of the NPY Y5 receptor.}, journal = {International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity}, volume = {28}, number = {4}, pages = {628-639}, doi = {10.1038/sj.ijo.0802435}, pmid = {14758341}, mesh = {Animals ; Appetite/physiology ; Conditioning, Psychological/physiology ; Eating/*drug effects/*physiology ; Male ; Mice ; Mice, Knockout ; Pica/physiopathology ; Rats ; Rats, Long-Evans ; Rats, Wistar ; Receptors, Neuropeptide Y/*antagonists & inhibitors/genetics/physiology ; Satiety Response/physiology ; Sodium Chloride, Dietary/administration & dosage ; Taste/physiology ; }, abstract = {AIM: These studies were performed to test the hypothesis that endogenous neuropeptide Y (NPY) acting on the NPY Y(5) receptor subtype contributes to the control of food intake. The hypothesis was tested using S 25585-a newly synthesized NPY Y(5) receptor antagonist.

METHODS AND RESULTS: S 25585 was shown to be a high-affinity antagonist of the NPY Y(5) receptor subtype (IC(50) 5 nM) with no significant affinity toward other NPY receptor subtypes and over 40 other receptors, channels or uptake systems. S 25585 (7.5 mg/kg, i.p.) did not induce a conditioned taste aversion, significantly alter need-induced sodium appetite or induce pica, suggesting that at this dose the compound did not induce illness or malaise. In satiated rats, S 25585 (5.0 and 7.5 mg/kg, i.p.) significantly decreased the overfeeding induced by i.c.v. injection of NPY (1 microg) and the highly selective NPY Y(5) receptor agonist [hPP(1-17), Ala(31), Aib(32)]NPY (0.7 microg). In rats fasted for 4 h immediately before the dark phase, analysis of the microstructure of feeding behavior revealed that S 25585 significantly increased latency to eat and significantly decreased the duration and size of the meals without altering the meal number or eating rate. Analysis of the behavioral satiety sequence at this time revealed that the animals passed through the normal pattern of feeding, grooming and resting. Although S 25585 appeared to be influencing a physiological system controlling appetite, this does not involve the NPY Y(5) receptor since the antagonist also markedly reduced food intake in the NPY Y(5) knockout mouse.

CONCLUSIONS: The results presented do not support a role for the NPY Y(5) receptor in the control of food intake. The results further illustrate that it is imperative that the activity of any new NPY Y(5) antagonist be assessed in the NPY Y(5) knockout mouse before assuming that its effect on food intake is due to blockade of this receptor.}, } @article {pmid14759596, year = {2004}, author = {Mormède, C and Palin, K and Kelley, KW and Castanon, N and Dantzer, R}, title = {Conditioned taste aversion with lipopolysaccharide and peptidoglycan does not activate cytokine gene expression in the spleen and hypothalamus of mice.}, journal = {Brain, behavior, and immunity}, volume = {18}, number = {2}, pages = {186-200}, doi = {10.1016/S0889-1591(03)00133-8}, pmid = {14759596}, issn = {0889-1591}, mesh = {Analysis of Variance ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Corticosterone/blood ; Cytokines/genetics/*metabolism ; Female ; Hippocampus/drug effects/*metabolism ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mitogen-Activated Protein Kinases/metabolism ; NF-kappa B/metabolism ; Neuroimmunomodulation/physiology ; Peptidoglycan ; RNA, Messenger/analysis ; Signal Transduction ; Spleen/drug effects/*metabolism ; Taste ; Taste Disorders/chemically induced/metabolism ; }, abstract = {Several reports show that behavioural and physiological components of the acute phase reaction can be conditioned. However, the mechanisms responsible for these effects remain obscure. The underlying assumption that the changes observed in conditioned animals are dependent on a conditioned production of cytokines has never been demonstrated. In the present study, the possibility of conditioning the production of cytokines or molecules implicated in their signalling pathways was tested by submitting mice to conditioned taste aversion with a new saccharin taste paired with intraperitoneal (i.p.) injections of lipopolysaccharide (LPS, 0.83 microg/g) or peptidoglycan (PGN, 20 microg/g). After two conditioning sessions, conditioned mice developed a clear aversion to saccharine that was not associated with activation of genes of the cytokine network either at the periphery, or in the hypothalamus, as demonstrated by a macroarray approach and confirmed by real time RT-PCR. In contrast, there was an activation of the genes coding for nuclear factor kappa B (NFkappaB) and mitogen activated protein kinase (MAPK) signalling pathways in the spleen and to a lesser extent in the hypothalamus. This modulation of the NFkappaB and MAPK signalling pathways is interpreted in terms of a possible conditioned sensitisation of the immune system.}, } @article {pmid14750976, year = {2004}, author = {Yin, HH and Knowlton, BJ and Balleine, BW}, title = {Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning.}, journal = {The European journal of neuroscience}, volume = {19}, number = {1}, pages = {181-189}, doi = {10.1111/j.1460-9568.2004.03095.x}, pmid = {14750976}, issn = {0953-816X}, support = {MH 56446/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/physiology ; Biofeedback, Psychology/physiology ; Cognition/*physiology ; Conditioning, Operant/physiology ; Denervation ; Extinction, Psychological/physiology ; Female ; *Habits ; Learning/*physiology ; Male ; Motivation ; Neostriatum/drug effects/*physiology ; Rats ; Rats, Long-Evans ; Reinforcement, Psychology ; }, abstract = {Habits are controlled by antecedent stimuli rather than by goal expectancy. Interval schedules of feedback have been shown to generate habits, as revealed by the insensitivity of behaviour acquired under this schedule to outcome devaluation treatments. Two experiments were conducted to assess the role of the dorsolateral striatum in habit learning. In Experiment 1, sham operated controls and rats with dorsolateral striatum lesions were trained to press a lever for sucrose under interval schedules. After training, the sucrose was devalued by inducing taste aversion to it using lithium chloride, whereas saline injections were given to the controls. Only rats given the devaluation treatment reduced their consumption of sucrose and this reduction was similar in both the sham and the lesioned groups. All rats were then returned to the instrumental chamber for an extinction test, in which the lever was extended but no sucrose was delivered. In contrast to sham operated controls, rats with dorsolateral striatum lesions refrained from pressing the lever if the outcome was devalued. To assess the specificity of the role of dorsolateral striatum in this effect a second experiment was conducted in which a group with lesions of dorsomedial striatum was added. In relation now to both the sham and the dorsomedial lesioned groups, only rats with lesions of dorsolateral striatum significantly reduced responding after outcome devaluation. In conclusion, this study provides direct evidence that the dorsolateral striatum is necessary for habit formation. Furthermore, it suggests that, when the habit system is disrupted, control over instrumental performance reverts to the system controlling the performance of goal-directed instrumental actions.}, } @article {pmid14747522, year = {2004}, author = {Gutiérrez, R and De la Cruz, V and Rodriguez-Ortiz, CJ and Bermudez-Rattoni, F}, title = {Perirhinal cortex muscarinic receptor blockade impairs taste recognition memory formation.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {11}, number = {1}, pages = {95-101}, pmid = {14747522}, issn = {1072-0502}, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Acetylcholine/physiology ; Animals ; Cerebral Cortex/*drug effects/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/physiology ; Male ; Memory/*drug effects/physiology ; Muscarinic Antagonists/*pharmacology ; Quinoxalines/pharmacology ; Rats ; Rats, Wistar ; Receptors, AMPA/antagonists & inhibitors/physiology ; Receptors, Muscarinic/drug effects/*physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Recognition, Psychology/*drug effects/physiology ; Scopolamine/*pharmacology ; Synaptic Transmission ; Taste/*drug effects/physiology ; }, abstract = {The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition memory using attenuation of neophobia as an index. In addition, learned taste aversion in both short- and long-term memory tests was exclusively impaired by scopolamine. These data provide neurochemical support for the theory that cholinergic activity of the perirhinal cortex participates in the formation of the taste memory trace and that it is independent of the NMDA and AMPA receptor activity. These results support the idea that cholinergic neurotransmission in the perirhinal cortex is also essential for acquisition and consolidation of taste recognition memory.}, } @article {pmid14733484, year = {2003}, author = {Bills, C and Smith, S and Myers, N and Schachtman, TR}, title = {Effects of context exposure during conditioning on conditioned taste aversions.}, journal = {Learning & behavior}, volume = {31}, number = {4}, pages = {369-377}, pmid = {14733484}, issn = {1543-4494}, support = {R01 MH59039-01/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Cues ; Female ; Lithium Chloride/toxicity ; Male ; *Memory, Short-Term ; Mental Recall ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology ; Social Environment ; *Taste ; }, abstract = {Rats were used in a conditioned taste aversion procedure in order to examine the effects of context exposure duration during the conditioning sessions on conditioned responding. One flavor was paired with lithium chloride during a long session in one context, whereas another flavor was conditioned during a short session in another context. Testing occurred in the home cage. The results showed that conditioning during short sessions produced strong conditioned taste aversions. Conditioning during long sessions produced strong conditioned taste aversions when the conditioned-stimulus-unconditioned-stimulus (CS-US) pairing occurred at the end of the lengthy session. Other results showed that context-US associations were formed during the short duration sessions and that these associations supported conditioned responding to the CS trained in that context. The results are discussed with respect to the different influences that contextual cues can exert on conditioned responding.}, } @article {pmid14725964, year = {2004}, author = {Grabus, SD and Glowa, JR and Riley, AL}, title = {Morphine- and cocaine-induced c-Fos levels in Lewis and Fischer rat strains.}, journal = {Brain research}, volume = {998}, number = {1}, pages = {20-28}, doi = {10.1016/j.brainres.2003.11.007}, pmid = {14725964}, issn = {0006-8993}, mesh = {Analgesics, Opioid/*pharmacology ; Anesthetics, Local/*pharmacology ; Animals ; Brain/anatomy & histology/*drug effects/metabolism ; Cocaine/*pharmacology ; Female ; Immunohistochemistry/methods ; Morphine/*pharmacology ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Species Specificity ; }, abstract = {Lewis (LEW) and Fischer 344 (F344) rat strains have been reported to differ in their sensitivity to the rewarding and aversive effects of both cocaine and morphine. Specifically, LEW rats self-administer morphine and cocaine to a greater extent than F344 rats, while LEW (compared to F344) rats are more sensitive to the aversive effects of cocaine but less sensitive to the aversive effects of morphine. Consistent with assessments of the rewarding effects of morphine and cocaine in these two strains, LEW rats have lower basal, and generally higher drug-induced, activity in brain regions associated with reward. Although the brain areas that mediate the aversive effects of drugs are becoming better defined, no studies have compared the activation of these areas by aversion-inducing drugs in the LEW and F344 strains. As such, the relationship between the ability of drugs to activate these aversion-associated brain areas and to induce a conditioned taste aversion (CTA) in these strains is unknown. To explore this relationship, LEW and F344 rats were injected with saline or doses of morphine or cocaine (32 mg/kg for both drugs) that have been shown to generate differential taste aversion learning in these strains. All animals were subsequently tested for c-Fos expression in areas of the brain associated with aversion learning (the lateral and medial parabrachial nucleus, intermediate and caudal nucleus tractus solitarius and area postrema), reward (the shell of the nucleus accumbens) and locomotion (the core of the nucleus accumbens and the caudate putamen). The present results indicated that patterns of morphine- and cocaine-induced c-Fos within CTA-associated, but not reward- or locomotor-associated, brain regions paralleled the differential behavioral sensitivities of LEW and F344 rats to these drugs within CTA learning. Analyses with other drugs that do and do not induce aversions differentially would further assess the role of these brain areas in aversion learning, in general, and in strain-dependent differences, in particular.}, } @article {pmid14709342, year = {2004}, author = {Sewards, TV}, title = {Dual separate pathways for sensory and hedonic aspects of taste.}, journal = {Brain research bulletin}, volume = {62}, number = {4}, pages = {271-283}, doi = {10.1016/j.brainresbull.2003.10.004}, pmid = {14709342}, issn = {0361-9230}, mesh = {Animals ; Humans ; Neural Pathways/*physiology ; Neurons, Afferent/*physiology ; *Reward ; Taste/*physiology ; }, abstract = {It is proposed that in the gustatory system there exist separate sensory and hedonic (reward-aversion) representations in each of the primary structures in which processing of gustatory stimuli occurs. Anatomical and physiological data are used to determine putative separate sensory and hedonic representations in the nucleus of the solitary tract, parabrachial complex, gustatory thalamus, and cortical gustatory areas. In the nucleus of the solitary tract, the sensory representation is located in the rostralmost part of the nucleus, and the hedonic representation most probably in the intermediate parts. In the parabrachial complex, the sensory representation is located in the central medial and ventral lateral subnuclei, and in the waist area, and the hedonic representation in the inner division of the external lateral subnucleus and in the external medial subnucleus. In the rodent gustatory thalamic relay, the sensory representation occurs in the dorsal lateral parts of the nucleus, and the hedonic representation in the ventromedial parts. In rodent gustatory insular cortex, the sensory representation is found in anterior parts of the gustatory area, and the hedonic representation caudal to the sensory representation. The function of the separate sensory and hedonic representations is discussed in relation to the conditioned taste aversion paradigm.}, } @article {pmid14709326, year = {2004}, author = {De Vry, J and Schreiber, R and Eckel, G and Jentzsch, KR}, title = {Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A.}, journal = {European journal of pharmacology}, volume = {483}, number = {1}, pages = {55-63}, doi = {10.1016/j.ejphar.2003.10.012}, pmid = {14709326}, issn = {0014-2999}, mesh = {Animals ; Behavior, Animal/*drug effects ; *Cannabinoid Receptor Agonists ; *Cannabinoid Receptor Antagonists ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects ; Female ; Food ; Male ; Motor Activity/drug effects ; Piperidines/*pharmacology ; Pyrazoles/*pharmacology ; Rats ; Rats, Wistar ; Rimonabant ; Self Stimulation ; Taste/drug effects ; }, abstract = {This study investigated the possible behavioral mechanisms underlying the anorectic effect of the cannabinoid CB(1) receptor antagonist/inverse agonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A). Male or female rats were food-restricted and trained to emit stable responding in daily 10-min, fixed ratio 10 food-reinforced operant sessions. Under these conditions, as well as under free-feeding conditions, SR141716A inhibited food-maintained responding (ED(50) values ranging from 0.92 to 2.52 mg/kg, i.p.). In the same operant procedure, SR141716A suppressed intracranial self-stimulation with a potency which was slightly lower than the anorectic potency (ED(50): 4.50 mg/kg). As assessed during a 10-min test period SR141716A (1-10 mg/kg) did not affect activity counts; suggesting that the observed inhibition of operant behavior is not a direct consequence of impairment of locomotor activity. SR141716A, however, attenuated saccharin-preference in a conditioned taste aversion paradigm (ED(50): 6.45 mg/kg). Although the data support the suggestion that the anorectic effect of SR141716A results from an attenuating effect on the rewarding effect of food, the contribution of drug-induced aversion/malaise cannot be excluded.}, } @article {pmid14690875, year = {2003}, author = {Quintanilla, ME and Tampier, L}, title = {Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.}, journal = {Addiction biology}, volume = {8}, number = {4}, pages = {387-397}, doi = {10.1080/13556210310001646446}, pmid = {14690875}, issn = {1355-6215}, mesh = {Acetaldehyde/blood/pharmacology ; Alcohol Drinking/*genetics ; Alcoholism/enzymology/*genetics ; Aldehyde Dehydrogenase/*genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Amino Acid Substitution/genetics ; Animals ; Arginine/genetics ; Association Learning ; *Avoidance Learning ; Brain/*enzymology ; *Conditioning, Classical ; Dose-Response Relationship, Drug ; Drinking/*genetics ; Gene Expression Regulation, Enzymologic/physiology ; Glutamine/genetics ; Injections, Intraperitoneal ; Male ; Point Mutation ; Rats ; Rats, Inbred Strains ; Species Specificity ; Taste/*genetics ; }, abstract = {Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose - response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity.}, } @article {pmid14684468, year = {2003}, author = {Elkins, RL and Orr, TE and Rausch, JL and Fei, YJ and Carl, GF and Hobbs, SH and Buccafusco, JJ and Edwards, GL}, title = {Cocaine-induced expression differences in PSD-95/SAP-90-associated protein 4 and in Ca2+/calmodulin-dependent protein kinase subunits in amygdalae of taste aversion-prone and taste aversion-resistant rats.}, journal = {Annals of the New York Academy of Sciences}, volume = {1003}, number = {}, pages = {386-390}, doi = {10.1196/annals.1300.068}, pmid = {14684468}, issn = {0077-8923}, mesh = {Amygdala/drug effects/enzymology/*metabolism ; Animals ; Avoidance Learning/*drug effects ; Calcium-Calmodulin-Dependent Protein Kinases/*biosynthesis/genetics ; Cocaine/*pharmacology ; Disks Large Homolog 4 Protein ; Drug Resistance ; Gene Expression/drug effects ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Nerve Tissue Proteins/*biosynthesis/genetics/*physiology ; Rats ; Rats, Sprague-Dawley ; SAP90-PSD95 Associated Proteins ; Taste/*drug effects/*genetics ; }, } @article {pmid14684467, year = {2003}, author = {Elkins, RL and Orr, TE and Rausch, JL and Fei, YJ and Carl, GF and Hobbs, SH and Buccafusco, JJ and Edwards, GL}, title = {Cocaine-induced expression differences in glutamate receptor subunits and transporters in amygdalae of taste aversion-prone and taste aversion-resistant rats.}, journal = {Annals of the New York Academy of Sciences}, volume = {1003}, number = {}, pages = {381-385}, doi = {10.1196/annals.1300.067}, pmid = {14684467}, issn = {0077-8923}, mesh = {Amino Acid Transport System X-AG/*biosynthesis/genetics ; Amygdala/*metabolism ; Animals ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Drug Resistance ; Gene Expression/drug effects ; Rats ; Receptors, Glutamate/*biosynthesis/genetics ; Species Specificity ; Taste/*drug effects/*genetics ; }, } @article {pmid14684243, year = {2004}, author = {Cross-Mellor, SK and Kavaliers, M and Ossenkopp, KP}, title = {Comparing immune activation (lipopolysaccharide) and toxin (lithium chloride)-induced gustatory conditioning: lipopolysaccharide produces conditioned taste avoidance but not aversion.}, journal = {Behavioural brain research}, volume = {148}, number = {1-2}, pages = {11-19}, doi = {10.1016/s0166-4328(03)00181-5}, pmid = {14684243}, issn = {0166-4328}, mesh = {Adjuvants, Immunologic/*toxicity ; Administration, Oral ; Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Body Weight/drug effects ; Conditioning, Operant/*drug effects ; Drinking/drug effects ; Eating/drug effects ; Food Preferences/drug effects ; Habituation, Psychophysiologic ; Lipopolysaccharides/*pharmacology ; Lithium Chloride/*toxicity ; Male ; Rats ; Rats, Long-Evans ; Sucrose ; Time Factors ; Water Deprivation ; }, abstract = {Feeding and drinking typically involve both appetitive and consummatory behaviors. Appetitive behaviors include those behaviors produced by an animal prior to the actual consumption, such as approach movements, whereas consummatory behaviors (such as licking and chewing) are involved in the actual consumption of food. The present research compared the gustatory conditioning effects of bacterial lipopolysaccharide (LPS) and lithium chloride (LiCl) in two different paradigms, conditioned taste avoidance and conditioned taste aversion which differentially affect the appetitive and consummatory components of feeding. Male rats were implanted with intraoral cannulae and habituated to a water deprivation schedule and afterwards received two conditioning days (Days 1 and 4). Each conditioning day consisted of 1 h access to a novel sucrose solution (0.3 M) immediately followed by a systemic injection of LPS (200 microg/kg), LiCl (0.15 M, 3 meq) or NaCl vehicle. Conditioned taste aversion was assessed using the taste reactivity test on Day 7, where orofacial and somatic responses were videotaped and analyzed during 3 brief (1 min) exposures to the sucrose solution. Conditioned taste avoidance was assessed on Days 8 and 9 using a two-bottle preference test (sucrose versus water). Animals conditioned with LiCl displayed typical aversive-like responses in the taste reactivity paradigm evidenced by significant reductions in positive ingestive responses (P<0.05) and an increase in active aversive responses (P<0.05) relative to controls. Furthermore, LiCl treatment resulted in conditioned avoidance of sucrose in the two-bottle preference test characterized by a decreased sucrose preference (P<0.05). Conditioning with LPS produced a reduced sucrose preference (P<0.05) relative to controls, comparable to the avoidance seen in LiCl-treated rats. In contrast, conditioning with LPS resulted in similar positive ingestive responses to intraorally infused sucrose as seen in controls. The present results demonstrate that LPS treatment produces conditioned avoidance but not aversion and suggest that LPS can selectively condition the appetitive aspects of feeding whereas the consummatory behaviors remain unaffected.}, } @article {pmid14674859, year = {2003}, author = {Koh, MT and Wilkins, EE and Bernstein, IL}, title = {Novel tastes elevate c-fos expression in the central amygdala and insular cortex: implication for taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {117}, number = {6}, pages = {1416-1422}, doi = {10.1037/0735-7044.117.6.1416}, pmid = {14674859}, issn = {0735-7044}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/*metabolism ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*metabolism ; Exploratory Behavior/physiology ; Male ; Mental Processes/physiology ; Practice, Psychological ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Long-Evans ; Taste/*physiology ; Tissue Distribution ; }, abstract = {Taste novelty strongly modulates the speed and strength of taste aversion conditioning. To identify molecular signals responsive to novel tastes, immunostaining for c-fos protein (Fos-like immunoreactivity [FLI]) was used to mark neurons that responded differentially to taste novelty. Novel saccharin induced larger increases in FLI than familiar saccharin. This pattern was seen in central amygdala and insular cortex, but not in basolateral amygdala, parabrachial nucleus, or nucleus of the solitary tract. Other parameters known to influence aversion learning were tested for effects on FLI. Manipulations known to reduce the strength of learning blunted the FLI response, supporting the idea that FLI marks neural pathways critical to taste processing during acquisition, and that c-fos expression is a key transcriptional event underlying this plasticity.}, } @article {pmid14672105, year = {2003}, author = {Dibattista, D and Hollis-Walker, L and Hague, L}, title = {The CS-preexposure effect in conditioned taste-aversion learning in golden hamsters.}, journal = {The Journal of general psychology}, volume = {130}, number = {4}, pages = {446-461}, doi = {10.1080/00221300309601169}, pmid = {14672105}, issn = {0022-1309}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Cricetinae ; Food Preferences/psychology ; Lithium Chloride/toxicity ; Male ; *Mental Recall ; Mesocricetus ; Species Specificity ; *Taste ; }, abstract = {In Experiment 1, golden hamsters were injected with either 0.9% saline or the nausea-inducing agent, lithium chloride (LiCL), immediately after consuming a flavored diet that was either novel or familiar. The LiCl-induced aversion was strong in hamsters for which the flavored diet was novel, but no significant aversion was observed in hamsters that were familiar with the flavored diet. In Experiment 2, the strength of the LiCl-induced aversion was related inversely to the amount of conditioned-stimulus (CS) preexposure and directly to the duration of the preexposure-conditioning interval. Thus, although some previous researchers have suggested that hamsters may not demonstrate the CS-preexposure effect in a conditioned taste-aversion paradigm, they clearly did so under the conditions of the present experiments, and moreover, the characteristics of the CS-preexposure effect in hamsters were generally similar to those observed in rats.}, } @article {pmid14657261, year = {2003}, author = {Wang, J and Ren, K and Pérez, J and Silva, AJ and Peña de Ortiz, S}, title = {The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {10}, number = {6}, pages = {503-509}, pmid = {14657261}, issn = {1072-0502}, support = {U54 NS039405/NS/NINDS NIH HHS/United States ; U54 NS39405/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Arabinofuranosylcytosine Triphosphate/*pharmacology ; Avoidance Learning/*drug effects ; Brain/*drug effects/physiology ; Conditioning, Classical/*drug effects ; Cytarabine/*pharmacology ; Injections, Intraventricular ; Male ; Memory/*drug effects/physiology ; Memory, Short-Term/drug effects ; Nucleic Acid Synthesis Inhibitors/*pharmacology ; Rats ; Rats, Long-Evans ; Recombination, Genetic ; *Taste ; Transcription, Genetic ; }, abstract = {We examined the hypothesis that processes related to DNA recombination and repair are involved in learning and memory. Rats received intracerebroventricular (i.c.v.) infusions of the antimetabolite 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) or its precursor cytosine arabinoside (ara-C) 30 min prior to conditioned taste aversion (CTA) training. Both ara-CTP and ara-C caused significant impairments in long-term memory (LTM) of CTA. Control experiments indicate that the effect of ara-CTP on CTA memory is related to interference with learning. Furthermore, as it was previously demonstrated for the protein synthesis inhibitor anisomycin, ara-CTP had no effect on CTA memory when it was injected 1 h after training. Importantly, although both ara-CTP and anisomycin significantly blocked LTM in the task, short-term memory (STM) measured 1 h after training was not affected by either of the drugs. Finally, ara-CTP had no effect on in vitro transcription, but it did effectively block nonhomologous DNA end joining (NHEJ) activity of brain protein extracts. We suggest that DNA ligase-mediated DNA recombination and repair processes are necessary for the expression of LTM in the brain.}, } @article {pmid14643837, year = {2003}, author = {Turgeon, SM and Hoge, SG}, title = {Prior exposure to phencyclidine decreases voluntary sucrose consumption and operant performance for food reward.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {76}, number = {3-4}, pages = {393-400}, doi = {10.1016/j.pbb.2003.08.019}, pmid = {14643837}, issn = {0091-3057}, mesh = {Animals ; Apomorphine/pharmacology ; Conditioning, Operant/*drug effects ; Dopamine Agonists/pharmacology ; *Food ; Hallucinogens/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Phencyclidine/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; *Reward ; Sucrose ; Water Deprivation/physiology ; }, abstract = {Prior exposure to the psychotomimetic drug phencyclidine (PCP) produces a number of schizophrenia-like behaviors in animals. The goal of the present study was to determine whether prior exposure to PCP produces decreased reward function, thereby modeling one aspect of negative schizophrenic symptomatology. To this aim, the consequences of prior exposure to PCP were assessed on two types of appetitive consumptive behavior. In the first set of experiments, the effects of PCP (15 mg/kg, 20 h before testing) on sucrose consumption were tested for three consecutive days under conditions of deprivation and nondeprivation. In the deprivation condition, animals were water deprived for 4 h prior to injection of PCP or saline (SAL). Twenty hours following the injection (24 h after the onset of water deprivation), animals were allowed access to either 5% sucrose or water for 30 min. In the nondeprivation condition, 5% sucrose consumption was measured for 30 min, 20 h after PCP or SAL injection and water consumption was measured during the 23.5 h preceding sucrose consumption. PCP decreased both sucrose and water consumption under deprivation conditions on the second and third day of testing but selectively decreased sucrose consumption under nondeprivation conditions on all three testing days. LiCl (50 mg/kg, 20 h before testing) did not significantly reduce sucrose consumption in the nondeprivation paradigm, indicating that the effect of PCP was not due to conditioned taste aversion. In the second experiment, PCP (15 mg/kg, 20 h before testing) decreased operant performance when animals were switched from a continuous reinforcement schedule of food delivery to a fixed ratio (FR4) schedule. Apomorphine (APO, 30 microg/kg, 30 min before testing), a positive control, induced a similar performance deficit. However, the PCP-induced deficit was not apparent until the third day of FR4 testing while the APO deficit was apparent on the first day. The effects of PCP on sucrose consumption demonstrate PCP-induced decreases in reward function. However, the delayed appearance of the PCP-induced decrease in operant performance suggests that these results may be better explained by a PCP-induced attentional deficit, also characteristic of schizophrenic psychopathology.}, } @article {pmid14650350, year = {2003}, author = {Bellisle, F}, title = {Why should we study human food intake behaviour?.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {13}, number = {4}, pages = {189-193}, doi = {10.1016/s0939-4753(03)80010-8}, pmid = {14650350}, issn = {0939-4753}, mesh = {*Appetite ; *Behavior ; *Eating ; Humans ; }, abstract = {Several aspects of human eating behaviour may be relevant for identifying effective measures to treat or prevent diseases like obesity, diabetes, or the metabolic syndrome, whose natural history is strongly influenced by nutritional factors. Physiological factors determine hunger, satiety and satiation, and a biological learning mechanism supports the acquisition of food likes and dislikes. The paradigm of "conditioned taste aversion" refers to the acquisition of a strong rejection response after the intake of a food has been followed by digestive disorder. Food likes are acquired following the experience of the beneficial post-ingestive effects of intake. Physiological mechanisms reinforce the liking for energy-rich foods and both environmental and biological conditions facilitate "passive overconsumption". Sensory factors are important determinants of appetite and food choices from birth to old age. The human newborn exhibits an innate repertoire of acceptance or rejection for taste substances. The progressive change of sensory functions associated with ageing affects appetite and the pleasure of eating. Many individual psychological characteristics affect food intake behaviour in a significant way. These include chronic dietary restraint, disinhibition, etc. These psychological traits can be objectively assessed using validated psychometric instruments. Various stimuli present in the environment also affect ingestive behaviours in humans. Portion size is one potent environmental determinant of how much a person eats, regardless of hunger. The general increase in portion sizes observed in North America over the last decades might have played an important role in the rapid rise of obesity prevalence. Socio-economic factors also affect food selection and food intake in human societies. Factors such as education level and income determine food choices and behaviours in a way that does affect the risk of obesity. Behavioural science has provided many insights about crucial cause-and-effect relationships that affect nutrition and health. Therefore, clinicians and nutritionists cannot neglect this important area if they wish to effectively modify the habitual diet of individual patients or the general population.}, } @article {pmid14638385, year = {2003}, author = {Reilly, S and Bornovalova, M and Dengler, C and Trifunovic, R}, title = {Effects of excitotoxic lesions of the gustatory thalamus on latent inhibition and blocking of conditioned taste aversion in rats.}, journal = {Brain research bulletin}, volume = {62}, number = {2}, pages = {117-128}, doi = {10.1016/j.brainresbull.2003.08.009}, pmid = {14638385}, issn = {0361-9230}, support = {DC04341/DC/NIDCD NIH HHS/United States ; }, mesh = {Acetic Acid ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/physiology ; Lithium Chloride/pharmacology ; Male ; Neural Inhibition/*physiology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; Sucrose ; Taste/*physiology ; Thalamus/*pathology/physiology ; }, abstract = {The influence of bilateral excitotoxic lesions of the gustatory thalamus on latent inhibition and blocking of conditioned taste aversion (CTA) was examined in two experiments. In Experiment 1, rats with thalamic lesions showed normal latent inhibition by acquiring a CTA that was significantly weaker when the conditioned stimulus (CS) was familiar than when it was novel. In Experiment 2, the preconditioned element (sodium chloride) of a compound CS blocked the acquisition of a CTA to the novel element (sucrose) in normal rats. Irrespective of whether sodium chloride was preconditioned or not, rats with thalamic lesions showed little or no aversion to sucrose following compound conditioning. Overall, the results provide no support for the experimental hypothesis that thalamic lesions disrupt decremental changes in the attentional processing of gustatory stimuli.}, } @article {pmid14627662, year = {2004}, author = {Lundy, RF and Norgren, R}, title = {Activity in the hypothalamus, amygdala, and cortex generates bilateral and convergent modulation of pontine gustatory neurons.}, journal = {Journal of neurophysiology}, volume = {91}, number = {3}, pages = {1143-1157}, doi = {10.1152/jn.00840.2003}, pmid = {14627662}, issn = {0022-3077}, support = {DC-00240/DC/NIDCD NIH HHS/United States ; DC-05156/DC/NIDCD NIH HHS/United States ; DC-05435/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Cerebral Cortex/*physiology ; Citric Acid/pharmacology ; Electric Stimulation ; Electrodes ; Electrophysiology ; Hypothalamus/*physiology ; Male ; Nerve Fibers/physiology ; Neural Pathways/physiology ; Neurons, Afferent/*physiology ; Pons/*physiology ; Prosencephalon/physiology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/pharmacology ; Sucrose/pharmacology ; Taste/*physiology ; }, abstract = {Evidence suggests that centrifugal modulation of brain stem gustatory cells might play a role in the elaboration of complex taste-guided behaviors like conditioned taste aversion and sodium appetite. We previously showed that activity in one forebrain area, the central nucleus of the amygdala (CeA), increased the chemical selectivity of taste cells in the parabrachial nucleus (PBN). The present study investigates how activity in 2 other similarly interconnected forebrain sites, the lateral hypothalamus (LH) and gustatory cortex (GC), might influence PBN gustatory processing in rats. The potential convergence of descending inputs from these sites, as well as the CeA, was also evaluated. After anesthesia (35 mg/kg Nembutal ip), 70 PBN gustatory neurons were tested before, during, and after electrical stimulation of these forebrain sites, while responding to 0.3 M sucrose, 0.1 M NaCl, 0.01 M citric acid, and 0.003 M QHCl. Although each forebrain site modulated taste-evoked responses, more PBN neurons were influenced by stimulation of the GC (67%) and CeA (73%) than of the LH (48%). Activation of cortex (71%) and amygdala (85%) most often produced inhibition, whereas inhibition and excitation occurred equally often during hypothalamic stimulation. Of the neurons tested for convergence (n = 60), 88% were influenced by > or =1 of the 3 sites. Twenty were modulated by stimulation at all 3 sites and another 17 by 2 of the 3 sites. The net effect of centrifugal modulation was to sharpen the across-stimulus response profiles of PBN cells, particular with regard to the NaCl- and citric acid-best cells.}, } @article {pmid14627536, year = {2003}, author = {Eylam, S and Tracy, T and Garcea, M and Spector, AC}, title = {Amiloride is an ineffective conditioned stimulus in taste aversion learning in C57BL/6J and DBA/2J mice.}, journal = {Chemical senses}, volume = {28}, number = {8}, pages = {681-689}, doi = {10.1093/chemse/bjg060}, pmid = {14627536}, issn = {0379-864X}, support = {R01 DC004574/DC/NIDCD NIH HHS/United States ; R01-DC04574/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/*pharmacology ; Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Feeding Behavior/*drug effects ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Sodium Chloride/pharmacology ; Taste/*drug effects/physiology ; Water ; }, abstract = {The epithelial sodium channel (ENaC) blocker amiloride has been shown to increase the behaviorally measured NaCl detection threshold in mice. In this study, a conditioned taste aversion (CTA) paradigm was used to examine whether 100 microM amiloride has a perceptible taste that could contribute to this observed decrease in behavioral responsiveness. Eighty-four C57BL/6J (B6) and 64 DBA/2J (D2) mice were divided into eight groups (n=8-12 per group), in which half received an injection of 0.15 M LiCl (2 mEq/kg) and the other half an equivalent saline injection, in three conditioning trials. The four conditioned stimuli were 100 microM amiloride hydrochloride, water, 0.1 and 0.3 M NaCl. Neither strain demonstrated acquisition of a CTA to amiloride in a brief-access (BA) taste test (5 s trials in the gustometer). Although 0.3 M NaCl is inherently aversive, its pairing with LiCl led to significantly further decreases in licking during the BA test on salt trials in both strains. The D2 strain clearly avoided 0.1 M NaCl, whereas avoidance of this stimulus was more equivocal in B6 mice. The inefficacy of amiloride to serve as a conditioned stimulus in taste aversion learning involving three LiCl pairings suggests that the effects of this ENaC blocker on taste-related behavioral responses to NaCl are likely due to its pharmacological interference with sodium taste transduction.}, } @article {pmid14622235, year = {2003}, author = {Fenu, S and Di Chiara, G}, title = {Facilitation of conditioned taste aversion learning by systemic amphetamine: role of nucleus accumbens shell dopamine D1 receptors.}, journal = {The European journal of neuroscience}, volume = {18}, number = {7}, pages = {2025-2030}, doi = {10.1046/j.1460-9568.2003.02899.x}, pmid = {14622235}, issn = {0953-816X}, mesh = {Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Benzazepines/pharmacology ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Classical/*drug effects ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Drug ; Drug Administration Routes/veterinary ; Drug Interactions ; Eating/drug effects ; Lithium Chloride/administration & dosage ; Male ; Nucleus Accumbens/*drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D1/antagonists & inhibitors/*metabolism ; Sucrose ; Taste/drug effects ; }, abstract = {The role of dopamine (DA) in associative learning was studied in a conditioned taste aversion (CTA) paradigm with sucrose as the conditioned stimulus (CS) and intraperitoneal lithium chloride as the unconditioned stimulus (US). Drinking on trial of a 15% sucrose solution followed 1 h later by lithium chloride (20 or 40 mg/kg i.p.) resulted in mild CTA, as shown by reduction of drinking of the sucrose solution 24 h later. Amphetamine sulphate (0.125, 0.25, 0.50 and 1.0 mg/kg s.c.), administered on trial 5 min after sucrose drinking, facilitated CTA with maximal effects at 0.25 mg/kg s.c. Amphetamine given in the absence of lithium or 45 min after sucrose did not affect sucrose intake. The DA D1 receptor antagonist SCH 39166, administered before amphetamine either systemically (0.0125 mg/kg s.c.) or in the nucleus accumbens shell (NAc; 0.025 micro g/ micro L on each side) prevented the facilitation of CTA induced by amphetamine. It is concluded that amphetamine facilitates CTA learning by strengthening the consolidation of gustatory short-term memory via D1 receptors of the NAc shell.}, } @article {pmid14622162, year = {2003}, author = {Miranda, MI and LaLumiere, RT and Buen, TV and Bermudez-Rattoni, F and McGaugh, JL}, title = {Blockade of noradrenergic receptors in the basolateral amygdala impairs taste memory.}, journal = {The European journal of neuroscience}, volume = {18}, number = {9}, pages = {2605-2610}, doi = {10.1046/j.1460-9568.2003.03008.x}, pmid = {14622162}, issn = {0953-816X}, support = {NIMH12526/MH/NIMH NIH HHS/United States ; }, mesh = {Adrenergic beta-Antagonists/pharmacology ; Amygdala/*drug effects/physiology/physiopathology ; Animals ; Avoidance Learning/*drug effects/physiology ; Conditioning, Classical/*drug effects/physiology ; Lithium Chloride ; Male ; Memory/*drug effects/physiology ; Nausea/chemically induced ; Norepinephrine/*physiology ; Propranolol/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/drug effects/*physiology ; Saccharin ; Sweetening Agents ; *Taste ; }, abstract = {In conditioned taste aversion (CTA), a subject learns to associate a novel taste (conditioned stimulus, CS) with visceral malaise (unconditioned stimulus, US). Considerable evidence indicates that the noradrenergic system in the amygdala plays an important role in memory consolidation for emotionally arousing experiences. The specific aim of the present set of experiments was to determine the involvement of noradrenergic activity in the basolateral amygdala (BLA) during the US presentation and consolidation of CTA as well as during the consolidation of a nonaversive/incidental gustatory memory. Selective bilateral microinfusions of the beta-adrenergic antagonist propranolol administered into the BLA immediately before intraperitoneal (i.p.) lithium chloride (LiCl) injections disrupted CTA memory. Additionally, propranolol infused into the BLA immediately after a pre-exposure to the saccharin (CS) significantly attenuated latent inhibition. The present findings indicating that alterations in noradrenergic function in the BLA affect taste memory formation, provide additional evidence that the BLA plays a critical role in modulating the consolidation of memory and that the influence is mediated by interactions with other brain regions that support memory for different kinds of experiences.}, } @article {pmid14609567, year = {2003}, author = {O'Connor, KA and Hansen, MK and Rachal Pugh, C and Deak, MM and Biedenkapp, JC and Milligan, ED and Johnson, JD and Wang, H and Maier, SF and Tracey, KJ and Watkins, LR}, title = {Further characterization of high mobility group box 1 (HMGB1) as a proinflammatory cytokine: central nervous system effects.}, journal = {Cytokine}, volume = {24}, number = {6}, pages = {254-265}, doi = {10.1016/j.cyto.2003.08.001}, pmid = {14609567}, issn = {1043-4666}, support = {MH00314/MH/NIMH NIH HHS/United States ; MH01558/MH/NIMH NIH HHS/United States ; MH45045/MH/NIMH NIH HHS/United States ; MH55283/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Central Nervous System/*drug effects/metabolism ; Central Nervous System Agents/*pharmacology ; Fever/metabolism ; HMGB1 Protein/*pharmacology ; Hypothalamus/drug effects ; Inflammation/*metabolism ; Interleukin-1/metabolism ; Rats ; }, abstract = {High mobility group box 1 (HMGB1), an abundant, highly conserved cellular protein, is widely known as a nuclear DNA-binding protein. HMGB1 has been recently implicated as a proinflammatory cytokine because of its role as a late mediator of endotoxin lethality and ability to stimulate release of proinflammatory cytokines from monocytes. Production of central cytokines is a critical step in the pathway by which endotoxin and peripheral proinflammatory cytokines, including interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF), produce sickness behaviors and fever. Intracerebroventricular (ICV) administration of HMGB1 has been shown to increase TNF expression in mouse brain and induce aphagia and taste aversion. Here we show that ICV injections of HMGB1 induce fever and hypothalamic IL-1 in rats. Furthermore, we show that intrathecal administration of HMGB1 produces mechanical allodynia (lowering of the response threshold to calibrated stimuli). Finally, while endotoxin (lipopolysaccharide, LPS) administration elevates IL-1 and TNF mRNA in various brain regions, HMGB1 mRNA is unchanged. It remains possible that HMGB1 protein is released in brain in response to LPS. Nonetheless, these data suggest that HMGB1 may play a role as an endogenous pyrogen and support the concept that HMGB1 has proinflammatory characteristics within the central nervous system.}, } @article {pmid14600800, year = {2004}, author = {Orsini, C and Buchini, F and Piazza, PV and Puglisi-Allegra, S and Cabib, S}, title = {Susceptibility to amphetamine-induced place preference is predicted by locomotor response to novelty and amphetamine in the mouse.}, journal = {Psychopharmacology}, volume = {172}, number = {3}, pages = {264-270}, pmid = {14600800}, issn = {0033-3158}, mesh = {Amphetamine/*pharmacology ; Animals ; Behavior, Animal/*drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Psychological/*drug effects ; Locomotion/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Species Specificity ; Taste/drug effects ; }, abstract = {RATIONALE: It has been demonstrated that major differences between mice of the C57BL/6J and DBA/2J inbred strains for amphetamine-induced place conditioning (preference and avoidance, respectively) are evident in standard housing conditions but abolished by temporary restricted feeding. This gene-experience model may be usefully exploited to dissect behavioral phenotypes related to place conditioning induced by addictive drugs.

OBJECTIVES: This study evaluated a number of behavioral phenotypes related to amphetamine-induced place preference for strain differences (C57BL/6J vs DBA/2J) susceptible to be abolished by temporary food restriction.

METHODS: Mice of the two inbred strains were tested for: (1) conditioned taste aversion and place preference induced by amphetamine within the same dose-range; (2) preference for a novel compartment 24 h after a single exposure to only one of two compartments; (3) amphetamine-induced behavioral sensitization and conditioned hyperactivity; and (4) locomotor activity during exploration of a novel environment.

RESULTS: The two strains showed consistent taste aversion at doses of amphetamine that promoted opposite strain-dependent place conditioning. Both strains spent more time exploring the novel rather than the known compartment of the place conditioning apparatus. Instead, only mice of the C57 strain showed amphetamine-induced behavioral sensitization and conditioned hyperactivity. However, temporary food restriction did not affect strain differences for these phenotypes. Finally, C57 mice were more active than DBA in a novel environment and restricted feeding abolished this strain-dependent difference.

CONCLUSIONS: These results relate individual differences for amphetamine-induced place conditioning with locomotor response to amphetamine and novelty.}, } @article {pmid14592964, year = {2004}, author = {Shigemura, N and Ohta, R and Kusakabe, Y and Miura, H and Hino, A and Koyano, K and Nakashima, K and Ninomiya, Y}, title = {Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures.}, journal = {Endocrinology}, volume = {145}, number = {2}, pages = {839-847}, doi = {10.1210/en.2003-0602}, pmid = {14592964}, issn = {0013-7227}, mesh = {Animals ; Behavior, Animal/*drug effects ; Diabetes Mellitus ; Female ; Gene Expression ; In Situ Hybridization ; Leptin/deficiency/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; RNA, Messenger/analysis ; Receptors, Cell Surface/deficiency/genetics/physiology ; Receptors, Leptin ; Reverse Transcriptase Polymerase Chain Reaction ; *Saccharin ; *Sucrose ; Taste/*drug effects ; Taste Buds/*chemistry ; }, abstract = {Leptin is a hormone that regulates body weight homeostasis mainly via the hypothalamic functional leptin receptor Ob-Rb. Recently, we proposed that the taste organ is a new peripheral target for leptin. Leptin selectively inhibits mouse taste cell responses to sweet substances and thereby may act as a sweet taste modulator. The present study further investigated leptin action on the taste system by examining expression of Ob-Rb in taste cells and behavioral responses to sweet substances in leptin-deficient ob/ob, and Ob-Rb-deficient db/db mice and their normal litter mates. RT-PCR analysis showed that Ob-Rb was expressed in taste cells in all strains tested. The db/db mice, however, had a RT-PCR product containing an abnormal db insertion that leads to an impaired shorter intracellular domain. In situ hybridization analysis showed that the hybridization signals for normal Ob-Rb mRNA were detected in taste cells in lean and ob/ob mice but not in db/db mice. Two different behavioral tests, one using sweet-bitter mixtures as taste stimuli and the other a conditioned taste aversion paradigm, demonstrated that responses to sucrose and saccharin were significantly decreased after ip injection of leptin in ob/ob and normal littermates, but not in db/db mice. These results suggest that leptin suppresses behavioral responses to sweet substances through its action on Ob-Rb in taste cells. Such taste modulation by leptin may be involved in regulation for food intake.}, } @article {pmid14584105, year = {2003}, author = {Jahng, JW and Choi, SH and Kim, DG and Houpt, TA}, title = {Central Nomega-nitro-L-arginine methyl ester does not influence lithium-induced c-Fos and conditioned taste aversion.}, journal = {Yonsei medical journal}, volume = {44}, number = {5}, pages = {869-874}, doi = {10.3349/ymj.2003.44.5.869}, pmid = {14584105}, issn = {0513-5796}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Brain/*physiology ; Conditioning, Psychological/*drug effects/physiology ; Immunohistochemistry ; Injections, Intraventricular ; Lithium/*pharmacology ; Male ; NG-Nitroarginine Methyl Ester/*pharmacology ; Nitric Oxide/physiology ; Proto-Oncogene Proteins c-fos/*analysis ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; }, abstract = {LiCl at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the brain regions implicated in CTA formation. It has been reported that nitric oxide (NO) may play a role in CTA learning and LiCl increases both the synthesis and activity of NO synthase (NOS) in the brain. In this study, we examined the effect of central Nomega-nitro-L- arginine methyl ester (L-NAME) on the brain c-Fos expression and CTA learning induced by lithium in rats. In the results, intracerebroventricular L-NAME given prior to lithium did not change either the lithium-induced CTA or c-Fos in the relevant brain regions. This suggests that the brain NO system may not be involved in the neuronal activation during lithium-induced CTA formation.}, } @article {pmid14578125, year = {2003}, author = {Heyer, BR and Taylor-Burds, CC and Tran, LH and Delay, ER}, title = {Monosodium glutamate and sweet taste: generalization of conditioned taste aversion between glutamate and sweet stimuli in rats.}, journal = {Chemical senses}, volume = {28}, number = {7}, pages = {631-641}, doi = {10.1093/chemse/bjg056}, pmid = {14578125}, issn = {0379-864X}, mesh = {Amiloride/pharmacology ; Animals ; Avoidance Learning/*physiology ; Flavoring Agents/*pharmacology ; Glucose/pharmacology ; Glutamic Acid/*pharmacology ; Guanidines/pharmacology ; Male ; Maltose/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Sodium Glutamate/*pharmacology ; Sucrose/pharmacology ; Sweetening Agents/*pharmacology ; Taste/*drug effects/physiology ; }, abstract = {Even though monosodium glutamate (MSG) is a prototypical umami substance, previous studies reported that a conditioned taste aversion (CTA) to MSG, mixed with amiloride to block the taste of sodium, generalizes to sucrose. These findings suggest that the taste of glutamate mimics the taste of sucrose and raise the question of whether glutamate has a broadly tuned sweet taste component. To test this hypothesis, CTA experiments were conducted to test for generalization between MSG and several sweet stimuli: sucrose, glucose, maltose, saccharin and SC-45647. Strong bidirectional generalization was seen between MSG mixed with amiloride and sucrose, glucose, saccharin and SC-45647. Weak generalization was seen between MSG and maltose, and sucrose and maltose. None of the CTAs generalized to NMDA. These findings support the hypothesis that the taste of MSG has broadly tuned, sweet-like characteristics, possibly due to the convergence of afferent signals for MSG, natural sugars and artificial sweeteners.}, } @article {pmid14568312, year = {2003}, author = {Salvy, SJ and Pierce, WD and Heth, DC and Russell, JC}, title = {Wheel running produces conditioned food aversion.}, journal = {Physiology & behavior}, volume = {80}, number = {1}, pages = {89-94}, doi = {10.1016/s0031-9384(03)00217-8}, pmid = {14568312}, issn = {0031-9384}, mesh = {Analysis of Variance ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Choice Behavior ; Conditioning, Operant/*physiology ; Eating/*physiology ; Male ; Motor Activity/physiology ; Physical Conditioning, Animal/*physiology ; Rats ; Taste ; }, abstract = {Previous investigations of conditioned taste aversion (CTA) induced by wheel running have used flavored liquids such as conditioned stimuli (CSs). Assuming that classical conditioning mediates activity anorexia, it is expected that CTA induced by physical activity should extend to food stimuli. The main purpose of the present experiment was to investigate this possibility. Rats were given a 60-min access to a running wheel [unconditioned stimulus (US)] either before or after being exposed to a novel distinctive flavored food (CS). An additional group had access to running wheels 4 h after receiving the CS food. Results from the present experiment indicate that regimented and contingent periods of wheel running decrease consumption of a food available before wheel running in nondeprived rats.}, } @article {pmid14550313, year = {2003}, author = {Sparkes, S and Grant, VL and Lett, BT}, title = {Role of conditioned taste aversion in the development of activity anorexia.}, journal = {Appetite}, volume = {41}, number = {2}, pages = {161-165}, doi = {10.1016/s0195-6663(03)00057-6}, pmid = {14550313}, issn = {0195-6663}, mesh = {Animals ; Anorexia/*psychology ; *Conditioning, Psychological ; Food ; Male ; *Physical Exertion ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {Activity anorexia (AA) occurs when rats are restricted to one meal period (60-90 min) each day and have unlimited access to a running wheel the rest of the time. This AA procedure also contains the conditions necessary for conditioned taste aversion (CTA). The food eaten during the meal period is the conditioned stimulus paired with the unconditioned stimulus produced by wheel running. Thus, CTA to food may account in part for the decreased eating in AA. To test this possibility, male rats were subjected to the AA procedure. They had daily 90-min exposures to their familiar chow and spent the rest of the day in running wheels (experimental condition) or home cages (control condition). A second, concurrent experiment had the same procedure except that novel, rather than familiar, food was used. In both experiments, AA occurred; the rats allowed to wheel run ate less than those in the control condition. Several days after AA training, a two-food preference test assessed whether CTA occurred. Wheel running induced CTA when food was novel but not when it was familiar. Since AA is typically studied with procedures using familiar food, the present findings indicate that CTA plays little or no role in AA.}, } @article {pmid14521874, year = {2003}, author = {Gutiérrez, R and Rodriguez-Ortiz, CJ and De La Cruz, V and Núñez-Jaramillo, L and Bermudez-Rattoni, F}, title = {Cholinergic dependence of taste memory formation: evidence of two distinct processes.}, journal = {Neurobiology of learning and memory}, volume = {80}, number = {3}, pages = {323-331}, doi = {10.1016/s1074-7427(03)00066-2}, pmid = {14521874}, issn = {1074-7427}, mesh = {Animals ; Behavior, Animal/drug effects ; Choice Behavior/drug effects ; Cholinergic Fibers/*drug effects ; Conditioning, Psychological/drug effects ; Male ; Memory/*drug effects ; Muscarinic Antagonists/administration & dosage/pharmacology ; Rats ; Rats, Wistar ; Scopolamine/administration & dosage/pharmacology ; Taste/*drug effects ; }, abstract = {Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animal's survival. A lack of recognition of a taste's consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.}, } @article {pmid14521864, year = {2003}, author = {Miranda, MI and Ferreira, G and Ramírez-Lugo, L and Bermúdez-Rattoni, F}, title = {Role of cholinergic system on the construction of memories: taste memory encoding.}, journal = {Neurobiology of learning and memory}, volume = {80}, number = {3}, pages = {211-222}, doi = {10.1016/s1074-7427(03)00061-3}, pmid = {14521864}, issn = {1074-7427}, mesh = {Amygdala/drug effects/metabolism ; Cerebral Cortex/metabolism ; Humans ; Memory, Short-Term/drug effects/*physiology ; Muscarinic Antagonists/administration & dosage/pharmacology ; Neuronal Plasticity/drug effects ; Phobic Disorders/metabolism ; Receptors, Cholinergic/metabolism/*physiology ; Receptors, Muscarinic/metabolism/physiology ; Receptors, N-Methyl-D-Aspartate/drug effects/metabolism ; Scopolamine/administration & dosage/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {There is a large body of evidence suggesting that cholinergic activity is involved in memory processes. It seems that cholinergic activity is essential to learn several tasks and recent works suggest that acetylcholine plays an important role during the early stages of memory formation. In this review, we will discuss the results related to taste memory formation, focusing particularly on the conditioned taste aversion paradigm. We will first give evidence that nucleus basalis magnocellularis is involved in taste memory formation, due to its cholinergic projections. We then show that the cholinergic activity of the insular (gustatory) cortex is related to the taste novelty, and that the cholinergic signals initiated by novelty are crucial for taste memory formation. Then we present recent data indicating that cortical activation of muscarinic receptors is necessary for taste trace encoding, and also for its consolidation under certain circumstances. Finally, interactions between the cholinergic and other neuromodulatory systems inducing intracellular mechanisms related to plastic changes will be proposed as important processes underlying gustatory memory trace storage.}, } @article {pmid13129831, year = {2003}, author = {McQuade, JA and Xu, M and Woods, SC and Seeley, RJ and Benoit, SC}, title = {Ethanol consumption in mice with a targeted disruption of the dopamine-3 receptor gene.}, journal = {Addiction biology}, volume = {8}, number = {3}, pages = {295-303}, doi = {10.1080/13556210310001602202}, pmid = {13129831}, issn = {1355-6215}, mesh = {Alcohol Drinking/*adverse effects/*genetics ; Animals ; Behavior, Animal ; Choice Behavior ; Ethanol/administration & dosage/blood ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Quinine/administration & dosage ; Receptors, Dopamine D2/*drug effects/*genetics ; Receptors, Dopamine D3 ; Saccharin/administration & dosage ; Time Factors ; }, abstract = {Considerable evidence suggests that the mesolimbic dopaminergic system is an important substrate for the rewarding effects of ethanol consumption. Previous data have demonstrated that pharmacological agents that alter dopamine signaling also influence the self-administration of ethanol. The present experiments were designed to assess the role of the dopamine-3 receptor (D3-R) on voluntary ethanol consumption in C57BL/6 mice. Mice with targeted disruption of the D3-R gene (D3-R - /-) were compared to wild-type controls in an ethanol intake paradigm. In Experiment 1, mice had 24-hour access to ethanol each day in a two-bottle choice paradigm for a period of 7 days per concentration. The concentrations tested were 3, 6, 10 and 15%. In Experiment 2, mice had I hour of access to ethanol each day in a two-bottle paradigm for a period of 7 days per concentration. The same concentrations in Experiment I were compared in Experiment 2. In Experiment 3 we sought to test the development of a conditioned taste aversion (CTA) after receiving an intraperitoneal (ip.) injection of 2.0 g/kg ethanol. In Experiment 4, blood ethanol levels where assessed following a 2.0 g/kg ip.injection of ethanol. Experiment 5 assessed taste preference for saccharine and quinine in wild-type and D3-R -/- mice. Contrary to our predictions, both D3-R -/- and wild-types on a CS57BL/6 background had similar intakes of ethanol, at all concentrations tested, in the 24-hour and 1-hour intake paradigms. Wild-type and D3-R -/- mice respond to injected ethanol similarly by developing a conditioned taste aversion. Metabolic analysis revealed mutant mice are slower in metabolizing a bolus injection of ethanol. Lastly, wild-type and D3-R -/- mice showed similar consumption to increasing concentration of both sweet and bitter tastes. These data suggest that deletion of the D3-R gene does not increase ethanol consumption above that found on the C57BL/6 genetic background. Furthermore, the D3-R -/- mice adequately learn a CTA to ethanol and do not ham differing taste reactivity to saccharin or quinine. However, D3-R -/- mice do appear to have a slower rate of ethanol metabolism.}, } @article {pmid12960505, year = {2003}, author = {Hori, H and Fujii, W and Hatanaka, Y and Suwa, Y}, title = {Effects of fusel oil on animal hangover models.}, journal = {Alcoholism, clinical and experimental research}, volume = {27}, number = {8 Suppl}, pages = {37S-41S}, doi = {10.1097/01.ALC.0000078828.49740.48}, pmid = {12960505}, issn = {0145-6008}, mesh = {Alcohol Drinking/psychology ; Alcoholic Beverages/*toxicity ; Alcohols/*toxicity ; Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; *Disease Models, Animal ; Dose-Response Relationship, Drug ; Male ; Pentanols/toxicity ; Saccharin ; Shrews ; Substance Withdrawal Syndrome/*etiology ; Taste/drug effects ; Vomiting/etiology ; }, abstract = {BACKGROUND: Fusel oil has been reported to have undesirable side effects such as hangover. However, the relationship between fusel oil and hangover has been investigated insufficiently. In this study, we investigated the effects of fusel oil and their ingredients contained in alcoholic beverages by using animal hangover models.

METHODS: Ethanol and fusel oil were simultaneously administered to Suncus murinus, and emetic responses were observed for 60 min. Ethanol and fusel oil were simultaneously administered to mice immediately after intake of saccharin solution; on the next day, the mouse's saccharin solution intake was measured.

RESULTS: The volatile fraction (fusel oil) of whisky had no remarkable effect on ethanol-induced emetic responses in suncus. Whisky had the most suppressive effect on ethanol-induced conditioned taste aversion in mice among the various alcoholic beverages tested. The volatile fraction (fusel oil) of whisky suppressed the ethanol-induced conditioned taste aversion. In contrast, the nonvolatile fraction of whisky had no effect. The administration of isoamyl alcohol (5 mg/kg) and isoamyl acetate (10 and 40 microg/kg), ingredients of fusel oil, significantly suppressed the ethanol-induced conditioned taste aversion.

CONCLUSIONS: The fusel oil in whisky had no effect on the ethanol-induced emetic response, but it suppressed taste-aversion behavior in animal models of hangover symptoms. These results suggest that the fusel oil in whisky alleviates hangover, contrary to the common belief.}, } @article {pmid12954420, year = {2003}, author = {Benoit, SC and Air, EL and Wilmer, K and Messerschmidt, P and Hodge, KM and Jones, MB and Eckstein, DM and McOsker, CC and Seeley, RJ and Woods, SC and Sheldon, RJ}, title = {Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents.}, journal = {Physiology & behavior}, volume = {79}, number = {4-5}, pages = {761-766}, doi = {10.1016/s0031-9384(03)00189-6}, pmid = {12954420}, issn = {0031-9384}, mesh = {Animals ; Appetite/drug effects/physiology ; Appetite Depressants/*pharmacology ; Appetite Regulation/drug effects/physiology ; Association Learning/drug effects/physiology ; Avoidance Learning/*physiology ; Behavior Control/methods ; Conditioning, Psychological/*physiology ; Dose-Response Relationship, Drug ; Eating/drug effects ; Feeding Behavior/*drug effects ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.}, } @article {pmid12946607, year = {2003}, author = {Bethus, I and Stinus, L and Goodall, G}, title = {Chronic interferon-alpha potentiates latent inhibition in rats.}, journal = {Behavioural brain research}, volume = {144}, number = {1-2}, pages = {167-174}, doi = {10.1016/s0166-4328(03)00071-8}, pmid = {12946607}, issn = {0166-4328}, mesh = {Animals ; Behavior, Animal ; Conditioning, Psychological/drug effects ; Drug Administration Schedule/veterinary ; Immunologic Factors/*pharmacology ; Interferon-alpha/*pharmacology ; Male ; Motor Activity/*drug effects ; Neural Inhibition/*drug effects ; Rats ; Rats, Sprague-Dawley ; Sucrose ; Time Factors ; }, abstract = {Several recent reports based on microdialysis have shown that repeated injections of IFN-alpha induce reduced dopamine (DA) activity in the rodent brain, and specifically within the striatum. This mesolimbic DA system is thought to play a central role in controlling latent inhibition (LI), which refers to the phenomenon in which conditioning proceeds more slowly to an irrelevant pre-exposed (PE) stimulus. The purpose of the present experiment was to evaluate whether chronic treatment with IFN-alpha may induce similar effects on LI as other DA-depleting manipulations. Rats were injected daily, for 24 days either with 10(4)IU IFN-alpha or vehicle, while monitoring their locomotor activity in photocell cages. No changes in locomotor activity, either during the acute period after the first injection, or progressively over the chronic period were observed. LI was then evaluated in these rats with a Conditioned Taste Aversion (CTA) paradigm. Half of each group of rats were pre-exposed to the 5% sucrose Conditioned Stimulus (CS) for 30 min on three successive days before the conditioning session in which the 30 min access to the 5% sucrose solution was followed by a 0.15M injection of 127 mg/kg LiCl. Two test sessions, in which rats were given a choice between the 5% sucrose solution and water, were given 48 and 72 h after the conditioning session. The results showed moderate LI in the control group, which was considerably potentiated in the IFN-alpha group despite the absence of any change in locomotor activity. These results are interpreted as providing indirect support for the theory that suggests that LI depends on DA activity in the nucleus accumbens (NAcc).}, } @article {pmid12934010, year = {2003}, author = {Eisenberg, M and Kobilo, T and Berman, DE and Dudai, Y}, title = {Stability of retrieved memory: inverse correlation with trace dominance.}, journal = {Science (New York, N.Y.)}, volume = {301}, number = {5636}, pages = {1102-1104}, doi = {10.1126/science.1086881}, pmid = {12934010}, issn = {1095-9203}, mesh = {Aminobenzoates/pharmacology ; Analysis of Variance ; Animals ; Anisomycin/administration & dosage/pharmacology ; Avoidance Learning ; Cerebral Cortex/drug effects ; Conditioning, Psychological ; Cues ; Electroshock ; *Extinction, Psychological/drug effects ; Fear ; Male ; *Memory ; *Mental Recall ; Oryzias ; Rats ; Rats, Wistar ; Taste ; meta-Aminobenzoates ; }, abstract = {In memory consolidation, the memory trace stabilizes and becomes resistant to certain amnesic agents. The textbook account is that for any memorized item, consolidation starts and ends just once. However, evidence has accumulated that upon activation in retrieval, the trace may reconsolidate. Whereas some authors reported transient renewed susceptibility of retrieved memories to consolidation blockers, others could not detect it. Here, we report that in both conditioned taste aversion in the rat and fear conditioning in the medaka fish, the stability of retrieved memory is inversely correlated with the control of behavior by that memory. This result may explain some conflicting findings on reconsolidation of activated memories.}, } @article {pmid12932429, year = {2003}, author = {Traverso, LM and Ruiz, G and De la Casa, LG}, title = {Latent inhibition disruption by MK-801 in a conditioned taste-aversion paradigm.}, journal = {Neurobiology of learning and memory}, volume = {80}, number = {2}, pages = {140-146}, doi = {10.1016/s1074-7427(03)00059-5}, pmid = {12932429}, issn = {1074-7427}, mesh = {Animals ; Conditioning, Psychological/*physiology ; Dizocilpine Maleate/*pharmacology ; *Inhibition, Psychological ; Male ; Memory/drug effects ; Neuroprotective Agents/*pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/metabolism ; Taste/*drug effects ; }, abstract = {N-Methyl-D-aspartate (NMDA) receptors appear to be involved in CS processing and memory consolidation. The present paper analyzed the effect of the non-competitive NMDA receptor antagonist Dizocilpine maleate (MK-801) on Latent Inhibition (LI)-retarded learning of a CS-US association after to-be-CS preexposures at time of testing, using Wistar rats as experimental subjects. If NMDA receptors are involved in CS processing, MK-801 administration should affect LI. In fact, previous experiments revealed that a 2.0mg/kg MK-801 dose, administered 20 h before preexposure and conditioning, abolished LI in a conditioned taste-aversion paradigm. In the present paper, MK-801 (0.2 mg/kg) was either injected after preexposure, after conditioning, or after both preexposure and conditioning stages. LI was abolished when MK-801 was injected after preexposure, but not when it was injected after conditioning. These results support the role of NMDA receptors in CS processing and memory consolidation.}, } @article {pmid12932425, year = {2003}, author = {Ohta, R and Shigemura, N and Sasamoto, K and Koyano, K and Ninomiya, Y}, title = {Conditioned taste aversion learning in leptin-receptor-deficient db/db mice.}, journal = {Neurobiology of learning and memory}, volume = {80}, number = {2}, pages = {105-112}, doi = {10.1016/s1074-7427(03)00046-7}, pmid = {12932425}, issn = {1074-7427}, mesh = {Animals ; Behavior, Animal/physiology ; Choice Behavior ; Conditioning, Psychological/*physiology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Cell Surface/*deficiency ; Receptors, Leptin ; Taste/*physiology ; }, abstract = {The db/db mouse has defective leptin receptors. The defects lead to impairments of leptin regulation of food intake and body weight, and result in the expression of diabetic symptoms such as hyperinsulinemia, hyperglicemia, and extreme obesity. Recent studies have proposed that leptin may also affect memory and learning processes. To examine this possibility, we compared the ability of leptin-receptor-deficient db/db mice and their normal lean litter mates to form and extinguish a conditioned taste aversion (CTA) for saccharin. We used a short-term (10 s) lick test and a long-term (48 h) two bottle preference test for measurement of consumption of test solutions. On the first day after conditioning to avoid saccharin, the db/db mice showed preference scores for saccharin as low, and aversion thresholds for sucrose lower than that of the lean mice. During the extinction test trials beginning from the second up to the 30th day after conditioning, numbers of licks and preference scores for aversive saccharin and sucrose appeared to be larger, and recovered faster to the control levels in db/db mice. These results indicate that db/db mice with leptin-receptor-deficiency may show equal capacity to form CTAs for saccharin, greater generalization from saccharin to sucrose, and a faster rate of extinction. This suggests that disruption of leptin signalling does not inhibit acquisition of CTA learning, but impairs its extinction. This differential contribution of the leptin system on CTA processes may be due to differential distribution of leptin receptors in the CTA-related brain areas.}, } @article {pmid12902993, year = {2003}, author = {Depoortere, R and Boulay, D and Perrault, G and Bergis, O and Decobert, M and Françon, D and Jung, M and Simiand, J and Soubrié, P and Scatton, B}, title = {SSR181507, a dopamine D2 receptor antagonist and 5-HT1A receptor agonist. II: Behavioral profile predictive of an atypical antipsychotic activity.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {28}, number = {11}, pages = {1889-1902}, doi = {10.1038/sj.npp.1300261}, pmid = {12902993}, issn = {0893-133X}, mesh = {Animals ; Antipsychotic Agents/*pharmacology ; Behavior, Animal/*drug effects/*physiology ; Dioxanes/*pharmacology ; *Dopamine D2 Receptor Antagonists ; Female ; Guinea Pigs ; Male ; Mice ; Mice, Inbred C57BL ; Predictive Value of Tests ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptor, Serotonin, 5-HT1A/physiology ; Receptors, Dopamine D2/physiology ; *Serotonin 5-HT1 Receptor Agonists ; Serotonin Antagonists/*pharmacology ; Serotonin Receptor Agonists/*pharmacology ; Tropanes/*pharmacology ; }, abstract = {SSR181507 ((3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane that displays antagonist activity at dopamine D(2) receptors and agonist activity at 5-HT(1A) receptors. SSR181507 antagonized apomorphine-induced climbing in mice and stereotypies in rats (ED(50) of 2 and 3.4 mg/kg i.p., respectively) and blocked D-amphetamine-induced hyperlocomotion in rats at lower doses (0.3-1 mg/kg i.p.). At 1-10 mg/kg, it was found to disrupt active avoidance in mice. SSR181507 did not induce catalepsy in rats (MED>60 mg/kg i.p.) and antagonized (3-10 mg/kg i.p.) haloperidol-induced catalepsy. SSR181507 was also active in two models sensitive to antidepressant/anxiolytic drugs: in a guinea-pig pup/mother separation test, it decreased (1-3 mg/kg i.p.) the time spent vocalizing during the separation episode, and in a lithium-induced taste aversion procedure in rats, it partially reversed (3 mg/kg i.p.) the decrease of intake of a saccharin solution. Furthermore, SSR181507 increased (3 mg/kg i.p.) the latency time to paradoxical sleep in rats, an effect commonly observed with antidepressants. Coadministration of the selective 5-HT(1A) blocker SL88.0338 produced catalepsy and antagonized the effects of SSR181507 in the depression/anxiety tests, confirming the view that activation of 5-HT(1A) receptors confers an atypical profile on SSR181507, and is responsible for its antidepressant/anxiolytic properties. Finally, SSR181507 (1-3 mg/kg) did not affect memory performance in a Morris water maze task in rats. The pharmacological profile of SSR181507 suggests that it should control the symptoms of schizophrenia, in the absence of extrapyramidal signs and cognitive deficits, with the additional benefit of antidepressant/anxiolytic activities.}, } @article {pmid12898122, year = {2003}, author = {Russig, H and Kovacevic, A and Murphy, CA and Feldon, J}, title = {Haloperidol and clozapine antagonise amphetamine-induced disruption of latent inhibition of conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {170}, number = {3}, pages = {263-270}, pmid = {12898122}, issn = {0033-3158}, mesh = {*Adrenergic Agents ; Amphetamine/*antagonists & inhibitors ; Animals ; Antipsychotic Agents/*pharmacology ; Clozapine/*pharmacology ; Haloperidol/*pharmacology ; Male ; Rats ; Rats, Wistar ; Reaction Time/drug effects ; Taste/*drug effects ; }, abstract = {RATIONALE: Latent inhibition (LI) describes a process by which repeated pre-exposure of a stimulus without any consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that LI is impaired in rats and in humans by injections of the indirect dopamine agonist amphetamine (AMPH), and that this disruption can be prevented by co-administration of either the typical neuroleptic haloperidol (HAL) or the atypical neuroleptic clozapine (CLZ).

OBJECTIVES: Most of what is known of the pharmacology of LI is derived from studies using either the conditioned emotional response or the conditioned active avoidance paradigm. The goal of the present study was to determine whether these results would generalize to the conditioned taste aversion assay.

METHODS: We tested whether AMPH (0.5 mg/kg) pretreatment would disrupt LI of a conditioned aversion to sucrose, and if so, which stage of the procedure is critical for mediating the disruption; in addition, we tested whether HAL (0.2 mg/kg) or CLZ (5.0 mg/kg) could restore such an expected LI disruption.

RESULTS: We determined that AMPH disrupted LI when it was injected before pre-exposure and prior to conditioning, but not if the rats were injected before either stage alone. When HAL or CLZ was given 40 min before AMPH (before both pre-exposure and conditioning), it blocked LI disruption.

CONCLUSION: These results are in line with the pharmacology of LI as derived from other conditioning paradigms. We conclude that the pharmacological regulation of LI in the CTA paradigm is similar to what has been observed previously in the conditioned emotional response and the conditioned active avoidance paradigms.}, } @article {pmid12882376, year = {2003}, author = {Batsell, WR and Trost, CA and Cochran, SR and Blankenship, AG and Batson, JD}, title = {Effects of postconditioning inflation on odor + taste compound conditioning.}, journal = {Learning & behavior}, volume = {31}, number = {2}, pages = {173-184}, pmid = {12882376}, issn = {1543-4494}, mesh = {Analysis of Variance ; Animals ; *Association Learning ; *Avoidance Learning ; Conditioning, Classical ; Generalization, Stimulus ; Male ; *Odorants ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {The within-compound association approach has been proposed as an account of synergistic conditioning in flavor aversion learning. One prediction from the within-compound association approach is that following taste + odor compound conditioning, postconditioning inflation of one element of the compound should increase responding to the second element. In four experiments with rats, the AX+/A+ design was used to determine whether postconditioning inflation of A would increase responding to X. In Experiments 1 and 3, responding to X was significantly stronger after AX+/A+ conditioning, as compared with AX+ conditioning. In Experiments 2 and 4, the specificity of the inflation effect was demonstrated, because AX+/A+ conditioning produced a stronger aversion to X than did AX+/B+ conditioning. Furthermore, it appears that the taste + odor association is symmetrical because inflation of the taste aversion increased responding to the odor (Experiments 1 and 2) and inflation of the odor aversion increased responding to the taste (Experiments 3 and 4).}, } @article {pmid12882375, year = {2003}, author = {Parker, LA}, title = {Taste avoidance and taste aversion: evidence for two different processes.}, journal = {Learning & behavior}, volume = {31}, number = {2}, pages = {165-172}, pmid = {12882375}, issn = {1543-4494}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Mental Processes ; Rats ; Rejection, Psychology ; Taste/*physiology ; }, abstract = {The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat consumes in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed with the taste reactivity test, which includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned rejection reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Treatments that produce nausea are not necessary for the establishment of taste avoidance, but they are necessary for the establishment of taste aversion. Furthermore, treatments that alleviate nausea modulate neither the establishment nor the expression of taste avoidance, but they interfere with both the establishment and the expression of taste aversion. Considerable evidence exists indicating that these two measures are independent of one another. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but taste aversion (as reflected by rejection reactions) may be motivated by conditioned nausea.}, } @article {pmid12881160, year = {2003}, author = {de Brugada, I and González, F and Cándido, A}, title = {The role of injection cues in the associative control of the US pre-exposure effect in flavour aversion learning.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {56}, number = {3}, pages = {241-252}, doi = {10.1080/02724990244000115}, pmid = {12881160}, issn = {0272-4995}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical ; *Cues ; Drinking Behavior/drug effects ; Extinction, Psychological ; Female ; Housing, Animal ; *Inhibition, Psychological ; Injections, Intraperitoneal ; Lithium Chloride/administration & dosage/pharmacology ; Rats ; Rats, Wistar ; Recognition, Psychology ; Saccharin ; Taste/*physiology ; }, abstract = {Two experiments, using rats as subjects, examined the role of contextual cues in producing the unconditioned stimulus (US) pre-exposure effect in conditioned taste aversion. Experiment 1 showed a significant US pre-exposure effect, when the pre-exposure was conducted in a familiar context, and that a change of context between the pre-exposure and conditioning phases did not attenuate this effect. Experiment 2 demonstrated that extinction of injection-related cues after the pre-exposure stage attenuated the US pre-exposure effect, when the pre-exposure was conducted in either a familiar or a novel context. Taken together, these results support the associative explanation of the US pre-exposure effect in terms of blocking, incorporating a role for injection-related cues in the context blocking analysis of the US pre-exposure effect.}, } @article {pmid12867515, year = {2003}, author = {Balschun, D and Wolfer, DP and Gass, P and Mantamadiotis, T and Welzl, H and Schütz, G and Frey, JU and Lipp, HP}, title = {Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory?.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {23}, number = {15}, pages = {6304-6314}, pmid = {12867515}, issn = {1529-2401}, mesh = {Animals ; Behavior, Animal/physiology ; Conditioning, Psychological ; Cyclic AMP Response Element-Binding Protein/*genetics/*metabolism ; Electric Stimulation ; Fear/physiology ; Gene Dosage ; Gene Targeting/methods ; Hippocampus/metabolism/*physiology ; In Vitro Techniques ; Long-Term Potentiation/genetics/physiology ; Long-Term Synaptic Depression/genetics/physiology ; Maze Learning/physiology ; Memory/*physiology ; Mice ; Mice, Knockout ; Mice, Mutant Strains ; Mice, Transgenic ; Neuronal Plasticity/genetics/*physiology ; Protein Isoforms/deficiency/genetics/metabolism ; Taste/genetics/physiology ; }, abstract = {Previous studies addressing the role of the transcription factor cAMP response element-binding protein (CREB) in mammalian long-term synaptic plasticity and memory by gene targeting were compromised by incomplete deletion of the CREB isoforms. Therefore, we generated conditional knock-out strains with a marked reduction or complete deletion of all CREB isoforms in the hippocampus. In these strains, no deficits could be detected in lasting forms of hippocampal long-term potentiation (LTP) and long-term depression (LTD). When tested for hippocampus-dependent learning, mutants showed normal context-dependent fear conditioning. Water maze learning was impaired during the early stages, but many mutants showed satisfactory scores in probe trials thought to measure hippocampus-dependent spatial memory. However, conditioned taste aversion learning, a putatively hippocampus-independent memory test, was markedly impaired. Our data indicate that in the adult mouse brain, loss of CREB neither prevents learning nor substantially affects performance in some hippocampus-dependent tasks. Furthermore, it spares LTP and LTD in paradigms that are sensitive enough to detect deficits in other mutants. This implies either a species-specific or regionally restricted role of CREB in the brain and/or a compensatory upregulation of the cAMP response element modulator (CREM) and other as yet unidentified transcription factors.}, } @article {pmid12853429, year = {2003}, author = {Desmedt, A and Hazvi, S and Dudai, Y}, title = {Differential pattern of cAMP response element-binding protein activation in the rat brain after conditioned aversion as a function of the associative process engaged: taste versus context association.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {23}, number = {14}, pages = {6102-6110}, pmid = {12853429}, issn = {1529-2401}, mesh = {Animals ; *Association ; Association Learning/*physiology ; Behavior, Animal/physiology ; Brain/*metabolism ; Cerebral Cortex/metabolism ; Conditioning, Classical/physiology ; Cyclic AMP Response Element-Binding Protein/*metabolism ; Male ; Parietal Lobe/metabolism ; Phosphorylation ; Rats ; Rats, Wistar ; Septum of Brain/metabolism ; Taste/*physiology ; }, abstract = {Ample data indicate that cAMP-response element-binding protein (CREB) is essential for the formation of long-term memory in various species and learning systems. This implies that activated CREB could delineate neuronal circuits that subserve items in memory, while leaving open the possibility that the specifics of CREB activation itself contribute to the specificity of the internal representation encoded by the relevant circuit. We describe here the differential activation of CREB in the rat brain as a function of two related yet distinct forms of aversive conditioning: conditioned taste aversion (CTA) and conditioned context aversion (CCA). We found that CTA induces strong CREB activation in the insular cortex (IC) and the lateral septum (LS), but not in the parietal cortex (PC) and the medial septum (MS). In contrast, CCA results in strong activation in the PC and MS, but not in the IC and LS. These findings are congruent with a model that links differential pattern of activity within the LS and the MS with the acquisition of elemental versus contextual conditioning and, more generally, with the notion that CREB activation delineates learning-dependent circuits as a function of the type of cognitive process engaged.}, } @article {pmid12849735, year = {2003}, author = {Ge, H and Chiesa, R and Peña de Ortiz, S}, title = {Hzf-3 expression in the amygdala after establishment of conditioned taste aversion.}, journal = {Neuroscience}, volume = {120}, number = {1}, pages = {1-4}, doi = {10.1016/s0306-4522(03)00265-3}, pmid = {12849735}, issn = {0306-4522}, support = {1 U54 NS39405-01/NS/NINDS NIH HHS/United States ; 5P20 RR15565-02/RR/NCRR NIH HHS/United States ; }, mesh = {Amygdala/*metabolism ; Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; DNA-Binding Proteins/*biosynthesis/genetics ; Gene Expression Regulation/physiology ; Male ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; Rats ; Rats, Long-Evans ; Taste/*physiology ; Transcription Factors/*biosynthesis/genetics ; }, abstract = {We studied the regulation of the expression of the inducible orphan nuclear receptor known as HZF-3 (or Nurr1) in acquisition of conditioned taste aversion in rats. Our results show that HZF-3 expression in the lateral/basolateral (LA/BLA) amygdala complex was significantly up-regulated when both the conditioned and the unconditioned stimuli were paired, but not when either of the stimuli was presented alone. Induction in the LA/BLA had a faster onset than induction in the central nucleus of the amygdala. The results implicate HZF-3 in the acquisition of associative aversive experiences.}, } @article {pmid12842296, year = {2003}, author = {Koh, MT and Clarke, SN and Spray, KJ and Thiele, TE and Bernstein, IL}, title = {Conditioned taste aversion memory and c-Fos induction are disrupted in RIIbeta-protein kinase A mutant mice.}, journal = {Behavioural brain research}, volume = {143}, number = {1}, pages = {57-63}, doi = {10.1016/s0166-4328(03)00024-x}, pmid = {12842296}, issn = {0166-4328}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/*metabolism ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Brain Stem/metabolism ; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit ; Cyclic AMP-Dependent Protein Kinases/*genetics ; Immunohistochemistry ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Knockout ; Nerve Net/metabolism ; Pons/metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Signal Transduction/genetics/physiology ; Taste ; }, abstract = {The cAMP-dependent protein kinase (PKA) signaling pathway has been implicated in many forms of learning. The present studies examined conditioned taste aversion (CTA) learning, an amygdala-dependent task, in mice with a targeted disruption of a gene for a specific regulatory subunit of PKA (RIIbeta), which is selectively expressed in amygdala. Null mutant (RIIbeta(-/-)) mice and littermate controls (RIIbeta(+/+)) were tested for protein synthesis-independent short-term memory (STM) and protein synthesis-dependent long-term memory (LTM) for CTAs. The ability of the unconditioned stimulus (US) drug, LiCl, to induce c-Fos in regions thought to be important in this learning was also determined. RIIbeta(-/-) mice showed significant impairment in CTA memory when tested 24h after training (LTM). In contrast, STM was normal. With regard to the c-Fos response to LiCl, the US drug, significant elevations were evident in brainstem (nucleus of the solitary tract) and pontine (parabrachial nucleus) regions, in mutants as well as wild-type controls. However, in amygdala, elevations were seen in controls but were absent in the mutants. These findings suggest that disruption of PKA signaling interferes with LTM consolidation of CTA and that a possible mediator of this effect is interference with c-Fos expression in amygdala which may be necessary for CTA memory.}, } @article {pmid12838040, year = {2003}, author = {Quertemont, E}, title = {Discriminative stimulus effects of ethanol with a conditioned taste aversion procedure: lack of acetaldehyde substitution.}, journal = {Behavioural pharmacology}, volume = {14}, number = {4}, pages = {343-350}, doi = {10.1097/01.fbp.0000082130.08343.47}, pmid = {12838040}, issn = {0955-8810}, mesh = {Acetaldehyde/*pharmacology ; Animals ; Conditioning, Psychological/*drug effects/physiology ; Diazepam/pharmacology ; Discrimination Learning/*drug effects/physiology ; Dizocilpine Maleate/pharmacology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; Nicotine/pharmacology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Taste/*drug effects/physiology ; }, abstract = {Acetaldehyde has been suggested to mediate a number of the pharmacological and behavioural effects of ethanol. Recently, several studies investigated the role of acetaldehyde in the subjective effects of ethanol, but obtained conflicting results. With the discriminative taste aversion (DTA) procedure, high acetaldehyde doses were shown to substitute for the discriminative stimulus effects of ethanol. In contrast, the operant drug discrimination protocol failed to show any substitution effect of acetaldehyde. Several methodological differences between the two procedures could explain these discrepancies, and particularly the absence of an individual discrimination criterion in the DTA procedure. In the present study, the DTA procedure was adapted to introduce such a criterion. In addition, the effects of acetaldehyde were compared with those of other drugs, for which the substitution effects for ethanol are well known. Rats were trained to discriminate 1.0 g/kg ethanol from saline in a DTA protocol. When the rats met the criterion of ethanol discrimination, various doses of several drugs were tested for their ethanol stimulus substitution effects: ethanol, acetaldehyde, dizocilpine, diazepam and nicotine. The results showed a clear dose-dependent discrimination of ethanol stimulus effects. In addition, dizocilpine fully substituted for ethanol, while diazepam only partially substituted. In contrast, both acetaldehyde and nicotine failed to substitute for ethanol. These results show that acetaldehyde is not significantly involved in the subjective and discriminative stimulus effects of ethanol. Acetaldehyde up to toxic doses did not substitute for the ethanol discriminative stimulus in the DTA protocol, when non-specific effects were carefully controlled.}, } @article {pmid12829316, year = {2003}, author = {De la Casa, LG and Diaz, E and Lubow, RE}, title = {Effects of post-treatment retention interval and context on neophobia and conditioned taste aversion.}, journal = {Behavioural processes}, volume = {63}, number = {3}, pages = {159-170}, doi = {10.1016/s0376-6357(03)00080-9}, pmid = {12829316}, issn = {1872-8308}, abstract = {We have repeatedly observed that a delay between acquisition and test, and the nature of the context in which the delay is spent, modulates latent inhibition (LI) of conditioned taste aversion (CTA; e.g. [Anim. Learn. Behav. 28 (2000) 389; Anim. Learn. Behav. 30 (2002) 112]). The present paper analysed the effects of delayed testing and treatment context after flavor exposure on the recovery of neophobia (Experiment 1) and on extinction after simple conditioning (Experiment 2). Two experiments were conducted with the same factorial design (2x2: 1 day versus 21 days of delay between first and second stage, and home versus experimental cages as place of experimental treatment). There were independent effects of both variables on habituation of neophobia and conditioning strength as measured on extinction trials. The long delay produced a reduction of neophobia (Experiment 1) and an increase in conditioning (Experiment 2). In addition, more of the flavored solution was consumed when the experimental treatment was conducted in the home cage than in the experimental cage (Experiment 1), and there was stronger conditioning when the delay period took place in the experimental cages than in the home cages (Experiment 2). The implications of these results for LI, as well as their relevance for experiments that use the CTA paradigm, are discussed.}, } @article {pmid12818700, year = {2003}, author = {Gorzalka, B and Hanson, L and Harrington, J and Killam, S and Campbell-Meiklejohn, D}, title = {Conditioned taste aversion: modulation by 5-HT receptor activity and corticosterone.}, journal = {European journal of pharmacology}, volume = {471}, number = {2}, pages = {129-134}, doi = {10.1016/s0014-2999(03)01790-4}, pmid = {12818700}, issn = {0014-2999}, mesh = {Administration, Oral ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; Corticosterone/administration & dosage/*pharmacokinetics ; Extinction, Psychological ; Hypothalamo-Hypophyseal System/physiology ; Injections ; Lithium Chloride/administration & dosage/adverse effects/antagonists & inhibitors ; Male ; Piperazines ; Pituitary-Adrenal System/physiology ; Rats ; Rats, Long-Evans ; Receptor, Serotonin, 5-HT1A/*physiology ; Receptor, Serotonin, 5-HT2A/*physiology ; Serotonin 5-HT1 Receptor Antagonists ; Serotonin 5-HT2 Receptor Agonists ; Solutions/administration & dosage ; Sucrose/administration & dosage ; Taste/*drug effects/physiology ; Time Factors ; Triazoles/administration & dosage/pharmacokinetics ; }, abstract = {Two experiments were designed to elucidate the involvement of the hypothalamic-pituitary-adrenal axis and the 5-hydroxytryptamine (5-HT) system in the acquisition of lithium chloride-conditioned taste aversion. In Experiment 1, rats were administered either vehicle or 50 mg/kg nefazodone daily for 4 weeks. Rats were treated with 22 mg/kg of lithium chloride in order to produce conditioned taste aversion to a sucrose solution. Three days later, nefazodone completely blocked the lithium chloride-conditioned taste aversion. In Experiment 2, the effects of chronic corticosterone administration on lithium chloride-conditioned taste aversion were investigated. Twenty male rats received either corticosterone at a dose of (50 mg/kg) or vehicle injections over a period of 14 consecutive days. Lithium chloride-conditioned taste aversion was potentiated in rats treated with corticosterone. Additionally, corticosterone-treated animals required more trials to reach extinction. These results suggest the involvement of both the 5-HT system and the hypothalamic-pituitary-adrenal axis in lithium chloride-conditioned taste aversion.}, } @article {pmid12782222, year = {2003}, author = {Lievens, S and Flo, G and Decuypere, E and Van Boven, M and Cokelaere, M}, title = {Simmondsin: effects on meal patterns and choice behavior in rats.}, journal = {Physiology & behavior}, volume = {78}, number = {4-5}, pages = {669-677}, doi = {10.1016/s0031-9384(03)00039-8}, pmid = {12782222}, issn = {0031-9384}, mesh = {Acetonitriles/*pharmacology ; Animals ; Appetite Depressants/*pharmacology ; Conditioning, Operant/drug effects ; Cyclohexanes/*pharmacology ; Feeding Behavior/*drug effects ; Food Preferences/*drug effects ; Glucosides/*pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; }, abstract = {Simmondsin, a glycoside from jojoba meal, decreases food intake after oral administration. The present experiments are designed to clarify the mechanism of simmondsin's anorectic activity. The meal pattern analysis shows that simmondsin supplementation at different doses results in a dose-dependent food intake reduction, which is more pronounced after prior simmondsin experience. The effect of simmondsin on meal patterns (decreased meal size, meal duration and eating rate, increased latency to eat) is most severe at the highest concentration. Rats familiar with simmondsin more seriously postpone their first meal than with first contact, resulting in a decrease of the meal frequency and the day/night feeding ratio. Rats given the choice between a control diet and a simmondsin-supplemented (0.5%) diet, after half an hour, have a significant preference for the control diet. Simmondsin seems to have a specific flavor when mixed in the food since rats recognise the feeder containing simmondsin. The ability of simmondsin to induce conditioned taste aversion (CTA) was also investigated. Rats receiving simmondsin at concentrations of 0.15%, 0.25% or 0.5% during their conditioning develop significant taste aversions to the saccharin solutions. The performed experiments indicate that the simmondsin activity shows some analogy with the satiating molecule cholecystokinin (CCK) at first contact, but shows more analogy with the illness-inducing agent lithium chloride (LiCl) after prior experience with simmondsin. Rats familiar with simmondsin avoid simmondsin-supplemented food by directly monitoring its presence, and by learning to relate it to the postingestive consequences of consumption.}, } @article {pmid12782218, year = {2003}, author = {Lockwood, DR and Kwon, B and Smith, JC and Houpt, TA}, title = {Behavioral effects of static high magnetic fields on unrestrained and restrained mice.}, journal = {Physiology & behavior}, volume = {78}, number = {4-5}, pages = {635-640}, doi = {10.1016/s0031-9384(03)00040-4}, pmid = {12782218}, issn = {0031-9384}, support = {NIDCD 04607/DC/NIDCD NIH HHS/United States ; T32 NS 7437/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*radiation effects ; Conditioning, Operant/physiology ; *Electromagnetic Fields ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/physiology ; Restraint, Physical/*psychology ; Stress, Psychological/*psychology ; Taste/physiology/radiation effects ; }, abstract = {High-strength static magnetic fields are common tools in clinical imaging, but the behavioral effects are not well characterized. Previous studies on rats showed that fields of 7 T or above produced locomotor circling, conditioned taste aversion (CTA) and c-Fos in vestibular nuclei. To determine the generality of the behavioral effects on a smaller species, we subjected restrained or unrestrained mice to 30-min exposures in a 14.1-T field. Mice were given saccharin immediately prior to magnet or sham exposure on 3 consecutive days. All mice exposed to the magnet developed a CTA, and a significant number displayed tight circling and suppression of rearing. Unrestrained mice exhibited larger effects than restrained mice. These effects, similar to the effects in rats, may be the result of a vestibular disturbance caused by the magnetic field.}, } @article {pmid12766619, year = {2003}, author = {Risinger, FO}, title = {Genetic analyses of ethanol-induced hyperglycemia.}, journal = {Alcoholism, clinical and experimental research}, volume = {27}, number = {5}, pages = {756-764}, doi = {10.1097/01.ALC.0000065697.73554.DF}, pmid = {12766619}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA 10520/AA/NIAAA NIH HHS/United States ; AA 10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Chromosome Mapping ; Conditioning, Psychological ; Ethanol/*adverse effects ; Female ; Hyperglycemia/*chemically induced/*genetics ; Hypothermia/chemically induced/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Inbred Strains ; Quantitative Trait Loci ; Sex Characteristics ; Species Specificity ; Taste ; }, abstract = {BACKGROUND: Genetic sensitivity to ethanol-induced hyperglycemia was hypothesized to be related to sensitivity to ethanol-induced hypothermia and conditioned taste aversion. These hypotheses were explored by characterizing blood glucose changes after ethanol exposure in BXD recombinant inbred mice.

METHODS: Adult male and female BXD recombinant inbred mice were acutely exposed to 4 g/kg of ethanol or saline with the order of exposure counterbalanced, and separated by a 1-week interval. Tail blood samples and rectal temperatures were determined immediately before ethanol/saline exposure and 2 hr after exposure.

RESULTS: Substantial strain differences in ethanol-induced hyperglycemia and hypothermia were noted. In addition, sex also determined sensitivity to ethanol-induced hyperglycemia and interacted with strain. Correlational analyses using strain means indicated that ethanol-induced hyperglycemia was genetically independent from ethanol-induced hypothermia or conditioned taste aversion. Quantitative trait locus (QTL) analyses indicated provisional QTL for ethanol-induced hyperglycemia on chromosomes 1, 3, 4, 6, 7, 9, 12, 14, and 18, which, in part, were sex specific.

CONCLUSIONS: These findings indicate important sex differences in the glycemic response to ethanol. In addition, multiple genes likely control this response, independent from genes that are important for the thermic or aversive effects of ethanol.}, } @article {pmid12752384, year = {2003}, author = {Ripley, TL and Brown, G and Dunworth, SJ and Stephens, DN}, title = {Aversive conditioning following repeated withdrawal from ethanol and epileptic kindling.}, journal = {The European journal of neuroscience}, volume = {17}, number = {8}, pages = {1664-1670}, doi = {10.1046/j.1460-9568.2003.02604.x}, pmid = {12752384}, issn = {0953-816X}, mesh = {Alcohol Withdrawal Seizures/*physiopathology ; Amygdala/*drug effects/physiology ; Animals ; Behavior, Animal/*drug effects ; Central Nervous System Depressants/pharmacology ; Conditioning, Operant ; Electric Stimulation ; Ethanol/pharmacology ; GABA Antagonists/pharmacology ; Kindling, Neurologic/*drug effects/physiology ; Male ; Pentylenetetrazole/pharmacology ; Rats ; Taste ; }, abstract = {Repeated withdrawal from ethanol, a procedure which resembles amygdala kindling in increasing seizure sensitivity, impairs the acquisition of fear conditioning (Stephens et al., 2001, Eur. J. Neurosci.,14, 2023-31). In contrast, rats previously kindled by repeated electrical stimulation of basolateral amygdala, or repeated administration of pentylenetetrazol, showed increased suppression of operant responding during the presentation of a stimulus conditioned to footshock when conditioning took place several weeks following the kindling experience. Neither form of kindling nor repeated ethanol withdrawal altered taste aversion conditioning, though rats treated chronically with ethanol and given a single withdrawal experience showed enhanced taste aversion conditioning. These results suggest that, despite evidence suggesting a common neuronal mechanism underlying seizure sensitivity following these types of kindling, they differ in their effects on fear conditioning.}, } @article {pmid12752373, year = {2003}, author = {Gutiérrez, R and Téllez, LA and Bermúdez-Rattoni, F}, title = {Blockade of cortical muscarinic but not NMDA receptors prevents a novel taste from becoming familiar.}, journal = {The European journal of neuroscience}, volume = {17}, number = {8}, pages = {1556-1562}, doi = {10.1046/j.1460-9568.2003.02608.x}, pmid = {12752373}, issn = {0953-816X}, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*metabolism ; Injections, Intraventricular ; Male ; Memory/drug effects ; Microinjections ; Muscarinic Antagonists/pharmacology ; Rats ; Receptors, Muscarinic/*metabolism ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Saccharin ; Scopolamine/administration & dosage/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Exposure to a novel taste solution in the rat is followed by a decrease in its intake known as neophobia. This effect gradually disappears, and consumption increases from the second presentation of the taste (attenuation of neophobia), reflecting that the animal learned that it is safe to drink it. Conversely, if gastric malaise is induced after first intake, the rat will develop a long-lasting aversion (conditioned taste aversion). Previous attempts to elucidate the physiological nature of taste memory trace stems only from procedures that require malaise to measure taste memory. Here we assess the relevance of both muscarinic and N-methyl-d-aspartate receptors, known to be involved in conditioned taste aversion, on taste memory using a nonaversive procedure (attenuation of neophobia learning). Attenuation of neophobia was impaired by the muscarinic receptor antagonist, scopolamine, microinjected 20 min before, immediately after or up to 2 h after the first taste experience, suggesting that muscarinic receptors are involved in the acquisition and consolidation of attenuation of neophobia learning. However, the N-methyl-d-aspartate receptor antagonist, d,l-2-amino-5-phosphonovaleric acid, did not affect attenuation of neophobia even when the same dose of the drug was able to disrupt conditioned taste aversion learning, which suggests that attenuation of neophobia learning would be independent of N-methyl-d-aspartate receptors activity in the insular cortex. The neophobic response induced by strong saccharin presentation was not affected by either of the treatments given, which rules out any impairment in taste perception. These results indicate that while cortical muscarinic receptors are important in the formation and consolidation of safe memory trace, N-methyl-d-aspartate receptor activity appears to be noncritical.}, } @article {pmid12742259, year = {2003}, author = {Ishitobi, S and Miyamoto, T and Oi, K and Toda, K}, title = {Subhypnotic doses of propofol accelerate extinction of conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {141}, number = {2}, pages = {223-228}, doi = {10.1016/s0166-4328(02)00375-3}, pmid = {12742259}, issn = {0166-4328}, mesh = {Anesthetics, Intravenous/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Extinction, Psychological/*drug effects ; Lithium Chloride/pharmacology ; Male ; Propofol/*pharmacology ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Subhypnotic doses of propofol accelerate extinction of conditioned taste aversion. Some intravenous anesthetic agents including propofol is known to induce anterograde and retrograde amnesia. We evaluated whether propofol affect the long-term memory formed by the conditioned taste aversion (CTA) paradigm. Rats were allowed a 4h access to water through the experiments. After preconditioning water intake, the rats were offered 0.1% sodium saccharin (Sac) as conditioned stimulus (CS) for 20 min. An intraperitoneal (i.p.) injection of several concentrations (0.5-100 mg/kg) of propofol 10 min after Sac exposure was followed by an i.p. injection of 0.15M LiCl (2% of body weight) as unconditioned stimulus (US) 30 min after CS-exposure. The volumes of intake of Sac for 20 min were measured on the successive 4 days. The rats, which acquired CTA by every CS-US paradigm, strongly avoided Sac on the first test day after conditioning and maintained the avoidance for 3 days. However, when subhypnotic dose of propofol was injected before LiCl-injection, Sac intake abruptly increased on the second test day and the almost complete extinction occurred on the third test day after conditioning. The extinction process of CTA was barely affected by hypnotic dose of propofol. These results suggest that propofol affects the retention mechanism of the CTA memory in a dose-dependent manner. Subhypnotic dose of propofol may affect the sub-cellular process of the memory consolidation in CTA.}, } @article {pmid12742254, year = {2003}, author = {Schachtman, TR and Bills, C and Ghinescu, R and Murch, K and Serfozo, P and Simonyi, A}, title = {MPEP, a selective metabotropic glutamate receptor 5 antagonist, attenuates conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {141}, number = {2}, pages = {177-182}, doi = {10.1016/s0166-4328(02)00378-9}, pmid = {12742254}, issn = {0166-4328}, support = {R01 MH59039-01/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Excitatory Amino Acid Antagonists/*pharmacology ; Indans/pharmacology ; Lithium Chloride/pharmacology ; Male ; Pyridines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/*antagonists & inhibitors ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Metabotropic glutamate receptors (mGluRs) have been implicated in several types of cognitive and associative learning. Although recent evidence indicates an influence of mGluRs in conditioned taste aversion (CTA), the subtype-specific involvement of mGluRs in this learning paradigm remained to be determined. The aim of this study was to examine the role of Group I mGluR subtypes in CTA using a selective mGluR5 antagonist (2-methyl-6-(phenylethynyl)-pyridine, MPEP) and a selective mGluR1 antagonist (1-aminoindan-1,5-dicarboxylic acid, AIDA). Male, water-deprived, Sprague-Dawley rats were injected i.p. with 6 or 12 mg/kg MPEP or saline. Twenty-five minutes later, all rats received 15-min access to a 0.1% saccharin solution (Sac) immediately followed by an injection of 0.15M LiCl at 1.33% body weight. The animals were tested with 15-min access to Sac on each of four test days. MPEP-treated animals consumed more Sac on the test trials than saline-treated rats. In another experiment, controlled access to Sac was used by infusing the solution on the conditioning trial. Consistent with the above results, MPEP attenuated the degree of CTA. Similar experiments using the mGluR1 antagonist AIDA, have found no effect on CTA learning. These results suggest that the two subtypes of Group I mGluRs are differentially involved in taste aversion learning.}, } @article {pmid12736193, year = {2003}, author = {Printz, MP and Jirout, M and Jaworski, R and Alemayehu, A and Kren, V}, title = {Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {94}, number = {6}, pages = {2510-2522}, doi = {10.1152/japplphysiol.00064.2003}, pmid = {12736193}, issn = {8750-7587}, support = {HL-35018/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Cardiovascular Physiological Phenomena ; Chromosome Mapping ; Fetus/physiology ; Genetics/trends ; *Genetics, Behavioral ; *Genomics ; Polydactyly/genetics ; Quantitative Trait Loci ; Rats ; Rats, Inbred BN/*genetics/growth & development ; Rats, Inbred SHR/*genetics/growth & development ; *Recombination, Genetic ; }, abstract = {This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.}, } @article {pmid12721779, year = {2003}, author = {Hill, KG and Alva, H and Blednov, YA and Cunningham, CL}, title = {Reduced ethanol-induced conditioned taste aversion and conditioned place preference in GIRK2 null mutant mice.}, journal = {Psychopharmacology}, volume = {169}, number = {1}, pages = {108-114}, pmid = {12721779}, issn = {0033-3158}, support = {AA13520/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Conditioning, Psychological/*drug effects ; Ethanol/administration & dosage/*pharmacology ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Genotype ; Mice ; Mice, Knockout ; Motivation ; Potassium Channels/*genetics ; *Potassium Channels, Inwardly Rectifying ; Reward ; Taste/*drug effects ; }, abstract = {RATIONALE: Previous studies have shown that GIRK2 channel function is enhanced by ethanol and that GIRK2 null mutant mice are less sensitive to some of ethanol's effects, including anxiolysis, habituated locomotor stimulation, and acute handling-induced convulsions than wild types. Under some conditions, GIRK2 knockout mice consume more ethanol than wild types, but it is unclear whether they do so because they are more sensitive to ethanol's rewarding effects or less sensitive to its aversive effects.

OBJECTIVE: To further assess the role of GIRK2 in ethanol action, GIRK2 null mutant and wild type mice were tested in conditioning models that measure the motivational effects of ethanol.

METHOD: In a conditioned taste aversion (CTA) procedure, knockout and wild type mice were given ethanol (0.0, 2.0, 2.5, or 3.5 g/kg, IP) following 1-h access to saccharin every 48 h over a 10 day period. In a conditioned place preference (CPP) procedure, knockout and wild type mice were given ethanol (2.0 or 3.0 g/kg, IP) paired with one stimulus (grid or hole floor) and saline paired with the other. After four 5-min trials with each stimulus, a 60-min choice test was done.

RESULTS: The results demonstrated a genotypic difference in both paradigms. In CTA, there was no difference between genotypes at 0.0 or 3.5 g/kg ethanol, but at the 2.0 and 2.5 g/kg doses, wild types developed a stronger aversion to saccharin than knockouts. In CPP, wild types developed place preference, but knockouts did not.

CONCLUSIONS: These studies show that GIRK2 deletion reduced ethanol's impact in tasks that are commonly used to index the drug's rewarding and aversive effects. These findings could reflect either a learning/memory deficit or decreased sensitivity to ethanol's motivational effects in null mutant mice. The latter interpretation is more consistent with previous data showing that knockout mice consume higher doses of ethanol than wild type mice.}, } @article {pmid12717851, year = {2003}, author = {Han, Z and Yan, JQ and Luo, GG and Liu, Y and Wang, YL}, title = {Leptin receptor expression in the basolateral nucleus of amygdala of conditioned taste aversion rats.}, journal = {World journal of gastroenterology}, volume = {9}, number = {5}, pages = {1034-1037}, pmid = {12717851}, issn = {1007-9327}, mesh = {Amygdala/*metabolism ; Animals ; Conditioning, Psychological/*physiology ; Gene Expression ; Immunohistochemistry ; In Situ Hybridization ; Leptin/blood ; Male ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface/*genetics/*metabolism ; Receptors, Leptin ; Taste ; }, abstract = {AIM: To determine whether serum leptin level and the leptin receptor (OB-R) expression in the basolateral amygdala (BLA) change following conditioned taste aversion (CTA) formation.

METHODS: The serum leptin concentration was measured by rat leptin RIA kit, long and short forms of leptin receptor (OB-Rb and OB-Ra) mRNA in the brain sections were examined by in situ hybridization (ISH) and the expression of OB-R was assessed by immunohistochemistry ABC method with a highly specific goat anti-OB-R antibody.

RESULTS: The level of serum leptin didn't show significant difference between CTA and control group. Comparing with the control group, the CTA group had an increase on count of OB-R immunohistochemistry positive-stained cells in the BLA (127+/-12 vs 48+/-9 per 1 mm(2)). The OB-Rb mRNA expression level enhanced by 11.9 % in the BLA, while OB-Ra mRNA level increased by 7.4 % on the choroid plexus in CTA group. So BLA was supposed to be a region where interactions between gustatory and vagal signals take place.

CONCLUSION: BLA is one of the sites, which are responsible for CTA formation in the brain. Leptin and OB-R maybe involved in neuronal communication for CTA. So leptin and its receptors probably take part in CTA and integration of autonomic and extroceptive information.}, } @article {pmid12714357, year = {2003}, author = {Vrang, N and Phifer, CB and Corkern, MM and Berthoud, HR}, title = {Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {285}, number = {2}, pages = {R470-8}, doi = {10.1152/ajpregu.00732.2002}, pmid = {12714357}, issn = {0363-6119}, support = {DK-47348/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite Regulation/physiology ; Gastric Dilatation/*metabolism/physiopathology ; *Gene Expression Regulation ; Glucagon/*analysis ; Glucagon-Like Peptide 1 ; Male ; Neurons/*metabolism ; Peptide Fragments/*analysis ; Peptides/*analysis ; Protein Precursors/*analysis ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/cytology/*metabolism ; }, abstract = {A group of neurons in the caudal nucleus of the solitary tract (NTS) processes preproglucagon to glucagon-like peptides (GLP)-1 and -2, peptides that inhibit food intake when administered intracerebroventricularly. The GLP-1/2-containing neural pathways have been suggested to play a role in taste aversion and nausea because LiCl activates these neurons, and LiCl-induced suppression of food intake can be blocked by the GLP-1 receptor antagonist exendin-9. As many gastrointestinal signals related to both satiety and nausea/illness travel via the vagus nerve to the caudal medulla, the present study assessed the capacity of different types of gastric distension (a purely mechanical stimulus) to activate GLP-1 neurons in the caudal NTS. Gastric balloon distension (1.4 ml/min first 5 min, 0.4 ml/min next 5 min, 9 ml total, held for 60 min) in nonanesthetized, freely moving rats produced 12- and 17-fold increases in c-Fos-expressing NTS neurons when distension was mainly in the fundus or corpus, respectively. Fundus and corpus distension increased the percentage of c-Fos-activated GLP-1 neurons to 21 +/- 9% and 32 +/- 5% compared with 1 +/- 1% with sham distension (P < 0.01). Thus gastric distension that may be considered within the physiological range activates GLP-1/2-containing neurons, suggesting some role in normal satiety. The results support the view that the medullary GLP system is involved in appetite control and is activated by stimuli within the behavioral continuum, ranging from satiety to nausea.}, } @article {pmid12713656, year = {2003}, author = {Bahar, A and Samuel, A and Hazvi, S and Dudai, Y}, title = {The amygdalar circuit that acquires taste aversion memory differs from the circuit that extinguishes it.}, journal = {The European journal of neuroscience}, volume = {17}, number = {7}, pages = {1527-1530}, doi = {10.1046/j.1460-9568.2003.02551.x}, pmid = {12713656}, issn = {0953-816X}, mesh = {Adrenergic beta-Antagonists/pharmacology ; Amygdala/drug effects/*physiology ; Animals ; Anisomycin/pharmacology ; Avoidance Learning/drug effects/*physiology ; *Conditioning, Psychological ; Extinction, Psychological/drug effects/*physiology ; Male ; Memory/drug effects/*physiology ; Neural Pathways/drug effects/physiology ; Propranolol/pharmacology ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Wistar ; Taste/*physiology ; Time Factors ; }, abstract = {Experimental extinction is the decline in the frequency or intensity of a conditioned behaviour resulting from repetitive performance of the behaviour in the absence of the unconditioned stimulus or reinforcer (Pavlov, 1927). Ample behavioural evidence indicates that experimental extinction does not reflect unlearning of the original trace, but rather a relearning process, in which the new association of the conditioned stimulus with the absence of the original reinforcer comes to control behaviour (Rescorla, 1996). If experimental extinction is indeed learning rather than forgetting, are the neuronal circuits that subserve learning and extinction identical? We address this question by double dissociation analysis of the role of the central (CeA) and the basolateral (BLA) nuclei of the rat's amygdala in the acquisition and extinction, respectively, of conditioned taste aversion (CTA). Whereas local blockade of protein synthesis or beta-adrenergic receptors in the CeA blocks acquisition but not extinction of CTA, a similar intervention in the BLA blocks extinction but not acquisition. Hence, the amygdalar circuit that acquires taste aversion memory differs functionally from the circuit that extinguishes it.}, } @article {pmid12708519, year = {2003}, author = {Frank, ME and Formaker, BK and Hettinger, TP}, title = {Taste responses to mixtures: analytic processing of quality.}, journal = {Behavioral neuroscience}, volume = {117}, number = {2}, pages = {228-235}, doi = {10.1037/0735-7044.117.2.228}, pmid = {12708519}, issn = {0735-7044}, support = {R01 DC04099/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal ; Conditioning, Psychological/drug effects/*physiology ; Cricetinae ; Discrimination Learning/physiology ; Generalization, Psychological ; Inhibition, Psychological ; Lithium Chloride/pharmacology ; Male ; Quinine/pharmacology ; Sodium Chloride/pharmacology ; Sucrose/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {The tastes of 100 mM sodium chloride (NaCl), 100 mM sucrose, and 1 mM quinine hydrochloride in mixtures were investigated in golden hamsters (Mesocricetus auratus) with a conditioned taste aversion (CTA) paradigm. CTAs, established in golden hamsters by injection of lithium chloride, were quantified as percent suppression of control 1-hr stimulus intake. CTAs for 10 of 15 stimulus pairs with common components symmetrically cross-generalized, suggesting that component qualities were recognized in binary and ternary mixtures. However, CTAs to quinine were hardly learned and were weakly expressed when quinine was mixed with NaCl, and generalizations from multiple to single stimuli were stronger than vice versa (i.e., asymmetric). The behaviors reflect peripheral inhibition and/or central mixture suppression. Nonetheless, components retain their distinct qualities in mixtures, suggesting that taste processing is analytic.}, } @article {pmid12704398, year = {2003}, author = {Benoit, SC and Sheldon, RJ and Air, EL and Messerschmidt, P and Wilmer, KA and Hodge, KM and Jones, MB and Eckstein, DM and McOsker, CC and Woods, SC and Seeley, RJ}, title = {Assessment of the aversive consequences of acute and chronic administration of the melanocortin agonist, MTII.}, journal = {International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity}, volume = {27}, number = {5}, pages = {550-556}, doi = {10.1038/sj.ijo.0802280}, pmid = {12704398}, mesh = {Animals ; Avoidance Learning ; Dose-Response Relationship, Drug ; Eating/drug effects ; Male ; Mice ; Obesity/*drug therapy ; Rats ; Taste Disorders/chemically induced ; alpha-MSH/administration & dosage/*adverse effects/*analogs & derivatives ; }, abstract = {BACKGROUND: The synthetic melanocortin (MC) agonist, melanotan-II (MTII), reduces food intake and body weight for hours to days after administration. One early report on the effect of MTII suggested that part of its anorexic action may be mediated by aversive consequences. In that experiment, MTII was found to support a mild conditioned taste aversion (CTA).

OBJECTIVE: The present experiments replicate and extend those findings in two additional CTA paradigms to further characterize the aversive effects of MTII in rats.

METHODS: Experiment 1 simultaneously assessed the ability of MTII to support CTA and reduce food intake, using a small oral infusion of a novel taste as the conditioned stimulus. Experiment 2 assessed the aversive consequences of chronic MTII administration. To accomplish this, we paired implantation of lithium chloride (LiCl)-, MTII- or saline-containing osmotic minipumps with a constantly available novel flavor. After 7 days, rats received a choice test between the minipump-paired flavor and a previously available neutral flavor.

RESULTS: Rats with saline minipumps exhibited no preference for either flavor. By contrast, rats in both the LiCl and MTII minipump groups significantly preferred the neutral flavor, indicating the development of a CTA. Additionally, CTA produced by administration of MTII was found to be more resistant to extinction than that produced by LiCl.

CONCLUSIONS: The reduction in food intake caused by MTII is accompanied by aversive consequences regardless of route of administration. These results present difficulties for the development of MCs-based therapies for obesity.}, } @article {pmid12681527, year = {2003}, author = {Quertemont, E and Escarabajal, MD and De Witte, P}, title = {Role of catalase in ethanol-induced conditioned taste aversion: a study with 3-amino-1,2,4-triazole.}, journal = {Drug and alcohol dependence}, volume = {70}, number = {1}, pages = {77-83}, doi = {10.1016/s0376-8716(02)00341-1}, pmid = {12681527}, issn = {0376-8716}, mesh = {Acetaldehyde/pharmacology ; Alcohol Drinking/metabolism ; Amitrole/*pharmacology ; Animals ; *Avoidance Learning ; Catalase/antagonists & inhibitors/*metabolism ; Central Nervous System Depressants ; *Conditioning, Psychological ; Enzyme Inhibitors/pharmacology ; *Ethanol ; Male ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Recent studies involved acetaldehyde, the first ethanol metabolite, in both the rewarding and aversive effects of ethanol consumption. Brain acetaldehyde is believed to originate mainly from local brain metabolism of ethanol by the enzyme catalase. Therefore, the inhibition of catalase by 3-amino-1,2,4-triazole (aminotriazole) may help to clarify the involvement of acetaldehyde in ethanol's hedonic effects. In the present study, multiple doses of both ethanol and aminotriazole were used to investigate the effects of catalase inhibition on ethanol-induced conditioned taste aversion (CTA). A separate microdialysis experiment investigated the effects of aminotriazole pretreatment on the time course of brain ethanol concentrations. Ethanol induced a dose-dependent CTA with a maximal effect after conditioning with 2.0 g/kg ethanol. Aminotriazole pretreatments dose-dependently potentiated the CTA induced by 1.0 g/kg ethanol. However, aminotriazole pretreatments did not alter the CTA induced by higher ethanol doses (1.5 and 2.0 g/kg) probably because a maximal aversion for saccharin was already obtained without aminotriazole. The results of the microdialysis experiment confirmed that the effects of aminotriazole cannot be attributed to local alterations of brain ethanol levels. The present study argues against a role for brain acetaldehyde in ethanol's aversive effects but in favor of its involvement in ethanol rewarding properties.}, } @article {pmid12672556, year = {2003}, author = {Fresquet, N and Yamamoto, J and Sandner, G}, title = {Frontal lesions do not alter the differential extinction of taste aversion conditioning in rats, when using two methods of sucrose delivery.}, journal = {Behavioural brain research}, volume = {141}, number = {1}, pages = {25-34}, doi = {10.1016/s0166-4328(02)00317-0}, pmid = {12672556}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal ; Conditioning, Psychological/*physiology ; *Discrimination, Psychological ; Drinking ; Extinction, Psychological ; Frontal Lobe/injuries/*physiology ; Gyrus Cinguli/injuries/physiology ; Male ; Perfusion ; Random Allocation ; Rats ; Rats, Long-Evans ; Self Administration ; Sucrose/*administration & dosage ; Taste/*physiology ; }, abstract = {The frontal cortex is involved in the planning of behavioural responses and in the processing of their outcomes. Thus it contributes to several learning mechanisms, including those of conditioned taste aversion (CTA). A solution of sucrose drunk freely by a rat from a drinking tube-self-drinking protocol (SD)-was used as a conditioned stimulus in CTA. The intake of this solution was followed by gastric malaise. It produced an aversion to sucrose that withstood extinction over a week of repetitive tests. But, when the sucrose was perfused intra-orally (IO), i.e. not depending on any specific action by the rat, the extinction of aversion was much faster. Several factors may explain this differential extinction including the contribution of contextual factors linked to the achievement of an action and/or the enhancement of the attention towards the outcome of the action (the taste). The processing of such factors is usually believed to require the prefrontal cortex or the cingulate cortex (CgC). In our first experiment, the frontal cortex was totally transected. In the second experiment, the CgC was removed by aspiration. None of these lesions elicited any change in CTA, either in IO or in SD conditions, meaning that the differential extinction remained. The surprising absence of a frontal lesion effect was thought to indicate the low attentional demand required in both CTA protocols.}, } @article {pmid12668209, year = {2003}, author = {Sheriff, S and Chance, WT and Iqbal, S and Rizvi, TA and Xiao, C and Kasckow, JW and Balasubramaniam, A}, title = {Hypothalamic administration of cAMP agonist/PKA activator inhibits both schedule feeding and NPY-induced feeding in rats.}, journal = {Peptides}, volume = {24}, number = {2}, pages = {245-254}, doi = {10.1016/s0196-9781(03)00037-8}, pmid = {12668209}, issn = {0196-9781}, support = {DK-53548/DK/NIDDK NIH HHS/United States ; GM-47122/GM/NIGMS NIH HHS/United States ; K01 MH 001545-01/MH/NIMH NIH HHS/United States ; MH-001545/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cyclic AMP/*analogs & derivatives/metabolism/*pharmacology ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Eating/*drug effects ; Enzyme Activation/drug effects ; Feeding Behavior/*drug effects ; Hypothalamus/*drug effects/metabolism ; Male ; Neuropeptide Y/*pharmacology ; Radioimmunoassay/methods ; Rats ; Rats, Sprague-Dawley ; Thionucleotides/pharmacology ; Time Factors ; }, abstract = {Following central administration, neuropeptides that decrease the level of cAMP induce feeding. Conversely, cAMP activating neuropeptides tend to elicit satiety. When the inhibitory effect of neuropeptide Y (NPY) on the hypothalamic cAMP production was blocked by pertussis toxin, the potent orexigenic effect of NPY was lost. These findings suggest that there may be a link between hypothalamic cAMP and the central regulation of food intake. In this report, we show that the injection of the membrane-permeable cAMP agonist, adenosine-3',5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMP), into perifornical hypothalamus (PFH) significantly inhibited schedule-induced and NPY-induced food intake for up to 4h. This inhibitory effect was normalized within 24h. A taste aversion could not be conditioned to Sp-cAMP treatment, suggesting that the anorectic response was not due to malaise. Sp-cAMP administration significantly increased the active protein kinase A (PKA) activity in dorsomedial (DMH) and ventromedial (VMH), but not in lateral (LH) hypothalamus. Consistently, food deprivation lowered, while refeeding normalized endogenous cAMP content in DMH and VMH, but not in LH areas. No significant effect of adenosine-3',5'-cyclic monophosphorothioate Rp-isomer (Rp-cAMP, cAMP antagonist) was observed on hypothalamic PKA activity, schedule-induced, or NPY-induced food intake. These findings suggest that the increase in cAMP level and PKA activity in DMH and VMH areas may trigger a satiety signal.}, } @article {pmid12667901, year = {2003}, author = {Maurice, T and Casalino, M and Lacroix, M and Romieu, P}, title = {Involvement of the sigma 1 receptor in the motivational effects of ethanol in mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {74}, number = {4}, pages = {869-876}, doi = {10.1016/s0091-3057(03)00002-9}, pmid = {12667901}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; Mice ; *Motivation ; Motor Activity/*drug effects/physiology ; Receptors, sigma/antagonists & inhibitors/*physiology ; }, abstract = {In the present study, we examined the involvement of the sigma(1) (sigma(1)) receptor in several behavioral manifestations of ethanol addiction. Administration of ethanol (0.5, 1, and 2 g/kg) in Swiss mice dose-dependently induced locomotor stimulation, conditioned place preference, and conditioned taste aversion, which are considered as behavioral index of drug-induced reward. Pretreatment with the selective sigma(1) receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047, 3-30 mg/kg) dose-dependently blocked ethanol (1 g/kg)-induced hyperlocomotion and taste aversion and ethanol (2 g/kg)-induced place preference. Pretreatment with the selective sigma(1) receptor agonist 2-(4-morpholino)ethyl 1-phenylcyclohexane-1-carboxylate (PRE-084, 1-10 mg/kg) before ethanol (0.5 g/kg) failed to affect the resulting locomotor stimulation, but dose-dependently enhanced the conditioned place preference. Each sigma(1) receptor ligand was devoid of behavioral effect by itself. These observations show that activation of the sigma(1) receptor is a necessary component of ethanol-induced motivational effects and suggest a new pharmacological target for alleviating ethanol addiction.}, } @article {pmid12655465, year = {2003}, author = {Escarabajal, MD and De Witte, P and Quertemont, E}, title = {Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats.}, journal = {Psychopharmacology}, volume = {167}, number = {2}, pages = {130-136}, pmid = {12655465}, issn = {0033-3158}, mesh = {Acetaldehyde/administration & dosage/metabolism/*pharmacology ; Alcohol Deterrents/administration & dosage/pharmacology ; Alcohol Drinking/*metabolism/psychology ; Animals ; Behavior, Animal/drug effects ; Choice Behavior/drug effects ; Conditioning, Psychological/*drug effects ; Cyanamide/administration & dosage/pharmacology ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Ethanol/administration & dosage/metabolism/*pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Sodium Chloride/administration & dosage ; Water/administration & dosage ; }, abstract = {RATIONALE: In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol.

OBJECTIVES: The present study reexamined the role of acetaldehyde in ethanol-induced conditioned taste aversion (CTA). A first experiment compared ethanol- and acetaldehyde-induced CTA. In a second experiment, cyanamide, an aldehyde dehydrogenase inhibitor, was administered before conditioning with either ethanol or acetaldehyde to investigate the effects of acetaldehyde accumulation.

METHODS: A classic CTA protocol was used to associate the taste of a saccharin solution with either ethanol or acetaldehyde injections. In experiment 1, saccharin consumption was followed by injections of either ethanol (0, 0.5, 1.0, 1.5 or 2.0 g/kg) or acetaldehyde (0, 100, 170 or 300 mg/kg). In experiment 2, the rats were pretreated with either saline or cyanamide (25 mg/kg) before conditioning with either ethanol or acetaldehyde.

RESULTS: Both ethanol and acetaldehyde induced significant CTA. However, ethanol produced a very strong CTA relative to acetaldehyde that induced only a weak CTA even at toxic doses. Cyanamide pretreatments significantly potentiated ethanol- but not acetaldehyde-induced CTA.

CONCLUSIONS: The present results indicate that ethanol-induced CTA does not result from brain acetaldehyde effects. In contrast, it is suggested that the reinforcing effects of brain acetaldehyde might actually reduce ethanol-induced CTA. Our results also suggest that the inhibition of brain catalase activity may contribute to the potentiating effects of cyanamide on ethanol-induced CTA.}, } @article {pmid12649393, year = {2003}, author = {Inoue, K and Valdez, GR and Reyes, TM and Reinhardt, LE and Tabarin, A and Rivier, J and Vale, WW and Sawchenko, PE and Koob, GF and Zorrilla, EP}, title = {Human urocortin II, a selective agonist for the type 2 corticotropin-releasing factor receptor, decreases feeding and drinking in the rat.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {305}, number = {1}, pages = {385-393}, doi = {10.1124/jpet.102.047712}, pmid = {12649393}, issn = {0022-3565}, support = {AA05563/AA/NIAAA NIH HHS/United States ; DK26741/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Corticotropin-Releasing Hormone/*pharmacology ; Eating/*drug effects ; Humans ; Male ; Proto-Oncogene Proteins c-fos/biosynthesis ; Rats ; Rats, Wistar ; Receptors, Corticotropin-Releasing Hormone/*agonists ; Urocortins ; Water ; }, abstract = {Corticotropin-releasing factor (CRF) has been hypothesized to modulate consummatory behavior through the Type 2 CRF (CRF(2)) receptor. However, behavioral functions subserved by the CRF(2) receptor remain poorly understood. Recently, human urocortin II (hUcn II), a selective CRF(2) receptor agonist, was identified. To study the effects of this neuropeptide on ingestive behavior, we examined the effects of centrally infused hUcn II (i.c.v. 0, 0.01, 0.1, 1.0, 10.0 micro g) on the microstructure of nose-poke responding for food and water in nondeprived, male rats. Malaise-inducing properties of the peptide were monitored using conditioned taste aversion (CTA) testing. To identify potential sites of action, central induction of Fos protein expression was examined. hUcn II dose dependently reduced the quantity and duration of responding for food and water at doses lower (0.01-1.0 micro g) than that forming a CTA (10 micro g). Effects were most evident during hours 4 to 6 of the dark cycle. Meal pattern analysis showed that hUcn II potently (0.1 micro g) increased the satiating value of food. Rats ate and drank smaller and shorter meals without changing meal frequency. Rats also ate more slowly. hUcn II induced Fos in regions involved in visceral sensory processing and autonomic/neuroendocrine regulation and resembling those activated by appetite suppressants. hUcn II is a promising neuropeptide for investigating the role of the CRF(2) receptor in ingestive behavior.}, } @article {pmid12634492, year = {2003}, author = {Koh, MT and Bernstein, IL}, title = {Inhibition of protein kinase A activity during conditioned taste aversion retrieval: interference with extinction or reconsolidation of a memory?.}, journal = {Neuroreport}, volume = {14}, number = {3}, pages = {405-407}, doi = {10.1097/00001756-200303030-00021}, pmid = {12634492}, issn = {0959-4965}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/drug effects/physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Cyclic AMP/*analogs & derivatives/pharmacology ; Cyclic AMP-Dependent Protein Kinases/*antagonists & inhibitors ; Enzyme Inhibitors/pharmacology ; Extinction, Psychological/drug effects/physiology ; Male ; Memory/drug effects/*physiology ; Rats ; Rats, Long-Evans ; Taste/*physiology ; Thionucleotides/pharmacology ; }, abstract = {The involvement of the cAMP-dependent protein kinase A (PKA) signaling pathway in protein synthesis-dependent memory consolidation has been supported by studies of fear conditioning and conditioned taste aversion (CTA). The present experiment examined whether inhibition of PKA activity at the time of memory retrieval impedes or promotes subsequent extinction. When Rp-cAMPS was infused into the amygdala at the time of CTA testing (retrieval), extinction was accelerated. Results confirm recent findings that stored memories become more labile when they are retrieved and extend these findings to CTA memories.}, } @article {pmid12626647, year = {2003}, author = {Blednov, YA and Walker, D and Alva, H and Creech, K and Findlay, G and Harris, RA}, title = {GABAA receptor alpha 1 and beta 2 subunit null mutant mice: behavioral responses to ethanol.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {305}, number = {3}, pages = {854-863}, doi = {10.1124/jpet.103.049478}, pmid = {12626647}, issn = {0022-3565}, support = {AA06399/AA/NIAAA NIH HHS/United States ; AA13520/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/physiopathology ; Animals ; Behavior, Animal ; Central Nervous System Depressants/metabolism/*pharmacology ; Conditioning, Classical/drug effects ; Ethanol/metabolism/*pharmacology ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/*drug effects ; Receptors, GABA-A/genetics/*metabolism ; }, abstract = {Mice lacking either the alpha1 or beta 2 subunit of the GABAA receptor were tested for ethanol, saccharin, or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and handling-induced seizures following chronic consumption of an ethanol liquid diet. The alpha1 null mutants showed decreased ethanol and saccharin consumption, increased aversion to ethanol, and a marked stimulation of motor activity after injection of ethanol. The beta 2 null mutants showed decreased consumption of saccharin and quinine, but not ethanol. Surprisingly, neither mutant showed marked changes in handling induced seizures before or after withdrawal of ethanol. The unique effects of deletion of these two GABAA receptor subunits on ethanol responses are discussed in terms of the distinct changes in different populations of GABAA receptors.}, } @article {pmid12615046, year = {2003}, author = {Oberbeck, R and Kromm, A and Exton, MS and Schade, U and Schedlowski, M}, title = {Pavlovian conditioning of endotoxin-tolerance in rats.}, journal = {Brain, behavior, and immunity}, volume = {17}, number = {1}, pages = {20-27}, doi = {10.1016/s0889-1591(02)00031-4}, pmid = {12615046}, issn = {0889-1591}, mesh = {Animals ; Avoidance Learning ; Conditioning, Classical/*physiology ; Drug Tolerance/physiology ; Endotoxins/*pharmacology ; Lipopolysaccharides/pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Taste/physiology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {The most fascinating example of the bi-directional interaction between the central nervous system (CNS) and immune system is the behavioral conditioning of immune functions. We therefore investigated the behavioral conditioning of lipopolysaccharide (LPS)-induced endotoxin tolerance using the taste aversion paradigm. The conditioned stimulus (CS) saccharin was paired with the unconditioned stimulus (UCS) LPS over a five (CONDl) or four (COND2) days learning trial. Controls received drinking water with (SHAM) or without (UNT) LPS. Endotoxin tolerance was tested by determination of LPS-induced tumor necrosis factor (TNF)-alpha release. After the avoidance of the induced endotoxin-tolerance the CS saccharin was re-presented in all experimental groups. A the end of the re-exposure period a complete endotoxin tolerance was noticed in the CONDl- and COND2-group. In contrast, no effect of saccharin administration was observed in the SHAM- or UNT-group. Our data demonstrate for the first time the behavioral conditioning of endotoxin tolerance. Furthermore, these results contribute new aspects to the mechanisms underlying the development and modulation of endotoxin tolerance.}, } @article {pmid12609394, year = {2001}, author = {Stewart, LS and Persinger, MA}, title = {Ketamine Prevents Learning Impairment When Administered Immediately after Status Epilepticus Onset.}, journal = {Epilepsy & behavior : E&B}, volume = {2}, number = {6}, pages = {585-591}, doi = {10.1006/ebeh.2001.0272}, pmid = {12609394}, issn = {1525-5069}, abstract = {Permanent cognitive impairment is common following status epilepticus (SE) in both humans and animals. We examined the effect of the NMDA antagonist ketamine administered after SE onset on two forms of associative learning in the rat: conditioned taste aversion and fear-conditioned analgesia. Following the onset of lithium/pilocarpine-induced SE, rats were administered either ketamine (100 mg/kg) or acepromazine (25 mg/kg). Acepromazine-treated animals show marked deficits in both learning measures at 1 month after SE. In contrast, ketamine-treated and nonepileptic control animals did not differ in performance for either task. Although studies have shown that ketamine is ineffective at controlling electrographic seizures early in SE, these results are consistent with previous studies showing that ketamine can preserve learning proficiency if administered shortly after seizure onset. As a clinically available drug, ketamine may prove useful in the treatment of SE when combined with conventional antiepileptic strategies.}, } @article {pmid12598638, year = {2003}, author = {Houpt, TA and Pittman, DW and Barranco, JM and Brooks, EH and Smith, JC}, title = {Behavioral effects of high-strength static magnetic fields on rats.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {23}, number = {4}, pages = {1498-1505}, pmid = {12598638}, issn = {1529-2401}, support = {03198//PHS HHS/United States ; }, mesh = {Animals ; *Behavior, Animal ; Conditioning, Psychological ; Eating ; *Magnetics ; Male ; Motor Activity ; Rats ; Rats, Sprague-Dawley ; Taste ; Time Factors ; }, abstract = {Advances in magnetic resonance imaging are driving the development of more powerful and higher-resolution machines with high-strength static magnetic fields. The behavioral effects of high-strength magnetic fields are largely uncharacterized, although restraint within a 9.4 T magnetic field is sufficient to induce a conditioned taste aversion (CTA) and induce brainstem expression of c-Fos in rats. To determine whether the behavioral effects of static magnetic fields are dependent on field strength, duration of exposure, and orientation with the field, rats were restrained within the bore of 7 or 14 T superconducting magnets for variable durations. Behavioral effects were assessed by scoring locomotor activity after release from the magnetic field and measuring CTA acquisition after pairing intake of a palatable glucose and saccharin (G+S) solution with magnetic field exposure. Magnetic field exposure at either 7 or 14 T suppressed rearing and induced tight circling. The direction of the circling was dependent on the rat's orientation within the magnetic field: if exposed head-up, rats circled counterclockwise; if exposed head-down, rats circled clockwise. CTA was induced after three pairings of taste and 30 min of 7 T exposure or after a single pairing of G+S and 1 min of 14 T exposure. These results suggest that magnetic field exposure has graded effects on rat behavior. We hypothesize that restraint with high-strength magnetic fields causes vestibular stimulation resulting in locomotor circling and CTA acquisition.}, } @article {pmid12593329, year = {2002}, author = {Lubow, RE and De la Casa, LG}, title = {Superlatent inhibition and spontaneous recovery: differential effects of pre- and postconditioning CS-alone presentations after long delays in different contexts.}, journal = {Animal learning & behavior}, volume = {30}, number = {4}, pages = {376-386}, pmid = {12593329}, issn = {0090-4996}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Drinking ; Extinction, Psychological ; *Inhibition, Psychological ; Lithium Chloride/toxicity ; Rats ; Rats, Wistar ; *Reaction Time ; *Retention, Psychology ; *Taste ; }, abstract = {In two pairs of three-stage conditioned taste aversion experiments, we examined the effects of delay interval (1 or 21 days) between the second and third stages, and of context in which the animals spent the delay (same as or different from the context of the other stages) on latent inhibition (LI) and spontaneous recovery following extinction. In the LI experiments (Experiments 1A and 1B), the first stage comprised nonreinforced presentations to saccharin or to water. In the second stage, rats were conditioned by saccharin paired with LiCl. In the extinction experiments (Experiments 2A and 2B), the order of the stages was reversed. For all experiments, Stage 3, the test stage, consisted of three presentations of saccharin alone. There was a super-LI effect in the saccharin-preexposed group that spent the 21-day delay in the different context (Experiment 1A). When the delay was spent in the same context, there was no difference in the amount of LI between the short- and long-delay groups (Experiment 1B). Conversely, there was a spontaneous recovery effect in the long-delay/same-context group (Experiment 2B), but not in the long-delay/different-context group (Experiment 2A). The pattern of results, incompatible with current explanations of delay-induced changes in memory performance, was interpreted in terms of an interaction between the delay conditions (same or different delay context), which modulate the extinction of previously acquired context-CS-nothing associations (during CS-alone presentations), and primacy effects.}, } @article {pmid12591226, year = {2003}, author = {Ramírez-Lugo, L and Miranda, MI and Escobar, ML and Espinosa, E and Bermúdez-Rattoni, F}, title = {The role of cortical cholinergic pre- and post-synaptic receptors in taste memory formation.}, journal = {Neurobiology of learning and memory}, volume = {79}, number = {2}, pages = {184-193}, doi = {10.1016/s1074-7427(02)00038-2}, pmid = {12591226}, issn = {1074-7427}, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Operant/drug effects/physiology ; Long-Term Potentiation/drug effects ; Male ; Memory/drug effects/*physiology ; Microdialysis ; Microinjections ; Muscarinic Antagonists/*pharmacology ; Pirenzepine/*analogs & derivatives/pharmacology ; Rats ; Rats, Wistar ; Receptors, Muscarinic/drug effects/*physiology ; Receptors, Presynaptic/drug effects/physiology ; Scopolamine/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {A number of studies have implicated cholinergic activity in the mediation of learning and memory processes. However, the specific role of muscarinic receptors in memory formation mechanisms is less known. The aim of the present study is to evaluate the effects of muscarinic antagonist M2 presynaptic receptor, AFDX-116 (0.5mM) and M1 and M3 post-synaptic receptor pirenzepine (100mM), as well as a non-selective muscarinic antagonist, scopolamine (136mM), in the insular cortex (IC) during acquisition and retrieval of conditioned taste aversion (CTA). In addition, we evaluate the effects of those antagonists in cortical ACh release by in vivo microdialysis and the effects on the induction of in vivo LTP in the BLA-IC projection. The results showed that the cortical microinjections of scopolamine and pirenzepine, but not AFDX-116, produced significant disruption in the acquisition of CTA, without effects during retrieval. Microinjections of scopolamine and AFDX-116 produced significant cortical ACh release, while infusions of pirenzepine did not produce any release. Application of scopolamine and pirenzepine diminished induction of LTP in the BLA-IC projection, but not AFDX-116, as compared with vehicle. The induction of BLA-CI LTP seems to be modulated by post-synaptic muscarinic acetylcholine receptors and not by pre-synaptic muscarinic receptors. These results suggest a differential involvement of cholinergic receptors during acquisition and retrieval of aversive memory formation, as well as a differential role of muscarinic receptors in the biochemical and electrophysiological processes that may underlay aversive memory.}, } @article {pmid12586757, year = {2003}, author = {Krasnow, SM and Fraley, GS and Schuh, SM and Baumgartner, JW and Clifton, DK and Steiner, RA}, title = {A role for galanin-like peptide in the integration of feeding, body weight regulation, and reproduction in the mouse.}, journal = {Endocrinology}, volume = {144}, number = {3}, pages = {813-822}, doi = {10.1210/en.2002-220982}, pmid = {12586757}, issn = {0013-7227}, support = {R01-HD-27142/HD/NICHD NIH HHS/United States ; T32-GM-07270/GM/NIGMS NIH HHS/United States ; U54-HD-12629/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Body Weight ; Conditioning, Psychological ; Dose-Response Relationship, Drug ; Eating/*physiology ; Follicle Stimulating Hormone/blood ; Galanin-Like Peptide ; Injections, Intraventricular ; Kinetics ; Leptin/pharmacology ; Luteinizing Hormone/blood ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Nerve Tissue Proteins/administration & dosage/pharmacology/*physiology ; Rats ; Rats, Sprague-Dawley ; Reproduction/*physiology ; Taste ; Testosterone/blood ; }, abstract = {Galanin-like peptide (GALP) shares sequence homology with galanin and binds to galanin receptors in vitro. GALP neurons in the arcuate nucleus coexpress leptin receptors, and GALP mRNA expression is up-regulated by leptin. Based on these observations, we postulated that GALP plays a role in mediating leptin's inhibitory effects on food intake (FI) and body weight (BW), as well as its stimulatory effect on the reproductive axis. To test these hypotheses, we performed several studies in which mice received intracerebroventricular injections of either GALP or vehicle. Acute GALP treatment elicited a dose-dependent suppression of FI and BW. Long-term treatment with GALP caused only transient reductions in FI and BW, demonstrating that the mice became refractory to continued exposure to GALP. GALP inhibited FI as early as 1 h post injection. Central injection of GALP suppressed locomotor activity and elicited the formation of a conditioned taste aversion. In male mice, serum levels of LH and testosterone were increased by GALP administration. Although we cannot rule out possible nonspecific effects of GALP on FI, the present observations are consistent with the argument that GALP is a downstream effector of leptin's actions within the central nervous system.}, } @article {pmid12577984, year = {2003}, author = {Rabin, BM and Joseph, JA and Shukitt-Hale, B}, title = {Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {31}, number = {1}, pages = {127-133}, doi = {10.1016/s0273-1177(02)00879-7}, pmid = {12577984}, issn = {0273-1177}, mesh = {Adjuvants, Immunologic/pharmacology ; Amphetamine/*pharmacology ; Animals ; Avoidance Learning/drug effects/*radiation effects ; Behavior, Animal/drug effects/*radiation effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Classical/drug effects/*radiation effects ; *Heavy Ions ; Iron ; Lithium Chloride/pharmacology ; Male ; Neurons/radiation effects ; Rats ; Rats, Sprague-Dawley ; Taste ; Time Factors ; }, abstract = {Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.}, } @article {pmid12576130, year = {2003}, author = {Bensaïd, A and Tomé, D and L'Heureux-Bourdon, D and Even, P and Gietzen, D and Morens, C and Gaudichon, C and Larue-Achagiotis, C and Fromentin, G}, title = {A high-protein diet enhances satiety without conditioned taste aversion in the rat.}, journal = {Physiology & behavior}, volume = {78}, number = {2}, pages = {311-320}, doi = {10.1016/s0031-9384(02)00977-0}, pmid = {12576130}, issn = {0031-9384}, mesh = {Animals ; Animals, Newborn/growth & development/psychology ; Avoidance Learning ; Behavior, Animal/drug effects ; Choice Behavior ; Conditioning, Psychological ; Dose-Response Relationship, Drug ; Feeding Behavior/drug effects ; Food Preferences ; Grooming ; Male ; Milk Proteins/*administration & dosage ; Motor Activity ; Rats ; Rats, Wistar ; Rest ; Satiety Response/*drug effects ; Taste ; }, abstract = {In order to determine the respective roles of conditioned food aversion, satiety and palatability, we studied behavioral responses to a 50% total milk protein diet, compared with those to a normal protein diet containing 14% total milk protein. Different paradigms were employed, including meal pattern analysis, two-choice testing, flavor testing, a behavioral satiety sequence (BSS) and taste reactivity. Our experiments showed that only behavioral and food intake parameters were disturbed during the first day when an animal ate the high-protein (P50) diet, and that most parameters returned to baseline values as soon as the second day of P50. Rats adapted to P50 did not acquire a conditioned taste aversion (CTA) but exhibited satiety, and a normal BSS. The initial reduction in high-protein diet intake appeared to result from the lower palatability of the food combined with the satiety effect of the high-protein diet and the delay required for metabolic adaptation to the higher protein level.}, } @article {pmid12551960, year = {2003}, author = {Berman, DE and Hazvi, S and Stehberg, J and Bahar, A and Dudai, Y}, title = {Conflicting processes in the extinction of conditioned taste aversion: behavioral and molecular aspects of latency, apparent stagnation, and spontaneous recovery.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {10}, number = {1}, pages = {16-25}, pmid = {12551960}, issn = {1072-0502}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Conditioning, Classical/physiology ; Cyclic AMP/agonists/metabolism/physiology ; Extinction, Psychological/*physiology ; Male ; Memory/*physiology ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta/metabolism ; Receptors, Muscarinic/metabolism ; *Taste ; Time Factors ; }, abstract = {The study of experimental extinction and of the spontaneous recovery of the extinguished memory could cast light on neurobiological mechanisms by which internal representations compete to control behavior. In this work, we use a combination of behavioral and molecular methods to dissect subprocesses of experimental extinction of conditioned taste aversion (CTA). Extinction of CTA becomes apparent only 90 min after the extinction trial. This latency is insensitive to muscarinic and beta-adrenergic modulation and to protein synthesis inhibition in the insular cortex (IC). Immediately afterwards, however, the extinguishing trace becomes sensitive to beta-adrenergic blockade and protein synthesis inhibition. The subsequent kinetics and magnitude of extinction depend on whether a spaced or massed extinction protocol is used. A massed protocol is highly effective in the short run, but results in apparent stagnation of extinction in the long-run, which conceals fast spontaneous recovery of the preextinguished trace. This recovery can be truncated by a beta-adrenergic agonist or a cAMP analog in the insular cortex, suggesting that spontaneous overtaking of the behavioral control by the original association is regulated at least in part by beta-adrenergic input, probably operating via the cAMP cascade, long after the offset of the conditioned stimulus. Hence, the performance of the subject in experimental extinction is the sum total of multiple, sometimes conflicting, time-dependent processes.}, } @article {pmid12543999, year = {2003}, author = {Chester, JA and Lumeng, L and Li, TK and Grahame, NJ}, title = {High- and low-alcohol-preferring mice show differences in conditioned taste aversion to alcohol.}, journal = {Alcoholism, clinical and experimental research}, volume = {27}, number = {1}, pages = {12-18}, doi = {10.1097/01.ALC.0000046340.06154.9F}, pmid = {12543999}, issn = {0145-6008}, support = {AA07462/AA/NIAAA NIH HHS/United States ; AA07612/AA/NIAAA NIH HHS/United States ; AA10722/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Ethanol/*pharmacology ; Female ; Male ; Mice ; Species Specificity ; Taste/drug effects/*genetics ; }, abstract = {BACKGROUND: Genetic differences in sensitivity to the aversive effects of alcohol may contribute to alcohol drinking behavior. The present study examined the development of conditioned taste aversion (CTA) to various doses of alcohol in two pairs of mouse lines selectively bred for high (HAP) and low (LAP) alcohol preference.

METHODS: Alcohol-naïve, male and female HAP and LAP mice from both replicate 1 (HAP n = 29; LAP n = 28) and replicate 2 (HAP n = 34; LAP n = 35) were adapted to a 2-hr per day water restriction regimen. During five conditioning trials at 48 hr intervals, mice received an intraperitoneal injection of saline or 2 g/kg or 4 g/kg alcohol immediately following 1 hr of access to a 0.20 M NaCl solution.

RESULTS: LAP mice of both replicates showed a significantly greater magnitude of CTA to both 2 g/kg and 4 g/kg alcohol compared with HAP mice of both replicates. There were no line differences in consumption of the NaCl solution in the saline control groups.

CONCLUSIONS: These data suggest that mice selectively bred for low alcohol preference are more sensitive to the development of alcohol CTA than mice selectively bred for high alcohol preference. The present findings indicate that common genes mediate both alcohol preference and the aversive effects of alcohol as measured in the CTA paradigm.}, } @article {pmid12536022, year = {2003}, author = {Liu, M and Maiorano, N and Shen, L and Pearson, K and Tajima, D and Zhang, DM and Woods, SC and Seeley, RJ and Davidson, WS and Tso, P}, title = {Expression of biologically active rat apolipoprotein AIV in Escherichia coli.}, journal = {Physiology & behavior}, volume = {78}, number = {1}, pages = {149-155}, doi = {10.1016/s0031-9384(02)00959-9}, pmid = {12536022}, issn = {0031-9384}, support = {DK17844/DK/NIDDK NIH HHS/United States ; DK53444/DK/NIDDK NIH HHS/United States ; DK54504/DK/NIDDK NIH HHS/United States ; DK54890/DK/NIDDK NIH HHS/United States ; DK56863/DK/NIDDK NIH HHS/United States ; DK56910/DK/NIDDK NIH HHS/United States ; HL62542-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Apolipoproteins A/*biosynthesis/genetics/pharmacology ; Avoidance Learning/drug effects ; Body Weight/drug effects ; DNA, Complementary/biosynthesis/genetics ; Eating/drug effects ; Escherichia coli/*metabolism ; Immunoblotting ; Injections, Intraventricular ; Lipoproteins/chemistry/isolation & purification ; Male ; Molecular Sequence Data ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/biosynthesis/pharmacology ; Spectrometry, Mass, Electrospray Ionization ; Taste/drug effects ; }, abstract = {Rat apolipoprotein AIV (apo AIV) is a 43-kDa intestinal apolipoprotein that is important in lipid metabolism and the suppression of food intake. In this study, a full-length rat apo AIV was expressed in Escherichia coli and purified in a bioactive form. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometric analysis revealed that the isolated recombinant protein has a molecular mass of approximately 43 kDa, similar to that of natural rat apo AIV. Immunoblot analysis and N-terminal amino acid sequencing confirmed the identity of the recombinant apo AIV protein as natural rat apo AIV. The recombinant protein was functional in lipoprotein binding assays. Biological activity was assessed behaviorally in that the recombinant protein suppressed food intake of fasted rats comparably to natural rat apo AIV. Neither native nor recombinant apo AIV elicited a conditioned taste aversion (CTA) at doses that suppress feeding. These results indicate that the recombinant apo AIV is structurally and functionally indistinguishable from rat natural apo AIV, making this overexpression and purification scheme a powerful tool for future structure and function studies.}, } @article {pmid12505176, year = {2003}, author = {De Brugada, I and González, F and Cándido, A}, title = {Repeated administration of LiCl produces an unconditioned stimulus preexposure effect in backward excitatory CTA but not habituation of the unconditioned increment in neophobia.}, journal = {Behavioural processes}, volume = {60}, number = {3}, pages = {227-233}, doi = {10.1016/s0376-6357(02)00125-0}, pmid = {12505176}, issn = {1872-8308}, abstract = {In one experiment using conditioned taste aversion and the unconditioned stimulus (US) preexposure procedure, one group of rats was given LiCl exposure for 3 days, whereas two other groups received saline. Following this phase, all groups were given a novel flavour (saccharine) to drink following either LiCl (group preexposed and one of the control groups) or saline injections (the remaining control group) and the consumption of the flavour was assessed. After this neophobia test, the acquired saccharine aversion was evaluated. The results show that three LiCl injections are enough to produce a US preexposure effect on backward excitatory taste aversion conditioning, whereas this number of injections procedure does not produce habituation of the increment in neophobia, an unconditioned response to the LiCl. The results are discussed taking into account different mechanisms involved in US preexposure effect.}, } @article {pmid12492305, year = {2002}, author = {Koh, MT and Thiele, TE and Bernstein, IL}, title = {Inhibition of protein kinase A activity interferes with long-term, but not short-term, memory of conditioned taste aversions.}, journal = {Behavioral neuroscience}, volume = {116}, number = {6}, pages = {1070-1074}, pmid = {12492305}, issn = {0735-7044}, support = {AA00258/AA/NIAAA NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/drug effects/*physiology ; Animals ; Avoidance Learning ; Cyclic AMP/administration & dosage/*analogs & derivatives/pharmacology ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/*pharmacology ; Enzyme Inhibitors/administration & dosage/pharmacology ; Male ; Memory, Short-Term/*physiology ; Protein Kinase Inhibitors ; Rats ; Rats, Long-Evans ; Stereoisomerism ; Taste ; Thionucleotides/administration & dosage/pharmacology ; }, abstract = {The present experiments examined whether inhibition of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activity interferes with conditioned taste aversion (CTA) memories. Rats were centrally infused with the selective PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS) before conditioning. Direct infusions of Rp-cAMPS into the amygdala showed no interference with short-term memory but did show significant attenuation of long-term memory and more rapid extinction. Results suggest that PKA activity is involved in the consolidation of long-term memory of CTAs, and that the amygdala may be 1 site that is important for this activity.}, } @article {pmid12482676, year = {2003}, author = {Atkinson, R and Bevilaqua, LR and Rostas, JA and Hunter, M}, title = {Discriminative taste aversion learning: a learning task for older chickens.}, journal = {Neurobiology of learning and memory}, volume = {79}, number = {1}, pages = {25-31}, doi = {10.1016/s1074-7427(02)00011-4}, pmid = {12482676}, issn = {1074-7427}, mesh = {Age Factors ; Animals ; Anisomycin/administration & dosage/pharmacology ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/physiology ; Chickens ; Corpus Striatum ; Discrimination Learning/drug effects/*physiology ; Imprinting, Psychological/drug effects/physiology ; Injections, Intraventricular ; Protein Synthesis Inhibitors/administration & dosage/pharmacology ; Taste/*physiology ; Time Factors ; }, abstract = {The study of learning and memory using the chicken model has relied on three learning paradigms, passive avoidance learning, imprinting and the pebble floor task. Passive avoidance learning and imprinting have been used predominantly in very young chickens and cannot be used to access learning and memory in older chickens. We have established a new behavioural learning paradigm, Discriminative Taste Aversion Learning (DTAL), that can be used with both young and older animals. The task requires chickens to discriminate between food crumbs dyed either red or yellow with one colour being associated with the aversive tasting substance, methylanthranilate. Learning can be tested at various times after the training session by presenting chickens with the coloured food crumbs without an aversive taste. Both chickens tested at 5 and 15 days post-hatch learned to avoid the aversive crumbs. Furthermore, the protein synthesis inhibitor anisomycin (30 mM; 10 microl per hemisphere) injected into the intermediate medial hyperstriatum ventrale 15 min pre-training or 45 min post-training blocked long-term memory for the DTAL task when tested 24 h later. Memory for the task was unaffected by anisomycin injection 120 min post-training or in control animals injected with saline at similar times. The timing of the cellular processes of protein synthesis needed for consolidation of the DTAL appears to be similar to those described for the other behavioural paradigms in young chickens.}, } @article {pmid12479957, year = {2003}, author = {Miranda, F and Hong, E and Sánchez, H and Velázquez-Martínez, DN}, title = {Further evidence that the discriminative stimulus properties of indorenate are mediated by 5-HT 1A/1B/2C receptors.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {74}, number = {2}, pages = {371-380}, doi = {10.1016/s0091-3057(02)01010-9}, pmid = {12479957}, issn = {0091-3057}, mesh = {5-Methoxytryptamine/*analogs & derivatives/*pharmacology ; Animals ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Generalization, Stimulus/drug effects ; Male ; Rats ; Receptor, Serotonin, 5-HT1B ; Receptor, Serotonin, 5-HT2C ; Receptors, Serotonin/*drug effects ; Receptors, Serotonin, 5-HT1 ; Serotonin Antagonists/pharmacology ; Serotonin Receptor Agonists/*pharmacology ; Taste/drug effects ; }, abstract = {Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors. Unlike other anxiolytics such as 5-HT receptor agonists, INDO may not share tolerance or dependency with the benzodiazepine anxiolytics. It has been reported that the discriminative stimulus properties of 5-HT(1A/1B/2C) agonists, but not those of 5-HT(3/4) agonists, generalize to INDO. Therefore, the aim of the present study was to obtain further evidence on the differential involvement of 5-HT(1A/1B/2C) receptors in the discriminative stimulus properties of INDO by evaluating its interactions with antagonists of the 5-HT(1A), 5-HT(1B), 5-HT(2C), and 5-HT(3/4) receptor subtypes. Rats were trained to discriminate INDO from saline in a conditioned taste aversion paradigm. For Group D(+)S(-), administration of INDO signalled that saccharin flavour was followed by LiCl, while injection of vehicle signalled safe consumption of saccharin solution. Group D(-)S(+) had the contingencies reversed. After this training, rats had generalization tests where INDO administration was preceded by different doses of the following antagonists: WAY100635 (5-HT(1A)), NAN190 (5-HT(1A)), methiothepin (5-HT(1A/1B/2C)), GR127935 (5-HT(1B/1D)), ketanserin (5-HT(2A/2C)), ritanserin (5-HT(2C/2A)), mesulergine (5-HT(2C/2A)), metergoline (5-HT(2C/2A)), SB206553 (5-HT(2B/2C)), and tropisetron (5-HT(3/4)). In Group D(+)S(-), the order of potency to block the discriminative stimulus properties of INDO was WAY100635>ketanserin>ritanserin>GR127935>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190, while in Group D(-)S(+), the order was WAY100635>GR127935>ketanserin>ritanserin>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190. Tropisetron did not produce any alteration of the discriminative control by INDO. These results suggest that the discriminative signal of INDO is mediated by 5-HT(1A/2C/1B) receptors and that blockade of any of its components produces a degradation of its discriminative effects.}, } @article {pmid12479783, year = {2002}, author = {Moron, I and Ballesteros, MA and Candido, A and Gallo, M}, title = {Taste aversion learning and aging: a comparison with the effect of dorsal hippocampal lesions in rats.}, journal = {Physiological research}, volume = {51 Suppl 1}, number = {}, pages = {S21-7}, pmid = {12479783}, issn = {0862-8408}, mesh = {Acetic Acid ; Aging/*physiology/*psychology ; Animals ; Avoidance Learning/*physiology ; Brain Diseases/physiopathology/psychology ; Brain Mapping ; Hippocampus/*physiology ; Injections, Intraperitoneal ; Lithium Chloride/administration & dosage ; Male ; Rats ; Rats, Wistar ; Sodium Chloride ; *Taste ; }, abstract = {The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning.}, } @article {pmid12479782, year = {2002}, author = {Greenshaw, AJ and Turrkish, S and Davis, BA}, title = {The enigma of conditioned taste aversion learning: stimulus properties of 2-phenylethylamine derivatives.}, journal = {Physiological research}, volume = {51 Suppl 1}, number = {}, pages = {S13-20}, pmid = {12479782}, issn = {0862-8408}, mesh = {Amphetamine/pharmacokinetics/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Brain/metabolism ; Conditioning, Psychological/*drug effects ; Male ; Monoamine Oxidase Inhibitors/pharmacology ; Motor Activity/drug effects ; Osmolar Concentration ; Phenethylamines/pharmacokinetics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; *Taste ; Time Factors ; }, abstract = {The functional aversive stimulus properties of several IP doses of (+/-)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg-1) were measured with the conditioned taste aversion (CTA) paradigm. A two-bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (+/-)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (+/-)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (+/-)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (+/-)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives.}, } @article {pmid12457941, year = {2002}, author = {Van A Redila, and Aliatas, E and Smith, BR and Amit, Z}, title = {Effects of ethanol on an acetaldehyde drug discrimination with a conditioned taste aversion procedure.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {28}, number = {2}, pages = {103-109}, doi = {10.1016/s0741-8329(02)00270-7}, pmid = {12457941}, issn = {0741-8329}, mesh = {Acetaldehyde/*pharmacology ; Animals ; Conditioning, Psychological/*drug effects/physiology ; Discrimination Learning/*drug effects/physiology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Long-Evans ; Taste/*drug effects/physiology ; }, abstract = {The current study was designed to investigate whether ethanol shares stimulus properties with acetaldehyde with the use of a discriminative taste aversion procedure. Animals were trained to discriminate a dose of acetaldehyde (0.2 or 0.3 g/kg, i.p.) from saline in eight consecutive cycles consisting of a pairing day (PD) and three nonpairing days (NPDs). On PDs, all animals were injected with a particular dose of acetaldehyde 30 min before a 20-min limited access to a saccharin solution [0.1% (wt./vol.)] and then injected immediately with either LiCl (0.15 M, 1.8 mEq) or saline. On the three following NPDs, animals were injected with saline and 30 min later were presented with the same saccharin solution for 20 min. All animals in each acetaldehyde training dose group acquired discriminative stimulus control before generalization tests were conducted. Results of generalization tests (ethanol doses of 0.8, 1.2, 1.6, and 2.0 g/kg) revealed that ethanol substituted for acetaldehyde at doses of 1.2 and 1.6 g/kg for both training doses of acetaldehyde. The findings for this study indicate that acetaldehyde and ethanol may share some stimulus properties.}, } @article {pmid12451438, year = {2003}, author = {Shoaib, M and Sidhpura, N and Shafait, S}, title = {Investigating the actions of bupropion on dependence-related effects of nicotine in rats.}, journal = {Psychopharmacology}, volume = {165}, number = {4}, pages = {405-412}, doi = {10.1007/s00213-002-1277-x}, pmid = {12451438}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/drug effects ; Bupropion/*therapeutic use ; Conditioning, Operant/drug effects ; Discrimination Learning/drug effects ; Disease Models, Animal ; Dopamine Uptake Inhibitors/*therapeutic use ; Dose-Response Relationship, Drug ; Drug Antagonism ; Male ; Nicotine/administration & dosage/*adverse effects ; Random Allocation ; Rats ; Reference Values ; Tobacco Use Disorder/*drug therapy ; }, abstract = {RATIONALE: The clinical success of the antidepressant bupropion, marketed as Zyban in smoking cessation, presents an ideal opportunity to unravel its mechanism of action utilising animal models of nicotine dependence.

OBJECTIVE: The present experiments utilise bupropion as a reference compound to examine putative interactions with stimulus properties of nicotine in rats.

METHODS AND RESULTS: In male hooded Lister rats, bupropion (10 and 30 mg/kg IP) administered 30 min prior to each intravenous nicotine (0.03 mg/kg per infusion) self-administration session failed to attenuate rates of nicotine intake. Moreover, following the large dose of bupropion, nicotine intake was enhanced and response rates remained elevated throughout the 28-day course of treatment. To examine interactions with subjective effects of nicotine, rats trained to discriminate nicotine (0.2 mg/kg SC) from vehicle were tested with bupropion (1, 3, 10 and 30 mg/kg IP). Bupropion pre-treatment failed to exert a "nicotine-like" action and also failed to attenuate the orderly dose-related discrimination function of nicotine (0.05-0.4 mg/kg SC) in rats. Using the conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake, bupropion (3, 10 and 30 mg/kg IP) pre-treatment failed to modify the aversive effects produced by a threshold dose of nicotine (0.2 mg/kg SC).

CONCLUSIONS: The results obtained with bupropion in these animal models of dependence suggest this antidepressant may not directly interact with stimulus properties of nicotine; rather its clinical efficacy may be exposed in animal models that are based upon chronic exposure to nicotine and upon abstinence effects.}, } @article {pmid12451146, year = {2002}, author = {Kinzig, KP and D'Alessio, DA and Seeley, RJ}, title = {The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {22}, number = {23}, pages = {10470-10476}, pmid = {12451146}, issn = {1529-2401}, support = {R01 DK054890/DK/NIDDK NIH HHS/United States ; DK54890/DK/NIDDK NIH HHS/United States ; }, mesh = {Amygdala/drug effects/physiology ; Animals ; *Anorexia/chemically induced/physiopathology ; Appetite Regulation/drug effects/*physiology ; Behavior, Animal/drug effects ; Catheterization ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects ; Fourth Ventricle/drug effects ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptides ; Injections, Intraperitoneal ; Injections, Intraventricular ; Lateral Ventricles/drug effects/physiology ; Lithium Chloride/administration & dosage ; Male ; Paraventricular Hypothalamic Nucleus/drug effects/physiology ; Peptide Fragments/pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Glucagon/antagonists & inhibitors/*metabolism ; Signal Transduction/drug effects/physiology ; Taste/drug effects/physiology ; Visceral Afferents/drug effects/*physiology ; }, abstract = {Intracerebroventricular administration of glucagon-like peptide-1 (7-36) amide (GLP-1) reduces food intake and produces symptoms of visceral illness, such as a conditioned taste aversion (CTA). The central hypothesis of the present work is that separate populations of GLP-1 receptors mediate the anorexia and taste aversion associated with GLP-1 administration. To test this hypothesis, we first compared the ability of various doses of GLP-1 to induce anorexia or CTA when administered into either the lateral or fourth ventricle. Lateral and fourth ventricular GLP-1 resulted in reduction of food intake at similar doses, whereas only lateral ventricular GLP-1 resulted in a CTA. Such data indicate that both hypothalamic and caudal brainstem GLP-1 receptors are likely to participate in the ability of GLP-1 to reduce food intake. We also hypothesized that the site that must mediate the ability of GLP-1 to induce visceral illness is in the central nucleus of the amygdala (CeA). Administration of 0.2 or 1.0 microg of GLP-1 (7-36) but not the inactive GLP-1 (9-36) resulted in a strong CTA with no accompanying anorexia. In addition, bilateral CeA administration of 2.5 microg of a GLP-1 receptor antagonist before intraperitoneal administration of the toxin lithium chloride resulted in a diminished CTA. Together, these data indicate that separate GLP-1 receptor populations mediate the multiple responses to GLP-1. These results indicate that GLP-1 is a flexible system that can be activated under various circumstances to alter the ingestion of nutrients and/or produce other visceral illness responses, depending on the ascending pathways of the GLP-1 system that are recruited.}, } @article {pmid12429393, year = {2002}, author = {Rodríguez, G and Alonso, G}, title = {Latent inhibition as a function of CS intensity in taste aversion learning.}, journal = {Behavioural processes}, volume = {60}, number = {1}, pages = {61-67}, doi = {10.1016/s0376-6357(02)00119-5}, pmid = {12429393}, issn = {0376-6357}, abstract = {An experiment is reported in which the relationship between the intensity of a preexposed stimulus and latent inhibition was investigated, using the taste aversion learning paradigm in rats. Two concentrations of a saline solution (high, 1%; and low, 0.25%) were used during preexposure and conditioning phases in a factorial design. Two control conditions without preexposure were added, one for each stimulus concentration during conditioning. The known effect of conditioned stimulus (CS) intensity during conditioning was confirmed: the more concentrated the solution used in conditioning, the higher the acquisition rate. A direct relationship was observed between the CS intensity used during preexposure and the latent inhibition effect: the more concentrated the solution during preexposure, the lower the acquisition rate of conditioning. The implications of these results for latent inhibition theories are considered.}, } @article {pmid12421860, year = {2002}, author = {Zuberbuehler, CA and Messikommer, RE and Wenk, C}, title = {Choice feeding of selenium-deficient laying hens affects diet selection, selenium intake and body weight.}, journal = {The Journal of nutrition}, volume = {132}, number = {11}, pages = {3411-3417}, doi = {10.1093/jn/132.11.3411}, pmid = {12421860}, issn = {0022-3166}, mesh = {Animals ; *Body Weight ; Chickens/*physiology ; Eating ; Female ; *Food Preferences ; Oviposition ; Selenium/*administration & dosage/*deficiency ; Self Administration/veterinary ; Taste ; }, abstract = {Inadequate selenium (Se) supply often in combination with low vitamin E status causes deficiency symptoms in many species. It is likely that a vague discomfort or sickness is perceived before clear deficiency signs become apparent. We investigated whether Se-deficient hens reduce their Se deficit by selecting a diet containing more selenium when offered two diets with different Se concentrations. A Low-Se diet (0.07 mg Se/kg) was supplemented with Se-enriched yeast (Sel-Plex 50) to produce Medium-Se (0.20 mg Se/kg) and High-Se (1.50 mg Se/kg) diets. Each of two consecutive study parts (I and II) with the same hens and treatments began with a 6-wk baseline period (Medium-Se diet), subsequently followed a 9-wk depletion period (Low-Se diet or Medium-Se diet), then a 6-wk choice feeding period in which two diets with different Se concentrations (Low-Se and Medium-Se, Medium-Se and High-Se, or Low-Se and High-Se) were offered. A control group received the Medium-Se diet throughout the study. Daily Se intake, calculated from daily feed intake, followed similar patterns in both parts of the study, but Se-deficient hens preferred (P < 0.05) the High-Se diet to the Low-Se diet during the first 3 wk of choice feeding only in part I. We conclude that young Se-deficient laying hens reduce their Se deficit if they have a choice between a Low-Se and a High-Se diet by preferentially selecting the High-Se diet, possibly based on learned place preference and/or learned taste aversion to the Low-Se diet, presumably in response to discomfort due to Se-deficiency.}, } @article {pmid12419520, year = {2002}, author = {Hadjimarkou, MM and Silva, RM and Rossi, GC and Pasternak, GW and Bodnar, RJ}, title = {Feeding induced by food deprivation is differentially reduced by G-protein alpha-subunit antisense probes in rats.}, journal = {Brain research}, volume = {955}, number = {1-2}, pages = {45-54}, doi = {10.1016/s0006-8993(02)03361-9}, pmid = {12419520}, issn = {0006-8993}, support = {DA00220/DA/NIDA NIH HHS/United States ; DA00310/DA/NIDA NIH HHS/United States ; DA07242/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Antisense Elements (Genetics)/genetics/*pharmacology ; Eating/*drug effects/physiology ; Feeding Behavior/*drug effects/physiology ; Food Deprivation/*physiology ; Heterotrimeric GTP-Binding Proteins/genetics/*pharmacology ; Male ; Oligodeoxyribonucleotides, Antisense/genetics/pharmacology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Antisense oligodeoxynucleotide (AS ODN) probes directed against the alpha-subunit of different G-proteins have been used to differentiate feeding responses in rats elicited by different opioid agonists, including morphine, beta-endorphin and dynorphin. Furthermore, antisense probes directed against G(o)alpha, but not G(s)alpha, G(q)alpha or G(i)alpha, significantly reduced nocturnal feeding in rats. The present study examined whether food intake and weight changes elicited by 24 h of food deprivation were significantly altered by ventricular administration of antisense probes directed against either G(i)alpha(1), G(i)alpha(2), G(i)alpha(3), G(s)alpha, G(o)alpha, G(q)alpha or G(x/z)alpha as well as a control nonsense probe in rats. Deprivation-induced weight loss was significantly enhanced by antisense probes directed against G(s)alpha and G(x/z)alpha, whereas weight recovery 24 h following reintroduction of food was significantly reduced by antisense probes directed against G(i)alpha(2), G(q)alpha and G(o)alpha. Selective antisense probe effects were noted for deprivation-induced intake with G(s)alpha and G(q)alpha probes exerting the greatest reductions, G(x/z)alpha, G(i)alpha(2), and G(i)alpha(3) probes exerting lesser effects, and G(i)alpha(1) and G(o)alpha probes failing to affect deprivation-induced intake. Importantly, the nonsense control probe failed to alter deprivation-induced intake or weight. The reductions in deprivation-induced intake by AS ODN probes directed against G(s)alpha or G(q)alpha were not accompanied by any evidence of a conditioned taste aversion. These data indicate important distinctions between G-protein mediation of different effector signaling pathways mediating feeding responses elicited under natural (e.g. nocturnal feeding) and regulatory challenge (e.g. food deprivation) conditions.}, } @article {pmid12419421, year = {2002}, author = {Houston, AJ and Wong, JC and Ebenezer, IS}, title = {Effects of subcutaneous administration of the gamma-aminobutyric acid(A) receptor agonist muscimol on water intake in water-deprived rats.}, journal = {Physiology & behavior}, volume = {77}, number = {2-3}, pages = {445-450}, doi = {10.1016/s0031-9384(02)00876-4}, pmid = {12419421}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects ; Bicuculline/administration & dosage/pharmacology ; Drinking/*drug effects ; Female ; GABA Agonists/administration & dosage/*pharmacology ; GABA Antagonists/administration & dosage/pharmacology ; Injections, Subcutaneous ; Male ; Muscimol/administration & dosage/*pharmacology ; Rats ; Rats, Wistar ; Receptors, GABA-A/*drug effects ; Sex Characteristics ; Taste/drug effects ; Water Deprivation/*physiology ; }, abstract = {The effects of the gamma-aminobutyric acid(A) (GABA(A)) receptor agonist muscimol were investigated on water intake in rats that had been deprived of water for 16 h. Muscimol (0.5-2.0 mg/kg sc) produced a dose-related inhibition of water consumption in both male (n=8) and female (n=8) rats, with maximal suppression of drinking occurring during the first 30 min after administration. Doses of 1 and 2 mg/kg produced significant decreases in water intake (P<.01), while a lower dose of 0.5 mg/kg was without effect. The hypodipsic effect of muscimol (1.0 mg/kg sc) was abolished by pretreatment of the animals with the GABA(A) receptor antagonist bicuculline (1 mg/kg sc). Furthermore, muscimol (2 mg/kg sc) did not produce aversion in a two-bottle conditioned taste aversion test, indicating that the suppressant effects of muscimol on water intake are not due to drug-induced malaise. The results suggest that systemic administration of muscimol produces a behaviourally specific suppression of primary drinking in rats by a GABA(A) receptor-mediated mechanism. Moreover, this action of muscimol appears to be independent of the gender of the animals.}, } @article {pmid12405514, year = {2002}, author = {Viggiano, D and Vallone, D and Welzl, H and Sadile, AG}, title = {The Naples High- and Low-Excitability rats: selective breeding, behavioral profile, morphometry, and molecular biology of the mesocortical dopamine system.}, journal = {Behavior genetics}, volume = {32}, number = {5}, pages = {315-333}, doi = {10.1023/a:1020210221156}, pmid = {12405514}, issn = {0001-8244}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Conditioning, Psychological ; Exploratory Behavior/physiology ; *Genetics, Behavioral ; Italy ; Maze Learning/physiology ; Prefrontal Cortex/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Inbred Strains ; Rats, Sprague-Dawley ; Receptors, Dopamine D1/genetics/metabolism ; }, abstract = {The Naples High- (NHE) and Low-Excitability (NLE) rat lines have been selected since 1976 on the basis of behavioral arousal to novelty (Làt-maze). Selective breeding has been conducted under continuous genetic pressure, with no brother-sister mating. The behavioral analyses presented here deal with (1) activity in environments of different complexity, i.e., holeboard and Làt maze; (2) maze learning in hexagonal tunnel, Olton, and Morris water mazes and; (3) two-way active avoidance and conditioned taste aversion tests. Morphometric analyses deal with central dopaminergic systems at their origin and target sites, as well as the density of dopamine transporter immunoreactivity. Molecular biology analyses are also presented, dealing with recent experiments on the prefrontal cortex (PFc), cloning and identifying differentially expressed genes using subtractive libraries and RNAase protection. The divergence between NLE and NHE rats varies as a function of the complexity level of the environment, with an impaired working and reference memory in both lines compared to random bred (NRB) controls. Moreover, data from the PFc of NHE rats show a hyperdopaminergic innervation, with overexpression of mRNA species involved in basal metabolism, and down-regulation of dopamine D1 receptors. Altogether, the evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.}, } @article {pmid12401710, year = {2002}, author = {Clegg, DJ and Wortman, MD and Benoit, SC and McOsker, CC and Seeley, RJ}, title = {Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion.}, journal = {Diabetes}, volume = {51}, number = {11}, pages = {3196-3201}, doi = {10.2337/diabetes.51.11.3196}, pmid = {12401710}, issn = {0012-1797}, support = {DK 17844/DK/NIDDK NIH HHS/United States ; DK 54080/DK/NIDDK NIH HHS/United States ; DK 56863/DK/NIDDK NIH HHS/United States ; }, mesh = {4-Butyrolactone/administration & dosage/*analogs & derivatives/*pharmacology ; Animals ; Anorexia/chemically induced ; Avoidance Learning/*drug effects ; Body Weight/*drug effects ; Cerebral Ventricles/drug effects/physiology ; Diet ; Dose-Response Relationship, Drug ; Energy Intake/*drug effects ; Enzyme Inhibitors/administration & dosage/*pharmacology ; Fatty Acid Synthases/*antagonists & inhibitors ; Injections, Intraperitoneal ; Injections, Intraventricular ; Male ; Mice ; Rats ; Rats, Long-Evans ; *Taste ; }, abstract = {Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be the critical site of action; however, a peripheral contribution cannot be ruled out. We compared doses of the FAS inhibitor C75 in the CNS (third ventricle [i3vt]) and periphery (intraperitoneal [IP]) to reduce food intake and body weight in rats. Centrally, the threshold dose was 3 micro g, whereas a dose of 10 mg/kg was required peripherally. Such data argue for FAS activity in the CNS as a potent target for the actions of C75. To control for nonspecific effects of FAS inhibition, we compared C75 administration in two models of illness, conditioned taste aversion and need-induced sodium appetite. Our results suggest the anorexia produced by IP C75 is accompanied by visceral illness, whereas the anorexia produced by i3vt is not. In addition, we placed animals in an indirect calorimeter after an IP injection of C75. We found that consistent with behavioral measures of visceral illness, peripheral C75 reduced heat expenditure and resulted in animals losing less weight than fasted control animals, suggesting that peripherally administered C75 has aversive properties. Understanding the mechanisms by which FAS inhibition in the CNS reduces food intake could lead to specific targets for the manipulation of energy balance and the treatment of obesity.}, } @article {pmid12394418, year = {2002}, author = {Allison, C and Claase, LA and Pratt, JA}, title = {Diazepam withdrawal-induced anxiety and place aversion in the rat: differential effects of two chronic diazepam treatment regimes.}, journal = {Behavioural pharmacology}, volume = {13}, number = {5-6}, pages = {417-425}, doi = {10.1097/00008877-200209000-00015}, pmid = {12394418}, issn = {0955-8810}, mesh = {Animals ; Anti-Anxiety Agents/administration & dosage/*adverse effects/blood ; Anxiety/*psychology ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Diazepam/administration & dosage/*adverse effects/blood ; Flumazenil/pharmacology ; GABA Modulators/pharmacology ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Male ; Rats ; Rats, Long-Evans ; Substance Withdrawal Syndrome/*psychology ; }, abstract = {The ability of the benzodiazepine antagonist flumazenil to precipitate a withdrawal subjective state in rats receiving chronic diazepam was investigated in a biased conditioned place aversion (CPA) procedure. Conditioning with flumazenil (10 mg/kg i.p.) in rats receiving chronic diazepam subcutaneously (s.c. in oil, 15 mg/kg/day for 28 days) but not intraperitoneally (i.p., 5 mg/kg for 28 days) resulted in the formation of a conditioned place aversion. These results indicate that precipitated withdrawal from diazepam injected s.c. but not i.p. produces a negative subjective state and that the conditioned place aversion paradigm may be useful in detecting the negative subjective effects of diazepam withdrawal. In parallel studies, the same s.c. treatment protocol produced an anxiogenic effect in the elevated plus-maze on spontaneous diazepam withdrawal, whereas rats treated with the i.p. protocol displayed no signs of withdrawal anxiety. The results of the present study are consistent with the interpretation that rats withdrawn from chronic i.p. diazepam did not demonstrate a CPA due to the 'repeated withdrawal' experiences induced by the i.p. injection route attenuating the subsequent ability of flumazenil to precipitate a subjective withdrawal state. Pharmacokinetic evidence and previous evidence showing that repeated withdrawal from diazepam in mice attenuates the aversive effects of the withdrawal experience in a conditioned taste aversion (CTA) paradigm support this interpretation.}, } @article {pmid12383243, year = {2002}, author = {Ferreira, G and Gutiérrez, R and De La Cruz, V and Bermúdez-Rattoni, F}, title = {Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory.}, journal = {The European journal of neuroscience}, volume = {16}, number = {6}, pages = {1139-1145}, doi = {10.1046/j.1460-9568.2002.02174.x}, pmid = {12383243}, issn = {0953-816X}, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Acetylcholine/metabolism ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*metabolism ; Drug Administration Schedule ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/metabolism ; Lithium Chloride ; Male ; Memory, Short-Term/drug effects/*physiology ; Models, Neurological ; Muscarinic Antagonists/pharmacology ; Nerve Net/drug effects/metabolism ; Rats ; Rats, Wistar ; Receptors, Muscarinic/drug effects/*metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism ; Scopolamine/pharmacology ; Synaptic Transmission/drug effects/physiology ; Taste/drug effects/*physiology ; }, abstract = {In conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste-illness association.}, } @article {pmid12379443, year = {2002}, author = {Brownson, EA and Brinton, RD and Chambers, KC}, title = {Vasopressin content in select brain regions during extinction of a conditioned taste aversion.}, journal = {Brain research bulletin}, volume = {59}, number = {2}, pages = {125-134}, doi = {10.1016/s0361-9230(02)00861-4}, pmid = {12379443}, issn = {0361-9230}, support = {MH46036/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Brain/*metabolism ; Conditioning, Psychological/*physiology ; Extinction, Psychological/*physiology ; Male ; Rats ; Rats, Inbred F344 ; Taste/*physiology ; Vasopressins/*biosynthesis ; }, abstract = {Previous studies have shown that low levels of vasopressin during extinction of conditioned taste avoidance are associated with a faster extinction, that fluid deprivation differentially alters vasopressin levels in various neural areas, and that extinction of conditioned taste avoidance is accelerated in fluid deprived male rats. The following study was designed to identify areas of the brain in which vasopressin levels are different in fluid deprived and nondeprived males during extinction of conditioned taste avoidance. Arginine vasopressin content was determined by radioimmunoassay in the paraventricular nucleus (PVN), medial amygdala (AMe), bed nucleus of the stria terminalis (BNST), nucleus tractus solitarius (NTS), medial septum (MS), lateral septum (LS), and insular cortex (IC) of unconditioned nondeprived males and conditioned males that were maintained on a 23-h fluid deprivation schedule or that were nondeprived. Vasopressin content in the PVN of deprived and nondeprived males differed during extinction. Based on comparisons with unconditioned nondeprived males, this difference was due to an elevation in the vasopressin content of the nondeprived but not the deprived males. These results raise the possibility that a vasopressinergic system in the PVN plays a critical role in the differential extinction rate of fluid deprived and nondeprived males, which will need to be verified by manipulating vasopressin levels in this brain site during extinction of a conditioned taste avoidance.}, } @article {pmid12377360, year = {2002}, author = {Boyce, JM and Risinger, FO}, title = {Dopamine D3 receptor antagonist effects on the motivational effects of ethanol.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {28}, number = {1}, pages = {47-55}, doi = {10.1016/s0741-8329(02)00237-9}, pmid = {12377360}, issn = {0741-8329}, support = {AA07468/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/drug effects/physiology ; Dopamine Antagonists/*pharmacology ; *Dopamine D2 Receptor Antagonists ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Indans/pharmacology ; Male ; Mice ; *Motivation ; Motor Activity ; Receptors, Dopamine D3 ; }, abstract = {Dopaminergic systems are thought to play important roles in the motivational effects of ethanol. In the present experiments, we examined the effects of U99194A, a putative dopamine D(3) receptor antagonist, on ethanol-induced conditioned place preference, locomotor stimulation, taste aversion, and self-administration. In two separate studies with the use of a place conditioning procedure, adult male Swiss-Webster mice received six pairings of a tactile stimulus with ethanol (1 or 3 g/kg, i.p.), U99194A (20 mg/kg, i.p.), or ethanol + U99194A. For determination of ethanol-stimulated activity, subjects received U99194A at a dose of 0, 10, 20, or 30 mg/kg 15 min before ethanol at 0, 1, or 2 g/kg immediately before a 30-min locomotor activity test. In a taste conditioning procedure, subjects received five 1-h access periods to 0.2 M NaCl. After the first four access periods, subjects received ethanol at 0, 2, or 4 g/kg and U99194A at 0, 10, or 20 mg/kg. In an oral self-administration procedure, male C57BL/6J mice received U99194A at 0, 10, or 20 mg/kg, followed by 30-min access to 10% (wt./vol.) sucrose or 10% (vol./vol.) ethanol in 10% sucrose. The acquisition of ethanol-induced conditioned place preference was enhanced by U99194A. However, U99194A did not produce significant preference alone. U99194A did not alter locomotor stimulation produced by an injection of ethanol at 2 g/kg. U99194A also did not alter the acquisition of ethanol-induced conditioned taste aversion and did not change oral ethanol self-administration. These results support the suggestion that dopamine D(3) receptors have specific involvement in ethanol reward, as measured by place conditioning, but are not important for ethanol-stimulated activity, ethanol taste aversion, or ethanol intake.}, } @article {pmid12376313, year = {2002}, author = {Kim, EK and Miller, I and Landree, LE and Borisy-Rudin, FF and Brown, P and Tihan, T and Townsend, CA and Witters, LA and Moran, TH and Kuhajda, FP and Ronnett, GV}, title = {Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {283}, number = {5}, pages = {E867-79}, doi = {10.1152/ajpendo.00178.2002}, pmid = {12376313}, issn = {0193-1849}, support = {CA-87850/CA/NCI NIH HHS/United States ; DC-02979/DC/NIDCD NIH HHS/United States ; DK-19302/DK/NIDDK NIH HHS/United States ; DK-35712/DK/NIDDK NIH HHS/United States ; F-32//PHS HHS/United States ; }, mesh = {4-Butyrolactone/*analogs & derivatives/*pharmacology ; Acetyl-CoA Carboxylase/genetics ; Adult ; Aged ; Amino Acid Sequence ; Animals ; Appetite/drug effects/physiology ; Arcuate Nucleus of Hypothalamus/cytology/*physiology ; Carboxy-Lyases/genetics ; Conditioning, Psychological/drug effects/physiology ; Eating/drug effects/*physiology ; Enzyme Inhibitors/*pharmacology ; Fasting/physiology ; Fatty Acid Synthases/analysis/*genetics ; Female ; Gene Expression Regulation, Enzymologic/drug effects/physiology ; Humans ; Immunohistochemistry ; Liver/chemistry ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Molecular Sequence Data ; Neurons/chemistry/*enzymology ; Neuropeptide Y/analysis/genetics ; Obesity/physiopathology ; Paraventricular Hypothalamic Nucleus/cytology/*physiology ; RNA, Messenger/analysis ; Taste ; }, abstract = {We previously demonstrated that C75, a specific and potent inhibitor of fatty acid synthase (FAS), reduced food intake and decreased body weight in mice. In the present study, we determined that these effects were not due to conditioned taste aversion. To investigate the mechanism of C75 action, we examined FAS brain expression. FAS was expressed in a number of brain regions, including arcuate and paraventricular nuclei (PVN) within regions that comprise the arcuate-PVN pathway in mouse and human. Although C75 and fasting significantly downregulated liver FAS, FAS levels remained high in hypothalamus, indicating that FAS levels were regulated differently in brain from those in liver. Double fluorescence in situ for FAS and neuropeptide Y (NPY) showed that FAS co-localized with NPY in neurons in the arcuate nucleus. NPY immnuoreactivity after C75 treatment was decreased in axon terminals that innervate the PVN and lateral hypothalamus. Collectively, these results demonstrate that FAS is present and active in neurons and suggests that C75 may alter food intake via interactions within the arcuate-PVN pathway mediated by NPY.}, } @article {pmid12369811, year = {2002}, author = {Aja, S and Robinson, BM and Mills, KJ and Ladenheim, EE and Moran, TH}, title = {Fourth ventricular CART reduces food and water intake and produces a conditioned taste aversion in rats.}, journal = {Behavioral neuroscience}, volume = {116}, number = {5}, pages = {918-921}, pmid = {12369811}, issn = {0735-7044}, support = {DK 19302/DK/NIDDK NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/*drug effects ; Eating/*drug effects ; Fourth Ventricle ; Injections, Intraventricular ; Lithium/pharmacology ; Lithium Chloride ; Male ; Nerve Tissue Proteins/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; Time Factors ; }, abstract = {Cocaine- and amphetamine-regulated transcript peptide (CART) reduces rats' intake of liquid diet if the peptide reaches the 4th ventricle (4V). To test for specificity of 4V CART effects on feeding, the authors compared its ability to reduce intakes of liquid diet and water and tested for conditioned taste aversion (CTA). CART reduced 30-min intakes of both water and Ensure at a threshold of 1 microg. Lithium chloride (0.15 M, 20 ml/kg i.p.) and 4V CART (1 microg) paired with novel saccharin solution reduced saccharin preferences similarly in subsequent 2-bottle tests, compared with saline. Thus, CART can produce CTA. These data demonstrate that 4V CART's actions in ingestive behavior are not specific to nutrients and suggest that aspects of 4V CART's actions in reducing intake may be secondary to the production of an aversive state.}, } @article {pmid12359831, year = {2002}, author = {Morón, I and Manrique, T and Molero, A and Ballesteros, MA and Gallo, M and Fenton, A}, title = {The contextual modulation of conditioned taste aversions by the physical environment and time of day is similar.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {9}, number = {5}, pages = {218-223}, doi = {10.1101/lm.52202}, pmid = {12359831}, issn = {1072-0502}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; *Circadian Rhythm ; Conditioning, Psychological/*physiology ; *Environment Design ; Extinction, Psychological/physiology ; Memory/physiology ; Rats ; Taste ; }, abstract = {In a pair of experiments, we have compared the ability of changes of place (Exp. 1) and changes of time of day (Exp. 2) to separately modulate learned saline-aversion memory phenomena in rats. Neither a spatial nor a temporal change disrupted latent inhibition using the present behavioral procedure. However, pre-exposure to the taste increased the contextual control of the learned aversion expression. The aversion reappeared in the place or at the time of conditioning after extinction in a different context. The results indicate that environmental and temporal contexts can independently, but similarly modulate taste aversion learning.}, } @article {pmid12351739, year = {2002}, author = {Laviolette, SR and Alexson, TO and van der Kooy, D}, title = {Lesions of the tegmental pedunculopontine nucleus block the rewarding effects and reveal the aversive effects of nicotine in the ventral tegmental area.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {22}, number = {19}, pages = {8653-8660}, pmid = {12351739}, issn = {1529-2401}, mesh = {Animals ; Behavior, Animal/drug effects/physiology ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Male ; Microinjections ; Motivation ; Motor Activity/drug effects/physiology ; Nicotine/*pharmacology ; Nicotinic Agonists/pharmacology ; Pons/*physiology ; Rats ; Rats, Wistar ; *Reward ; Spatial Behavior/drug effects/physiology ; Stimulation, Chemical ; Taste/drug effects/physiology ; Tegmentum Mesencephali/cytology/*drug effects/*physiology ; Ventral Tegmental Area/cytology/drug effects/physiology ; }, abstract = {Nicotine, the primary psychoactive component of tobacco smoke, is known to possess potent rewarding and aversive stimulus properties. The mammalian ventral tegmental area (VTA) is involved importantly in the mediation of the motivational effects of nicotine. However, the neural outputs from the VTA that may be involved in the transmission of the rewarding and aversive motivational effects of nicotine are not well understood. We report that bilateral lesions of the tegmental pedunculopontine nucleus (TPP) double dissociate the rewarding and aversive motivational effects of nicotine. Using a conditioned place preference paradigm, bilateral TPP lesions blocked a nicotine reward signal and revealed the aversive motivational properties of intra-VTA nicotine. These same TPP lesions did not block an aversive nicotine signal, as measured in a conditioned taste aversion paradigm. TPP lesions also produce an attenuation in nicotine-induced locomotor activity; however, neither learning nor performance deficits can account for these observed effects, because TPP-lesioned animals still showed clear aversive nicotine conditioning in two separate behavioral paradigms. Our results suggest that the rewarding effects of nicotine in the VTA are dependent on a nondopaminergic, descending reward pathway to the brainstem TPP.}, } @article {pmid12350287, year = {2002}, author = {Loy, I and Hall, G}, title = {Taste aversion after ingestion of lithium chloride: an associative analysis.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {55}, number = {4}, pages = {365-380}, doi = {10.1080/02724990244000070}, pmid = {12350287}, issn = {0272-4995}, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/drug effects ; Conditioning, Operant ; Drinking/drug effects ; Inhibition, Psychological ; Lithium Chloride/administration & dosage/*pharmacology ; Male ; Rats ; Rats, Wistar ; Sodium Chloride/administration & dosage ; Sucrose/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {In five experiments with rats we examined the aversion established by consumption of a solution of lithium chloride (LiCl). Experiment 1 showed that consumption of LiCl established an aversion to saline (NaCl). Experiment 2 showed that the size of the aversion was reduced in rats given pre-exposure to saline (a latent inhibition effect). Experiment 3 showed that experience of a sucrose-saline compound prior to consumption of LiCl generated an aversion to sucrose (a sensory preconditioning effect). Experiments 4 and 5 examined the effects produced by consumption of a sucrose-LiCl compound and demonstrated reciprocal overshadowing between the two tastes. These results confirm that consumption of LiCl establishes an aversion to the taste of this substance. Their implications for the use of orally consumed LiCl as a technique for the control of predatory behaviour are discussed.}, } @article {pmid12218511, year = {2002}, author = {Miranda, F and Orozco, G and Velázquez-Martínez, DN}, title = {Full substitution of the discriminative cue of a 5-HT(1A/1B/2C) agonist with the combined administration of a 5-HT(1B/2C) and a 5-HT(1A) agonist.}, journal = {Behavioural pharmacology}, volume = {13}, number = {4}, pages = {303-311}, doi = {10.1097/00008877-200207000-00007}, pmid = {12218511}, issn = {0955-8810}, mesh = {5-Methoxytryptamine/*analogs & derivatives/*pharmacology ; Animals ; Behavior, Animal ; Cues ; Discrimination Learning/*drug effects/physiology ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Generalization, Psychological/drug effects ; Male ; Rats ; Rats, Wistar ; Receptor, Serotonin, 5-HT1B ; Receptor, Serotonin, 5-HT2C ; Receptors, Serotonin/*drug effects ; Receptors, Serotonin, 5-HT1 ; Serotonin Receptor Agonists/*pharmacology ; }, abstract = {The present study examined whether animals attend to the individual components of the cue produced by a drug that stimulates different 5-hydroxytryptamine (5-HT) receptor populations, using a drug discrimination task based on the conditioned taste aversion (CTA) procedure. The training drug was indorenate (5-methoxytryptamine beta-methylcarboxylate) (INDO) that has been described as a 5-HT(1A/2C/1B) agonist able to exert discriminative control in both operant and CTA procedures. The principal objective was to examine generalization with the combined administration of agonists for the different receptor sites that may mimic the mechanism of action of the training drug. Male Wistar rats, deprived of water, were trained to discriminate INDO from saline; during the drug trials, the administration of INDO preceded saccharin-LiCl pairings, while, during the saline trials, the administration of saline preceded the saccharin-saline pairings. In generalization tests, INDO, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT(1A) agonist), 1-(3-trifluoromethylphenyl)piperazine (TFMPP, a 5-HT(1B) agonist), alpha-methyl-5-HT (a 5-HT(2C) agonist) or 2-methyl-5-HT (a 5-HT(3) agonist), were administered alone or in combination. The results showed that 8-OH-DPAT, TFMPP and alpha-methyl-5-HT produced dose-dependent generalization, up to 88% in the case of 8-OH-DPAT. The combined administration of the following pairs of drugs, 8-OH-DPAT+TFMPP or 8-OH-DPAT+ alpha-methyl-5-HT, at doses that produced only 15-55% generalization when administered alone, produced greater than 80% generalization to INDO. However, the single administration of 2-methyl-5-HT produced only saline-like responding and its combined administration with 8-OH-DPAT did not modify the generalization produced by the single administration of 8-OH-DPAT. These results suggest that animals attend to the individual components of the drug cue; in the case of INDO, which has three elements, each mediated by a different receptor subpopulation (5-HT(1A), 5-HT(1B) and 5-HT(2C)), the separate stimulation of at least two receptor subpopulations was 'interpreted' by the subject as the presence of the training drug.}, } @article {pmid12217932, year = {2002}, author = {Lucas, LA and McMillen, BA}, title = {Conditioned taste aversion and the Myers' high-ethanol-preferring rat.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {37}, number = {5}, pages = {427-431}, doi = {10.1093/alcalc/37.5.427}, pmid = {12217932}, issn = {0735-0414}, mesh = {Alcohol Drinking/genetics ; Animals ; Avoidance Learning/*drug effects/physiology ; Choice Behavior/physiology ; Conditioning, Operant/*drug effects/physiology ; Ethanol/*pharmacology ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sex Characteristics ; Species Specificity ; Taste/*drug effects/physiology ; }, abstract = {AIMS: Male and female Myers' high-ethanol-preferring (mHEP) rats were compared to outbred controls in a taste aversion paradigm.

METHODS: Alcohol-naïve rats were adapted to a 2-h access to water. Each rat was given either 0.05% saccharin (w/v) or 7% ethanol (v/v) as a novel solution for 1 h, after which either 0.5 M LiCl, as the aversive stimulus, or NaCl, as the control, was injected intraperitoneally. Each rat was tested 48 h later by presentation of the same solution.

RESULTS: After LiCl injections, saccharin consumption declined 21.6% in female Sprague-Dawley, 9.5% in female mHEP, 33.3% in male Wistar, and 38.3% in male mHEP rats. Ethanol consumption in these groups declined by 88.5, 30, 45 and 52%, respectively. These mHEP rats were then screened for 24-h alcohol consumption on a 10-day 3-30% ethanol vs water 'step-up' procedure. During the step-up procedure, only the male mHEP rats trained with ethanol for taste aversion drank less ethanol at the 3-5% concentrations than did rats trained with saccharin. The female mHEP rats did not learn an aversion to either saccharin or ethanol.

CONCLUSIONS: The female mHEP rat consumes copious amounts of ethanol, but the basis for this consumption may be different from that of the male mHEP rat.}, } @article {pmid12213523, year = {2002}, author = {Grakalic, I and Riley, AL}, title = {Asymmetric serial interactions between ethanol and cocaine in taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {73}, number = {4}, pages = {787-795}, doi = {10.1016/s0091-3057(02)00905-x}, pmid = {12213523}, issn = {0091-3057}, mesh = {Animals ; Cocaine/*pharmacology ; Drinking/drug effects/physiology ; Drug Interactions/physiology ; Ethanol/*pharmacology ; Female ; Learning/*drug effects/physiology ; Rats ; Rats, Long-Evans ; Saccharin/pharmacology ; Taste/*drug effects/physiology ; }, abstract = {Although the interaction between ethanol and cocaine is well documented, it has generally been limited to situations in which the two drugs are given concurrently. Little exists on the interaction between ethanol and cocaine when one drug is given prior to the other. In Experiment 1, female Long-Evans rats were given five exposures to ethanol (2 g/kg ip) or vehicle prior to taste aversion conditioning with cocaine (32 mg/kg sc) for a total of five conditioning trials. In Experiment 2, rats were given five exposures to cocaine (32 mg/kg sc) or vehicle prior to taste aversion conditioning with ethanol (2 g/kg ip) for a total of five conditioning trials. Ethanol-preexposed, cocaine-conditioned animals (Experiment 1) displayed attenuated aversions to the cocaine-associated solution, drinking significantly greater amounts of saccharin than vehicle-preexposed, conditioned subjects. Conversely, cocaine-preexposed, ethanol-conditioned animals (Experiment 2) displayed robust aversions to the ethanol-associated solution, drinking levels comparable to those consumed by vehicle-preexposed, conditioned subjects and drinking significantly less than controls. Although the basis for these asymmetric effects is not known, they may have implications for abuse vulnerability in that drug history may impact subsequent drug toxicity that, in turn, may alter drug acceptability.}, } @article {pmid12191830, year = {2002}, author = {Morón, I and Ramírez-Lugo, L and Ballesteros, MA and Gutiérrez, R and Miranda, MI and Gallo, M and Bermúdez-Rattoni, F}, title = {Differential effects of bicuculline and muscimol microinjections into the nucleus basalis magnocellularis in taste and place aversive memory formation.}, journal = {Behavioural brain research}, volume = {134}, number = {1-2}, pages = {425-431}, doi = {10.1016/s0166-4328(02)00056-6}, pmid = {12191830}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*drug effects ; Basal Nucleus of Meynert/anatomy & histology/*physiology ; Bicuculline/administration & dosage/*pharmacology ; GABA Agonists/administration & dosage/*pharmacology ; GABA Antagonists/administration & dosage/*pharmacology ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; Male ; Memory/*drug effects ; Microinjections ; Muscimol/administration & dosage/*pharmacology ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*drug effects ; gamma-Aminobutyric Acid/physiology ; }, abstract = {The role of the nucleus basalis magnocellularis (NBM) in learning and memory has been demonstrated in different learning paradigms such as conditioned taste aversion (CTA) and inhibitory avoidance (IA). This participation has been related to the cholinergic system, but recent studies have reported the potential role of other neurotransmitters such as GABA. The effects of acute intracerebral administration of the GABAergic antagonist bicuculline (0.05 microg) and the GABAergic agonist muscimol (0.05 microg) into the NBM of male Wistar rats were assessed in CTA and IA learning. In both learning tasks, the drug administration was performed before the acquisition. Taste aversion learning was not affected by the infusion of any of the drugs administered. IA acquisition was not affected by the administration of bicuculline or muscimol, requiring similar number of trials to reach the learning criterion. However, when the rats were tested 24 h later, those injected with bicuculline or muscimol showed an impairment of the IA learning. The present results support a role of the GABAergic system in the consolidation process of IA learning.}, } @article {pmid12175594, year = {2002}, author = {Echo, JA and Lamonte, N and Ackerman, TF and Bodnar, RJ}, title = {Alterations in food intake elicited by GABA and opioid agonists and antagonists administered into the ventral tegmental area region of rats.}, journal = {Physiology & behavior}, volume = {76}, number = {1}, pages = {107-116}, doi = {10.1016/s0031-9384(02)00690-x}, pmid = {12175594}, issn = {0031-9384}, mesh = {Administration, Oral ; Analgesics, Opioid/pharmacology ; Animals ; Baclofen/administration & dosage/pharmacology ; Eating/*drug effects ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/administration & dosage/pharmacology ; Food Preferences/drug effects ; GABA Agonists/administration & dosage/*pharmacology ; GABA Antagonists/administration & dosage/*pharmacology ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; GABA-B Receptor Agonists ; GABA-B Receptor Antagonists ; Male ; Microinjections ; Muscimol/administration & dosage/pharmacology ; Naltrexone/administration & dosage/pharmacology ; *Narcotic Antagonists/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/*agonists ; Receptors, Opioid, mu/agonists ; Ventral Tegmental Area/anatomy & histology/*physiology ; }, abstract = {Food intake is significantly increased following administration of mu-selective opioid agonists into the ventral tegmental area (VTA) region acting through multiple local opioid receptor subtypes. Since GABA receptor agonists in the VTA region are capable of eliciting feeding, the present study investigated whether feeding elicited by the mu-selective opioid agonist [D-Ala(2), NMe(4), Gly-ol(5)]-enkephalin (DAMGO) in the VTA region was altered by pretreatment into the same site with equimolar doses of either GABA(A) (bicuculline) or GABA(B) (saclofen) antagonists, and further, whether pretreatment with either general opioid or selective GABA receptor antagonists decreased feeding elicited by GABA(A) (muscimol) or GABA(B) (baclofen) agonists in the VTA region. DAMGO-induced feeding in the VTA region was dose-dependently decreased following pretreatment with either GABA(A) or GABA(B) antagonists in the absence of significant alterations in food intake by the antagonists per se. However, the presence of short-lived seizures following bicuculline in the VTA region suggests that this ingestive effect was caused by nonspecific actions. In contrast, GABA(B) receptors are involved in the full expression of mu-opioid agonist-induced feeding in this region since saclofen failed to elicit either seizure activity or a conditioned taste aversion. Pretreatment with naltrexone in the VTA region reduced intake elicited by baclofen, but not muscimol. Finally, baclofen-induced feeding was significantly reduced by saclofen, but not bicuculline, pretreatment in the VTA region. Therefore, possible coregulation between GABA(B) and opioid receptors in the VTA region, as suggested by immunocytochemical evidence, is supported by these behavioral effects upon ingestion.}, } @article {pmid12175588, year = {2002}, author = {Salvy, SJ and Pierce, WD and Heth, DC and Russell, JC}, title = {Pre-exposure to wheel running disrupts taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {76}, number = {1}, pages = {51-56}, doi = {10.1016/s0031-9384(02)00687-x}, pmid = {12175588}, issn = {0031-9384}, mesh = {Aging/physiology/psychology ; Animals ; Avoidance Learning/*physiology ; Hunger/physiology ; Male ; Motor Activity/*physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Thirst/physiology ; }, abstract = {When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.}, } @article {pmid12175460, year = {2002}, author = {Grakalic, I and Riley, AL}, title = {Ethanol preexposure attenuates the interaction of ethanol and cocaine in taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {72}, number = {3}, pages = {633-641}, doi = {10.1016/s0091-3057(02)00726-8}, pmid = {12175460}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Cocaine/pharmacokinetics/*pharmacology ; Drug Administration Schedule ; Drug Combinations ; Drug Interactions/physiology ; Ethanol/*administration & dosage/pharmacokinetics ; Female ; Rats ; Rats, Long-Evans ; Taste/*drug effects/physiology ; }, abstract = {Although the potentiating effects of ethanol and cocaine have been well documented, little has been reported regarding the effects of ethanol or cocaine history on this interaction. In the present study, female Long-Evans rats received five exposures to ethanol (3.5 g/kg ip) or vehicle prior to taste aversion conditioning in which a novel saccharin solution was paired with either ethanol (0.56 g/kg ip), cocaine (25 mg/kg sc) or the combination (or the drugs' vehicle) for a total of five conditioning trials. Nonpreexposed subjects conditioned with the ethanol/cocaine combination displayed aversions, drinking levels significantly less than nonpreexposed subjects conditioned with either drug alone. Further, the aversions produced by the combination were greater than the sum of the aversions produced by ethanol and cocaine, alone. Ethanol-preexposed animals conditioned with the combination displayed an attenuated aversion, drinking significantly greater amounts of saccharin than nonpreexposed conditioned subjects and not differing from controls. Although the basis for the attenuation by ethanol of the aversions induced by the drug combination is not known, the present findings may have implications for the use and abuse of the combination in that alcohol history may reduce the subsequent toxicity of the combination that in turn may affect its acceptability.}, } @article {pmid12175451, year = {2002}, author = {McKay, BE and Lado, WE and Martin, LJ and Galic, MA and Fournier, NM}, title = {Learning and memory in agmatine-treated rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {72}, number = {3}, pages = {551-557}, doi = {10.1016/s0091-3057(02)00724-4}, pmid = {12175451}, issn = {0091-3057}, mesh = {Agmatine/*pharmacology ; Animals ; Avoidance Learning/drug effects/physiology ; Dose-Response Relationship, Drug ; Fear/drug effects/physiology ; Female ; Learning/*drug effects/physiology ; Male ; Maze Learning/drug effects/physiology ; Memory/*drug effects/physiology ; N-Methylaspartate/antagonists & inhibitors ; Rats ; Rats, Wistar ; Taste/drug effects/physiology ; }, abstract = {Agmatine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, was examined for its role in water maze place learning, contextual and auditory-cued (discrete) fear learning and conditioned taste aversion learning, when administered systemically. Male Wistar rats were given saline or 1, 5, 10 or 50 mg/kg agmatine ip 20 min prior to or 30 min following daily training sessions in a hidden-platform (place learning) water maze task. Agmatine did not affect latencies to find the hidden platform or preference for the training quadrant during probe trials. When administered 20 min prior to contextual or auditory-cued fear-conditioning sessions, these doses of agmatine evoked a linear dose-dependent impairment in the magnitude of learned fear to the contextual stimuli when assessed during extinction trials 24 h later, but had no effect on the magnitude of learned fear to the auditory stimulus. Inferences of baseline motor activity and ability to respond to the presentation of footshock stimuli were not affected by the treatment. Injections of 50 mg/kg agmatine concurrently with a malaise-evoking agent following presentations to a novel sucrose solution abolished learned taste aversions; this agent did not evoke conditioned taste aversions alone. These studies indicate that systemically administered agmatine selectively impairs behavioral inferences of specific types of learning and memory.}, } @article {pmid12168690, year = {2002}, author = {Feurté, S and Tomé, D and Gietzen, DW and Even, PC and Nicolaïdis, S and Fromentin, G}, title = {Feeding patterns and meal microstructure during development of a taste aversion to a threonine devoid diet.}, journal = {Nutritional neuroscience}, volume = {5}, number = {4}, pages = {269-278}, doi = {10.1080/10284150290032003}, pmid = {12168690}, issn = {1028-415X}, mesh = {Animals ; *Diet ; *Eating ; Food ; Male ; Photoperiod ; Rats ; Rats, Wistar ; Threonine/*administration & dosage/*deficiency ; Time Factors ; }, abstract = {Food intake decreases and a conditioned taste aversion is induced when rats are fed a diet that is devoid of an indispensable amino acid. The purpose of this study was to characterize the meal patterns associated with (1) the onset of anorexia after the initial recognition of a threonine deficiency and (2) after the development of the conditioned taste aversion to this deficient diet. When rats ate the threonine-devoid diet for the first time, meal patterns were characterized by an increase in intermeal interval (IMI) between 3 and 6 h after food presentation, which was followed by a decrease in meal size and ingestion rate, between 6 and 12 h. Meal patterns on days 2 and 10 were associated with expression of the taste aversion, characterized by meals of smaller size, longer duration and by a reduction in ingestion rate, without variations in either IMI or meal frequency. Meals of the threonine-deficient group were composed of more frequent bouts, smaller size and shorter duration, with large within-meal pauses, which accounted for the reduced ingestion rate. This study presents the first analysis in terms of feeding patterns and meal microstructure of a conditioned taste aversion induced by a food rather than a toxin.}, } @article {pmid12167678, year = {2002}, author = {Miranda, MI and Ferreira, G and Ramirez-Lugo, L and Bermudez-Rattoni, F}, title = {Glutamatergic activity in the amygdala signals visceral input during taste memory formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, number = {17}, pages = {11417-11422}, pmid = {12167678}, issn = {0027-8424}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Psychological ; Glutamic Acid/administration & dosage/*physiology ; Male ; Memory/*physiology ; Microinjections ; Rats ; Rats, Wistar ; Saccharin ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is a learning paradigm in which an animal avoids a taste (conditioned stimulus) previously associated with visceral toxic effects [or unconditioned stimulus (US)]. Although many studies have implicated glutamate-mediated neurotransmission in memory consolidation of different types of learning tasks, including CTA, the exact role of this neurotransmitter system in memory formation is not known. Thus, we set out to determine whether glutamate mediates signaling of the US in CTA. We present evidence obtained by in vivo microdialysis that the US (i.p. injection of lithium chloride) induced a dramatic increase in glutamate release in the amygdala and a modest but significant release in the insular cortex. Moreover, CTA can be elicited by intra-amygdalar microinjections of glutamate; consequently, when glutamate is administered just before the presentation of a weak US, a clear CTA is induced. In contrast, the injection of glutamate alone or glutamate 2 h after the suboptimal US did not have any effect on the acquisition of CTA. These results indicate that glutamate activation of the amygdala can partially substitute the US in CTA, thus providing a clear indication that the amygdala conveys visceral information for this kind of memory.}, } @article {pmid12151802, year = {2002}, author = {Wirth, MM and Olszewski, PK and Levine, AS and Giraudo, SQ}, title = {Effect of Agouti-related protein on development of conditioned taste aversion and oxytocin neuronal activation.}, journal = {Neuroreport}, volume = {13}, number = {10}, pages = {1355-1358}, doi = {10.1097/00001756-200207190-00028}, pmid = {12151802}, issn = {0959-4965}, support = {DK 50456/DK/NIDDK NIH HHS/United States ; DK 59836/DK/NIDDK NIH HHS/United States ; }, mesh = {Agouti Signaling Protein ; Agouti-Related Protein ; Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Psychological/drug effects ; Hypothalamus, Anterior/cytology ; Injections, Intraventricular ; *Intercellular Signaling Peptides and Proteins ; Lithium Chloride/pharmacology ; Male ; Neurons/*chemistry/*drug effects ; Oxytocin/*analysis ; Paraventricular Hypothalamic Nucleus/cytology ; Proteins/*pharmacology ; Proto-Oncogene Proteins c-fos/analysis ; Rats ; Rats, Sprague-Dawley ; Taste ; }, abstract = {Agouti-related protein (Agrp) is an orexigenic peptide that acts as an antagonist of the melanocortin-3 and -4 receptors. Initial studies suggest similarities between the effects of Agrp and opioid peptides on ingestive behavior. Given these observations, we examined whether Agrp, similarly to opioids, alleviates conditioned taste aversion (CTA) generated by peripheral injection of LiCl. Agrp (1 nmol) delivered to the lateral cerebral ventricle, a dose known to cause orexigenic effects, was shown to partially block acquisition of LiCl-induced CTA. Agrp also decreased the percentage of c-Fos-positive oxytocin neurons induced by LiCl in the hypothalamic paraventricular and supraoptic nuclei. Inhibitory effects of Agrp on acquisition of CTA and aversion-associated activation of oxytocin neurons parallel what has previously been shown with opioid receptor agonists.}, } @article {pmid12141132, year = {2002}, author = {De la Casa, LG and Lubow, RE}, title = {An empirical analysis of the super-latent inhibition effect.}, journal = {Animal learning & behavior}, volume = {30}, number = {2}, pages = {112-120}, pmid = {12141132}, issn = {0090-4996}, mesh = {Animals ; *Association Learning ; Attention ; *Avoidance Learning ; *Conditioning, Classical ; *Inhibition, Psychological ; Male ; Mental Recall ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {In three conditioned taste aversion experiments, we examined the roles of several variables in producing super-latent inhibition (LI). This effect, greater LI after a long interval than after a short interval between the conditioning and the test stages (De la Casa & Lubow, 2000), was shown to increase with the number of stimulus preexposures (0, 2, or 4; Experiment 1) and with the length of the delay interval (1, 7, 14, or 21 days; Experiment 2). Furthermore, super-LI was obtained when the delay interval was introduced between the conditioning and the test stages (Experiments 1 and 2), but not when it was introduced between the preexposure and the conditioning stages (Experiment 3). The results are discussed in relation to interference explanations of LI.}, } @article {pmid12139926, year = {2002}, author = {Howe, DG and Wiley, JC and McKnight, GS}, title = {Molecular and behavioral effects of a null mutation in all PKA C beta isoforms.}, journal = {Molecular and cellular neurosciences}, volume = {20}, number = {3}, pages = {515-524}, doi = {10.1006/mcne.2002.1119}, pmid = {12139926}, issn = {1044-7431}, support = {1 F32 AG05884-01A1/AG/NIA NIH HHS/United States ; GM82375/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Brain/enzymology ; Conditioning, Psychological/physiology ; Cues ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits ; Cyclic AMP-Dependent Protein Kinases/*genetics/*physiology ; Fear/*physiology/psychology ; *Gene Deletion ; Isoenzymes/*deficiency/*genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/genetics ; Protein Subunits ; Taste/genetics/physiology ; }, abstract = {The cAMP-dependent protein kinase (PKA) Cbeta gene encodes three isoforms, two of which (Cbeta2 and Cbeta3) are transcribed from neural-specific promoters. Here we report the effects of knocking out all PKA Cbeta subunit isoforms in mice. Total PKA activity was unaffected in the hippocampus and amygdala, while basal PKA activity was reduced by 26% in the brains of Cbetaall(-/-) mice despite a compensatory increase in Calpha protein. Cued fear conditioning was disrupted in Cbetaall(-/-) mice when tested on a mixed C57BL/6/129 background but was indistinguishable from wild type mice when bred onto a 98% C57BL/6 background. This suggests an amygdala-specific deficit in the Cbetaall null mice that is sensitive to strain-specific genetic modifiers. Behavioral testing including locomotor activity, contextual fear conditioning, and conditioned taste aversion was normal in Cbetaall null mice on the 50% C57BL/6J background. We conclude that Cbeta protein is not essential for neuronal development or function but may play a more subtle role in memory that is modulated by strain-specific genetic modifiers.}, } @article {pmid12126646, year = {2002}, author = {Agnello, D and Wang, H and Yang, H and Tracey, KJ and Ghezzi, P}, title = {HMGB-1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion.}, journal = {Cytokine}, volume = {18}, number = {4}, pages = {231-236}, doi = {10.1006/cyto.2002.0890}, pmid = {12126646}, issn = {1043-4666}, mesh = {Animals ; Anorexia ; Appetite ; Body Weight ; Brain/*metabolism ; Cerebral Ventricles/metabolism ; Cytokines/metabolism ; Eating ; HMGB1 Protein/metabolism/*physiology ; Interleukin-6/*metabolism ; Male ; Mice ; Mice, Inbred C3H ; Taste ; Time Factors ; Tumor Necrosis Factor-alpha/*metabolism ; }, abstract = {High-mobility group protein-1 (HMG-1 also termed HMGB-1), a DNA-binding protein, regulates gene transcription and stabilizes nucleosome formation. HMG-1 was recently implicated as a cytokine, because it is a late-acting mediator of endotoxin lethality that induces the release of pro-inflammatory cytokines from monocytes. Here it is shown that administration of HMG-1 into the cerebral ventricles decreases food intake (food intake=4.6g/mouse in controls vs 1.6g/mouse after 1 microg HMG-1 i.c.v.; P <0.05). Intracerebroventricular HMG-1 induced an increased in TNF and IL-6 expression in the brain, and mediated taste aversion with potencies equivalent to LPS. In a model of endotoxemia, passive immunization with anti-HMG-1 antibodies attenuated the development of hypophagia, indicating that HMG-1 is a mediator of sickness behaviour associated with endotoxemia.}, } @article {pmid12121849, year = {2002}, author = {Wang, C and Kotz, CM}, title = {Urocortin in the lateral septal area modulates feeding induced by orexin A in the lateral hypothalamus.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {283}, number = {2}, pages = {R358-67}, doi = {10.1152/ajpregu.00558.2001}, pmid = {12121849}, issn = {0363-6119}, mesh = {Animals ; Appetite Regulation/drug effects/physiology ; Behavior, Animal/drug effects ; Carrier Proteins/administration & dosage/*pharmacology ; Choice Behavior/drug effects ; Corticotropin-Releasing Hormone/administration & dosage/*pharmacology ; Feeding Behavior/*drug effects ; Food Deprivation/physiology ; Hypothalamus/*drug effects/physiology ; *Intracellular Signaling Peptides and Proteins ; Male ; Microinjections ; Neuropeptides/administration & dosage/*pharmacology ; Orexin Receptors ; Orexins ; Rats ; Rats, Sprague-Dawley ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors ; Receptors, G-Protein-Coupled ; Receptors, Neuropeptide ; Saccharin/pharmacology ; Septum of Brain/*drug effects/physiology ; Taste/physiology ; Urocortins ; }, abstract = {The intermediate portion of the lateral septum (LSi) contains high levels of urocortin (UCN) peptide and type 2 corticotropin-releasing hormone (CRH) receptor (CRHR2) and has anatomic and functional connections with the lateral hypothalamus (LH). We tested the effect of UCN in the LSi on feeding. Injection of 10 or 30 pmol UCN into LSi significantly decreased feeding in food-deprived rats for 24 h without producing conditioned taste aversion (CTA). Pretreatment with a CRH receptor antagonist, alpha-helical CRH (alpha-hCRH), blocked the inhibitory effect of UCN on deprivation-induced feeding at 1 and 2 h postinjection. Furthermore, UCN in the LSi significantly decreased feeding induced by LH-injected orexin A at 2 and 4 h postinjection, and addition of alpha-hCRH blocked the inhibitory effect of UCN on orexin A-induced feeding. In conclusion, UCN significantly inhibits feeding induced by deprivation and LH-injected orexin A without producing a CTA, an effect that is mediated by CRHR2. These data define the LSi as an important site for UCN-induced anorexia and indicate that LSi UCN may influence orexin A feeding signals in the LH.}, } @article {pmid12121820, year = {2002}, author = {Trifunovic, R and Reilly, S}, title = {Medial versus lateral parabrachial nucleus lesions in the rat: effects on mercaptoacetate-induced feeding and conditioned taste aversion.}, journal = {Brain research bulletin}, volume = {58}, number = {1}, pages = {107-113}, doi = {10.1016/s0361-9230(02)00766-9}, pmid = {12121820}, issn = {0361-9230}, support = {DC02821/DC/NIDCD NIH HHS/United States ; DC04341/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Denervation ; Excitatory Amino Acid Agonists ; Feeding Behavior/*drug effects ; Ibotenic Acid ; Male ; Pons/*drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; Thioglycolates/*pharmacology ; }, abstract = {The two experiments of the present study examined the influence of bilateral electrophysiologically-guided ibotenic acid lesions of the medial (gustatory) and lateral (viscerosensory) subdivisions of the parabrachial nucleus (PBN) on lipoprivic feeding and on the acquisition of a conditioned taste aversion. In Experiment 1, mercaptoacetate (0, 400, 600, or 800 micromol/kg) failed to enhance food intake in normal rats maintained and tested on standard laboratory chow. In the same procedure, rats with lesions of the medial or lateral PBN consumed less food during baseline but nonetheless were sensitive to the orexigenic action of mercaptoacetate. In Experiment 2, both types of PBN lesions prevented acquisition of a conditioned taste aversion induced by the oral self administration of lithium chloride. The results suggest that PBN neurons essential for conditioned taste aversion are not involved in the mercaptoacetate-induced feeding of rats maintained and tested on standard laboratory chow.}, } @article {pmid12110445, year = {2002}, author = {Ward-Robinson, J and Wilton, LA and Muir, JL and Honey, RC and Vann, SD and Aggleton, JP}, title = {Sensory preconditioning in rats with lesions of the anterior thalamic nuclei: evidence for intact nonspatial 'relational' processing.}, journal = {Behavioural brain research}, volume = {133}, number = {2}, pages = {125-133}, doi = {10.1016/s0166-4328(01)00465-x}, pmid = {12110445}, issn = {0166-4328}, mesh = {Acoustic Stimulation ; Animals ; Anterior Thalamic Nuclei/anatomy & histology/*physiology ; Conditioning, Operant/*physiology ; Electroshock ; Hot Temperature ; Male ; Maze Learning/physiology ; Rats ; Space Perception/*physiology ; Taste/physiology ; }, abstract = {Rats with neurotoxic lesions centered in the anterior thalamic nuclei were trained in two versions of a nonspatial, sensory preconditioning procedure. In both versions, two stimulus compounds (AX and BY) were first presented and then X, but not Y, was paired with an aversive unconditioned stimulus. This procedure resulted in greater conditioned responding to A than B. Anterior thalamic lesions had no apparent effect on these two examples of sensory preconditioning, nor did they affect fear conditioning or conditioned taste aversion. In contrast, the same lesions led to a severe deficit on a test of spatial memory. These results help to refine our understanding of the contribution of the anterior thalamic nuclei to spatial memory.}, } @article {pmid12093887, year = {2002}, author = {Yamamoto, H and Lee, CE and Marcus, JN and Williams, TD and Overton, JM and Lopez, ME and Hollenberg, AN and Baggio, L and Saper, CB and Drucker, DJ and Elmquist, JK}, title = {Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons.}, journal = {The Journal of clinical investigation}, volume = {110}, number = {1}, pages = {43-52}, pmid = {12093887}, issn = {0021-9738}, support = {P01 DK056116/DK/NIDDK NIH HHS/United States ; DK 56116/DK/NIDDK NIH HHS/United States ; DK 59751/DK/NIDDK NIH HHS/United States ; }, mesh = {Adrenal Glands/anatomy & histology/drug effects/metabolism ; Animals ; Autonomic Nervous System/drug effects/*physiology ; Blood Pressure/drug effects/*physiology ; Brain/anatomy & histology/drug effects/metabolism ; Catecholamines/metabolism ; Exenatide ; Glucagon-Like Peptide-1 Receptor ; Heart Rate/drug effects/*physiology ; Male ; Models, Neurological ; Neural Pathways/drug effects/physiology ; Peptides/pharmacology ; Proto-Oncogene Proteins c-fos/biosynthesis ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucagon/*agonists/*physiology ; Spinal Cord/anatomy & histology/drug effects/metabolism ; *Venoms ; }, abstract = {Glucagon-like peptide-1 (GLP-1) released from the gut functions as an incretin that stimulates insulin secretion. GLP-1 is also a brain neuropeptide that controls feeding and drinking behavior and gastric emptying and elicits neuroendocrine responses including development of conditioned taste aversion. Although GLP-1 receptor (GLP-1R) agonists are under development for the treatment of diabetes, GLP-1 administration may increase blood pressure and heart rate in vivo. We report here that centrally and peripherally administered GLP-1R agonists dose-dependently increased blood pressure and heart rate. GLP-1R activation induced c-fos expression in the adrenal medulla and neurons in autonomic control sites in the rat brain, including medullary catecholamine neurons providing input to sympathetic preganglionic neurons. Furthermore, GLP-1R agonists rapidly activated tyrosine hydroxylase transcription in brainstem catecholamine neurons. These findings suggest that the central GLP-1 system represents a regulator of sympathetic outflow leading to downstream activation of cardiovascular responses in vivo.}, } @article {pmid12090509, year = {2002}, author = {Hinderliter, CF and Goodhart, M and Anderson, MJ and Misanin, JR}, title = {Extended lowered body temperature increases the effective CS-US interval in conditioned taste aversion for adult rats.}, journal = {Psychological reports}, volume = {90}, number = {3 Pt 1}, pages = {800-802}, doi = {10.2466/pr0.2002.90.3.800}, pmid = {12090509}, issn = {0033-2941}, mesh = {Animals ; *Avoidance Learning ; Behavior, Animal ; *Conditioning, Classical ; *Hypothermia, Induced ; Male ; Random Allocation ; Rats ; Rats, Wistar ; *Taste ; Time Factors ; }, abstract = {Assuming body temperature correlates with metabolic activities, rate of body temperature recovery was manipulated to assess effects on long-trace conditioning in a conditioned taste-aversion paradigm. Following 10 min. access to a .1% saccharin solution and then 10 min. immersion in 0-0.5 degrees C water, two groups of 16 Wistar-derived, 81-113 day-old, male albino rats received either saline or lithium chloride injections 3 hr. later. These two groups were subdivided on basis of warming rate during the 3-hr. interval. Half of the rats recovered at room temperature (20 degrees to 21 degrees C), and half recovered in an incubator maintained at 30 degrees C. Maintaining a lowered body temperature between the conditioned stimulus and unconditioned stimulus allowed an association to be made at 3 hr., an interval that normally does not support conditioning. In contrast, lowering body temperature and then inducing a fast warming rate did not produce evidence of an aversion. It is suggested that maintaining a low body temperature over the interval between the presentation of the conditioned stimulus and unconditioned stimulus slows a metabolic clock that extends the measured interval at which associations can be made using conditioned taste-aversion procedures.}, } @article {pmid12084531, year = {2002}, author = {Rushing, PA and Seeley, RJ and Air, EL and Lutz, TA and Woods, SC}, title = {Acute 3rd-ventricular amylin infusion potently reduces food intake but does not produce aversive consequences.}, journal = {Peptides}, volume = {23}, number = {5}, pages = {985-988}, doi = {10.1016/s0196-9781(02)00022-0}, pmid = {12084531}, issn = {0196-9781}, support = {DK17844/DK/NIDDK NIH HHS/United States ; DK54080/DK/NIDDK NIH HHS/United States ; }, mesh = {Amyloid/*administration & dosage/adverse effects/*pharmacology ; Animals ; Appetite Depressants/administration & dosage/adverse effects/pharmacology ; Conditioning, Psychological ; Energy Metabolism ; Feeding Behavior/*drug effects/psychology ; Injections, Intraperitoneal ; Islet Amyloid Polypeptide ; Lithium Chloride/administration & dosage/pharmacology ; Male ; Rats ; Rats, Long-Evans ; Saccharin/administration & dosage/pharmacology ; Taste/physiology ; Time Factors ; }, abstract = {In this study, a conditioned taste aversion (CTA) paradigm was used to assess the possibility that 3rd-ventricular (i3vt) administration of the pancreatic hormone amylin produces aversive consequences that secondarily reduce food intake independently of the normal regulation of energy balance. After 1-h daily access to water for 7 days, rats were given 1-h access to a 0.15% saccharin solution, followed immediately by i3vt amylin (100 pmol) in one group (n=7) and i3vt CSF vehicle in another (n=7). As positive control for the formation of a CTA, a third group of seven rats received intraperitonial (i.p.) lithium chloride (LiCl). Saline was given i.p. to a fourth group (n=7) as control for i.p. LiCl. As expected, the LiCl rats exhibited a marked aversion to the saccharin in a subsequent two-bottle intake test. In contrast, although the 100 pmol i3vt amylin dose is substantially higher than that required to reduce food intake, no evidence of a CTA was observed in the rats that had received i3vt amylin. In summary, these data are consistent with the conclusion that acute i3vt amylin infusion does not reduce food intake by producing aversive consequences.}, } @article {pmid12062321, year = {2002}, author = {Sederholm, F and Ammar, AA and Södersten, P}, title = {Intake inhibition by NPY: role of appetitive ingestive behavior and aversion.}, journal = {Physiology & behavior}, volume = {75}, number = {4}, pages = {567-575}, doi = {10.1016/s0031-9384(02)00648-0}, pmid = {12062321}, issn = {0031-9384}, mesh = {Animals ; Appetite Stimulants/*pharmacology ; Appetitive Behavior/*drug effects ; Drinking Behavior/drug effects ; Eating/drug effects ; Female ; Injections, Intraventricular ; Male ; Neuropeptide Y/adverse effects/*pharmacology ; Quinine/pharmacology ; Rats ; Rats, Wistar ; Sexual Behavior, Animal/*drug effects ; Sucrose/pharmacology ; Taste/drug effects ; }, abstract = {Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of times the rats visit a bottle filled with sucrose (appetitive behavior). In this study, we investigated if the suppression of consummatory behavior was dependent upon the increase of appetitive behavior. The shift from consummatory to appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to the sucrose solution in the bottle. However, the intraoral intake of the sucrose solution was still decreased in NPY-treated rats. NPY did not modify taste reactivity as measured by aversive responses during continuous intraoral infusion of sucrose or ingestive and aversive responses to brief intraoral infusion of sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a bottle and intake from the bottle and inhibited sexual behavior in male rats but had no effect on the sexual behavior in the absence of a bottle. The visits and the intake were suppressed, but sexual behavior was not activated by adding QHCl (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior, therefore, does not indiscriminately facilitate consummatory behavior. Male rats showed aversive or ingestive behavior and sexual behavior simultaneously during intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases intraoral intake and increases appetitive ingestive behavior via partially separable mechanisms that are independent of taste aversion.}, } @article {pmid12057778, year = {2002}, author = {Brunetti, G and Carai, MA and Lobina, C and Melis, S and Serra, S and Vacca, G and Gessa, GL and Colombo, G}, title = {Differences in ethanol-induced conditioned taste aversion in Sardinian alcohol-preferring and Sardinian alcohol-nonpreferring rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {26}, number = {3}, pages = {167-172}, doi = {10.1016/s0741-8329(02)00195-7}, pmid = {12057778}, issn = {0741-8329}, mesh = {Alcohol Drinking/blood/*genetics ; Animals ; Avoidance Learning/*drug effects/physiology ; Choice Behavior/physiology ; Conditioning, Psychological/*drug effects/physiology ; Ethanol/blood/*pharmacology ; Male ; Rats ; Saccharin/pharmacology ; Species Specificity ; }, abstract = {In the present study, we investigated whether aversion to the pharmacological effects of ethanol developed to a differential extent in selectively bred Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats, and whether this different response was consistent with their genetically determined differences in ethanol preference and consumption. To this purpose, a conditioned taste aversion paradigm was used. Male sP and sNP rats were exposed to five sessions in which a 20-min availability of a saccharin solution (1 g/l) was paired to the injection of ethanol (0, 0.5, or 1 g/kg, i.p.), delivered immediately after removal of the saccharin bottle (conditioning phase). Subsequently, the choice between saccharin solution and water was offered for 18 consecutive daily 20-min sessions (postconditioning phase). Ethanol at 1g/kg produced a marked aversion to saccharin in sNP rats: The reduction in saccharin intake was already evident on the second day of the conditioning phase and lasted for 15 days of the postconditioning phase. In contrast, this dose of ethanol elicited a modest, if any, conditioned taste aversion in sP rats, although blood ethanol levels were comparable to those assessed in sNP rats. These results indicate the existence of a differential degree of aversion to the postingestional effects of ethanol between sP and sNP rats, and support the suggestion that it may contribute, at least in part, to the opposite preference for and consumption of ethanol monitored in these rat lines.}, } @article {pmid12057774, year = {2002}, author = {Chester, JA and Cunningham, CL}, title = {GABA(A) receptor modulation of the rewarding and aversive effects of ethanol.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {26}, number = {3}, pages = {131-143}, doi = {10.1016/s0741-8329(02)00199-4}, pmid = {12057774}, issn = {0741-8329}, support = {AA05489/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Ethanol/adverse effects/*pharmacology ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; Humans ; Receptors, GABA-A/*physiology ; *Reward ; }, abstract = {Ethanol has been shown to exert many of its biochemical and behavioral effects through an interaction with the gamma-aminobutyric acid (GABA) receptor system. This review focuses on a subset of studies that has used self-administration, as well as place and taste conditioning, procedures to investigate a role for the GABA(A) receptor system in modulating the rewarding and aversive effects of ethanol. Potential advantages and disadvantages of each procedure are also discussed. A significant amount of evidence supports the suggestion that GABA(A) receptors are important modulators of the motivational effects of ethanol, although most of the findings have been obtained from studies examining oral ethanol self-administration. Relatively fewer studies have investigated ethanol place and taste conditioning. All self-administration studies reviewed used rats, whereas most conditioning studies used mice. Results of these studies show that GABA(A) antagonists and inverse agonists reduce ethanol self-administration under limited-access conditions. The effect of GABA(A) agonists on ethanol self-administration is less clear due to their bidirectional effects. GABA(A) receptor antagonists have been shown to increase ethanol-induced conditioned place preference and conditioned taste aversion in mice and decrease ethanol-induced conditioned taste aversion in rats. Issues related to interpretation and integration of these findings across models and species are considered. The integration of data from self-administration and conditioning procedures is necessary to define the role of GABA(A) receptors in modulating the rewarding and aversive effects of ethanol and may lead to the development of pharmacotherapies that target GABA(A) receptors to treat alcoholism in human beings.}, } @article {pmid12041874, year = {2002}, author = {Scalera, G}, title = {Effects of conditioned food aversions on nutritional behavior in humans.}, journal = {Nutritional neuroscience}, volume = {5}, number = {3}, pages = {159-188}, doi = {10.1080/10284150290013059}, pmid = {12041874}, issn = {1028-415X}, mesh = {Alcoholism/therapy ; Animals ; *Behavior ; Brain/physiology ; *Conditioning, Psychological ; Food Preferences/*psychology ; Humans ; Neoplasms/physiopathology ; *Nutritional Physiological Phenomena ; Taste ; }, abstract = {Conditioned food aversion (CFA) and taste aversion (CTA) are widely occurring phenomena mediating rejection of solids or liquids, the ingestion of which has induced the onset of post-ingestional malaise. It is a powerful and durable imprint learning that may influence food choice and intake in all animals, including humans. For ethical reasons, CTA has been extensively investigated in a wide variety of laboratory animal's species but only incidentally in humans. Nevertheless, convincing evidence has been provided that CFA and CTA learning are possible in a wide range of human subjects. The results in humans may have some limitations in accuracy since data are sparse, sometimes indirect, and poorly controlled. There is only limited information on the extent of CFA in the elderly since most studies have employed questionnaire and/or interview methods on young people (i.e. college students). The present review evaluates the literature derived both from laboratory animals and humans. In the first instance, the salient features of food and taste aversion learning and the neural mechanisms involved in this learning behavior will be examined. Then, the problems encountered when trying to assess the role of learned food and taste aversions in the nutritional status of healthy as well as sick young or elderly people will be considered. In particular, the importance of CFA on the nutritional status of cancer patients and treatment of alcoholism will be examined. It is concluded that the data are compelling enough to warrant further research and, some indications and recommendations are suggested.}, } @article {pmid12038496, year = {2002}, author = {Lambert, JV and Whitehouse, WG}, title = {Conditioned inhibition of cyclophosphamide-induced taste aversion.}, journal = {The Journal of general psychology}, volume = {129}, number = {1}, pages = {68-75}, doi = {10.1080/00221300209602033}, pmid = {12038496}, issn = {0022-1309}, mesh = {Analysis of Variance ; Animals ; *Conditioning, Classical ; *Cyclophosphamide ; Depression/immunology ; *Immunosuppressive Agents ; *Inhibition, Psychological ; Male ; Psychoneuroimmunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Statistics, Nonparametric ; *Taste ; }, abstract = {Rats in an experimental group received trials during which 1 flavor (saccharin) was always followed by cyclophosphamide, an immunosuppressive drug, but another (vanilla) was not. An unconditioned stimulus-only group served as a control. Flavor-preference tests revealed that conditioned excitation and conditioned inhibition occurred in the conditioned group subjects but not in the control group subjects. This demonstration suggests that a conditioned inhibitor might be used to modify conditioned and unconditioned immune system functions, for example, natural killer-cell activity.}, } @article {pmid12022178, year = {1999}, author = {Wang, SP and Liu, XM and Shang, WF and Song, J and Yu, SR and Sun, SM}, title = {[Effect of Gastrodia on rotation induced motion sickness in mice].}, journal = {Hang tian yi xue yu yi xue gong cheng = Space medicine & medical engineering}, volume = {12}, number = {5}, pages = {342-345}, pmid = {12022178}, issn = {1002-0837}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal/pharmacology/*therapeutic use ; Free Radical Scavengers/pharmacology/*therapeutic use ; Maze Learning/drug effects ; Mice ; Motion Sickness/*drug therapy/etiology ; Motor Activity/drug effects ; Rotation/*adverse effects ; Spatial Behavior/drug effects ; Taste/drug effects ; Water ; }, abstract = {OBJECTIVE: To observe the effect of Gastrodia on motion sickness induced by rotation in mice.

METHOD: Clockwise and anticlockwise accelerated rotations up to 180 degrees/s for 10 min were used to induce symptoms of motion sickness such as condition taste aversion (CTA), decrease of spontaneous locomotion and impaired ability of space identification in water-maze.

RESULT: Gastrodia could improve the response of CTA, increase spontaneous locomotion, and enhance the ability of learning and memory in water-maze in mice after the rotation.

CONCLUSION: Symptoms of motion sickness induced by rotation could be improved by Gastrodia treatment.}, } @article {pmid12020741, year = {2002}, author = {Misanin, JR and Collins, M and Rushanan, S and Anderson, MJ and Goodhart, M and Hinderliter, CF}, title = {Aging facilitates long-trace taste-aversion conditioning in rats.}, journal = {Physiology & behavior}, volume = {75}, number = {5}, pages = {759-764}, doi = {10.1016/s0031-9384(02)00671-6}, pmid = {12020741}, issn = {0031-9384}, mesh = {Aging/*physiology/psychology ; Animals ; Association Learning/drug effects/*physiology ; Conditioning, Operant/drug effects/*physiology ; Female ; Lithium Chloride/administration & dosage ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Taste/*physiology ; Time Factors ; }, abstract = {In order to examine age-related changes in long-trace conditioning, five age groups (0.25, 1, 1.5, 2, and 2.5 years) of Wistar-derived female albino rats were subjected to taste-aversion conditioning at one of five conditioned stimulus-conditioned stimulus (CS-US) intervals (0, 45, 90, 180, and 360 min). Age differences in the strength of the aversion were evident at CS-US intervals greater than 0 min and the strength of the aversion was directly related to age. An aversion was conditioned in only the two oldest age groups when the CS-US interval was 360 min. The age differences in taste-aversion and the superior long-trace conditioning in old-age rats were attributed to factors that accompany aging, for example, the gradual slowing down of a metabolic pacemaker.}, } @article {pmid12007581, year = {2002}, author = {Quintanilla, ME and Callejas, O and Tampier, L}, title = {Aversion to acetaldehyde: differences in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {26}, number = {2}, pages = {69-74}, doi = {10.1016/s0741-8329(01)00197-5}, pmid = {12007581}, issn = {0741-8329}, mesh = {*Acetaldehyde/administration & dosage/blood/pharmacology ; Alcohol Drinking/blood/genetics/*physiopathology ; Animals ; *Avoidance Learning ; Brain/blood supply/metabolism ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Rats ; Rats, Inbred Strains ; Species Specificity ; *Taste/drug effects/physiology ; }, abstract = {We have previously found the existence of a relation between activity of the brain mitochondrial aldehyde dehydrogenase (ALDH2) and consumption of ethanol in rats of the low-alcohol-drinking (UChA) and the high-alcohol-drinking (UChB) strains. The aim of the present study was to determine whether UChA and UChB rats also differed in sensitivity to the aversive effects of acetaldehyde (AcH). Aversion to AcH was studied by using a conditioned taste aversion (CTA) paradigm. Ethanol naive UChA and UChB rats were administered AcH intraperitoneally (50, 100, or 150 mg/kg) or saline and exposed to a banana-flavored solution during five conditioning trials. A strong dose-dependent CTA to AcH was found in UChA rats, whereas UChB rats did not show a CTA to any dose of AcH. At equal doses of AcH, cerebral venous blood AcH levels in UChA rats were consistently higher than in UChB rats, a finding that may reflect the previously observed differences in the activity of ALDH2 between these strains. However, this observation is unlikely to explain fully the differences observed because aversion to AcH was developed in the UChA strain at blood levels of AcH that did not produce any aversion in the UChB strain. These results support the suggestion that, for the first time, differences in central or systemic effects of AcH per se may play a major role in determining the aversion to AcH in drinker and nondrinker animals.}, } @article {pmid12006377, year = {2002}, author = {Stapleton, JR and Luellig, M and Roper, SD and Delay, ER}, title = {Discrimination between the tastes of sucrose and monosodium glutamate in rats.}, journal = {Chemical senses}, volume = {27}, number = {4}, pages = {375-382}, doi = {10.1093/chemse/27.4.375}, pmid = {12006377}, issn = {0379-864X}, support = {DC03013/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/pharmacology ; Animals ; Discrimination Learning/drug effects ; Discrimination, Psychological/*drug effects ; Diuretics/pharmacology ; Electroshock ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Glutamate/*pharmacology ; Sucrose/*pharmacology ; Taste/*drug effects ; Taste Threshold/drug effects ; }, abstract = {Conditioned taste aversion studies have demonstrated that rats conditioned to avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of the sodium component of MSG taste, will generalize an aversion for MSG to sucrose and vice versa. This suggests that taste transduction for sodium, sucrose and MSG may intersect at some point. Generalization of conditioned taste aversion indicates that two substances share similar taste features, but it does not reveal the extent of their differences. In this study, we tested how well rats can discriminate sucrose and MSG under a variety of conditions. Water-deprived rats were trained on a combination of water reinforcement and shock avoidance to discriminate between MSG and sucrose, both with and without amiloride, and with and without equimolar NaCl in all solutions. In the absence of amiloride, rats reliably distinguished between MSG and sucrose down to 10 mM solutions. However, they could correctly identify solutions only above 50 mM in the presence of amiloride, equimolar sodium chloride, or both. These results suggest that gustatory stimulation by MSG and sucrose interact somewhere in taste transduction, perhaps within taste receptor cells or gustatory afferent pathways.}, } @article {pmid11958542, year = {2002}, author = {Bielavská, E and Kren, V and Musilová, A and Zídek, V and Pravenec, M}, title = {Genome scanning of the HXB/BXH sets of recombinant inbred strains of the rat for quantitative trait loci associated with conditioned taste aversion.}, journal = {Behavior genetics}, volume = {32}, number = {1}, pages = {51-56}, doi = {10.1023/a:1014407928865}, pmid = {11958542}, issn = {0001-8244}, mesh = {Animals ; Avoidance Learning/*physiology ; *Chromosome Mapping ; Conditioning, Classical/*physiology ; Genetic Markers/genetics ; Male ; *Quantitative Trait, Heritable ; Rats ; Rats, Inbred BN ; Rats, Inbred SHR ; Recombination, Genetic/*genetics ; Taste/*genetics ; }, abstract = {In the current study, we searched for quantitative trait loci (QTL) responsible for a conditioned taste aversion (CTA) measured as a decrease in the intake of a saccharin conditioned stimulus followed by an i.p. injection of 0.15 M LiCl (lithium chloride) (2 ml/100 g body weight). A genome scanning for QTL associated with CTA was performed in the HXB/BXH sets of recombinant inbred (RI) strains derived from the Brown Norway (BN-Lx) rat and the spontaneously hypertensive rat (SHR). The BN-Lx progenitor showed a significantly stronger CTA (8.3+/-2.8%) than the SHR progenitor (27.8+/-3.3%, p < .0001). The distribution of CTA values among RI strains was continuous, suggesting a polygenic mode of inheritance. Genome scanning of RI strains with more than 700 gene markers revealed a significant association of CTA with the D2Cebr11s4 marker on chromosome 2 (LRS = 22.7) and with the D4Cebrp149s8 marker on chromosome 4 (LRS = 23.4). The chromosome 2 putative QTL was confirmed by detecting a significant difference in CTA between the SHR progenitor (27.8+/-3.3%) and the SHR-2 (SHR.BN-D2Rat171/D2Arb24) congenic strain (13.1+/-4.4%, p < .01) that are genetically identical except for a segment of chromosome 2 that was transferred onto the genetic background of the SHR from the BN strain.}, } @article {pmid11955523, year = {2002}, author = {Shoaib, M and Gommans, J and Morley, A and Stolerman, IP and Grailhe, R and Changeux, JP}, title = {The role of nicotinic receptor beta-2 subunits in nicotine discrimination and conditioned taste aversion.}, journal = {Neuropharmacology}, volume = {42}, number = {4}, pages = {530-539}, doi = {10.1016/s0028-3908(01)00194-0}, pmid = {11955523}, issn = {0028-3908}, mesh = {Animals ; Conditioning, Psychological/*drug effects/physiology ; Discrimination, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nicotine/*pharmacology ; Nicotinic Agonists/pharmacology ; Receptors, Nicotinic/*deficiency/genetics/*physiology ; Taste/*drug effects/physiology ; }, abstract = {The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. These experiments use mice lacking the beta2 subunit of nicotinic receptors to investigate its role in nicotine discrimination and conditioned taste aversion (CTA). Wild-type and mutant mice were trained either in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement, or in a counterbalanced two-flavour CTA procedure. Rates of lever-pressing of wild-type and mutant mice did not differ. Wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) rapidly and exhibited steep dose-response curves. Mutant mice failed to acquire these nicotine discriminations and exhibited flat dose-response curves. Both wild-type and mutant mice acquired discrimination of nicotine (1.6 mg/kg) although discrimination performance was weak in the mutants. Nicotine initially reduced response rates in wild-type and mutant mice, and tolerance developed to this effect in each genotype. Both genotypes acquired discrimination of morphine (3 mg/kg) with similar degrees of accuracy, and dose-response curves for morphine discrimination in the two genotypes were indistinguishable. Nicotine produced dose-related CTA in both genotypes, but the magnitude of the effect was less in the mutants than in the wild-type controls. It is concluded that nicotinic receptors containing the beta2 subunit play a major role in the discriminative stimulus and taste aversion effects of nicotine that may reflect psychological aspects of tobacco dependence. Such receptors appear to have a less crucial role in the response-rate, reducing effects of nicotine and in nicotine tolerance.}, } @article {pmid11954557, year = {2002}, author = {Selcher, JC and Weeber, EJ and Varga, AW and Sweatt, JD and Swank, M}, title = {Protein kinase signal transduction cascades in mammalian associative conditioning.}, journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, volume = {8}, number = {2}, pages = {122-131}, doi = {10.1177/107385840200800208}, pmid = {11954557}, issn = {1073-8584}, support = {HD24064/HD/NICHD NIH HHS/United States ; MH57014/MH/NIMH NIH HHS/United States ; NS37444/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Brain/enzymology ; Conditioning, Psychological/*physiology ; Humans ; Mammals/*physiology ; Protein Kinases/*physiology ; Signal Transduction/*physiology ; }, abstract = {One of the most intriguing and intensely studied questions facing contemporary neuroscientists involves the elucidation of the physiological mechanisms that underlie learning and memory. Recent advances have given us a much more detailed understanding of the signal transduction mechanisms subserving learning in the intact animal. One fact that has become clear is that activation of protein kinases and phosphorylation of their downstream effectors play a critical role. Four protein kinase cascades have garnered considerable attention in the study of information storage at both the synaptic and behavioral levels: Ca++/phospholipid-dependent protein kinase (PKC), Ca++/calmodulin-dependent protein kinase II (CaMKII), cAMP-dependent protein kinase (PKA), and extracellular signal-regulated kinase (ERK). This review will concentrate on studies of two behavioral tasks, conditioned fear and conditioned taste aversion, that provide evidence for the involvement of these kinase systems in associative learning. The authors will also examine a number of potential kinase substrates and how each could participate in the formation of long-term memories.}, } @article {pmid11925064, year = {2002}, author = {Cailhol, S and Mormède, P}, title = {Conditioned taste aversion and alcohol drinking: strain and gender differences.}, journal = {Journal of studies on alcohol}, volume = {63}, number = {1}, pages = {91-99}, pmid = {11925064}, issn = {0096-882X}, mesh = {Administration, Oral ; Alcohol Drinking/*genetics ; Animals ; Avoidance Learning/drug effects/*physiology ; Central Nervous System Depressants/administration & dosage ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage ; Female ; Male ; Rats ; Rats, Inbred WKY ; Saccharin/administration & dosage ; Self Administration ; *Sex Characteristics ; Species Specificity ; Taste/*physiology ; }, abstract = {OBJECTIVE: The present study examined the relationship between ethanol-induced conditioned taste aversion (CTA) and ethanol oral self-administration (OSA) in male and female rats (N = 183) from three related strains not genetically selected for their ethanol preference and differing in their emotional reactivity profile. The strains used were the Wistar Kyoto (WKY), Spontaneously Hypertensive (SHR) and Wistar Kyoto Hyperactive (WKHA). We hypothesized that differences between strains in sensitivity to the aversive properties of alcohol could explain the different propensities to drink alcohol solutions.

METHOD: All animals were given three conditioning trials consisting of 20-minute access to saccharin solution followed by saline or ethanol injections (0.5, 1 or 1.5 g/kg, intraperitoneally). Animals subsequently had free access to ethanol OSA for 3 weeks, followed by two CTA trials.

RESULTS: Ethanol injections produce a dose-dependent reduction of saccharin consumption in all animals; moreover, the strength of the CTA is gender- and strain-dependent. Taste avoidance induced by ethanol injections disturbed the initiation of ethanol OSA in two strains (WKY and WKHA) but did not change subsequent long-term ethanol consumption in either strain. In addition, voluntary alcohol drinking experience does not attenuate ethanol-induced CTA, and no association was found between ethanol-induced CTA and ethanol OSA.

CONCLUSIONS: The data confirm the large variation among strains and between genders in alcohol drinking and taste-aversion learning, but suggest that there is no relationship between the sensitivity to the aversive properties of alcohol and alcohol drinking.}, } @article {pmid11919669, year = {2002}, author = {Cunningham, CL and Tull, LE and Rindal, KE and Meyer, PJ}, title = {Distal and proximal pre-exposure to ethanol in the place conditioning task: tolerance to aversive effect, sensitization to activating effect, but no change in rewarding effect.}, journal = {Psychopharmacology}, volume = {160}, number = {4}, pages = {414-424}, doi = {10.1007/s00213-001-0990-1}, pmid = {11919669}, issn = {0033-3158}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Central Nervous System Depressants/administration & dosage ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Drug Tolerance/*physiology ; Ethanol/*administration & dosage ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred DBA ; Motor Activity/*drug effects/physiology ; *Reward ; }, abstract = {RATIONALE: The literature offers many examples of tolerance to ethanol's inhibitory/depressant effects and sensitization to its activating effects. There are also many examples of tolerance to ethanol's aversive effects as measured in the conditioned taste aversion and conditioned place aversion (CPA) procedures. However, there are very few demonstrations of either tolerance or sensitization to ethanol's rewarding or reinforcing effects.

OBJECTIVE: The present studies were designed to examine effects of two forms of ethanol pre-exposure (distal or proximal) on ethanol's rewarding and aversive effects as indexed by the place conditioning procedure.

METHOD: Male inbred (DBA/2J) mice were exposed to ethanol (2 g/kg IP) in an unbiased place conditioning procedure that normally produces either conditioned place preference (CPP) (ethanol injection before CS exposure) or CPA (ethanol injection after CS exposure). In the distal pre-exposure studies (experiments 1 and 2), mice initially received a series of four ethanol injections (0, 2, or 4 g/kg) in the home cage at 48-h intervals during the week before place conditioning. In the proximal pre-exposure studies (experiments 3-4), mice were injected with ethanol 65 min before (experimental groups) or 65 min after (control groups) each paired ethanol injection on CS+ trials.

RESULTS: Distal pre-exposure produced a robust sensitization to ethanol's activating effect, whereas proximal pre-exposure generally reduced the activation normally produced by the paired ethanol injection. Both forms of pre-exposure interfered with CPA, but had no effect on CPP.

CONCLUSIONS: These studies suggest that both forms of pre-exposure reduced ethanol's aversive effect, but had no impact on ethanol's rewarding effect. In general, the detrimental effects of pre-exposure on CPA are explained best in terms of a reduction in ethanol's efficacy as an aversive unconditioned stimulus (i.e. tolerance), although explanations based on other types of associative interference are also possible. The failure to affect CPP with pre-exposure treatments that reduced or eliminated CPA suggests that these behaviors are mediated by independent, motivationally opposite effects of ethanol. Moreover, these results indicate dissociation between sensitization to ethanol's locomotor activating effect and changes in its rewarding effect. To the extent that motivational processes measured by CPP and CPA normally contribute to ethanol drinking, the present findings suggest that increases in ethanol intake seen after chronic ethanol exposure are more likely caused by tolerance to ethanol's aversive effect rather than sensitization to its rewarding or reinforcing effect.}, } @article {pmid11897266, year = {2002}, author = {Yamamoto, J and Fresquet, N and Sandner, G}, title = {Conditioned taste aversion using four different means to deliver sucrose to rats.}, journal = {Physiology & behavior}, volume = {75}, number = {3}, pages = {387-396}, doi = {10.1016/s0031-9384(01)00671-0}, pmid = {11897266}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Drinking/physiology ; Extinction, Psychological/physiology ; Male ; Rats ; Rats, Long-Evans ; Reinforcement, Psychology ; Reproducibility of Results ; Self Administration ; Sucrose/*administration & dosage/*pharmacology ; Taste/physiology ; }, abstract = {A solution of sucrose either to be drunk from a drinking tube-self-drinking procedure (SD)-or perfused intraorally as a consequence of nose-pokes-self-administration procedure (SA)-or perfused as a consequence of licking an empty tube (LA)-was paired with an LiCl-induced malaise in rats. The effects were compared to those of a procedure consisting of intraoral administration (IO) of sucrose not contingent to any specific action of the rat. Similar levels of conditioned taste aversion (CTA) were obtained but extinction in the IO procedure was quicker than in the SA procedure, which was itself quicker than in the SD procedure. Extinctions in the IO and LA procedures resembled one another and were quicker than in the SD procedure. A step towards deciding between several explanatory hypotheses of these differences was made by conducting two more experiments. The third experiment was based on reinstatement, or not, of the conditioning procedure for the test after standard IO extinction. CTA was produced only when SD was used both at conditioning and test. A fourth experiment was based on latent inhibition where the procedure was changed, or not, between preexposure and conditioning. Latent inhibition was absent only when the rats had been preexposed to sucrose with the SA procedure and conditioned with the SD procedure.}, } @article {pmid11897165, year = {2002}, author = {Ballesteros, MA and González, F and Morón, I and DeBrugada, I and Cándido, A and Gallo, M}, title = {Dissociation of the associative and visceral sensory components of taste aversion learning by tetrodotoxin inactivation of the parabrachial nucleus in rats.}, journal = {Neuroscience letters}, volume = {322}, number = {3}, pages = {169-172}, doi = {10.1016/s0304-3940(02)00094-0}, pmid = {11897165}, issn = {0304-3940}, mesh = {Animals ; *Association ; Avoidance Learning/*drug effects ; Brachial Plexus/*physiology ; Drinking/drug effects ; Lithium Chloride ; Male ; Memory/drug effects ; Rats ; Rats, Wistar ; Taste/*drug effects ; Tetrodotoxin/administration & dosage/*pharmacology ; Water Deprivation ; }, abstract = {The parabrachial nucleus (PBN) has been proposed as the associative site for conditioned taste aversion. Previous evidence has shown that functional blockade of the PBN by tetrodotoxin (TTX) produces retrograde disruption of lithium-induced taste aversions in rats. However, given the PBN role in processing visceral cues and the long duration of the lithium-induced aversive effects, an interpretation based on lithium chloride processing deficits can not be ruled out. The aim of the present study was to use the unconditioned stimulus (US) pre-exposure phenomenon to explore the effect of PBN inactivation by intracerebral TTX microinjections on visceral processing. Three intraperitoneal (i.p.) lithium chloride injections (0.15 M; 2% b.w.) applied before the conditioning session, but not isotonic saline i.p. injections, interfered with the acquisition of a learned aversion to a cider vinegar solution (3%) in cannulated control rats. Bilateral PBN inactivation by TTX (10 ng) applied immediately after each LiCl injections disrupted the US pre-exposure effect, thus confirming its sensory role. However, PBN inactivation 30 min after LiCl injections did not interfere with the US pre-exposure effect, in spite of the fact that an identically timed PBN blockade after the acquisition trial disrupted the acquisition of taste aversions. These results stand for the associative role of PBN in taste aversion learning induced by lithium chloride, independent of its sensory role. It is concluded that PBN activity is required after the conditioning trial for the taste-visceral association to take place.}, } @article {pmid11895179, year = {2002}, author = {Yin, HH and Knowlton, BJ}, title = {Reinforcer devaluation abolishes conditioned cue preference: evidence for stimulus-stimulus associations.}, journal = {Behavioral neuroscience}, volume = {116}, number = {1}, pages = {174-177}, doi = {10.1037//0735-7044.116.1.174}, pmid = {11895179}, issn = {0735-7044}, mesh = {Animals ; *Association Learning ; *Avoidance Learning ; *Choice Behavior ; *Conditioning, Classical ; Cues ; Male ; *Motivation ; Orientation ; Rats ; Rats, Long-Evans ; *Taste ; }, abstract = {In the conditioned cue preference (CCP) task, the subject is presented with a cue paired with food reward, resulting in a preference for the paired cue when allowed to choose later. To clarify the learning involved, the authors devalued the reinforcer after training by inducing a taste aversion to the food. In five 30-min sessions, rats were confined in 1 arm of a radial arm maze and presented with food. These reinforced sessions alternated with 5 unreinforced sessions in a nonadjacent arm. Devaluation was then accomplished in 1 group by inducing taste aversion; controls received either saline or unpaired lithium chloride treatment. When tested later, both the saline group and the unpaired group preferred the previously reinforced arm, but the devalued group showed aversion to it. Thus, CCP is mediated by the stimulus-reinforcer association; when the reinforcer is devalued, the preference is also abolished.}, } @article {pmid11895176, year = {2002}, author = {Broadbent, J and Muccino, KJ and Cunningham, CL}, title = {Ethanol-induced conditioned taste aversion in 15 inbred mouse strains.}, journal = {Behavioral neuroscience}, volume = {116}, number = {1}, pages = {138-148}, pmid = {11895176}, issn = {0735-7044}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Alcohol Withdrawal Delirium/genetics ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*toxicity ; *Genotype ; Male ; Mice ; Mice, Inbred Strains ; Phenotype ; Taste/*drug effects/genetics ; }, abstract = {This study used a genetic correlational strategy to characterize the neurobiological basis of ethanol's (0, 2, or 4 g/kg) aversive effects as indexed by conditioned taste aversion. Substantial strain differences in taste aversion and hypothermia were observed, but the genetic correlation between these phenotypes was not significant. However, significant genetic correlations were observed between taste aversion and ethanol-related behaviors measured in previous studies, including home-cage ethanol preference (r = .68) and ethanol withdrawal severity (r = -.69). Strains showing stronger taste aversion tended to show lower ethanol preference and higher withdrawal severity. This pattern of findings is consistent with previous studies suggesting a commonality in neurobiological mechanisms underlying these phenotypes. These results do not support the hypothesis that ethanol-induced taste aversion is mediated by the drug's rewarding properties.}, } @article {pmid11889493, year = {2002}, author = {Dunworth, SJ and Stephens, DN}, title = {Provision of cues to signal a withdrawal US prevents the US pre-exposure effect in a diazepam-withdrawal conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {160}, number = {3}, pages = {245-252}, doi = {10.1007/s00213-001-0982-1}, pmid = {11889493}, issn = {0033-3158}, mesh = {Animals ; Anti-Anxiety Agents/*adverse effects ; Avoidance Learning/drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; *Cues ; Diazepam/*adverse effects ; Male ; Mice ; Mice, Inbred C57BL ; Substance Withdrawal Syndrome/*psychology ; Taste/*drug effects/physiology ; }, abstract = {RATIONALE: Prior experience of withdrawal from chronic diazepam treatment reduces the aversiveness of withdrawal when precipitated withdrawal is made the US in a conditioned taste aversion (CTA) paradigm. Some accounts of US pre-exposure reducing its effectiveness in CTA postulate that US pre-exposure leads to the formation of associations with the environment, resulting in blocking of taste conditioning, but a test of a blocking explanation failed to provide support for such an account.

OBJECTIVE: The present experiments tested alternative explanations.

METHODS: Male mice (C57BLx129sv derived) made dependent upon diazepam (15 mg/kg per day, SC) were subjected to precipitated withdrawal with IP flumazenil (20 mg/kg) as the unconditioned stimulus (US) in a conditioned taste aversion (CTA) paradigm, in which sucrose was the conditioned stimulus (CS). The conditioning trial took place in either the same or different environment from that in which the mice had received pre-exposure to the withdrawal US.

RESULTS: No evidence was found that a place conditioned to withdrawal was capable of supporting a second-order CTA. A second experiment showed that whether withdrawal supported a CTA depended upon whether the previous experience of withdrawal had been predicted by an environmental stimulus.

CONCLUSIONS: Prior experience of an unpredictable aversive US disrupts the subsequent formation of a CTA to the same US. Since prior experience of withdrawal, if it was predictable by an environmental event, did not prevent withdrawal from being a US in a subsequent CTA experiment, withdrawal retains its aversive nature even following prior experience. An explanation in terms of the nature of US predictability following repeated withdrawal from diazepam is consistent both with the current data and our previous findings.}, } @article {pmid11889491, year = {2002}, author = {Risinger, FO and Boyce, JM}, title = {Conditioning tastant and the acquisition of conditioned taste avoidance to drugs of abuse in DBA/2J mice.}, journal = {Psychopharmacology}, volume = {160}, number = {3}, pages = {225-232}, doi = {10.1007/s00213-001-0973-2}, pmid = {11889491}, issn = {0033-3158}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Cocaine/administration & dosage ; Conditioning, Psychological/*drug effects/physiology ; Ethanol/administration & dosage ; Illicit Drugs/*pharmacology ; Lithium/administration & dosage ; Male ; Mice ; Mice, Inbred DBA ; Morphine/administration & dosage ; Saccharin/administration & dosage ; Sodium Chloride/administration & dosage ; Taste/*drug effects/physiology ; }, abstract = {RATIONALE: Conditioned taste aversion (CTA) produced by drugs of abuse such as morphine and cocaine has been interpreted as representing the rewarding actions of these drugs. Evidence for this interpretation is based, in part, on findings in rats indicating saccharin is a more effective conditioning flavor compared to salt (NaCl). However, our studies with ethanol have found salt to be a highly effective conditioning flavor in mice.

OBJECTIVES: The present series of studies examined the acquisition of CTA to morphine, ethanol, lithium chloride, and cocaine. Further, saccharin and salt were utilized in each experiment in order to determine effectiveness of each flavor to serve as a conditioning stimulus.

METHODS: In four separate experiments, adult male DBA/2J mice were acclimated to a 2 h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1 h access to either 0.15% w/v saccharin or 0.1 M salt followed by 0, 10 or 20 mg/kg morphine (experiment 1), 0, 2, or 4 g/kg ethanol (experiment 2), 0, 1.5 or 3.0 milliequivalents/kg lithium chloride (experiment 3) or 0, 10 or 20 mg/kg cocaine (experiment 4). A fifth flavor access period (trial 5) was not followed by drug exposure. Following trial 5, each subject received 24-h access to the conditioning flavor and water (two-bottle test 1). Control subjects (0 dose groups from each experiment) received a second two-bottle test with 24-h access to both saccharin and salt flavors.

RESULTS: Reduced flavor intake and reduced flavor preference was noted in all drug-paired groups in each experiment. However, more rapid development of CTA was seen with the saccharin flavor in morphine- or cocaine-paired groups. In contrast, ethanol-induced CTA appeared more rapidly with the salt flavor. Lithium-induced CTA was modest, and emerged equally with either flavor.

CONCLUSIONS: CTA induced by morphine or cocaine in mice occurs in a similar pattern to that seen in rats, and these findings agree with an interpretation based on drug reward. In contrast, ethanol-induced CTA is more likely attributable to aversive effects.}, } @article {pmid11883917, year = {2002}, author = {Bayley, TM and Dye, L and Jones, S and DeBono, M and Hill, AJ}, title = {Food cravings and aversions during pregnancy: relationships with nausea and vomiting.}, journal = {Appetite}, volume = {38}, number = {1}, pages = {45-51}, doi = {10.1006/appe.2002.0470}, pmid = {11883917}, issn = {0195-6663}, mesh = {Adult ; Female ; Food Preferences/*psychology ; Humans ; Nausea/*psychology ; Pregnancy ; Surveys and Questionnaires ; Time Factors ; Vomiting/*psychology ; }, abstract = {Food cravings and food aversions are common during pregnancy. A mechanism that may explain these changes in food preference is taste aversion learning. Accordingly, this study examined the temporal association between the first occurrences of nausea, vomiting, food cravings and food aversions during pregnancy. Ninety-nine women completed a questionnaire that asked about the occurrence, timing of first onset, duration, strength and targets of these symptoms. Nausea and vomiting were reported by 80% and 56% of the women, food cravings and aversions by 61% and 54% respectively. Although more women experienced both food cravings and aversions than either symptom alone, cravings and aversions were statistically unrelated. There was a significant positive correlation between week of onset of nausea and of aversions. In 60% of women reporting both nausea and food aversions, the first occurrence of each happened in the same week of pregnancy. No such association was found for cravings. These retrospective accounts provide good support for taste aversion learning as a mechanism for the development of some but not all food aversions during pregnancy. Prospective data are needed to confirm these temporal relationships and to assist understanding of the emergence of food cravings.}, } @article {pmid11857327, year = {2002}, author = {Misanin, JR and Goodhart, MG and Anderson, MJ and Hinderliter, CF}, title = {The interaction of age and unconditioned stimulus intensity on long-trace conditioned flavor aversion in rats.}, journal = {Developmental psychobiology}, volume = {40}, number = {2}, pages = {131-137}, doi = {10.1002/dev.10018}, pmid = {11857327}, issn = {0012-1630}, mesh = {Aging/*physiology ; Animals ; Arousal/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Female ; Mental Recall/*physiology ; Motivation ; Psychophysiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {To see if the neural representation of the conditioned stimulus (CS) is available to old-age rats beyond the time it is available to young adults, the intensity of the unconditioned stimulus (US) and the length of the CS-US interval were systematically varied in a trace conditioning experiment. Results indicated that increasing US intensity extends the interval over which trace conditioning is evident in old-age rats but not in young adults, suggesting that trace decay occurs more rapidly in young rats. Results were interpreted in terms of age differences in the workings of hypothesized biochemical timing mechanisms that may directly influence the ability to associate stimuli over trace intervals in conditioned taste-aversion procedures.}, } @article {pmid11844587, year = {2002}, author = {Grancha, ML and Navarro, M and Cubero, I and Thiele, TE and Bernstein, IL}, title = {Induction of a brainstem correlate of conditioned taste aversion expression: role of the pontine parabrachial nucleus.}, journal = {Behavioural brain research}, volume = {131}, number = {1-2}, pages = {205-209}, doi = {10.1016/s0166-4328(01)00385-0}, pmid = {11844587}, issn = {0166-4328}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Brain Stem/*physiology ; Conditioning, Operant ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Male ; Pons/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Long-Evans ; Solitary Nucleus/cytology/metabolism ; Taste/*physiology ; }, abstract = {Increases in Fos-like immunoreactivity (FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) are seen following the expression of a conditioned taste aversion (CTA). In studies limited to behavioral assessment, the pontine parabrachial nucleus (PBN) has been demonstrated to play a critical role in the acquisition, but not the expression, of CTAs. To better define the role of the PBN in taste aversion learning, the present study examined the effects of PBN lesions on FLI in iNTS in animals with lesions placed either before or after CTA training. As is the case with behavioral expression of a CTA, timing of PBN lesions was found to be critical. Lesions placed prior to conditioning blocked evidence of conditioning, including both taste rejection and FLI in iNTS. Lesions placed after conditioning, but before testing, did not interfere with either taste rejection or FLI. These results support and extend prior claims that PBN is critical for CTA acquisition but not expression. They also demonstrate that input from PBN to iNTS is not necessary for the FLI seen there during CTA expression.}, } @article {pmid11840214, year = {2001}, author = {Tang-Christensen, M and Vrang, N and Larsen, PJ}, title = {Glucagon-like peptide containing pathways in the regulation of feeding behaviour.}, journal = {International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity}, volume = {25 Suppl 5}, number = {}, pages = {S42-7}, doi = {10.1038/sj.ijo.0801912}, pmid = {11840214}, mesh = {Angiotensin II/pharmacology ; Animals ; Behavior, Animal/physiology ; Drinking/drug effects/physiology ; Eating/*physiology ; Fasting/physiology ; Glucagon/*physiology ; Glucagon-Like Peptide 1 ; *Homeostasis ; Male ; Neuropeptide Y/pharmacology ; Peptide Fragments/*physiology ; Protein Precursors/*physiology ; Rats ; }, abstract = {The pre-proglucagon derived peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are both involved in a wide variety of peripheral functions, such as glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Pre-proglucagon is also found in the brainstem in a small population of nerve cells in the nucleus of the solitary tract (NTS) that process the pre-propeptide as in the gut to yield GLP-1 and GLP-2. GLP-1 containing nerve fibres and the GLP-1 receptor are found predominantly in hypothalamic midline nuclei. GLP-1 given centrally to naive rats results in a marked induction of c-Fos protein in the supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN) and central nucleus of the amygdala, but only a moderate increase in the arcuate nucleus. The pattern of c-Fos activation is compatible with the appetite suppressing effects of GLP-1. This anorectic effect of GLP-1 appears to be mediated by the PVN, as direct injections of GLP-1 into this nucleus cause anorexia without concomitant taste aversion, suggesting a specific action upon neuronal circuits involved in the regulation of feeding. Recent experiments have also shown that GLP-1 is implicated in mediating signals from the gastrointestinal tract pertaining to discomfort and malaise. The distribution of the co-localised peptide, GLP-2, displays a perfect overlap with GLP-1 in the CNS with the highest concentration in the diffuse ventral part of the dorsomedial nucleus (DMHv). In contrast to the widely distributed GLP-1 receptor mRNA, GLP-2 receptor mRNA is exclusively expressed in the compact part of the DMH (DMHc). Interestingly, the DMHc is also the only nucleus responding to central administration of GLP-2 with a significant increase in the number of c-Fos positive cells. When injected into the lateral ventricle, GLP-2 has a marked inhibitory effect on feeding. The effect of GLP-2 on feeding is both behaviourally and pharmacologically specific. Future experiments will elucidate whether or not GLP-1 and GLP-2 are involved in the long-term or short-term regulation of feeding behaviour and hence have an impact on bodyweight.}, } @article {pmid11839613, year = {2002}, author = {Shimura, T and Tokita, K and Yamamoto, T}, title = {Parabrachial unit activities after the acquisition of conditioned taste aversion to a non-preferred HCl solution in rats.}, journal = {Chemical senses}, volume = {27}, number = {2}, pages = {153-158}, doi = {10.1093/chemse/27.2.153}, pmid = {11839613}, issn = {0379-864X}, mesh = {Animals ; Avoidance Learning/*physiology ; Hydrochloric Acid/*chemistry ; Lithium Chloride/*chemistry ; Male ; Neurons/*physiology ; Rats ; Rats, Wistar ; *Taste ; Urethane/pharmacology ; }, abstract = {Abstract In a behavioral experiment, rats reliably acquired a taste aversion to non-preferred 0.01 M HCl that had been previously paired with intraperitoneal injection of 0.15 M LiCl. These rats showed aversions to other acidic solutions such as malic acid and tartaric acid. In a neurophysiological experiment, the neuronal activities of the parabrachial nucleus (PBN) were recorded after the acquisition of conditioned taste aversion (CTA) to 0.01 M HCl in urethane-anesthetized rats. Neuronal responses to the conditioned stimulus (CS) did not change on the whole but decreased in the dorsal region to the brachium conjunctivum. The proportion of HCl-best to NaCl-best units was lower in the CTA group than in controls. The spontaneous firing rate was lower in the CTA group than in controls. Correlation coefficients between the HCl CS and normally preferred tastes (sucrose and NaCl) were more negative and those between HCl and quinine were more positive in the CTA group than in the controls. These results may be explained by the notion that gustatory responses of PBN neurons are concerned with alterations in taste hedonics after the acquisition of conditioned taste aversions.}, } @article {pmid11829323, year = {2001}, author = {Sroubek, J and Hort, J and Komárek, V and Langmeier, M and Brozek, G}, title = {Acquisition and retrieval of conditioned taste aversion is impaired by brain damage caused by two hours of pilocarpine-induced status epilepticus.}, journal = {Physiological research}, volume = {50}, number = {6}, pages = {609-617}, pmid = {11829323}, issn = {0862-8408}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/physiology ; Hippocampus/pathology/physiopathology ; Male ; Memory/physiology ; Muscarinic Agonists ; Pilocarpine ; Rats ; Rats, Long-Evans ; Status Epilepticus/chemically induced/pathology/*physiopathology ; Taste ; }, abstract = {The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.}, } @article {pmid11814433, year = {2002}, author = {Sullivan, RM and Gratton, A}, title = {Behavioral effects of excitotoxic lesions of ventral medial prefrontal cortex in the rat are hemisphere-dependent.}, journal = {Brain research}, volume = {927}, number = {1}, pages = {69-79}, doi = {10.1016/s0006-8993(01)03328-5}, pmid = {11814433}, issn = {0006-8993}, mesh = {Animals ; Anxiety/physiopathology ; Apomorphine/pharmacology ; Avoidance Learning/physiology ; Behavior, Animal/physiology ; Carbohydrates ; Denervation ; Dopamine Agonists/pharmacology ; Excitatory Amino Acid Agonists ; Functional Laterality/*physiology ; Ibotenic Acid ; Male ; Maze Learning/physiology ; Milk ; Motor Activity/drug effects/physiology ; Prefrontal Cortex/*pathology/*physiology ; Quinine ; Rats ; Rats, Long-Evans ; Reflex, Startle/drug effects/physiology ; Stress, Physiological/physiopathology ; Taste ; }, abstract = {The ventral region of the medial prefrontal cortex (mPFC) is highly sensitive to stressful inputs and implicated in a variety of behaviors. Studies have also demonstrated numerous functional hemispheric asymmetries within this brain area of the rat. The present study examines the effects of ibotenic acid or sham lesions targeting the left, right or bilateral infralimbic cortex, on a variety of behaviors. Lesions (which destroyed infralimbic and ventral prelimbic cortex) were without effect on acquisition or reversal of a spatial learning task in the Morris water maze. Similarly unaffected were spontaneous and amphetamine-induced locomotor activity and sensitization, and prepulse inhibition of the acoustic startle response. In contrast, lesions significantly affected behavior in the elevated plus maze, as right-lesioned animals spent more time exploring the open arms of the maze than shams or left-lesioned rats, while not differing in closed arm entries. As well, in a simple taste aversion paradigm, right-lesioned rats drank significantly more of a sweetened milk/quinine solution than shams and left-lesioned rats, despite not differing in consumption of sweetened milk alone. The anxiolytic effects of right, but not left lesions of ventral mPFC, parallel the asymmetrical suppression of physiological stress responses previously reported for similar lesions. It is suggested that the right ventral mPFC plays a primary role in optimizing cautious and adaptive behavior in potentially threatening situations.}, } @article {pmid11812534, year = {2002}, author = {Stevenson, GW and Cañadas, F and Gomez-Serrano, M and Ullrich, T and Zhang, X and Rice, KC and Riley, AL}, title = {Delta opioid discrimination learning in the rat: assessment with the selective delta agonist SNC80.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {71}, number = {1-2}, pages = {283-292}, doi = {10.1016/s0091-3057(01)00658-x}, pmid = {11812534}, issn = {0091-3057}, mesh = {Animals ; Benzamides/*pharmacology ; Discrimination Learning/*drug effects/physiology ; Dose-Response Relationship, Drug ; Female ; Piperazines/*pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Opioid, delta/*agonists/physiology ; }, abstract = {The majority of reports assessing opioid drug discrimination learning (DDL) have concentrated on characterizing the stimulus properties of compounds selective for mu and kappa opioid receptors. Assessments of delta opioid DDL have been limited and, to date, these assessments have been restricted to the monkey and pigeon. No assessment of delta stimulus control has been examined in rodents. To that end, the present experiment examined discriminative control by the selective delta agonist SNC80 in rats and its generalization to and antagonism by compounds relatively selective to the delta and mu receptor subtypes using the conditioned taste aversion baseline of DDL. Animals injected with 5.6 mg/kg of SNC80 prior to a saccharin-LiCl pairing and with the SNC80 vehicle prior to saccharin alone acquired the discrimination within seven conditioning cycles. The discriminative effects of SNC80 were maximal at 20 min, partial at 120 min, and lost at 240 min. The discrimination was dose dependent in that as the dose of SNC80 increased, the amount of saccharin consumed decreased. In subsequent generalization tests, the delta agonist SNC162 produced SNC80-appropriate responding at a dose of 18 mg/kg. Conversely, the mu agonist morphine produced vehicle-appropriate responding at all doses tested. These selective generalization patterns with SNC162 and morphine suggest that the discriminative effects of SNC80 are mediated at the delta, but not the mu, receptor, a conclusion supported by the fact that SNC80's discriminative control was completely blocked by the delta-selective antagonist NTI, but not by the mu-selective antagonist naltrexone. The present findings indicate that not only do rats readily discriminate both mu- and kappa-selective agonists from their respective vehicles, but they also discriminate compounds that are selective for the delta receptor subtype, thus extending the class of compounds that can serve such discriminative functions for the rat.}, } @article {pmid11809500, year = {2002}, author = {Escobar, ML and Alcocer, I and Bermúdez-Rattoni, F}, title = {In vivo effects of intracortical administration of NMDA and metabotropic glutamate receptors antagonists on neocortical long-term potentiation and conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {129}, number = {1-2}, pages = {101-106}, doi = {10.1016/s0166-4328(01)00329-1}, pmid = {11809500}, issn = {0166-4328}, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Benzoates/administration & dosage/pharmacology ; Excitatory Amino Acid Agonists/administration & dosage/*pharmacology ; Excitatory Amino Acid Antagonists/*pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Glycine/administration & dosage/*analogs & derivatives/pharmacology ; Long-Term Potentiation/*drug effects ; Male ; Microinjections ; N-Methylaspartate/administration & dosage/*pharmacology ; Neocortex/*physiology ; Piperazines/administration & dosage/pharmacology ; Rats ; Rats, Wistar ; Receptors, Metabotropic Glutamate/*antagonists & inhibitors ; Taste/*drug effects ; }, abstract = {It has been proposed that long-term potentiation (LTP), a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-D-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonists CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid, 0.03 microg per hemisphere) and AP-5 (D(-)-2-amino-5-phosphonopentanoic, 2.5 microg per hemisphere) disrupt the acquisition of conditioned taste aversion, as well as IC-LTP induction in vivo. In contrast, administration of the metabotropic glutamate receptor antagonist MCPG ((RS)-alpha-methyl-4-carboxyphenylglycine, 2.5 microg per hemisphere) does not disrupt the acquisition of CTA nor IC-LTP induction. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA-dependent neocortical LTP constitute a possible mechanism for the learning-related functions performed by the IC.}, } @article {pmid11797072, year = {2001}, author = {Kunin, D and Bloch, RT and Smith, BR and Amit, Z}, title = {Caffeine, nicotine and mecamylamine share stimulus properties in the preexposure conditioned taste aversion procedure.}, journal = {Psychopharmacology}, volume = {159}, number = {1}, pages = {70-76}, doi = {10.1007/s002130100888}, pmid = {11797072}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Caffeine/*pharmacology ; Central Nervous System Stimulants/*pharmacology ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Male ; Mecamylamine/*pharmacology ; Nicotine/*pharmacology ; Nicotinic Agonists/*pharmacology ; Nicotinic Antagonists/*pharmacology ; Rats ; Rats, Wistar ; Taste/*drug effects/physiology ; }, abstract = {RATIONALE: The present study examined whether nicotine and caffeine, two of the most widely used psychoactive drugs, share stimulus properties in the preexposure conditioned taste aversion (CTA) procedure.

OBJECTIVES: To determine whether nicotine would attenuate the formation of a caffeine-induced CTA and further assess whether pretreatment with mecamylamine, a nicotinic receptor antagonist, would reverse nicotine's attenuating effect of a caffeine-induced CTA.

METHODS: Male Wistar rats were preexposed with one of three doses of nicotine (0.6, 1.2 and 2.0 mg/kg, s.c.) for three consecutive days, then 24 h following the final preexposure injection were conditioned with caffeine (20 mg/kg and 30 mg/kg, i.p.) in a standard two-bottle test. There were four conditioning trials and four drug-free test days. In a follow-up study, rats were pretreated with mecamylamine (2 mg/kg, i.p.) prior to preexposure injections with nicotine (0.6 mg/kg, i.p.), then subsequently conditioned with caffeine (20 mg/kg, i.p.) as described above.

RESULTS: The lowest nicotine dose (0.6 mg/kg) attenuated the caffeine induced CTAs (20 mg/kg and 30 mg/kg) but the higher nicotine doses showed no such attenuating effect. In addition, mecamylamine reversed the nicotine-induced attenuation of the caffeine-induced CTA and also directly attenuated it.

CONCLUSIONS: These results suggested that caffeine, nicotine and mecamylamine share overlapping stimulus properties and that the nature of this relationship may involve action at the nicotinic-cholinergic receptor.}, } @article {pmid11796487, year = {2002}, author = {Lawrence, CB and Ellacott, KL and Luckman, SM}, title = {PRL-releasing peptide reduces food intake and may mediate satiety signaling.}, journal = {Endocrinology}, volume = {143}, number = {2}, pages = {360-367}, doi = {10.1210/endo.143.2.8609}, pmid = {11796487}, issn = {0013-7227}, mesh = {Animals ; Avoidance Learning/drug effects ; Brain Stem/cytology/metabolism/physiology ; Eating/*drug effects ; Exploratory Behavior/drug effects ; Grooming/drug effects ; Hypothalamic Hormones/*pharmacology ; Immunohistochemistry ; Male ; Neurons/metabolism/physiology ; Neuropeptides/*pharmacology ; Prolactin/metabolism ; Prolactin-Releasing Hormone ; Proto-Oncogene Proteins c-fos/biosynthesis ; Rats ; Rats, Sprague-Dawley ; Satiety Response/*drug effects ; Signal Transduction/*drug effects ; Taste/drug effects ; }, abstract = {PRL-releasing peptide (PrRP) administered centrally inhibits food intake and body weight gain. To elucidate the role of PrRP, its actions were compared with those of a homeostatic regulator of food intake, the satiety factor, cholecystokinin (CCK), and a nonhomeostatic regulator, lithium chloride (LiCl), which reduces food intake due to visceral illness. Immunohistochemical analysis of the protein product of the c-fos gene, showed that central administration of PrRP activated some areas of the brain in common with both CCK and LiCl administered peripherally. However, PrRP was more similar to CCK than to LiCl in its behavioral effects. PrRP did not cause conditioned taste aversion, but instead enhanced the normal behavioral satiety sequence. Furthermore, brainstem PrRP neurons were strongly activated by CCK, but not by LiCl. These data provide evidence that pathways from the gut to the brain that are involved in signaling satiety and visceral illness may have some independent components and suggest that PrRP may mediate some of the central satiating actions of CCK.}, } @article {pmid11790406, year = {2001}, author = {Fouquet, N and Oberling, P and Sandner, G}, title = {Differential effect of free intake versus oral perfusion of sucrose in conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {74}, number = {4-5}, pages = {465-474}, doi = {10.1016/s0031-9384(01)00585-6}, pmid = {11790406}, issn = {0031-9384}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; *Drinking ; Extinction, Psychological ; Lithium Chloride/toxicity ; Perfusion ; Rats ; Rats, Long-Evans ; Self Administration ; Sucrose/administration & dosage ; *Taste ; }, abstract = {Five experiments were designed to investigate LiCl-induced conditioned taste aversion (CTA) obtained in rats whether after free intake of a sucrose solution (active mode) or after forced administration through an intraoral cannula (passive mode). It was found in Experiment 1 that actively conditioned rats showed a slower extinction rate as revealed by repeated two-bottle tests (active testing) as opposed to passively conditioned ones. As these rats underwent a mode change between conditioning and testing, the differential extinction rate might have arisen from this change inducing a generalization decrement effect or acting as a contextual shift. In Experiment 2, no evidence for any generalization decrement was found. The possibility that the mode of sucrose delivery could have contextual properties in CTA through a "renewal test" after extinction and a latent inhibition experiment was further tested in Experiments 3 and 4. When active testing followed passive extinction, a CTA was afresh obtained in rats actively conditioned in active conditions. Latent inhibition was attenuated in rats preexposed in passive conditions and conditioned in active conditions (i.e., when a shift in the drinking mode occurred between preexposure and conditioning). In Experiment 5, intraoral perfusion was used in both groups. The active subjects had to nose poke for intraoral administration of sucrose. The yoked control passive subjects received simultaneously the same amount of sucrose. The levels of CTA differed also from the actively to the passively conditioned subjects. Results are discussed in terms of free intake activity acting as a contextual modulator of CTA.}, } @article {pmid11790398, year = {2001}, author = {Bárdos, G}, title = {Conditioned taste aversion to gut distension in rats.}, journal = {Physiology & behavior}, volume = {74}, number = {4-5}, pages = {407-413}, doi = {10.1016/s0031-9384(01)00483-8}, pmid = {11790398}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking/physiology ; Intestine, Large/*physiology ; Intestine, Small/*physiology ; Male ; Mechanoreceptors/*physiology ; Motivation ; Rats ; Rats, Long-Evans ; Satiety Response/physiology ; Taste/*physiology ; }, abstract = {The aim of this work was to study the negative effects of the intestinal stimulation by a method that is sensitive to assess internal malaise and discomfort. Effects of volumetric and "isometric" gut distension on the behavior were compared in the small and the large intestines, respectively. Chronically separated (Thiry-Vella) intestinal loops prepared from the upper jejunum and/or from the uppermost segment of the colon were stimulated with a rubber balloon. Conditioned taste aversion (CTA) series were accompanied with recording satiety and aversive behavioral indexes. Both isometric and volumetric stimuli elicited taste aversion. No essential differences between the two intestinal parts were found. Behavioral indices supported intake data: satiety indexes were similar to each other, whereas aversive indexes were high during stimulation and lower during testing. Data were consistent over conditions and time, proving the reliability of the method. Results are compared to earlier taste reactivity records.}, } @article {pmid11744004, year = {2002}, author = {Turgeon, SM and Reichstein, DA}, title = {Decreased striatal c-Fos accompanies latent inhibition in a conditioned taste aversion paradigm.}, journal = {Brain research}, volume = {924}, number = {1}, pages = {120-123}, doi = {10.1016/s0006-8993(01)03245-0}, pmid = {11744004}, issn = {0006-8993}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Dietary Sucrose/pharmacology ; Dopamine/metabolism ; Dopamine Uptake Inhibitors/pharmacology ; Down-Regulation/*physiology ; Eating/physiology ; Immunohistochemistry ; Male ; Neostriatum/cytology/*metabolism ; Neural Inhibition/*physiology ; Neurons/cytology/metabolism ; Nucleus Accumbens/cytology/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Reward ; Taste/physiology ; }, abstract = {Latent inhibition (LI) is a phenomenon whereby previous exposure to a stimulus retards subsequent acquisition of a conditioned response to that stimulus. The present study investigated the neuronal substrates of LI as assessed in a conditioned taste aversion paradigm by comparing regional c-Fos activation in pre- vs. non-pre-exposed animals. The LI paradigm involved a pre-exposure phase in which water-deprived rats were allowed access to either water (non-pre-exposed; NPE) or 5% sucrose (pre-exposed; PE), followed by a conditioning phase in which animals were allowed access to sucrose and subsequently injected with lithium chloride, and a test phase in which animals were allowed access to both sucrose and water. LI was assessed by comparing the %-sucrose consumed in PE and NPE groups on the test day. Two hours following the onset of the test phase, animals were perfused and their brains processed for c-Fos immunohistochemistry. PE animals drank significantly more sucrose on the test day, indicating the presence of LI. PE animals had significantly fewer FLI-positive cells in the striatum than NPE animals; however, no differences were seen in the nucleus accumbens. This difference in FLI was not due to a difference in sucrose consumption on the test day as there was no correlation between c-Fos and amount of sucrose consumed in the PE group. These data are consistent with previous data supporting a role for the striatum in the disruption of LI as assessed by CTA.}, } @article {pmid11742833, year = {2002}, author = {Zheng, H and Patterson, C and Berthoud, HR}, title = {Behavioral analysis of anorexia produced by hindbrain injections of AMPA receptor antagonist NBQX in rats.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {282}, number = {1}, pages = {R147-55}, doi = {10.1152/ajpregu.2002.282.1.R147}, pmid = {11742833}, issn = {0363-6119}, support = {DK-47348/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anorexia/chemically induced/*physiopathology ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Dietary Sucrose/pharmacology ; Drinking/drug effects ; Eating/drug effects ; Excitatory Amino Acid Antagonists/*pharmacology ; Feeding Behavior/drug effects ; Fourth Ventricle ; Glutamic Acid/metabolism ; Injections, Intraventricular ; Male ; Quinoxalines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/*antagonists & inhibitors/metabolism ; Satiation/drug effects ; Solitary Nucleus/*physiopathology ; Taste ; }, abstract = {The caudal brain stem integrates short-term feedback signals from the oral cavity and the food-handling abdominal viscera, as well as long-term homeostatic, cognitive, and emotional signals from the forebrain, to control ingestive behavior. Glutamate, acting on various receptor subtypes, plays a prominent role in this integrative process. Fourth ventricular injection of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor blocker 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX, 0.5-5 nmol/3 microl) dose dependently suppressed intake of 15% sucrose in food-deprived and non-food-deprived rats compared with saline injection. Two consecutive paired NBQX injections (5 nmol) into the fourth ventricle did not produce conditioned taste aversion to saccharin, but LiCl did. Intraburst lick rate and lick efficiency were not affected, but burst size and number and initial lick rate were significantly decreased by NBQX. Local injection of NBQX (2 nmol) into and near the nucleus tractus solitarius also suppressed sucrose intake. These results suggest a general role for non-N-methyl-D-aspartate receptors in the transmission of positive (feedforward) signals, but do not identify the exact processing step involved, such as taste input, sensory-motor processing, or descending facilitation. More localized injections and response measures will be necessary.}, } @article {pmid11738836, year = {2001}, author = {Kobayashi, K and Kobayashi, T}, title = {Genetic evidence for noradrenergic control of long-term memory consolidation.}, journal = {Brain & development}, volume = {23 Suppl 1}, number = {}, pages = {S16-23}, doi = {10.1016/s0387-7604(01)00329-1}, pmid = {11738836}, issn = {0387-7604}, mesh = {Amygdala/growth & development/metabolism/physiopathology ; Animals ; Central Nervous System/*growth & development/metabolism/physiopathology ; Cerebral Cortex/growth & development/metabolism/physiopathology ; Conditioning, Psychological/physiology ; Gene Expression Regulation, Developmental/physiology ; Maze Learning/physiology ; Memory/physiology ; Memory Disorders/genetics/*metabolism/physiopathology ; Mice ; Mice, Knockout ; Neural Pathways/*growth & development/metabolism/physiopathology ; Neurons/*metabolism ; Norepinephrine/*biosynthesis ; Thalamus/growth & development/metabolism/physiopathology ; Tyrosine 3-Monooxygenase/*deficiency/genetics ; }, abstract = {Memory formation involves dynamic interactions among many brain structures and their linking pathways. The noradrenaline (NA) system in the CNS plays an important role in a wide variety of neurological and psychological functions. Alteration in the NA system is implicated in the pathological states of some neuropsychiatric disorders. Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines. The regulatory mechanism of the TH reaction is generally considered to play a key role in controlling the catecholaminergic actions. Mice heterozygous for the mutation of the gene encoding TH exhibit the reduced TH activity in tissues. These mice have a moderate reduction in NA accumulation and release in brain regions. The mutant mice exhibit deficits in the water-finding task associated with latent learning performance, suggesting the impairment in memory formation. Spatial learning performance measured by the water maze task is normal in the mutants. However, they display deficits in long-term memory formation of conditioned learning evaluated with three distinct behavioral paradigms, including active avoidance, cued fear conditioning, and conditioned taste aversion, without affecting short-term memory. These memory deficits are restored by the drug-induced stimulation of NA activity at the postconditioning phase. Analysis of the mutant mice indicates that the central NA system is essential for the consolidation process in long-term memory of conditioned learning. The process appears to be implicated in the NA activity in the cerebral cortex and/or amygdaloid complex.}, } @article {pmid11699605, year = {2001}, author = {Conti, LH and Palmer, AA and Vanella, JJ and Printz, MP}, title = {Latent inhibition and conditioning in rat strains which show differential prepulse inhibition.}, journal = {Behavior genetics}, volume = {31}, number = {3}, pages = {325-333}, doi = {10.1023/a:1012287527438}, pmid = {11699605}, issn = {0001-8244}, mesh = {Acoustic Stimulation ; Animals ; Association Learning/physiology ; Avoidance Learning/physiology ; Conditioning, Classical/*physiology ; Disease Models, Animal ; Habituation, Psychophysiologic/*genetics ; Humans ; Male ; Models, Genetic ; Neural Inhibition/*genetics ; Rats ; Rats, Inbred BN ; Rats, Inbred WKY ; Reflex, Startle/*genetics ; Schizophrenia/genetics ; Species Specificity ; Taste/genetics ; }, abstract = {Latent inhibition (LI) is the retardation of associative conditioning resulting from preexposure of the conditioned stimulus (CS) alone prior to conditioning. Schizophrenic patients show deficient prepulse inhibition (PPI) and, at least acutely, deficient LI as well. We recently found that Brown Norway (BN) rats show a PPI deficit compared to Wistar-Kyoto (WKY) rats. If PPI and LI depend on neural processes with common genetic substrates, then LI should be deficient in BN rats as well. Here, LI of a conditioned taste aversion was examined in BN and WKY rats. One group from each strain was preexposed to a saccharin-flavored solution (CS) the day prior to conditioning. For taste aversion conditioning, these two groups again consumed saccharin and were injected with lithium chloride (unconditioned stimulus) 10 min later. A second group from each strain was not preexposed to the CS and was treated identically during conditioning, while a third group was not conditioned (injected with sodium chloride). To test for taste aversion conditioning, saccharin was offered for 20 min/day for 3 days. Nonconditioned BN and WKY rats consumed equal amounts of saccharin on test days. In both strains, conditioned rats showed a saccharin aversion. However, conditioning was less robust in BN than in WKY rats. WKY rats showed good LI of the conditioned taste aversion in that preexposed WKY rats consumed significantly more saccharin on test days than conditioned, nonpreexposed WKY rats. Preexposed BN rats did not consume significantly more saccharin on test days than conditioned, nonpreexposed BN rats. The previously reported deficiency in PPI in the BN rats was confirmed here 1 week after the taste aversion experiment. These results suggest that BN rats show deficient LI as well as PPI and display poor associative learning, a trait also reported in schizophrenia.}, } @article {pmid11684058, year = {2001}, author = {Na, ES and Fitts, DA}, title = {Conditioned taste aversion and c-Fos expression in cholestatic rats.}, journal = {Brain research}, volume = {918}, number = {1-2}, pages = {187-190}, doi = {10.1016/s0006-8993(01)02982-1}, pmid = {11684058}, issn = {0006-8993}, support = {NS-22274/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/physiology ; Bile Ducts/injuries/surgery ; Chemoreceptor Cells/cytology/metabolism ; Cholestasis/*complications ; Conditioning, Psychological/drug effects/*physiology ; Fourth Ventricle/cytology/metabolism ; Immunohistochemistry ; Male ; Neurons/cytology/drug effects/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Long-Evans ; Saccharin/pharmacology ; Solitary Nucleus/cytology/drug effects/*metabolism ; Taste/drug effects/*physiology ; }, abstract = {Rats in which a ligation of the bile duct (BDL) was paired with a saccharin taste developed a persistent conditioned taste aversion in both preference and taste reactivity tests. All BDL animals regardless of pairing had increased c-Fos-like immunoreactivity (FLI) in the area postrema and the nucleus of the solitary tract. This FLI may reflect the illness associated with BDL, but there was no evidence of conditioned FLI.}, } @article {pmid11682112, year = {2001}, author = {Welzl, H and D'Adamo, P and Lipp, HP}, title = {Conditioned taste aversion as a learning and memory paradigm.}, journal = {Behavioural brain research}, volume = {125}, number = {1-2}, pages = {205-213}, doi = {10.1016/s0166-4328(01)00302-3}, pmid = {11682112}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/physiology ; Conditioning, Classical/*physiology ; Gene Expression Regulation/physiology ; Mental Recall/*physiology ; Mice ; *Phenotype ; Rats ; Species Specificity ; Taste/*genetics ; }, abstract = {Conditioned taste aversion (CTA) is a well established learning and memory paradigm in rats and mice that is considered to be a special form of classical conditioning. Rodents--as well as many other species including man--learn to associate a novel taste (CS) with nausea (US), and as a consequence avoid drinking fluid with this specific taste. In contrast to other types of classical conditioning, even CS-US intervals lasting several hours lead to an aversion to the gustatory CS. With increasing CS-US delay duration, however, the aversion against the CS gradually decreases. Mice differ from rats in their reaction to the CS as well as the US. They tolerate a much higher concentration of saccharin and they do not show any clear signs of nausea when injected with the US. Advantages of this task are its relative independence of motor behavior, well described pathways for the CS and partly the US, and the wealth of available anatomical and pharmacological data implying several brain structures (e.g. parabrachial nucleus, amygdala, insular cortex), neurotransmitters and their receptors (e.g. cholinergic system, NMDA-receptors), and cellular processes (e.g. expression of immediate early genes, Ras-MAP kinase signaling pathway, CREB phosphorilation, protein tyrosine phosphorilation, protein synthesis) in CTA. The CTA paradigm has also been successfully used to phenotype mouse mutants.}, } @article {pmid11673096, year = {2001}, author = {Gomez, F}, title = {Induction of conditioned taste aversion with a self-administered substance in rats.}, journal = {Brain research. Brain research protocols}, volume = {8}, number = {2}, pages = {137-142}, doi = {10.1016/s1385-299x(01)00097-6}, pmid = {11673096}, issn = {1385-299X}, support = {DA 12933/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning ; Cocaine/administration & dosage ; *Conditioning, Operant ; Male ; Milk ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Self Administration ; Taste/*physiology ; }, abstract = {Drugs of abuse such as cocaine induce a paradoxical aversive effect when paired with a novel taste. When a novel gustatory cue is paired with drugs of abuse the resulting conditioned effect is the avoidance of the novel taste. A conditioning paradigm was developed in order to pair saccharin with self-administered cocaine. Rats were trained to lever-press for sweetened milk in an operant chamber and then implanted with an intrajugular catheter for cocaine self-administration (SA). After recovery from surgery, food and water access were restricted and the operant behavior was reestablished using contingent milk. Pairings of 10-min saccharin access followed by 1-h cocaine (0.125 mg/kg per injection) SA sessions were alternated daily with pairings of 10-min water access followed by 30-min SA sessions of oral milk and i.v. saline, delivered simultaneously. Pairings were conducted once a day for 10 days. After four sessions of cocaine self-administration there was no significant decrease in saccharin intake. However, rats that avoided saccharin also self-administered more cocaine than non-avoiding rats. These results suggest that the development of taste aversion is accompanied by an acceptance of the drug rather than an aversion to it.}, } @article {pmid11641717, year = {2001}, author = {Bachmanov, AA and Li, X and Li, S and Neira, M and Beauchamp, GK and Azen, EA}, title = {High-resolution genetic mapping of the sucrose octaacetate taste aversion (Soa) locus on mouse Chromosome 6.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {12}, number = {9}, pages = {695-699}, pmid = {11641717}, issn = {0938-8990}, support = {R01 DC000882/DC/NIDCD NIH HHS/United States ; 5 R37 DEO3658/DE/NIDCR NIH HHS/United States ; R01 DC00882/DC/NIDCD NIH HHS/United States ; R03 DC03854/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Animals, Outbred Strains ; Chromosome Mapping/methods ; *Chromosomes ; Cricetinae ; Female ; Genotype ; Linkage Disequilibrium ; Male ; Mice ; Mice, Inbred C3H/genetics ; Mice, Inbred C57BL ; Mice, Inbred Strains/*genetics ; Phenotype ; Sucrose/*analogs & derivatives/*metabolism ; Taste/*genetics ; Taste Threshold/physiology ; }, abstract = {An acetylated sugar, sucrose octaacetate (SOA), tastes bitter to humans and has an aversive taste to at least some mice and other animals. In mice, taste aversion to SOA depends on allelic variation of a single locus, Soa. Three Soa alleles determine 'taster' (Soa(a)), 'nontaster' (Soa(b)), and 'demitaster' (Soa(c)) phenotypes of taste sensitivity to SOA. Although Soa has been mapped to distal Chromosome (Chr) 6, the limits of the Soa region have not been defined. In this study, mice from congenic strains SW.B6-Soa(b), B6.SW-Soa(a), and C3.SW-Soa(a/c) and from an outbred CFW strain were genotyped with polymorphic markers on Chr 6. In the congenic strains, the limits of introgressed donor fragments were determined. In the outbred mice, linkage disequilibrium and haplotype analyses were conducted. Positions of the markers were further resolved by using radiation hybrid mapping. The results show that the Soa locus is contained in an approximately 1-cM (3.3-4.9 Mb) region including the Prp locus.}, } @article {pmid11598919, year = {2001}, author = {Kojima, S and Hosono, T and Fujito, Y and Ito, E}, title = {Optical detection of neuromodulatory effects of conditioned taste aversion in the pond snail Lymnaea stagnalis.}, journal = {Journal of neurobiology}, volume = {49}, number = {2}, pages = {118-128}, doi = {10.1002/neu.1069}, pmid = {11598919}, issn = {0022-3034}, mesh = {Action Potentials ; Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Central Nervous System/cytology/physiology ; Chemoreceptor Cells/*physiology ; Conditioning, Classical/*physiology ; Electric Stimulation ; Equipment Design ; Feeding Behavior/physiology ; Fluorescent Dyes ; Ganglia, Invertebrate/cytology/physiology ; Interneurons/physiology ; Lip/innervation ; Lymnaea/*physiology ; Neuronal Plasticity ; Photometry/instrumentation/*methods ; Potassium Chloride ; Sucrose ; Taste/*physiology ; }, abstract = {Multiple site optical recording was used to analyze the neural activity changes caused by conditioned taste aversion (CTA) training in the pond snail Lymnaea stagnalis. In response to electrical stimulation of the median lip nerve, which transmits chemosensory signals of appetitive taste to the central nervous system, we optically detected large numbers of spikes in several parts of the buccal ganglion. The effects of CTA training on the spike responses were examined in two areas of the ganglion where the most active neural responses occurred. In one area (termed Area I) that included the N1 medial (N1M) cells, a class of central pattern generator interneurons involved in feeding behavior, the number of spikes in a period 1500-2000 ms after median lip nerve stimulation was significantly reduced in conditioned animals compared to control animals. In another area (termed Area II) positioned between buccal motoneurons, the B3 and B4CL (cluster) cells, the evoked spike responses were unaffected by CTA training. These results, taken together with our previous results indicating an enhancement of an inhibitory input to the N1M cells during CTA, suggest that an appetitive taste signal transmitted to the N1M cells through the median lip nerves is suppressed during CTA, resulting in a decrease of the feeding response.}, } @article {pmid11584074, year = {2001}, author = {Stafstrom-Davis, CA and Ouimet, CC and Feng, J and Allen, PB and Greengard, P and Houpt, TA}, title = {Impaired conditioned taste aversion learning in spinophilin knockout mice.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {8}, number = {5}, pages = {272-278}, pmid = {11584074}, issn = {1072-0502}, support = {P01 MH040899/MH/NIMH NIH HHS/United States ; MH40899/MH/NIMH NIH HHS/United States ; P01 DA010044/DA/NIDA NIH HHS/United States ; DC03198/DC/NIDCD NIH HHS/United States ; R01 DC003198/DC/NIDCD NIH HHS/United States ; DA10044/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Lithium Chloride/pharmacology/toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microfilament Proteins/*genetics/*physiology ; Nerve Tissue Proteins/*genetics/*physiology ; Taste/*genetics/*physiology ; }, abstract = {Plasticity in dendritic spines may underlie learning and memory. Spinophilin, a protein enriched in dendritic spines, has the properties of a scaffolding protein and is believed to regulate actin cytoskeletal dynamics affecting dendritic spine morphology. It also binds protein phosphatase-1 (PP-1), an enzyme that regulates dendritic spine physiology. In this study, we tested the role of spinophilin in conditioned taste aversion learning (CTA) using transgenic spinophilin knockout mice. CTA is a form of associative learning in which an animal rejects a food that has been paired previously with a toxic effect (e.g., a sucrose solution paired with a malaise-inducing injection of lithium chloride). Acquisition and extinction of CTA was tested in spinophilin knockout and wild-type mice using taste solutions (sucrose or sodium chloride) or flavors (Kool-Aid) paired with moderate or high doses of LiCl (0.15 M, 20 or 40 mL/kg). When sucrose or NaCl solutions were paired with a moderate dose of LiCl, spinophilin knockout mice were unable to learn a CTA. At the higher dose, knockout mice acquired a CTA but extinguished more rapidly than wild-type mice. A more salient flavor stimulus (taste plus odor) revealed similar CTA learning at both doses of LiCl in both knockouts and wild types. Sensory processing in the knockouts appeared normal because knockout mice and wild-type mice expressed identical unconditioned taste preferences in two-bottle tests, and identical lying-on-belly responses to acute LiCl. We conclude that spinophilin is a candidate molecule required for normal CTA learning.}, } @article {pmid11564451, year = {2001}, author = {Heth, CD and Inglis, P and Russell, JC and Pierce, WD}, title = {Conditioned taste aversion induced by wheel running is not due to novelty of the wheel.}, journal = {Physiology & behavior}, volume = {74}, number = {1-2}, pages = {53-56}, doi = {10.1016/s0031-9384(01)00553-4}, pmid = {11564451}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Body Weight/physiology ; Drinking Behavior/physiology ; Environment ; Feeding Behavior/physiology ; Male ; Motor Activity/*physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {Under a within-subjects design, food- and water-restricted rats showed a significant reduction in consumption of a flavor associated with the opportunity to run compared to another flavor associated with a novel wheel without the opportunity to run. Furthermore, there was no evidence that consumption of the flavor paired with the novel wheel differed from a home cage control.}, } @article {pmid11563419, year = {2001}, author = {Christian, MS and York, RG and Hoberman, AM and Diener, RM and Fisher, LC and Gates, GA}, title = {Biodisposition of dibromoacetic acid (DBA) and bromodichloromethane (BDCM) administered to rats and rabbits in drinking water during range-finding reproduction and developmental toxicity studies.}, journal = {International journal of toxicology}, volume = {20}, number = {4}, pages = {239-253}, doi = {10.1080/109158101750408064}, pmid = {11563419}, issn = {1091-5818}, mesh = {Acetates/*pharmacokinetics/*toxicity ; Animals ; Drinking ; Embryonic and Fetal Development/*drug effects ; Female ; Fetal Viability/drug effects ; Gestational Age ; Male ; Pregnancy ; Rabbits ; Rats ; Reproduction/*drug effects ; Sex Characteristics ; Teratogens/*toxicity ; Tissue Distribution ; Trihalomethanes/*pharmacokinetics/*toxicity ; Water Supply ; }, abstract = {Dibromoacetic acid (DBA) and bromodichloromethane (BDCM), by-products of chlorine disinfection of water, were provided in drinking water in range-finding reproductive/developmental toxicity studies (rats) and a developmental toxicity study (BDCM) in rabbits. Studies included absorption and biodisposition of DBA and BDCM, including passage into placentas, amniotic fluid, fetuses (rats and rabbits), or milk (rats). The DBA and BDCM range-finding reproductive/developmental toxicity studies each included 50 Sprague-Dawley rats/sex/group. DBA (0, 125, 250, 500, or 1000 ppm) or BDCM (0, 50, 150, 450, or 1350 ppm) was provided in drinking water 14 days premating through gestation and lactation (63 to 70 days). The developmental toxicity range-finding study included 25 time-mated New Zealand white rabbits/group given 0, 50, 150, 450, or 1350 ppm BDCM in drinking water on gestation days (GDs) 6 through 29. Satellite groups (6 male, 17 female rats/group/study and 4 rabbits/group) were used for bioanalytical sampling. Rats and rabbits had exposure-related reduced water consumption caused by apparent taste aversion to DBA or BDCM, especially in the parental animals at the two highest exposure levels (500 and 1000 ppm DBA; 450 and 1350 ppm BDCM). Female rats consumed slightly higher mg/kg/day doses of DBA than male rats, especially during gestation and lactation; weanling rats consumed the highest mg/kg/day doses. DBA produced detectable and quantifiable concentrations in plasma, placentas, amniotic fluid, and milk. Plasma samples confirmed that rats drink predominately during the dark; this drinking pattern, not accumulation, produced detectable plasma concentrations for 18 to 24 hours/day. No quantifiable concentrations of BDCM occurred in plasma, placentas, amniotic fluid, or milk, suggesting that BDCM is rapidly degraded or metabolized in vivo. DBA (500 and 1000 ppm, rats) and BDCM (450 and 1350 ppm, rats and rabbits) produced secondary toxicity in the parental generation by reducing water consumption, which caused severe exposure-related apparent dehydration, reduced feed intake and weight gain. Reproductive and developmental parameters were essentially unaffected (mating possibly reduced [DBA at 1000 ppm]; exposure-related decreases in body weights of pups secondary to reduced water and feed consumption [DBA at 250, 500, and 1000 ppm; BDCM at 150, 450, and 1350 ppm]). No effects on development of rabbit fetuses occurred at BDCM concentrations as high as 1350 ppm. Results from these preliminary studies, in which DBA and BDCM were provided in the drinking water at concentrations thousands of times higher than those to which humans are exposed, suggest that neither DBA nor BDCM are reproductive/developmental risks for humans.}, } @article {pmid11547516, year = {2001}, author = {Killcross, S}, title = {Loss of latent inhibition in conditioned taste aversion following exposure to a novel flavour before test.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {54}, number = {3}, pages = {271-288}, doi = {10.1080/02724990143000063}, pmid = {11547516}, issn = {0272-4995}, mesh = {Animals ; Behavior, Animal/physiology ; Conditioning, Classical/*physiology ; *Inhibition, Psychological ; Male ; Random Allocation ; Rats ; Taste/*physiology ; Time Factors ; }, abstract = {Killcross, Kiernan, Dwyer, and Westbrook (1998b) observed that latent inhibition (LI) of contextual fear was attenuated if animals received post-conditioning exposure to a novel context similar to the pre-exposure context. Six experiments used a conditioned taste aversion (CTA) procedure to examine this effect. Experiments 1A-1C demonstrated that LI of CTA was attenuated by a similar post-conditioning manipulation, establishing the generality of previous findings. Experiment 2A manipulated the taste elements to which animals were exposed after conditioning, revealing that exposure to a common element X, present at pre-exposure and conditioning, was not responsible for loss of LI. Experiment 2B manipulated test solution and showed that loss of LI depended on the presence of the full pre-exposed cue AX at test. These two results are contrary to predictions derived from the Dickinson-Burke (Dickinson & Burke, 1996) theory of retrospective revaluation or comparator theory (Miller & Matzel, 1988), and they support recent findings suggesting that retrospective effects may occur by several mechanisms. Experiment 3 showed that a novel element B had to be present during post-conditioning exposure for an attenuation of LI to be observed. Implications for the loss of LI following a retention interval between conditioning and test and retrieval-failure theories of LI are discussed.}, } @article {pmid11542858, year = {2000}, author = {Rabin, BM and Joseph, JA and Shukitt-Hale, B and McEwen, J}, title = {Effects of exposure to heavy particles on a behavior mediated by the dopaminergic system.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {25}, number = {10}, pages = {2065-2074}, doi = {10.1016/s0273-1177(99)01014-5}, pmid = {11542858}, issn = {0273-1177}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/drug effects/*radiation effects ; Behavior, Animal/drug effects/radiation effects ; Cobalt Radioisotopes ; Conditioning, Psychological/radiation effects ; Dopamine/metabolism ; Dopamine Agents/pharmacology ; Dose-Response Relationship, Radiation ; Gamma Rays ; *Heavy Ions ; *Iron ; Linear Energy Transfer ; Lithium Chloride/pharmacology ; Male ; Neutrons ; Nuclear Fission ; Particle Accelerators ; Rats ; Rats, Sprague-Dawley ; Relative Biological Effectiveness ; Taste/drug effects/physiology/*radiation effects ; Time Factors ; }, abstract = {The effects of exposure to heavy particles on behaviors mediated by the central nervous system (CNS) are qualitatively different than the effects produced by exposure to other types of radiation. One behavior mediated by the CNS is the amphetamine-induced taste aversion, which is produced by pairing a novel tasting solution with injection of amphetamine. When the conditioning day is three days following irradiation, exposing rats to low doses of 56Fe particles (600 MeV/n or 1 GeV/n) eliminates the taste aversion produced by injection of amphetamine, which is dependent upon the integrity of the central dopaminergic system, but has no effect on the aversion produced by injection of lithium chloride which is mediated by the gastrointestinal system. In contrast to the effects obtained using heavy particles, exposing rats to 60CO gamma rays or to fission spectrum neutrons has no selective effect upon the acquisition of either amphetamine- or lithium chloride-induced taste aversions. When the conditioning day occurs four months following exposure to 1 GeV/n 56Fe particles, there is an enhancement of the amphetamine-induced taste aversion. The implications of these findings for approaches to risk assessment are considered.}, } @article {pmid11541399, year = {1998}, author = {Rabin, BM and Joseph, JA and Erat, S}, title = {Effects of exposure to different types of radiation on behaviors mediated by peripheral or central systems.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {22}, number = {2}, pages = {217-225}, doi = {10.1016/s0273-1177(98)80013-6}, pmid = {11541399}, issn = {0273-1177}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/drug effects/*radiation effects ; Behavior, Animal/drug effects/*radiation effects ; Cobalt Radioisotopes ; Dopamine Agents/pharmacology ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Radiation ; *Gamma Rays ; Haloperidol/pharmacology ; *Iron ; Linear Energy Transfer ; Lithium Chloride/pharmacology ; *Neutrons ; Particle Accelerators ; Rats ; Relative Biological Effectiveness ; Taste/*radiation effects ; Vomiting ; }, abstract = {The effects of exposure to ionizing radiation on behavior may result from effects on peripheral or on central systems. For behavioral endpoints that are mediated by peripheral systems (e.g., radiation-induced conditioned taste aversion or vomiting), the behavioral effects of exposure to heavy particles (56Fe, 600 MeV/n) are qualitatively similar to the effects of exposure to gamma radiation (60Co) and to fission spectrum neutrons. For these endpoints, the only differences between the different types of radiation are in terms of relative behavioral effectiveness. For behavioral endpoints that are mediated by central systems (e.g., amphetamine-induced taste aversion learning), the effects of exposure to 56Fe particles are not seen following exposure to lower LET gamma rays or fission spectrum neutrons. These results indicate that the effects of exposure to heavy particles on behavioral endpoints cannot necessarily be extrapolated from studies using gamma rays, but require the use of heavy particles.}, } @article {pmid11534543, year = {2001}, author = {Kunin, D and Bloch, RT and Terada, Y and Rogan, F and Smith, BR and Amit, Z}, title = {Caffeine promotes an ethanol-induced conditioned taste aversion: a dose-dependent interaction.}, journal = {Experimental and clinical psychopharmacology}, volume = {9}, number = {3}, pages = {326-333}, doi = {10.1037//1064-1297.9.3.326}, pmid = {11534543}, issn = {1064-1297}, mesh = {Animals ; Avoidance Learning/*drug effects ; Caffeine/*pharmacology ; Central Nervous System Depressants/blood/*pharmacology ; Central Nervous System Stimulants/*pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Ethanol/blood/*pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {The present study examined whether caffeine administered within a dose range previously shown to promote ethanol drinking would also alter an ethanol-induced conditioned taste aversion (CTA). The results revealed a dose-dependent interaction between caffeine and ethanol where caffeine (2.5 and 10 mg/kg) promoted an ethanol-induced CTA at a low ethanol dose (1.0 g/kg) but had no effect in blocking CTA at the higher ethanol dose (1.5 g/kg). These results were found to be unrelated to an alteration in ethanol metabolism, as caffeine had no effect in altering blood ethanol levels at the doses tested. In agreement with the reward comparison hypothesis, the present results suggest that rather than attenuate ethanol's "aversive" effects, caffeine may have promoted an ethanol-induced CTA by increasing the reinforcing efficacy of ethanol.}, } @article {pmid11525252, year = {2001}, author = {Krivanek, J}, title = {Conditioned taste aversion and Ca/calmodulin-dependent kinase II in the parabrachial nucleus of rats.}, journal = {Neurobiology of learning and memory}, volume = {76}, number = {1}, pages = {46-56}, doi = {10.1006/nlme.2000.3987}, pmid = {11525252}, issn = {1074-7427}, mesh = {Animals ; Brachial Plexus/*metabolism ; Calcium/*metabolism ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Conditioning, Psychological/*physiology ; Male ; Rats ; Rats, Long-Evans ; Taste/*physiology ; }, abstract = {Bielavska and colleagues (Bielavska, Sacchetti, Baldi, & Tassoni, 1999) have recently shown that KN-62, an inhibitor of calcium/calmodulin-dependent kinase II (CaCMK), induces conditioned taste aversion (CTA) when introduced into the parabrachial nucleus (PBN) of rats. The aim of the present report was to assess whether activity of CaCMK in the PBN is changed during CTA. We induced CTA in one group of rats by pairing saccharin consumption with an ip injection of lithium chloride. Another group of rats received lithium alone (without being paired with saccharin consumption) to test whether lithium has an effect on CaCMK in the PBN, independent of those effects due to training. In animals receiving CTA training, CaCMK activity in extracts of PBN was reduced by approximately 30% at the postacquisition intervals of 12, 24, and 48 h, compared to control animals receiving saccharin with saline injection. By 120 h after CTA training, no effect on CaCMK was present. At those postacquisition intervals showing CaCMK activity effects due to CTA, there were no effects attributable to lithium alone. Lithium alone produced only a short-lasting reduction in CaCMK activity (at 20 min a 30% decrease, at 60 min a 23% decrease; and at 6, 12, and 24 h no decrease). The time course of lithium-induced effects differed markedly from that of CTA training. All changes were Ca2+/- -dependent; we did not observe any changes in Ca-independent activity. CTA effects on CaCMK were selective for PBN, insofar as we did not observe any CTA effects on CaCMK in the visual cortex, a brain region unrelated to taste pathways. Since CTA produces a relatively long-lasting reduction in CaCMK activity (lasting 2 days or more) specifically in the PBN, which is critical a relay for taste information, the reduction of CaCMK activity may enable the consolidation of taste memory in an aversive situation.}, } @article {pmid11524177, year = {2001}, author = {Piasecki, J and Bienkowski, P and Dudek, K and Koros, E and Kostowski, W}, title = {Ethanol-induced conditioned taste aversion in the rat: effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {24}, number = {1}, pages = {9-14}, doi = {10.1016/s0741-8329(01)00138-0}, pmid = {11524177}, issn = {0741-8329}, mesh = {5,7-Dihydroxytryptamine ; Animals ; Avoidance Learning/*physiology ; Brain/*drug effects/metabolism ; Central Nervous System Depressants/*administration & dosage ; Conditioning, Psychological/*drug effects/physiology ; Ethanol/*administration & dosage ; Male ; Raphe Nuclei/physiology ; Rats ; Rats, Wistar ; Serotonin/*metabolism ; Serotonin Agents ; Stereotaxic Techniques ; Taste/*drug effects/physiology ; }, } @article {pmid11517277, year = {2001}, author = {Fenu, S and Bassareo, V and Di Chiara, G}, title = {A role for dopamine D1 receptors of the nucleus accumbens shell in conditioned taste aversion learning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {21}, number = {17}, pages = {6897-6904}, pmid = {11517277}, issn = {1529-2401}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Benzazepines/pharmacology ; Cacao ; Conditioning, Classical/drug effects/*physiology ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Drug ; Drug Administration Routes ; Lithium Chloride/administration & dosage ; Male ; Microinjections ; Nucleus Accumbens/drug effects/*metabolism ; Raclopride/pharmacology ; Rats ; Receptors, Dopamine D1/antagonists & inhibitors/*metabolism ; Saccharin/pharmacology ; Sucrose/pharmacology ; Taste/drug effects/physiology ; Time Factors ; }, abstract = {The involvement of dopamine (DA) in conditioned taste aversion (CTA) learning was studied with saccharin or sucrose as the conditioned stimulus (CS) and intraperitoneal lithium as the unconditioned stimulus (US). The dopamine D(1) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) (12.5-50 microg/kg, s.c.), given 5 min after the CS, impaired the acquisition of CTA in a paradigm consisting of three or a single CS-lithium association. SCH 23390 failed to impair CTA acquisition given 45 min after, 30 min before, or right before the CS. (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5a-benzo-(d)-naphtho-(2,1b) azepine (SCH 39166) (12.5-50.0 microg/kg, s.c), a SCH 23390 analog that does not bind to 5HT(2) receptors, also impaired CTA. No significant impairment of CTA was obtained after administration of the specific D(2)/D(3) antagonist raclopride (100 and 300 microg/kg, s.c.). The ability of SCH 23390 to impair CTA learning was confirmed by its ability to reduce the conditional aversive reactions to a gustatory CS (sweet chocolate) as estimated in a taste reactivity paradigm. SCH 39166 impaired CTA also when infused in the nucleus accumbens (NAc) shell 5 min after the CS. No impairment was obtained from the NAc core or from the bed nucleus stria terminalis. The results indicate that D(1) receptor blockade impairs CTA learning by disrupting the formation of a short-term memory trace of the gustatory CS and that endogenous dopamine acting on D(1) receptors in the NAc shell plays a role in short-term memory processes related to associative gustatory learning.}, } @article {pmid11508731, year = {2001}, author = {Sclafani, A and Azzara, AV and Touzani, K and Grigson, PS and Norgren, R}, title = {Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.}, journal = {Behavioral neuroscience}, volume = {115}, number = {4}, pages = {920-933}, doi = {10.1037/0735-7044.115.4.920}, pmid = {11508731}, issn = {0735-7044}, support = {DC00240/DC/NIDCD NIH HHS/United States ; DC02016/DC/NIDCD NIH HHS/United States ; DK-31135/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical ; Food Preferences ; Male ; Neural Pathways ; Pons/pathology ; Rats ; Rats, Sprague-Dawley ; Smell/*physiology ; Solitary Nucleus/pathology/*physiology ; Taste/*physiology ; }, abstract = {Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available.}, } @article {pmid11508708, year = {2001}, author = {Nakashima, K and Katsukawa, H and Sasamoto, K and Ninomiya, Y}, title = {Behavioral taste similarities and differences among monosodium L-glutamate and glutamate receptor agonists in C57BL mice.}, journal = {Journal of nutritional science and vitaminology}, volume = {47}, number = {2}, pages = {161-166}, doi = {10.3177/jnsv.47.161}, pmid = {11508708}, issn = {0301-4800}, mesh = {Animals ; Avoidance Learning ; Excitatory Amino Acid Agonists/administration & dosage/*pharmacology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; N-Methylaspartate/administration & dosage/pharmacology ; Plant Proteins/pharmacology ; Propionates/administration & dosage/pharmacology ; Receptors, N-Methyl-D-Aspartate/physiology ; Sodium Glutamate/administration & dosage/*pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Monosodium L-glutamate (MSG) and 5'-ribonucleotides elicit umami taste in humans and probably in some species of animals. Previous studies suggest that taste-mGluR4 and NMDA receptor may be involved in taste transduction for umami, but behavioral responses in rats do not support the involvement of NMDA receptor. In the present study, behavioral similarities and differences among MSG, mGluR4 agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4), and NMDA receptor agonist N-methyl-D-aspartate (NMDA) were compared in C57BL mice by using a conditioned taste aversion paradigm. Mice conditioned to avoid either MSG or 10 mM L-AP4 appeared to avoid MSG, disodium 5'-inosinate (IMP), a mixture of MSG and IMP, and L-AP4, but not NMDA. Aversive conditioning to either sucrose or NMDA was generalized only to a mixture of MSG+IMP or NaCl. However, aversive conditioning to L-AP4 at 1 mM was generalized to NMDA and the umami substances. Lick rates for L-AP4 increased by mixing with (RS)-alpha-cycloprophy-4-phosphonophenylglycine (mGluR4 antagonist) when animals were conditioned to avoid MSG or L-AP4. Lick rates for NMDA also either decreased or increased by mixing with glycine (NMDA receptor coagonist) or D(-)-2-amino-5-phosphonopentanoic acid (NMDA receptor antagonist) when animals were conditioned to avoid L-AP4 or NMDA. In sucrose-conditioned mice. gurmarin (a sweet inhibiting peptide) suppressed the avoidance of sucrose and a mixture of MSG and IMP, but not L-AP4 and NMDA. The results suggest the possibility that to C 57BL mice MSG may taste similar to L-AP4 but different from NMDA, although both types of glutamate receptors as well as gurmarin-sensitive sweet receptor may be involved in perception of umami taste.}, } @article {pmid11502150, year = {2001}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {Effects of a flavor-placement reversal test after different modalities of taste aversion learning.}, journal = {Neurobiology of learning and memory}, volume = {76}, number = {2}, pages = {209-224}, doi = {10.1006/nlme.2000.3990}, pmid = {11502150}, issn = {1074-7427}, mesh = {Animals ; Cues ; Discrimination Learning/*physiology ; Male ; Proprioception/physiology ; Rats ; Rats, Wistar ; Smell/physiology ; Space Perception/physiology ; *Taste ; Time Factors ; }, abstract = {Taste aversion learning is induced through two different behavioral procedures: a short-term or concurrent (two-daily flavors) and a long-term or sequential (one-daily flavor) procedure. For the concurrent group of animals, two gustatory/olfactory stimuli are presented separately but at the same time on a daily basis. One is paired with simultaneous intragastric administration of hypertonic NaCl and the other with physiological saline. For the sequential group, the two stimuli are presented on alternate days, one of them followed by intragastric injection of the aversive stimulus and the other by saline, both after a delay of 15 min. The two groups learned the task, but when they were subjected to a flavor-placement reversal test only the sequential group was successful in achieving it. In a second experiment, three groups of animals had to learn concurrent or sequential discrimination tasks (with either simultaneous or delayed administration of the visceral stimulus) using only spatial/proprioceptive cues. The data show that none of the groups learned them under these conditions. The results are discussed in terms of the different modalities of learning. Short-term and long-term taste aversion learning are different in the anatomical structures involved, the number of trials required for acquisition and, as shown in this paper, flexibility.}, } @article {pmid11489343, year = {2001}, author = {Reilly, S and Trifunovic, R}, title = {Lateral parabrachial nucleus lesions in the rat: neophobia and conditioned taste aversion.}, journal = {Brain research bulletin}, volume = {55}, number = {3}, pages = {359-366}, doi = {10.1016/s0361-9230(01)00517-2}, pmid = {11489343}, issn = {0361-9230}, support = {DC02821/DC/NIDCD NIH HHS/United States ; DC03379/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Exploratory Behavior/*physiology ; Fear/*physiology ; Male ; Pons/*physiology ; Rats ; Rats, Sprague-Dawley ; Stimulation, Chemical ; Taste/*physiology ; }, abstract = {The present study investigated the hypothesis that the conditioned taste aversion (CTA) deficit consequent to lesions of the lateral parabrachial nucleus (LPBN) may be due to a disruption of neophobia. In Experiment 1, subjects were tested with one of three taste stimuli (alanine, saccharin, or quinine) and two nontaste stimuli (capsaicin and almond odor). Ibotenic acid lesions of the LPBN eliminated neophobia to alanine and saccharin but had no influence on the neophobic response to quinine, capsaicin, or almond odor. In Experiment 2, all the LPBN-lesioned (LPBNX) rats failed to develop a CTA. These results do not support the experimental hypothesis. Not only was the lesion-induced disruption of neophobia restricted to taste stimuli, the deficit was selective within that category. It is already known that LPBNX rats are unable to acquire conditioned aversions to capsaicin as well as alanine. Thus, the absence of a conditioned ingestional aversion in LPBNX rats is not predicated upon the absence of a neophobic response to the target stimulus. The present results, although exposing a stimulus selective disruption of neophobia, suggest that this deficit is independent of, rather than responsible for, the absence of conditioned ingestional aversions in rats with LPBN lesions.}, } @article {pmid11435028, year = {2001}, author = {Quintanilla, ME and Callejas, O and Tampier, L}, title = {Differences in sensitivity to the aversive effects of ethanol in low-alcohol drinking (UChA) and high-alcohol drinking (UChB) rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {23}, number = {3}, pages = {177-182}, doi = {10.1016/s0741-8329(01)00128-8}, pmid = {11435028}, issn = {0741-8329}, mesh = {*Alcohol Drinking ; Animals ; Brain/blood supply ; Breeding ; Conditioning, Psychological ; Drug Tolerance ; Ethanol/administration & dosage/blood/*pharmacology ; Female ; Food Preferences ; Rats ; Rats, Wistar ; Self Administration ; Species Specificity ; Taste ; }, abstract = {A conditioned taste aversion paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to differences in voluntary ethanol consumption in rats of the low-alcohol drinking (UChA) and the high-alcohol drinking (UChB) strains. "Alcohol-naive" UChA and UChB rats were injected intraperitoneally with ethanol (0.5, 1.0, 1.5, or 2.0 g/kg) or saline, paired with consumption of a banana-flavored solution during five conditioning trials. Repeated pairings of banana-flavored solution and ethanol at a dose of 1.5 g/kg produced aversion to the banana-flavored solution in UChA rats, but not in UChB rats, at comparable blood ethanol levels. In addition, the highest dose of ethanol tested (2.0 g/kg) produced stronger aversion to the banana-flavored solution in UChA rats, compared with findings in UChB rats. From these results it is suggested that rats of the UChA strain find the postingestional effects of high-dose ethanol more aversive than do UChB rats. Differences in voluntary ethanol consumption seem to be associated with differences in sensitivity to the aversive effects of ethanol.}, } @article {pmid11420081, year = {2001}, author = {Cubero, I and Lopez, M and Navarro, M and Puerto, A}, title = {Lateral parabrachial lesions impair taste aversion learning induced by blood-borne visceral stimuli.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {69}, number = {1-2}, pages = {157-163}, doi = {10.1016/s0091-3057(01)00494-4}, pmid = {11420081}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain Stem/*physiology ; Central Nervous System Depressants/pharmacology ; Ethanol/pharmacology ; Injections, Intraperitoneal ; Male ; N-Methylscopolamine/pharmacology ; Parasympatholytics/pharmacology ; Rats ; Rats, Wistar ; Saline Solution, Hypertonic/pharmacology ; Taste/*drug effects ; Toxins, Biological/*blood ; Vagus Nerve/drug effects/physiology ; }, abstract = {The lateral parabrachial area (LPB), main relay from the area postrema (AP), plays a role in processing visceral information and is thus of potential importance in taste aversion learning (TAL). This study used a lesion approach to address whether LPB functional relevance depends upon the features of toxins that serves as visceral stimuli in TAL. In addition, we explored whether LPB involvement in TAL is restricted to those toxic events detected by the AP or whether it has a more general role. Results showed that LPB-lesioned animals were disrupted in acquiring a TAL induced by blood-borne AP-dependent aversive stimuli (intraperitoneal methylscopolamine) and by AP-independent stimulus (intraperitoneal ethanol), but still, clearly developed strong aversions when intragastric hypertonic sodium chloride, a vagally processed aversive stimulus, served as the aversive stimulus. These findings suggest that the LPB plays a critical role in TAL induced by blood-borne toxins, such as methylscopolamine or ethanol, but is not necessary for vagally mediated stimulus, such as sodium chloride. The present results are discussed in the context of the hypothesis holding separable and independent neural systems underlying TAL.}, } @article {pmid11420071, year = {2001}, author = {Fox, MA and Levine, ES and Riley, AL}, title = {The inability of CCK to block (or CCK antagonists to substitute for) the stimulus effects of chlordiazepoxide.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {69}, number = {1-2}, pages = {77-84}, doi = {10.1016/s0091-3057(01)00505-6}, pmid = {11420071}, issn = {0091-3057}, mesh = {Animals ; Benzodiazepinones/pharmacology ; Chlordiazepoxide/*pharmacology ; Cholecystokinin/*antagonists & inhibitors/*pharmacology ; Cues ; Devazepide/pharmacology ; Discrimination Learning/drug effects ; Discrimination, Psychological/drug effects ; Drinking Behavior/drug effects ; Flumazenil/pharmacology ; GABA Modulators/*pharmacology ; Generalization, Psychological/drug effects ; Male ; Phenylurea Compounds/pharmacology ; Rats ; Rats, Long-Evans ; }, abstract = {To further examine the relationship between cholecystokinin (CCK) and GABA, the present study assessed the ability of the CCK-A antagonist devazepide and the CCK-B antagonist L-365,260 to substitute for the stimulus effects of chlordiazepoxide (CDP), as well as the ability of CCK-8s to block these effects, in female Long-Evans rats within the conditioned taste aversion baseline of drug discrimination learning. Both devazepide and L-365,260 failed to substitute for the discriminative stimulus properties of CDP, and CCK-8s failed to block its stimulus effects. The benzodiazepine diazepam did substitute for, and the benzodiazepine antagonist flumazenil did block, the stimulus effects of CDP. This suggests that the lack of substitution for, or antagonism of, CDP by the CCK antagonists and CCK-8s, respectively, was not due to the inability of the present design to assess such effects. Possible bases for the current findings, e.g., necessity of an anxiogenic baseline, drug and receptor specificity, as well as the dose-response nature of the interaction, were discussed. Given that a relationship between CCK and GABA has been reported in other designs, the present results suggest that such a relationship may be preparation specific.}, } @article {pmid11410911, year = {2001}, author = {Christian, MS and Brent, RL}, title = {Teratogen update: evaluation of the reproductive and developmental risks of caffeine.}, journal = {Teratology}, volume = {64}, number = {1}, pages = {51-78}, doi = {10.1002/tera.1047}, pmid = {11410911}, issn = {0040-3709}, mesh = {Abortion, Spontaneous/etiology ; Animals ; Animals, Newborn ; Behavior/drug effects ; Caffeine/*adverse effects/pharmacokinetics/toxicity ; Central Nervous System/drug effects/growth & development ; Coffee/*adverse effects/*toxicity ; Congenital Abnormalities/etiology ; Dose-Response Relationship, Drug ; Female ; Fertility/drug effects ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Maternal-Fetal Exchange ; Neurotoxins/toxicity ; Pregnancy ; Teratogens/*toxicity ; }, abstract = {Caffeine is a methylated xanthine that acts as a mild central nervous system stimulant. It is present in many beverages, including coffee, tea, and colas, as well as chocolate. Caffeine constitutes 1-2% of roasted coffee beans, 3.5% of fresh tea leaves, and approximately 2% of mate leaves (Spiller, '84; Graham, '84a,b). Many over-the-counter medications, such as cold and allergy tablets, headache medicines, diuretics, and stimulants also contain caffeine, although they lead to relatively minimal intake (FDA, '86). In epidemiological studies, it is assumed that one cup of coffee contains < or =100 mg of caffeine, and soft drinks, such as colas, contain 10-50 mg of caffeine per 12-ounce serving. The per-capita consumption of caffeine from all sources is estimated to be about 3-7 mg/kg per day, or approximately 200 mg/day (Barone and Roberts, '96). Consumption of caffeinated beverages during pregnancy is quite common (Hill et al., '77) and is estimated to be approximately 144 mg/day, or 2.4 mg/kg for a 60-kg human (Morris and Weinstein, '81). However, pregnant women appear to consume slightly less than do other adults, approximately 1 mg/kg per day (Barone and Roberts, '96). This decrease may be interrelated with taste aversion (Hook, '76; Little, '82). The medical literature contains many varied references that appear to indicate that human adverse reproductive/developmental effects are produced by caffeine. If caffeine indeed causes such effects, the reproductive consequences could be very serious because caffeine-containing foods and beverages are consumed by most of the human populations of the world, and consumption in the United States is estimated to be 4.5-kg/person/year (Narod et al., '91). Therefore, the medical literature dealing with developmental and reproductive risks of caffeine was reviewed, and the biological plausibility of the epidemiological and animal findings, as well as the methods and conclusions of previous investigators, were evaluated. The epidemiological studies describe exposures of women to caffeine during pregnancy, as well as the occurrence of congenital malformations, fetal growth retardation, small-for-date babies, miscarriages (spontaneous abortions), behavioral effects, and maternal fertility problems that presumably resulted from the caffeine consumption. A few epidemiological studies were concerned with the genetic effects of preconception exposures to caffeine. Animal studies, conducted mostly in pregnant rats and mice, were designed to produce malformations. The objectives of the present review are to summarize the findings from the various clinical and animals studies, objectively discuss the merits and/or faults inherent in the studies and establish a global reproductive risk assessment for caffeine consumption in humans during pregnancy. It should be noted that evaluation of the developmental risks of caffeine based solely on epidemiological studies is difficult because the findings are inconsistent. Even more important, is the fact that caffeine users are subject to multiple confounding factors that make analyses difficult and prevent investigators from reaching definitive conclusions. For example, the caffeine content of foods and beverages can vary considerably, which can interfere with obtaining valid interpretations from many human studies. Isolated epidemiological studies dealing with the risk of abortion, without evaluating other developmental and reproductive effects, are the most difficult to interpret, because they present special problems that are sometimes ignored in epidemiological studies. The results of animal studies are probably most helpful in solving some of the dilemmas created by the epidemiological studies. An animal study reported in 1960 first focused our attention on the potential developmental effects of caffeine. However, the exposure reported by Nishimura and Nakai ('60) was an intraperitoneal dosage of 250 mg/kg in the mouse, an extremely high dosage that would result in a blood plasma level that could never be obtained from consuming caffeine containing products. More recent animal studies have demonstrated, that depending on the method of administration and species, the developmental NOEL in rodents is approximately 30 mg/kg per day, the teratogenic NOEL is 8,100 mg/kg per day, and the reproductive NOEL approximately 80-120 mg/kg per day. Lack of biological plausibility to support the concept that caffeine has been responsible for human malformations is another important part of this analysis. For example, no one has described the Caffeine "teratogenic syndrome," a cluster of malformations associated with caffeine ingestion. Proven human teratogens have an identifiable syndrome. The malformations described in the animal studies at very high doses fit the description of vascular disruptive types of malformations. (ABSTRACT TRUNCATED)}, } @article {pmid11399290, year = {2001}, author = {Shobi, V and Goel, HC}, title = {Protection against radiation-induced conditioned taste aversion by Centella asiatica.}, journal = {Physiology & behavior}, volume = {73}, number = {1-2}, pages = {19-23}, doi = {10.1016/s0031-9384(01)00434-6}, pmid = {11399290}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*radiation effects ; Cobalt Radioisotopes ; Conditioning, Classical/*radiation effects ; Dose-Response Relationship, Radiation ; Male ; Ondansetron/pharmacology ; Radiation-Protective Agents/*pharmacology ; Radioisotope Teletherapy ; Rats ; Rats, Wistar ; Taste/*radiation effects ; Triterpenes/*pharmacology ; Weight Loss/radiation effects ; Whole-Body Irradiation ; }, abstract = {Radiations are known to cause behavioural perturbations like conditioned taste aversion (CTA), performance decrement, learning, etc., even at very low doses. The manifestation of radiation-induced behavioural degradation has not been understood well and requires further studies. Therefore, the effects of low-dose whole-body 60Co gamma-irradiation in male rats were studied in terms of body weight and CTA learning. For CTA, the consumption of saccharin solution was considered as a parameter. To protect against the adverse effects of radiation, Centella asiatica (aqueous extract) was tested and compared with ondansetron, a standard antiemetic drug. A dose of 2 Gy incurred significant body weight loss [t(9)=9.00, P<.05] and induced CTA in rats [t(26)=9.344, P<.01]. Administration of C. asiatica (100 mg/kg bw ip, 2 Gy, -1 h) rendered significant radioprotection against radiation-induced body weight loss and CTA that became evident on the second postirradiation day [t(7)=0.917, P>>.05; t(7)=4.016, P>.05]. Ondansetron (1 mg/kg bw) elicited higher degree of protection against CTA [t(7)=3.641, P>.05] than C. asiatica [t(7)=7.196, P>.05] on the first postirradiation day, but on the second postirradiation day, both were equally effective [t(7)=3.38, P>.05; t(7)=4.01, P>.05]. In case of C. asiatica-treated animals, however, there was a consistently declining CTA from the second to the fifth postirradiation day whereas in ondansetron-treated animals it was inconsistent. Present investigation suggests that C. asiatica could be useful in preventing radiation-induced behavioural changes during clinical radiotherapy.}, } @article {pmid11348834, year = {2001}, author = {Gabriel, KI and Weinberg, J}, title = {Effects of prenatal ethanol exposure and postnatal handling on conditioned taste aversion.}, journal = {Neurotoxicology and teratology}, volume = {23}, number = {2}, pages = {167-176}, doi = {10.1016/s0892-0362(01)00117-9}, pmid = {11348834}, issn = {0892-0362}, support = {AA07789/AA/NIAAA NIH HHS/United States ; R01 AA007789/AA/NIAAA NIH HHS/United States ; R37 AA007789/AA/NIAAA NIH HHS/United States ; R56 AA007789/AA/NIAAA NIH HHS/United States ; F31 AA05499/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects ; Body Weight/drug effects ; Conflict, Psychological ; Diet ; Eating/drug effects ; Ethanol/*toxicity ; Female ; *Handling, Psychological ; Hydrocortisone/blood ; Male ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological/*psychology ; Taste/drug effects/*physiology ; }, abstract = {Studies have shown that animals prenatally exposed to ethanol (E) exhibit deficits in conditioned taste aversion as well as displaying hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness during exposure to stressors. In contrast, postnatal handling has been shown to attenuate both emotional and HPA reactivity under certain conditions. The present study tested the hypothesis that handling could attenuate adverse effects of prenatal ethanol exposure on consummatory behavior and HPA activity in a conditioned taste aversion task. We found that both prenatal ethanol exposure and handling independently increased saccharin consumption over 5 days of pretoxicosis exposure, suggesting that neophobia decreased at a faster rate in these animals. When conditioned aversion was assessed in handled animals under nondeprived conditions, E animals showed increased consumption compared to controls. Furthermore, across prenatal groups, lower corticosterone (CORT) levels were found in handled compared to nonhandled animals during reexposure under food-deprived conditions, emphasizing the importance of assessing both behavior and HPA function when examining an animal's response to a task and indicating that handling may not be effective at attenuating some deficits in E animals.}, } @article {pmid11345959, year = {2001}, author = {Clarke, HA and Skinner, DM and van der Kooy, D}, title = {Combined hippocampal and amygdala lesions block learning of a response-independent form of occasion setting.}, journal = {Behavioral neuroscience}, volume = {115}, number = {2}, pages = {341-357}, pmid = {11345959}, issn = {0735-7044}, mesh = {Amygdala/*physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Corpus Striatum/physiology ; Escape Reaction/physiology ; Hippocampus/*physiology ; Male ; Maze Learning/physiology ; Mental Recall/physiology ; Nerve Net/physiology ; Orientation/physiology ; Prefrontal Cortex/physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {This study compared rats with dorsal striatal, ventrolateral prefrontal cortical, and combined lesions of the hippocampus and amygdala to sham controls on a conditional discrimination task in which contextual cues modulated a taste aversion. All groups were able to acquire this occasion setting task. The 2nd experiment functionally minimized the stimulus-response component of the paradigm, creating a "tasteless" form of occasion setting. Rats with pretraining lesions of the hippocampus and amygdala were impaired compared with shams on the acquisition of this tasteless occasion setting task. Rats with posttraining combined lesions did not retain the ability to perform the tasteless occasion setting task learned preoperatively. Rats with selective lesions of either the hippocampus or the amygdala alone were not impaired in the acquisition of the tasteless occasion setting task. The findings suggest that this occasion setting task may be learned by several redundant neural systems.}, } @article {pmid11337006, year = {2001}, author = {Rollins, BL and Stines, SG and McGuire, HB and King, BM}, title = {Effects of amygdala lesions on body weight, conditioned taste aversion, and neophobia.}, journal = {Physiology & behavior}, volume = {72}, number = {5}, pages = {735-742}, doi = {10.1016/s0031-9384(01)00433-4}, pmid = {11337006}, issn = {0031-9384}, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/*physiology ; Body Weight/*physiology ; Fear/*physiology/psychology ; Female ; Rats ; Rats, Long-Evans ; Social Environment ; Taste/*physiology ; }, abstract = {Female rats with posterodorsal amygdala (PDA), basolateral amygdala (BLA), or sham lesions were compared regarding ad libitum food intake, weight gain, consumption of a novel food, and acquisition of a conditioned taste aversion (CTA). While only the rats with PDA lesions evidenced substantial weight gains at 10 days after surgery eating standard lab chow (25-45 g more than the other groups), only the rats with BLA lesions demonstrated significant deficits in the CTA and neophobia paradigms. Rats with basolateral lesions, on average, took less than 30 s to begin drinking the novel sweetened condensed milk after pairing with illness while the other groups took approximately 15 min to begin drinking. Also, rats with basolateral lesions ate, on average, 5 g of the novel Froot Loops while the other groups ate approximately 2 g. It is concluded that the changes in food-motivated behavioral tests frequently observed in animals with amygdala lesions do not coexist with the hyperphagia and weight gain of animals with PDA lesions.}, } @article {pmid11325395, year = {2001}, author = {Miranda, F and Hong, E and Velázquez-Martínez, DN}, title = {Discriminative stimulus properties of indorenate in a conditioned taste aversion paradigm.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {68}, number = {3}, pages = {427-433}, doi = {10.1016/s0091-3057(00)00482-2}, pmid = {11325395}, issn = {0091-3057}, mesh = {5-Methoxytryptamine/*analogs & derivatives/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Generalization, Psychological/drug effects ; Male ; Rats ; Rats, Wistar ; Receptors, Serotonin/*drug effects ; Receptors, Serotonin, 5-HT1 ; Receptors, Serotonin, 5-HT3 ; Receptors, Serotonin, 5-HT4 ; Serotonin Receptor Agonists/*pharmacology ; Taste/*drug effects ; }, abstract = {Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors. It possesses anxiolytic and antihypertensive actions mediated by 5-HT(1A) receptors and anorectic activity mediated by 5-HT(2C/1B) receptors. This study examined whether INDO may exert discriminative control using a conditioned taste aversion (CTA) paradigm, and whether differential participation of 5-HT receptor subtypes may be involved in its cue. Male Wistar rats trained to drink their daily water in a 30-min period were trained to discriminate INDO from saline. One group received the intraperitoneal administration of INDO (10.0 mg/kg) before saccharin-LiCl pairings; on alternate days, rats received saline before the saccharin-saline pairings (Group D(+)S(-)). The other group had the contingencies reversed (i.e., the administration of INDO preceded saccharin-saline pairings: Group D(-)S(+)). In two-bottle generalization tests (one bottle containing saccharin, the other plain water), the preference for saccharin was evaluated after different doses of INDO, [3H]-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (5-HT(1A)), buspirone (5-HT(1A)), RU24969 (5-HT(1A/1B)), TFMPP (5-HT(1B/2C)), MK212 (5-HT(2C)), alpha-Me-5-HT (5-HT(2C/2A)), 2-Me-5-HT (5-HT(3)) and cisapride (5-HT(4)). The results showed that INDO, RU24969, TFMPP, alpha-Me-5-HT and MK 212 produced a dose-dependent generalization; 8-OH-DPAT and buspirone produced only partial generalization, while 2-Me-5-HT and cisapride did not produce generalization. The results indicate that INDO administration may exert discriminative control over saccharin preference mediated mainly by 5-HT(1B/2C) receptors, but with an important contribution of 5-HT(1A) receptors.}, } @article {pmid11300732, year = {2001}, author = {Sacchetti, B and Baldi, E and Tassoni, G and Bielavska, E}, title = {CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion in rats.}, journal = {Neurobiology of learning and memory}, volume = {75}, number = {3}, pages = {253-261}, doi = {10.1006/nlme.2000.3978}, pmid = {11300732}, issn = {1074-7427}, mesh = {1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Brachial Plexus/*drug effects ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*pharmacology ; *Conditioning, Psychological ; Enzyme Inhibitors/pharmacology ; *Inhibition, Psychological ; Male ; Random Allocation ; Rats ; Rats, Long-Evans ; *Taste ; }, abstract = {The conditioned taste aversion (CTA) paradigm was used to assess the role of Ca(2+)/calmodulin-dependent protein kinase (CAMKII) in associative learning. KN62, a specific inhibitor of CAMKII, was injected into the parabrachial nuclei (PBN) either immediately after saccharin drinking (CS) or after saccharin drinking and i.p. injection of LiCl (US). Injection of KN62 into the PBN after saccharin drinking elicited clear CTA (Exp. 1). This effect was dosage-dependent and site-specific (Exp. 2). The results are discussed in relation with an earlier report showing that CTA acquisition is disrupted by injection of Ca(2+)/phospholipid-dependent protein kinase (PKC) inhibitor chelerythrine into the PBN during CS-US interval. It is suggested that the principal serine/threonine kinases play different roles in CTA learning: whereas PKC activity is necessary for the gustatory short-term memory formation, CAMKII acts similarly to the US itself-an unexpected role of CAMKII in associative learning.}, } @article {pmid11289036, year = {2001}, author = {Makimura, H and Mizuno, TM and Yang, XJ and Silverstein, J and Beasley, J and Mobbs, CV}, title = {Cerulenin mimics effects of leptin on metabolic rate, food intake, and body weight independent of the melanocortin system, but unlike leptin, cerulenin fails to block neuroendocrine effects of fasting.}, journal = {Diabetes}, volume = {50}, number = {4}, pages = {733-739}, doi = {10.2337/diabetes.50.4.733}, pmid = {11289036}, issn = {0012-1797}, mesh = {Animals ; Body Weight/*drug effects ; Cerulenin/*pharmacology ; Drug Resistance/genetics ; Eating/*drug effects ; Endocrine Glands/drug effects/physiology/physiopathology ; Fasting/*physiology ; Hypothalamus/drug effects/physiology/physiopathology ; Leptin/pharmacology ; Male ; Melanocyte-Stimulating Hormones/physiology ; Metabolism/*drug effects ; Mice ; Mice, Inbred CBA ; Mice, Inbred Strains/genetics ; Neurosecretory Systems/*physiology ; Obesity/pathology/physiopathology ; }, abstract = {Cerulenin and a related compound, C75, have recently been reported to reduce food intake and body weight independent of leptin through a mechanism hypothesized, like leptin, to involve hypothalamic nutrition-sensitive neurons. To assess whether these inhibitors act through mechanisms similar to mechanisms engaged by leptin, ob/ob and Ay (agouti) mice, as well as fed and fasted wild-type mice, were treated with cerulenin. Like leptin, cerulenin reduced body weight and food intake and increased metabolic rate in ob/ob mice, and cerulenin produced the same effects in wild-type mice, whereas lithium chloride, at doses that produce conditioned taste aversion, reduced metabolic rate. However, in contrast to leptin, cerulenin did not prevent effects of fasting on plasma corticosterone or hypothalamic levels of neuropeptide Y, agouti-related peptide, pro-opiomelanocortin, or cocaine- and amphetamine-related peptide mRNA. Also, in contrast to leptin, cerulenin was highly effective to reduce body weight in Ay mice, in which obesity is caused by blockade of the melanocortin receptor. These data demonstrate that cerulenin produces metabolic effects similar to effects of leptin, but through mechanisms that are independent of, or down-stream from, both leptin and melanocortin receptors.}, } @article {pmid11287385, year = {2001}, author = {Clarke, SN and Koh, MT and Bernstein, IL}, title = {NaCl detection thresholds: comparison of Fischer 344 and Wistar rats.}, journal = {Chemical senses}, volume = {26}, number = {3}, pages = {253-257}, doi = {10.1093/chemse/26.3.253}, pmid = {11287385}, issn = {0379-864X}, support = {DC00248/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/pharmacology ; Animals ; Conditioning, Psychological ; Diuretics/pharmacology ; Dose-Response Relationship, Drug ; Male ; Rats ; Rats, Inbred F344 ; *Sensory Thresholds ; Sodium Channel Blockers ; Sodium Chloride/*chemistry ; Species Specificity ; *Taste ; Time Factors ; }, abstract = {Adult Fischer 344 (F344) rats fail to display any preference for NaCl solutions at concentrations typically preferred by other rat strains. To determine whether this behavior is due to a strain difference in NaCl detection threshold, a conditioned taste aversion (CTA) was first established to a suprathreshold concentration of NaCl (0.1 M). Then, a series of dilute NaCl solutions, ranging from 0.0 to 0.011 M NaCl, were presented to F344 (n = 16) and Wistar (n = 16) rats. The lowest concentration at which there was a reliable difference in the preference scores of conditioned and control rats was defined as the detection threshold. Results indicate that the detection threshold for NaCl lies between 0.001 and 0.002 M NaCl for both F344 and Wistar rats. The addition of the sodium channel blocker amiloride to the NaCl solutions raised the detection threshold 10-fold to 0.03-0.04 M NaCl for both strains of rats. These results suggest that the NaCl detection thresholds of F344 and Wistar rats are similar and that these strains do not differ in the degree to which amiloride raises this threshold.}, } @article {pmid11287075, year = {2001}, author = {Heinrichs, SC and Joppa, M}, title = {Dissociation of arousal-like from anxiogenic-like actions of brain corticotropin-releasing factor receptor ligands in rats.}, journal = {Behavioural brain research}, volume = {122}, number = {1}, pages = {43-50}, doi = {10.1016/s0166-4328(01)00174-7}, pmid = {11287075}, issn = {0166-4328}, support = {NINDS 33489/DS/DS NIH HHS/United States ; }, mesh = {Animals ; Arousal/*drug effects ; Avoidance Learning/drug effects ; Carrier Proteins/*antagonists & inhibitors ; Conditioning, Psychological/drug effects ; Corticotropin-Releasing Hormone/agonists/antagonists & inhibitors/metabolism/*physiology ; Dose-Response Relationship, Drug ; Fear/*drug effects ; Ligands ; Male ; Rats ; Rats, Wistar ; Receptors, Corticotropin-Releasing Hormone/*agonists ; }, abstract = {Behavioral actions of centrally administered corticotropin-releasing factor (CRF) are likely subserved by multiple brain targets and functional effector systems. The present studies compared effects of two CRF ligands, a full, post-synaptic CRF receptor agonist (rat/human CRF(1-41)) and a CRF binding protein ligand inhibitor (rat/human CRF(6-33)) in a behavioral testing battery sensitive to arousal, fear-like and aversive processes in Wistar rats. The profile of global efficacy for the centrally administered CRF receptor agonist was characterized by low dose (0.5-1.0 microg) arousal-like effects in locomotor and conditioned ambulation contexts and by high dose (5-25 microg) conditioned immobility, taste aversion and place aversion. In contrast, a profile of limited efficacy for the centrally administered CRF binding protein ligand inhibitor included only dose dependent motor activating and facilitation of fear conditioning effects without any of the anxiogenic-like or aversive properties of CRF agonist administration. These results suggest that arousal-like activation is a fundamental, physiologically relevant consequence of brain CRF system stimulation whereas aversive and anxiety-like effects reflect pharmacological actions of a CRF receptor agonist.}, } @article {pmid11282139, year = {2001}, author = {Flanagan-Cato, LM and Grigson, PS and King, JL}, title = {Estrogen-induced suppression of intake is not mediated by taste aversion in female rats.}, journal = {Physiology & behavior}, volume = {72}, number = {4}, pages = {549-558}, doi = {10.1016/s0031-9384(01)00411-5}, pmid = {11282139}, issn = {0031-9384}, support = {DA09815/DA/NIDA NIH HHS/United States ; MH43787/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Body Weight/drug effects ; Depression, Chemical ; Eating/*drug effects ; Estradiol/pharmacology ; Estrogens/*pharmacology ; Female ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Sexual Behavior, Animal/drug effects ; Taste/*drug effects ; }, abstract = {Estrogen treatment can suppress the intake of a previously presented gustatory conditioned stimulus (CS). This finding has been interpreted as an estrogen-induced conditioned taste aversion. However, a distinction must be made between taste aversion and taste avoidance. In particular, tastes are only considered aversive if they elicit a stereotypic behavioral response, otherwise the reduction in intake is classified as an avoidance. Although aversive orofacial responses have been reported in male rats after taste-estrogen pairings, they have not been examined in ovariectomized female rats. The goal of the present investigation, then, was to use similar procedures to determine whether conditioned aversion also mediates the estrogen-induced reduction of intake in female rats. Animals were introduced to a novel 0.1% saccharin solution and immediately thereafter were given a subcutaneous injection of vehicle or estradiol benzoate (10 microg). Responses were assessed using a two-bottle preference test, a one-bottle acceptance test, and a taste reactivity (TR) test. The results confirmed previous reports of a reduced preference for saccharin after saccharin-estradiol pairing using the two-bottle test. The reduction in intake during the one-bottle test, however, was not accompanied by stereotypic aversive responses, such as gaping. Surprisingly, a similar reduction in intake also occurred when using a backward conditioning procedure in which estrogen was injected before, rather than after, CS access. Thus, the present results show that the suppressive effects of estrogen reflect an avoidance, rather than aversion and, moreover, that the reduced intake may be due to an unconditioned, rather than a conditioned, response.}, } @article {pmid11270513, year = {2001}, author = {Kunin, D and Gaskin, S and Borjas, MB and Smith, BR and Amit, Z}, title = {Differences in locomotor response to an inescapable novel environment predict sensitivity to aversive effects of amphetamine.}, journal = {Behavioural pharmacology}, volume = {12}, number = {1}, pages = {61-67}, doi = {10.1097/00008877-200102000-00007}, pmid = {11270513}, issn = {0955-8810}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dextroamphetamine/*pharmacology ; Dopamine Uptake Inhibitors/*pharmacology ; *Environment ; Lithium Chloride/pharmacology ; Male ; Motor Activity/*drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; }, abstract = {Differences in locomotor response to an inescapable novel environment have previously been shown to predict sensitivity to amphetamine reward, where high responders (HR), compared to low responders (LR), showed greater initial sensitivity to amphetamine self-administration. The present experiments sought to extend these findings and assessed the relationship between locomotor response to an inescapable novel environment and conditioned taste aversion (CTA) with amphetamine and lithium chloride (LiCl). Male Sprague-Dawley rats were tested for their locomotor response to an inescapable novel environment and divided into high (HR) or low (LR) responders, based on whether their locomotor scores were above or below the median activity level of the subject sample. After several days, the animals were tested in a CTA procedure and conditioned with either amphetamine or lithium chloride. Compared to HR rats, LR rats showed greater sensitivity to amphetamine CTA at the doses tested. In contrast, the results with LiCl showed no relationship between locomotor response to an inescapable novel environment and CTA. Taken together, the present results suggest that LR, compared to HR, rats show less sensitivity to the rewarding effects of amphetamine because they are more sensitive to aversive effects of amphetamine, as reflected in CTA. In contrast, HR rats display less sensitivity to aversive effects of amphetamine, which may explain their greater propensity to self-administer amphetamine.}, } @article {pmid11264539, year = {2001}, author = {Berman, DE and Dudai, Y}, title = {Memory extinction, learning anew, and learning the new: dissociations in the molecular machinery of learning in cortex.}, journal = {Science (New York, N.Y.)}, volume = {291}, number = {5512}, pages = {2417-2419}, doi = {10.1126/science.1058165}, pmid = {11264539}, issn = {0036-8075}, mesh = {Adrenergic beta-Antagonists/pharmacology ; Animals ; Anisomycin/pharmacology ; Cerebral Cortex/metabolism/*physiology ; Conditioning, Psychological ; Extinction, Psychological/*physiology ; Learning/*physiology ; Lithium Chloride/pharmacology ; MAP Kinase Signaling System ; Male ; Memory/*physiology ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; Muscarinic Antagonists/pharmacology ; *Protein Biosynthesis ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta/*metabolism ; Receptors, Muscarinic/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Reinforcement, Psychology ; Saccharin ; Taste ; }, abstract = {The rat insular cortex (IC) subserves the memory of conditioned taste aversion (CTA), in which a taste is associated with malaise. When the conditioned taste is unfamiliar, formation of long-term CTA memory depends on muscarinic and beta-adrenergic receptors, mitogen-activated protein kinase (MAPK), and protein synthesis. We show that extinction of CTA memory is also dependent on protein synthesis and beta-adrenergic receptors in the IC, but independent of muscarinic receptors and MAPK. This resembles the molecular signature of the formation of long-term memory of CTA to a familiar taste. Thus, memory extinction shares molecular mechanisms with learning, but the mechanisms of learning anew differ from those of learning the new.}, } @article {pmid11256438, year = {2001}, author = {Lessov, CN and Risinger, FO and Phillips, TJ}, title = {Attenuation of ethanol-induced conditioned taste aversion in mice sensitized to the locomotor stimulant effects of ethanol.}, journal = {Behavioral neuroscience}, volume = {115}, number = {1}, pages = {146-153}, doi = {10.1037/0735-7044.115.1.146}, pmid = {11256438}, issn = {0735-7044}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; F31 AA05520/AA/NIAAA NIH HHS/United States ; P50 AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Ethanol/*adverse effects ; Female ; Habituation, Psychophysiologic/drug effects ; Locomotion/*drug effects ; Mice ; Mice, Inbred Strains ; Taste/*drug effects ; }, abstract = {This study examined the effect of repeated ethanol (EtOH) injections that induced behavioral sensitization on subsequent acquisition of EtOH- and lithium chloride (LiCl)-induced conditioned taste aversion (CTA). CTA acquisition was assessed in independent groups of EtOH-sensitized and nonsensitized genetically heterogeneous female mice after injections of saline; 1, 2, or 4 g/kg EtOH; or 2 or 4 mEq/kg LiCl. Saline and 1 g/kg EtOH did not induce CTA. Four g/kg EtOH and 4 mEq/kg LiCl induced similar levels of CTA in EtOH-sensitized and nonsensitized groups. CTA induced by 2 g/kg EtOH and 2 mEq/kg LiCl was attenuated in EtOH-sensitized mice compared with nonsensitized counterparts. Thus, a sensitizing regimen of EtOH preexposure resulted in both a decrease in EtOH and LiCl aversion and an increase in EtOH locomotor sensitivity; such changes could ultimately contribute to enhanced EtOH intake and potentially to EtOH abuse.}, } @article {pmid11239672, year = {2000}, author = {Aja, S and Sisouvong, S and Barrett, JA and Gietzen, DW}, title = {Basolateral and central amygdaloid lesions leave aversion to dietary amino acid imbalance intact.}, journal = {Physiology & behavior}, volume = {71}, number = {5}, pages = {533-541}, doi = {10.1016/s0031-9384(00)00378-4}, pmid = {11239672}, issn = {0031-9384}, support = {DK09271/DK/NIDDK NIH HHS/United States ; DK35747/DK/NIDDK NIH HHS/United States ; DK42274/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acids/*physiology ; Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/physiology ; Diet ; Eating/physiology ; Food Preferences/*physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/physiology ; }, abstract = {Expression of c-fos is increased in the central amygdaloid nucleus (CE) of rats ingesting a diet with a severely imbalanced essential amino acid profile (IMB), at a time associated with development of a conditioned taste aversion (CTA). The CE and the basolateral amygdaloid nucleus (BL) both are reported to be involved in the development of CTA. Large amygdaloid lesions involving CE and BL mitigate the normal decrease in intake of IMB; this treatment also impairs CTA to a flavor cue associated with gastrointestinal discomfort. To differentiate their potential roles in aversive responses to IMB, we electrolytically lesioned CE and BL separately. Neither lesion attenuated IMB-induced anorexia, or prevented the avoidance of flavored solutions previously paired with IMB. In contrast, after saccharin-LiCl pairing, CE-lesioned animals showed attenuated CTA to saccharin solution in a two-bottle test. We conclude that neither the CE nor the BL is essential for the reduction of IMB intake, or for CTA associated with IMB. Furthermore, these results suggest that the aversive consequences of IMB intake do not involve gastrointestinal malaise-evoked neurotransmission involving the CE.}, } @article {pmid11238773, year = {2001}, author = {Gietzen, DW and Magrum, LJ}, title = {Molecular mechanisms in the brain involved in the anorexia of branched-chain amino acid deficiency.}, journal = {The Journal of nutrition}, volume = {131}, number = {3}, pages = {851S-855S}, doi = {10.1093/jn/131.3.851S}, pmid = {11238773}, issn = {0022-3166}, support = {DK35747/DK/NIDDK NIH HHS/United States ; DK42274/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acids, Branched-Chain/blood/*deficiency/*metabolism ; Animals ; Anorexia/*physiopathology ; Brain/metabolism/*physiopathology ; Calcium/metabolism ; Diet ; Food Deprivation ; Gene Expression ; Genes, fos ; Neural Pathways/physiopathology ; Neurotransmitter Agents/*metabolism ; Phosphorylation ; Rats ; Signal Transduction ; Taste ; }, abstract = {The anterior piriform cortex (APC) of the rat is thought to be the site of indispensable amino acid (IAA) chemosensation in the brain. The branched-chain amino acids, including leucine, are among the IAA that are recognized in the APC. The behavioral outcome of IAA deficiency is an anorectic response. The specific transduction mechanisms by which IAA deficiency and repletion activate the APC are not fully understood, but clearly phosphorylation of proteins, increases in intracellular calcium, and expression of the immediate early gene c-fos, which are among the earliest events occurring after the initial drop in the concentration of the limiting IAA, cause stimulation in the APC. Subsequently, several neurotransmitter systems, including those for norepinephrine, GABA, serotonin, dopamine and nitric oxide, are activated in the APC of rats that have consumed an IAA-imbalanced diet. These systems appear to modulate the output cells from the APC, glutamatergic pyramidal cells that send neural signals to activate subsequent relays in the brain. Ultimately, the feeding circuits of the brain carry out the anorectic response. Continued consumption of a diet containing an IAA imbalance causes a conditioned taste aversion to the diet in all animals that have been studied. Such learning involves synaptic reorganization, requiring both degradation and synthesis of protein, along with alterations in genomic activity.}, } @article {pmid11208577, year = {2001}, author = {Wang, C and Mullet, MA and Glass, MJ and Billington, CJ and Levine, AS and Kotz, CM}, title = {Feeding inhibition by urocortin in the rat hypothalamic paraventricular nucleus.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {280}, number = {2}, pages = {R473-80}, doi = {10.1152/ajpregu.2001.280.2.R473}, pmid = {11208577}, issn = {0363-6119}, support = {DA-03999/DA/NIDA NIH HHS/United States ; DK-50456/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Brain/drug effects/*physiology ; Circadian Rhythm ; Corticotropin-Releasing Hormone/administration & dosage/*pharmacology ; Dose-Response Relationship, Drug ; Energy Intake/drug effects/physiology ; Feeding Behavior/*drug effects ; Food Deprivation ; Genes, fos ; Male ; Microinjections ; Neuropeptide Y/administration & dosage/pharmacology ; Paraventricular Hypothalamic Nucleus/drug effects/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Urocortins ; }, abstract = {Ventricular administration of urocortin (UCN) inhibits feeding, but specific site(s) of UCN action are unknown. In the current studies we examined the effect of UCN in the hypothalamic paraventricular nucleus (PVN) on feeding. We tested UCN administered into the PVN in several paradigms: deprivation-induced, nocturnal, and neuropeptide Y (NPY)-induced feeding. We compared the effect of equimolar doses of UCN and corticotrophin releasing hormone (CRH) on NPY-induced and nocturnal feeding, determined whether UCN in the PVN produced a conditioned taste aversion (CTA) and induced changes in c-Fos immunoreactivity (c-Fos-ir) after UCN and NPY administration in the PVN. UCN in the PVN significantly decreased NPY and nocturnal and deprivation-induced feeding at doses of 1, 10, and 100 pmol, respectively. UCN anorectic effects lasted longer than those attributed to CRH. Ten and thirty picomoles UCN did not induce a CTA, whereas 100 pmol UCN produced a CTA. UCN (100 pmol) in the PVN neither increased c-Fos-ir in any brain region assayed nor altered c-Fos-ir patterns resulting from PVN NPY administration. These data suggest the hypothalamic PVN as a site of UCN action.}, } @article {pmid11199513, year = {2001}, author = {Batsell, WR and Paschall, GY and Gleason, DI and Batson, JD}, title = {Taste preconditioning augments odor-aversion learning.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {27}, number = {1}, pages = {30-47}, pmid = {11199513}, issn = {0097-7403}, mesh = {Animals ; *Avoidance Learning ; Generalization, Stimulus ; Male ; *Odorants ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {On the basis of previous work that has shown a taste can potentiate odor-aversion conditioning in AX+ conditioning, 6 experiments used rats to examine the effects of pairing a preconditioned taste (A) with a novel odor cue (X) in an A+/AX+ aversion conditioning design. Experiments 1A and 1B demonstrated that a preconditioned taste produced a robust odor aversion that was significantly stronger than a potentiated odor aversion. The results of Experiment 2 showed that the robust odor aversion produced by A+/AX+ conditioning was not the result of the potentiated odor aversion summating with generalization from the taste aversion. The augmented odor aversion was produced only when the taste and odor stimuli were presented simultaneously (Experiment 3) and the preconditioned taste aversion was intact at compound conditioning (Experiment 4). Pairing a novel odor with a preconditioned taste was not sufficient to condition an aversion to odor (Experiment 5), although other results implicated a role for an association between odor and taste in the odor augmentation effect (Experiment 6). The present results have implications for current models of taste + odor interactions in flavor-aversion conditioning.}, } @article {pmid11179839, year = {2000}, author = {Hernádi, I and Karádi, Z and Vígh, J and Petykó, Z and Egyed, R and Berta, B and Lénárd, L}, title = {Alterations of conditioned taste aversion after microiontophoretically applied neurotoxins in the medial prefrontal cortex of the rat.}, journal = {Brain research bulletin}, volume = {53}, number = {6}, pages = {751-758}, doi = {10.1016/s0361-9230(00)00361-0}, pmid = {11179839}, issn = {0361-9230}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Body Weight/drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Drinking/drug effects/physiology ; Eating/drug effects/physiology ; Excitatory Amino Acid Agonists/pharmacology ; Iontophoresis ; Kainic Acid/pharmacology ; Male ; Neurons/drug effects/physiology ; Neurotoxins/*pharmacology ; Oxidopamine/pharmacology ; Prefrontal Cortex/cytology/*drug effects/physiology ; Psychomotor Performance/drug effects/physiology ; Rats ; Saline Solution, Hypertonic/pharmacology ; Sympatholytics/pharmacology ; Taste/*drug effects/physiology ; }, abstract = {The prefrontal cortex (PFC) has been reported to be essential in neural control of feeding. In the present study, we aimed to provide a complex characterization of behavioral consequences of PFC microlesions in CFY rats. Kainic acid (KA) was microiontophoretically applied into the mediodorsal division of PFC to damage intrinsic neurons, whereas in another group of rats, 6-hydroxydopamine (6-OHDA) was microiontophoretized into the same region to destroy catecholaminergic (CA) projection fiber terminals. Body weights, food and fluid intake of both lesioned and (sham-operated or intact) control animals were daily measured. Effects of intracellular dehydration and water deprivation were also studied. Open field activity, stereotyped behaviors, and orientation towards visual and somesthetic stimuli were pre- and postoperatively tested. To examine hypothesized consequences of mPFC microlesions on central taste information processing, the acquisition and retention of saccharine conditioned taste aversion (CTA) were studied. No major changes were recorded in body weights, food and water consumption. Dehydration or deprivation similarly increased water intake in all animals. Scores of open field activity and stereotyped behaviors in the 6-OHDA group were significantly higher than those of the other groups. As the main findings of the present studies, both KA and 6-OHDA lesioned rats displayed significant deficits in CTA acquisition and retention tests. These results suggest that the medial PFC has a substantial role in both the formation and the retrieval of CTA. Furthermore, the present findings also indicate the general significance of prefrontal CA mechanisms in the organization of goal-directed, adaptive behaviors.}, } @article {pmid11179607, year = {2001}, author = {Wirth, MM and Olszewski, PK and Yu, C and Levine, AS and Giraudo, SQ}, title = {Paraventricular hypothalamic alpha-melanocyte-stimulating hormone and MTII reduce feeding without causing aversive effects.}, journal = {Peptides}, volume = {22}, number = {1}, pages = {129-134}, doi = {10.1016/s0196-9781(00)00367-3}, pmid = {11179607}, issn = {0196-9781}, support = {DK 50456/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Eating/drug effects/*physiology ; Hypothalamus/*physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Melanocortin, Type 3 ; Receptor, Melanocortin, Type 4 ; Receptors, Corticotropin/agonists/*physiology ; alpha-MSH/administration & dosage/analogs & derivatives/pharmacology/*physiology ; }, abstract = {alpha-Melanocyte-stimulating hormone (alpha-MSH) appears to play a tonic inhibitory role in feeding and energy storage. MTII, a specific synthetic MC3-R/MC4-R agonist, has similar effects on feeding in rats. The current studies demonstrate that PVN administration of alpha-MSH or MTII decreases nocturnal and NPY-stimulated food intake without causing aversive effects. Co-administration with NPY of 600 pmol alpha-MSH or 1 pmol MTII into the PVN caused a significant decrease in NPY-induced feeding. PVN administration of MTII or alpha-MSH at doses effective to suppress feeding did not cause conditioned taste aversion (CTA). ICV administration of alpha-MSH, however, did cause weak CTA. These results indicate that the potent effects on feeding of MC3-R and MC4-R agonists when injected into the PVN are not due to aversive effects.}, } @article {pmid11164800, year = {2001}, author = {Turgeon, SM and Kegel, G and Davis, MM}, title = {Electrolytic lesions of the medial septum enhance latent inhibition in a conditioned taste aversion paradigm.}, journal = {Brain research}, volume = {890}, number = {2}, pages = {333-337}, doi = {10.1016/s0006-8993(00)03192-9}, pmid = {11164800}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Denervation/adverse effects ; Drinking Behavior/physiology ; Eating/physiology ; Male ; Neural Inhibition/*physiology ; Rats ; Rats, Sprague-Dawley ; Reaction Time/physiology ; Schizophrenia/physiopathology ; Septal Nuclei/anatomy & histology/*physiology/surgery ; Taste/*physiology ; }, abstract = {The effects of medial septal lesions on latent inhibition (LI) were assessed in a conditioned taste aversion paradigm. Animals were tested in a LI paradigm 2 weeks after receiving medial septal or sham lesions. The LI paradigm involved a pre-exposure phase in which water-deprived rats were allowed access to either water (non-pre-exposed; NPE) or 5% sucrose (pre-exposed; PE), followed by a conditioning phase in which animals were allowed access to sucrose and subsequently injected with lithium chloride, and a test phase in which animals were allowed access to both sucrose and water. LI was assessed by comparing the %-sucrose consumed in PE and NPE groups on the test day. There was a significantly greater LI effect in the lesion group than in the sham group, suggesting that electrolytic lesions to the medial septum can enhance LI in a CTA paradigm.}, } @article {pmid11164517, year = {2001}, author = {Wegener, G and Volke, V and Bandpey, Z and Rosenberg, R}, title = {Nitric oxide modulates lithium-induced conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {118}, number = {2}, pages = {195-200}, doi = {10.1016/s0166-4328(00)00329-6}, pmid = {11164517}, issn = {0166-4328}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Arginine/pharmacology ; Avoidance Learning/*drug effects ; Enzyme Inhibitors/pharmacology ; Fenclonine/pharmacology ; Indazoles/pharmacology ; Lithium/*pharmacology ; Male ; Methylene Blue/pharmacology ; Nitric Oxide/*physiology ; Nitric Oxide Synthase/antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Serotonin/physiology ; Serotonin Antagonists/pharmacology ; Serotonin Receptor Agonists/pharmacology ; Sweetening Agents ; Taste/*drug effects ; }, abstract = {Nitric oxide (NO) has been shown to affect the behaviour in animal models of depression, anxiety and avoidance learning. Lithium has marked effect in avoidance learning, an effect that can be modulated via the 5-HT system. Experiments were carried out using the conditioned taste aversion (CTA) paradigm to investigate whether administration of NO-modifying drugs, serotonergic drugs and lithium, alone or in combination, induced or affected a CTA. The NO-precursor L-arginine (L-Arg), the non-specific inhibitor of NOS and guanylate cyclase, methylene blue (MB) and the specific NOS inhibitor 7-Nitroindazole (7-NI) all produced CTAs in a dose-dependent fashion. Furthermore, we found that L-Arg counteracted the CTAs induced by LiCl or MB but failed to modulate the CTA produced by 7-NI. The administration of the selective 5-HT1A agonist, 8-OH-DPAT, counteracted the CTAs produced by MB and 7-NI. In contrast, depletion of 5-HT by p-Chlorophenylalanine did not affect the aversions produced by MB and 7-NI, but counteracted the CTA produced by L-Arg. Our results suggest that NO plays a role in the acquisition of the CTA induced by LiCl. Furthermore, the results suggest that the 5-HT1A receptor plays an important role in the CTA induced by MB and 7-NI, thus indicating a possible interaction between the 5-HT and NO systems.}, } @article {pmid11150555, year = {2000}, author = {Choleris, E and Thomas, AW and Ossenkopp, K and Kavaliers, M and Valsecchi, P and Prato, FS}, title = {Sex differences in conditioned taste aversion and in the effects of exposure to a specific pulsed magnetic field in deer mice Peromyscus maniculatus.}, journal = {Physiology & behavior}, volume = {71}, number = {3-4}, pages = {237-249}, doi = {10.1016/s0031-9384(00)00323-1}, pmid = {11150555}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Beverages ; Conditioning, Psychological/*physiology ; Drinking/drug effects ; Electromagnetic Fields ; Female ; Food Preferences ; Fruit ; Lithium Chloride/pharmacology ; *Magnetics ; Male ; Peromyscus/*physiology ; *Sex Characteristics ; Solutions ; Sucrose ; Taste/*physiology ; Time Factors ; }, abstract = {Although conditioned taste aversion (CTA) has been investigated and described in laboratory rodents and domestic animals, less is known regarding wild rodents. Here, we describe CTA in males and females of a "wild" species of rodent, the deer mouse (Peromyscus maniculatus). In addition, as CTA has often been induced by exposure to intense electromagnetic, X or gamma, radiation, in a second study, we also investigated the effects of a specifically designed, pulsed extremely low-frequency and low-intensity magnetic field on the flavor preferences of male and female deer mice. The results of these investigations showed that: (i) deer mice quickly developed a marked CTA for a novel flavor after a single pairing with LiCl; (ii) although the intensity of the CTA was the same in males and females, there was a sex difference in the duration of the flavor aversion, with males displaying it for a longer period (4 days) than females (3 days); (iii) both males and females showed a rapid and complete extinction of the aversion, in contrast to what has been reported for laboratory rodents; (iv) there was no recovery of CTA on re-test 10 days after extinction; (v) neither male or female deer mice developed a taste aversion as a consequence of exposure to a weak electromagnetic field; and (vi) there was a sex difference in response to the magnetic field, with exposure to the magnetic field significantly enhancing novel taste preference in male but not in female deer mice. Overall, our results show that there are several sex differences in the behavior of deer mice, both in the characteristics of the CTA and in the response to magnetic field exposure. The sex differences are discussed in terms of a sexually dimorphic sensitivity to experimental manipulation and the induction of stress and/or anxiety.}, } @article {pmid11150351, year = {2001}, author = {Risinger, FO and Freeman, PA and Greengard, P and Fienberg, AA}, title = {Motivational effects of ethanol in DARPP-32 knock-out mice.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {21}, number = {1}, pages = {340-348}, pmid = {11150351}, issn = {1529-2401}, support = {P01 MH040899/MH/NIMH NIH HHS/United States ; P50 AA010760/AA/NIAAA NIH HHS/United States ; P01 DA010044/DA/NIDA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; DA10044/DA/NIDA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Conditioning, Psychological/drug effects ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage ; Injections, Intraperitoneal ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Motivation ; Motor Activity/drug effects ; *Nerve Tissue Proteins ; Phosphoproteins/*deficiency/genetics ; Reinforcement, Psychology ; Reward ; Saccharin/administration & dosage ; Self Administration ; Sodium Chloride/administration & dosage ; Taste/physiology ; }, abstract = {DARPP-32 (dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein, 32 kDa) is an important component of dopaminergic function in brain areas thought to be important for drug and alcohol addiction. The present experiments characterized the acquisition of ethanol-induced conditioned taste aversion, ethanol-induced conditioned place preference, and ethanol self-administration in DARPP-32 knock-out (KO) mice compared to wild-type (WT) controls. For taste conditioning, KO and WT mice received access to 0.2 m NaCl solution followed immediately by intraperitoneal injection of 0-4 gm/kg ethanol. Ethanol produced dose-dependent conditioned taste aversion that was the same in both genotypes. For place conditioning, KO and WT mice received eight pairings of a tactile stimulus with ethanol (2 gm/kg, i.p.), and a different stimulus with saline. Ethanol produced increases in locomotor activity during conditioning, with KO mice showing higher activity levels after ethanol compared to WT mice. WT mice, but not KO mice, acquired conditioned preference for the ethanol-paired stimulus. In the self-administration procedure, KO and WT mice were trained to lever press for access to 10% v/v ethanol. Subsequently, the mice had 23 hr/d access to food, ethanol, and water. Response patterns were determined using 0-30% v/v ethanol concentrations. WT mice displayed concentration-dependent responding for ethanol. Responding on the ethanol lever by KO mice did not change as a function of ethanol concentration. Saccharin (0.2% w/v) was subsequently added to the ethanol mixture, and responding was examined at 0, 5, 10, and 20% ethanol concentrations. Ethanol responding increased in both genotypes, although WT mice showed higher rates at all concentrations.}, } @article {pmid11134702, year = {2000}, author = {Misanin, JR and Hoefel, TD and Riedy, CA and Wilson, HA and Hinderliter, CF}, title = {Multiple remote-US preexposures and the blocking effect produced by a proximal-US.}, journal = {Physiology & behavior}, volume = {71}, number = {1-2}, pages = {199-202}, doi = {10.1016/s0031-9384(00)00330-9}, pmid = {11134702}, issn = {0031-9384}, mesh = {Aging/psychology ; Animals ; Avoidance Learning/drug effects ; Conditioning, Operant/*drug effects ; Female ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*physiology ; }, abstract = {Weanling, young-adult, and old-age Wistar albino rats were used to determine whether number of unconditioned stimulus (US) presentations, given 24 h or more (remote preexposure) prior to conditioning, alters the blocking effect of a single-US preexposure given 2 h before (proximal) taste aversion conditioning. As the number of remote-US preexposures increased from 0 to 6, the ability of the proximal-US preexposure to block conditioning initially increased then decreased for all age groups. Of the models put forth to explain US preexposure effects on conditioned taste aversion (CTA), only Wagner's information processing model adequately explained the reduction of the blocking effect of the proximal-US preexposure produced as a result of increasing remote-US preexposures.}, } @article {pmid11134640, year = {2000}, author = {Navarro, M and Spray, KJ and Cubero, I and Thiele, TE and Bernstein, IL}, title = {cFos induction during conditioned taste aversion expression varies with aversion strength.}, journal = {Brain research}, volume = {887}, number = {2}, pages = {450-453}, doi = {10.1016/s0006-8993(00)03032-8}, pmid = {11134640}, issn = {0006-8993}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning/*physiology ; Brain/cytology/*physiology ; Conditioning, Operant/*physiology ; Gene Expression Regulation ; *Genes, fos ; Lithium Chloride ; Male ; Medulla Oblongata/physiology ; Mesencephalon/physiology ; Pons/physiology ; Prosencephalon/physiology ; Proto-Oncogene Proteins c-fos/*analysis ; Rats ; Rats, Long-Evans ; Saccharin ; Solitary Nucleus/*physiology ; *Taste ; }, abstract = {Fos-like immunoreactivity (FLI) can indicate the location of neurons activated following expression of conditioned taste aversion (CTA). After one conditioning trial FLI has been identified in the intermediate nucleus of the solitary tract (iNTS) with little expression in other brain regions. The present study assessed the effect of increasing aversion strength on the magnitude and anatomical distribution of FLI during CTA expression. When animals received three rather than one conditioning trial, significant FLI was seen not only in the iNTS but also in the parabrachial nucleus (PBN), and the central nucleus of the amygdala (CNA), regions thought to be important in taste aversion learning.}, } @article {pmid11134632, year = {2000}, author = {Bielavska, E and Miksik, I and Krivanek, J}, title = {Glutamate in the parabrachial nucleus of rats during conditioned taste aversion.}, journal = {Brain research}, volume = {887}, number = {2}, pages = {413-417}, doi = {10.1016/s0006-8993(00)02986-3}, pmid = {11134632}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Operant ; Glutamic Acid/*metabolism ; Male ; Mesencephalon/*physiology ; Microdialysis ; Pons/*physiology ; Rats ; Rats, Long-Evans ; Saccharin ; *Taste ; }, abstract = {Brain microdialysis combined with HPLC and spectroscopic detection was used to monitor extracellular glutamate in the parabrachial nucleus (PBN) of rats during acquisition of a conditioned taste aversion (CTA). Microdialysis fractions taken every 20 min were used to assess the effects of presentation of the conditioned stimulus alone (CS, consumption of 0.1% saccharin), the unconditioned stimulus alone (US, intraperitoneal injection of 0.15 M LiCl, 2% b.w. induced malaise after water drinking) as well as that of CS-US pairing. After 15 min of saccharin drinking, the glutamate concentration in the eluate (20 microl/20 min) reached 80% above the baseline but returned to the basal value in the next fraction. LiCl alone (applied 1 h after 15 min drinking of water) increased glutamate only following some delay, i.e. in the second and third post-lithium fraction by 90 and 67%, respectively. However, when LiCl was injected 1 h after the onset of saccharin intake, the glutamate concentration rose significantly (by 95%) already in the first post-LiCl fraction and by 120% in the second one. It appears, therefore, that the 'saccharin trace' facilitates the effect of lithium on extracellular concentration of glutamate in PBN during acquisition of CTA.}, } @article {pmid11113479, year = {2000}, author = {Risinger, FO and Cunningham, CL}, title = {DBA/2J mice develop stronger lithium chloride-induced conditioned taste and place aversions than C57BL/6J mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {67}, number = {1}, pages = {17-24}, doi = {10.1016/s0091-3057(00)00310-5}, pmid = {11113479}, issn = {0091-3057}, support = {AA09612/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Lithium Chloride/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Species Specificity ; Taste ; }, abstract = {Genetic differences in lithium-induced conditioned aversion were examined using both place- and taste-conditioning procedures. In the place-conditioning procedure, adult male C57BL/6J (B6) and DBA/2J (D2) mice were exposed to a differential conditioning procedure in which each mouse received four 30-min pairings of a distinctive floor cue immediately after IP injections of either 0.75, 1.5, or 3. 0 mEq/kg LiCl. A different floor cue was paired with saline injections. A separate group of control mice received saline injections paired with both floor types. Subsequent floor preference testing revealed greater conditioned aversion in D2 mice compared to B6 mice in groups receiving 3.0 mEq/kg LiCl. Lower LiCl doses did not produce conditioning in either strain. In a conditioned taste-aversion procedure, fluid-restricted mice received four trials in which access to 0.2 M NaCl solution was followed by IP injection of either 0.75, 1.5, 3.0, or 6.0 mEq/kg LiCl. D2 mice showed stronger conditioned taste aversion than B6 mice at all doses, suggesting that taste conditioning may be a more sensitive index of aversive drug sensitivity than place conditioning. These findings are not well explained by strain differences in general learning ability or by strain differences in stimulus salience or innate preference. Rather, these data appear more consistent with previous studies showing strain differences in lithium pharmacokinetics and in general sensitivity to aversive events.}, } @article {pmid11103913, year = {2000}, author = {Stephens, DN and Dunworth, SJ}, title = {Previous experience of diazepam withdrawal prevents the formation of a withdrawal-conditioned taste aversion: test of a blocking hypothesis.}, journal = {Behavioural pharmacology}, volume = {11}, number = {6}, pages = {471-481}, doi = {10.1097/00008877-200009000-00004}, pmid = {11103913}, issn = {0955-8810}, mesh = {Animals ; Anti-Anxiety Agents/*pharmacology ; *Avoidance Learning ; Conditioning, Classical ; Diazepam/*pharmacology ; Mice ; Rats ; Substance Withdrawal Syndrome/*psychology ; Taste ; }, abstract = {Prior experience of withdrawal from chronic diazepam treatment reduces the aversiveness of withdrawal when precipitated withdrawal is made the unconditioned stimulus in a conditioned taste aversion (CTA) paradigm. Accounts of the mechanism by which unconditioned stimulus pre-exposure reduces its effectiveness in CTA postulate that unconditioned stimulus pre-exposure leads to the formation of associations with the environment, resulting in blocking of taste conditioning. We tested whether a blocking explanation accounted for the reduced effectiveness of withdrawal as a unconditioned stimulus in a CTA following prior exposure. Mice received chronic diazepam (15mg/kg/day, s.c. in sesame oil), or sesame oil vehicle, for three periods of 7 days, interspersed with 3-day withdrawal periods. The first two withdrawals occurred either in the home cage, or in one compartment of a place-conditioning apparatus (PCA). Animals which experienced withdrawal in the home cage were given equivalent experience of the PCA outside the withdrawal period. The third withdrawal was precipitated by i.p. administration of flumazenil (20mg/kg). Thirty minutes before injection, all animals were placed individually in the compartment of the PCA to which they had been previously exposed, allowed to drink a novel 10% sucrose solution, injected with flumazenil, and replaced in the PCA for 2 h, before being returned to the home cage. When sucrose consumption was measured 24 h later, only that group which had experienced all three withdrawals in the PCA showed evidence of a CTA. These animals (but not those that had experienced withdrawal in the home cage, or vehicle-treated mice) also showed strong avoidance of the chamber in which they had experienced withdrawal. Thus, no evidence was adduced that prior conditioning of an environment-conditioned stimulus to a withdrawal unconditioned stimulus blocked the formation of a CTA. When the CTA conditioning was repeated in the home cage, again only the mice that had experienced withdrawal in the place-conditioning apparatus showed evidence of conditioning. These observations are discussed in the context of blocking explanations of unconditioned stimulus pre-exposure.}, } @article {pmid11091032, year = {2000}, author = {Redila, VA and Smith, BR and Amit, Z}, title = {The effects of aminotriazole and acetaldehyde on an ethanol drug discrimination with a conditioned taste aversion procedure.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {21}, number = {3}, pages = {279-285}, doi = {10.1016/s0741-8329(00)00096-3}, pmid = {11091032}, issn = {0741-8329}, mesh = {Acetaldehyde/*pharmacology ; Amitrole/pharmacology ; Analysis of Variance ; Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Psychological/*drug effects/physiology ; Discrimination Learning/*drug effects/physiology ; Enzyme Inhibitors/pharmacology ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Long-Evans ; Saccharin/administration & dosage ; Sweetening Agents/administration & dosage ; Taste/drug effects/physiology ; }, abstract = {The present study was designed to investigate whether acetaldehyde shares stimulus properties with ethanol using the conditioned taste aversion (CTA) baseline of drug discrimination learning. Animals were trained to discriminate ethanol (0.8 g/kg, i.p.) from saline using 11 consecutive cycles consisting of a pairing day and three nonpairing days. On pairing days, all animals were injected with ethanol 30 min prior to a 20-min limited access to a saccharin solution (0.1% w/v) and then immediately injected with either LiCl (0.15 M, 1.8 meq) or distilled water. On the three following nonpairing days, animals were injected with saline and 30 min later presented with the same saccharin solution for 20 min. No injections followed on these nonpairing days. Results showed that animals acquired discriminative stimulus control for ethanol after seven pairings. Pretreatment with the catalase inhibitor did not alter the discriminative control for ethanol. Generalization tests revealed that acetaldehyde substituted for ethanol at a dose of 0.3 g/kg. The results of the present study suggest that catalase inhibition did not reverse or alter the discriminative stimulus effects of ethanol. However, generalization tests showed that acetaldehyde (0.3 g/kg) will substitute for ethanol suggesting that these two drugs share some similar properties.}, } @article {pmid11090888, year = {2000}, author = {González, CL and Miranda, MI and Gutiérrez, H and Ormsby, C and Bermúdez-Rattoni, F}, title = {Differential participation of the NBM in the acquisition and retrieval of conditioned taste aversion and Morris water maze.}, journal = {Behavioural brain research}, volume = {116}, number = {1}, pages = {89-98}, doi = {10.1016/s0166-4328(00)00250-3}, pmid = {11090888}, issn = {0166-4328}, mesh = {Acetylcholinesterase/metabolism ; Animals ; Avoidance Learning/*physiology ; Basal Nucleus of Meynert/enzymology/*physiology ; Choline O-Acetyltransferase/metabolism ; Conditioning, Operant/*physiology ; Excitatory Amino Acid Agonists/toxicity ; Male ; Maze Learning/*physiology ; Memory/physiology ; N-Methylaspartate/toxicity ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Deficits in both learning and memory after lesions of the cholinergic basal forebrain, in particular the nucleus basalis magnocellularis (NBM), have been widely reported. However, the participation of the cholinergic system in either acquisition or retrieval of memory process is still unclear. In this study, we tested the possibility that excitotoxic lesions of the NBM affect either acquisition or retrieval of two tasks. In the first experiment, animals were trained for two conditioned taste aversion tasks using different flavors, saccharine and saline. The acquisition of the first task was before NBM lesions (to test retrieval) and the acquisition of the second task was after the lesions (to test acquisition). Accordingly, in the first part of the second experiment, animals were trained in the Morris water maze (MWM), lesioned and finally tested. In the final part of this experiment, another set of animals was lesioned, then trained in the MWM and finally tested. All animals were able to retrieve conditioned taste aversion (CTA) and MWM when learned before NBM lesions; however, lesions disrupted the acquisition of CTA and MWM. The results suggest that the NBM and cholinergic system may play an important role in acquisition but not during retrieval of aversive memories.}, } @article {pmid11085601, year = {2000}, author = {Tassoni, G and Lorenzini, CA and Baldi, E and Sacchetti, B and Bucherelli, C}, title = {Role of the perirhinal cortex in rats' conditioned taste aversion response memorization.}, journal = {Behavioral neuroscience}, volume = {114}, number = {5}, pages = {875-881}, pmid = {11085601}, issn = {0735-7044}, mesh = {Animals ; Behavior, Animal/physiology ; Choice Behavior/*physiology ; Discrimination Learning/physiology ; Male ; Memory/*physiology ; Olfactory Pathways/*physiology ; Rats ; Rats, Long-Evans ; Taste/*physiology ; }, abstract = {The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses.}, } @article {pmid11082852, year = {2000}, author = {Batson, JD and Batsell, WR}, title = {Augmentation, not blocking, in an A+/AX+ flavor-conditioning procedure.}, journal = {Psychonomic bulletin & review}, volume = {7}, number = {3}, pages = {466-471}, pmid = {11082852}, issn = {1069-9384}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Cues ; Emetics ; Generalization, Stimulus ; Male ; *Odorants ; Rats ; Rats, Sprague-Dawley ; Research Design ; *Taste ; }, abstract = {An A+/AX+ Pavlovian conditioning design typically produces weakened or blocked conditioning to stimulus X. Two experiments were conducted in which rats first received an odor (A+) paired with an emetic US, and then received odor and taste (AX+) paired with the US. In both experiments, the preconditioned odor facilitated conditioning to the taste. In Experiment 1, a group that received two odor-illness pairings in A+ conditioning had a stronger taste aversion than a group that only had a single odor-illness pairing. Experiment 2 demonstrated that the strengthened taste aversion in the A+/AX+ condition was not due to stimulus generalization. The results represent a unique outcome in the flavor-aversion literature that is similar to potentiation. We propose that this facilitated conditioning to X in the A+/AX+ design be termed augmentation.}, } @article {pmid11081832, year = {2000}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {The role of the lateral parabrachial nuclei in concurrent and sequential taste aversion learning in rats.}, journal = {Experimental brain research}, volume = {134}, number = {4}, pages = {497-505}, doi = {10.1007/s002210000497}, pmid = {11081832}, issn = {0014-4819}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Lithium Chloride ; Male ; Pons/*physiology ; Rats ; Rats, Wistar ; Reticular Formation/*physiology ; Saline Solution, Hypertonic ; Sodium Chloride ; Taste/*physiology ; Time Factors ; Vagus Nerve/physiology ; }, abstract = {The purpose of this study was to examine the role of the external lateral parabrachial subnucleus (PBNLe) in two different taste aversion learning (TAL) procedures. For the first, short-term (concurrent) TAL, two different-flavored stimuli were presented at the same time, one associated with simultaneous intragastric administration of an aversive product, hypertonic NaCl, and the other with saline. In the second, long-term (sequential/delayed) TAL, each gustatory stimulus was presented every other day and the intragastric products LiCl and saline were administered after a 15-min delay. Electrolytic lesions in the PBNLe blocked acquisition of concurrent TAL, in which the vagal visceral information is critical. But the same lesions failed to interrupt sequential TAL. This result was independent of the order in which the two tasks (concurrent and sequential) were presented. However, as found by other authors, the latter type of learning was impaired in the presence of larger lesions in this same area. This supports the existence of sensory information needed to establish sequential TAL in other subnuclei of the parabrachial complex. The results of these experiments suggest that the different modalities of TAL are anatomically specific.}, } @article {pmid11054587, year = {2000}, author = {Houpt, TA}, title = {Molecular neurobiology of ingestive behavior.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {16}, number = {10}, pages = {827-836}, doi = {10.1016/s0899-9007(00)00420-2}, pmid = {11054587}, issn = {0899-9007}, mesh = {Animals ; Feeding Behavior/*physiology ; Gene Expression Regulation/physiology ; Homeostasis ; Humans ; Hypothalamus/*physiology ; Learning/*physiology ; *Models, Neurological ; Neuropeptides/*physiology ; Taste ; Time Factors ; }, abstract = {The concepts and tools of molecular biology may be applied to almost any component of the animal involved in ingestion, but two categories of model system are particularly relevant for molecular analysis: homeostatic regulation of neuropeptide expression in the hypothalamus and neuronal plasticity underlying persistent changes in ingestive behavior. Molecular approaches to these models are reviewed, focusing on our strategy for analyzing conditioned taste aversion learning. Three questions must be answered: Where do the long-term changes occur within the distributed neural network that mediates feeding? This answer reveals the site of neuronal restructuring mediated by gene expression. When does the transition occur from short-term expression to long-term persistence of the change in behavior? This transition reveals the critical time of gene expression. What genes are expressed during the change in behavior? The expression of thousands of genes in discrete subpopulations of cells is likely to be required during critical periods of neuronal restructuring. The identification of these genes is a general challenge for molecular neurobiology. The analysis of ingestive behavior can profit from molecular tools, but ingestion also provides informative models that elucidate the principles of time- and neuron-specific gene expression mediating complex behaviors.}, } @article {pmid11044754, year = {2000}, author = {Gommans, J and Stolerman, IP and Shoaib, M}, title = {Antagonism of the discriminative and aversive stimulus properties of nicotine in C57BL/6J mice.}, journal = {Neuropharmacology}, volume = {39}, number = {13}, pages = {2840-2847}, doi = {10.1016/s0028-3908(00)00130-1}, pmid = {11044754}, issn = {0028-3908}, mesh = {Aconitine/analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Dihydro-beta-Erythroidine/pharmacology ; Discrimination Learning/drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Male ; Mice ; Mice, Inbred C57BL ; Nicotine/*antagonists & inhibitors/pharmacology ; Nicotinic Agonists/*pharmacology ; Nicotinic Antagonists/pharmacology ; Receptors, Nicotinic/drug effects ; Reinforcement, Psychology ; Taste/drug effects ; }, abstract = {Mice of the C56BL/6J strain were trained to discriminate between nicotine (1.2 mg/kg) and saline in a two-lever drug discrimination procedure under a tandem variable-interval 60 s fixed-ratio 10 schedule of food reinforcement. Mice of the same strain were trained in conditioned taste aversion (CTA) experiments where drinking a saccharin or saline solution was paired with injection of nicotine or vehicle. During testing with both flavours presented simultaneously, a reduction in the intake of the nicotine-paired solution indicated CTA. The nicotine discrimination was acquired successfully and nicotine yielded a steep dose-response curve. The competitive nicotinic antagonist dihydro-beta-erythroidine (DHbetaE, 0.6-3.0 mg/kg) shifted the dose-response for the discriminative stimulus effect of nicotine to the right; the alpha7 nicotinic receptor antagonist methyllycaconitine (MLA, 1.0-10 mg/kg) had no effect. The mice showed strong CTA to 2.0 mg/kg of nicotine and marginally to 0.6 and 1.2 mg/kg of nicotine. DHbetaE (3.0-5.6 mg/kg) attenuated the CTA while MLA (1.0-10 mg/kg) had no effect. These studies show that nicotine has discriminative and aversive stimulus properties in C57BL/6J mice and that the effects are mediated primarily by receptors sensitive to DHbetaE; there was no evidence for the involvement of alpha7 nicotinic receptors.}, } @article {pmid11026740, year = {2000}, author = {Gauvin, DV and Baird, TJ and Briscoe, RJ}, title = {Differential development of behavioral tolerance and the subsequent hedonic effects of alcohol in AA and ANA rats.}, journal = {Psychopharmacology}, volume = {151}, number = {4}, pages = {335-343}, doi = {10.1007/s002130000477}, pmid = {11026740}, issn = {0033-3158}, mesh = {Alcohol Drinking/*genetics ; Animals ; Behavior, Animal/*drug effects ; Conditioning, Psychological/*drug effects ; Disease Models, Animal ; Drug Tolerance ; Ethanol/blood/*pharmacology ; Male ; Rats ; }, abstract = {RATIONALE: There at least two ways in which tolerance development to alcohol's behavioral effects could interact with its subsequent intake: 1) tolerance to alcohol's reward or reinforcing effects per se could lead to increased consumption, and 2) tolerance to alcohol's aversive effects could unmask alcohol's rewarding effects. These two mechanisms may differentially interact with preexisting genetic traits underlying alcoholism.

OBJECTIVES: Alcohol's subjective attributes were assessed in selectively bred AA and ANA rats after the development of tolerance to alcohol's behaviorally disruptive effects on lever-press performance.

METHODS: Rats were trained to press a lever under an FR30 schedule of food presentations. Group-dependent differential access to intoxicated practice, using a typical pre-post drug administration design, was utilized to promote the development of alcohol tolerance in only the group receiving intoxicated practice sessions. Subsequently, rats were trained to associate alcohol with unique place and taste stimuli in order to assess the relative changes in the approach towards, or avoidance of alcohol-related cues in each group.

RESULTS: Groups of AA and ANA rats given access to intoxicated practice demonstrated tolerance development. These groups subsequently conditioned place preferences and failed to develop conditioned taste aversions to alcohol. Passive alcohol exposure in the ANA rats set the occasion for the development of a place preference and delayed taste conditioning. AA rats exposed to passive alcohol exposure failed to condition place preferences and developed rapid taste aversions. Saline control rats failed to develop tolerance or place preferences but did condition a robust alcohol-induced taste aversion.

CONCLUSIONS: AA and ANA rats differ in their behavioral and pharmacokinetic response to chronic alcohol exposure. Compensatory responses interacting with approach-avoidance behaviors appear to be learned during intoxicated practice in the AA rats and during both intoxicated practice and passive exposure in the ANA rat line.}, } @article {pmid11020097, year = {2000}, author = {Klosterhalfen, S and Rüttgers, A and Krumrey, E and Otto, B and Stockhorst, U and Riepl, RL and Probst, T and Enck, P}, title = {Pavlovian conditioning of taste aversion using a motion sickness paradigm.}, journal = {Psychosomatic medicine}, volume = {62}, number = {5}, pages = {671-677}, doi = {10.1097/00006842-200009000-00011}, pmid = {11020097}, issn = {0033-3174}, mesh = {Adrenocorticotropic Hormone/metabolism ; Adult ; Analysis of Variance ; Aversive Therapy/*methods ; Conditioning, Classical/*physiology ; Disease Susceptibility ; Female ; Humans ; Male ; Motion Sickness/*psychology ; Pancreatic Polypeptide/metabolism ; Random Allocation ; Surveys and Questionnaires ; Taste/*physiology ; Vasopressins/metabolism ; }, abstract = {OBJECTIVE: Pavlovian conditioning of taste aversion has rarely been investigated in healthy humans using motion sickness as the unconditioned stimulus (US).

METHODS: Ninety subjects were pretested for susceptibility to illusory motion (vection) in a rotating drum. Thirty-two subjects susceptible to pseudomotion were assigned randomly to two groups and received either water 1 hour before rotation and a novel taste (elderberry juice, conditioned stimulus, [CS]) immediately before rotation in a rotating chair (conditioning group), or the sequence of water and juice was reversed (control group). During the test session 1 week later, all subjects were exposed to water 1 hour before and juice immediately before rotation. The amount of liquids ingested, nausea ratings, rotation tolerance, and blood levels of hormones (ACTH, ADH, PP) were evaluated.

RESULTS: Subjects in the conditioning group developed taste aversion toward the novel taste, but not subjects in the control group. Postrotation nausea rating was affected marginally by conditioning, but rotation tolerance was not changed by conditioning. ACTH and ADH but not PP levels increased with rotation, but were unaffected by conditioning.

CONCLUSIONS: Pavlovian conditioning of behavioral, but not of endocrine, indicators was effective in susceptible subjects using a rotating chair as US and a single CS-US pairing.}, } @article {pmid11004021, year = {2000}, author = {Olszewski, PK and Shi, Q and Billington, CJ and Levine, AS}, title = {Opioids affect acquisition of LiCl-induced conditioned taste aversion: involvement of OT and VP systems.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {279}, number = {4}, pages = {R1504-11}, doi = {10.1152/ajpregu.2000.279.4.R1504}, pmid = {11004021}, issn = {0363-6119}, support = {DA-03999/DA/NIDA NIH HHS/United States ; DK-42698/DK/NIDDK NIH HHS/United States ; P30-DK-50456/DK/NIDDK NIH HHS/United States ; }, mesh = {Analgesics, Opioid/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Butorphanol/pharmacology ; Lithium Chloride/*pharmacology ; Male ; Morphine/pharmacology ; Neurons/drug effects/*physiology ; Opioid Peptides/pharmacology ; Oxytocin/*physiology ; Paraventricular Hypothalamic Nucleus/*physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/agonists ; Supraoptic Nucleus/*physiology ; *Taste ; Vasopressins/*physiology ; }, abstract = {Aversive properties of lithium chloride (LiCl) are mediated via pathways comprising neurons of the nucleus of the solitary tract (NTS) and oxytocin (OT) and vasopressin (VP) cells in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Because opioids act on brain regions that mediate effects of LiCl, we evaluated whether administration of opioids shortly before LiCl in rats influences 1) development of conditioned taste aversion (CTA) and 2) activation of NTS neurons and OT/VP cells. Neuronal activation was assessed by applying c-Fos immunohistochemical staining. Three opioids were used: morphine (MOR), a mu-agonist, butorphanol tartrate (BT), a mixed mu/kappa-agonist, and nociceptin/orphanin FQ (N/OFQ), which binds to an ORL1 receptor. BT and N/OFQ completely blocked acquisition of CTA. MOR alleviated but did not eliminate the aversive effects. Each of the opioids decreased LiCl-induced activation of NTS neurons as well as OT and VP cells in the PVN and SON. We conclude that opioids antagonize aversive properties of LiCl, presumably by suppressing activation of pathways that encompass OT and VP cells and NTS neurons.}, } @article {pmid11003197, year = {2000}, author = {Hood, HM and Buck, KJ}, title = {Allelic variation in the GABA A receptor gamma2 subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BXD/Ty recombinant inbred mice.}, journal = {Alcoholism, clinical and experimental research}, volume = {24}, number = {9}, pages = {1327-1334}, pmid = {11003197}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; P50AA10760/AA/NIAAA NIH HHS/United States ; R29AA11114/AA/NIAAA NIH HHS/United States ; T32DA0762/DA/NIDA NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Ataxia/*genetics ; Central Nervous System Depressants/*adverse effects ; Ethanol/*adverse effects ; Hypothermia/*genetics ; Mice ; Mice, Inbred Strains ; Polymorphism, Genetic/genetics ; Receptors, GABA-A/*genetics ; Substance Withdrawal Syndrome/*genetics ; Taste/*genetics ; }, abstract = {BACKGROUND: Behavioral genomics has made dramatic progress toward mapping quantitative trait loci (QTLs) that contain genes responsible for phenotypic differences in a variety of behavioral responses to alcohol (ethanol). We previously identified a QTL on mouse Chromosome 11 that affects genetic predisposition to acute alcohol withdrawal. Among mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains, this QTL (Alcw3) accounts for 12% of the genetic variability in withdrawal liability. Candidate genes within this QTL encode the gamma-aminobutyric acid type A (GABA A) receptor gamma2, alpha1, alpha6, and beta2 subunits. We recently identified a coding sequence polymorphism between the B6 and D2 strains for the GABA A receptor gamma2 subunit gene (Gabrg2). In this study, we expand our analysis to a panel of BXD strains derived from the B6 and D2 progenitor strains. These BXD strains provide 26 fixed recombinant genotypes that can be used to examine genetic correlations, for example, between a phenotype of interest and allelic variation in a candidate gene.

METHODS: Gabrg2 was cloned and sequenced from the 26 BXD recombinant inbred strains. We analyzed genetic correlations between allelic variation in Gabrg2 and alcohol phenotypes previously measured in the BXD strain means.

RESULTS: Allelic variation in Gabrg2 is correlated genetically with predisposition to acute alcohol withdrawal and may underlie the Alcw3 locus. In addition, Gabrg2 is associated with ethanol-conditioned taste aversion, ethanol-induced motor incoordination, and ethanol-induced hypothermia. A trend is observed for chronic ethanol withdrawal, ethanol-induced loss of righting reflex, and tolerance to ethanol-induced hypothermia and ataxia.

CONCLUSIONS: Functionally relevant variation in Gabrg2, or a closely linked gene, is correlated genetically with some, but not all, behavioral responses to alcohol. The alcohol-related phenotypes associated with Gabrg2 generally may be characterized as debilitating or motivationally negative.}, } @article {pmid10976943, year = {2000}, author = {Snyder, DJ and Jahng, JW and Smith, JC and Houpt, TA}, title = {c-Fos induction in visceral and vestibular nuclei of the rat brain stem by a 9.4 T magnetic field.}, journal = {Neuroreport}, volume = {11}, number = {12}, pages = {2681-2685}, doi = {10.1097/00001756-200008210-00015}, pmid = {10976943}, issn = {0959-4965}, support = {NIDCD 03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/physiology ; Brain Stem/*metabolism ; Immunohistochemistry ; Magnetics ; Male ; Neurons, Afferent/metabolism ; Physical Stimulation ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Rotation ; Tissue Distribution ; Vestibular Nuclei/*metabolism ; Viscera/innervation/*metabolism ; }, abstract = {Recently, it has been shown that rats placed in a 9.4T static magnetic field for 30 min after drinking a glucose-saccharin solution develop a conditioned taste aversion (CTA) to glucose-saccharin. We sought to identify brain stem regions that are activated by the 9.4 T magnetic field exposure using c-Fos immunohistochemistry. Rats were restrained in a 9.4 T magnet for 30 min; sham-exposed rats were restrained but not exposed to the magnetic field. The magnetic field induced significantly more c-Fos-positive cells than sham treatment in the solitary tract, parabrachial, medial vestibular, prepositus, and supragenualis nuclei. These results suggest that magnetic field exposure causes neural activation in visceral and vestibular nuclei that may promote CTA learning.}, } @article {pmid10973525, year = {2000}, author = {Stevenson, GW and Cañadas, F and Zhang, X and Rice, KC and Riley, AL}, title = {Morphine discriminative control is mediated by the mu opioid receptor: assessment of delta opioid substitution and antagonism.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {4}, pages = {851-856}, doi = {10.1016/s0091-3057(00)00280-x}, pmid = {10973525}, issn = {0091-3057}, mesh = {Animals ; Benzamides/pharmacology ; Discrimination Learning/drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Female ; Generalization, Response/drug effects ; Methadone/pharmacology ; Morphine/*pharmacology ; Naloxone/pharmacology ; Naltrexone/analogs & derivatives/pharmacology ; Narcotic Antagonists/pharmacology ; Narcotics/*pharmacology ; Piperazines/pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Opioid, delta/antagonists & inhibitors/*drug effects ; Receptors, Opioid, mu/*drug effects ; }, abstract = {Morphine is an effective training drug in drug discrimination procedures. In subsequent generalization tests in which other opioids are administered, mu opioid agonists selectively substitute for the training drug. Given the relative selectivity of morphine for the mu receptor, such substitution patterns suggest that the mu opioid receptor is mediating the discriminative control of this compound. The present study assessed this selective mediation by examining the ability of the delta opioid agonist SNC80 to substitute for (and the delta opioid antagonist naltrindole to antagonize) morphine stimulus effects in rats trained to discriminate morphine from its vehicle in the conditioned taste aversion baseline of drug discrimination learning. Although morphine and methadone produced dose-related substitution for morphine (10 mg/kg), there was no evidence of substitution for morphine by SNC80 at any dose tested. Further, although naloxone (3.2 mg/kg) completely blocked the discriminative effects of morphine, naltrindole (3.2-10 mg/kg) did not significantly affect the morphine stimulus. These data suggest that the discriminative control established to morphine is mediated by its activity at the mu, but not the delta, receptor.}, } @article {pmid10973518, year = {2000}, author = {De Vry, J and Eckel, G and Kuhl, E and Schreiber, R}, title = {Effects of serotonin 5-HT(1) and 5-HT(2) receptor agonists in a conditioned taste aversion paradigm in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {4}, pages = {797-802}, doi = {10.1016/s0091-3057(00)00248-3}, pmid = {10973518}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Male ; Rats ; Rats, Wistar ; Receptors, Serotonin/*drug effects ; Receptors, Serotonin, 5-HT1 ; Serotonin Receptor Agonists/*pharmacology ; Taste/*drug effects ; }, abstract = {Although 5-HT(1/2) receptor agonists can inhibit ingestive behavior, it remains unclear whether this effect is confounded by drug-induced "malaise." The present study assessed the potential of such compounds to induce conditioned taste aversion (CTA), a possible correlate of aversive stimulus properties. Male Wistar rats were tested in a two-bottle saccharin versus water choice paradigm. DOI [5-HT(2A/2C) receptor agonist; ED(50) (95% confidence limits) in mg/kg, IP: 0.29 (0.14-0.63)], m-CPP [5-HT(2C/1B); 1.69 (0.96-2.99)], TFMPP [5-HT(1B/2C); 2.45 (1.46-4.11)], ORG 37684 [5-HT(2C); 2.96 (1. 17-7.52)], BW 723C86 [5-HT(2B); 3.49 (1.29-9.47)], CP-94,253 [5-HT(1B); 3.74 (1.54-9.08)], and ipsapirone [5-HT(1A); 20.15 (11. 25-36.09)] dose dependently suppressed saccharin preference, with potencies that correlated with their previously reported potencies to inhibit ingestive behavior in operant- and free feeding paradigms. Although these results did not necessarily imply that such hypophagic effects result from a drug-induced "malaise," it can be hypothesized that they involve, at least partly, the same physiological mechanism/substrate underlying CTA. As the hypophagic effects of serotonergic compounds have been ascribed to their effects on satiety processes and generally occur at doses that are lower than those inducing CTA, it is speculated that weak activation of this substrate results in satiety, whereas strong activation will result in aversive effects, or drug-induced "malaise."}, } @article {pmid10973516, year = {2000}, author = {Hutchinson, AC and Simpson, GR and Randall, JF and Zhang, X and Calderon, SN and Rice, KC and Riley, AL}, title = {Assessment of SNC 80 and naltrindole within a conditioned taste aversion design.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {4}, pages = {779-787}, doi = {10.1016/s0091-3057(00)00278-1}, pmid = {10973516}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Benzamides/*pharmacology ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Female ; Morphine/pharmacology ; Naltrexone/*analogs & derivatives/pharmacology ; Narcotic Antagonists/*pharmacology ; Narcotics/pharmacology ; Piperazines/*pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Opioid, delta/*agonists/*antagonists & inhibitors ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {Although compounds with relative selectivity for the mu and kappa opiate receptors subtypes have been reported to condition taste aversions, it is not known whether systemically administered delta compounds have the ability to produce aversions. To that end, female Long-Evans rats were adapted to water deprivation and were given pairings of a novel saccharin solution and various doses of the selective delta agonist SNC 80 (0.32-10.0 mg/kg; Experiment 1) or the selective delta antagonist naltrindole (1.0-18.0 mg/kg; Experiment 2). For comparison, the relatively selective mu agonist morphine (Experiment 1) and mu antagonist naloxone (Experiment 2) were assessed under identical conditions. Both SNC 80 (Experiment 1) and naltrindole (Experiment 2) were effective as unconditioned stimuli within this design, inducing dose-dependent taste aversions with repeated conditioning trials. Although at no dose did animals injected with SNC 80 differ from those injected with morphine, aversions induced by SNC 80 were acquired at a faster rate than those induced by morphine. Subjects injected with naloxone drank significantly less than those injected with naltrindole at the 10 mg/kg dose, and aversions induced by naloxone at 5.6 and 10 mg/kg were acquired at a faster rate than those induced by naltrindole. Although the basis for opioid agonist- and antagonist-induced taste aversions is not known, the differences between aversions induced by SNC 80 and naltrindole and those induced by morphine and naloxone, respectively, may be a function of their relative selectivity for specific opiate receptor subtypes.}, } @article {pmid10973505, year = {2000}, author = {Kunin, D and Latendresse, MW and Gaskin, S and Smith, BR and Amit, Z}, title = {Preexposure effects of nicotine and acetaldehyde on conditioned taste aversion induced by both drugs.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {4}, pages = {695-699}, doi = {10.1016/s0091-3057(00)00284-7}, pmid = {10973505}, issn = {0091-3057}, mesh = {Acetaldehyde/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Male ; Nicotine/administration & dosage/*pharmacology ; Nicotinic Agonists/administration & dosage/*pharmacology ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Previous assessments have demonstrated an interaction between ethanol and nicotine in the conditioned taste-aversion (CTA) paradigm. The present study assessed whether acetaldehyde, the primary reinforcing metabolite of ethanol, would interact with nicotine as well. In six experiments, water-deprived male Wistar rats were preexposed to either acetaldehyde (0.2 or 0.3 g/kg, IP) or nicotine (0.8, 1.2, or 2 mg/kg, SC) for 3 consecutive days and then subsequently conditioned, 24 h later, with either nicotine (0.8, 1.2, or 2 mg/kg, SC) or acetaldehyde (0.2 or 0.3 g/kg, IP), respectively. There were 4 conditioning days and 4 drug-free test days, each spaced 72 h apart. On test days, animals were offered a free choice between water and saccharin. The results of the following set of experiments demonstrated a dose-related interaction between nicotine and acetaldehyde, where lower doses of each drug failed to attenuate CTA induced by one another, but a higher nicotine dose (2 mg/kg) attenuated the formation of a CTA induced by acetaldehyde (0.3 g/kg). It was argued that the primary metabolite of ethanol may play a role in the interaction between nicotine and ethanol previously observed.}, } @article {pmid10933897, year = {2000}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {Electrolytic lesions of the pedunculopontine nucleus disrupt concurrent learned aversion induced by NaCl.}, journal = {Neurobiology of learning and memory}, volume = {74}, number = {2}, pages = {105-118}, doi = {10.1006/nlme.1999.3941}, pmid = {10933897}, issn = {1074-7427}, mesh = {Animals ; Behavior, Animal/drug effects ; Discrimination Learning/*physiology ; Electrolytes/*adverse effects ; Male ; Pons/*drug effects ; Rats ; Rats, Wistar ; Sodium Chloride/*adverse effects ; Taste/drug effects ; }, abstract = {Bilateral electrolytic lesions in the pedunculopontine nucleus (PPN) impair acquisition of short-term, or concurrent, Taste Aversion Learning (TAL) in rats. This type of TAL is characterized by the daily presentation of two different flavor stimuli at the same time, one associated with simultaneous intragastric administration of an aversive product (hypertonic NaCl) and the other with physiological saline. Sham-lesioned control animals learn this taste discrimination task, but both lesioned animals and control animals learn a long-term, or delayed, TAL task in which each gustatory stimulus is presented individually every other day and the intragastric products, LiCl (0.15 M) and physiological saline, are administered after a 15-min delay. These results are analyzed in the context of the cerebellar circuits involved in learning and in relation to the two TAL modalities described above.}, } @article {pmid10924690, year = {2000}, author = {Olszewski, PK and Shaw, TJ and Grace, MK and Billington, CJ and Levine, AS}, title = {Nocistatin inhibits food intake in rats.}, journal = {Brain research}, volume = {872}, number = {1-2}, pages = {181-187}, doi = {10.1016/s0006-8993(00)02535-x}, pmid = {10924690}, issn = {0006-8993}, support = {DA03999/DA/NIDA NIH HHS/United States ; DK42698/DK/NIDDK NIH HHS/United States ; P30DK50456/DK/NIDDK NIH HHS/United States ; }, mesh = {Analgesics, Opioid/administration & dosage/metabolism ; Animals ; Avoidance Learning/drug effects ; Eating/*drug effects/*physiology ; Excitatory Amino Acids/agonists ; Immunohistochemistry ; Injections, Intraventricular ; Male ; Microinjections ; Neurons/cytology/drug effects/metabolism ; Opioid Peptides/*administration & dosage/antagonists & inhibitors/*metabolism ; Oxytocin/metabolism ; Paraventricular Hypothalamic Nucleus/drug effects/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Supraoptic Nucleus/drug effects/metabolism ; Taste/drug effects ; Vasopressins/metabolism ; }, abstract = {Nocistatin, a product of the same precursor as nociceptin/orphanin FQ (N/OFQ), has been shown to antagonize effects of N/OFQ. N/OFQ stimulates feeding, most probably by inhibiting activation of neurons containing oxytocin (OT) and vasopressin (VP), peptides considered as satiety factors, and implicated in the development of conditioned taste aversion (CTA). The present study was designed to investigate whether intracerebroventricularly (ICV) injected nocistatin (a) affects deprivation- and N/OFQ-induced feeding, (b) causes CTA, and (c) induces activation of hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, as well as OT and VP neurons present in these regions. C-Fos immunohistochemistry was used as a marker of cellular activation. Nocistatin (1-3 nmol) significantly reduced food intake in deprived rats during the first and second hour post-injection. Doses of 1-3 nmol suppressed N/OFQ-induced feeding. Nocistatin at the highest (3 nmol) dose did not cause CTA. It also did not affect activation of the PVN or SON. In nocistatin-treated animals, the percentage of Fos-positive OT and VP neurons was similar to controls. We conclude that nocistatin antagonizes the influence of N/OFQ on feeding and suppresses deprivation-induced food consumption through mechanisms other than aversion. Nocistatin does not, however, activate the PVN or SON. It does not exert its effects via VP or OT neurons.}, } @article {pmid10913789, year = {2000}, author = {Swank, MW}, title = {Pharmacological antagonism of tyrosine kinases and MAP kinase in brainstem blocks taste aversion learning in mice.}, journal = {Physiology & behavior}, volume = {69}, number = {4-5}, pages = {499-503}, doi = {10.1016/s0031-9384(00)00225-0}, pmid = {10913789}, issn = {0031-9384}, support = {HD33138-01/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Brain Stem/*enzymology/physiology ; Drug Antagonism ; Enzyme Inhibitors/administration & dosage ; Immunohistochemistry ; Injections, Intraperitoneal ; Injections, Intraventricular ; Lithium Chloride/administration & dosage ; *MAP Kinase Kinase Kinase 1 ; Male ; Mice ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphorylation/drug effects ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Saccharin/pharmacology ; Signal Transduction/drug effects/physiology ; Sodium Chloride/administration & dosage ; Solitary Nucleus/drug effects/enzymology ; Taste/*physiology ; }, abstract = {Although c-Fos induction in the brainstem is a reliable correlate of taste aversion learning and appears necessary for the encoding of the unconditioned stimulus, little is known about the intracellular signaling pathways in the brainstem that regulate c-Fos expression during taste aversion learning. Infusion of the tyrosine kinase inhibitor genistein and the MAP kinase kinase (MEK) inhibitor PD98059 into the fourth ventricle of mice potently blocks acquisition of a learned taste aversion. The unconditioned stimulus LiCl produces a rapid and robust phosphorylation of MAP kinase, as revealed by immunohistochemistry with an antibody specific to the dually phosphorylated active form of MAP kinase. This immunoreactivity is localized to the same region of the intermediate nucleus tractus solitarius in which we have shown large increases in c-Fos immunoreactive cells, suggesting that in at least a subset of these cells, MAP kinase activation may lead to c-fos induction.}, } @article {pmid10899378, year = {2000}, author = {Elkins, RL and Orr, TE and Li, JQ and Walters, PA and Whitford, JL and Carl, GF and Rausch, JL}, title = {Serotonin reuptake is less efficient in taste aversion resistant than in taste aversion-prone rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {3}, pages = {609-614}, doi = {10.1016/s0091-3057(00)00263-x}, pmid = {10899378}, issn = {0091-3057}, mesh = {Animals ; Binding Sites ; Brain/drug effects/*metabolism ; Carrier Proteins/metabolism ; Cell Membrane/drug effects/metabolism ; Male ; Membrane Glycoproteins/metabolism ; *Membrane Transport Proteins ; *Nerve Tissue Proteins ; Paroxetine/pharmacology ; Rats ; Serotonin/*metabolism ; Serotonin Plasma Membrane Transport Proteins ; Serotonin Uptake Inhibitors/pharmacology ; Synaptosomes/drug effects/metabolism ; Taste/*physiology ; }, abstract = {We have previously reported the development of rat lines bred selectively for differences in taste aversion conditionability. Earlier studies demonstrated that the taste aversion resistant (TAR) animals exhibited lower concentrations of brain serotonin and consumed greater amounts of ethanol than their taste aversion prone (TAP) counterparts. In the present study, TAR rats demonstrated significantly less efficient brain serotonin transport compared to TAP rats, but the rat lines demonstrated similar levels of serotonin transporter or V(max) and similar whole brain paroxetine (a specific serotonin reuptake inhibitor) binding (B(max)). These results suggest that the rat lines differ in the mechanisms that transport serotonin into nerve endings, but do not differ in the binding of serotonin to the transporter or in the number of serotonin transport sites. The data support the hypothesis that genetically determined differences in the serotonin system contribute to individual differences in taste aversion conditionability. The findings further suggest that differences in serotonin transport may influence the propensity to self-administer ethanol.}, } @article {pmid10899377, year = {2000}, author = {Grigson, PS and Twining, RC and Carelli, RM}, title = {Heroin-induced suppression of saccharin intake in water-deprived and water-replete rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {3}, pages = {603-608}, doi = {10.1016/s0091-3057(00)00253-7}, pmid = {10899377}, issn = {0091-3057}, support = {DA09815/DA/NIDA NIH HHS/United States ; DA10006/DA/NIDA NIH HHS/United States ; DC02016/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Body Weight/drug effects ; Drinking Behavior/*drug effects ; Eating/drug effects ; Heroin/*pharmacology ; Male ; Narcotics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Reward ; *Saccharin ; Taste/drug effects ; *Water Deprivation ; }, abstract = {Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with an aversive unconditioned stimulus such as lithium chloride. This phenomenon is referred to as a conditioned taste aversion (CTA). Rats also suppress intake of a saccharin CS when paired with a rewarding sucrose solution and when paired with a drug of abuse. Although the suppressive effects of drugs of abuse have long been interpreted as CTAs, evidence suggests that rats may suppress intake of the saccharin CS following taste-drug pairings because they are anticipating the rewarding rather than the aversive properties of the drug. Oddly, however, while all other drugs of abuse tested suppress intake of a gustatory CS, the highly reinforcing drug, heroin, is reportedly ineffective. The present study reexamined this issue in both water-deprived and water-replete rats using procedures that sustain both morphine- and cocaine-induced suppression of CS intake. The results showed that heroin greatly reduced CS intake following saccharin-heroin pairings and that this effect was less variable when assessed in water-replete subjects. When taken with other reports, these data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of all drugs of abuse tested.}, } @article {pmid10899366, year = {2000}, author = {Turgeon, SM and Auerbach, EA and Duncan-Smith, MK and George, JR and Graves, WW}, title = {The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {3}, pages = {533-539}, doi = {10.1016/s0091-3057(00)00223-9}, pmid = {10899366}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dizocilpine Maleate/*pharmacology ; Drug Interactions ; Eating/drug effects ; Excitatory Amino Acid Antagonists/pharmacology ; Food Preferences/drug effects ; Guanidines/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Receptors, sigma/agonists/metabolism ; Sucrose ; Taste/*drug effects ; }, abstract = {The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. Published by Elsevier Science Inc., 2000}, } @article {pmid10882790, year = {2000}, author = {Cubero, I and Puerto, A}, title = {Lateral parabrachial lesions impair intraperitoneal but not intraventricular methylscopolamine-induced taste aversion learning.}, journal = {Brain research}, volume = {871}, number = {1}, pages = {113-119}, doi = {10.1016/s0006-8993(00)02453-7}, pmid = {10882790}, issn = {0006-8993}, mesh = {Analysis of Variance ; Avoidance Learning/*drug effects ; Cerebral Ventricles/drug effects/physiology ; Injections, Intraperitoneal ; Injections, Intraventricular ; Learning/drug effects/*physiology ; N-Methylscopolamine/administration & dosage/*pharmacology ; Pons/drug effects/*physiology ; Prosencephalon/physiology ; *Taste ; }, abstract = {The role of the lateral parabrachial area (lPB) in the acquisition of a delayed taste aversion learning task (TAL) was examined by delivering the peripherally acting aversive compound, methylscopolamine (MSP), through two different routes, intraperitoneal and intraventricular. Consistent with previous anatomical, behavioral and molecular work, electrolytic lesions centered at the lPB did impair TAL when the MSP was injected intraperitoneally. However, lPB-lesioned animals exhibited intact learning capacities when MSP was administered intraventricularly. These results are interpreted in terms of the lPB as a critical anatomical relay involved in bottom-up visceral processing of aversive stimuli and also in relation to the relevance of forebrain structures in TAL.}, } @article {pmid10880703, year = {2000}, author = {Castro, L and De Castro-E-Silva, E and Lima, AK and Souza, FS and Maldonado, I and Macêdo, DF and Ferreira, MG and Santamaria, GF and Bandeira, IP and Amor, AL and Carvalho, FL and Rocha, MA and Oliveira, IR and Fregoneze, JB}, title = {Central 5-HT(4) receptors and drinking behavior.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {66}, number = {2}, pages = {443-448}, doi = {10.1016/s0091-3057(00)00226-4}, pmid = {10880703}, issn = {0091-3057}, mesh = {Animals ; Dioxanes/administration & dosage ; Drinking/drug effects/physiology ; Drinking Behavior/drug effects/*physiology ; Indoles/administration & dosage ; Injections, Intraventricular ; Male ; Piperidines/administration & dosage ; Rats ; Rats, Wistar ; Receptors, Serotonin/*physiology ; Receptors, Serotonin, 5-HT4 ; Serotonin Antagonists/administration & dosage ; Sulfonamides/administration & dosage ; Thirst/drug effects/physiology ; Water Deprivation/physiology ; }, abstract = {The aim of the present study was to investigate the effect of acute third ventricle injections of two different 5-HT(4) receptor antagonists, GR 113808 and SB 204070, on water intake in different situations. Injections of 80 nmol/rat of both GR 113808 and SB 204070 were unable to modify water intake in normohydrated rats. Pretreatment with GR 113808 (40 and 80 nmol/rat) and SB 204070 (80 and 160 nmol/rat) blunted water intake after third ventricle injections of angiotensin II (9.6 pmol/rat) compared to saline-pretreated controls. Pretreatment with 80 nmol/rat of both antagonists potentiated drinking induced by third ventricle injections of carbachol (11.0 nmol/rat) compared to saline-pretreated control. In all doses employed, none of the compounds was able to modify water intake in dehydrated rats. A separate control test using one-bottle taste aversion paradigm indicated that the reduction in water intake observed in some of the present experiments could not be attributed to a drug-induced malaise. It is suggested that central 5-HT(4) receptors exert a dualistic role on the control of water intake potentiating angiotensin II-induced drinking and inhibiting thirst induced by central cholinergic activation}, } @article {pmid10869804, year = {2000}, author = {Irie, M and Asami, S and Nagata, S and Miyata, M and Kasai, H}, title = {Classical conditioning of oxidative DNA damage in rats.}, journal = {Neuroscience letters}, volume = {288}, number = {1}, pages = {13-16}, doi = {10.1016/s0304-3940(00)01194-0}, pmid = {10869804}, issn = {0304-3940}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Avoidance Learning/drug effects/*physiology ; Carcinogens ; Conditioning, Classical/*physiology ; DNA Damage/*physiology ; Deoxyguanosine/analogs & derivatives/biosynthesis ; Ferric Compounds ; Kidney/drug effects/metabolism ; Liver/drug effects/metabolism ; Male ; Neoplasms, Experimental/chemically induced/metabolism ; Nitrilotriacetic Acid/analogs & derivatives ; Oxidative Stress/*physiology ; Pain/chemically induced/physiopathology ; Rats ; Rats, Wistar ; Saccharin ; Stimulation, Chemical ; Stress, Psychological/physiopathology ; Sweetening Agents ; Taste/*physiology ; }, abstract = {This study investigated whether the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA modification relevant to carcinogenicity, can be classically conditioned to a novel taste in order to clarify the possible role of the central nervous system (CNS) or psychological stress on cancer initiation via a classical conditioning mechanism. Male Wistar rats underwent one or two conditioned taste aversion (CTA) experiments in which ferric nitrilotriacetate (Fe-NTA), which has renal toxicity and can induce renal cell carcinoma, served as a visceral unconditioned stimulus (US), and a saccharin solution (SAC) was used as a conditioned stimulus (CS). The 8-OH-dG levels in the group conditioned with the combination of SAC and Fe-NTA significantly increased as compared to those of the uncombined groups by two repeats of the conditioning procedure (P=0.013). The rats that showed a painful response at the Fe-NTA administration had significantly higher values of 8-OH-dG than those without pain (P=0. 003). These results not only provide the first evidence regarding classical conditioning of oxidative DNA damage using the CTA procedure, but also suggest the involvement of the CNS and psychological stress in the pathogenesis of cancer via oxidative DNA damage.}, } @article {pmid10865054, year = {2000}, author = {Yasoshima, Y and Morimoto, T and Yamamoto, T}, title = {Different disruptive effects on the acquisition and expression of conditioned taste aversion by blockades of amygdalar ionotropic and metabotropic glutamatergic receptor subtypes in rats.}, journal = {Brain research}, volume = {869}, number = {1-2}, pages = {15-24}, doi = {10.1016/s0006-8993(00)02397-0}, pmid = {10865054}, issn = {0006-8993}, mesh = {Amygdala/cytology/drug effects/*metabolism ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/metabolism ; Lithium Chloride/adverse effects ; Male ; Rats ; Rats, Wistar ; Receptors, AMPA/antagonists & inhibitors/drug effects/*metabolism ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/drug effects/*metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/drug effects/*metabolism ; Saccharin/pharmacology ; Taste/drug effects/*physiology ; Water/pharmacology ; }, abstract = {Conditioned taste aversion (CTA) is based on the gustatory long-term memory established after association of the taste of food (conditioned stimulus, CS) with visceral signals of poisoning (unconditioned stimulus, US). After the acquisition of CTA, hedonics of the taste CS changes from positive to negative as indicated by reduced ingestive and increased aversive taste reactivities in response to re-exposures to the CS. We examined the effects of reversible and selective blockades of the amygdalar glutamate receptor subtypes, AMPA, NMDA and metabotropic glutamate receptors, on the formation of CTA. Blockades of each of the three receptor subtypes between ingestion of saccharin (CS) and malaise-inducing LiCl (US) disrupted the acquisition of CTA. After the acquisition of CTA, however, blockades of only AMPA receptors, but not NMDA or metabotropic receptors, impaired the expression of CTA. This effect was seen only during the period when the antagonistic action to AMPA receptors lasted. These results indicate that both ionotropic and metabotropic glutamate receptor subtypes in the amygdala are indispensable for the acquisition of CTA, but that the expression of acquired CTA is mediated only by AMPA receptors. The present results also suggest that the amygdalar glutamatergic neural transmission is involved in the formation and storage of long-term gustatory memory associated with the altered hedonics from positive to negative.}, } @article {pmid10856962, year = {2000}, author = {Shukitt-Hale, B and Casadesus, G and McEwen, JJ and Rabin, BM and Joseph, JA}, title = {Spatial learning and memory deficits induced by exposure to iron-56-particle radiation.}, journal = {Radiation research}, volume = {154}, number = {1}, pages = {28-33}, doi = {10.1667/0033-7587(2000)154[0028:slamdi]2.0.co;2}, pmid = {10856962}, issn = {0033-7587}, mesh = {Analysis of Variance ; Animals ; Iron Radioisotopes ; Learning/*radiation effects ; Male ; Memory/*radiation effects ; Memory Disorders/*etiology ; Psychomotor Performance/radiation effects ; Radiation Dosage ; Rats ; Rats, Sprague-Dawley ; Space Perception/*radiation effects ; }, abstract = {It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.}, } @article {pmid10856824, year = {2000}, author = {Reilly, S and Trifunovic, R}, title = {Lateral parabrachial nucleus lesions in the rat: aversive and appetitive gustatory conditioning.}, journal = {Brain research bulletin}, volume = {52}, number = {4}, pages = {269-278}, doi = {10.1016/s0361-9230(00)00263-x}, pmid = {10856824}, issn = {0361-9230}, support = {DC02821/DC/NIDCD NIH HHS/United States ; DC03379/DC/NIDCD NIH HHS/United States ; }, mesh = {Alanine/pharmacology ; Animals ; Appetitive Behavior/*physiology ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Food Preferences/drug effects/physiology ; Ibotenic Acid/pharmacology ; Lithium Chloride/pharmacology ; Male ; Pons/drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/physiology ; }, abstract = {Previous research involving tests of innate preferences and aversions shows that bilateral ibotenic acid lesions of the visceral neurons located in the lateral parabrachial nucleus of the pons selectively disrupt consumption of those gustatory stimuli whose intake is augmented or restricted by their postoral consequences. The present study examined the performance of the same experimental subjects in learned preference and aversion tasks. The lesioned rats failed to develop a conditioned taste aversion (Experiment 1), a conditioned flavor preference (Experiment 2), and a conditioned aversion to the oral trigeminal stimulus, capsaicin (Experiment 3). The pattern of results from both types of taste-guided behaviors (innate and learned) suggests that excitotoxic lesions of the lateral parabrachial nucleus diminish sensitivity to gastrointestinal feedback which, in the present experiments, precludes aversive and appetitive associative learning.}, } @article {pmid10854585, year = {2000}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {Retention of concurrent taste aversion learning after electrolytic lesioning of the interpositus-dentate region of the cerebellum.}, journal = {Brain research}, volume = {868}, number = {2}, pages = {329-337}, doi = {10.1016/s0006-8993(00)02351-9}, pmid = {10854585}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebellar Nuclei/cytology/*physiology ; Denervation ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Lesions in the interpositus-dentate region of the cerebellum impair short-term, or concurrent, TAL. In this type of learning, animals must discriminate between two flavor stimuli presented at the same time, one of which is associated with an aversive product. The task is learned by the control animals, and within this group the animals that acquire it adequately enough (15/22, 70% criterion) retain the learned taste discrimination when they are subjected to it again after being lesioned in the interpositus-dentate region. These results suggest that the deep nuclei are essential in the concurrent TAL acquisition process, but not in its retention.}, } @article {pmid10852213, year = {2000}, author = {Swank, MW}, title = {Phosphorylation of MAP kinase and CREB in mouse cortex and amygdala during taste aversion learning.}, journal = {Neuroreport}, volume = {11}, number = {8}, pages = {1625-1630}, doi = {10.1097/00001756-200006050-00006}, pmid = {10852213}, issn = {0959-4965}, support = {T32 MH18390/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*metabolism ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*metabolism ; Cyclic AMP Response Element-Binding Protein/*metabolism ; Emetics/pharmacology ; Immunohistochemistry ; Lithium Chloride/pharmacology ; Male ; Mice ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphorylation ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*physiology ; Tissue Distribution ; }, abstract = {Mice were subjected to a taste aversion conditioning procedure in which they drank water, familiar saccharin, or novel saccharin, followed by injection of either NaCl or the emetic agent LiCl. Immunohistochemistry was used to localize phosphorylated MAP kinase (ppERK) and phosphoCREB (pCREB) in the brain shortly after conditioning. An examination of insular cortex and amygdala revealed specific phosphorylation of MAP kinase by novel saccharin and LiCl, and CREB by LiCl. Pairing of novel saccharin with LiCl was the only stimulus sufficient to increase ppERK and pCREB immunoreactivity in the lateral amygdala, suggesting this as a site of CS-US convergence. ppERK immunoreactivity was localized to both nuclear and non-nuclear compartments, suggesting multiple functional roles of MAP kinase during learning.}, } @article {pmid10832796, year = {2000}, author = {Grigson, PS and Freet, CS}, title = {The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: evidence for the reward comparison hypothesis.}, journal = {Behavioral neuroscience}, volume = {114}, number = {2}, pages = {353-363}, doi = {10.1037//0735-7044.114.2.353}, pmid = {10832796}, issn = {0735-7044}, support = {DA 09815/DA/NIDA NIH HHS/United States ; DC 02016/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Appetitive Behavior ; Association Learning ; *Avoidance Learning ; Cocaine/*administration & dosage ; *Conditioning, Classical ; Lithium Chloride/*administration & dosage ; Male ; *Motivation ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Saccharin/administration & dosage ; Self Administration/psychology ; Species Specificity ; Sucrose/*administration & dosage ; Taste ; }, abstract = {Rats suppress intake of a saccharin conditioned stimulus (CS) when it is paired with an aversive unconditioned stimulus (US), an appetitive US, or a drug of abuse such as morphine or cocaine. It is unclear, however, whether the reduction in intake induced by these drugs is mediated by their aversive or their rewarding properties. The present set of experiments addressed this question by comparing the suppressive effects of a known aversive US (LiCl), a known reinforcing US (sucrose), and a drug of abuse (cocaine) in two strains of rats (i.e., Lewis and Fischer 344 rats) that differ in their preference for rewarding stimuli. The results show that, although both strains readily acquired a LiCl-induced conditioned taste aversion (CTA), the suppressive effects of sucrose and cocaine were robust in the drug-preferring Lewis rats and absent in the Fischer rats. These data argue against a CTA account and in favor of the reward comparison hypothesis.}, } @article {pmid10832791, year = {2000}, author = {Sage, JR and Knowlton, BJ}, title = {Effects of US devaluation on win-stay and win-shift radial maze performance in rats.}, journal = {Behavioral neuroscience}, volume = {114}, number = {2}, pages = {295-306}, doi = {10.1037//0735-7044.114.2.295}, pmid = {10832791}, issn = {0735-7044}, support = {MH 11061/MH/NIMH NIH HHS/United States ; MH 12247/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Extinction, Psychological ; Male ; *Maze Learning ; Mental Recall ; *Motivation ; Rats ; Rats, Long-Evans ; Reaction Time ; *Taste ; }, abstract = {Previous studies have shown double dissociations between win-stay and win-shift radial maze learning in terms of their underlying neural substrates. To examine the content of the associations formed in the two tasks, the authors devalued the food unconditioned stimulus (US) by taste aversion to differentiate stimulus-stimulus(CS-US) and stimulus-response (CS-CR) learning. US devaluation was performed in rats that were over- or undertrained on the win-stay task. Devaluation substantially reduced food consumption on the maze but failed to disrupt choice accuracy, regardless of the amount of training. Devaluation did not affect latency in overtrained rats but did increase latency in undertrained rats. In the win-shift task, devaluation caused rats to reject the reinforcer, yet they continued to accurately win-shift, but with significantly longer latencies (Experiment 3). The results suggest that an S-R association may mediate performance after extended win-stay training. In contrast, a US representation appears to be recalled during early win-stay and win-shift performance.}, } @article {pmid10832509, year = {2000}, author = {Nissani, M}, title = {Can taste aversion prevent bruxism?.}, journal = {Applied psychophysiology and biofeedback}, volume = {25}, number = {1}, pages = {43-54}, doi = {10.1023/a:1009585422533}, pmid = {10832509}, issn = {1090-0586}, mesh = {*Aversive Therapy ; Biofeedback, Psychology ; Bruxism/*therapy ; Humans ; Male ; Middle Aged ; Taste/*physiology ; }, abstract = {The first part of this note sketches a biofeedback modality for the treatment of bruxism. A mildly aversive, safe liquid is inserted into, and sealed in, small, bilaterally sleeved, polyethylene capsules. Two capsules are attached to a simple dental appliance that comfortably and securely places them between the lower and upper back teeth. The appliance and capsules are worn at night or at other times when bruxism is suspected to occur. Whenever a sleeping or an awake patient attempts to brux, one or both capsules rupture and the liquid is released into the mouth. The liquid then draws the patient's conscious attention to, and forestalls, any attempt of teeth clenching or grinding. Variations of the method and device can be used to diagnose bruxism. The second part of this note describes the long-term application of this taste-based approach to one chronic bruxer.}, } @article {pmid10805608, year = {2000}, author = {Shoaib, M and Zubaran, C and Stolerman, IP}, title = {Antagonism of stimulus properties of nicotine by dihydro-beta-erythroidine (DHbetaE) in rats.}, journal = {Psychopharmacology}, volume = {149}, number = {2}, pages = {140-146}, doi = {10.1007/s002139900348}, pmid = {10805608}, issn = {0033-3158}, mesh = {Analysis of Variance ; Animals ; Conditioning, Psychological/drug effects ; Dihydro-beta-Erythroidine/*pharmacology ; Discrimination Learning/drug effects ; Drug Antagonism ; Male ; Nicotine/*antagonists & inhibitors/pharmacology ; Nicotinic Agonists/pharmacology ; Nicotinic Antagonists/*pharmacology ; Rats ; Taste/drug effects ; }, abstract = {RATIONALE: Previous work has shown that a dose of DHbetaE, a competitive nicotinic receptor antagonist that blocked the discriminative stimulus properties of nicotine, was insufficient to block locomotor depression or operant rate-reducing effects of nicotine in rats. Examination of DHbetaE against other behavioural effects of nicotine may help in understanding its diverse actions.

OBJECTIVE: The present experiments examine the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake. Furthermore, to characterise the duration of pharmacological blockade produced by DHbetaE, the antagonist was examined in the drug discrimination (DD) procedure.

METHODS: Using the conditioned taste aversion (CTA) paradigm, male hooded rats were trained to avoid one of two distinctively flavoured solutions paired with nicotine (0.2 or 0.4 mg/kg) administration. In rats trained to discriminate 0.2 mg/kg s.c. nicotine in a two-lever procedure maintained under a tandem V160''-FR10 schedule of food reinforcement, the offset of antagonism by DHbetaE was examined 5, 15 and 30 min following injection of nicotine (0.2 or 0.4 mg/kg s.c.) or vehicle.

RESULTS: Administration of DHbetaE (0.5, 1.6 and 5.0 mg/kg s.c.) 30 min before nicotine failed to block nicotine (0.4 mg/kg) CTA, while co-administration of DHbetaE (5.0 mg/kg s.c.) with nicotine (0.2 and 0.4 mg/kg s.c.) prevented the development of CTAs. This blockade complemented nicotine discrimination data in which DHbetaE blocked the discriminative stimulus effect of nicotine (0.2 or 0.4 mg/kg s.c.) for 45 min after its administration.

CONCLUSIONS: These observations of DHbetaE's short-lasting antagonism against the aversive and discriminative stimulus effects of nicotine support the involvement of the similar subtypes of nicotinic receptor in the mediation of these diverse behavioural effects.}, } @article {pmid10799678, year = {2000}, author = {Swank, MW}, title = {Conditioned c-Fos in mouse NTS during expression of a learned taste aversion depends on contextual cues.}, journal = {Brain research}, volume = {862}, number = {1-2}, pages = {138-144}, doi = {10.1016/s0006-8993(00)02101-6}, pmid = {10799678}, issn = {0006-8993}, support = {HD33138-01/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Exploratory Behavior/drug effects/physiology ; Feeding Behavior/drug effects/*physiology ; Immunoenzyme Techniques ; Lithium Chloride/pharmacology ; Male ; Mice ; Pons/chemistry/physiology ; Proto-Oncogene Proteins c-fos/*analysis ; Sodium Chloride/pharmacology ; Solitary Nucleus/*chemistry/*physiology ; Taste/*physiology ; }, abstract = {c-Fos expression in the nucleus tractus solitarius (NTS) of the rat has been found to follow administration of a variety of pharmacologically diverse unconditioned stimuli (US), and it has been proposed that NTS is a critical structure in transduction of the US during taste aversion learning. Before conditioning, the conditioned stimulus (CS) taste does not induce c-Fos in NTS, but following pairing of the CS and US, subsequent CS presentation induces c-Fos in NTS. Although it has been suggested that the shift in the c-Fos response following conditioning represents a molecular correlate of taste aversion learning, i.e. the formerly neutral CS now predicts the toxicity associated with the US, the data presented here suggest a more cautious interpretation of c-Fos expression in NTS. In mice, post-conditioning c-Fos expression to the CS depends on contextual cues: when conditioning and testing occur in a novel environment, CS saccharin causes an increase in c-Fos expression, and when conditioning and testing occur in the home cage, CS saccharin produces a decrease in c-Fos expression relative to controls. Furthermore, we show that merely placing an animal into a novel environment is sufficient to drive c-Fos expression in NTS. These data suggest that c-Fos expression in NTS can be driven by a number of different stimuli and conditions, and that these responses may depend on context-dependent activation of forebrain structures shown to drive conditioned c-Fos expression in NTS.}, } @article {pmid10793215, year = {2000}, author = {Benoit, SC and Thiele, TE and Heinrichs, SC and Rushing, PA and Blake, KA and Steeley, RJ}, title = {Comparison of central administration of corticotropin-releasing hormone and urocortin on food intake, conditioned taste aversion, and c-Fos expression.}, journal = {Peptides}, volume = {21}, number = {3}, pages = {345-351}, doi = {10.1016/s0196-9781(00)00153-4}, pmid = {10793215}, issn = {0196-9781}, mesh = {Amygdala/drug effects/metabolism ; Animals ; Avoidance Learning/*drug effects ; Cerebral Ventricles/drug effects/*physiology ; Corticotropin-Releasing Hormone/administration & dosage/*pharmacology ; Energy Intake/*drug effects ; Feeding Behavior/drug effects ; Gene Expression Regulation/drug effects ; *Genes, fos ; Injections, Intraventricular ; Male ; Rats ; Rats, Long-Evans ; Reaction Time ; Saccharin ; Solitary Nucleus/drug effects/metabolism ; *Taste ; Urocortins ; }, abstract = {Corticotropin-releasing hormone (CRH) is a potent regulator of the hypothalamic-pituitary-adrenal axis, and reduces food intake when administered into the third cerebral ventricle (i3vt). However, CRH also promotes conditioned taste aversion (CTA) learning which indicates that its anorectic effects are accompanied by aversive consequences that would reduce food intake independently of energy regulation. Urocortin (Ucn) is a closely related mammalian peptide that binds to both identified CRH receptor subtypes and also reduces food intake when administered i3vt. The present experiments compared the aversive consequences of i3vt administration of CRH and Ucn at doses that produced comparable decrements in food intake. Experiment 1 found that 1.0 microg Ucn and 2.0 microg CRH produced similar reductions in food intake. Experiment 2 demonstrated that, at these doses, CRH but not Ucn promoted robust and reliable CTA learning. A third experiment showed comparable increased c-Fos-like immunoreactivity after Ucn and CRH in forebrain and hindbrain structures associated with food intake. It is concluded that Ucn, at doses that reduce food intake to levels like that observed after administration of CRH, do not produce similarly aversive consequences.}, } @article {pmid10792055, year = {2000}, author = {Ferguson, GD and Anagnostaras, SG and Silva, AJ and Herschman, HR}, title = {Deficits in memory and motor performance in synaptotagmin IV mutant mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {97}, number = {10}, pages = {5598-5603}, pmid = {10792055}, issn = {0027-8424}, support = {AG13622/AG/NIA NIH HHS/United States ; R37 AG013622/AG/NIA NIH HHS/United States ; R01 NS028660/NS/NINDS NIH HHS/United States ; R01 AG013622/AG/NIA NIH HHS/United States ; F32 NS010932/NS/NINDS NIH HHS/United States ; U01 AG013622/AG/NIA NIH HHS/United States ; NS07107/NS/NINDS NIH HHS/United States ; NS28660/NS/NINDS NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Animals ; *Calcium-Binding Proteins ; Conditioning, Classical/*physiology ; Cues ; Fear/physiology ; Food Preferences ; Homozygote ; Locomotion ; Membrane Glycoproteins/deficiency/*genetics/*physiology ; Memory/*physiology ; Memory Disorders/*genetics ; Mice ; Mice, Knockout ; Motor Activity/genetics/*physiology ; Nerve Tissue Proteins/deficiency/*genetics/*physiology ; Rats ; Reflex ; Social Behavior ; Synaptotagmins ; Taste ; }, abstract = {Synaptotagmin (Syt) IV is a synaptic vesicle protein. Syt IV expression is induced in the rat hippocampus after systemic kainic acid treatment. To examine the functional role of this protein in vivo, we derived Syt IV null [Syt IV(-/-)] mutant mice. Studies with the rotorod revealed that the Syt IV mutants have impaired motor coordination, a result consistent with constitutive Syt IV expression in the cerebellum. Because Syt IV is thought to modulate synaptic function, we also have examined Syt IV mutant mice in learning and memory tests. Our studies show that the Syt IV mutation disrupts contextual fear conditioning, a learning task sensitive to hippocampal and amygdala lesions. In contrast, cued fear conditioning is normal in the Syt IV mutants, suggesting that this mutation did not disrupt amygdala function. Conditioned taste aversion, which also depends on the amygdala, is normal in the Syt IV mutants. Consistent with the idea that the Syt IV mutation preferentially affects hippocampal function, Syt IV mutant mice also display impaired social transmission of food preference. These studies demonstrate that Syt IV is critical for brain function and suggest that the Syt IV mutation affects hippocampal-dependent learning and memory, as well as motor coordination.}, } @article {pmid10780803, year = {1999}, author = {Järbe, TU and Lamb, RJ}, title = {Effects of lithium dose (UCS) on the acquisition and extinction of a discriminated morphine aversion: tests with morphine and delta9-THC.}, journal = {Behavioural pharmacology}, volume = {10}, number = {4}, pages = {349-358}, doi = {10.1097/00008877-199907000-00002}, pmid = {10780803}, issn = {0955-8810}, support = {DA 09064/DA/NIDA NIH HHS/United States ; KO2-DA 00253/DA/NIDA NIH HHS/United States ; R01-DA 08395/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Dronabinol/*pharmacology ; Extinction, Psychological/*drug effects ; Hallucinogens/*pharmacology ; Injections, Intraperitoneal ; Lithium Chloride/administration & dosage/*pharmacology ; Male ; Morphine/*pharmacology ; Narcotics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The effects of varying the lithium dose (unconditioned stimulus [UCS]; LiCl range 30-180 mg/kg) on the acquisition and extinction of stimulus control by 5.6 mg/kg of morphine in a discriminated taste aversion (DTA) procedure were examined in rats. In addition, pharmacological specificity was examined by substituting (-)-delta-9-tetrahydrocannabinol (delta9-THC) for morphine during a test phase intervening between acquisition and extinction. DTA acquisition was more rapid at higher LiCl doses. The lowest dose of LiCl, 30 mg/kg, did not robustly maintain a DTA. Two groups treated with 60 mg/kg LiCl, differing only in the type of drinking nozzle used (ball-bearing vs standard non-ball-bearing), behaved similarly. Suppression of drinking was related to the morphine dose, in an orderly manner (dose range 0.3-10 mg/kg), in rats for which morphine was followed by LiCl. No significant decline in drinking occurred for rats for which morphine was followed by saline, except perhaps at the 10 mg/kg test dose of morphine. The control of drinking was pharmacologically specific; both experimental and control animals were equally affected in tests with delta9-THC (0.3-10 mg/kg). Low doses of delta9-THC increased water consumption; this did not occur with morphine. During extinction the reinstitution of drinking was similar across groups that had been effectively conditioned, i.e. there was no apparent effect of lithium dose on extinction. After extinction, a much attenuated reaction occurred to morphine in tests with 3 and 10 mg/kg. These doses of morphine had significantly suppressed drinking before the extinction phase. Collectively, these data add to the formal similarities between sensory and drug discriminative stimuli.}, } @article {pmid10777779, year = {2000}, author = {Weinshenker, D and Rust, NC and Miller, NS and Palmiter, RD}, title = {Ethanol-associated behaviors of mice lacking norepinephrine.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {20}, number = {9}, pages = {3157-3164}, pmid = {10777779}, issn = {1529-2401}, mesh = {Alcohol Drinking/*genetics ; Animals ; Body Temperature/drug effects ; Central Nervous System Depressants/*blood/pharmacology ; Conditioning, Psychological/drug effects/*physiology ; Dopamine beta-Hydroxylase/*genetics ; Ethanol/*blood/pharmacology ; Extinction, Psychological ; Female ; Hypothermia/chemically induced/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Norepinephrine/deficiency/genetics/*physiology ; Sex Factors ; Taste/drug effects/*physiology ; }, abstract = {Although norepinephrine (NE) has been implicated in animal models of ethanol consumption for many years, the exact nature of its influence is not clear. Lesioning and pharmacological studies examining the role of NE in ethanol consumption have yielded conflicting results. We took a genetic approach to determine the effect of NE depletion on ethanol-mediated behaviors by using dopamine beta-hydroxylase knockout (Dbh -/-) mice that specifically lack the ability to synthesize NE. Dbh -/- males have reduced ethanol preference in a two-bottle choice paradigm and show a delay in extinguishing an ethanol-conditioned taste aversion, suggesting that they drink less ethanol in part because they find its effects more aversive. Both male and female Dbh -/- mice are hypersensitive to the sedative and hypothermic effects of systemic ethanol administration, and the sedation phenotype can be rescued pharmacologically by acute replacement of central NE. Neither the decreased body temperature nor changes in ethanol metabolism can explain the differences in consumption and sedation. These results demonstrate a significant role for NE in modulating ethanol-related behaviors and physiological responses.}, } @article {pmid10776660, year = {2000}, author = {Blizard, DA and McClearn, GE}, title = {Association between ethanol and sucrose intake in the laboratory mouse: exploration via congenic strains and conditioned taste aversion.}, journal = {Alcoholism, clinical and experimental research}, volume = {24}, number = {3}, pages = {253-258}, pmid = {10776660}, issn = {0145-6008}, support = {AA-08125/AA/NIAAA NIH HHS/United States ; DC-02230/DC/NIDCD NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Central Nervous System Depressants/pharmacology ; Conditioning, Psychological/drug effects ; Ethanol/pharmacology ; Female ; Male ; Mice ; Mice, Congenic ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Sucrose/pharmacology ; Taste/*genetics ; }, abstract = {BACKGROUND: A substantial body of literature indicates that intakes of "sweet" solutions and ethanol are positively correlated across inbred strains of rats and mice but there has been speculation that the correlation is fortuitous and there is no agreement on the underlying mechanism.

METHODS AND RESULTS: We assessed the correlation between intake of sucrose and ethanol in congenic mice created by backcrossing alleles favoring sucrose intake from the BXD RI-5 strain into DBA/2J. In addition, to probe more specifically the interrelationship between intake of the two solutions, we examined aversion generalization from sucrose to ethanol in C57BL/6J mice. Among the congenic mice, a statistically significant product-moment correlation of r = 0.36 (p < 0.02) was found between 6-hr intake of sucrose corrected for differences in baseline water intake and preference for 10% ethanol presented in a 96-hr 2-bottle test. Furthermore, C57BL/6J male mice conditioned to avoid a 0.2 M sucrose solution generalized their aversion to a 10% ethanol solution presented in the same 2-bottle test, drinking 42.1 +/- 9.38% (mean +/- SE) of their total fluid intake from the ethanol tube, compared with the control group mean of 69.86 +/- 8.84%.

CONCLUSIONS: The positive association between intake of sucrose and ethanol in congenic mice provides strong evidence that the previously demonstrated genetic correlation between intake of these solutions is not the result of fortuitous fixation of unrelated alleles and provides suggestive evidence that, at least in the B6/D2 lineage, the genetic association between intakes of the two solutions reflects close linkage or the pleiotropic effects of the same genes. The demonstration that a conditioned taste aversion to sucrose generalized to ethanol in the C57BL/6J inbred mouse strain is an extension of similar observations in outbred rats and specifically demonstrates that intake of the two solutions is controlled by some of the same physiologic or neurological processes and thus is consistent with the pleiotropic interpretation of the genetic correlation.}, } @article {pmid10762378, year = {2000}, author = {Dunworth, SJ and Mead, AN and Stephens, DN}, title = {Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbens.}, journal = {The European journal of neuroscience}, volume = {12}, number = {4}, pages = {1501-1508}, doi = {10.1046/j.1460-9568.2000.00036.x}, pmid = {10762378}, issn = {0953-816X}, mesh = {Amygdala/drug effects/metabolism ; Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/drug effects ; Corpus Striatum/drug effects/metabolism ; Diazepam/*pharmacology ; Epilepsy/chemically induced/metabolism/physiopathology ; GABA Modulators/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Nucleus Accumbens/*drug effects/*metabolism ; Prefrontal Cortex/drug effects/metabolism ; Proto-Oncogene Proteins c-fos/*biosynthesis ; Substance Withdrawal Syndrome/metabolism/*physiopathology ; Taste ; }, abstract = {Flumazenil (20 mg/kg, i.p.)-precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21-day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c-fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli.}, } @article {pmid10736531, year = {2000}, author = {Gill, EL and Whiterow, A and Cowan, DP}, title = {A comparative assessment of potential conditioned taste aversion agents for vertebrate management.}, journal = {Applied animal behaviour science}, volume = {67}, number = {3}, pages = {229-240}, doi = {10.1016/s0168-1591(99)00122-7}, pmid = {10736531}, issn = {0168-1591}, abstract = {A conditioned taste aversion (CTA) is acquired through an association between the taste of a food and a feeling of illness experienced after ingestion. It can be induced deliberately by the addition of an undetectable illness-inducing chemical to food. Harnessing the CTA response could provide humane and effective means of controlling vertebrate pest problems. For field use, the ideal illness-inducing chemical should induce a robust CTA after a single oral dose, at which it must cause neither chronic illness nor persistent detrimental effects in the target or any non-target species at risk of exposure; it must also be undetectable and physically stable in the bait substrate. At present, no compound that satisfactorily meets all of these criteria has been identified. 17alpha ethinyl oestradiol meets most but, as a synthetic oestrogenic hormone, it can affect reproductive processes. The ability of two potentially safe compounds, cinnamamide (160 mg/kg) and thiabendazole (100 and 200 mg/kg) to generate a CTA in the laboratory rat Rattus norvegicus11 post-treatment tests (6 months). Thiabendazole at 200 mg/kg induced the next best CTA, persisting for five post-treatment tests. Cinnamamide and thiabendazole could provide safe alternative CTA agents to 17alpha ethinyl oestradiol for field use; the use of a second dose of these compounds to improve longevity of the CTA warrants further study.}, } @article {pmid10725651, year = {2000}, author = {Nakajima, S and Hayashi, H and Kato, T}, title = {Taste aversion induced by confinement in a running wheel.}, journal = {Behavioural processes}, volume = {49}, number = {1}, pages = {35-42}, doi = {10.1016/s0376-6357(00)00071-1}, pmid = {10725651}, issn = {1872-8308}, abstract = {Opportunities of spontaneous wheel running induced aversion in rats to the taste consumed before the running. Eight thirsty rats of Wistar strain were daily allowed to drink one of two taste solutions (sucrose or sodium chloride, say A) followed by confinement in a wheel or another taste solution (say B) followed by confinement in a Skinner box. Repeated training with Tastes A and B made the rats drink Taste A less than Taste B. Post-training two-bottle choice tests also showed clear demonstration of wheel-running-induced aversion to Taste A. These results confirmed those from Lett's laboratory and expanded the generality of the phenomenon in respect to strain of rats, deprivation conditions of the subjects, tastes, and other details. Furthermore, our procedure rejected three accounts alternative to wheel-induced aversion to Taste A.}, } @article {pmid10718265, year = {2000}, author = {Schafe, GE and Fitts, DA and Thiele, TE and LeDoux, JE and Bernstein, IL}, title = {The induction of c-Fos in the NTS after taste aversion learning is not correlated with measures of conditioned fear.}, journal = {Behavioral neuroscience}, volume = {114}, number = {1}, pages = {99-106}, pmid = {10718265}, issn = {0735-7044}, support = {NS22274/NS/NINDS NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; R01-MH46516/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Blood Pressure/physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Fear/*physiology ; Heart Rate/physiology ; Male ; Motor Activity/physiology ; Neurons/physiology ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Long-Evans ; Solitary Nucleus/*physiology ; Taste/*physiology ; }, abstract = {The induction of c-Fos-like immunoreactivity (c-FLI) in the nucleus of the solitary tract (NTS) has been shown to be correlated with behavioral expression of a conditioned taste aversion (CTA). However, because this cellular response is also dependent on an intact amygdala, it may represent the activation of a stress-related autonomic response. The present experiments addressed this possibility by evaluating the correlation between c-FLI in the intermediate division of the NTS (iNTS) and 2 measures of conditioned fear: freezing and changes in mean arterial pressure (MAP) and heart rate (HR). Exposure to the taste conditioned stimulus (CS) resulted in a marked induction of c-FLI in the iNTS, whereas exposure to a fear CS did not. Further, exposure to a taste CS did not selectively lead to increases in MAP or HR. Results suggest that induction of c-FLI in the iNTS may reflect the activation of a cell population whose function is unique to the CTA paradigm.}, } @article {pmid10716554, year = {2000}, author = {Feurté, S and Nicolaidis, S and Berridge, KC}, title = {Conditioned taste aversion in rats for a threonine-deficient diet: demonstration by the taste reactivity test.}, journal = {Physiology & behavior}, volume = {68}, number = {3}, pages = {423-429}, doi = {10.1016/s0031-9384(99)00202-4}, pmid = {10716554}, issn = {0031-9384}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; Food Preferences ; Male ; Nutritional Requirements ; Rats ; Rats, Wistar ; Satiety Response ; *Taste ; Threonine/*deficiency ; }, abstract = {Rats avoid a diet that is deficient in one or more essential amino acids (EAAs). This phenomenon is thought to involve the development of a "learned aversion" for the sensory properties or spatial placement associated with the deficient diet. The dietary self-selection technique has been widely used to show this avoidance of the deficient diet. Because avoidance does not necessarily imply taste aversion, we used the Taste Reactivity Test initially created by Grill and Norgren (1978) to analyze the affective reactivity pattern of rats that ingested a threonine-deficient diet. The results showed that there was an increase in the aversive responses when ingesting the threonine-deficient (Thr-Dev) diet, compared to a control diet, without changes in the hedonic responses. The aversive reactions were mainly gaping, and to a lesser extent chin rubbing and head shaking. This asymmetrical shift in the Thr-Dev diet palatability is consistent with a two-dimensional hypothesis of palatability, indicating that the aversive palatability of the deficient diet was increased while the positive palatability did not change. Further evidence indicates that rats do not develop a normal behavioral satiety sequence after ingesting the threonine-deficient diet. These results indicate that a true aversion is formed to the taste of a diet that is deficient in an essential amino acid.}, } @article {pmid10708684, year = {2000}, author = {Grigson, PS and Lyuboslavsky, P and Tanase, D}, title = {Bilateral lesions of the gustatory thalamus disrupt morphine- but not LiCl-induced intake suppression in rats: evidence against the conditioned taste aversion hypothesis.}, journal = {Brain research}, volume = {858}, number = {2}, pages = {327-337}, doi = {10.1016/s0006-8993(00)01939-9}, pmid = {10708684}, issn = {0006-8993}, support = {DA 09815/DA/NIDA NIH HHS/United States ; DC 02016/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Psychological/drug effects ; Denervation ; Drinking/drug effects ; Excitatory Amino Acid Agonists ; Ibotenic Acid ; Lithium Chloride/*pharmacology ; Male ; Morphine/*pharmacology ; Narcotics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Sweetening Agents ; Taste ; Thalamus/drug effects/pathology/*physiopathology ; }, abstract = {Rats decrease intake of a saccharin conditioned stimulus (CS) when followed by: (1) the administration of an aversive agent such as lithium chloride (referred to as a conditioned taste aversion, CTA); (2) access to a very palatable concentration of sucrose (referred to as an anticipatory contrast effect, ACE); or (3) the administration of a drug of abuse. It is not clear, however, whether the suppressive effects of drugs of abuse are mediated by their aversive or rewarding properties. The present set of experiments addressed this issue by examining the suppressive effects of morphine in rats with a lesion thought to dissociate the two phenomena (i.e., CTA and ACE). The results show that bilateral ibotenic acid lesions of the gustatory thalamus eliminate the suppressive effects of morphine, but fail to disrupt the suppressive effects of the aversive agent, lithium chloride. This pattern of results argues against the CTA account in favor of the reward comparison hypothesis. Specifically, the data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of a preferred drug of abuse and that the gustatory thalamus is essential for this type of reward comparison process.}, } @article {pmid10704516, year = {2000}, author = {Kobayashi, K and Noda, Y and Matsushita, N and Nishii, K and Sawada, H and Nagatsu, T and Nakahara, D and Fukabori, R and Yasoshima, Y and Yamamoto, T and Miura, M and Kano, M and Mamiya, T and Miyamoto, Y and Nabeshima, T}, title = {Modest neuropsychological deficits caused by reduced noradrenaline metabolism in mice heterozygous for a mutated tyrosine hydroxylase gene.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {20}, number = {6}, pages = {2418-2426}, pmid = {10704516}, issn = {1529-2401}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/physiology ; Brain Chemistry/genetics ; Chimera ; Fear ; Female ; Frontal Lobe/cytology/enzymology ; Heterozygote ; Hippocampus/cytology/*physiology ; Long-Term Potentiation/physiology ; Male ; Memory/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Neurologic Mutants ; Microdialysis ; Neurons/enzymology ; Norepinephrine/*metabolism ; Space Perception/physiology ; Tyrosine 3-Monooxygenase/*genetics/metabolism ; }, abstract = {Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines that are considered to be involved in a variety of neuropsychiatric functions. Here, we report behavioral and neuropsychological deficits in mice carrying a single mutated allele of the TH gene in which TH activity in tissues is reduced to approximately 40% of the wild-type activity. In the mice heterozygous for the TH mutation, noradrenaline accumulation in brain regions was moderately decreased to 73-80% of the wild-type value. Measurement of extracellular noradrenaline level in the frontal cortex by the microdialysis technique showed a reduction in high K(+)-evoked noradrenaline release in the mutants. The mutant mice displayed impairment in the water-finding task associated with latent learning performance. They also exhibited mild impairment in long-term memory formation in three distinct forms of associative learning, including active avoidance, cued fear conditioning, and conditioned taste aversion. These deficits were restored by the drug-induced stimulation of noradrenergic activity. In contrast, the spatial learning and hippocampal long-term potentiation were normal in the mutants. These results provide genetic evidence that the central noradrenaline system plays an important role in memory formation, particularly in the long-term memory of conditioned learning.}, } @article {pmid10688054, year = {2000}, author = {Ballesteros, MA and Gallo, M}, title = {Bilateral tetrodotoxin blockade of the rat vestibular nuclei substitutes the natural unconditioned stimulus in taste aversion learning.}, journal = {Neuroscience letters}, volume = {279}, number = {3}, pages = {161-164}, doi = {10.1016/s0304-3940(99)00977-5}, pmid = {10688054}, issn = {0304-3940}, mesh = {Animals ; Avoidance Learning/*drug effects/*physiology ; Male ; Motion Sickness/physiopathology ; Rats ; Rats, Wistar ; Taste/*drug effects/*physiology ; Tetrodotoxin/*pharmacology ; Vestibular Nuclei/*drug effects/*physiology ; }, abstract = {The aversive effects of bilateral transient blockade of the lateral vestibular nucleus caused by tetrodotoxin microinjections were tested using conditioned taste aversion in the first experiment. Male Wistar rats received tetrodotoxin injections (10 ng) after drinking a coffee solution (0.5%), either in the lateral vestibular nucleus (LVN), the parabrachial nucleus or the dopaminergic area A8. Two days later they drank a cider vinegar solution (3%) not followed by injections. In a later choice test, only the group receiving the injection in the lateral vestibular nucleus displayed a coffee aversion. In a second experiment the role of the peripheral vestibular symptoms induced by LVN inactivation on substituting the aversive stimulus was explored in the same behavioral task. Rats anesthetized (Pentobarbital, 25 mg/kg) before tetrodoxin LVN blockade, that did not show peripheral symptoms, did not develop learned aversions. The coffee preference ratios did not differ to those animals receiving only anesthesia or those that remained undisturbed. These results showed that the bilateral blockade of the vestibular nuclei may induce peripheral vestibular symptoms that that may substitute the aversive stimulus in taste aversion learning.}, } @article {pmid10683477, year = {2000}, author = {Tuomisto, JT and Viluksela, M and Pohjanvirta, R and Tuomisto, J}, title = {Changes in food intake and food selection in rats after 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {65}, number = {3}, pages = {381-387}, doi = {10.1016/s0091-3057(99)00209-9}, pmid = {10683477}, issn = {0091-3057}, mesh = {Animals ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Dietary Proteins/administration & dosage ; Energy Intake ; Feeding Behavior/*drug effects ; Female ; Food Preferences/*drug effects ; Male ; Polychlorinated Dibenzodioxins/*toxicity ; Rats ; Rats, Long-Evans ; Rats, Wistar ; }, abstract = {Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on food selection were studied in TCDD-resistant Han/Wistar and TCDD-sensitive Long-Evans rats and their crosses. The rats were offered a selection diet consisting of chocolate, cheese, and chow, and TCDD was given at the same time or 4 or 16 days later. TCDD persistently reduced the chocolate intake. When the selection diet was started at the time of or less than 11 h after TCDD exposure, TCDD almost completely prevented the intake of chocolate and also cheese in all strains already on the first day, while controls started to consume large amounts of both foods. This may be due to conditioned taste aversion. The effect on food selection with familiar foods seemed to reduce fat intake, while protein and carbohydrate intakes were more variable. There were no major strain differences in the chocolate intake inhibition despite a 1000-fold sensitivity difference in TCDD lethality.}, } @article {pmid10662851, year = {2000}, author = {Seeley, RJ and Blake, K and Rushing, PA and Benoit, S and Eng, J and Woods, SC and D'Alessio, D}, title = {The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {20}, number = {4}, pages = {1616-1621}, pmid = {10662851}, issn = {0270-6474}, support = {R01 DK017844/DK/NIDDK NIH HHS/United States ; DK54080/DK/NIDDK NIH HHS/United States ; R01 DK054080/DK/NIDDK NIH HHS/United States ; DK54890/DK/NIDDK NIH HHS/United States ; DK17844/DK/NIDDK NIH HHS/United States ; R01 DK054890/DK/NIDDK NIH HHS/United States ; R37 DK017844/DK/NIDDK NIH HHS/United States ; }, mesh = {Angiotensins/administration & dosage ; Animals ; Avoidance Learning/*drug effects ; Cerebral Ventricles/drug effects/*physiology ; Drinking Behavior/drug effects ; Energy Intake/*drug effects ; Feeding Behavior/drug effects ; Glucagon/physiology ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptides ; Injections, Intraventricular ; Kaolin/pharmacology ; Lithium Chloride/antagonists & inhibitors/*toxicity ; Male ; Peptide Fragments/administration & dosage/*pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Glucagon/antagonists & inhibitors/*physiology ; Sodium, Dietary ; Taste/*drug effects ; Time Factors ; }, abstract = {Peripheral administration of large doses of lithium chloride (LiCl) to rats causes a spectrum of effects that are consistent with visceral illness. LiCl reduces food intake, decreases salt ingestion after sodium depletion, induces pica, and produces robust conditioned taste aversions. Because some of the effects of peripheral LiCl are mimicked by centrally administered glucagon-like peptide-1 (7-36) amide (GLP-1), we hypothesized that this peptide is involved in the neural pathways by which LiCl causes visceral illness. To test this hypothesis, we pretreated rats with a selective and potent GLP-1 receptor antagonist given directly into the third ventricle via an indwelling cannula before administration of peripheral LiCl. The GLP-1 receptor antagonist completely blocked the effect of LiCl to reduce food intake, induce pica, and produce a conditioned taste aversion. The same dose of GLP-1 receptor antagonist did not reverse the LiCl-induced reduction in NaCl intake. The data indicate a role for GLP-1 receptors in the CNS pathway that mediates some of the effects of visceral illness.}, } @article {pmid10661518, year = {2000}, author = {Spray, KJ and Halsell, CB and Bernstein, IL}, title = {c-Fos induction in response to saccharin after taste aversion learning depends on conditioning method.}, journal = {Brain research}, volume = {852}, number = {1}, pages = {225-227}, doi = {10.1016/s0006-8993(99)02203-9}, pmid = {10661518}, issn = {0006-8993}, support = {DC02891/DC/NIDCD NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Avoidance Learning/*physiology ; *Conditioning, Psychological ; Injections ; Lithium Chloride/pharmacology ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Long-Evans ; Reaction Time/physiology ; Saccharin/*administration & dosage/pharmacology ; Sodium Chloride/pharmacology ; Sweetening Agents/*administration & dosage/pharmacology ; Taste/*physiology ; }, abstract = {Increases in c-Fos-like immunoreactivity (FLI) in the intermediate nucleus of the solitary tract (iNTS) have been seen consistently as a correlate of the expression of a conditioned taste aversion (CTA) when conditioning occurs using taste delivery through intraoral (I/O) infusions. The present study examined whether a similar FLI response would occur when conditioning was accomplished by presenting the taste solution in a bottle. I/O and bottle methods generated aversions that were comparable, when judged by the behavioral response of solution rejection. However, elevations in FLI were seen only in animals conditioned with the I/O method. This finding adds to evidence that the neural pathways underlying CTA learning differ as a function of the type of conditioning method used.}, } @article {pmid10661514, year = {2000}, author = {Escobar, ML and Bermúdez-Rattoni, F}, title = {Long-term potentiation in the insular cortex enhances conditioned taste aversion retention.}, journal = {Brain research}, volume = {852}, number = {1}, pages = {208-212}, doi = {10.1016/s0006-8993(99)02134-4}, pmid = {10661514}, issn = {0006-8993}, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Long-Term Potentiation/*physiology ; Male ; Rats ; Rats, Wistar ; Retention, Psychology/*physiology ; Synaptic Transmission/physiology ; Taste/*physiology ; Temporal Lobe/*physiology ; }, abstract = {Long-lasting changes in synaptic strength, such as long-term potentiation (LTP), are thought to underlie memory formation. Recent studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and retention of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce LTP in the IC of adult rats in vivo, as well as, that blockade of N-methyl-D-aspartate (NMDA) receptors disrupts CTA and IC-LTP induction in vivo. Here, we present experimental data showing that induction of LTP in the Bla-IC projection previous to CTA training enhances the retention of this task. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying neocortical LTP may contribute to memory related functions performed by the IC.}, } @article {pmid10643814, year = {2000}, author = {Yamanaka, M and Hatakeyama, D and Sadamoto, H and Kimura, T and Ito, E}, title = {Development of key neurons for learning stimulates learning ability in Lymnaea stagnalis.}, journal = {Neuroscience letters}, volume = {278}, number = {1-2}, pages = {113-116}, doi = {10.1016/s0304-3940(99)00916-7}, pmid = {10643814}, issn = {0304-3940}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Feeding Behavior/*drug effects ; Ganglia, Invertebrate/cytology/*growth & development/physiology ; Lymnaea/drug effects/growth & development/*physiology ; Neurons/*physiology ; Neuropil/ultrastructure ; Serotonin/*physiology ; Taste/*physiology ; }, abstract = {The pond snails, Lymnaea stagnalis, change their ability of conditioned taste aversion (CTA) during their development, for example, stage 29 embryos can acquire the CTA, whereas immature snails come to use a long-term memory to maintain the conditioned response. We thus examined the relationships between the learning ability and the development of key neurons (cerebral giant cells: CGCs) for this CTA. The immunoreactivity of serotonin, which is a main neurotransmitter employed in the feeding circuitry, was first observed in the CGCs at the stage 29. After hatching, the CGCs developed their neuropile faster than other cells in the buccal and cerebral ganglia, resulting in their early innervation at the immature stage. The present results, therefore, indicate that the development of key neurons for learning stimulates the developmental changes in learning ability.}, } @article {pmid10642120, year = {2000}, author = {Clausing, P and Mothes, HK and Opitz, B}, title = {Preweaning experience as a modifier of prenatal drug effects in rats and mice--a review.}, journal = {Neurotoxicology and teratology}, volume = {22}, number = {1}, pages = {113-123}, doi = {10.1016/s0892-0362(99)00051-3}, pmid = {10642120}, issn = {0892-0362}, mesh = {Animals ; Animals, Suckling ; Behavior, Animal/drug effects ; Brain/*drug effects/physiopathology ; Environment ; Female ; Male ; Mice ; Pituitary-Adrenal System/drug effects/physiology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Receptors, GABA-A/drug effects/physiology ; }, abstract = {The effects of preweaning experience in rats and mice on neuroendocrine and behavioral end points and their implications for prenatal drug effects are reviewed. The hypothalamo-pituitary-adrenal axis and the dopaminergic system were shown to be affected. Behavior related to hippocampal, adrenocortical functions and to the benzodiazepine receptor system was also modified. Other paradigms (nociception, conditioned taste aversion) exhibited susceptibility to such preweaning manipulations also. The effects of these early experiences seem to be mediated through complex factors including neuroendocrine responses of the pup to hypothermia and a permanent alteration of mother-infant interactions, with subsequent effects on neuroendocrine functions that are important for postnatal brain organization. Studies of interactions between prenatal drug effects and preweaning manipulations have been performed only with ethanol. When extending this work to other compounds, the systems and functions described above may provide some guidance in looking for possible interactions. In most cases the preweaning manipulations alleviated the effects of prenatal ethanol exposure. These findings may have important implications regarding the controversy about environmental influences affecting the outcome of exposure to neurobehavioral teratogens.}, } @article {pmid10641767, year = {1999}, author = {Clarke, MS and Prendergast, MA and Terry, AV}, title = {Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {6}, number = {6}, pages = {634-649}, pmid = {10641767}, issn = {1072-0502}, mesh = {Animals ; Avoidance Learning/drug effects ; Carbon Radioisotopes ; Cell Membrane/drug effects/*metabolism ; Discrimination Learning/drug effects ; Learning Disabilities/*chemically induced/physiopathology ; Male ; Maze Learning/drug effects ; Memory Disorders/*chemically induced/physiopathology ; Motor Activity/drug effects ; Nicotine/pharmacology ; Nicotinic Agonists/pharmacology ; Norepinephrine/*pharmacokinetics ; PC12 Cells ; Poloxamer/*pharmacology ; Postural Balance/drug effects ; Psychomotor Performance/drug effects ; Rats ; Rats, Wistar ; Reaction Time/drug effects ; Surface-Active Agents/*pharmacology ; Sympathomimetics/*pharmacokinetics ; Synaptic Transmission/drug effects ; Taste ; Tritium ; Visual Acuity/drug effects ; }, abstract = {A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.}, } @article {pmid10636301, year = {1999}, author = {Benoit, SC and Morell, JR and Davidson, TL}, title = {Lesions of the amygdala central nucleus abolish lipoprivic-enhanced responding during oil-predicting conditioned stimuli.}, journal = {Behavioral neuroscience}, volume = {113}, number = {6}, pages = {1233-1241}, doi = {10.1037//0735-7044.113.6.1233}, pmid = {10636301}, issn = {0735-7044}, support = {R01-HD2879Z-05/HD/NICHD NIH HHS/United States ; }, mesh = {Amygdala/drug effects/*physiology ; Animals ; Appetitive Behavior/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/drug effects/*physiology ; Excitatory Amino Acid Agonists/administration & dosage/pharmacology ; Ibotenic Acid/administration & dosage/pharmacology ; Male ; Microinjections ; Rats ; Rats, Sprague-Dawley ; Thioglycolates/administration & dosage/pharmacology ; }, abstract = {T. L. Davidson, A. M. Altizer, S. C. Benoit, E. K. Walls, and T. L. Powley (1997) reported that rats show facilitated responding to conditioned stimuli (CSs) that predict oil, after administration of the lipoprivic agent, Na-2-mercaptoacetate (MA). This facilitation was blocked by vagal deafferentation. The present article extends that investigation to another structure, the amygdala central nucleus (CN). The CN receives inputs from dorsal vagal nuclei, and neurotoxic lesions of this nucleus are reported to abolish feeding in response to lipoprivic challenges. In Experiment 1, rats with ibotenic acid (IBO) lesions of the CN failed to show enhanced appetitive responding during oil-predicting CSs after administration of MA. Experiment 2 used a conditioned taste-aversion procedure to establish that rats with IBO lesions of the CN were able to discriminate the tastes of sucrose and peanut oil and had intact CS-US representations. It is concluded that the amygdala CN is a necessary structure for the detection of lipoprivic challenges.}, } @article {pmid10627084, year = {1999}, author = {Stephan, FK and Smith, JC and Fisher, E}, title = {Profound conditioned taste aversion induced by oral consumption of 2-deoxy-D-glucose.}, journal = {Physiology & behavior}, volume = {68}, number = {1-2}, pages = {221-226}, doi = {10.1016/s0031-9384(99)00179-1}, pmid = {10627084}, issn = {0031-9384}, support = {R01-DC 02641/DC/NIDCD NIH HHS/United States ; R01-DK 50224/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Antimetabolites/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Deoxyglucose/*pharmacology ; Drinking/drug effects ; Female ; Injections, Intraperitoneal ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {In a previous experiment rats avidly avoided a solution of 2-deoxy-d-glucose in 0.2% saccharin (2-DG+S), drinking less than 1 mL over 3 days. The present study investigated taste avoidance and conditioned taste aversion (CTA) to orally presented 2-DG+S as well as CTA in response to i.p. injections of 2-DG. In Experiment 1, rats were given either a glucose/saccharin(G +S) solution or 2-DG+S for eight 30-s test periods. Four seconds into the first 30-s test, rats in the 2-DG+S group licked significantly less than rats in the G+S group, and licking almost totally ceased in the remaining seven tests. Overnight water intake was not different between the groups, but when offered a G+S solution, rats in the 2-DG+S group almost totally avoided the solution and still showed a significant aversion to G+S when retested 6 days later. In Experiment 2, rats were allowed to drink G +S, and were then injected i.p. with 500 mg 2-DG/kg, 500 mg D-glucose/kg body weight in 0.3 mL water, or with 0.3 mL saline. When tested with a G +S solution the next day, rats in the 2-DG group showed a highly significant avoidance, while rats in the glucose group were not different from those in the saline group. The results of the second experiment are consistent with earlier studies of CTA induced by i.p. injections of 2-DG. The present study indicates that small amounts of orally ingested 2-DG produce a CTA as strong or even stronger than that following injected 2-DG, most likely by inducing malaise. Whether the onset of malaise is fast enough to account for the rapid initial avoidance of this solution or a taste factor is also involved is not yet clear.}, } @article {pmid10627078, year = {1999}, author = {Singer, LK and York, DA and Berthoud, HR and Bray, GA}, title = {Conditioned taste aversion produced by inhibitors of fatty acid oxidation in rats.}, journal = {Physiology & behavior}, volume = {68}, number = {1-2}, pages = {175-179}, doi = {10.1016/s0031-9384(99)00172-9}, pmid = {10627078}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Carnitine O-Palmitoyltransferase/antagonists & inhibitors ; Conditioning, Classical/*drug effects ; Eating/drug effects ; Epoxy Compounds/*pharmacology ; Fatty Acid Desaturases/antagonists & inhibitors ; Fatty Acids/*metabolism ; Male ; Oxidation-Reduction ; Propionates/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; Thioglycolates/*pharmacology ; }, abstract = {The aversive effects of mercaptoacetate (MA) and methyl palmoxirate (MP) were examined in the present experiment. We used a conditioned taste aversion (CTA) paradigm for Sprague-Dawley rats maintained on a low- or high-fat diet, and determined that MA and MP both produce profound aversions to a novel saccharin solution. Because it is known that the stimulation of food intake brought about by MA administration is blocked by destruction of vagal afferents. we repeated the CTA experiment in control and capsaicin-treated rats. Results show that although the capsaicin-treated rats did not increase food intake after MA administration, the CTA produced by MA remained. Therefore, the neural pathways for the aversive and orexigenic effects of MA are distinct. We conclude that MA and MP are aversive, and that the aversive signal generated by MA does not involve vagal afferents or other fibers damaged by capsaicin.}, } @article {pmid10625523, year = {1999}, author = {Nakajima, S and Ka, H and Imada, J}, title = {Summation of overshadowing and latent inhibition in rats' conditioned taste aversion: scapegoat technique works for familiar meals.}, journal = {Appetite}, volume = {33}, number = {3}, pages = {299-307}, doi = {10.1006/appe.1999.0247}, pmid = {10625523}, issn = {0195-6663}, mesh = {Analysis of Variance ; Animals ; *Appetite ; Avoidance Learning ; Conditioning, Psychological ; Feeding Behavior/*psychology ; *Food ; Male ; Rats ; Rats, Wistar ; Scapegoating ; *Taste ; }, abstract = {In rats' taste aversion learning, presentation of another taste with a target taste alleviates aversion for the target taste (overshadowing), and exposure of a target taste prior to its conditioning alleviates aversion for that taste (latent inhibition). The present study demonstrated summation of these effects, resulting in the least aversion in the rats that had received both overshadowing and latent inhibition treatments. The finding that overshadowing and latent inhibition summate is contrary to the prediction by the comparator hypothesis that they counteract, as recently reported in conditioned suppression of licking in thirsty rats. The present result supports the employment of the so-called "scapegoat technique" in cancer patients receiving chemotherapy after taking familiar meals.}, } @article {pmid10619667, year = {1999}, author = {Swank, MW}, title = {Coordinate regulation of Fos and Jun proteins in mouse brain by LiCl.}, journal = {Neuroreport}, volume = {10}, number = {17}, pages = {3685-3689}, doi = {10.1097/00001756-199911260-00041}, pmid = {10619667}, issn = {0959-4965}, support = {HD33138-01/HD/NICHD NIH HHS/United States ; }, mesh = {Amygdala/drug effects/metabolism ; Animals ; Avoidance Learning/physiology ; Brain Stem/*drug effects/metabolism ; Fluorescent Antibody Technique ; Lithium Chloride/*pharmacology ; Male ; Mice ; Proto-Oncogene Proteins c-fos/*metabolism ; Proto-Oncogene Proteins c-jun/*metabolism ; Sensitivity and Specificity ; Signal Transduction/drug effects ; Solitary Nucleus/drug effects/metabolism ; Taste/physiology ; Up-Regulation/drug effects ; }, abstract = {Expression of the bZIP transcription factor c-Fos in the nucleus tractus solitarius (NTS) of the brain stem may allow for genomic encoding of an unconditioned stimulus (US) during taste aversion learning. Dimerization of c-Fos with other bZIP proteins of the Jun family is necessary to enable transcriptional efficacy at the AP-1 sequence of putative target gene promoter regions. The present study examined the regulation of Fos and Jun proteins by LiCl. Double immunofluorescence labelling revealed that LiCl causes a coordinate upregulation of c-Fos, FosB and JunB, and these proteins are colocalized in a majority of cells examined in NTS, parabrachial nucleus (PBN), and central nucleus of the amygdala (CeA). This study demonstrates that a coordinate signalling response occurs in relevant brain regions in response to LiCl.}, } @article {pmid10603292, year = {1999}, author = {Yuan, DL and Chambers, KC}, title = {Estradiol accelerates extinction of lithium chloride-induced conditioned taste aversions through its illness-associated properties.}, journal = {Hormones and behavior}, volume = {36}, number = {3}, pages = {287-298}, doi = {10.1006/hbeh.1999.1551}, pmid = {10603292}, issn = {0018-506X}, support = {HD20970/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Apomorphine/pharmacology ; Avoidance Learning/*drug effects/physiology ; Brain/drug effects/physiology ; Conditioning, Classical/drug effects/physiology ; Drinking/drug effects ; Estradiol/administration & dosage/adverse effects/blood/*pharmacology ; Extinction, Psychological/*drug effects ; Female ; Lithium Chloride/administration & dosage/adverse effects/*pharmacology ; Models, Psychological ; Nausea/*chemically induced ; Ovariectomy ; Rats ; Rats, Inbred F344 ; Sucrose/administration & dosage/metabolism ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {Estradiol accelerates extinction of LiCl-induced conditioned taste aversions when it is present during a period that starts 2-3 days after acquisition and extends throughout extinction (before and during extinction). It has been suggested that estradiol acts before, not during, extinction and that its effect on extinction is associated with its illness-inducing properties. This hypothesis is based on previous work which shows an attenuation of conditioned taste aversion learning when rats are exposed to illness-inducing agents during a period that starts 2 days after acquisition and ends 2 days before extinction trials are initiated. Four experiments were designed to test elements of this hypothesis. The first two experiments demonstrated that if an estradiol-filled Silastic capsule is implanted before extinction of a LiCl-induced aversion, when the conditioned taste is not present, it accelerates extinction, but if it is implanted during extinction, when the conditioned taste is present, it prolongs extinction. The third experiment showed that the same dose of estradiol that accelerates extinction of a LiCl-induced aversion was effective in producing a conditioned taste aversion when it was present for 18 h after consumption of a novel sucrose solution. The fourth experiment indicated that serum levels of estradiol were elevated during the 18 h. These results are consistent with the hypothesis that the acceleration of extinction by estradiol is associated with its illness-inducing properties. It is suggested that estradiol acts on neural areas that mediate illness information and that one of these areas, the area postrema is necessary for estradiol to accelerate extinction of a LiCl-induced aversion.}, } @article {pmid10573570, year = {1999}, author = {Chotro, MG and Alonso, G}, title = {Effects of stimulus preexposure on the generalization of conditioned taste aversions in infant rats.}, journal = {Developmental psychobiology}, volume = {35}, number = {4}, pages = {304-317}, doi = {10.1002/(sici)1098-2302(199912)35:4<304::aid-dev5>3.0.co;2-o}, pmid = {10573570}, issn = {0012-1630}, mesh = {Animals ; Animals, Newborn/physiology ; Behavior, Animal/*physiology ; *Conditioning, Psychological ; Discrimination Learning/physiology ; Female ; *Generalization, Psychological ; Male ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {Generalization of a conditioned taste aversion in infant rats and how this is affected by stimulus preexposure was investigated in a series of experiments. In Experiment 1 generalization of a conditioned aversion between two tastes (sweet and salty) was found, and the effect of tastes preexposure was a reduction in generalization (Experiment 2). However, when these tastes were combined with a common taste (acid) that was less (Experiment 3) or more intense (Experiment 3b), the effect of stimulus preexposure was a stronger generalization of the conditioned aversion. In this case, a reduction on generalization was again observed by increasing the number of preexposure trials to the taste compounds (Experiment 4). In all cases the generalization levels were directly related to the effect of stimulus preexposure on the acquisition rate of conditioning. It can be concluded that, with the appropriate parameters, a reduction of generalization of a conditioned taste aversion can be obtained after taste exposure in preweanling rats.}, } @article {pmid10555164, year = {1999}, author = {Sakai, N and Yamamoto, T}, title = {Possible routes of visceral information in the rat brain in formation of conditioned taste aversion.}, journal = {Neuroscience research}, volume = {35}, number = {1}, pages = {53-61}, doi = {10.1016/s0168-0102(99)00067-x}, pmid = {10555164}, issn = {0168-0102}, mesh = {Amygdala/drug effects/physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Axonal Transport ; Brain/drug effects/*physiology ; *Brain Mapping ; Conditioning, Operant ; Drinking Behavior/drug effects ; Ibotenic Acid/toxicity ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin ; *Taste ; Thalamus/drug effects/physiology ; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate ; }, abstract = {When ingestion of a taste stimulus is paired with internal malaise, the animal remembers the taste and rejects its ingestion thereafter. This learning is referred to as conditioned taste aversion (CTA). To establish CTA in adult male Wistar rats, 0.1% saccharin and an i.p. injection of 0.15 M LiCl were used as the conditioned and unconditioned stimuli, respectively. Neuroanatomical study using the tracer method was performed to examine the ascending routes from the lateral part of the parabrachial nucleus (PBlat) which receives general visceral information and suggested the three possible routes to the amygdala: (1) direct route to the central nucleus of the amygdala (CeA); (2) diencephalic route to the basolateral nucleus of the amygdala (BLA) involving the zona incerta (ZI) and the midline and intralaminar thalamic complex (MITC); and (3) cortical route to the BLA involving insular cortex (IC). Rats with excitotoxic lesions of each of the CeA, ZI, MITC or IC had only a small or negligible effect on the acquisition of CTA. However, single lesions of the BLA and combined lesions of the ZI and IC, but not CeA and IC, almost completely abolished the acquisition of CTA. These results together with previous findings suggest that visceral (or unconditioned stimulus) information in the PBlat is sent to the BLA which is essential for the acquisition of CTA via the functionally important two parallel routes, the diencephalic and cortical routes, with either being able to create the aversion.}, } @article {pmid10549904, year = {1999}, author = {Kunin, D and Smith, BR and Amit, Z}, title = {Cocaine and ethanol interaction in the conditioned taste aversion paradigm.}, journal = {Physiology & behavior}, volume = {67}, number = {4}, pages = {627-630}, doi = {10.1016/s0031-9384(99)00105-5}, pmid = {10549904}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/*pharmacology ; Cocaine/*pharmacology ; Dopamine Uptake Inhibitors/*pharmacology ; Drug Interactions ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {The aim of this study was to examine the relationship between cocaine and ethanol in a variant of the conditioned taste aversion (CTA) paradigm. The preexposure CTA procedure formed the basis of the following set of experiments. Experiments 1a and 1b assessed whether cocaine and ethanol were functionally related with overlapping stimulus properties as reflected in the preexposure CTA procedure. Male Wistar rats with restricted water access were preexposed to cocaine or ethanol for 3 consecutive days. Twenty-four hours after the last preexposure session, rats were conditioned to either ethanol or cocaine, respectively. The results of this set of experiments revealed a symmetrical interaction between cocaine and ethanol, where cocaine and ethanol effectively blocked CTA to one another. These findings suggested that there may be overlapping stimulus properties between cocaine and ethanol, which may be detected in this procedure.}, } @article {pmid10548272, year = {1999}, author = {Ciccocioppo, R and Angeletti, S and Chhada, M and Perfumi, M and Froldi, R and Massi, M}, title = {Conditioned taste aversion induced by ethanol in alcohol-preferring rats: influence of the method of ethanol administration.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {64}, number = {3}, pages = {563-566}, doi = {10.1016/s0091-3057(99)00104-5}, pmid = {10548272}, issn = {0091-3057}, mesh = {Alcohol Drinking/genetics/*psychology ; Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/administration & dosage/blood/*pharmacology ; Ethanol/administration & dosage/blood/*pharmacology ; Injections, Intraperitoneal ; Intubation, Gastrointestinal ; Male ; Rats ; Taste/*drug effects ; }, abstract = {A recent study of our group has shown that ethanol evokes conditioned place preference (CPP) in Marchigian Sardinian alcohol-preferring (msP) rats following intragastric (IG) administration by means of an indwelling IG catheter, but not following administration by gavage or by intraperitoneal (IP) injection. The present study evaluated in ethanol-naive msP rats the influence of the method of administration (IG injection by indwelling catheter vs. IP injection) on ethanol-induced conditioned taste aversion (CTA). The dose of 0.35 g/kg of ethanol did not evoke aversion either by IG or by IP administration. Following IG injection, 0.7 g/kg of ethanol, the amount that msP rats voluntarily ingest in a short (2-5 min) drinking episode, did not evoke CTA, and 1.5 g/kg induced a modest CTA. On the other hand, IP injection of 0.7 g/kg of ethanol evoked CTA, and 1.5 g/kg induced a very pronounced CTA. These findings show that the aversive properties of ethanol in msP rats are influenced by the method of administration, and suggest that the IG injection by catheter may reveal more faithfully than the IP injection the motivational properties of amounts of ethanol that alcohol-preferring rats voluntarily ingest.}, } @article {pmid10519056, year = {1999}, author = {Cubero, I and Thiele, TE and Bernstein, IL}, title = {Insular cortex lesions and taste aversion learning: effects of conditioning method and timing of lesion.}, journal = {Brain research}, volume = {839}, number = {2}, pages = {323-330}, doi = {10.1016/s0006-8993(99)01745-x}, pmid = {10519056}, issn = {0006-8993}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/drug effects/physiology ; Cerebral Cortex/chemistry/pathology/*physiopathology ; Conditioning, Classical/drug effects/*physiology ; Denervation ; Lithium Chloride/pharmacology ; Male ; Proto-Oncogene Proteins c-fos/analysis ; Rats ; Rats, Long-Evans ; Reaction Time/physiology ; Saccharin ; Solitary Nucleus/chemistry/physiology ; Sweetening Agents ; Taste/*physiology ; Time Factors ; Water Deprivation ; }, abstract = {The specific role of insular cortex in acquisition and expression of a conditioned taste aversion was assessed using two different conditioning methods, which vary mode of taste delivery. Involvement of insular cortex in the induction of c-Fos-immunoreactivity in the nucleus of the solitary tract, a cellular correlate of the behavioral expression of a conditioned taste aversion, was also assessed. Electrolytic lesions of insular cortex blocked behavioral expression of a conditioned taste aversion and this was evident not only when lesions were placed prior to conditioning, but also when they were made after conditioning but before testing. In contrast to the effects on behavior, lesions did not completely block the c-Fos-immunoreactivity which accompanies re-exposure to the aversive taste. In addition, the blocking of behavioral evidence of aversion conditioning by cortical lesions was seen both in animals trained under an intraoral acquisition procedure and those trained with bottle-conditioning. This contrasts with previous work with amygdala lesions which showed that amygdala was absolutely necessary for taste aversions conditioned with the intraoral method but not for those conditioned using bottle presentation of the taste. Overall, these findings imply that the details of the neural circuitry involved in taste aversion learning, including its anatomical distribution, complexity and degree of redundancy, vary with the type of conditioning method employed.}, } @article {pmid10515321, year = {1999}, author = {Järbe, TU and Lamb, RJ}, title = {Discriminated taste aversion and context: a progress report.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {64}, number = {2}, pages = {403-407}, doi = {10.1016/s0091-3057(99)00052-0}, pmid = {10515321}, issn = {0091-3057}, support = {DA 09064/DA/NIDA NIH HHS/United States ; KO2DA 00253/DA/NIDA NIH HHS/United States ; R01-DA 08395/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/*drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Lithium Chloride/pharmacology ; Male ; Morphine/pharmacology ; Narcotics/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {The research described here concerns the interaction between the environment (context), the organism, and the effects of opiates, focusing on how conditioning and contextual cues affect drug controlled behaviors. This analysis applies the powerful tool of drug discrimination to a respondent conditioning procedure (discriminated taste aversion, DTA). Data show that the use of DTA is feasible in that it is sensitive to morphine dose and saccharin concentration. Swifter control over DTA was achieved by increasing the LiCl dose (UCS magnitude). It is also clear that morphine alone can serve as a discriminative stimulus not requiring saccharin as a contextual element (which has been the case for most DTA studies to date), or saccharin being part of a compounded stimulus. Pharmacological specificity was demonstrated in substitution tests with delta-9-tetrahydrocannabinol. This research continues a systematic experimental analysis of the interaction between drug-controlled behavior and context.}, } @article {pmid10515307, year = {1999}, author = {De Beun, R}, title = {Hormones of the hypothalamo-pituitary-gonadal axis in drug discrimination learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {64}, number = {2}, pages = {311-317}, doi = {10.1016/s0091-3057(99)00056-8}, pmid = {10515307}, issn = {0091-3057}, mesh = {Animals ; Discrimination Learning/*drug effects ; Discrimination, Psychological/*drug effects ; Female ; Gonadal Steroid Hormones/*pharmacology ; Humans ; Hypothalamo-Hypophyseal System/*physiology ; Male ; Pituitary Hormones/*pharmacology ; Rats ; }, abstract = {More than 30 years ago, T-maze studies with progesterone indicated that sex hormones have the potential to act as a discriminative stimulus in rats. Despite these early positive findings, the interest in discriminative stimulus properties of sex hormones remained low; few studies were dedicated to the investigation of discriminative stimulus properties of hypothalamo-pituitary-gonadal axis hormones (i.e., LHRH, LH/FSH, sex steroids). Nevertheless, the few studies that were published showed some interesting, and often sex-dependent results. Applying various methodologies (T-, or Y-maze, two-lever drug discrimination, taste aversion procedures), it was found that not only progesterone but also the two other principal sex steroids estradiol and testosterone can serve as discriminative stimuli in rodents. In addition to these gonadal hormones, the hypothalamic peptide LHRH (having a key role in the neuroendocrine regulation of steroid release from the gonads) appears to generate discriminative stimulus properties. Interestingly, recent (but preliminary) studies in postmenopausal women suggest that estradiol (and possibly progesterone) may also function as a discriminative stimulus in human subjects.}, } @article {pmid10515294, year = {1999}, author = {Olivier, B and Gommans, J and van der Gugten, J and Bouwknecht, JA and Herremans, AH and Patty, T and Hijzen, TH}, title = {Stimulus properties of the selective 5-HT reuptake inhibitor fluvoxamine in conditioned taste aversion procedures.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {64}, number = {2}, pages = {213-220}, doi = {10.1016/s0091-3057(99)00082-9}, pmid = {10515294}, issn = {0091-3057}, mesh = {Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/*drug effects ; Fluvoxamine/*pharmacology ; Glucose/pharmacology ; Lithium Chloride/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Serotonin Uptake Inhibitors/*pharmacology ; Stimulation, Chemical ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {Previous attempts to train pigeons and rats to discriminate between the antidepressant fluvoxamine and its vehicle as assessed in a drug discrimination paradigm have been without success. The present experiments were, therefore, designed to assess in a conditioned taste aversion procedure (CTA) whether or not fluvoxamine possesses stimulus properties. Rats were exposed to a conditioned taste aversion (CTA) procedure. In Experiment I, subjects were given 15 mg/kg fluvoxamine p.o. or vehicle after drinking a novel tasting saccharin solution. In Experiment II, a comparison was made between the effects of 15 mg/kg fluvoxamine i.p., 30 mg/kg fluvoxamine i.p., NaCl, and lithium chloride (LiCl). In Experiment III, subjects were treated with either 10 mg/kg fluoxetine i.p., 30 mg/kg fluvoxamine i.p., or LiCl. CTA was observed after treatment with LiCl, but never after treatment with fluvoxamine or fluoxetine, suggesting that fluvoxamine does not have clear stimulus properties, which can serve as a discriminative stimulus in operant procedures. In a crossfamiliarization CTA procedure in mice, however, fluvoxamine elicited a reliable CTA, suggesting that under certain conditions (species, dose?) selective serotonin reuptake inhibitors (SSRIs) may lead to certain discriminable effects. It is as yet unclear why SSRIs apparently produce such weak and species or situation-dependent discriminable effects.}, } @article {pmid10515293, year = {1999}, author = {De Vry, J and Schreiber, R and De Beun, R}, title = {Discriminative and affective stimulus effects of dihydropyridine calcium channel modulators: relationship to antialcohol effects.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {64}, number = {2}, pages = {203-211}, doi = {10.1016/s0091-3057(99)00078-7}, pmid = {10515293}, issn = {0091-3057}, mesh = {Affect/*drug effects ; Alcohol Deterrents/*pharmacology ; Animals ; Calcium Channel Agonists/*pharmacology ; Calcium Channel Blockers/*pharmacology ; Dihydropyridines/*pharmacology ; Discrimination, Psychological/*drug effects ; Humans ; Rats ; }, abstract = {Voltage-operated calcium channels (VOCCs) have been implicated in alcoholism. Thus, dihydropyridine (DHP) VOCC antagonists, such as nimodipine, reduce ethanol (EtOH) intake and preference in a variety of animal models of alcoholism. Paradoxically, the DHP VOCC agonist BAY k 8644 also demonstrates antialcohol effects in such models. The antialcohol effects of BAY k 8644 are stereoselective [the "agonistic" (-)-enantiomer being more potent than the "antagonistic" (+)-enantiomer], and are not blocked by pretreatment with nimodipine. The present review summarizes studies on the effects of DHPs in drug discrimination (DD), conditioned taste aversion (CTA), and conditioned place preference (CPP) paradigms, and discusses the possibility that the apparent antialcohol effect of these compounds is related to their discriminative and/or affective stimulus effects. In rats trained to discriminate nimodipine from vehicle, (-)-BAY k 8644 completely generalizes to the nimodipine cue; whereas, in rats trained to discriminate (-)-BAY k 8644, nimodipine completely generalizes to, and is unable to block, the (-)-BAY k 8644 cue. The same stereoselectivity is obtained for BAY k 8644 in DD paradigms and models of alcoholism. The apparent similarity of these profiles of activity suggests that a common neurobiological mechanism underlies the discriminative stimulus and antialcohol effects of DHPs. It appears unlikely, however, that the antialcohol effects of DHPs are based on substitution for, or blockade of, the EtOH cue, as these compounds were not found to generalize to, or block, the EtOH cue. Comparison of the effects of DHPs in CTA and CPP paradigms suggests that the affective stimulus effects of these compounds are dissimilar, and that the mechanism underlying the latter effects is probably not related to the mechanism underlying the antialcohol effects of DHP VOCC modulators.}, } @article {pmid10495090, year = {1999}, author = {Madden, LJ and Seeley, RJ and Woods, SC}, title = {Intraventricular neuropeptide Y decreases need-induced sodium appetite and increases pica in rats.}, journal = {Behavioral neuroscience}, volume = {113}, number = {4}, pages = {826-832}, pmid = {10495090}, issn = {0735-7044}, support = {DK 17844/DK/NIDDK NIH HHS/United States ; DK 54890/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/drug effects/*physiology ; Eating/drug effects/*physiology ; Feeding Behavior/drug effects/*physiology ; Injections, Intraventricular ; Kaolin ; Male ; Neuropeptide Y/administration & dosage/*physiology ; Neurotransmitter Agents/administration & dosage/physiology ; Pica/*chemically induced ; Rats ; Rats, Long-Evans ; Sodium/*deficiency ; Sodium, Dietary/*administration & dosage ; }, abstract = {Neuropeptide Y (NPY) is a potent endogenous stimulator of food intake. In addition to stimulating increased food intake, when paired with a novel-flavored solution, NPY produces an aversion to that flavor. Hence, exogenous NPY elicits 2 seemingly opposing behaviors, increased feeding and the formation of a conditioned taste aversion. One interpretation of these data is that NPY produces some form of malaise or visceral illness. NPY's orexigenic and malaise-inducing properties were tested in rats with 2 measures sensitive to malaise, increased kaolin consumption (pica behavior) and failure to express need-induced sodium intake. Administration of NPY resulted in increased food intake, increased kaolin consumption, and decreased need-induced sodium intake. These data support the hypothesis that exogenous NPY has both orexigenic and malaise-inducing properties.}, } @article {pmid10489263, year = {1998}, author = {Schafe, GE and Thiele, TE and Bernstein, IL}, title = {Conditioning method dramatically alters the role of amygdala in taste aversion learning.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {5}, number = {6}, pages = {481-492}, pmid = {10489263}, issn = {1072-0502}, support = {R01 NS037040/NS/NINDS NIH HHS/United States ; NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Choice Behavior/physiology ; Conditioning, Operant/*physiology ; Drinking Behavior/physiology ; Habituation, Psychophysiologic/physiology ; Male ; Rats ; Rats, Long-Evans ; Reaction Time/physiology ; Taste/*physiology ; }, abstract = {Although an important role for the amygdala in taste aversion learning has been suggested by work in a number of laboratories, results have been inconsistent and interpretations varied. The present series of studies reevaluated the role of the amygdala in taste aversion learning by examining the extent to which conditioning methods, testing methods and lesioning methods, influence whether amygdala lesions dramatically affect conditioned taste aversion (CTA) learning. Results indicated that when animals are conditioned with an intraoral (I/O) taste presentation, lesions of amygdala eliminate evidence of conditioning whether animals are tested intraorally or with a two-bottle solution presentation. Dramatic effects of amygdala lesions on CTA learning were seen whether lesions were made electrolytically or using an excitotoxin. In contrast, when animals were conditioned using bottle presentation of the taste, electrolytic lesions attenuated CTAs but did not eliminate them, and excitotoxic lesions had no effect. These results are consistent with the hypothesis that neural structures critical for CTA learning may differ depending on the extent to which the method of conditioned stimulus delivery incorporates a response component.}, } @article {pmid10480681, year = {1999}, author = {Stapleton, JR and Roper, SD and Delay, ER}, title = {The taste of monosodium glutamate (MSG), L-aspartic acid, and N-methyl-D-aspartate (NMDA) in rats: are NMDA receptors involved in MSG taste?.}, journal = {Chemical senses}, volume = {24}, number = {4}, pages = {449-457}, doi = {10.1093/chemse/24.4.449}, pmid = {10480681}, issn = {0379-864X}, support = {1 RO1DC03013/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Aspartic Acid ; Avoidance Learning ; Male ; *N-Methylaspartate ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/*physiology ; *Sodium Glutamate ; Taste/*physiology ; }, abstract = {Monosodium glutamate (MSG) is believed to elicit a unique taste perception known as umami. We have used conditioned taste aversion assays in rats to compare taste responses elicited by the glutamate receptor agonists MSG, L-aspartic acid (L-Asp), and N-methyl-D-aspartate (NMDA), and to determine if these compounds share a common taste quality. This information could shed new light upon the receptor mechanisms of glutamate taste transduction. Taste aversions to either MSG, L-Asp or NMDA were produced by injecting rats with LiCl after they had ingested one of these stimuli. Subsequently, rats were tested to determine whether they would ingest any of the above compounds. The results clearly show that a conditioned aversion to MSG generalized to L-Asp in a dose-dependent manner. Conversely, rats conditioned to avoid L-Asp also avoided MSG. Conditioned aversions to MSG or L-Asp generalized to sucrose when amiloride was included in all solutions. Importantly, aversions to MSG or L-Asp did not generalize to NMDA, NaCl or KCl, and aversions to NMDA did not generalize to MSG, L-Asp, sucrose or KCl. These data indicate that rats perceive MSG and L-Asp as similar tastes, whereas NMDA, NaCl and KCl elicit other tastes. The results do not support a dominant role for the NMDA subtype of glutamate receptors in taste transduction for MSG (i.e. umami) in rats.}, } @article {pmid10477060, year = {1999}, author = {Grigson, PS and Lyuboslavsky, PN and Tanase, D and Wheeler, RA}, title = {Water-deprivation prevents morphine-, but not LiCl-induced, suppression of sucrose intake.}, journal = {Physiology & behavior}, volume = {67}, number = {2}, pages = {277-286}, doi = {10.1016/s0031-9384(99)00080-3}, pmid = {10477060}, issn = {0031-9384}, support = {DA 09815/DA/NIDA NIH HHS/United States ; DC 02016/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Association ; Avoidance Learning/physiology ; Behavior, Addictive/physiopathology ; *Conditioning, Psychological/drug effects/physiology ; *Cues ; Dietary Sucrose/administration & dosage ; Drinking Behavior/drug effects/physiology ; Food Preferences/drug effects/physiology ; Lithium Chloride/*pharmacology ; Male ; Morphine/*pharmacology ; Narcotics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; *Reward ; Taste/drug effects/physiology ; Water Deprivation/*physiology ; }, abstract = {Intake of a saccharin-conditioned stimulus (CS) can be suppressed following pairing with an aversive agent such as lithium chloride (LiCl) or x-rays (referred to as a conditioned taste aversion or CTA), a highly rewarding sucrose solution (referred to as an anticipatory contrast effect), or a drug of abuse such as morphine or cocaine. Although the suppressive effects of LiCl and sucrose are clear examples of aversive and appetitive conditioning, respectively, it is not certain which properties (aversive or appetitive) mediate the suppressive effects of drugs of abuse. It is known, however, that the suppressive effects of a rewarding sucrose US are attenuated when using a caloric sucrose CS in food deprived rats, while LiCl induced CTAs are much less effected. Standard CTA testing typically is conducted in water-deprived rather than food-deprived rats and, although LiCl is known to suppress intake of a sucrose CS in water-deprived rats, the suppressive effects of drugs of abuse have not been evaluated under these conditions. The present experiment, then, compared the suppressive effects of a standard dose of morphine (15 mg/kg) and a matched dose of LiCl (0.009 M) on intake of a sucrose CS in water-deprived and free-feeding rats. The results showed that both drugs suppressed intake in free-feeding subjects, but only the aversive agent, LiCl, reduced CS intake in the water-deprived rats. This finding dissociates the suppressive effects of morphine and LiCl and, in so doing, aligns the suppressive effects of morphine with those of an appetitive sucrose US.}, } @article {pmid10470981, year = {1999}, author = {Thrasher, MJ and Freeman, PA and Risinger, FO}, title = {Clozapine's effects on ethanol's motivational properties.}, journal = {Alcoholism, clinical and experimental research}, volume = {23}, number = {8}, pages = {1377-1385}, pmid = {10470981}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/psychology ; Animals ; Central Nervous System Depressants/*administration & dosage ; Clozapine/*administration & dosage ; Conditioning, Psychological/drug effects ; Dopamine Antagonists/*administration & dosage ; Dopamine D2 Receptor Antagonists ; Ethanol/*administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Receptors, Dopamine D2/*drug effects/physiology ; Receptors, Dopamine D4 ; }, abstract = {BACKGROUND: Although dopamine D1 and D2 receptors have been implicated in ethanol's motivational effects, little is known about the contribution of dopamine D4 receptors. The present experiments examined the effects of clozapine, a dopamine D4 receptor antagonist, on ethanol's aversive, rewarding, stimulant, and reinforcing properties.

METHODS: For taste conditioning, adult male Swiss-Webster mice received five conditioning trials consisting of 1-hr access to 0.2 M NaCl. After NaCl access on trials 1-4, subjects received clozapine (0, 1, or 2 mg/kg) followed 30 min later by 0, 2, or 4 g/kg ethanol. For place conditioning, Swiss-Webster mice received six pairings of a tactile stimulus with ethanol (2 g/kg, intraperitoneally), clozapine (1 mg/kg, intraperitoneally) + ethanol, or clozapine alone. Locomotor activity in a 30-min test was determined in Swiss-Webster mice receiving 0, 0.5, or 1.0 mg/kg clozapine and 0, 1, or 2 g/kg ethanol. In a drinking study, separate groups of adult male C57BL/6J mice were allowed 30-min access to either 10% v/v ethanol mixed in 10% w/v sucrose or 10% sucrose without ethanol. During testing, both groups were given 0 or 1 mg/kg clozapine 30 min before fluid access.

RESULTS: Ethanol flavor pairings during taste conditioning reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Clozapine reduced the magnitude of 4 g/kg ethanol-conditioned aversion only on trial 4 at the 2 mg/kg dose. Conditioned place preference for the ethanol-paired stimulus was not altered by clozapine. Clozapine alone did not produce either conditioned preference or aversion. Ethanol-stimulated activity was reduced by clozapine treatment. However, clozapine alone did not alter locomotor activity levels. Clozapine reduced sucrose consumption but did not alter ethanol/sucrose intake.

CONCLUSIONS: These data suggest that clozapine influences a limited range of ethanol-motivated behaviors. Specifically, dopamine D4 receptors appear important for ethanol's stimulant effect and possibly ethanol aversion, but not ethanol reward and reinforcement.}, } @article {pmid10460272, year = {1999}, author = {Gutiérrez, H and Gutiérrez, R and Ramírez-Trejo, L and Silva-Gandarias, R and Ormsby, CE and Miranda, MI and Bermúdez-Rattoni, F}, title = {Redundant basal forebrain modulation in taste aversion memory formation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {19}, number = {17}, pages = {7661-7669}, pmid = {10460272}, issn = {1529-2401}, mesh = {Acetylcholinesterase/analysis ; Amygdala/physiology ; Animals ; Antibodies, Monoclonal/administration & dosage/pharmacology ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/physiology ; Cholinergic Agents/administration & dosage/pharmacology ; Corpus Striatum/physiology ; Immunotoxins/administration & dosage/pharmacology ; Male ; Memory/*physiology ; Microinjections ; Models, Neurological ; N-Glycosyl Hydrolases ; N-Methylaspartate/administration & dosage/*pharmacology ; Nerve Fibers/enzymology/physiology/ultrastructure ; Prosencephalon/drug effects/*physiology ; Rats ; Rats, Wistar ; Ribosome Inactivating Proteins, Type 1 ; Saporins ; Taste/*physiology ; }, abstract = {Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. It has been demonstrated that in spite of the strong cholinergic depletion after injections into the basal forebrain of the immunotoxin 192IgG-saporin, no detectable deficit can be found in the acquisition of several learning tasks, including conditioned taste aversion. Conversely, NMDA-induced lesions of the basal forebrain strongly impair taste aversion learning. In this study we show that 192IgG-saporin produces an efficient and selective cholinergic deafferentation of the rat neocortex but not the amygdala. Furthermore, a stronger relationship between severity of memory impairment after NMDA lesions and basoamygdaloid cholinergic deafferentation was found. Therefore, in a second experiment, we show that combining NMDA-induced lesions into the basolateral amygdala with 192IgG-saporin injections into the basal forebrain results in a strong disruption of taste aversion learning, whereas none of these treatments were by themselves capable of producing any detectable impairment in this learning task. The double lesion effect was only paralleled by simple NMDA lesions into the basal forebrain, suggesting that the learning deficits associated to excitotoxic lesions of the basal forebrain are the result of the simultaneous destruction of the corticopetal and basoamygdaloid interaction. A model is proposed, according to which the modulation of learning processes exerted by the basal forebrain can be redundantly performed by both the basocortical and basoamygdaloid pathway.}, } @article {pmid10456564, year = {1999}, author = {Risinger, FO and Brown, MM and Oakes, RA and Love, JA}, title = {Effects of haloperidol or SCH-23390 on ethanol-induced conditioned taste aversion.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {18}, number = {2-3}, pages = {139-145}, doi = {10.1016/s0741-8329(98)00076-7}, pmid = {10456564}, issn = {0741-8329}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA01760/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Benzazepines/*pharmacology ; Central Nervous System Depressants/*antagonists & inhibitors ; Conditioning, Psychological/*drug effects ; Dopamine Antagonists/*pharmacology ; Dopamine D2 Receptor Antagonists ; Ethanol/*administration & dosage ; Haloperidol/*pharmacology ; Male ; Mice ; Receptors, Dopamine D1/antagonists & inhibitors ; Sodium Chloride/administration & dosage ; Taste/*drug effects ; }, abstract = {Dopaminergic systems are thought to play an important role in the motivational effects of ethanol. The present experiments examined the effects of haloperidol (a D2 antagonist) and SCH-23390 (a D1 antagonist) on the acquisition of ethanol-induced conditioned taste aversion. In four separate experiments, adult male Swiss-Webster mice were acclimated to a 2-h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1-h access to either 0.2 M NaCl (experiments 1-3) or 0.15 % w/v saccharin (experiment 4). After flavor access on trials 1-3, subjects received either haloperidol (0.1, 0.15, or 0.3 mg/kg), SCH-23390 (0.05 mg/kg), or saline followed 30 min later by 0, 2, or 4 g/kg ethanol. Ethanol-flavor pairings reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Neither haloperidol of SCH-23390 reduced flavor intakes in the absence of ethanol. However, both haloperidol and SCH-23390 reduced ethanol-conditioned aversion depending on ethanol dose and conditioned flavor. These results are consistent with the notion that dopaminergic processes are important for the development of ethanol-induced conditioned taste aversion, and the notion that dopaminergic receptor systems influence both positive and negative motivational effects of ethanol.}, } @article {pmid10435409, year = {1999}, author = {Chester, JA and Cunningham, CL}, title = {GABA(A) receptors modulate ethanol-induced conditioned place preference and taste aversion in mice.}, journal = {Psychopharmacology}, volume = {144}, number = {4}, pages = {363-372}, doi = {10.1007/s002130051019}, pmid = {10435409}, issn = {0033-3158}, support = {AA05489/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Bicuculline/pharmacology ; Central Nervous System Depressants/*pharmacology ; Conditioning, Psychological/*drug effects ; Ethanol/blood/*pharmacology ; GABA Antagonists/*pharmacology ; *GABA-A Receptor Antagonists ; Male ; Mice ; Mice, Inbred DBA ; Picrotoxin/pharmacology ; Taste/*drug effects ; }, abstract = {RATIONALE: GABA(A) receptor antagonists have been shown to reduce ethanol self-administration and ethanol-induced conditioned taste aversion (CTA) in rats, suggesting a role for the GABA(A) receptor in modulating ethanol's motivational effects.

OBJECTIVES: The present experiments examined the effects of the GABA(A) receptor antagonists, bicuculline and picrotoxin, on the acquisition of ethanol-induced conditioned place preference (CPP) and CTA in male DBA/2J mice.

METHODS: Mice in the CPP experiments received four pairings of ethanol (2 g/kg) with a distinctive floor stimulus for a 5-min conditioning session (CS+ sessions). During CS+ sessions, mice also received bicuculline (0, 1.0, 3.0, or 5.0 mg/kg) or picrotoxin (2.0 mg/kg) before an injection of ethanol. On intervening days (CS- sessions), the pretreatment injection was always vehicle followed by saline injections that were paired with a different floor type. For the preference test, all mice received saline injections and were placed on a half grid and half hole floor for a 60-min session. For the CTA experiments, mice were adapted to a 2-h per day water restriction regimen followed by five conditioning trials every 48 h. During conditioning trials, subjects received an injection of vehicle, bicuculline (0.5 and 2.0 mg/kg), or picrotoxin (0.75 and 2.5 mg/kg) before injection of 2 g/kg ethanol or saline following 1-h access to a saccharin solution.

RESULTS: Both picrotoxin and the lowest dose of bicuculline (1.0 mg/kg) significantly increased the magnitude of CPP relative to vehicle-treated controls. Picrotoxin alone did not produce place conditioning. Ethanol-stimulated locomotor activity was significantly reduced during conditioning trials with picrotoxin and the higher doses of bicuculline (3.0 and 5.0 mg/kg). Bicuculline did not alter ethanol-induced CTA; however, picrotoxin dose-dependently increased the magnitude of ethanol-induced CTA. Bicuculline and picrotoxin did not produce CTA when administered alone.

CONCLUSIONS: Overall, these results suggest that blockade of GABA(A) receptors with bicuculline and picrotoxin enhances ethanol's motivational effects in the CPP paradigm; however, only picrotoxin enhances ethanol's motivational effects in the CTA paradigm.}, } @article {pmid10433882, year = {1999}, author = {Yuan, DL and Chambers, KC}, title = {Estradiol accelerates extinction of a conditioned taste aversion in female and male rats.}, journal = {Hormones and behavior}, volume = {36}, number = {1}, pages = {1-16}, doi = {10.1006/hbeh.1999.1520}, pmid = {10433882}, issn = {0018-506X}, support = {HD 20970/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drug Implants ; Extinction, Psychological/*drug effects ; Female ; Lithium Chloride ; Male ; Rats ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; Receptors, Opioid/drug effects ; Retention, Psychology/drug effects ; Taste/*drug effects ; Testosterone/pharmacology ; }, abstract = {Exogenous testosterone treatment prolongs extinction of conditioned taste aversions and estradiol treatment prevents testosterone from prolonging extinction in both gonadectomized males and females. Estradiol could require the presence of testosterone for its effect or its action alone could accelerate extinction. The first series of experiments were designed to test the hypothesis that estradiol accelerates extinction when it is given in the absence of testosterone. The results showed that estradiol accelerates extinction of conditioned taste aversions in the absence of testosterone in gonadectomized Sprague-Dawley females and Fischer 344 females and males. The second series of experiments were designed to determine whether estradiol and testosterone differ in the temporal requirements for their opposite effects on extinction. The results showed that estradiol can accelerate extinction when it is present before and during acquisition (from 8 days before until 3 days after acquisition) or when it is present before and during extinction (from 2 days after acquisition, which was 23 days before extinction, until extinction trials were terminated). This is in contrast to a previous finding that testosterone prolongs extinction only when it is present before and during extinction. The following two hypotheses were suggested to account for the temporal effects of estradiol on extinction of conditioned taste aversions: (1) the presence of estradiol during acquisition reduces the effectiveness of LiCl through its action on the opioid system, and the presence of estradiol during extinction activates a neural pathway, such as that associated with activity levels, that accelerates extinction of passive avoidance tasks in general or (2) the presence of estradiol before, not during, acquisition or extinction accelerates extinction because of its illness-inducing properties. Most of the evidence supports the second hypothesis.}, } @article {pmid10423857, year = {1999}, author = {Batsell, WR and Batson, JD}, title = {Augmentation of taste conditioning by a preconditioned odor.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {25}, number = {3}, pages = {374-388}, pmid = {10423857}, issn = {0097-7403}, mesh = {Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Drinking ; Humans ; Lithium Chloride/toxicity ; Male ; *Mental Recall ; Rats ; *Smell ; *Taste ; }, abstract = {Five experiments explored facilitated taste-aversion conditioning (odor-mediated taste augmentation), using rats that experienced odor (A) and taste (X) in an A+/AX+ design. Augmentation occurred when the stimuli were presented simultaneously during AX+ conditioning, and significantly weaker conditioning occurred after a sequential presentation (Experiment 1). Experiments 2 and 3 demonstrated that augmented conditioning decreased if the odor aversion was reduced through preexposure or extinction following A+ conditioning. A second-order conditioning explanation was not supported by the results of Experiment 4. Experiment 5 showed that extinction of the odor aversion after AX+ conditioning did not alter the strength of the augmented taste aversion. Odor-mediated taste augmentation is similar to potentiation, in which odor and taste cues operate in a synergistic, not competitive, manner.}, } @article {pmid10422896, year = {1999}, author = {Berendsen, HH and Broekkamp, CL}, title = {Antagonism of the 5-HT1A receptor stimulus in a conditioned taste aversion procedure.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {9}, number = {4}, pages = {345-349}, doi = {10.1016/s0924-977x(99)00004-8}, pmid = {10422896}, issn = {0924-977X}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Conditioning, Psychological/drug effects ; Drug Antagonism ; Male ; Mice ; Mice, Inbred ICR ; Piperazines/pharmacology ; Pyridines/pharmacology ; Receptors, Serotonin/drug effects/*metabolism ; Receptors, Serotonin, 5-HT1 ; Serotonin Receptor Agonists/*pharmacology ; Serotonin Uptake Inhibitors/*pharmacology ; Taste/*drug effects ; }, abstract = {The conditioned taste aversion procedure in mice was used to test for blockade of the drug stimulus of the 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT), 1-(4-trifluoromethyl-2-pyridinyl)-4- [4-[2-oxo-1-pyrrolidinyl]butyl]piperazine (E)-2-butenedioate (Org 13011) and the 5-HT reuptake inhibitor fluoxetine. The conditioned taste aversion induced by 8-OH-DPAT (0.22 mg/kg) and Org 13011 (0.5 mg/kg) was readily blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) (0.1 mg/kg). The conditioned taste aversion induced by fluoxetine could not be antagonized by WAY-100635 nor by the 5-HT2 receptor antagonist mianserin. It is concluded that the conditioned taste aversion induced by 8-OH-DPAT or Org 13011 is mediated via 5-HT1A receptors. The results suggest that the conditioned taste aversion induced by fluoxetine is not exclusively mediated by 5-HT1A receptors nor exclusively by 5-HT2 receptors. The results also indicate that the conditioned taste aversion paradigm can be used to test for antagonism of stimulus properties of compounds.}, } @article {pmid10418791, year = {1999}, author = {Grabus, SD and Smurthwaite, ST and Riley, AL}, title = {Nalorphine's ability to substitute for morphine in a drug discrimination procedure is a function of training dose.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {63}, number = {3}, pages = {481-488}, doi = {10.1016/s0091-3057(99)00008-8}, pmid = {10418791}, issn = {0091-3057}, mesh = {Animals ; Discrimination Learning/*drug effects ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Female ; Generalization, Response/drug effects ; Methadone/administration & dosage/pharmacology ; Morphine/administration & dosage/*pharmacology ; Nalorphine/administration & dosage/*pharmacology ; Narcotic Antagonists/administration & dosage/*pharmacology ; Narcotics/administration & dosage/*pharmacology ; Rats ; Rats, Long-Evans ; }, abstract = {Rats trained to discriminate the mu agonists fentanyl or morphine from their respective vehicles generalize to the partial mu agonist nalorphine incompletely and inconsistently. Any number of factors may influence the generalization patterns obtained, one of which being the specific dose of the full opioid agonist used during training, a factor reported to influence generalization with other partial opioid agonists. To assess if training dose influences stimulus generalization to nalorphine and to support its role in the aforementioned variability across studies, in the present experiments rats were trained to discriminate either a low (5.6 mg/kg) or a high (10 mg/kg) dose of morphine from distilled water within the taste aversion baseline of drug discrimination learning. Subjects were then given a range of doses of morphine, nalorphine, methadone, or naloxone to assess the degree of substitution (if any) of these compounds for the training dose of morphine. For all subjects, morphine fully substituted for itself, and the opioid antagonist naloxone failed to substitute for the morphine cue. Rats generalized the morphine cue to nalorphine in subjects trained at the lower dose but not in subjects trained at the higher dose. Rats generalized the morphine cue to methadone in the latter group (the high dose group), indicating that the failure to generalize to nalorphine in this group was not a general inability of an opioid agonist to substitute for morphine. Naloxone blocked morphine stimulus control in all subjects and nalorphine control in the low-dose group for which nalorphine substituted for morphine, suggesting that morphine control (and the nalorphine substitution) was based on opioid activity. These results indicate that the substitution patterns of nalorphine in morphine-trained subjects are a function in part of the dose of morphine used in training and support the position that nalorphine is a partial opioid agonist with intermediate efficacy.}, } @article {pmid10414988, year = {1999}, author = {Gallagher, M and McMahan, RW and Schoenbaum, G}, title = {Orbitofrontal cortex and representation of incentive value in associative learning.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {19}, number = {15}, pages = {6610-6614}, pmid = {10414988}, issn = {0270-6474}, support = {K05-MH01149/MH/NIMH NIH HHS/United States ; K08-AG00882-01/AG/NIA NIH HHS/United States ; R01 MH53667/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/physiology ; Brain Mapping ; Conditioning, Classical/physiology ; Feeding Behavior/physiology ; Frontal Lobe/*physiology ; Lithium Chloride/pharmacology ; Male ; Orbit ; Rats ; Rats, Long-Evans ; Reinforcement, Psychology ; }, abstract = {Clinical evidence indicates that damage to ventromedial prefrontal cortex disrupts goal-directed actions that are guided by motivational and emotional factors. As a consequence, patients with such damage characteristically engage in maladaptive behaviors. Other research has shown that neurons in the corresponding orbital region of prefrontal cortex in laboratory animals encode information regarding the incentive properties of goals or expected events. The present study investigates the effect of neurotoxic orbitofrontal cortex (OFC) lesions in the rat on responses that are normally influenced by associations between a conditioned stimulus (CS) and the incentive value of reinforcement. Rats were first trained to associate a visual CS with delivery of food pellets to a food cup. As a consequence of learning, rats approached the food cup during the CS in anticipation of reinforcement. In a second training phase, injection of LiCl followed consumption of the food unconditioned stimulus (US) in the home cage, a procedure used to alter the incentive value of the US. Subsequently, rats were returned to the conditioning chamber, and their responding to the CS in the absence of the food US was tested. Lesions of OFC did not affect either the initial acquisition of a conditioned response to the light CS in the first training phase or taste aversion learning in the second training phase. In the test for devaluation, however, OFC rats exhibited no change in conditioned responding to the visual CS. This outcome contrasts with the behavior of control rats; after devaluation of the US a significant decrease occurred in approach to the food cup during presentation of the CS. The results reveal an inability of a cue to access representational information about the incentive value of associated reinforcement after OFC damage.}, } @article {pmid10407102, year = {1999}, author = {Gutiérrez, H and Gutiérrez, R and Silva-Gandarias, R and Estrada, J and Miranda, MI and Bermúdez-Rattoni, F}, title = {Differential effects of 192IgG-saporin and NMDA-induced lesions into the basal forebrain on cholinergic activity and taste aversion memory formation.}, journal = {Brain research}, volume = {834}, number = {1-2}, pages = {136-141}, doi = {10.1016/s0006-8993(99)01519-x}, pmid = {10407102}, issn = {0006-8993}, mesh = {Acetylcholine/*metabolism ; Animals ; Antibodies, Monoclonal/*pharmacology ; Avoidance Learning/*physiology ; Choline O-Acetyltransferase/metabolism ; Cholinergic Agents/*pharmacology ; Immunotoxins/*pharmacology ; Male ; Memory/*physiology ; Muscarinic Antagonists/pharmacology ; N-Glycosyl Hydrolases ; Nitroso Compounds/*pharmacology ; Prosencephalon/drug effects/enzymology/pathology/*physiopathology ; Rats ; Rats, Wistar ; Ribosome Inactivating Proteins, Type 1 ; Saporins ; Scopolamine/pharmacology ; Taste/*physiology ; }, abstract = {Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. In this study, we have performed a detailed analysis of the cholinergic status of the insular cortex (IC) following local injections of either 192IgG-saporin (192IgG-sap) or N-methyl-D-aspartate (NMDA) directly into the nucleus basalis magnocellularis (NBM). By means of in vivo microdialysis, we show that the immunotoxin lesion results in an almost complete lack of extracellular acetylcholine release, whereas NMDA-induced lesions result in a marginal reduction in cortical cholinergic activity. Choline-acetyltransferase activity in the IC further confirmed this differential pattern of cortical deafferentation. Surprisingly, however, only NMDA-induced lesions showed a strong disruptive effect upon taste aversion learning whereas no detectable deficits could be found following 192IgG-sap lesions. By combining intrabasal injections of 192IgG-sap with acute pre-training infusions of the cholinergic antagonist scopolamine into the IC, a strong disruption of taste aversion was attained. These results imply that residual cholinergic activity, following 192IgG-saporin lesions, might be still critical for normal cortical mediation of memory processing. They also support the role of basal forebrain in mediating learning and memory processes, and demonstrate that mnemonic deficits resulting from excitotoxic lesions of the basal forebrain are not the sole result of cortical acetylcholine activity hypofunction.}, } @article {pmid10405115, year = {1999}, author = {Yamada, K and Wada, E and Imaki, J and Ohki-Hamazaki, H and Wada, K}, title = {Hyperresponsiveness to palatable and aversive taste stimuli in genetically obese (bombesin receptor subtype-3-deficient) mice.}, journal = {Physiology & behavior}, volume = {66}, number = {5}, pages = {863-867}, doi = {10.1016/s0031-9384(99)00032-3}, pmid = {10405115}, issn = {0031-9384}, mesh = {Analysis of Variance ; Animals ; Brain/metabolism ; Choice Behavior/*physiology ; Conditioning, Classical/physiology ; Disease Models, Animal ; Feeding and Eating Disorders/*genetics ; Gene Expression/physiology ; Male ; Mice ; Mice, Knockout ; Mice, Obese ; Obesity/*genetics/psychology ; Receptors, Bombesin/analysis/*physiology ; Taste/*physiology ; }, abstract = {Taste preference in obese mice was examined using genetically obese (bombesin receptor subtype-3: BRS-3 deficient) animals. Preference for either sodium saccharin (0.2%). sodium chloride (0.9%), citric acid (0.1%), or quinine sulfate (0.002%) solution was examined using a two-bottle test situation, and BRS-3 deficient mice not only showed a stronger preference for saccharin solution, but also a stronger aversive response to quinine solution, relative to wild-type littermates. Furthermore, a conditioned taste-aversion test measured the consumption of sodium saccharin (0.2%) and sodium chloride (0.9%) solutions after intraperitoneal injection of LiCl (0.3 M, 1 mg/kg), and BRS-3-deficient mice exhibited stronger aversion to both solutions than did control animals. In situ hybridization demonstrated that the BRS-3 gene is expressed in the parabrachial nucleus, the medial and central nuclei of the amygdala, and the hypothalamic nuclei such as paraventricular nucleus, all of which are known to be involved in taste perception. These results suggest that expression of the BRS-3 gene in these nuclei is important for the modulation of taste preference, as well as the development of obesity.}, } @article {pmid10405100, year = {1999}, author = {Metzger, MM and Riccio, DC}, title = {Ketaset-Rompun extends the temporal gradient for hypothermia-induced retrograde amnesia.}, journal = {Physiology & behavior}, volume = {66}, number = {5}, pages = {737-740}, doi = {10.1016/s0031-9384(99)00008-6}, pmid = {10405100}, issn = {0031-9384}, support = {MH37535/MH/NIMH NIH HHS/United States ; }, mesh = {*Adrenergic alpha-Agonists ; Amnesia, Retrograde/*etiology/physiopathology ; Analysis of Variance ; *Anesthetics, Dissociative ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Drug Therapy, Combination ; Female ; Hypothermia/*complications/physiopathology ; *Ketamine ; Rats ; Rats, Long-Evans ; Retention, Psychology/drug effects ; Statistics, Nonparametric ; Time Factors ; *Xylazine ; }, abstract = {In studies of experimentally induced retrograde amnesia (RA), as the interval between training and the amnestic treatment is lengthened, amnesia decreases (4). This temporal gradient for RA has been reported with a wide variety of amnestic agents, including RA produced by thermoregulatory disturbances (8). This temporal gradient for RA is not unlike certain characteristics of classical conditioning, where weaker conditioned responding occurs when the interval between the conditioned stimulus (CS) and unconditioned stimulus (US) is lengthened. Furthermore, there is evidence that administration of anesthetics can lengthen the "effective conditioning" interval between the CS and US, as demonstrated in a conditioned taste-aversion (CTA) procedure (10). In that study, little conditioning was observed when a 3-h delay (or more) was incorporated between presentations of the CS (flavor) and the US (toxin). However, if subjects were anesthetized immediately after the CS was delivered and remained anesthetized during the CS-US interval, strong conditioning was observed with CS-US intervals of up to 9 h. The aim of the present experiment was to determine if the temporal gradient for hypothermia-induced RA could also be lengthened. That is, we tested whether the interval between training and hypothermia treatment could be lengthened by anesthetizing subjects with Ketaset-Rompun. The results indicate that the training-to-amnestic agent interval could be lengthened within moderate limits. The implications for hypothermia-induced RA is further discussed.}, } @article {pmid10401982, year = {1999}, author = {Nakamura, H and Kojima, S and Kobayashi, S and Ito, I and Fujito, Y and Suzuki, H and Ito, E}, title = {Physiological characterization of lip and tentacle nerves in Lymnaea stagnalis.}, journal = {Neuroscience research}, volume = {33}, number = {4}, pages = {291-298}, doi = {10.1016/s0168-0102(99)00020-6}, pmid = {10401982}, issn = {0168-0102}, mesh = {Animals ; Association Learning/drug effects/physiology ; Chemoreceptor Cells/anatomy & histology/drug effects/*physiology ; Electrophysiology ; Evoked Potentials/drug effects ; Feeding Behavior/drug effects/physiology ; Lip/drug effects/*innervation/physiology ; Lymnaea ; Neurons, Afferent/drug effects/*physiology ; Potassium Chloride/pharmacology ; Stimulation, Chemical ; Sucrose/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {The lip and tentacle nerves of the pond snail, Lymnaea stagnalis, were characterized using electrophysiological techniques. When the activity of those nerves was induced in lip-tentacle preparations, aversive taste signals were transmitted through all the lip and tentacle nerves, but appetitive signals could be recorded only through the superior lip nerve. In the CNS immersed in high Mg2+ -high Ca2+ saline, electrical stimuli applied to any of the nerves failed to induce action potentials in one of the regulatory neurons (cerebral giant cell: CGC) involved in feeding responses, implying that the signals are polysynaptically transmitted to the CGC. Intracellular recordings revealed that the CGCs in semi-intact half-body preparations received both appetitive and aversive taste signals not only through the superior lip nerve but also through the median lip nerve. In addition, an osphradium was ruled out as a candidate for appetitive reception. The present results, together with our preceding data arrived at by the histochemical analyses, indicate that the appetitive taste transduction responsible for generating feeding responses is performed through the superior lip nerve with some contribution of the median lip nerve. The data showing that the CGC can receive various taste signals suggests that it may play a crucial role in feeding behavior as demonstrated in the study of conditioned taste-aversion.}, } @article {pmid10371712, year = {1999}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {Inferior olive lesions impair concurrent taste aversion learning in rats.}, journal = {Neurobiology of learning and memory}, volume = {72}, number = {1}, pages = {13-27}, doi = {10.1006/nlme.1998.3899}, pmid = {10371712}, issn = {1074-7427}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Male ; Nerve Net/*physiology ; Olivary Nucleus/*physiology/surgery ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Taste aversion learning can be established according to two different procedures, concurrent and sequential. For the concurrent task, two different taste stimuli are offered at the same time, one associated with simultaneous intragastric administration of an aversive stimulus and the other associated with physiological saline. This discrimination is learned by sham-lesioned control animals and by animals with lesions in the cerebellar cortex but not by rats lesioned in the inferior olive. At the same time, animals with lesions in the inferior olive and sham-lesioned animals achieve sequential learning when the gustatory stimuli are offered individually during each daily session. The results obtained show that electrolytic lesions in the inferior olive impair acquisition of concurrent learning and are analyzed in terms of an anatomical system consisting of the vagus nerve, inferior olive, and cerebellum, which differentiates between the two modalities of taste aversion learning, concurrent and sequential.}, } @article {pmid10371663, year = {1999}, author = {Chester, JA and Cunningham, CL}, title = {Baclofen alters ethanol-stimulated activity but not conditioned place preference or taste aversion in mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {63}, number = {2}, pages = {325-331}, doi = {10.1016/s0091-3057(98)00253-6}, pmid = {10371663}, issn = {0091-3057}, support = {AA05489/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Baclofen/*pharmacology ; Conditioning, Psychological/*drug effects/physiology ; Ethanol/*pharmacology ; GABA Agonists/*pharmacology ; Male ; Mice ; Mice, Inbred DBA ; Motivation ; Motor Activity/*drug effects/physiology ; Receptors, GABA-B/physiology ; Reward ; Taste/drug effects/physiology ; }, abstract = {The present experiments examined the effects of the GABA(B) receptor agonist, baclofen, on the acquisition of ethanol-induced conditioned place preference (CPP) and conditioned taste aversion (CTA) in male DBA/2J mice. Mice in the CPP experiment received four pairings of ethanol (2g/kg) with a distinctive floor stimulus for a 5-min conditioning session (CS+ sessions). On intervening days (CS- sessions), mice received saline injections paired with a different floor type. On CS+ days, mice also received one of four doses of baclofen (0.0. 2.5, 5.0, or 7.5 mg/kg) 15 min before an injection of ethanol. For the preference test, all mice received saline injections, and were placed on a half-grid and half-hole floor for a 60-min session. Baclofen dose dependently reduced ethanol-stimulated activity, but did not alter the magnitude of ethanol-induced CPP at any dose. For the CTA experiment, mice were adapted to a 2-h per day water restriction regimen followed by five conditioning trials every 48 h. During conditioning trials, subjects received an injection of saline or baclofen (2.0 and 6.0 mg/kg) 15 min before injection of 2 g/kg ethanol or saline following 1-h access to a saccharin solution. Baclofen did not alter the magnitude of ethanol-induced CTA at any dose. In addition, baclofen alone did not produce a CTA. Overall, these studies show that activation of GABA(B) receptors with baclofen reduces ethanol-induced locomotor activation, but does not alter ethanol's rewarding or aversive effects in the CPP and CTA paradigms in DBA/2J mice.}, } @article {pmid10357454, year = {1999}, author = {Morris, R and Frey, S and Kasambira, T and Petrides, M}, title = {Ibotenic acid lesions of the basolateral, but not the central, amygdala interfere with conditioned taste aversion: evidence from a combined behavioral and anatomical tract-tracing investigation.}, journal = {Behavioral neuroscience}, volume = {113}, number = {2}, pages = {291-302}, doi = {10.1037//0735-7044.113.2.291}, pmid = {10357454}, issn = {0735-7044}, mesh = {Amygdala/injuries/*pathology/*physiopathology ; Animals ; Avoidance Learning/*physiology ; Brain Injuries/*chemically induced ; Brain Mapping/*methods ; Conditioning, Classical ; Ibotenic Acid ; Inhibition, Psychological ; Male ; Nerve Net/physiology ; Rats ; Rats, Long-Evans ; Taste/*physiology ; }, abstract = {Rats (Rattus norvegicus) with almost complete ibotenic acid lesions (at least 90%) of the basolateral amygdaloid complex (BLA) failed to learn a conditioned taste aversion (CTA; Experiment 1A). In these same BLA rats, the bidirectional parabrachial-insular pathway that courses through the central nucleus of the amygdala (Ce) was shown to be spared (Experiment 1B), indicating that the BLA per se is critical for CTA learning. In contrast to the deleterious effect of BLA lesions on CTA, ibotenic acid lesions of the Ce did not block CTA learning (Experiment 2). Nonreinforced preexposure to the gustatory stimulus attenuated CTA acquisition in normal rats, and, under these conditions, rats with BLA lesions were no longer impaired (Experiment 3). Thus, ibotenic acid lesions centered over the Ce, sparing a considerable extent of the BLA, together with the testing procedure used in previous experiments (e.g., L. T. Dunn & B. J. Everitt, 1988), led to the belief that the CTA deficits reported after electrolytic lesions of the amygdala were the result of incidental damage to fibers of passage.}, } @article {pmid10355522, year = {1999}, author = {Houpt, TA and Berlin, R}, title = {Rapid, labile, and protein synthesis-independent short-term memory in conditioned taste aversion.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {6}, number = {1}, pages = {37-46}, pmid = {10355522}, issn = {1072-0502}, support = {R01 DC003198/DC/NIDCD NIH HHS/United States ; DC03198/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/*physiology ; Cycloheximide/pharmacology ; Lithium Chloride/toxicity ; Male ; Memory, Short-Term/*physiology ; Nerve Tissue Proteins/*biosynthesis ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sucrose/pharmacology ; Taste/*physiology ; Time Factors ; }, abstract = {Short-term memory is a rapid, labile, and protein-synthesis-independent phase of memory. The existence of short-term memory in conditioned taste aversion (CTA) learning has not been demonstrated formally. To determine the earliest time at which a CTA is expressed, we measured intraoral intake of sucrose at 15 min, 1 hr, 6 hr, or 48 h after contingent pairing of an intraoral infusion of 5% sucrose (6.6 ml over 6 min) and toxic lithium chloride injection (76 mg/kg). Rats were implanted with intraoral catheters to allow presentation of taste solutions at arbitrary times. Intraoral intake was measured under conditions of long-delay, single-trial learning typical of CTA. Rats decreased intraoral intake of sucrose at 15 min after contingent pairing of sucrose and LiCl, but not after noncontingent LiCl or sucrose. Thus CTA learning can be expressed rapidly. To determine if short-term CTA memory is labile and decays in the absence of long-term memory, we measured intraoral intake of sucrose after pairing sucrose with low doses of LiCl. Rats received an intraoral infusion of 5% sucrose (6 ml/6 min); 30 min later LiCl was injected at three different doses (19, 38, or 76 mg/kg). A second intraoral infusion of sucrose was administered 15 min, 1 hr, 3 hr, 4.5 hr, 6 hr, or 48 hr later. The formation of long-term CTA memory was dependent on the dose of LiCl paired with sucrose during acquisition. Low doses of LiCl induced a CTA that decayed within 6 hr after pairing. Central administration of the protein synthesis inhibitor cycloheximide prior to LiCl injection blocked long-term CTA expression at 6 and 48 hr, but not short-term CTA expression at 1 hr. Thus, short-term memory for CTA learning exists that is acquired rapidly and independent of protein synthesis, but labile in the absence of long-term memory formation.}, } @article {pmid10341253, year = {1999}, author = {Kusnecov, AW and Liang, R and Shurin, G}, title = {T-lymphocyte activation increases hypothalamic and amygdaloid expression of CRH mRNA and emotional reactivity to novelty.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {19}, number = {11}, pages = {4533-4543}, pmid = {10341253}, issn = {1529-2401}, support = {T32 MH018903/MH/NIMH NIH HHS/United States ; MH18903/MH/NIMH NIH HHS/United States ; MH51051/MH/NIMH NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/biosynthesis ; Amygdala/immunology/*metabolism ; Animals ; Corticotropin-Releasing Hormone/*genetics ; *Emotions ; Enterotoxins/pharmacology ; Exploratory Behavior/*physiology ; Hypothalamus/immunology/*metabolism ; Interleukin-2/genetics ; *Lymphocyte Activation ; Male ; Mice ; Mice, Inbred BALB C ; RNA, Messenger/*biosynthesis ; Spleen/drug effects/metabolism ; Staphylococcus aureus ; *T-Lymphocytes ; }, abstract = {Stimulation of T-cells with staphylococcal enterotoxin B (SEB) significantly elevates interleukin-2 (IL-2) and contemporaneous activation of the hypothalamic-pituitary-adrenal (HPA) axis and c-fos in the paraventricular nucleus (PVN) of BALB/cByJ mice. Such neural signaling may promote cognitive and emotional adaptation before or during infectious illness. Because corticotropin-releasing hormone (CRH) is an anxiogenic neuropeptide that may mediate the stressor-like effects of immunological stimuli, we measured neuronal CRH mRNA alterations in mice challenged with SEB. Increased CRH mRNA levels were observed in the PVN and central nucleus of the amygdala (ceA) 4-6 hr after SEB administration. This was associated with plasma ACTH increases, which could be abrogated by the systemic administration of anti-CRH antiserum. Additional experiments did not support a role for IL-2 or prostaglandin synthesis in activating the HPA axis. Behavioral experiments testing for conditioned taste aversion did not confirm that SEB challenge promotes malaise. However, consistent with the notion that central CRH alterations induced by SEB may affect emotionality (e.g., fear), SEB challenge augmented appetitive neophobia in a context-dependent manner, being marked in a novel and stressful environment. It is hypothesized that immunological stimuli generate a cascade of events that solicit integrative neural processes involved in emotional behavior. As such, these data support the contention that affective illness may be influenced by immunological processes and the production of cytokines and are consistent with other evidence demonstrating that autoimmune reactivity is associated with enhanced emotionality.}, } @article {pmid10340531, year = {1999}, author = {McMahon, LR and Jones, SL and Gilliland, TR and Hall, WD and Wellman, PJ}, title = {Effects of ephedrine enantiomers on conditioned taste aversion and kaolin intake in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {63}, number = {1}, pages = {119-124}, doi = {10.1016/s0091-3057(98)00248-2}, pmid = {10340531}, issn = {0091-3057}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Ephedrine/*pharmacology ; Feeding Behavior/*drug effects ; Kaolin/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Stereoisomerism ; Sympathomimetics/*pharmacology ; }, abstract = {The ephedrine (EPH) enantiomers, (-)-EPH and (+)-EPH, have different biological activity in the rat, with the (-)-EPH enantiomer exerting a greater impact on suppression of feeding, induction of locomotion, and activation of brown adipose tissue thermogenesis. Recent studies document that (-)-EPH treatment produces an alteration of extracellular dopamine in the brain, an effect that is consistent with the locomotor-stimulating and reinforcing effects of this drug. Whether the EPH enantiomers exert aversive actions in the rat is unknown. Experiment 1 examined the impact of systemically administered (+)-EPH (0, 5, 10, or 20 mg/kg) or (-)-EPH (0, 5, 10, or 20 mg/kg) on conditioned taste aversion (CTA) in adult male rats relative to the effect of 32 mg/kg lithium chloride (LiCl). No dose of either enantiomer produced CTA, whereas strong CTA was evident for LiCl. In Experiment 2, consumption of kaolin (a nonnutritive clay) over a 24-h period was used to assess drug toxicity. Rats treated with either 0, 5, 10, 20, or 40 mg/kg (+)-EPH or 0, 5, 10, 20, or 40 mg/kg (-)-EPH did not exhibit alteration of kaolin intake. In contrast, systematic increases in kaolin intake were observed in rats after systemic administration of LiCl (0, 16, 32, 64, and 96 mg/kg). These findings suggest that the enantiomers of EPH do not exert aversive effects at behaviorally relevant doses.}, } @article {pmid10339613, year = {1999}, author = {Miranda, MI and Bermúdez-Rattoni, F}, title = {Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {96}, number = {11}, pages = {6478-6482}, pmid = {10339613}, issn = {0027-8424}, mesh = {Acetylcholine/*metabolism ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Operant/drug effects/*physiology ; Infusions, Parenteral ; Male ; Memory/*physiology ; Microdialysis ; Rats ; Rats, Wistar ; Substantia Innominata/drug effects/pathology/*physiology ; Taste ; Tetrodotoxin/administration & dosage/*pharmacology ; }, abstract = {The basal forebrain complex, which includes the nucleus basalis magnocellularis (NBM), provides widespread cholinergic and gamma-aminobutyric acid-containing projections throughout the brain, including the insular and pyriform cortices. A number of studies have implicated the cholinergic neurons in the mediation of learning and memory processes. However, the role of basal forebrain activity in information retrieval mechanisms is less known. The aim of the present study is to evaluate the effects of reversible inactivation of the NBM by tetrodotoxin (TTX, a voltage-sensitive sodium channel blocker) during the acquisition and retrieval of conditioned taste aversion (CTA) and to measure acetylcholine (ACh) release during TTX inactivation in the insular cortex, by means of the microdialysis technique in free-moving rats. Bilateral infusion of TTX in the NBM was performed 30 min before the presentation of gustative stimuli, in either the CTA acquisition trial or retrieval trial. At the same time, levels of extracellular ACh release were measured in the insular cortex. The behavioral results showed significant impairment in CTA acquisition when the TTX was infused in the NBM, whereas retrieval was not affected when the treatment was given during the test trial. Biochemical results showed that TTX infusion into the NBM produced a marked decrease in cortical ACh release as compared with the controls during consumption of saccharin in the acquisition trial. Depleted ACh levels were found during the test trial in all groups except in the group that received TTX during acquisition. These results suggest a cholinergic-dependent process during acquisition, but not during memory retrieval, and that NBM-mediated cholinergic cortical release may play an important role in early stages of learning, but not during recall of aversive memories.}, } @article {pmid10327205, year = {1999}, author = {Gallo, M and Marquez, SL and Ballesteros, MA and Maldonado, A}, title = {Functional blockade of the parabrachial area by tetrodotoxin disrupts the acquisition of conditioned taste aversion induced by motion-sickness in rats.}, journal = {Neuroscience letters}, volume = {265}, number = {1}, pages = {57-60}, doi = {10.1016/s0304-3940(99)00209-8}, pmid = {10327205}, issn = {0304-3940}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Male ; Motion Sickness/*physiopathology ; Pons/*drug effects ; Rats ; Rats, Wistar ; Taste/*physiology ; Tetrodotoxin/*pharmacology ; }, abstract = {The role of the parabrachial area in conditioned taste aversion (CTA) induced by motion-sickness was studied in male Wistar rats. In the first experiment, one-trial conditioned taste aversion, to a 0.5% decaffeinated coffee solution, was induced by 30 min of vertical rotatory motion (80 rev./min) in intact rats. In the second experiment, reversible blockade of the neural activity in various brainstem sites was induced by bilateral intracerebral injections of tetrodotoxin (TTX) (10 ng/microl) after conditioning. Blockade of the parabrachial area, but neither A8 nor lateral vestibular nucleus, disrupted the acquisition of (CTA). The results are discussed in terms of an associative role of the parabrachial area in body rotation-induced taste aversion learning, as the area was intact during sensory processing and testing.}, } @article {pmid10235307, year = {1999}, author = {Williams, KL and Woods, JH}, title = {Conditioned effects produced by naltrexone doses that reduce ethanol-reinforced responding in rhesus monkeys.}, journal = {Alcoholism, clinical and experimental research}, volume = {23}, number = {4}, pages = {708-715}, pmid = {10235307}, issn = {0145-6008}, support = {AA-11424/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Conditioning, Classical/drug effects ; Conditioning, Operant/*drug effects ; Drinking Behavior/drug effects ; Ethanol/administration & dosage/*pharmacology ; Macaca mulatta ; Male ; Naltrexone/*pharmacology ; Reward ; Sodium Chloride/administration & dosage/pharmacology ; Taste/*drug effects ; }, abstract = {Clinical trials have shown that naltrexone is effective in treating alcohol dependence; nausea and dysphoria have been reported as "side effects" in many of these studies. In primates, naltrexone reduces reinforced responding for oral ethanol, sucrose, and phencyclidine. This study was designed to determine if naltrexone reduces reinforced responding for various solutions by producing an interoceptive stimulus that may result in a conditioned taste aversion. Four opioid antagonist-naive rhesus monkeys responded for solutions from a two-spout operant panel for 30 min per day. During a conditioning phase, the monkeys received novel Kool-Aid solutions paired with either saline or naltrexone (0.32 mg/kg) given 30 min before the session. The monkeys then had seven choice sessions between the saline-paired solution or the naltrexone-paired solution. During the conditioning phase, the naltrexone reduced responding after five naltrexone/solution pairings. In addition, a conditioned taste aversion was produced; the naltrexone-paired solution maintained significantly less responding than did the saline-paired solution during the choice phase. In the next phase, the saline and naltrexone were given "unpaired" from any distinct part of the operant session, and another seven choice sessions followed. Naltrexone had no effect when given "unpaired" from the operant session. Then, another conditioning phase was undertaken followed by another series of choice sessions. During the replication of the conditioning, naltrexone reduced responding by the second pairing, although no conditioned aversion was observed in the subsequent choice sessions. Thus, given in the same manner (dose, route, and pretreatment time) as situations in which naltrexone reduces oral ethanol-, sucrose-, and phencyclidine-reinforced responding, naltrexone produced a conditioned taste aversion. These results suggest that naltrexone-induced nausea and its conditioned effects should be considered in naltrexone's effect in alcoholics.}, } @article {pmid10229331, year = {1999}, author = {Reilly, S}, title = {The parabrachial nucleus and conditioned taste aversion.}, journal = {Brain research bulletin}, volume = {48}, number = {3}, pages = {239-254}, doi = {10.1016/s0361-9230(98)00173-7}, pmid = {10229331}, issn = {0361-9230}, support = {DC02821/DC/NIDCD NIH HHS/United States ; DC03379/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Discrimination Learning/*physiology ; Pons/*physiology ; Taste/*physiology ; }, abstract = {The parabrachial nucleus (PBN) surrounds the brachium conjunctivum in the dorsolateral pons. Although composed of numerous subnuclei, the PBN is typically organized into medial and lateral subdivisions according to their location relative to the brachium. In rodents, the medial PBN is part of the central gustatory system, whereas the lateral PBN is a component of the visceral sensory system. Lesions of the PBN disrupt conditioned taste aversion, a critically important learning mechanism that prevents the repeated ingestion of toxic food. Relevant neurobehavioral literature is reviewed to elucidate the role of the PBN in taste aversion learning.}, } @article {pmid10212064, year = {1999}, author = {De Oliveira Mora, P and Fouquet, N and Oberling, P and Gobaille, S and Graeff, FG and Sandner, G}, title = {A neurotoxic lesion of serotonergic neurones using 5,7-dihydroxytryptamine does not disrupt latent inhibition in paradigms sensitive to low doses of amphetamine.}, journal = {Behavioural brain research}, volume = {100}, number = {1-2}, pages = {167-175}, doi = {10.1016/s0166-4328(98)00128-4}, pmid = {10212064}, issn = {0166-4328}, mesh = {5,7-Dihydroxytryptamine/*pharmacology ; Animals ; Avoidance Learning/drug effects ; Brain Mapping ; Conditioning, Classical/*drug effects ; Dextroamphetamine/*pharmacology ; Dose-Response Relationship, Drug ; Electroshock ; Hippocampus/drug effects ; Male ; Neural Inhibition/*drug effects ; Neurotoxins/*pharmacology ; Rats ; Rats, Long-Evans ; Reaction Time/drug effects ; Receptors, Dopamine/drug effects ; Receptors, Serotonin/*drug effects ; Taste/drug effects ; }, abstract = {Testing the effects of low doses of d-amphetamine on latent inhibition (LI) in two different conditioning paradigms, passive avoidance and conditioned taste aversion, provided evidence of their pharmacological equivalence. For passive avoidance, LI was expressed by the decreased latency to enter a shock compartment in preexposed rats placed 5 min in the compartment during 3 consecutive days before conditioning. In the conditioned taste aversion paradigm, a group of rats was preexposed to a solution of sucrose also for 3 consecutive days prior to the establishment of an association between sucrose and sickness elicited by an injection of LiCl. On the following day, the preexposed rats drunk more sucrose when allowed to choose between one tube containing water and an other containing sucrose. In both paradigms, 0.25 mg/kg d-amphetamine, injected daily on the 3 preexposure days and on the conditioning day, decreased LI. A dose of 0.5 mg/kg suppressed LI in the passive avoidance paradigm. The effect of a serotonergic lesion induced by i.c.v. injection of 5,7-dihydroxytryptamine (5,7-DHT) was evaluated in the same paradigms. The lesion procedure that lowered hippocampal serotonin and 5 HIAA levels by more than 80% did not affect LI. Taken together, the present results lessens the hypothesis that LI is prone to an opposing influence of the two monoaminergic systems considered in this work.}, } @article {pmid10199610, year = {1999}, author = {Gutiérrez, H and Hernández-Echeagaray, E and Ramírez-Amaya, V and Bermúdez-Rattoni, F}, title = {Blockade of N-methyl-D-aspartate receptors in the insular cortex disrupts taste aversion and spatial memory formation.}, journal = {Neuroscience}, volume = {89}, number = {3}, pages = {751-758}, doi = {10.1016/s0306-4522(98)00360-1}, pmid = {10199610}, issn = {0306-4522}, mesh = {2-Amino-5-phosphonovalerate/administration & dosage/*pharmacology ; Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Operant/drug effects/physiology ; Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology ; Male ; Maze Learning/drug effects/*physiology ; Memory/drug effects/*physiology ; Microinjections ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology ; Spatial Behavior/drug effects/*physiology ; Synaptic Transmission/drug effects ; Taste/drug effects/*physiology ; }, abstract = {The present experiments examined the effects of direct intracortical microinjections of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid directly into the insular cortex of rats, before or immediately after training of conditioned taste aversion and the water maze spatial learning task. In the first series of experiments animals received bilateral injections of 2-amino-5-phosphonovaleric acid prior to taste aversion conditioning or spatial training. A strong disruptive effect was found in the acquisition of training tasks. To determine the possible involvement of N-methyl-D-aspartate receptors in the early post-training processes taking place in the cortex during both learning paradigms, in a second series of experiments, animals received bilateral 2-amino-5-phosphonovaleric acid microinjections 30, 60 or 120 min after the acquisition trial, and 15 min before the retention test. For spatial learning successive treatments were independently done either starting at the onset of the asymptotic phase of the learning curve, 0, 30 or 120 min after finishing the training session, as well as 15 min before the retention test trial. The conditioned taste aversion task remained sensitive to N-methyl-D-aspartate blockade during a period of at least 2 h after the first presentation of the gustatory stimulus, while in the case of the spatial learning task, a gradually decreasing effect was observed from the onset of the asymptotic phase onwards. Taken together, these results provide direct evidence for N-methyl-D-aspartate receptor involvement in cortical regulation of memory formation. Furthermore, our results suggest that in the same cortical region, a different time-course for the activation of N-methyl-D-aspartate-dependent mechanisms occurs during the early formation of cortically mediated memories, depending on the particular behavioural task.}, } @article {pmid10198919, year = {1999}, author = {Bernstein, IL}, title = {Taste aversion learning: a contemporary perspective.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {15}, number = {3}, pages = {229-234}, doi = {10.1016/s0899-9007(98)00192-0}, pmid = {10198919}, issn = {0899-9007}, support = {NS37040/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Anorexia/etiology ; Conditioning, Psychological/physiology ; Food ; Foodborne Diseases/prevention & control ; Humans ; Learning/*physiology ; Neoplasms/complications ; Neuronal Plasticity/physiology ; Odorants ; Taste/*physiology ; }, abstract = {Food aversion learning has attracted widespread interest because it is a highly adaptive, powerful type of learning with both practical and theoretical ramifications. It has features that make it unusual and robust when compared with other learning paradigms. It has relevance to human problems in that it is likely to contribute to food choice and appetite problems in certain clinical situations. And the robustness of this learning makes it a promising model for neurobiologists interested in understanding neural mechanisms of plasticity. This review provides a broad overview of these aspects of taste aversion learning and points to areas where questions remain and additional research is needed.}, } @article {pmid9972686, year = {1999}, author = {Kunin, D and Smith, BR and Amit, Z}, title = {Nicotine and ethanol interaction on conditioned taste aversions induced by both drugs.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {62}, number = {2}, pages = {215-221}, doi = {10.1016/s0091-3057(98)00155-5}, pmid = {9972686}, issn = {0091-3057}, mesh = {Analysis of Variance ; Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Psychological/drug effects ; Drug Interactions ; Ethanol/*pharmacology ; Ganglionic Stimulants/*pharmacology ; Male ; Nicotine/*pharmacology ; Rats ; Rats, Wistar ; Saccharin/metabolism ; Taste/*drug effects ; }, abstract = {The present study was designed to explore the interactive effects of nicotine and ethanol in the pretreatment and preexposure conditioned taste aversion (CTA) paradigm. The first experiment examined the effects of ethanol pretreatment on a nicotine induced CTA. The second experiment examined the effects of nicotine pretreatment on an ethanol CTA. The results of these two experiments revealed an asymmetrical interaction between ethanol and nicotine. Although nicotine pretreatment blocked an ethanol induced CTA, ethanol pretreatment merely attenuated a nicotine-induced CTA. These findings demonstrated that ethanol and nicotine interact pharmacologically in a unidirectional fashion, suggesting some unique and unshared pharmacological properties of each agent. The third experiment of this study examined the effects of preexposure with ethanol on a nicotine-induced CTA, while the fourth experiment examined the effects of preexposure with nicotine on an ethanol-induced CTA. These results revealed a symmetrical interaction between ethanol and nicotine in that both agents equally blocked CTA to one and the other. In contrast to the pretreatment CTA paradigm, these results suggested that both ethanol and nicotine appear to be functionally related and share common stimulus properties. Taken together, the present study demonstrates that while ethanol and nicotine are functionally related, they may also be endowed with unique unshared properties.}, } @article {pmid9934668, year = {1999}, author = {Reynolds, NR and Neidig, JL and Brashers, DE}, title = {Patient appraisal of mandarin orange didanosine: implications for adherence and well-being.}, journal = {The Journal of the Association of Nurses in AIDS Care : JANAC}, volume = {10}, number = {1}, pages = {35-41}, doi = {10.1016/S1055-3290(06)60230-6}, pmid = {9934668}, issn = {1055-3290}, support = {AI25924/AI/NIAID NIH HHS/United States ; }, mesh = {Administration, Oral ; Anti-HIV Agents/administration & dosage/*therapeutic use ; Didanosine/administration & dosage/*therapeutic use ; Female ; Flavoring Agents ; Focus Groups ; HIV Infections/*drug therapy/nursing ; Humans ; Male ; *Patient Compliance ; Tablets ; Taste ; }, abstract = {Didanosine (Videx, ddI) has been shown to be an effective agent in the treatment of HIV disease. However, patients have had difficulties adhering to didanosine preparations due to taste aversion and/or associated nausea. The efficacy of didanosine may, therefore, be compromised. This is of concern to clinicians who seek to promote patient adherence to medication regimes and to foster the quality of patient well-being. In this study, focus groups were used to gather exploratory data about patient (n = 15) response to the new mandarin orange didanosine preparation. Data were audiotaped, transcribed verbatim, and systematically analyzed by the investigators using inductive techniques. Findings provide information regarding client evaluation of the new didanosine preparation and patterns of usage. Although clients generally find the mandarin orange preparation more tolerable, they describe engaging in numerous strategies aimed at attenuating what they experience as the inconvenience of taking the medication. Mental tricks, systematic restructuring of daily routines and environment, and dietary schemes were among the strategies devised by patients through trial and error to self-promote their adherence.}, } @article {pmid9929638, year = {1998}, author = {Smith, DV and Li, CS and Davis, BJ}, title = {Excitatory and inhibitory modulation of taste responses in the hamster brainstem.}, journal = {Annals of the New York Academy of Sciences}, volume = {855}, number = {}, pages = {450-456}, doi = {10.1111/j.1749-6632.1998.tb10605.x}, pmid = {9929638}, issn = {0077-8923}, support = {DC00066/DC/NIDCD NIH HHS/United States ; DC00207/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Brain Stem/*physiology ; Cricetinae ; Electrophysiology ; Neurotransmitter Agents/agonists/antagonists & inhibitors/physiology ; Taste/*physiology ; }, abstract = {The rostral portion of the nucleus of the solitary tract (NST) contains second-order gustatory neurons, sends projections to the parabrachial complex and brainstem reticular formation, and receives descending projections from several nuclei of the ascending gustatory pathway. Electrophysiological responses of NST neurons can be modulated by several factors, including blood glucose and insulin levels and taste aversion conditioning. We are using extracellular electrophysiological recording in vivo, combined with local microinjection of neurotransmitter agonists and antagonists, to study the mechanisms by which taste responses of cells in the hamster NST can be modulated. Afferent fibers of the chorda tympani (CT) nerve make excitatory synaptic contact with NST neurons; this excitation is probably mediated by the excitatory amino acid glutamate. Microinjection of kynurenic acid, a nonspecific glutamate receptor antagonist, into the NST completely and reversibly blocks afferent input from the CT nerve, produced by either anodal electrical or chemical stimulation of the anterior tongue. The non-NMDA ((RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) also completely blocks gustatory input to these cells, whereas the N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) produces only a small effect. There are many gamma-aminobutyric acid (GABA)-containing neurons within the NST and taste-responsive NST cells are maintained under a tonic GABAergic inhibition. Microinjection of the GABAA receptor antagonist bicuculline methiodide increases the taste responsiveness of NST neurons, whereas application of GABA inhibits taste responses in these cells. Preliminary data show that GABAergic inhibition can be produced by stimulation of the gustatory cortex. There are both intrinsic substance P (SP)-containing neurons and extrinsic SP-immunoreactive fibers in the rostral NST. Microinjection of SP into the NST enhances the responses of many NST cells to gustatory stimulation; NaCl-best neurons are preferentially excited by SP.}, } @article {pmid9920687, year = {1998}, author = {Lett, BT and Grant, VL and Gaborko, LL}, title = {Wheel running simultaneously induces CTA and facilitates feeding in non-deprived rats. Conditioned taste aversion.}, journal = {Appetite}, volume = {31}, number = {3}, pages = {351-360}, doi = {10.1006/appe.1998.0171}, pmid = {9920687}, issn = {0195-6663}, mesh = {Animals ; Citric Acid ; *Conditioning, Psychological ; Drinking ; Eating/*physiology ; Food Deprivation ; Male ; Physical Exertion/*physiology ; Rats ; Rats, Sprague-Dawley ; Saccharin ; Sodium Chloride ; Sodium Glutamate ; Solutions ; *Taste ; }, abstract = {Previous findings indicate that wheel running can have either an aversive or an appetitive effect. That is, wheel running for 30 min induces conditioned taste aversion (CTA) in rats trained while hungry and thirsty but facilitates feeding in non-deprived rats. In Experiment 1, wheel running was also found to be effective in producing CTA in non-deprived rats. Therefore, Experiment 2 tested whether wheel running produces the aversive and appetitive effects simultaneously. During each of four training trials, two groups of non-deprived rats were given a flavored solution to drink for 10 min. Then those in the wheel group were put in running wheels for 30 min whereas those in the cage group spent 30 min in small cages. Finally, all rats were given a 60-min feeding test. After the first trial, the wheel group drank less flavored solution than the cage group during each of the remaining trials. The wheel group also ate more than the cage group on each feeding test. These results indicate that wheel running produces CTA and facilitates eating at the same time. A role for the mesolimbic dopamine reward system in these effects was considered.}, } @article {pmid9920659, year = {1999}, author = {Masugi, M and Yokoi, M and Shigemoto, R and Muguruma, K and Watanabe, Y and Sansig, G and van der Putten, H and Nakanishi, S}, title = {Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {19}, number = {3}, pages = {955-963}, pmid = {9920659}, issn = {0270-6474}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Fear/*physiology ; Mice ; Mice, Knockout/genetics ; Presynaptic Terminals/metabolism ; Receptors, Metabotropic Glutamate/genetics/*physiology ; Taste/*physiology ; }, abstract = {Metabotropic glutamate receptors (mGluRs) consist of eight different subtypes and exert their effects on second messengers and ion channels via G-proteins. The function of individual mGluR subtypes in the CNS, however, largely remains to be clarified. We examined the fear response of freezing after electric shock in wild-type and mGluR7(-/-) knockout littermates. Wild-type mice displayed freezing immediately after and 1 d after footshock. In comparison, mGluR7(-/-) knockout mice showed significantly reduced levels in both immediate postshock and delayed freezing responses. However, the knockout mice exhibited no abnormalities in pain sensitivity and locomotor activity. To further examine amygdala-dependent behavior, we performed conditioned taste aversion (CTA) experiments. In wild-type mice, the administration of saccharin followed by intraperitoneal injection of the malaise-inducing agent LiCl resulted in an association between saccharin and LiCl. This association caused strong CTA toward saccharin. In contrast, mGluR7(-/-) knockout mice failed to associate between the taste and the negative reinforcer in CTA experiments. Again, the knockout mice showed no abnormalities in taste preference and in the sensitivity to LiCl toxicity. These results indicate that mGluR7 deficiency causes an impairment of two distinct amygdala-dependent behavioral paradigms. Immunohistochemical and immunoelectron-microscopic analyses showed that mGluR7 is highly expressed in amygdala and preferentially localized at the presynaptic axon terminals of glutamatergic neurons. Together, these findings strongly suggest that mGluR7 is involved in neural processes subserving amygdala-dependent averse responses.}, } @article {pmid9915113, year = {1998}, author = {Formaker, BK and Kearns, CE and Frank, ME}, title = {The taste of polycose in hamsters.}, journal = {Chemical senses}, volume = {23}, number = {6}, pages = {675-682}, doi = {10.1093/chemse/23.6.675}, pmid = {9915113}, issn = {0379-864X}, support = {DC-00058/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Conditioning, Classical ; Cricetinae ; Drinking ; Drinking Behavior/*drug effects ; Glucans/*administration & dosage ; Male ; Perceptual Masking/*physiology ; Sucrose/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {Hamsters show a preference for Polycose, a mixture of starch-derived glucose polymers, that is as strong as their preference for sucrose. However, in the hamster, taste aversions to Polycose may be less easily acquired than taste aversions to sucrose and the qualitative aspects of Polycose are unknown in this species. In order to examine the taste of Polycose in the hamster, we utilized a taste-aversion protocol with two conditioning trials. Animals were trained to avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were conditioned with deionized water. After the second conditioning trial, generalization testing began for the three conditioning stimuli plus 3 mM citric acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose, sucrose or the Polycose/sucrose mixture cross-generalized, demonstrating that Polycose and sucrose share a common taste percept in the hamster. None of the aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among the patterns of taste generalizations indicated that the tastes of Polycose and sucrose also had distinct qualitative components. Finally, although the taste of 100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of sucrose could still be detected in a mixture with Polycose.}, } @article {pmid9890258, year = {1998}, author = {Gardell, LR and Whalen, CA and Chambers, MD and Boswell, KJ and Hubbell, CL and Reid, LD}, title = {Valproate reduces intake of alcoholic beverage among rats.}, journal = {Behavioural pharmacology}, volume = {9}, number = {8}, pages = {683-689}, doi = {10.1097/00008877-199812000-00004}, pmid = {9890258}, issn = {0955-8810}, support = {DA-08937/DA/NIDA NIH HHS/United States ; }, mesh = {Administration, Oral ; Alcohol Drinking/*physiopathology ; Animals ; Conditioning, Psychological/drug effects ; Ethanol/toxicity ; Injections, Intraperitoneal ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; Valproic Acid/administration & dosage/*pharmacology ; }, abstract = {A series of experiments was carried out to assess the effects of valproate (VAL) on the intake of ethanol by rats. In Experiment 1, the effects of VAL (150 and 200 mg/kg, i.p.) were assessed across 10 days. Compared with controls, the 200 mg/kg dose reliably reduced intake of ethanol while also reliably increasing intake of water. The 150 mg/kg dose did not reliably reduce the intake of ethanol across the initial days, but it did across later days. Neither dose affected the total intake of fluids. Similarly, 5 days of oral dosing with VAL (400 and 600 mg/kg) reliably reduced the intake of ethanol without affecting the intake of water. However, body weights were reduced by the oral doses across the procedure. In another procedure, VAL (200 mg/kg, i.p.) produced a mild conditioned taste aversion to a saccharin solution, suggesting that VAL may reduce intake of ethanol because it produces a general malaise. However, this dose of VAL enhanced the intoxicating effects of ethanol (2.0 g/kg). Overall, the results are equivocal with respect to VAL as a potential medicine for treating alcohol misuse and alcoholism.}, } @article {pmid9888626, year = {1998}, author = {Gommans, J and Bouwknecht, JA and Hijzen, TH and Berendsen, HH and Broekkamp, CL and Maes, RA and Olivier, B}, title = {Stimulus properties of fluvoxamine in a conditioned taste aversion procedure.}, journal = {Psychopharmacology}, volume = {140}, number = {4}, pages = {496-502}, doi = {10.1007/s002130050794}, pmid = {9888626}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Fluoxetine/pharmacology ; Fluvoxamine/*pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Receptor, Serotonin, 5-HT2A ; Receptors, Serotonin/drug effects ; Receptors, Serotonin, 5-HT1 ; Serotonin Receptor Agonists/pharmacology ; Serotonin Uptake Inhibitors/*pharmacology ; Taste/*drug effects ; }, abstract = {A conditioned taste aversion (CTA) procedure in mice was used to investigate the stimulus effects of the serotonin reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine. Fluvoxamine elicited a reliable CTA (ED50 = 24 mg/kg, SC) and a number of drugs were tested as pre-exposure drugs. Pre-exposure to the serotonin (5-HT)1A receptor agonists flesinoxan and +/- -8-hydroxy-dipropylaminotetralin (8-OH-DPAT) prevented the CTA induced by fluvoxamine (50 mg/kg, SC). Pre-exposure with the 5-HT2C receptor agonist MK 212 [6-chloro-2(1-piperazinyl)pyrazine] partially prevented the fluvoxamine-induced CTA, pre-exposure with the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] did not prevent the CTA induced by fluvoxamine. Flesinoxan pre-exposure also prevented the taste aversion induced by fluoxetine (10 mg/kg, SC) completely. This contrasts previous results obtained with fluoxetine, where was found that its stimulus is primarily mediated by 5-HT2C, and to a lesser degree by 5-HT1A receptors. Therefore, we compared the two SSRIs directly. Pre-exposure to fluvoxamine prevented the fluoxetine-induced CTA, whereas pre-exposure to fluoxetine only partially prevented the fluvoxamine-induced CTA. We conclude that 5-HT1A receptors are involved in the stimulus properties of both fluvoxamine and fluoxetine, that 5-HT2C receptors are involved in fluvoxamine and especially fluoxetine, and, based primarily on the cross-comparison tests, that the two SSRIs have somewhat different stimulus properties.}, } @article {pmid9880656, year = {1998}, author = {Phillips, TJ and Belknap, JK and Buck, KJ and Cunningham, CL}, title = {Genes on mouse chromosomes 2 and 9 determine variation in ethanol consumption.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {9}, number = {12}, pages = {936-941}, doi = {10.1007/s003359900903}, pmid = {9880656}, issn = {0938-8990}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; P50AA10760/AA/NIAAA NIH HHS/United States ; R29AA11114/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Animals ; Chromosome Mapping ; Chromosomes/*genetics ; Crosses, Genetic ; Female ; Genetic Markers ; Genetic Variation ; Lod Score ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; *Quantitative Trait, Heritable ; }, abstract = {Quantitative trait locus (QTL) mapping efforts in alcohol (ethanol) research are beginning to generate promising data that may ultimately lead to the identification of genes influencing alcohol addiction. Rodents have been extensively utilized to study ethanol's rewarding and aversive effects, and to demonstrate the existence of genetic influences on traits such as free-choice ethanol-consumption, ethanol-conditioned place preference and ethanol-conditioned taste aversion. The purpose of the current investigation was to verify or eliminate from further consideration putative QTLs for free-choice ethanol consumption originally identified in BXD Recombinant Inbred (RI) strains and other informative genetic crosses. B6D2F2 mice were utilized in a verification testing strategy to evaluate the viability of putative ethanol consumption QTLs. When data were combined from BXD RI, B6D2F2 and short-term selected line (STSL) mapping studies, verification was obtained for two QTLs, one on Chromosome (Chr) 9 (proximal-mid) and another on Chr 2 (distal), and suggestive verification was obtained for QTLs on Chrs 2 (proximal), 3, 4, 7, and 15. In addition, the possible genetic association of ethanol consumption with conditioned place preference was evaluated. Genetic correlations were estimated from BXD RI strain means, and QTL maps for these traits were compared to evaluate the possibility of a genetic association. The correlational analysis yielded a trend (r = 0.34, p = 0.09), but no statistically significant results. However, comparisons of QTL mapping results between phenotypes suggested some possible genetic overlap for these traits, both putative measures of ethanol reward. These data suggest that the determinants of these two measures are genetically diverse, but may share some common genetic elements.}, } @article {pmid9858756, year = {1998}, author = {Berridge, KC and Robinson, TE}, title = {What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?.}, journal = {Brain research. Brain research reviews}, volume = {28}, number = {3}, pages = {309-369}, doi = {10.1016/s0165-0173(98)00019-8}, pmid = {9858756}, mesh = {Animals ; Brain Chemistry/*physiology ; Dopamine/*physiology ; Humans ; Learning/*physiology ; Limbic System/physiology ; Neostriatum/physiology ; Rats ; *Reward ; }, abstract = {What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is 'no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the 'taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary for 'wanting' incentives, but not for 'liking' them or for learning new 'likes' and 'dislikes'.}, } @article {pmid9854049, year = {1998}, author = {Criscione, L and Rigollier, P and Batzl-Hartmann, C and Rüeger, H and Stricker-Krongrad, A and Wyss, P and Brunner, L and Whitebread, S and Yamaguchi, Y and Gerald, C and Heurich, RO and Walker, MW and Chiesi, M and Schilling, W and Hofbauer, KG and Levens, N}, title = {Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.}, journal = {The Journal of clinical investigation}, volume = {102}, number = {12}, pages = {2136-2145}, pmid = {9854049}, issn = {0021-9738}, mesh = {Animals ; Appetite Regulation/*physiology ; Binding, Competitive ; Blood Glucose/metabolism ; Body Composition/drug effects ; Body Weight/drug effects ; Calcium/metabolism ; Cell Line ; Conditioning, Psychological/drug effects ; Diabetes Mellitus, Experimental/physiopathology ; Drinking/drug effects ; Eating/drug effects ; Humans ; Hypothalamus/metabolism/physiology ; Insulin/blood/pharmacology ; Male ; Mice ; Naphthalenes/*pharmacology ; Neuropeptide Y/*metabolism ; Pyrimidines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Neuropeptide Y/metabolism/*physiology ; Triglycerides/blood ; }, abstract = {The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.}, } @article {pmid9850963, year = {1998}, author = {Kassil, VG and Vataeva, LA and Makukhina, GV}, title = {Role of the vagus nerves in neophobia and conditioned-reflex taste aversion.}, journal = {Neuroscience and behavioral physiology}, volume = {28}, number = {6}, pages = {678-685}, pmid = {9850963}, issn = {0097-0549}, mesh = {Animals ; Anxiety/*physiopathology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking ; Laparotomy ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*physiology ; Vagotomy ; Vagus Nerve/*physiology/physiopathology ; }, abstract = {Combination of ingestion of water with discomfort in rats with intact vagus nerves on selection between water and saccharine solution (an unknown taste) produced aversion not to water but to saccharine, with sharp increases in water consumption. In vagotomized rats, this combination led to a significant increase in saccharine consumption with no change in water intake. After extinction of neophobia to saccharine, combination of ingestion of water with rotation induced aversion to water in both groups (this being delayed in vagotomized rats). Vagus nerve signaling activity in selection conditions appears to determine the choice of behavior strategy.}, } @article {pmid9832984, year = {1997}, author = {Herrera, FM and Velazquez Martinez, DN}, title = {Discriminative stimulus properties of amphetamine in a conditioned taste aversion paradigm.}, journal = {Behavioural pharmacology}, volume = {8}, number = {5}, pages = {458-464}, pmid = {9832984}, issn = {0955-8810}, mesh = {Amphetamine/*pharmacology ; Animals ; Apomorphine/pharmacology ; Conditioning, Psychological/*drug effects ; Discrimination, Psychological/*drug effects/physiology ; Dopamine Agents/*pharmacology ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Food Preferences/*drug effects ; Haloperidol/pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Dopamine/drug effects ; Taste/*drug effects/physiology ; }, abstract = {It has been proposed that the conditioned taste aversion paradigm may be used to achieve rapid training of subjects in drug discrimination studies. We report here that amphetamine (1.0 mg/kg) may acquire discriminative control over the preference of rats for a distinctive flavour when its administration precedes access to a saccharin solution (0.15% w/v), versus the occasions when the injection of saline precedes no toxicosis after access to the same flavour. Other doses of amphetamine (0.18-1.0 mg/kg) or apomorphine (0.1-1.0 mg/kg) produced a dose-dependent generalization to the stimulus cue of amphetamine (1.0 mg/kg), and haloperidol (0.01-0.1 mg/kg) was able to prevent the stimulus control exerted by amphetamine. No stimulus control was seen in a control group where no distinctive outcomes followed the administration of either amphetamine or saline before the subjects had access to the saccharin-flavoured solution. In the experimental group only, changes in the preference for saccharin were observed, with no changes in the total amount of water and saccharin ingested. Taken together, the present results suggest the usefulness of the conditioned taste aversion procedure to train subjects in drug discrimination.}, } @article {pmid9829788, year = {1998}, author = {Grigson, PS and Reilly, S and Scalera, G and Norgren, R}, title = {The parabrachial nucleus is essential for acquisition of a conditioned odor aversion in rats.}, journal = {Behavioral neuroscience}, volume = {112}, number = {5}, pages = {1104-1113}, pmid = {9829788}, issn = {0735-7044}, support = {DA-09815/DA/NIDA NIH HHS/United States ; DC-02016/DC/NIDCD NIH HHS/United States ; DC-02821/DC/NIDCD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Cues ; Exploratory Behavior/*physiology ; Linear Models ; Lithium Chloride/administration & dosage ; Male ; Pons/*physiology/surgery ; Rats ; Rats, Sprague-Dawley ; Smell/*physiology ; Taste ; }, abstract = {Rats with bilateral ibotenic acid lesions of the gustatory zone of the parabrachial nuclei (PBN) failed to acquire a conditioned taste aversion (CTA) in Experiment 1. They also failed to acquire a conditioned odor aversion (COA) when the olfactory cue was presented on an odor disk in Experiment 2 or when it was presented in water in Experiment 3. The failure to acquire the COA was not due to an inability to detect or use olfactory stimuli because the lesioned rats displayed neophobia to a novel odor in Experiment 3 and used an olfactory cue to predict the availability of an aversive capsaicin solution in Experiment 4. Together, the results demonstrate that, as with CTA learning, PBN cell bodies are essential for the establishment of a specific association between an olfactory conditioned stimulus and a lithium chloride unconditioned stimulus.}, } @article {pmid9824664, year = {1998}, author = {Tucci, S and Rada, P and Hernandez, L}, title = {Role of glutamate in the amygdala and lateral hypothalamus in conditioned taste aversion.}, journal = {Brain research}, volume = {813}, number = {1}, pages = {44-49}, doi = {10.1016/s0006-8993(98)00884-1}, pmid = {9824664}, issn = {0006-8993}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/*physiology ; Dizocilpine Maleate/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Glutamic Acid/*physiology ; Hypothalamic Area, Lateral/*physiology ; Male ; Microdialysis ; Microinjections ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {The role of glutamate in conditioned taste aversion was investigated. Both, in the amygdala (AMYG) and in the lateral hypothalamus (LH) extracellular levels of glutamate were assessed by microdialysis and capillary electrophoresis with laser induced fluorescence detection. Rats were conditioned by pairing a novel flavor (strawberry flavor) with an intraperitoneal injection of lithium chloride. When the conditioned stimulus (strawberry flavored solution) was injected into the mouth of conditioned rats, there was an increase of glutamate release in the AMYG, and a decrease in glutamate release in the LH. These results predicted that glutamate release in the AMYG and the LH was involved in CTA. This possibility was tested by MK-801 (glutamate antagonist) and glutamate microinjections. MK-801 injections in AMYG attenuated the rejection of the novel flavor, and in the LH did not cause any effect on CTA. Glutamate microinjections in the AMYG caused CTA. These results suggest that glutamatergic activity in the AMYG might be a relevant neurochemical correlate and cause of conditioned taste aversion.}, } @article {pmid9822758, year = {1998}, author = {Berman, DE and Hazvi, S and Rosenblum, K and Seger, R and Dudai, Y}, title = {Specific and differential activation of mitogen-activated protein kinase cascades by unfamiliar taste in the insular cortex of the behaving rat.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {18}, number = {23}, pages = {10037-10044}, pmid = {9822758}, issn = {0270-6474}, mesh = {Animals ; Behavior, Animal/*physiology ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cerebral Cortex/chemistry/*enzymology ; Conditioning, Psychological/physiology ; Exploratory Behavior/physiology ; JNK Mitogen-Activated Protein Kinases ; Male ; Memory/physiology ; Mitogen-Activated Protein Kinase 1 ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase 9 ; *Mitogen-Activated Protein Kinases ; Protein Kinases/metabolism ; Rats ; Rats, Wistar ; Taste/*physiology ; p38 Mitogen-Activated Protein Kinases ; }, abstract = {Rats were given to drink an unfamiliar taste solution under conditions that result in long-term memory of that taste. The insular cortex, which contains the taste cortex, was then removed and assayed for activation of mitogen-activated protein kinase (MAPK) cascades by using antibodies to the activated forms of various MAPKs. Extracellular responsive kinase 1-2 (ERK1-2) in the cortical homogenate was significantly activated within <30 min of drinking the taste solution, without alteration in the total level of the ERK1-2 proteins. The activity subsided to basal levels within <60 min. In contrast, ERK1-2 was not activated when the taste was made familiar. The effect of the unfamiliar taste was specific to the insular cortex. Jun N-terminal kinase 1-2 (JNK1-2) was activated by drinking the taste but with a delayed time course, whereas the activity of Akt kinase and p38MAPK remained unchanged. Elk-1, a member of the ternary complex factor and an ERK/JNK downstream substrate, was activated with a time course similar to that of ERK1-2. Microinjection of a reversible inhibitor of MAPK/ERK kinase into the insular cortex shortly before exposure to the novel taste in a conditioned taste aversion training paradigm attenuated long-term taste aversion memory without significantly affecting short-term memory or the sensory, motor, and motivational faculties required to express long-term taste aversion memory. It was concluded that ERK and JNK are specifically and differentially activated in the insular cortex after exposure to a novel taste, and that this activation is required for consolidation of long-term taste memory.}, } @article {pmid9813352, year = {1998}, author = {Escobar, ML and Alcocer, I and Chao, V}, title = {The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo.}, journal = {Brain research}, volume = {812}, number = {1-2}, pages = {246-251}, doi = {10.1016/s0006-8993(98)00931-7}, pmid = {9813352}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*drug effects ; Excitatory Amino Acid Antagonists/*pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Long-Term Potentiation/*drug effects ; Male ; Piperazines/*pharmacology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Taste/*physiology ; Temporal Lobe/*drug effects ; }, abstract = {It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-d-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC.}, } @article {pmid9811361, year = {1998}, author = {Mediavilla, C and Molina, F and Puerto, A}, title = {Bilateral lesions in the cerebellar interpositus-dentate region impair taste aversion learning in rats.}, journal = {Physiology & behavior}, volume = {65}, number = {1}, pages = {25-33}, doi = {10.1016/s0031-9384(98)00083-3}, pmid = {9811361}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebellum/anatomy & histology/*physiology ; Male ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Taste Aversion Learning (TAL) has been induced through two different behavioral procedures: a short-term o concurrent (two-daily flavors) and a long-term (one-daily flavor) procedure. For the first, two gustatory/olfactory stimuli are presented separately but at the same time on a daily basis. One of the flavors is paired with simultaneous intragastric administration of hypertonic NaCl and the other is paired with physiological saline. In the long-term procedure, the two stimuli are presented on alternate days, one of them followed by intragastric injection of the aversive stimulus, and the other by saline. The subjects for both types of tests were animals that had been lesioned in the interpositus-dentate region of the cerebellum. The experiments show that the lesions disrupt short-term TAL, but have no effect on long-term TAL. The results are discussed in terms of the role of the cerebellum in relation to TAL and the different anatomical substrates of both learning modalities.}, } @article {pmid9802842, year = {1998}, author = {Ciccocioppo, R and Panocka, I and Polidori, C and Froldi, R and Angeletti, S and Massi, M}, title = {Mechanism of action for reduction of ethanol intake in rats by the tachykinin NK-3 receptor agonist aminosenktide.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {61}, number = {4}, pages = {459-464}, doi = {10.1016/s0091-3057(98)00090-2}, pmid = {9802842}, issn = {0091-3057}, mesh = {*Alcohol Drinking ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects ; Choice Behavior ; Ethanol/blood/*pharmacokinetics ; Injections, Intraventricular ; Male ; Peptide Fragments/*pharmacology ; Rats ; Receptors, Neurokinin-3/*agonists ; Substance P/*analogs & derivatives/pharmacology ; }, abstract = {Intracerebroventricular (i.c.v.) injection of tachykinin (TK) NK-3 receptor agonists inhibits alcohol intake in genetically selected alcohol-preferring rats. The present study investigated the mechanism of action by which the selective TK NK-3 receptor agonist aminosenktide (NH2-SENK) attenuates ethanol intake in Marchigian Sardinian alcohol-preferring (msP) rats. The effect of NH2-SENK was studied by i.c.v. injection in the conditioned taste aversion (CTA) and in the conditioned place preference (CPP) paradigms; moreover, the effect of NH2-SENK on blood alcohol levels (BAL) following intragastric ethanol administration was investigated. The i.c.v. dose of 125 ng/rat of NH2-SENK, that markedly reduces ethanol intake, did not modify BAL, nor did it increase the CTA induced by intraperitoneal injection of ethanol, 1 g/kg body weight. These findings suggest that the effect of NH2-SENK on alcohol consumption is not related to modification of the pharmacokinetics of ethanol, nor to increase of the aversive properties of ethanol. On the other hand, the same i.c.v. dose of NH2-SENK evoked a pronounced and statistically significant CPP. This finding indicates that the TK NK-3 receptor agonist NH2-SENK possesses rewarding properties in msP rats and suggests that its inhibitory effect on ethanol consumption may be due to substitution of the rewarding properties of ethanol, thus making its consumption redundant.}, } @article {pmid9802436, year = {1998}, author = {Woods, SC and Figlewicz, DP and Madden, L and Porte, D and Sipols, AJ and Seeley, RJ}, title = {NPY and food intake: discrepancies in the model.}, journal = {Regulatory peptides}, volume = {75-76}, number = {}, pages = {403-408}, doi = {10.1016/s0167-0115(98)00095-0}, pmid = {9802436}, issn = {0167-0115}, support = {DK 12829/DK/NIDDK NIH HHS/United States ; DK 17844/DK/NIDDK NIH HHS/United States ; DK 40943/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/drug effects/physiology ; Brain/drug effects/physiology ; Conditioning, Psychological ; Consummatory Behavior/drug effects/physiology ; Eating/drug effects/*physiology ; Injections, Intraventricular ; *Models, Neurological ; Neuropeptide Y/administration & dosage/pharmacology/*physiology ; Pica/chemically induced/physiopathology ; Rats ; }, abstract = {The evidence that NPY is an endogenous neurotransmitter that modulates both sides of the energy equation is clear and compelling. While agreeing with this (and indeed contributing to the growing literature supporting the concept), we have found that the interpretation of the increased food intake stimulated by intraventricular (i.v.t.) NPY is more complex than first appears. We discuss evidence suggesting that NPY additionally (and presumably at other receptor populations in the brain) causes sensations that produce aversion or illness. Specifically, the i.v.t. administration of NPY at doses that stimulate eating also cause the formation of a conditioned taste aversion and the animal engages in a form of pica behavior (kaolin consumption). It also suppresses an otherwise robust increase of sodium consumption. We discuss evidence suggesting that whereas NPY activates feeding behavior by stimulating the complex sequence of behaviors beginning with the seeking and finding of food and ending with food ingestion, NPY does not stimulate increased eating in the absence of the anticipatory preliminary behaviors. Finally, we briefly review evidence suggesting that whatever sensation is aroused by i.v.t. NPY, it is not necessarily the same sensation that is aroused when animals are food-deprived. Hence, one must be cautious in interpreting NPY as solely an orexigen.}, } @article {pmid9772264, year = {1998}, author = {Danilova, V and Hellekant, G and Tinti, JM and Nofre, C}, title = {Gustatory responses of the hamster Mesocricetus auratus to various compounds considered sweet by humans.}, journal = {Journal of neurophysiology}, volume = {80}, number = {4}, pages = {2102-2112}, doi = {10.1152/jn.1998.80.4.2102}, pmid = {9772264}, issn = {0022-3077}, mesh = {Animals ; Avoidance Learning/physiology ; Choice Behavior/physiology ; Chorda Tympani Nerve/*physiology ; Cluster Analysis ; Cricetinae ; Female ; Humans ; Male ; Mesocricetus/*physiology ; Nerve Fibers/physiology ; Taste/*physiology ; }, abstract = {The taste of 30 compounds was studied in the golden hamster with three different methods: single-fiber recordings, two-bottle preference (TBP), and conditioned taste aversion (CTA) tests. On the whole, the results showed that the sense of taste in the hamster differs in many respects from that in humans because, of 26 tested compounds known as sweet to humans, 11 had no taste or tasted differently. The results also supported the notion that activity in S-fibers elicits liking and activity in Q- or H-fibers rejection. Specifically hierarchial cluster analysis of 36 single fibers from the chorda tympani proper nerve separated N-, H-, and S-clusters consisting of 11 sucrose-, 14 NaCl-, and 11 citric-best fibers. Ace-K, cyanosuosan, N-4-cyanophenyl-N'-cyanoguanidineacetate (CCGA), -tryptophan, N-3, 5-dichlorophenyl-N'-(S)-alpha-methylbenzylguanidineacetate (DMGA), saccharin, SC-45647, and suosan stimulated only the S-fibers, were significantly preferred in TBP tests, and generalized to sucrose in the CTA tests. Ethylene glycol stimulated the N-fibers in addition to the S-fibers. This explains its generalization to sucrose in CTA. Its toxicity may contribute to its rejection in TBP tests. Sodium cyclamate stimulated a few N- but no S-fibers, which may explain the nondiscriminatory TBP and CTA results. Glycine elicited its largest response in the S-fibers, although it also stimulated other fibers. The resulting mixed taste sensation may explain why it was not preferred in TBP, although it generalized to sucrose in the CTA. Alitame, aspartame, N-4-cyanophenylcarbamoyl--aspartyl-(R)-alpha-methylbenzylamine (CAM), N-4-cyanophenylcarbamoyl-(R, S)-3-amino-3-(3, 4-methylenedioxyphenyl) propionic acid (CAMPA), N-(S)-2-methylhexanoyl--glutamyl-5-amino-2-pyridinecarbonitrile (MAGAP), N-1-naphthoyl--glutamyl-5-amino-2-pyridinecarbonitrile (NAGAP), NHDHC, superaspartame, and thaumatin were among the compounds considered sweet by humans that gave no response, were not discriminated in the TBP test, and gave no generalization in the CTA tests.}, } @article {pmid9765348, year = {1998}, author = {Froehlich, JC and Badia-Elder, NE and Zink, RW and McCullough, DE and Portoghese, PS}, title = {Contribution of the opioid system to alcohol aversion and alcohol drinking behavior.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {287}, number = {1}, pages = {284-292}, pmid = {9765348}, issn = {0022-3565}, support = {AA08312/AA/NIAAA NIH HHS/United States ; AI10709/AI/NIAID NIH HHS/United States ; }, mesh = {Alcohol Drinking/*psychology ; Animals ; Conditioning, Psychological ; Dose-Response Relationship, Drug ; Endorphins/*physiology ; Enkephalins/*physiology ; Ethanol/blood ; Female ; Naltrexone/analogs & derivatives/pharmacology ; Rats ; Rats, Wistar ; Receptors, Opioid, delta/antagonists & inhibitors ; }, abstract = {The effect of blocking delta opioid receptors on alcohol aversion was examined in female alcohol-preferring (P) rats using a conditioned taste aversion (CTA) paradigm. In experiment 1, alcohol naive P rats were given i.p injections of 0.5, 1.0 or 1.5 g alcohol/kg BW or saline, paired with consumption of a banana-flavored solution during 5 conditioning trials. Alcohol in a dose of 0.5 g/kg was not aversive while the two higher doses (1.0 and 1.5 g/kg) were both aversive in the CTA paradigm. In experiment 2, the effect of the selective delta opioid receptor antagonist, naltrindole (NTI), on alcohol aversion was examined. Rats were pretreated with NTI in doses of 2.5, 5.0, 10.0 or 20.0 mg/kg before conditioning using the nonaversive dose of alcohol from Experiment 1. As in experiment 1, the 0.5 g/kg dose of alcohol did not produce a CTA. Administration of NTI alone in doses of 2.5, 5.0 or 10.0 mg/kg did not produce a CTA. However, when the nonaversive dose of alcohol (0.5 g/kg) was combined with NTI in a dose of either 5.0 or 10.0 mg/kg, an aversion to alcohol was seen. The highest dose of NTI (20 mg/kg) produced a CTA when given either alone and in combination with alcohol. The results indicate that blocking the action of opioid peptides at the delta opioid receptor can make a nonaversive dose of alcohol aversive which suggests that opioid peptides, acting via the delta opioid receptor, play an important role in regulating alcohol aversion.}, } @article {pmid9756038, year = {1998}, author = {Risinger, FO and Cunningham, CL}, title = {Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice.}, journal = {Alcoholism, clinical and experimental research}, volume = {22}, number = {6}, pages = {1234-1244}, pmid = {9756038}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA08621/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/genetics ; Alcoholism/genetics ; Animals ; Avoidance Learning/drug effects/*physiology ; Chromosome Mapping ; Conditioning, Classical/drug effects/*physiology ; Dose-Response Relationship, Drug ; Ethanol/*toxicity ; Genetic Predisposition to Disease/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Motivation ; Phenotype ; Quantitative Trait, Heritable ; Recombination, Genetic/*genetics ; Taste/drug effects/*genetics ; }, abstract = {Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.}, } @article {pmid9751227, year = {1998}, author = {Wang, T and Edwards, GL and Baile, CA}, title = {Glucagon-like peptide-1 (7-36) amide administered into the third cerebroventricle inhibits water intake in rats.}, journal = {Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)}, volume = {219}, number = {1}, pages = {85-91}, doi = {10.3181/00379727-219-44320}, pmid = {9751227}, issn = {0037-9727}, mesh = {Animals ; Avoidance Learning/drug effects ; Cerebral Ventricles/*drug effects ; Drinking/*drug effects ; Eating/drug effects ; Glucagon/administration & dosage/*pharmacology ; Glucagon-Like Peptide 1 ; Injections, Intraventricular ; Male ; Peptide Fragments/administration & dosage/*pharmacology ; Protein Precursors/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/physiology ; Water Deprivation/physiology ; }, abstract = {Intracerebroventricular (icv) injection of glucagon-like peptide-1 (7-36) amide (GLP-1) has been shown to reduce food intake in rats. In these studies, we confirmed that injection of 10 microg of GLP-1 into the third cerebroventricle suppressed food intake. Moreover, we observed a reduction in water intake associated with the decreased food intake. We further examined whether GLP-1 injected icv in rats has a specific inhibitory effect on water intake. It was found that GLP-1 reduced water deprivation-induced drinking. Furthermore, the same dose of GLP-1 (10 microg) was sufficient to condition taste aversion. Finally, when 2 microg of GLP-1 were injected into the third ventricle, it only suppressed water deprivation-induced water intake and failed to influence spontaneous food and water intakes or induce conditioned taste aversion. These observations indicate that GLP-1 is a potent inhibitor of water intake in the rat and may play a role in the control of fluid homeostasis.}, } @article {pmid9748108, year = {1998}, author = {Mickley, GA and Schaldach, MA and Snyder, KJ and Balogh, SA and Len, T and Neimanis, K and Goulis, P and Hug, J and Sauchak, K and Remmers-Roeber, DR and Walker, C and Yamamoto, BK}, title = {Ketamine blocks a conditioned taste aversion (CTA) in neonatal rats.}, journal = {Physiology & behavior}, volume = {64}, number = {3}, pages = {381-390}, doi = {10.1016/s0031-9384(98)00097-3}, pmid = {9748108}, issn = {0031-9384}, support = {DA 07606/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn/*physiology ; Avoidance Learning/drug effects/*physiology ; Brain/metabolism ; Excitatory Amino Acid Antagonists/pharmacokinetics/*pharmacology ; Female ; Food Preferences/drug effects ; Ketamine/pharmacokinetics/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {These experiments explored the effects of glutamate, N-methyl-D-aspartate (NMDA) receptor blockade on the formation, retention, and expression of conditioned taste aversion (CTA) in young rats. Previous data from our laboratory suggested that ketamine administration potentiates a CTA in E18 rat fetuses. The current studies investigated this phenomenon in neonates. High-pressure liquid chromatography (HPLC) methods were used to determine the amount of ketamine that must be injected intraperitoneally (i.p.) to achieve brain ketamine levels in neonates comparable to those found in the fetuses from our previous experiments. Then, on their day of birth, Sprague-Dawley rat pups received injections of either 0.1, 10, or 70 mg/kg of ketamine HCI, i.p. or a Sal control injection. One-half hour later, pups were injected orally with either Saccharin (Sac; 10 microL of 0.3%) or water followed by an injection of either lithium chloride (LiCl; 81 mg/kg) or Sal (i.p.). The CTA was evaluated in two different tests. Two weeks after conditioning, the dam was anesthetized and the frequency with which pups attached to Sac-painted nipples versus nipples painted with water was measured (i.e., the nipple taste test, NTT). Controls for state-dependent learning were run in which 10 mg/kg of ketamine or saline (Sal) was administered before both taste aversion conditioning and the NTT. After weaning, the CTA was also evaluated by measuring the amount of Sac (0.3%) or water consumed during a two-bottle test. Neonates that received Sal control injections before the Sac + LiCl pairing acquired CTAs and avoided Sac-painted nipples. However, the pups injected with ketamine on the conditioning day only (P0) did not avoid Sac-painted nipples (as compared to controls). Pups that had ketamine both at the time of CTA training and testing, or just before the NTT, also failed to avoid Sac-painted nipples. Ketamine's acute effects apparently influenced the outcome of the NTT of state-dependent control subjects. Rat pups that received the highest doses of ketamine (10 or 70 mg/kg) and tasted Sac on P0 later failed to show a neophobia for Sac-painted nipples. Whereas, rat pups that received the high dose of ketamine and water on P0, later exhibited a neophobic response. These data suggest that ketamine did not impair the animal's ability to taste Sac. These data reflecting a ketamine-induced blockade of neonatal CTAs may be contrasted with our previous findings in which ketamine potentiated fetal CTAs. However, they are in consonance with data from adult rats suggesting that ketamine can cause an amnesia for CTAs. NMDA receptor blockade may shape memory formation in a manner that is dependent on the stage of brain development.}, } @article {pmid9729264, year = {1998}, author = {Chance, WT and Tao, Z and Sheriff, S and Balasubramaniam, A}, title = {WRYamide, a NPY-based tripeptide that antagonizes feeding in rats.}, journal = {Brain research}, volume = {803}, number = {1-2}, pages = {39-43}, doi = {10.1016/s0006-8993(98)00574-5}, pmid = {9729264}, issn = {0006-8993}, support = {GM 47122/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Appetite Depressants/*pharmacology ; Catheterization ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Hypothalamus/drug effects ; Injections, Intravenous ; Male ; Neuropeptide Y/administration & dosage/*analogs & derivatives/*chemistry/pharmacology ; Oligopeptides/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Time Factors ; }, abstract = {Modifications of (D-Trp32) neuropeptide Y (NPY) led to the development of potential peptide-based lower molecular weight (500-800 Da) NPY feeding antagonists. One compound, WRYamide (N-Ac-Trp-Arg-Tyr-NH2), blocked NPY-induced feeding for 1 to 4 h when injected intrahypothalamically (i.h.t.) at 1 to 40 microgram. Schedule-induced feeding was also antagonized for up to 24 h by 20 microgram of WRYamide, i.h.t. Injection of 2.5 mg/kg (1 mg/rat) of WRYamide, i.v., also reduced significantly schedule-induced feeding for 4 h. A conditioned taste aversion could not be classically conditioned to saccharin using WRYamide as the unconditioned stimulus. These results may lead to the development of systemically active anti-obesity drugs.}, } @article {pmid9728669, year = {1998}, author = {Olivier, B and van Oorschot, R and Waldinger, MD}, title = {Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour.}, journal = {International clinical psychopharmacology}, volume = {13 Suppl 6}, number = {}, pages = {S9-14}, doi = {10.1097/00004850-199807006-00003}, pmid = {9728669}, issn = {0268-1315}, mesh = {Animals ; Humans ; Receptors, Serotonin/*metabolism ; Serotonin/*metabolism ; Serotonin Uptake Inhibitors/*adverse effects ; Sexual Behavior/*drug effects ; Sexual Behavior, Animal/*drug effects ; }, abstract = {The serotonergic system in the brain modulates many types of behavioural and physiological processes. An example of this modulatory function is seen with the selective serotonin reuptake inhibitors (SSRIs) which enhance serotonin transmission and influence mood, anxiety states, aggression, feeding and sexual behaviour. At present, 14 different serotonin receptors have been described and, although the function and localization of many of these receptors is becoming increasingly clear, much remains unknown. The SSRIs are intriguing drugs; by blocking presynaptic and somatodendritic serotonin transporters, they enhance serotonergic neurotransmission and thereby activate serotonin receptors. It is this effect which leads to the characteristic effects of the SSRIs. Theoretically, however, it appears possible that they may have differential effects on the various subpopulations of serotonin receptors. Differences between the SSRIs have recently been reported in males with rapid ejaculation; fluvoxamine, in contrast to other SSRIs, did not affect rapid ejaculation. What difference in the mechanism of action between the SSRIs is responsible for this differential profile? A conditioned taste aversion procedure has been used in mice to investigate the discriminatory stimuli (cues) of fluvoxamine and fluoxetine. It appeared that the discriminatory stimulus of fluvoxamine is primarily mediated via 5-hydroxytryptamine (HT)1A receptors, whilst that of fluoxetine is primarily mediated via 5-HT2C receptors. Both types of receptors have been implicated in depression and it is conceivable that different SSRIs have intrinsic activity at these receptors. Investigations are now ongoing to determine whether this differential mechanism of action also applies to the other SSRIs and whether there are differences between the SSRIs with respect to their effect on sexual behaviour in rodents.}, } @article {pmid9726644, year = {1998}, author = {McAllister, KH and Pratt, JA}, title = {GR205171 blocks apomorphine and amphetamine-induced conditioned taste aversions.}, journal = {European journal of pharmacology}, volume = {353}, number = {2-3}, pages = {141-148}, doi = {10.1016/s0014-2999(98)00405-1}, pmid = {9726644}, issn = {0014-2999}, mesh = {Amphetamines/*pharmacology ; Animals ; Apomorphine/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Classical ; *Neurokinin-1 Receptor Antagonists ; Ondansetron/pharmacology ; Piperidines/*pharmacology ; Rats ; Receptors, Serotonin/drug effects ; Receptors, Serotonin, 5-HT3 ; Serotonin Antagonists/pharmacology ; Taste/*drug effects ; Tetrazoles/*pharmacology ; }, abstract = {The tachykinin NK1 receptor antagonist, GR205171 ([2-methoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-(2S-phenyl -piperidin-3S-yl)-amine), is a potent inhibitor of emesis induced by a wide variety of emetogens. This is in contrast to 5-HT3 (5-hydroxytryptamine3) receptor antagonists, such as ondansetron, which have a more restricted antiemetic profile. The present study evaluated the efficacy of GR205171, in comparison with ondansetron to block the acquisition of a conditioned taste aversion induced by either apomorphine (0.25 mg kg(-1) s.c.) or by amphetamine (0.5 mg kg(-1) s.c.) in rats. Pretreatment with GR205171 (0.1-1.0 mg kg(-1) s.c.) and ondansetron (0.001-0.1 mg kg(-1) s.c.) produced a dose-dependent blockade of conditioned taste aversions evoked by apomorphine. In contrast, the acquisition of conditioned taste aversions induced by amphetamine was inhibited by GR205171 (0.3-0.5 mg kg(-1) s.c.), but only attenuated by ondansetron (0.001-0.1 mg kg(-1) s.c.). These results suggest that tachykinin NK1 receptor antagonists may have potential in the treatment of drug-induced conditioned aversive behaviour and nausea.}, } @article {pmid9725749, year = {1998}, author = {Hatcher, JP and Loudon, JM and Hagan, JJ and Clark, MS}, title = {Sabcomeline (SB-202026), a functionally selective M1 receptor partial agonist, reverses delay-induced deficits in the T-maze.}, journal = {Psychopharmacology}, volume = {138}, number = {3-4}, pages = {275-282}, doi = {10.1007/s002130050672}, pmid = {9725749}, issn = {0033-3158}, mesh = {Animals ; Cholinesterase Inhibitors/pharmacology ; Imines/*pharmacology ; Male ; Maze Learning/*drug effects ; Muscarinic Agonists/*pharmacology ; Quinuclidines/*pharmacology ; Rats ; Receptor, Muscarinic M1 ; *Receptors, Muscarinic/metabolism ; Succinimides/pharmacology ; Tacrine/pharmacology ; Taste/drug effects ; }, abstract = {Sabcomeline, (SB-202026 [R-(Z)-alpha-(methoxyimino)-1 -azabicyclo [2.2.2] octane-3-acetonitrile]), a functionally selective muscarinic M1 receptor partial agonist, was tested in rats trained to perform a delayed, reinforced alternation task in a T maze, a test of short-term spatial memory. For comparison the cholinesterase inhibitor tacrine (THA-9-amino- 1,2,3,4-tetrahydroaminoacridine) and the non-selective muscarinic receptor agonist RS86 (2-ethyl-8-methyl-2,8 diazospiro [4.5]-decane-1,3-dione hydrobromide) were also tested and all three compounds were also compared using a conditioned taste aversion (CTA) task. Sabcomeline (0.001-1.0 mg/kg i.p.) significantly reversed the T-maze choice accuracy deficit induced by a 20-s delay at 0.03 and 0.1 mg/kg. RS86 (0.1-3.0 mg/kg i.p.) reversed the deficit at 1.0 mg/kg and THA (0.1-3.0 mg/kg i.p.) had no effect at any dose. All three compounds induced conditioned taste aversion with minimum effective doses (MED) of 0.3, 1.0 and 3.0 mg/kg, respectively. The results show that sabcomeline reverses delay induced deficits in T-maze choice accuracy in a rewarded alternation task at doses approximately 10 times lower than those required to induce conditioned taste aversion. RS86 was equipotent in both tests. These data support the findings of clinical studies which have shown that SB-202026 provides significant symptomatic improvement in patients with probable Alzheimer's disease at doses which do not induce cholinergic side effects.}, } @article {pmid9716348, year = {1998}, author = {Rudd, JA and Ngan, MP and Wai, MK}, title = {5-HT3 receptors are not involved in conditioned taste aversions induced by 5-hydroxytryptamine, ipecacuanha or cisplatin.}, journal = {European journal of pharmacology}, volume = {352}, number = {2-3}, pages = {143-149}, doi = {10.1016/s0014-2999(98)00359-8}, pmid = {9716348}, issn = {0014-2999}, mesh = {Animals ; Antineoplastic Agents/adverse effects ; Avoidance Learning/physiology ; Cisplatin/adverse effects/*pharmacology ; Conditioning, Classical ; Drinking Behavior ; Granisetron/pharmacology ; Ipecac/*pharmacology ; Male ; Ondansetron/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin/*physiology ; Receptors, Serotonin, 5-HT3 ; Serotonin/*pharmacology ; Serotonin Antagonists/pharmacology ; Taste/*physiology ; }, abstract = {We have used the rat to examine the involvement of the 5-HT3 receptor in the mechanism(s) of conditioned taste aversion induced by 5-hydroxytryptamine (5-HT) and selected emetic drugs. 5-HT, ipecacuanha and cisplatin all induced conditioned taste aversion at doses known to induce emesis in other species but the responses were resistant to treatment with the 5-HT3 receptor antagonists ondansetron and granisetron. Further, m-chlorophenylbiguanide, a selective and potent 5-HT3 receptor agonist, failed to induce a conditioned taste aversion. The data provide strong evidence that the 5-HT3 receptor is not involved in conditioned taste aversion mechanisms in the rat. Results are discussed in terms of the usefulness of the rat conditioned taste aversion paradigm to anti-emetic research.}, } @article {pmid9685579, year = {1998}, author = {Schafe, GE and Bernstein, IL}, title = {Forebrain contribution to the induction of a brainstem correlate of conditioned taste aversion. II. Insular (gustatory) cortex.}, journal = {Brain research}, volume = {800}, number = {1}, pages = {40-47}, doi = {10.1016/s0006-8993(98)00492-2}, pmid = {9685579}, issn = {0006-8993}, support = {DC00248/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Biomarkers ; *Brain Mapping ; Brain Stem/*physiology ; Conditioning, Operant ; Functional Laterality ; Habituation, Psychophysiologic ; Male ; Prosencephalon/*physiology ; Proto-Oncogene Proteins c-fos/analysis/biosynthesis ; Rats ; Reference Values ; Taste/*physiology ; }, abstract = {The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) has been shown to be a cellular correlate of the behavioral expression of a conditioned taste aversion (CTA). To further define neuroanatomical structures and pathways that contribute to this cellular response and to CTA learning in general, electrolytic lesions of insular (gustatory) cortex (IC) were combined with immunostaining for c-FLI. Rats were given either unilateral or bilateral electrolytic lesions of insular cortex or 'sham' operations. Following surgery, 'paired' animals were given a single conditioning trial consisting of intraoral infusion of 5-ml 0.15% sodium-saccharin followed by injection with LiCl (0.15 M, 20 ml/kg, i.p.) while 'unpaired' controls received a non-contingent saccharin-LiCl presentation. Rats with bilateral lesions showed no behavioral evidence of having acquired a CTA. Increases in c-FLI in iNTS were evident, but reduced, relative to 'sham' animals. Rats with unilateral-lesions displayed a CTA by rejecting the saccharin, although increases in c-FLI on the side of the iNTS ipsilateral to the lesion were reduced relative to that seen in 'sham' animals. A comparison of these results with those obtained after amygdala lesions supports the conclusion that amygdala and insular cortex are necessary, but not sufficient, for the behavioral expression of a CTA.}, } @article {pmid9678659, year = {1998}, author = {Riley, AL and Diamond, HF}, title = {The effects of cocaine preexposure on the acquisition of cocaine-induced taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {60}, number = {3}, pages = {739-745}, doi = {10.1016/s0091-3057(98)00052-5}, pmid = {9678659}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/administration & dosage/*pharmacology ; Female ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Narcotics/administration & dosage/*pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {In separate experiments, rats received either five intraperitoneal or five subcutaneous injections of cocaine (once daily or spaced every fourth day) prior to receiving repeated saccharin-cocaine pairings (during taste aversion conditioning). Both spaced and massed subcutaneous cocaine preexposure attenuated the subsequent acquisition of taste aversions induced by cocaine. Specifically, aversions in the preexposed subjects were acquired at a slower rate and/or to a lesser degree than those acquired by subjects preexposed to the cocaine vehicle and injected with cocaine during conditioning. Spaced and massed intraperitoneal cocaine preexposure had only a weak or no effect, respectively, on the subsequent acquisition of cocaine-induced taste aversions. Specifically, subjects receiving spaced intraperitoneal injections of cocaine during preexposure differed from nonpreexposed subjects on only a single conditioning trial, and subjects receiving massed intraperitoneal injections of cocaine during preexposure displayed aversions comparable to those of nonpreexposed subjects. Although the effects of subcutaneous cocaine preexposure were similar to those reported with other drugs within the aversion design, it is clear that the preexposure effect with cocaine is dependent upon the specific parameters of preexposure. Several possibilities for these differential effects of cocaine preexposure were discussed, including the influence of changing the route of administration from preexposure to conditioning (i.e., from i.p. to s.c.) and the differential masking of the aversive effects of cocaine during conditioning by differential sensitization to cocaine's reinforcing properties following s.c. and i.p. preexposure. Although the present series of experiments did not directly address the mechanism(s) underlying the attenuating effects of cocaine preexposure on aversion learning, several possibilities were noted, including adaptation or tolerance to the aversive effects of cocaine and sensitization to its rewarding effects.}, } @article {pmid9666086, year = {1998}, author = {Sacchetti, B and Bielavska, E}, title = {Chelerythrine, a specific PKC inhibitor, blocks acquisition but not consolidation and retrieval of conditioned taste aversion in rat.}, journal = {Brain research}, volume = {799}, number = {1}, pages = {84-90}, doi = {10.1016/s0006-8993(98)00460-0}, pmid = {9666086}, issn = {0006-8993}, mesh = {Alkaloids ; Animals ; Avoidance Learning/*drug effects ; Benzophenanthridines ; Brain Stem/drug effects/physiology ; Conditioning, Psychological/*drug effects ; Enzyme Inhibitors/*pharmacology ; Injections ; Male ; Memory, Short-Term/drug effects ; Phenanthridines/*pharmacology ; Protein Kinase C/*antagonists & inhibitors ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {Association of the short-term memory of the gustatory conditioned stimulus (CS) with visceral malaise (unconditioned stimulus, US) in conditioned taste aversion (CTA) paradigm takes place in the parabrachial nuclei (PBN) of brainstem. In order to ascertain the role of protein-kinase C (PKC) during different phases of CTA acquisition and retrieval, four experimental series were carried out. In Experiment 1, 1 microl of 10 mM of PKC inhibitor chelerythrine prevented CTA acquisition when applied into PBN in the CS-US interval. In Experiment 2, the necessity of PKC activity in different phases of CTA acquisition was tested by prolonging the time interval between PBN administration of chelerythrine and i.p. LiCl. CTA acquisition was prevented when chelerythrine-induced blockade of PKC coincided with GSTM persistence but not with CTA consolidation. In Experiment 3, the interval between saccharin drinking and LiCl injection was prolonged to 120 min. Again, chelerythrine blockade of PKC activity prevented CTA formation when it interfered with GSTM persistence. In Experiment 4, the possibility that PKC activity is necessary also for CTA retrieval was tested by chelerythrine application into PBN 5 min before retrieval testing. In this case, the chelerythrine-induced PKC blockade did not impair CTA retrieval. It is concluded that PKC is important for GSTM formation and persistence but not for CTA consolidation or retrieval.}, } @article {pmid9663450, year = {1998}, author = {Mosher, JT and Birkemo, LS and Johnson, MF and Ervin, GN}, title = {Sulfated cholecystokinin (26-33) induces mild taste aversion conditioning in rats when administered by three different routes.}, journal = {Peptides}, volume = {19}, number = {5}, pages = {849-857}, doi = {10.1016/s0196-9781(98)00025-4}, pmid = {9663450}, issn = {0196-9781}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Injections, Intraperitoneal ; Injections, Intravenous ; Injections, Intraventricular ; Male ; Rats ; Sincalide/*analogs & derivatives/pharmacology ; Sulfuric Acid Esters/*pharmacology ; Taste/*physiology ; }, abstract = {We investigated the ability of sulfated cholecystokinin (26-33) (CCK-8) and cholecystokinin (30-33) (CCK-4) to induce taste aversion or avoidance conditioning (TAC) in a one-bottle testing paradigm after either intravenous (i.v.), intracerebroventricular (i.c.v.), or intraperitoneal (i.p.) administration. Significant TAC was induced by i.p. administration of CCK-8 at 0.1 but not at 0.025, 0.5, or 1.0 micromol/kg; the TAC was not robust and, in this case, not even dose related. I.p. administration of CCK-4 at 0.05, 0.1, 0.5, or 1.0 micromol/kg did not induce TAC, replicating other studies from our lab. Mild but significant TAC was also induced by i.v. administration of CCK-8 (at 0.025 and 1.0 but not 0.1 or 0.5 micromol/kg) but not by i.v. administration of CCK-4 (at 0.05, 0.1, 0.5, or 1.0 micromol/kg). Finally, mild but significant TAC was induced by i.c.v. (i.e., lateral ventricular) administration of CCK-8 (at 0.0015 but not at 0.015 micromol/brain) but not by i.c.v. administration of CCK-4 (at 0.005 or 0.010 micromol/brain). Because CCK-4 failed to induce TAC, CCK-8 apparently induced TAC via all three routes by an action at a CCK(a), not CCK(B), receptor mechanism. Because i.c.v. or i.v. administrations of CCK-8 were not more efficacious than i.p. administration, the taste avoidance induced by i.p. administration of CCK-8 was not so mild simply because it failed to reach a critical central locus adequately or because it failed to be delivered at a critical speed (i.e., via i.v. injections). We demonstrate that CCK-8 can induce mild TAC at either peripheral or central sites and suggest that these effects of CCK-8 may be independent and may be a sign of salience but not necessarily of toxicosis.}, } @article {pmid9659987, year = {1998}, author = {Sakai, N and Yamamoto, T}, title = {Role of the medial and lateral parabrachial nucleus in acquisition and retention of conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {93}, number = {1-2}, pages = {63-70}, doi = {10.1016/s0166-4328(97)00133-2}, pmid = {9659987}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Functional Laterality/*physiology ; Male ; Memory/*physiology ; Pons/anatomy & histology/*physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {When ingestion of a taste stimulus is paired with internal malaise, the animal remembers the taste and rejects its ingestion thereafter. This learning is referred to as conditioned taste aversion (CTA). To establish CTA in adult male Wistar rats, 0.1% saccharin and an i.p. injection of 0.15 M LiCl were used as the conditioned and unconditioned stimuli, respectively. To elucidate the functional role of the medial part of the parabrachial nucleus (PBmed) which receives taste information and the lateral part (PBlat) which receives general visceral information, confined electrolytic lesions were made to either of these regions. Rats with bilateral lesions of the PBlat impaired the acquisition of CTA, but those lesions made after the acquisition of CTA had no effect on the retention of this learning. The bilateral lesions of the PBmed abolished the acquisition and retention of CTA. The PBlat-lesioned rats showed normal taste preference behavior, but PBmed-lesioned rats showed impaired sensibility to taste stimuli. These results suggest that both the PBlat and PBmed are essential for the acquisition of taste aversion learning, but the PBlat is not necessary for retrieval of CTA.}, } @article {pmid9649608, year = {1998}, author = {Bellinger, LL and Evans, JF and Gietzen, DW}, title = {Dorsomedial hypothalamic lesions alter intake of an imbalanced amino acid diet in rats.}, journal = {The Journal of nutrition}, volume = {128}, number = {7}, pages = {1213-1217}, doi = {10.1093/jn/128.7.1213}, pmid = {9649608}, issn = {0022-3166}, support = {NS33347/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acids/*administration & dosage ; Amino Acids, Essential/deficiency ; Animals ; Body Weight ; Dietary Proteins/*administration & dosage ; Eating/drug effects ; Hypothalamus, Middle/*physiology/*surgery ; Indoles/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Serotonin Antagonists/pharmacology ; Tropisetron ; }, abstract = {Within 3 h of ingesting an imbalanced amino acid diet (IAAD), rats show attenuated intake. The associated conditioned taste aversion can be ameliorated by giving the serotonin3 receptor blocker, tropisetron (TROP). A recent c-fos study indicated that the dorsomedial hypothalamic nucleus (DMN) may be activated 2-3 h after ingestion of IAAD. In Experiment 1, DMN-lesioned rats (DMNL) or sham-operated (SHAM) rats were injected with saline (SAL) or TROP just before introduction of IAAD. By 3 h, SAL-DMNL rats consumed more (P < 0.01) of the IAAD than did the SAL-SHAM rats. Thereafter, over the next 21 h, the intake of the SAL-DMNL group returned to control levels. TROP treatment enhanced the intake of the treated groups; the TROP and the lesion effect were additive (P < 0.01). By d 4 of receiving the IAAD, the DMNL groups were eating less than SHAM rats (P < 0.05). The data suggest that the DMN may be involved in the early detection of the amino acid deficiency induced by IAAD, is not involved in the TROP effect and is necessary for proper long-term adaptation to an IAAD.}, } @article {pmid9646939, year = {1998}, author = {Ramírez-Amaya, V and Alvarez-Borda, B and Bermúdez-Rattoni, F}, title = {Differential effects of NMDA-induced lesions into the insular cortex and amygdala on the acquisition and evocation of conditioned immunosuppression.}, journal = {Brain, behavior, and immunity}, volume = {12}, number = {2}, pages = {149-160}, doi = {10.1006/brbi.1998.0518}, pmid = {9646939}, issn = {0889-1591}, mesh = {Amygdala/*drug effects/*physiopathology ; Animals ; Avoidance Learning/physiology ; Brain Mapping ; Cerebral Cortex/*drug effects/*physiopathology ; Conditioning, Psychological/*physiology ; Excitatory Amino Acid Agonists/*pharmacology ; *Immunosuppression Therapy ; Male ; N-Methylaspartate/*pharmacology ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {It has been established that the insular cortex (IC) mediates conditioned taste aversion, and recently we have demonstrated that lesions of this structure disrupt the acquisition of conditioned immunosuppression (CIS). The IC is functionally and reciprocally interconnected with the amygdala (AM) which has been suggested to be involved in neural-immune interactions. The aim of this work was to test the effects of NMDA-induced lesions in either the IC or AM in the acquisition (lesions made before conditioning) and evocation (lesions made after conditioning) of a conditioned immunosuppression task, obtained by one single pairing of saccharin taste and the immunosuppressive drug, cyclophosphamide. AM and IC lesioned rats were separated into four groups: the first two received lesions before and the other two were lesioned after the acquisition of conditioned immunosuppression. Twenty days after conditioning, animals were reexposed to saccharin and immunized with ovalbumin. After immunization, blood samples were taken, and analyzed by ELISA. The results showed that IC lesions disrupted the acquisition and evocation of CTA and CIS. Conversely, AM lesions disrupted only the acquisition of CIS. These data suggest that the IC is involved in the neural mechanisms underlying the acquisition and evocation of conditioned immunosuppression, and the amygdala could be important in mediating the input of the immune information necessary for the acquisition of conditioned immunosuppression.}, } @article {pmid9632240, year = {1998}, author = {Turgeon, SM and Auerbach, EA and Heller, MA}, title = {The delayed effects of phencyclidine (PCP) disrupt latent inhibition in a conditioned taste aversion paradigm.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {60}, number = {2}, pages = {553-558}, doi = {10.1016/s0091-3057(98)00026-4}, pmid = {9632240}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology ; Male ; Phencyclidine/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {The acute effects of a low dose of phencyclidine (PCP) and the delayed effects of a high dose of PCP on latent inhibition (LI) were assessed in a series of experiments using conditioned taste aversion paradigms. Each paradigm involved a preexposure phase in which water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE), followed by a conditioning phase in which animals were allowed access to sucrose and subsequently injected with the negative reinforcer lithium chloride, and a test phase in which animals were allowed access to both sucrose and water. LI was assessed by comparing the %-sucrose consumed in PE and NPE groups on the test day. The effects of low-dose PCP (2.5 mg/kg) were assessed by comparing LI in animals treated with vehicle or PCP 15 min prior to the onset of the preexposure and conditioning phases. A 4-day paradigm involved 2 days of preexposure followed by a day of conditioning and a test day. This paradigm produced comparable levels of LI in vehicle and PCP-treated animals. A 5-day extinction paradigm involved 2 days of preexposure followed by 2 days of conditioning and a test day. This paradigm abolished LI in vehicle and PCP-treated animals. A 3-day paradigm involved 1 day of preexposure followed by a day of conditioning and a test day. One day of preexposure induced a modified LI effect in both in vehicle and PCP-treated animals. The delayed effects of high dose PCP (8.6 mg/kg) were assessed by comparing LI in animals treated with vehicle or PCP 20 h prior to the onset of the preexposure and conditioning phases in the 4-day paradigm. PCP disrupted latent inhibition in this paradigm. The results are discussed in the context of their relevance to the ability for PCP to model schizophrenic symptomatology.}, } @article {pmid9630402, year = {1998}, author = {Onaka, T and Yagi, K}, title = {Oxytocin release from the neurohypophysis after the taste stimuli previously paired with intravenous cholecystokinin in anaesthetized rats.}, journal = {Journal of neuroendocrinology}, volume = {10}, number = {4}, pages = {309-316}, doi = {10.1046/j.1365-2826.1998.00209.x}, pmid = {9630402}, issn = {0953-8194}, mesh = {Anesthetics, Intravenous ; Animals ; Avoidance Learning/*physiology ; Cholecystokinin/*pharmacology ; Conditioning, Operant/*physiology ; Injections, Intravenous ; Male ; Osmolar Concentration ; Oxytocin/*metabolism ; Pituitary Gland, Posterior/*drug effects/metabolism ; Rats ; Secretory Rate/drug effects/physiology ; Sodium Chloride/pharmacology ; Stimulation, Chemical ; Taste/*physiology ; Urethane ; }, abstract = {Intravenously administered cholecystokinin octapeptide (CCK) induces oxytocin release from the neurohypophysis in anaesthetised rats. Memory of conditioned taste aversion can be acquired under anaesthesia. The present experiments aimed at investigating whether taste stimuli previously paired with i.v. CCK evoke oxytocin release from the neurohypophysis in urethane-anaesthetised male rats. Sucrose solution (0.75-2.0 M) paired with i.v. CCK or the vehicle was applied to the tongue. After 3 h, sucrose solution was applied again. The second sucrose slightly increased plasma oxytocin concentration in rats that had received the first sucrose solution paired with the vehicle. Plasma oxytocin concentration after the second sucrose application, however, was significantly higher in CCK-injected than in vehicle-injected rats. In rats that received CCK 1 h before the first sucrose application, a second sucrose application did not produce the oxytocin response. The magnitude of the oxytocin response to the second sucrose solution was increased in a manner related to CCK doses. In separate experiments, NaCl solution (0.75 M) paired with CCK or the vehicle was applied to the tongue. The second NaCl solution applied 3 h after the first one facilitated oxytocin release both in the rats that had received CCK or the vehicle. The increase in plasma oxytocin, however, was significantly larger in CCK than in vehicle-injected rats. In rats that had received the first sucrose solution paired with CCK, a second sucrose solution evoked a significantly larger increase in plasma oxytocin concentrations than a testing NaCl solution did. In rats that had received NaCl solution paired with CCK, a testing sucrose solution did not significantly change plasma oxytocin concentrations. These data suggest that the taste stimulus previously paired with i.v. CCK induces oxytocin release from the neurohypophysis in urethane-anaesthetised rats.}, } @article {pmid9630168, year = {1998}, author = {von Hörsten, S and Exton, MS and Schult, M and Nagel, E and Stalp, M and Schweitzer, G and Vöge, J and del Rey, A and Schedlowski, M and Westermann, J}, title = {Behaviorally conditioned effects of Cyclosporine A on the immune system of rats: specific alterations of blood leukocyte numbers and decrease of granulocyte function.}, journal = {Journal of neuroimmunology}, volume = {85}, number = {2}, pages = {193-201}, doi = {10.1016/s0165-5728(98)00011-3}, pmid = {9630168}, issn = {0165-5728}, mesh = {Animals ; *Conditioning, Psychological ; Corticosterone/blood ; Cyclosporine/*pharmacology ; Granulocytes/*drug effects/physiology ; Immune System/*drug effects ; Immunosuppressive Agents/*pharmacology ; Luminescent Measurements ; Lymphocyte Subsets/*drug effects ; Male ; Rats ; }, abstract = {Immunosuppression induced by Cyclosporine A (CsA) can be behaviorally conditioned. It is unknown, however, whether a taste aversion paradigm using CsA as an unconditioned stimulus (UCS) induces alterations of blood leukocyte numbers and function. Results obtained by three-colour flow cytometry and granulocyte chemiluminescence response demonstrate that in conditioned rats, absolute numbers of lymphocyte subsets, including B, CD8+ T cells and CD4+ naive and memory T cells, and granulocyte numbers and function were significantly decreased. In contrast to the conditioned response, CsA treatment alone increased lymphocyte numbers and did not affect granulocyte function. Thus, our data demonstrate that behaviorally conditioned CsA effects can be monitored in the blood. In addition, results indicate that the CNS mediates the behaviorally conditioned immunosuppression by reducing the availability and function of granulocytes and lymphocytes.}, } @article {pmid9623713, year = {1998}, author = {Yamamoto, T and Nagai, T and Shimura, T and Yasoshima, Y}, title = {Roles of chemical mediators in the taste system.}, journal = {Japanese journal of pharmacology}, volume = {76}, number = {4}, pages = {325-348}, doi = {10.1254/jjp.76.325}, pmid = {9623713}, issn = {0021-5198}, mesh = {Animals ; Avoidance Learning ; Neurotransmitter Agents/*physiology ; Signal Transduction/physiology ; Taste/*physiology ; Taste Buds/physiology ; }, abstract = {Recent advances in neural mechanisms of taste are reviewed with special reference to neuroactive substances. In the first section, taste transduction mechanisms of basic tastes are explained in two groups, whether taste stimuli directly activate ion channels in the taste cell membrane or they bind to cell surface receptors coupled to intracellular signaling pathways. In the second section, putative transmitters and modulators from taste cells to afferent nerves are summarized. The candidates include acetylcholine, catecholamines, serotonin, amino acids and peptides. Studies favor serotonin as a possible neuromodulator in the taste bud. In the third section, the role of neuroactive substances in the central gustatory pathways is introduced. Excitatory and inhibitory amino acids (e.g., glutamate and GABA) and peptides (substance P and calcitonin gene-related peptide) are proved to play roles in transmission of taste information in both the brainstem relay and cortical gustatory area. In the fourth section, conditioned taste aversion is introduced as a model to study gustatory learning and memory. Pharmacobehavioral studies to examine the effects of glutamate receptor antagonists and protein kinase C inhibitors on the formation of conditioned taste aversion show that both glutamate and protein kinase C in the amygdala and cortical gustatory area play essential roles in taste aversion learning. Recent molecular and genetic approaches to disclose biological mechanisms of gustatory learning are also introduced. In the last section, behavioral and pharmacological approaches to elucidate palatability, taste pleasure, are described. Dopamine, benzodiazepine derivatives and opioid substances may play some roles in evaluation of palatability and motivation to ingest palatable edibles.}, } @article {pmid9619685, year = {1998}, author = {Bienkowski, P and Piasecki, J and Koros, E and Stefanski, R and Kostowski, W}, title = {Studies on the role of nicotinic acetylcholine receptors in the discriminative and aversive stimulus properties of ethanol in the rat.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {8}, number = {2}, pages = {79-87}, doi = {10.1016/s0924-977x(97)00052-7}, pmid = {9619685}, issn = {0924-977X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/*pharmacology ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; Mecamylamine/pharmacology ; Nicotine/pharmacology ; Nicotinic Agonists/pharmacology ; Nicotinic Antagonists/pharmacology ; Rats ; Rats, Wistar ; Receptors, Nicotinic/drug effects/*physiology ; Taste/*drug effects ; }, abstract = {The role of the nicotinic acetylcholine receptor (nAChR) in the discriminative and aversive stimulus effects of ethanol was studied in rats. In the operant drug discrimination procedure the rats were trained to discriminate between 1.0 g/kg ethanol and saline under the FR10 schedule of sweetened milk reinforcement. Neither the nAChR agonist, nicotine (0.1-0.6 mg/kg) nor the nAChR antagonist, mecamylamine (3.0-6.0 mg/kg) substituted for the ethanol stimulus. Moreover, mecamylamine (0.5-6.0 mg/kg) did not antagonise the ethanol stimulus. The cross-familiarisation conditioned taste aversion procedure was used as an alternative method to study stimulus resemblance between ethanol and nicotine. Six daily injections of nicotine (0.6 mg/kg) significantly decreased a subsequent ethanol-induced taste aversion conditioning. The aversive stimulus effects of ethanol were investigated with the conditioned taste aversion (CTA) paradigm. Mecamylamine (1.0-3.0 mg/kg) did not attenuate an ethanol-induced CTA. These results suggest that: (1) nAChRs are not primarily involved in the discriminative stimulus effects of ethanol when studied with the operant drug discrimination test; (2) nAChRs are not critically involved in the ethanol-induced CTA.}, } @article {pmid9608344, year = {1998}, author = {Bevins, RA and Bardo, MT}, title = {Morphine-conditioned changes in locomotor activity: role of the conditioned stimulus.}, journal = {Experimental and clinical psychopharmacology}, volume = {6}, number = {2}, pages = {131-138}, doi = {10.1037//1064-1297.6.2.131}, pmid = {9608344}, issn = {1064-1297}, support = {DA05312/DA/NIDA NIH HHS/United States ; DA05623/DA/NIDA NIH HHS/United States ; DA07746/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Male ; Morphine/*pharmacology ; Motor Activity/*drug effects ; Narcotics/*pharmacology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {When a multisensory environment was reliably paired with morphine (2 mg/kg) in rats, that environment, in a drug-free test, evoked a hyperactive conditioned response (CR). When an olfactory cue (banana odor) was the only stimulus element reliably paired with morphine, it also elicited a hyperactive CR. However, a gustatory cue (saccharin solution) evoked a hypoactive CR. This taste-elicited decrease in activity was dose dependent; morphine at 2 and 4 mg/kg conditioned hypoactivity, whereas a higher dose (8 mg/kg) did not. A robust conditioned saccharin aversion occurred only at the highest dose of morphine, suggesting disassociation between the hypoactive CR and taste aversion. A taste cue present during context conditioning also prevented either acquisition or expression of the hyperactive CR to the context. The modality of the conditioned stimulus is a critical determinant of the form of the CR in a morphine locomotor conditioning paradigm.}, } @article {pmid9586858, year = {1998}, author = {Bienkowski, P and Iwinska, K and Koros, E and Panocka, I and Piasecki, J and Kostowski, W}, title = {Prior repeated exposure to a 5-HT3 receptor agonist does not alter the ethanol-induced conditioned taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {59}, number = {4}, pages = {975-980}, doi = {10.1016/s0091-3057(97)00522-4}, pmid = {9586858}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Biguanides/pharmacology ; Central Nervous System Depressants/*pharmacology ; Ethanol/*pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Wistar ; Serotonin Receptor Agonists/*pharmacology ; Taste/*drug effects ; }, abstract = {Several reports have indicated that the brain serotonergic 5-HT3 receptors are involved in at least some central effects of ethanol in rats. However, using an operant drug discrimination procedure, we have shown that these receptors are not primarily involved in the discriminative stimulus effects of ethanol. The aim of the present study was to further elucidate the role of 5-HT3 receptors in the formation of the ethanol-cueing effects in rats. To this purpose, a crossfamiliarization conditioned taste aversion (CF-CTA) procedure was used. Four daily injections of 1.5 g/kg ethanol (10% v/v) resulted in a significant attenuation of the subsequent ethanol-induced CTA. In contrast, four daily injections of the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG; 50 microg per rat, i.c.v.) did not alter the subsequent ethanol-induced CTA. The 50 microg dose of mCPBG produced a marked CTA in a control experiment. These results taken together with some previous findings from our laboratory suggest that the brain 5-HT3 receptors do not play any crucial role in the mediation of the discriminative stimulus effects of ethanol.}, } @article {pmid9586843, year = {1998}, author = {Lehmann, J and Stöhr, T and Schuller, J and Domeney, A and Heidbreder, C and Feldon, J}, title = {Long-term effects of repeated maternal separation on three different latent inhibition paradigms.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {59}, number = {4}, pages = {873-882}, doi = {10.1016/s0091-3057(97)00529-7}, pmid = {9586843}, issn = {0091-3057}, mesh = {Amphetamine/pharmacology ; Animals ; Apomorphine/pharmacology ; Avoidance Learning/physiology ; Conditioning, Operant/*physiology ; Dopamine Agonists/pharmacology ; Dopamine Uptake Inhibitors/pharmacology ; Emotions/physiology ; Female ; Male ; *Maternal Deprivation ; Motor Activity/drug effects ; Rats ; Rats, Wistar ; Stereotyped Behavior/drug effects ; Taste/physiology ; }, abstract = {In the present study we investigated the effect of repeated maternal separation on postnatal days 12, 14, 16, and 18 for 6 h/day on Wistar rats on three latent inhibition (LI) paradigms: two-way active avoidance, conditioned emotional response (CER), and conditioned taste aversion (CTA). In addition, hyperactivity induced by d-amphetamine and stereotypies induced by apomorphine were evaluated. In all three LI experiments, the control animals showed only marginal LI, whereas the maternally separated animals showed enhanced LI (only males in CTA). In two-way active avoidance within the nonpreexposed condition maternally separated animals showed improved acquisition of avoidance learning compared with the control animals. Sensitivity in response to amphetamine and apomorphine was not altered by the maternal separation procedure. Thus, maternal separation in this study, contrary to previous reports, but in line with results obtained following early handling before weaning, led to enhancement of the LI phenomenon as assessed in each of the three procedures. As our maternal separation procedure (6 h on days 12, 14, 16, and 18) led to behavioral outcomes that differed from those reported by Ellenbroek and Cools (24 h on day 10), it is suggested that maternal separation regimens that are dissimilar may lead to different and sometimes opposite behavioral effects.}, } @article {pmid9582226, year = {1998}, author = {Hanamori, T and Kunitake, T and Kato, K and Kannan, H}, title = {Responses of neurons in the insular cortex to gustatory, visceral, and nociceptive stimuli in rats.}, journal = {Journal of neurophysiology}, volume = {79}, number = {5}, pages = {2535-2545}, doi = {10.1152/jn.1998.79.5.2535}, pmid = {9582226}, issn = {0022-3077}, mesh = {Afferent Pathways/physiology ; Animals ; Brain Mapping ; Cerebral Cortex/cytology/*physiology ; Chemoreceptor Cells/drug effects/*physiology ; Electric Stimulation ; Female ; Glossopharyngeal Nerve/physiology ; Laryngeal Nerves/physiology ; Neurons/*physiology ; Nociceptors/*physiology ; Pain/*physiopathology ; Pressoreceptors/*physiology ; Rats ; Rats, Sprague-Dawley ; Tail/physiopathology ; Taste/*physiology ; Tongue/innervation/physiology ; Viscera/*innervation ; }, abstract = {Extracellular unit responses to baroreceptor and chemoreceptor stimulation, gustatory stimulation of the posterior tongue, electrical stimulation of the superior laryngeal (SL) nerve, and tail pinch were recorded from the insular cortex of anesthetized and paralyzed rats. Forty-three neurons identified responded to stimulation by at least one of the stimuli used in the present study. Of the 43 neurons, 33 responded to tail pinch, and the remaining 10 had no response; 18 showed an excitatory response, and 15 showed an inhibitory response. Of the 43 neurons, 35 responded to electrical stimulation of the SL nerve; 27 showed an excitatory response, and 8 showed an inhibitory response. Of the 20 neurons that responded to baroreceptor stimulation by an intravenous injection of methoxamine hydrochloride (Mex), 11 were excitatory and 9 were inhibitory. Twenty-seven neurons were responsive to an intravenous injection of sodium nitroprusside (SNP); 10 were excitatory and 17 were inhibitory. Ten neurons were excited and 16 neurons were inhibited by arterial chemoreceptor stimulation by an intravenous injection of sodium cyanide (NaCN). Twenty-six neurons were responsive to at least one of the gustatory stimuli (1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose): four to six excitatory neurons and three to nine inhibitory neurons for each stimulus. A large number of the neurons (42/43) received convergent inputs from more than one stimulus among the nine stimuli used in the present study. Most neurons (38/43) were responsive to two or more stimulus groups when the natural stimuli used in the present study are grouped into three, gustatory, visceral, and nociceptive stimuli. The neurons recorded were located in the insular cortex between 2.8 mm anterior and 1.1 mm posterior to the anterior edge of the joining of the anterior commissure (AC); the mean location was 1.0 mm (n = 43) anterior to the AC. This indicates that most of the neurons identified in the present study were located in the region posterior to the taste area and anterior to the visceral area in the insular cortex. These results indicate that the insular cortex neurons distributing between the taste area and the visceral area receive convergent inputs from baroreceptor, chemoreceptor, gustatory, and nociceptive organs and may have roles in taste aversion or in regulation of visceral responses.}, } @article {pmid9581655, year = {1998}, author = {Chester, JA and Risinger, FO and Cunningham, CL}, title = {Ethanol reward and aversion in mice bred for sensitivity to ethanol withdrawal.}, journal = {Alcoholism, clinical and experimental research}, volume = {22}, number = {2}, pages = {468-473}, pmid = {9581655}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics ; Alcohol Withdrawal Delirium/*genetics ; Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Ethanol/toxicity ; *Genotype ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred Strains ; *Motivation ; Species Specificity ; Taste/*genetics ; }, abstract = {The present study examined mice selectively bred for sensitivity to ethanol withdrawal for differences in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms. Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice and High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were selectively bred for differences in chronic and acute ethanol withdrawal, respectively. For the CPP experiment, male HAW and LAW (generation 5) mice received four pairings of ethanol (2 g/kg), with a distinctive floor stimulus. On intervening days, mice received saline paired with an alternate floor type. During the preference test, all mice received an injection of saline before 60-min access to both floor types. HAW mice showed conditioned preference for the ethanol-paired floor, whereas LAW mice did not. For the CTA experiments, male HAW, LAW, WSP, and WSR mice were adapted to a 2-hr/day water restriction regimen and subsequently received ethanol injections (0, 2, 2.5, or 4 g/kg, i.p.) immediately after 1-hr access to a NaCl-flavored solution. Dose-dependent reductions in NaCl intake reflected the development of CTA in both HAW/LAW and WSP/WSR lines. However, a smaller magnitude of CTA was observed in WSP mice relative to WSR mice after the first ethanol-NaCl pairing. WSP/WSR mice showed similar reductions of NaCl intake on subsequent conditioning trials. Overall, these data suggest that HAW mice selectively bred for high sensitivity to acute ethanol withdrawal are more sensitive to the rewarding effects of ethanol in the CPP paradigm. This outcome is consistent with a previous study showing greater CPP in WSP mice relative to WSR mice. In the CTA paradigm, sensitivity to ethanol withdrawal in the HAW/ LAW selected lines does not appear to be genetically correlated with sensitivity to the aversive properties of ethanol. However, the difference in acquisition of CTA in WSP/WSR lines suggest that some genes determining ethanol withdrawal severity may also influence initial sensitivity to ethanol's aversive effects.}, } @article {pmid9547249, year = {1998}, author = {De Oca, BM and DeCola, JP and Maren, S and Fanselow, MS}, title = {Distinct regions of the periaqueductal gray are involved in the acquisition and expression of defensive responses.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {18}, number = {9}, pages = {3426-3432}, pmid = {9547249}, issn = {0270-6474}, support = {MH 39786/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cats ; Conditioning, Operant/*physiology ; Electroshock ; *Fear ; Female ; Male ; Periaqueductal Gray/*physiology ; Rats ; Vocalization, Animal/physiology ; }, abstract = {In fear conditioning, a rat is placed in a distinct environment and delivered footshock. The response to the footshock itself is called an activity burst and includes running, jumping, and vocalization. The fear conditioned to the distinct environment by the footshock elicits complete immobility termed freezing. Lesions of the ventral periaqueductal gray (vPAG) strongly attenuate freezing. However, lesions of the dorsolateral periaqueductal gray (dlPAG) increase the amount of freezing seen to conditional fear cues acquired under conditions in which intact rats do not demonstrate much fear conditioning. To examine the necessity of these regions in the acquisition and expression of fear, we performed five experiments that examined the effects of electrolytic lesions of the dlPAG and the vPAG in learned and unlearned fear. In experiment 1, lesions of the vPAG strongly attenuated, whereas lesions of the dlPAG enhanced, unconditional freezing to a cat. In experiment 2, lesions of the dlPAG made before but not after training enhanced the amount of freezing shown to conditional fear cues acquired via immediate footshock delivery. In experiment 3, vPAG lesions made either before or after training with footshock decreased the level of freezing to conditional fear cues. Neither dlPAG lesions nor vPAG lesions affected footshock sensitivity (experiment 4) or consumption on a conditioned taste aversion test that does not elicit antipredator responses (experiment 5). On the basis of these results, it is proposed that activation of the dlPAG produces inhibition of the vPAG and forebrain structures involved with defense. In contrast, the vPAG seems to be necessary for postencounter freezing defensive behavior.}, } @article {pmid9507139, year = {1998}, author = {Miranda, MI and Bermúdez-Rattoni, F}, title = {Acetylcholine determination of microdialysates of fetal neocortex grafts that induce recovery of learning.}, journal = {Brain research. Brain research protocols}, volume = {2}, number = {3}, pages = {215-222}, doi = {10.1016/s1385-299x(97)00046-9}, pmid = {9507139}, issn = {1385-299X}, mesh = {Acetylcholine/*analysis ; Animals ; Avoidance Learning/*physiology ; Chromatography, High Pressure Liquid ; Conditioning, Operant/*physiology ; *Fetal Tissue Transplantation ; Male ; Microdialysis ; Neocortex/*chemistry/transplantation ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {The microdialysis technique for acetylcholine (ACh) first became possible when sensitive and specific assays for ACh (pmol/sample range) were developed [G. Damsma, B.H.C. Westerink, P. de Boer, J.B. de Vries, A.S. Horn, Determination of basal acetylcholine release in freely moving rats by transstriatal dialysis coupled to on-line HPLC analysis: pharmacological aspects, Life Sci. 43 (1988) 1161-1168; G. Damsma, B.H.C. Westerink, A. Imperato, H. Rollema, J.B. de Vries, A. S. Horn, Automated brain dialysis of acetylcholine in freely moving rats: detection of basal acetylcholine, Life Sci. 41 (1987) 873-876; P.E. Potter, J.L. Meek, N.H. Neff, Acetylcholine and choline in neural tissue measured by HPLC with electrochemical detection, J. Neurochem. 41 (1983) 188-194; B.H.C. Westerink, G. Damsma, Determination of acetylcholine in microdialysates by HPLC and electrochemical detection, Neurosci. Protocols 20 (1993) 1-9.]. In the present protocol, the microdialysis technique was used to correlate ACh release with the recovery of the ability to acquire a conditioning taste aversion (CTA), by fetal brain grafts in insular cortex (IC) lesioned rats [M.I. Miranda, A.M. Lopez-Colome, F. Bermúdez Rattoni, Recovery of conditional taste aversion induced by fetal neocortex grafts. In vivo correlation of acetylcholine levels, Brain Res. 759 (1997) 141-148]. Three groups of IC lesioned rats showing disrupted CTA received cell suspension grafts of fetal tissue dissected from either the IC or occipital cortex (OC) of 16-day-old rat fetuses. One of the groups of IC-grafted animals was tested after 15 days post-graft; the other groups, IC- and OC-grafted animals, were tested after a recovery time of 45 days, as well as the groups of lesioned and unoperated animals used as control. After the CTA test, guide cannulas were stereotaxically implanted into the IC of all groups. Two days later, microdialysis was performed to determine the extracellular levels of ACh inside the graft. The dialysates were analyzed by high-performance liquid chromatography and electrochemical detection. The ACh was converted by the enzyme acetylcholinesterase to choline, and subsequently by choline oxidase to hydrogen peroxide [J.L. Meek, C. Eva, Enzymes adsorbed on an ion exchanger as a post-column reactor: application to acetylcholine measurement, J. Chromatogr. 317 (1984) 343-347.]. The reactor with these enzymes was placed between the analytical column and the electrochemical detector. The hydrogen peroxide produced was detected with a platinum electrode, and choline was determined concurrently. We believe that the application of free-moving microdialysis as a method to measure the cholinergic levels inside the transplant at two post-graft periods, is a good, direct technique to correlate the effects of ACh levels from the fetal grafts in lesioned rats.}, } @article {pmid9568683, year = {1998}, author = {Tang-Christensen, M and Vrang, N and Larsen, PJ}, title = {Glucagon-like peptide 1(7-36) amide's central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment.}, journal = {Diabetes}, volume = {47}, number = {4}, pages = {530-537}, doi = {10.2337/diabetes.47.4.530}, pmid = {9568683}, issn = {0012-1797}, mesh = {Angiotensin II/pharmacology ; Animals ; Animals, Newborn ; Arcuate Nucleus of Hypothalamus/drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Blood Glucose/metabolism ; Blood-Brain Barrier/physiology ; Brain/drug effects/*physiology ; Cerebral Ventricles/drug effects/physiology ; Drinking/drug effects/*physiology ; Eating/drug effects/*physiology ; Food Additives/*toxicity ; Food Deprivation ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptides ; Male ; Neuropeptide Y/metabolism/pharmacology ; Peptide Fragments/*metabolism ; Rats ; Rats, Wistar ; Sodium Glutamate/*toxicity ; Subfornical Organ/drug effects/physiology ; Taste/drug effects/physiology ; }, abstract = {In the rat, the glucagon-like peptide 1 (GLP-1)(7-36) amide inhibits neurones in the central nervous system responsible for food and water intake. GLP-1-induced inhibition of food intake may involve the hypothalamic arcuate nucleus, whereas rostral sensory circumventricular organs may be responsible for the inhibitory action of GLP-1 on drinking. To further investigate the role of these blood-brain-barrier-free areas in GLP-1-induced inhibition of ingestive behavior, neonatal Wistar rats were subjected to monosodium glutamate (MSG) treatment, which causes extensive damage to the arcuate nucleus as well as to parts of the sensory circumventricular organs. The inhibitory effect of GLP-1 on feeding induced by food deprivation was completely abolished in MSG-lesioned rats. This effect was not due to either a loss of sensitivity to anorectic agents or a loss of taste aversion because MSG-treated animals displayed normal anorectic responses to central administration of corticotropin-releasing factor and normal aversive responses to peripheral administration of both lithium chloride and D-amphetamine. In non-lesioned rats, neuropeptide Y (NPY)-induced feeding was significantly reduced by concomitant GLP-1 administration. In contrast, GLP-1 had no effect on NPY-induced feeding in MSG-lesioned rats, suggesting that the GLP-1 receptors that mediate inhibition of feeding are localized upstream to the NPY-sensitive neurones inducing feeding behavior. The inhibitory effect of GLP-1 on water intake was tested using an ANG II-elicited drinking paradigm. Central administration of GLP-1 inhibited ANG II drinking in both MSG-treated rats and their nontreated littermates. In contrast, peripheral administration of GLP-1 did not inhibit ANG II-induced drinking behavior in MSG-treated rats. Thus it is evident that centrally acting GLP-1 modulates feeding and drinking behavior via neurones sensitive to MSG lesioning in the arcuate nucleus and circumventricular organs, respectively.}, } @article {pmid9566472, year = {1998}, author = {Bienkowski, P and Koros, E and Piasecki, J and Kostowski, W}, title = {Prior exposure to MK-801 sensitizes rats to ethanol-induced conditioned taste aversion.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {33}, number = {2}, pages = {116-120}, doi = {10.1093/oxfordjournals.alcalc.a008366}, pmid = {9566472}, issn = {0735-0414}, mesh = {Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Operant/*drug effects ; Discrimination, Psychological/drug effects ; Dizocilpine Maleate/*pharmacology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Excitatory Amino Acid Antagonists/*pharmacology ; Male ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Pretreatment with an uncompetitive NMDA receptor antagonist, dizocilpine [(+)MK-801; six daily injections of 0.1 or 0.2 mg/kg, i.p.] significantly enhanced subsequent 1.5 g/kg ethanol-induced conditioned taste aversion (CTA). In a control experiment, dizocilpine (0.05-.2 mg/kg) produced only a marginal CTA. Thus, pre-exposure to low, non-aversive doses of MK-801 may sensitize rats to the aversive stimulus effects of ethanol.}, } @article {pmid9539375, year = {1998}, author = {McMillen, BA and Williams, HL}, title = {Role of taste and calories in the selection of ethanol by C57BL/6NHsd and Hsd:ICR mice.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {15}, number = {3}, pages = {193-198}, doi = {10.1016/s0741-8329(97)00111-0}, pmid = {9539375}, issn = {0741-8329}, support = {AA04200-14/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking ; Animals ; Aspartame/administration & dosage ; Behavior, Animal ; Cacao ; *Energy Intake ; *Ethanol ; *Food Preferences ; Glucose/administration & dosage ; Lithium Chloride/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Quinine/administration & dosage ; Saccharin/administration & dosage ; Solutions ; *Taste ; }, abstract = {The C57BL/6 mouse (C57) is used as a model for the human consumption of ethanol. Previous studies on the taste preferences of the C57 mouse indicate that ethanol drinking by this animal is for calories and not for a pharmacological effect. The purpose of this study, therefore, was to further determine the role of calories and taste in the selection of ethanol by the C57 mouse. C57 and outbred Hsd:ICR (ICR or CD-1) mice were housed two per cage with three drinking tubes. A standard 10-day preference test of 3-30% ethanol (v/v) vs. water was performed: the mean maximally preferred concentrations of ethanol were 17.9% for C57 and 6.8% for ICR mice. Once drinking of the preferred concentration for each cage had stabilized at 13.2 and 0.9 g/kg/day, respectively, the third tube was filled with water, 0.5% aspartame, isocaloric dextrose, or diluted chocolate Ultra Slim-Fast plus dextrose. Five days of dextrose or chocolate drink reduced the amount of ethanol consumed by 41% and 44% by C57 mice, but aspartame did not affect their drinking. Additional groups of C57 and ICR mice were habituated to a 2-h limited access to water. When offered a 0.5 mM quinine solution as the only fluid, both strains consumed the same volumes as water. Presentation of a saccharin solution was followed by an i.p. injection of either 0.5 M LiCl or NaCl. When given the saccharin solution 48 h later, the LiCl-treated mice of both strains drank less saccharin. The C57 mouse did not exhibit a LiCl-induced taste aversion when ethanol was the novel solution. As a test of response to novelty, a cork stopper was placed in each cage. The ICR mice gnawed much more of the cork than did the C57 mice. Thus, both C57 and ICR mice learned a taste aversion, but the C57 mouse altered its large consumption of ethanol based on more palatable sources of calories. These data support the earlier concept that the consumption of ethanol represents a preferred source of calories for the C57 mouse. Extrapolation of genetic or biochemical differences between these mice to differences between the human alcoholic and the nonalcoholic should thus be made with caution.}, } @article {pmid9533645, year = {1998}, author = {Lin, L and York, DA}, title = {Changes in the microstructure of feeding after administration of enterostatin into the paraventricular nucleus and the amygdala.}, journal = {Peptides}, volume = {19}, number = {3}, pages = {557-562}, doi = {10.1016/s0196-9781(97)00460-9}, pmid = {9533645}, issn = {0196-9781}, support = {NIDDK 45278/DK/NIDDK NIH HHS/United States ; }, mesh = {Amygdala/*drug effects ; Animals ; Appetite/drug effects ; Colipases/*administration & dosage ; Enzyme Precursors ; Feeding Behavior/*drug effects ; Male ; Paraventricular Hypothalamic Nucleus/*drug effects ; Protein Precursors/*administration & dosage ; Rats ; Satiation/drug effects ; }, abstract = {The effects of enterostatin (ENT) injected into the paraventricular nucleus (PVN) and the amygdala (AMYG) on the microstructure of feeding was studied by using an automated feeding apparatus. In rats adapted to a 6-h meal feeding regime, ENT reduced the size and duration of the first meal after injection in both the PVN and the AMYG. Similar effects were observed when ENT was given at the beginning of the dark cycle in rats fed ad libitum although the onset of feeding was also delayed in this situation. The number of meals and the size of subsequent meals was unaffected by ENT but the eating rate within the first meal was reduced after ENT injection into the AMYG of meal-fed rats. Enterostatin injected into the AMYG at a dose that suppressed feeding did not produce a conditioned taste aversion. ENT given centrally therefore appears to reduce food intake by delaying the initiation of feeding and/or advancing meal termination suggesting that it affects both appetite and satiation mechanisms.}, } @article {pmid9523923, year = {1998}, author = {Roth, JD and Rowland, NE}, title = {Effects of L-arginine on angiotensin II-related water and salt intakes.}, journal = {Physiology & behavior}, volume = {63}, number = {4}, pages = {729-732}, doi = {10.1016/s0031-9384(97)00522-2}, pmid = {9523923}, issn = {0031-9384}, mesh = {Angiotensin II/administration & dosage/*pharmacology ; Animals ; Arginine/administration & dosage/*pharmacology ; Diuretics/pharmacology ; Drinking/*drug effects ; Food Deprivation/physiology ; Food Preferences/*drug effects ; Furosemide/pharmacology ; Injections, Intraventricular ; Injections, Subcutaneous ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium/physiology ; Sodium, Dietary ; Water Deprivation/physiology ; }, abstract = {Nitric oxide (NO) has been implicated centrally as an inhibitory neuromodulator, acting in short feedback loops. Neurons capable of NO synthesis have been localized in various thirst-related hypothalamic nuclei. Intracerebroventricular (icv) injection of L-arginine (L-arg), the precursor for NO, has previously been shown to attenuate both dehydration- and angiotensin II (Ang II)-induced drinking behavior. The present study further examines the effects of L-arg on drinking. We confirmed that icv administration of L-arg (50 microg) reduced water intakes induced by both 24 h water deprivation and icv Ang II (250 ng). We additionally showed that L-arg inhibited the water intake induced by peripheral injection of Ang II and the intake of 0.3 M NaCl following 24 h sodium depletion. We demonstrated the behavioral specificity of L-arg treatment by showing that it did not inhibit the intake of sucrose in food deprived rats and did not act as an unconditional stimulus for the formation of a conditioned taste aversion. These results lend further support to the idea that NO plays a role in modulating fluid balance and drinking behavior.}, } @article {pmid9523915, year = {1998}, author = {Nolte, CM and Pittman, DW and Kalevitch, B and Henderson, R and Smith, JC}, title = {Magnetic field conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {63}, number = {4}, pages = {683-688}, doi = {10.1016/s0031-9384(97)00526-x}, pmid = {9523915}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; *Electromagnetic Fields ; Glucose/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion is a common classic conditioning procedure used to identify noxious stimuli. When a rat is given a taste solution, the conditioned stimulus (CS), followed by an unpleasant experience, the unconditioned stimulus (US), the rat will avoid consumption of the CS in future presentations. These experiments use the taste aversion procedure to examine the effect of exposure to a high magnetic field. A solution consisting of 3.0 g glucose and 1.25 g saccharin per 1 L of solution (G+S) was used as the CS and a 9.4-T magnet served as the US. In Experiment 1, all rats received a 10 min presentation of the G+S solution followed by either a 30 min exposure to the magnetic field (Magnet, n = 8), a 30-min exposure in a container with similar conditions but lacking the magnetic field (Sham, n = 8), or no exposure (Control, n = 8). The Magnet Group showed a taste aversion on the first day of preference testing (p < 0.05). Experiment 2 employed the same US-CS protocol for 3 consecutive days of conditioning. The Magnet Group demonstrated a taste aversion for the postexposure Days 1-8 (p < 0.01). There was no difference between the Sham and Control Groups in either experiment. The results of this study clearly demonstrate that the rats associated the G+S solution with the experience of being exposed to the high magnetic field and avoided the solution in subsequent presentations.}, } @article {pmid9522356, year = {1998}, author = {Yasoshima, Y and Yamamoto, T}, title = {Short-term and long-term excitability changes of the insular cortical neurons after the acquisition of taste aversion learning in behaving rats.}, journal = {Neuroscience}, volume = {84}, number = {1}, pages = {1-5}, doi = {10.1016/s0306-4522(97)00636-2}, pmid = {9522356}, issn = {0306-4522}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/cytology/drug effects/*physiology ; Conditioning, Psychological/physiology ; Lithium Chloride/pharmacology ; Male ; Neurons/drug effects/*physiology ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*physiology ; Time Factors ; }, abstract = {Conditioned taste aversion, a long-lasting type of learning established after a single pairing of a novel taste and subsequent internal malaise, is an adaptive behavior to prevent animals from repeated intakes of poisonous substances. The present study was designed to identify the time-dependent excitability changes of cortical neurons to gustatory stimuli after the acquisition of conditioned taste aversion in freely behaving rats. Conditioned taste aversion to saccharin was established by an intraperitoneal injection of lithium chloride, a sickness-inducing agent, soon after an intraoral infusion of saccharin. Twenty minutes after the pairing, 25 (29%) of 86 rats showed aversive taste reactivities to saccharin, and 30 min after the pairing, all of the rats showed aversive behaviors to saccharin; these behavioral changes lasted throughout the test session (over 360 min). When unit activities were recorded from the insular cortex simultaneously with the behavioral test, 14 (11%) of 122 neurons showed a significant enhancement of excitability in response to saccharin, but not to other taste stimuli, after the acquisition of taste aversion. Eight of these 14 neurons showed a short-term enhancement: significant effects were detected only 30 min after the pairing. The remaining six neurons exhibited a long-term enhancement: the effects lasted over 360 min after the pairing. The existence of such short-term and long-term excitability changes suggests that the gustatory insular cortex is involved in different aspects of taste aversion learning.}, } @article {pmid9517825, year = {1998}, author = {Ormsby, CE and Ramírez-Amaya, V and Bermúdez-Rattoni, F}, title = {Long-term memory retrieval deficits of learned taste aversions are ameliorated by cortical fetal brain implants.}, journal = {Behavioral neuroscience}, volume = {112}, number = {1}, pages = {172-182}, pmid = {9517825}, issn = {0735-7044}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Brain Tissue Transplantation/*physiology ; Cerebral Cortex/physiology/*transplantation ; Conditioning, Classical/*physiology ; Fetal Tissue Transplantation/*physiology ; Male ; Mental Recall/physiology ; Nerve Growth Factors/physiology ; Nerve Regeneration/*physiology ; Neural Inhibition/physiology ; Rats ; Rats, Wistar ; Retention, Psychology/*physiology ; Taste/*physiology ; }, abstract = {In this study, the effects that fetal brain implants have on the ability to retrieve the memory for a previously acquired conditioned taste aversion (CTA) in insular cortex (IC) lesioned rats were tested. Several groups of rats were trained for a CTA, were lesioned in the IC 4 days later, were implanted with different fetal cortical tissues, were treated or untreated with nerve growth factor (NGF), and then were tested for recall either 15 or 45 days later. Rats were then retrained and tested with a different taste and in the inhibitory avoidance (IA) task. All implanted animals recovered the retrieval of CTAs learned before IC lesions; however, only the homotopic IC implants at 45 days or NGF supplemented at 15 days induced recovery of the ability to learn CTA. The latter effect was also true for IA learning. The results suggest that the brain mechanisms for recovery of memory functions are different from those of learning abilities.}, } @article {pmid9517824, year = {1998}, author = {Grigson, PS and Reilly, S and Shimura, T and Norgren, R}, title = {Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion: further evidence for an associative deficit in rats.}, journal = {Behavioral neuroscience}, volume = {112}, number = {1}, pages = {160-171}, pmid = {9517824}, issn = {0735-7044}, support = {DC-00240/DC/NIDCD NIH HHS/United States ; DC-02016/DC/NIDCD NIH HHS/United States ; DC-02821/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Capsaicin ; Conditioning, Classical/*physiology ; Ibotenic Acid ; Lithium Chloride/toxicity ; Male ; Mental Recall/*physiology ; Pons/*physiology ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/*physiology ; Taste/*physiology ; Trigeminal Nerve/physiology ; }, abstract = {Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning.}, } @article {pmid9513975, year = {1998}, author = {Kassil', VG and Bondarenko MYu, and Mikhailenko, VA}, title = {Conditioned reflex responses of the sympathetico-adrenal system to an aversive taste stimulus.}, journal = {Neuroscience and behavioral physiology}, volume = {28}, number = {1}, pages = {31-37}, pmid = {9513975}, issn = {0097-0549}, mesh = {Adrenal Glands/*physiology ; Animals ; Avoidance Learning/*physiology ; Catecholamines/urine ; Conditioning, Classical/*physiology ; Female ; Male ; Rats ; Rats, Wistar ; Reinforcement, Psychology ; Sex Factors ; Sympathetic Nervous System/*physiology ; Taste/*physiology ; }, abstract = {Studies were carried out on male and female rats in which the effects of isolated presentation of a conditioned stimulus (a saccharine solution) to which the animals had previously developed conditioned reflex taste aversion (RTA) on the level of urinary catecholamine secretion were determined. The studies showed that presentation of an aversive taste stimulus without reinforcement by a negative stimulus increased the levels of urinary adrenaline, noradrenaline, and dopamine secretion; this repeated, albeit more weakly, the effects of the negative reinforcement (angular acceleration) used for development of RTA. After presentation of the isolated aversive taste stimulus, the greatest increase in catecholamine excretion affected adrenaline, which indicates an anxiety state (fear). There was also a significant increase in noradrenaline excretion in these conditions. The accompanying increase in dopamine excretion in experimental and control animals showed this change to be largely nonspecific in nature, and to result from the experimental procedures. Isolated presentation of the conditioned taste stimulus elicited significantly greater increases in urinary catecholamine excretion in males than in females. It is suggested that the time for which the RTA is retained could be increased by activation of the sympathetico-adrenal system resulting from presentation of the nonreinforced taste stimulus which had acquired aversive properties.}, } @article {pmid9512067, year = {1998}, author = {Etkind, SA and Fantegrossi, WE and Riley, AL}, title = {Cocaine and alcohol synergism in taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {59}, number = {3}, pages = {649-655}, doi = {10.1016/s0091-3057(97)00476-0}, pmid = {9512067}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/administration & dosage/*pharmacology ; Cocaine/administration & dosage/analogs & derivatives/blood/*pharmacology ; Dopamine Uptake Inhibitors/blood ; Drug Synergism ; Ethanol/administration & dosage/*pharmacology ; Female ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Narcotics/administration & dosage/*pharmacology ; Rats ; }, abstract = {Female Long-Evans rats were given 20-min access to saccharin followed by injections of alcohol and cocaine, alone and in combination. Although there was no significant interaction between alcohol and cocaine when cocaine was given intraperitoneally (IP), aversions induced by the drug combination when cocaine was administered subcutaneously (SC) were significantly greater than those induced by either drug alone. Further, the aversions induced by the combination were significantly greater than the summed effects of the individual drugs administered alone, indicating a synergistic interaction between cocaine and alcohol. It was suggested that this synergism might result from a summation of the effects of alcohol, cocaine, and cocaethylene, a unique and toxic metabolite of cocaine produced when alcohol is coadministered. To assess the role of cocaethylene in the present design, additional taste aversion assessments were performed in which saccharin was paired with either IP or SC injections of cocaethylene. Although cocaethylene was found to induce aversions, the summed changes in consumption from baseline produced by cocaine, alcohol, and cocaethylene were significantly less than the changes produced by cocaine and alcohol in combination. These results indicate that the synergistic interaction between cocaine and alcohol in the present design cannot be attributed solely to summation of the effects of the individual drugs and the metabolite cocaethylene. Additional mechanisms by which cocaethylene might contribute to the synergistic interaction between cocaine and alcohol, as well as the role pharmacokinetic interactions between cocaine and alcohol might have in the interaction, were discussed.}, } @article {pmid9493864, year = {1998}, author = {Flynn, FW and Smith, ME}, title = {Lateral ventricular injections of the NK3 agonist senktide affect salt taste-elicited responses.}, journal = {Peptides}, volume = {19}, number = {2}, pages = {319-324}, doi = {10.1016/s0196-9781(97)00374-4}, pmid = {9493864}, issn = {0196-9781}, support = {DK50586/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/drug effects/physiology ; Avoidance Learning ; Conditioning, Psychological ; Injections, Intraventricular ; Lithium Chloride ; Male ; Peptide Fragments/*administration & dosage ; Rats ; Receptors, Neurokinin-3/*agonists/physiology ; Sodium Chloride ; Substance P/administration & dosage/*analogs & derivatives ; Taste/*drug effects/*physiology ; }, abstract = {Central injections of the selective tachykinin NK3 receptor agonist senktide (SENK) suppresses salt appetite. Also, following SENK, intraoral infusions of hypertonic NaCl elicit fewer ingestive taste reactivity responses and more aversive responses than following intraventricular injections of isotonic saline. This pattern of taste reactivity results suggest that SENK affects the oral stimulating properties of salt taste. Before accepting this interpretation, however, alternative explanations need to be examined. The following experiments evaluated whether the effects of intraventricular SENK injection on taste reactivity could be due to: 1) a general oral motor impairment that reduces ingestive responding to tastes (Experiment 1) or; 2) SENK having aversive consequences (Experiment 2). In Experiment 1, the effects of intraventricular injections of SENK (200 ng) on taste reactivity responses to 0.5 M NaCl and 0.1 M sucrose were measured in sodium deficient rats. Intraoral infusions of 0.5 M NaCl elicited fewer ingestive taste reactivity responses following SENK than injections of isotonic saline in sodium deficient rats. Sucrose continued to elicit the same high number of ingestive taste reactivity responses following intraventricular injections of isotonic saline and SENK. Thus, SENK did not cause a general decrease in ingestive responding. A conditioned taste aversion test was employed in Experiment 2 to determine if SENK had aversive consequences. Rats were given 30 min access to alanine (0.3 M) and were then administered either lithium chloride (LiCl) or intraventricular injections of SENK (200 ng) on three consecutive days. Rats avoided alanine that was paired with LiCl, but those rats that had alanine paired with SENK showed no avoidance of the taste even after three pairings. These results replicate findings that intraventricular injections of the NK3 agonist SENK decreases the palatability of NaCl (as measured by taste reactivity) and suggest that its effect on NaCl-elicited taste reactivity is not due to the treatment causing a motor impairment or malaise.}, } @article {pmid9487062, year = {1997}, author = {Kassil', VG and Vataeva, LA and Makukhina, GV}, title = {[The role of the vagus nerves in the manifestations of neophobia and conditioned-reflex taste aversion].}, journal = {Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova}, volume = {83}, number = {9}, pages = {1-11}, pmid = {9487062}, issn = {0869-8139}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Male ; Phobic Disorders/*physiopathology ; Rats ; Rats, Wistar ; Saccharin ; Taste/*physiology ; Time Factors ; Vagotomy ; Vagus Nerve/*physiology ; }, abstract = {Vagotomized rats given a choice between water and an unfamiliar 0.2% saccharin solution ingest comparable amounts of both fluids over 2.5 weeks of testing. Saccharin intake in sham-operated rats grows steadily (attenuation of taste neophobia), with water intake being unchanged. After the pairing of water intake with rotation saccharin intake in vagotomized rats grows and in sham-operated animals decreases significantly, whereas water intake in the latter increases sharply. Thus, the rats with retained vagal innervation exhibit aversion to saccharin, substance with an unfamiliar taste, but not to water paired with a discomfort. After two-week elimination of neophobia to saccharin, the pairing of water intake with rotation brings into the acquisition of aversion to water in the first days of choice testing in sham-operated rats; similar aversion in vagotomized rats appears with retardation (on the 4th to 6th day).}, } @article {pmid9486472, year = {1998}, author = {Gallo, M and Bielavska, E and Roldán, G and Bures, J}, title = {Tetrodotoxin inactivation of the gustatory cortex disrupts the effect of the N-methyl-D-aspartate antagonist ketamine on latent inhibition of conditioned taste aversion in rats.}, journal = {Neuroscience letters}, volume = {240}, number = {2}, pages = {61-64}, doi = {10.1016/s0304-3940(97)00897-5}, pmid = {9486472}, issn = {0304-3940}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cerebral Cortex/*drug effects/physiology ; Conditioning, Psychological/drug effects ; Female ; Injections, Intraperitoneal ; Ketamine/*administration & dosage ; Male ; N-Methylaspartate/*antagonists & inhibitors ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Tetrodotoxin/*administration & dosage ; }, abstract = {The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine on latent inhibition of taste aversion learning was studied in rats. Systemic injections of ketamine (50 mg/kg) applied after each of three preexposures to sodium saccharin (0.1%) disrupted the latent inhibition effect. The blockade was not due to aversive properties of ketamine, because three saccharin-ketamine pairings did not produce saccharin aversion. Moreover, the ketamine-induced blockade of latent inhibition was disrupted by tetrodotoxin injections (10 ng/microl)-induced reversible inactivation of gustatory cortex, applied after each preexposure. A specific gustatory cortex mediation of the ketamine effect is discussed.}, } @article {pmid9476985, year = {1998}, author = {Smith, JK and Neill, JC and Costall, B}, title = {The influence of postweaning housing conditions on drug-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {59}, number = {2}, pages = {379-386}, doi = {10.1016/s0091-3057(97)00370-5}, pmid = {9476985}, issn = {0091-3057}, mesh = {Animals ; Antimanic Agents/pharmacology ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/pharmacology ; Central Nervous System Stimulants/pharmacology ; Dose-Response Relationship, Drug ; Female ; Housing, Animal ; Lithium Chloride/pharmacology ; Narcotics/pharmacology ; Psychotropic Drugs/*pharmacology ; Rats ; Social Isolation/*psychology ; Substance-Related Disorders ; Taste/*drug effects ; }, abstract = {Postweaning social isolation can influence the sensitivity of rats to several effects of drugs of abuse. The present study investigated the influence of postweaning housing conditions on the sensitivity of rats to the aversive effects of a number of psychoactive agents using a conditioned taste aversion (CTA) test procedure. Development of a CTA was assessed by pairing administration of the drug with the consumption of a 0.05% (weight/volume) saccharin solution in water-deprived (18 h) rats in a 20 min drinking period. Saccharin consumption was then measured in 20 min test sessions over the next 4 consecutive days. Consumption of saccharin solution was significantly reduced in both isolated and enriched rats following administration of d-amphetamine (2 mg/kg), cocaine (30 mg/kg), morphine (10 mg/kg), nicotine (1.0 mg/kg), caffeine (20 mg/kg), alcohol (1.5 g/kg), and LiCl (0.15 M, 4 ml/kg). There was no significant effect of housing conditions on the CTA induced by cocaine, nicotine, alcohol, or LiCl; however, isolation-reared rats were found to be less sensitive to the aversive effects of d-amphetamine, morphine, and caffeine in this paradigm. These results suggest that rearing rats in social isolation induces an attenuation in sensitivity to the aversive effects of some psychoactive agents.}, } @article {pmid9473708, year = {1998}, author = {Escobar, ML and Chao, V and Bermúdez-Rattoni, F}, title = {In vivo long-term potentiation in the insular cortex: NMDA receptor dependence.}, journal = {Brain research}, volume = {779}, number = {1-2}, pages = {314-319}, doi = {10.1016/s0006-8993(97)01175-x}, pmid = {9473708}, issn = {0006-8993}, mesh = {Amygdala/drug effects/*physiology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Electric Stimulation ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/drug effects/physiology ; *Long-Term Potentiation ; Male ; Neural Pathways/drug effects/physiology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology ; Temporal Lobe/drug effects/*physiology ; Tetany ; }, abstract = {It has been demonstrated that the insular cortex (IC) plays an important role in the acquisition and storage of different aversive motivated learning tasks like conditioned taste aversion, spatial maze and inhibitory avoidance. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here, we address this issue by examining the induction of synaptic plasticity, long-term potentiation (LTP) in in vivo preparations. The results showed that high frequency stimulation of the basolateral amygdaloid nucleus (Bla) induced LTP in the IC. The LTP induced by tetanus was blocked by application of the N-methyl-D-aspartate (NMDA) receptor antagonists CPP and MK-801, indicating that NMDA receptors were responsible for its induction. These results suggest that in vivo tetanus induced LTP of the Bla-IC projection is a possible mechanism for the memory-related functions performed by the IC.}, } @article {pmid9458925, year = {1998}, author = {Thiele, TE and van Dijk, G and Yagaloff, KA and Fisher, SL and Schwartz, M and Burn, P and Seeley, RJ}, title = {Central infusion of melanocortin agonist MTII in rats: assessment of c-Fos expression and taste aversion.}, journal = {The American journal of physiology}, volume = {274}, number = {1}, pages = {R248-54}, doi = {10.1152/ajpregu.1998.274.1.R248}, pmid = {9458925}, issn = {0002-9513}, support = {AA-07455/AA/NIAAA NIH HHS/United States ; DC-00248/DC/NIDCD NIH HHS/United States ; DK-17844/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Amygdala/drug effects/*physiology ; Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Cerebral Ventricles/drug effects/*physiology ; Feeding Behavior/*drug effects ; Infusions, Parenteral ; Leptin ; Male ; Melanocyte-Stimulating Hormones/*agonists ; Obesity ; Paraventricular Hypothalamic Nucleus/drug effects/*physiology ; Proteins/administration & dosage/*pharmacology ; Proto-Oncogene Proteins c-fos/*biosynthesis ; Rats ; Saccharin/administration & dosage/pharmacology ; *Taste ; alpha-MSH/*analogs & derivatives/pharmacology ; }, abstract = {Like leptin (OB protein), central infusion of the nonspecific melanocortin agonist MTII reduces food intake for relatively long periods of time (i.e., 12 h; W. Fan, B. A. Boston, R. A. Kesterson, V. J. Hruby, and R. D. Cone, Nature; 385: 165-168, 1997). To test the hypothesis that MTII may influence ingestive behavior via mechanisms similar to those that mediate the effects of leptin, we infused a single dose of MTII into the third ventricle (i3vt) of Long-Evans rats and examined three dependent measures that have been studied following i3vt infusion of leptin: 1) effects on long-term food intake and body weight (48 h), 2) patterns of c-Fos expression in the brain, and 3) conditioned taste aversion learning. Similar to leptin, MTII reduced 48-h food intake (1.0 nmol dose), reduced body weight at 24 and 48 h (0.1 and 1.0 nmol doses, respectively), and induced c-Fos expression in the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala. In contrast to leptin, MTII was found to produce conditioned taste aversions. These results are consistent with the hypothesis that MTII may influence regulatory behavior via mechanisms similar to those that mediate the effects of leptin.}, } @article {pmid9458894, year = {1998}, author = {McMahon, LR and Wellman, PJ}, title = {PVN infusion of GLP-1-(7-36) amide suppresses feeding but does not induce aversion or alter locomotion in rats.}, journal = {The American journal of physiology}, volume = {274}, number = {1}, pages = {R23-9}, doi = {10.1152/ajpregu.1998.274.1.R23}, pmid = {9458894}, issn = {0002-9513}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cerebral Ventricles/drug effects/physiology ; Drinking Behavior/drug effects ; Feeding Behavior/*drug effects ; Gastrointestinal Hormones/pharmacology ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptides ; Infusions, Parenteral ; Male ; Motor Activity/*drug effects ; Paraventricular Hypothalamic Nucleus/drug effects/*physiology ; Peptide Fragments/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Stereotaxic Techniques ; Stereotyped Behavior/drug effects ; Time Factors ; }, abstract = {Intracerebroventricular infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) reduces feeding in rats, an effect that could be localized to the hypothalamic paraventricular nucleus (PVN). Intracerebroventricular GLP-1, however, may also induce conditioned taste aversion (CTA), thereby putting into question the specificity of the action of GLP-1 on feeding. The present experiments evaluated the action of PVN GLP-1 (0, 100, or 200 ng) on induction of CTA, on locomotion, and finally, on feeding and drinking in rats. PVN infusion of GLP-1 (100 or 200 ng) did not support the induction of CTA and did not reliably alter locomotion, but did suppress feeding and drinking. The present study suggests that GLP-1 infusions into the PVN reduce food and water intake without producing illness or disrupting locomotor behavior. These data, in conjunction with reports of increased feeding following antagonism of central GLP-1 receptors, support the notion that endogenous GLP-1, perhaps within the PVN, functions to suppress feeding in the rat.}, } @article {pmid9443533, year = {1998}, author = {Parker, LA and Limebeer, CL and Simpson, GR}, title = {Chlordiazepoxide-induced conditioned place and taste aversion learning in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {59}, number = {1}, pages = {33-37}, doi = {10.1016/s0091-3057(97)00333-x}, pmid = {9443533}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlordiazepoxide/*pharmacology ; Choice Behavior/*drug effects ; Conditioning, Operant/*drug effects ; Cues ; Male ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {The hedonic properties of chlordiazepoxide (CDP) were examined using the place conditioning and the taste conditioning paradigms. Following four conditioning trials, CDP (5-20 mg/kg) produced a conditioned place aversion in an "unbiased" paradigm in which the chamber paired with CDP was counterbalanced among two equally preferred chambers. In a "biased" place-conditioning paradigm, CDP (5 and 20 mg/ kg) prevented the dissipation of the natural aversion to the nonpreferred chamber. Finally, although CDP unconditionally potentiated sucrose consumption, it produced a sucrose aversion in the taste reactivity test and sucrose avoidance in the taste avoidance test when the taste conditionally preceded injections of CDP. The pattern of findings suggest that, when novel to rats, CDP is hedonically aversive.}, } @article {pmid9442819, year = {1997}, author = {Ikeda, T and Takahashi, M}, title = {Active posture control during experimental motion sickness in guinea-pigs.}, journal = {Acta oto-laryngologica}, volume = {117}, number = {6}, pages = {815-818}, doi = {10.3109/00016489709114206}, pmid = {9442819}, issn = {0001-6489}, mesh = {Animals ; Guinea Pigs ; Motion Sickness/*physiopathology ; Postural Balance/physiology ; Posture/*physiology ; Rotation ; }, abstract = {This study evaluated active posture control in guinea-pigs under motion sickness stimulation. Twelve guinea-pigs, which received training to stay on a moving perch, were divided into two groups: a motion sickness stimulation group and a control group. The motion sickness group was given a combined stimulation of turntable rotation and optokinetic drum rotation, and the control group was given turntable stimulation alone. Motion sickness was evaluated by conditioned taste aversion to saccharin solution. Active posture control was evaluated by the angle of nose tip displacement and the staying duration (length of time that guinea-pigs stayed on the turntable). The consumption of saccharin solution increased in the control group but did not increase in the motion sickness group. The motion sickness group showed a significant increase in the mean angle of nose tip displacement and a significant decrease in the staying duration on the turntable. These results indicate that active posture control was disturbed by motion sickness stimulation.}, } @article {pmid9426837, year = {1998}, author = {Bedingfield, JB and Holloway, FA}, title = {Methylnaltrexone attenuates taste aversion conditioned by low-dose ethanol.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {15}, number = {1}, pages = {51-54}, doi = {10.1016/s0741-8329(97)00097-9}, pmid = {9426837}, issn = {0741-8329}, support = {5T32 AA07222/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Chromatography, Gas ; *Conditioning, Psychological ; Ethanol/*administration & dosage/blood ; Kinetics ; Naltrexone/*analogs & derivatives/pharmacology ; Narcotic Antagonists/*pharmacology ; Quaternary Ammonium Compounds ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Previous research has shown that activation of a subset of peripheral opioid receptors located in the gut produce aversive effects as measured in the place and taste conditioning (CTA) paradigms. Endogenous opioid activity and tetrahydroisoquinolines (TIQs) are stimulated or formed after ethanol (EtOH) administration and both are known to activate opioid receptors. We therefore examined the hypothesis that a portion of the aversive effects of EtOH may be mediated through peripheral opioid receptors, activated by EtOH-induced opioids or TIQs. EtOH CTAs were slightly attenuated when animals were pretreated with the putative peripheral opioid receptor antagonist methylnaltrexone. By itself MNTX did not condition a taste preference or aversion. However, blood EtOH levels (BELs) in animals pretreated with MNTX were lower than those of saline-pretreated subjects, an effect that just reached statistical significance and was not present at specific EtOH doses. The results indicate that a portion of the aversive conditioning effects of EtOH (using a two-bottle CTA paradigm) may be receptor-mediated effects, exerted by an action on peripheral opioid receptors, but the specific mechanism of attenuation is unclear.}, } @article {pmid9423965, year = {1998}, author = {Exton, MS and Von Hörsten, S and Vöge, J and Westermann, J and Schult, M and Nagel, E and Schedlowski, M}, title = {Conditioned taste aversion produced by cyclosporine A: concomitant reduction in lymphoid organ weight and splenocyte proliferation.}, journal = {Physiology & behavior}, volume = {63}, number = {2}, pages = {241-247}, doi = {10.1016/s0031-9384(97)00432-0}, pmid = {9423965}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cell Division/drug effects ; Conditioning, Classical/*drug effects ; Cyclosporine/*toxicity ; Immunosuppressive Agents/*toxicity ; Lymphocyte Subsets/drug effects/immunology ; Male ; Organ Size/drug effects ; Rats ; Saccharin/pharmacology ; Spleen/cytology/*drug effects/immunology ; Sweetening Agents/pharmacology ; Taste/*drug effects/immunology ; Thymus Gland/drug effects ; }, abstract = {The classical conditioning of immune parameters is commonly conducted within a conditioned taste aversion (CTA) paradigm. In this study, the immunosuppressive drug cyclosporine A (CsA) was investigated for its ability to produce both taste aversion to a novel stimulus and conditioned alterations in immune functioning. The paradigm comprised the pairing of a 0.2% saccharin solution (the conditioned stimulus; CS) with an intraperitoneal injection of 20 mg/kg CsA (the unconditioned stimulus; UCS). Upon saccharin re-presentation, a marked reduction in fluid consumption was observed, indicating aversion to the novel substance (=CTA). By using a single CsA/saccharin pairing the CTA lasted for one CS representation. However, by implementing three pairings, this effect could be extended for up to seven representations. No noticeable difference was recorded by adjusting the saccharin representation from every consecutive day to every second day. The most effective paradigm in creating CTA was subsequently investigated for its effectiveness in producing conditioned immune alterations. Animals were killed on the day of the third CS re-presentation, and immune functions assessed. Conditioned animals displayed a significant reduction in thymus and spleen weights. Effects on the spleen were further investigated, revealing a significantly reduced proliferative ability of isolated splenocytes to concanavalin A. These results demonstrate that the physiological effects produced by CsA are sufficiently salient to elicit CTA. Furthermore, the reduction in lymphoid organ weight and splenocyte proliferation induced by CsA are also conditionable using this paradigm.}, } @article {pmid9404941, year = {1997}, author = {Krivanek, J}, title = {Protein kinase C in the parabrachial nucleus of rats during conditioned taste aversion induced by amphetamine.}, journal = {Neuroscience letters}, volume = {236}, number = {1}, pages = {17-20}, doi = {10.1016/s0304-3940(97)00737-4}, pmid = {9404941}, issn = {0304-3940}, mesh = {Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Male ; Pons/*drug effects/enzymology ; Protein Kinase C/*metabolism ; Rats ; Taste/*physiology ; }, abstract = {D-Amphetamine (AM) is a potent inducer of conditioned taste aversion (CTA) the mechanism of which differs from that induced by lithium. The aim of the present communication is to see whether AM-induced CTA will produce shift in the protein kinase (PKC) activity in the parabrachial nucleus (PBN). Activity of PKC was measured in PBN of rats during AM-induced CTA. In the control experiments a single intraperitoneal (i.p.) injection of AM (3 mg/kg) alone (not paired with saccharin drinking) resulted in rise of particulate bound PKC by 77% and a tendency to decrease its activity in cytosol 60 min but not 24 and 48 h after AM administration. The results suggest translocation of the enzyme from cytosol to membrane. Cytosolic PKC increased by 17 and 50%, 24 and 48 h, respectively, after acquisition of CTA (15 min after the retrieval test), when the direct effect of AM on PKC had already disappeared. Particulate PKC did not change at either of the two time intervals. Thus the total PKC activity was increased. Since we have previously observed the same PKC shifts using LiCl or CuSO4 as CTA unconditioned stimuli, we assume that any CTA inducer will elicit the same alteration of PKC in PBN.}, } @article {pmid9404622, year = {1997}, author = {Touzani, K and Taghzouti, K and Velley, L}, title = {Increase of the aversive value of taste stimuli following ibotenic acid lesion of the central amygdaloid nucleus in the rat.}, journal = {Behavioural brain research}, volume = {88}, number = {2}, pages = {133-142}, doi = {10.1016/s0166-4328(96)02273-5}, pmid = {9404622}, issn = {0166-4328}, mesh = {Amygdala/drug effects/*physiology ; Animals ; Avoidance Learning/*physiology ; Body Weight ; Conditioning, Psychological/physiology ; Drinking ; Ibotenic Acid/*toxicity ; Male ; Quinine/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reward ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {Male Sprague-Dawley rats received bilateral ibotenic acid lesions of the central amygdaloid nucleus (CeA) and were compared to sham-lesioned rats in their response to different concentrations of saccharin and quinine solutions. In two-bottle choice test situation, the lesioned rats exhibited a lower saccharin preference at concentrations of 2.5; 7.5 and 25 mM, while their aversion towards quinine and the highest concentration of saccharin (50 mM) was increased. In a one-bottle test, the lesioned rats showed consistent decreases in their consumption of 2.5 and 7.5 mM saccharin solutions whereas their intake of 0.9 mM solution of saccharin was equal to that of the sham-lesioned rats. The lesion of the CeA had no significant effects on the acquisition of conditioned taste aversion. There was less postoperative weight gain in lesioned rats as compared to sham-lesioned animals but the lesion had no significant effect on daily water intake. These findings suggest that the CeA plays an important role in the normal response to exteroceptive food stimuli via modulation of the aversive value of taste stimuli. The results are discussed in the context of an interaction between the CeA and the lateral hypothalamus (LH) in the modulation of palatability and feeding behavior.}, } @article {pmid9401710, year = {1997}, author = {Gallo, M and Valouskova, V and Cándido, A}, title = {Fetal hippocampal transplants restore conditioned blocking in rats with dorsal hippocampal lesions: effect of age.}, journal = {Behavioural brain research}, volume = {88}, number = {1}, pages = {67-74}, doi = {10.1016/s0166-4328(97)02311-5}, pmid = {9401710}, issn = {0166-4328}, mesh = {Aging/*psychology ; Animals ; Conditioning, Operant/*physiology ; Female ; Fetal Tissue Transplantation/*physiology ; Hippocampus/anatomy & histology/*physiology/*transplantation ; Male ; Nerve Regeneration/physiology ; Pregnancy ; Rats ; Rats, Wistar ; Taste/physiology ; }, abstract = {Previous studies have shown that conditioned blocking of taste aversion learning in 3-month-old Wistar rats depends on the hippocampal system integrity. Thus, the aim was to demonstrate that enough connectivity would develop after a graft to support the attention mechanism required for conditioned blocking. In the first experiment, bilateral homotopic grafts of 16-17 day-old hippocampal fetal tissue applied to 3-month-old male Wistar rats after electrolytical lesions of the dorsal hippocampus reinstated conditioned blocking tested 5 months after the transplantation. Unexpectedly, an early age-dependent impairment of conditioned blocking, similar to that induced by hippocampal lesions, was found in the 8-month-old control group. This finding was further supported by the results of the second experiment. Non-operated 3-month-old but not 8-month-old Wistar rats showed conditioned blocking. The results are discussed in terms of early hippocampal vulnerability, prevented by fetal grafts.}, } @article {pmid9394123, year = {1997}, author = {Orr, TE and Walters, PA and Elkins, RL}, title = {Differences in free-choice ethanol acceptance between taste aversion-prone and taste aversion-resistant rats.}, journal = {Alcoholism, clinical and experimental research}, volume = {21}, number = {8}, pages = {1491-1496}, pmid = {9394123}, issn = {0145-6008}, support = {AA06465/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*genetics/physiopathology ; Alcoholism/genetics/physiopathology ; Animals ; Avoidance Learning/*physiology ; Choice Behavior/*physiology ; Conditioning, Classical/*physiology ; Cyclophosphamide/toxicity ; Female ; *Genotype ; Individuality ; Male ; Pregnancy ; Rats ; Rats, Inbred Strains ; Selection, Genetic ; Species Specificity ; Taste/*genetics ; }, abstract = {Taste aversion (TA)-prone (TAP) and TA-resistant (TAR) rats were tested for naive, nonforced acceptance of ethanol. Ethanol acceptance had played no role in line development. Rather, the lines had been developed via bidirectional, nonsibling matings based on susceptibility to develop cyclophosphamide-induced conditioned TAs to a 0.1% saccharin solution (at cyclophosphamide doses of 12.5 mg/kg for males and 15.0 mg/kg for females, i.p.). Rats from the 23rd selectively bred generations, with no prior exposure to ethanol, were given 24-hr access to a two-bottle choice between plain tap water and a solution of ethanol in water. Rats were initially given access to 1% ethanol in water, and the ethanol concentration was increased by 1% every 3 days to a maximum of 10%. Ethanol consumption (g ethanol consumed/kg body weight) and preference scores (volume ethanol solution consumed/total fluid intake) were determined by daily bottle weighings. At 1% ethanol concentration, there were no differences between the rat lines in terms of ethanol consumption or preference. At concentrations of 2 to 10%, TAP rats consumed less ethanol and showed a decreased preference for the ethanol solutions than TAR rats. Maximum ethanol consumption was reached at the 6% concentration for both lines. The mean (+/- SE) values of consumption at 6% ethanol were 1.8 (+/- 0.8) and 5.6 (+/- 0.5) g of ethanol/kg body weight for TAP and TAR rats, respectively. Mean (+/- SE) preference scores at 6% ethanol were 26 (+/- 12) and 76 (+/- 6) for TAP and TAR rats, respectively. These findings indicate that differences in TA conditionability may be associated with the propensity of rats to be high or low consumers of ethanol. Based on these data, it is hypothesized that high susceptibility for TA conditionability may deter many individuals from consuming the high levels of ethanol that usually precede alcohol tolerance and dependence.}, } @article {pmid9394117, year = {1997}, author = {Overstreet, DH and McArthur, RA and Rezvani, AH and Post, C}, title = {Selective inhibition of alcohol intake in diverse alcohol-preferring rat strains by the 5-HT2A antagonists amperozide and FG 5974.}, journal = {Alcoholism, clinical and experimental research}, volume = {21}, number = {8}, pages = {1448-1454}, pmid = {9394117}, issn = {0145-6008}, mesh = {Alcohol Drinking/*genetics/physiopathology ; Alcoholism/*genetics/physiopathology ; Animals ; Consummatory Behavior/drug effects ; Dose-Response Relationship, Drug ; *Motivation ; Nicotinic Acids/*pharmacology ; Piperazines/*pharmacology ; Rats ; Rats, Inbred Strains ; Receptor, Serotonin, 5-HT2A ; Receptors, Serotonin/drug effects/*genetics/physiology ; Selection, Genetic ; Serotonin Antagonists/*pharmacology ; }, abstract = {The present studies sought to elucidate the role of 5-HT2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol-preferring rats: P, Alko Alcohol (AA), and Fawn-Hooded (FH). Both amperozide and FG 5974 have 5-HT2A receptor antagonist properties, but FG 5974 also shows presynaptic 5-HT1A receptor agonist activity. After establishment of stable baselines for intake measures in a two-bottle continuous access paradigm, rats (n = 10) were injected with 1 of 5 doses (0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose-dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose-dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5-HT2A receptor antagonism (e.g., 5-HT1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.}, } @article {pmid9361334, year = {1997}, author = {Berendsen, HH and Broekkamp, CL}, title = {Indirect in vivo 5-HT1A-agonistic effects of the new antidepressant mirtazapine.}, journal = {Psychopharmacology}, volume = {133}, number = {3}, pages = {275-282}, doi = {10.1007/s002130050402}, pmid = {9361334}, issn = {0033-3158}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Amphetamines/pharmacology ; Animals ; Antidepressive Agents, Tricyclic/*pharmacology ; Behavior, Animal/drug effects ; Conditioning, Operant/drug effects ; Fluoxetine/pharmacology ; Male ; Mianserin/*analogs & derivatives/pharmacology ; Mice ; Mice, Inbred ICR ; Mirtazapine ; Pyrazines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin/*drug effects ; Serotonin Receptor Agonists/*pharmacology ; Serotonin Uptake Inhibitors/pharmacology ; Taste/drug effects ; }, abstract = {The new antidepressant mirtazapine was tested in two experimental procedures which can reveal direct or indirect 5-HT1A receptor agonistic effects. These procedures were observation for induction of lower lip retraction in rats and comparison of stimulus properties in cross-familiarization experiments with conditioned taste aversion in mice. Mirtazapine induced lower lip retraction in rats, as did the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). However, the response to mirtazapine at doses up to 22 mg/kg remained below the maximum score obtained with 8-OH-DPAT (0.46 mg/kg). Blockade of the 5-HT1A receptors with pindolol (10 mg/kg) caused a strong reduction of the lower lip retraction induced both with mirtazapine and 8-OH-DPAT. In the cross-familiarization conditioned taste aversion experiments it was found that the conditioned taste aversion induced by mirtazapine (0.32 mg/kg) could be prevented if the mice were pre-exposed to injections with mirtazapine (0.22 and 0.46 mg/kg), 8-OH-DPAT (0.22 and 0.46 mg/kg) and after pre-exposure to the 5-HT reuptake inhibitor fluoxetine (22 mg/kg). No familiarization for the mirtazapine stimulus was obtained by pre-exposure to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) (0.46-4.6 mg/kg) and MK212 (2.2-22 mg/kg), being agonists for the 5-HT2A and 5-HT2C receptors, respectively. With the reversed sequence, the conditioned taste aversion induced by 8-OH-DPAT (0.22 mg/kg), DOI (1.0 mg/kg) and fluoxetine could be prevented only partially by pre-exposure to mirtazapine in a dose of 1 mg/kg. The conditioned taste aversion induced by MK 212 (4.6 mg/kg) was not affected by pre-exposure to mirtazapine (0.1-1.0 mg/kg). On the basis of these results, it can be concluded that mirtazapine has indirect 5-HT1A receptor agonistic properties which may play an important role in the therapeutic effect of this compound.}, } @article {pmid9335080, year = {1997}, author = {Wegener, G and Smith, DF and Rosenberg, R}, title = {5-HT1A receptors in lithium-induced conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {133}, number = {1}, pages = {51-54}, doi = {10.1007/s002130050370}, pmid = {9335080}, issn = {0033-3158}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Body Temperature/drug effects ; Feeding Behavior/*drug effects ; Lithium/*pharmacology ; Male ; Pindolol/pharmacology ; Rats ; Receptors, Serotonin/drug effects/*physiology ; Receptors, Serotonin, 5-HT1 ; Saccharin ; *Taste ; }, abstract = {Experiments were carried out using rats to investigate whether 5-HT1A neural mechanisms are involved in lithium-induced conditioned taste aversion (CTA). We found that the 5-HT1A antagonists p-MPPI and pindolol caused CTA similar to that produced by LiCl. The 5-HT1A agonist 8-OH-DPAT counteracted lithium-induced CTA. Pindolol dose-dependently abolished effects of 8-OH-DPAT on LiCl-induced CTA. These findings support the notion that lithium has antagonistic actions on 5-HT1A receptors. Inhibition of 5-HT synthesis by PCPA failed, however, to prevent lithium-induced CTA. Evidently, mechanisms other than those governed solely by 5-HT are also involved in lithium-induced CTA.}, } @article {pmid9334416, year = {1997}, author = {Lamprecht, R and Hazvi, S and Dudai, Y}, title = {cAMP response element-binding protein in the amygdala is required for long- but not short-term conditioned taste aversion memory.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {17}, number = {21}, pages = {8443-8450}, pmid = {9334416}, issn = {0270-6474}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/physiology ; Cyclic AMP Response Element-Binding Protein/genetics/*physiology ; Gene Expression Regulation/physiology ; Image Processing, Computer-Assisted ; Lithium Chloride/toxicity ; Male ; Memory/drug effects/*physiology ; Memory, Short-Term/drug effects/physiology ; Mental Recall/physiology ; Microinjections ; Nerve Tissue Proteins/*physiology ; Oligonucleotides, Antisense/administration & dosage/pharmacology ; Rats ; Rats, Wistar ; Saccharin ; Taste/*physiology ; }, abstract = {In conditioned taste aversion (CTA) organisms learn to avoid a taste if the first encounter with that taste is followed by transient poisoning. The neural mechanisms that subserve this robust and long-lasting association of taste and malaise have not yet been elucidated, but several brain areas have been implicated in the process, including the amygdala. In this study we investigated the role of amygdala in general, and the cAMP response element-binding protein (CREB) in the amygdala in particular, in CTA learning and memory. Toward that end, we combined antisense technology in vivo with behavioral, molecular, and histochemical analysis. Local microinjection of phosphorothioate-modified oligodeoxynucleotides (ODNs) antisense to CREB into the rat amygdala several hours before CTA training transiently reduced the level of CREB protein during training and impaired CTA memory when tested 3-5 d later. In comparison, sense ODNs had no effect on memory. The effect of antisense was not attributable to differential tissue damage and was site-specific. CREB antisense in the amygdala had no effect on retrieval of CTA memory once it had been formed, and did not affect short-term CTA memory. We propose that the amygdala, specifically the central nucleus, is required for the establishment of long-term CTA memory in the behaving rat; that the process involves long-term changes, subserved by CRE-regulated gene expression, in amygdala neurons; and that the amygdala may retain some CTA-relevant information over time rather than merely modulating the gustatory trace during acquisition of CTA.}, } @article {pmid9333218, year = {1997}, author = {Racotta, IS and Arzuffi, R and Garduño, I and Racotta, R}, title = {Antiemetic inhibits conditioned taste aversion, but not the hypophagia induced by epinephrine.}, journal = {Physiology & behavior}, volume = {62}, number = {5}, pages = {1189-1191}, doi = {10.1016/s0031-9384(97)00190-x}, pmid = {9333218}, issn = {0031-9384}, mesh = {Animals ; Antiemetics/*pharmacology ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Benzamides/*pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Epinephrine/*pharmacology ; Injections, Intraperitoneal ; Male ; Motivation ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {It has been shown that relatively high doses of epinephrine (E) injected intraperitoneally (IP) produce hypophagia and conditioned taste aversion (CTA) in rats. We examined the possibility that E effects involve malaise. For this purpose, changes in saccharin preference induced by E injected IP (100 microg/kg) were determined after a previous administration of trimethobenzamide (TMB, 5 mg/kg), an antiemetic agent. E alone decreased saccharin preference by 54% (p < 0.01), but only by 16% (not significant) in the presence of TMB. In contrast, the injection of 75 or 100 microg/kg E reduced food intake by 50 and 85%, respectively (p < 0.01), regardless of previous injection of TMB. In conclusion, the results suggest that E-induced malaise is not the direct cause of the hypophagia it elicits.}, } @article {pmid9322260, year = {1997}, author = {Aguado, L and del Valle, R and Pérez, L}, title = {The NMDA-receptor antagonist ketamine as an unconditioned stimulus in taste aversion learning.}, journal = {Neurobiology of learning and memory}, volume = {68}, number = {2}, pages = {189-196}, doi = {10.1006/nlme.1997.3773}, pmid = {9322260}, issn = {1074-7427}, mesh = {Animals ; Association Learning/*drug effects/physiology ; Avoidance Learning/*drug effects/physiology ; Brain/drug effects/physiology ; Conditioning, Classical/*drug effects/physiology ; Dietary Sucrose/administration & dosage ; Excitatory Amino Acid Antagonists/*pharmacology ; Ketamine/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Mental Recall/*drug effects/physiology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology ; Taste/*drug effects/physiology ; }, abstract = {Three experiments studied the effectiveness of ketamine acting as an aversive unconditioned stimulus (UCS) in a conditioned flavor aversion procedure. In Experiment 1a, three conditioning trials where sucrose was paired with ketamine produced a weak but significant aversion to sucrose; Experiment 1b showed that this effect was not due to a reduced consumption of sucrose caused by ketamine-induced neophobia. In Experiment 2, acquisition of an aversion to sucrose paired with lithium chloride (LiCl) injections was retarded by prior repeated exposure to LiCl but not to ketamine. These results are not consistent with an interpretation of previous results, showing that ketamine impairs the acquisition of flavor aversions based on LiCl-induced illness, as an example of the UCS preexposure effect.}, } @article {pmid9305458, year = {1997}, author = {Bienkowski, P and Iwinska, K and Piasecki, J and Kostowski, W}, title = {5,7-dihydroxytryptamine lesion does not affect ethanol-induced conditioned taste and place aversion in rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {14}, number = {5}, pages = {439-443}, doi = {10.1016/s0741-8329(96)00191-7}, pmid = {9305458}, issn = {0741-8329}, mesh = {5,7-Dihydroxytryptamine/*pharmacology ; Animals ; Brain/*drug effects/*physiology ; Conditioning, Psychological/*physiology ; Ethanol/*pharmacology ; Male ; Neural Pathways/drug effects/physiology ; Rats ; Rats, Wistar ; Serotonin/*physiology ; Taste ; }, abstract = {The effect of the lesion of central serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), on ethanol-induced taste and place aversion conditioning was studied in male Wistar rats. Control biochemical analysis revealed that 5,7-DHT (250 micrograms per rat, free base, i.c.v.) produced marked and selective depletion of serotonin (5-HT) in the hippocampal formation and the limbic forebrain complex. Ethanol-induced (1.5 g/kg, i.p.) conditioned taste aversion (CTA) to saccharin solution was unaffected by the lesion of central serotonergic neurons. The 5,7-DHT-lesioned and sham-lesioned rats showed comparable ethanol-induced CTA even 30 days after the last ethanol injection. Similarly, ethanol-induced (1.5 g/kg, i.p.) conditioned place aversion (CPA) was unaffected by 5,7-DHT administration. These results suggest that central serotonergic pathways are not primarily involved in the aversive effects of high ethanol doses in rats.}, } @article {pmid9300416, year = {1997}, author = {Shimura, T and Tanaka, H and Yamamoto, T}, title = {Salient responsiveness of parabrachial neurons to the conditioned stimulus after the acquisition of taste aversion learning in rats.}, journal = {Neuroscience}, volume = {81}, number = {1}, pages = {239-247}, doi = {10.1016/s0306-4522(97)00188-7}, pmid = {9300416}, issn = {0306-4522}, mesh = {Animals ; Association Learning/physiology ; Conditioning, Classical/*physiology ; Hydrochloric Acid ; Male ; Neurons/physiology ; Pons/cytology/*physiology ; Quinine ; Rats ; Rats, Wistar ; Sodium Chloride ; Sucrose ; Taste/*physiology ; }, abstract = {The pontine parabrachial nucleus is considered to be one of the most critical regions for the acquisition of conditioned taste aversion which is an associative learning of taste and illness. To further clarify the possible involvement of the parabrachial nucleus in conditioned taste aversion, we recorded neuronal responses to taste stimuli from the parabrachial nucleus of rats under deep urethane anaesthesia. Animals were separated into two groups: the conditioned taste aversion group that had acquired a taste aversion to 0.1 M NaCl (conditioned stimulus) after paired presentations of the taste stimulus with intraperitoneal injection of LiCl (unconditioned stimulus), and the control group that had received only the unconditioned stimulus before experiments. Taste-responsive neurons in the conditioned taste aversion group showed larger responses to NaCl at below 0.1 M, but similar responses to 0.3 M and 0.5 M NaCl when compared with those in the control group. Furthermore, hierarchical cluster analyses revealed a strong similarity among responses to sodium salts in neurons of the conditioned taste aversion group compared with the control group. These results suggest that the aversive conditioning to NaCl modified parabrachial units so that the sodium taste was more salient than other tastes. This modification may reflect a long-term plastic change persisting without support of forebrain structures, and would facilitate the gustatory discrimination of the conditioned stimulus, which is required by conditioned animals.}, } @article {pmid9272671, year = {1997}, author = {Franchina, JJ and Moon, C and Peters, S}, title = {Effects of toxin magnitude on taste aversion and taste-potentiated aversion to visual cues in chicks (Gallus domesticus).}, journal = {Physiology & behavior}, volume = {62}, number = {3}, pages = {605-609}, doi = {10.1016/s0031-9384(97)00172-8}, pmid = {9272671}, issn = {0031-9384}, mesh = {Animals ; Chickens ; Cues ; Lithium Chloride/*toxicity ; Taste/*drug effects ; Toxins, Biological/*toxicity ; Visual Perception/*drug effects ; }, abstract = {Chicks (n = 208) received CS solutions of red water, red 2.0% vinegar, clear water, or clear 2.0% vinegar, followed by an I.P. injection of 0.4 M lithium chloride at 0.2% or 0.5% body weight, and then received 2 test trials with red water or clear 2.0% vinegar. In testing with red water, measures of latency to start drinking, latency to make 9 more drinks after the first, and amount drunk provided reliable evidence of potentiated aversion to visual cues with a greater magnitude of potentiation shown following the 0.2% injection than the 0.5% injection. In testing with clear vinegar, the "9-drink" latency measure and amount drunk yielded reliable evidence of taste aversion, with greater aversion shown following the 0.5% injection than the 0.2% injection. Findings are discussed in terms of associative and taste primacy views of potentiation effects.}, } @article {pmid9331470, year = {1997}, author = {Ossenkopp, KP and Ladowsky, RL and Eckel, LA}, title = {Forced-choice discrimination of equimolar NaCl and LiCl solutions in rats: effects of ablating the chemosensitive area postrema on acquisition and retention.}, journal = {Behavioural brain research}, volume = {87}, number = {1}, pages = {15-24}, doi = {10.1016/s0166-4328(97)02279-1}, pmid = {9331470}, issn = {0166-4328}, mesh = {Animals ; Behavior, Animal/drug effects/physiology ; Cerebral Ventricles/anatomy & histology/*physiology ; Discrimination Learning/drug effects/physiology ; Discrimination, Psychological/*drug effects ; Drinking/drug effects/physiology ; Lithium Chloride/*pharmacology ; Male ; Memory/drug effects/physiology ; Rats ; Sodium Chloride/*pharmacology ; Taste/*drug effects ; }, abstract = {The area postrema (AP), a chemosensitive organ located in the fourth ventricle, has been shown to mediate the formation of a lithium-induced conditioned taste avoidance (CTA) in rats. The present experiments examined the role of the AP in the discrimination between two equimolar solutions of sodium chloride (NaCl) and lithium chloride (LiCl). In the first experiment adult male rats were trained to discriminate between equimolar (0.12 M) solutions of NaCl and LiCl in a forced-choice procedure over a 10-day acquisition phase. Subsequently half of the rats (n = 7) received AP lesions (APX) and the other half (n = 7) were given sham lesions (SHAM). In the retention phase all animals were again exposed to the same salt solutions over a 10-day period. Good discrimination (P < 0.001) between the two salt solutions was demonstrated by the end of the acquisition phase and both the APX and SHAM groups exhibited robust retention (P < 0.01) of this discrimination in the second phase. However, when only a LiCl solution was available the APX group ingested significantly more (P < 0.01) than the SHAM rats. No significant group difference emerged when only NaCl was available. In the second experiment rats received ablations of AP or sham lesions and were then trained to discriminate between 0.12 M NaCl and LiCl solutions in a forced-choice procedure over a 10-day period. Both groups exhibited a clear discrimination (P < 0.01) between the two solutions by the end of the acquisition phase. APX rats ingested significantly more LiCl (P < 0.01) than did the SHAM group when this was the only type of fluid available. Again, no such difference was evident when only NaCl was available. These experiments demonstrate that the AP is not necessary for either the acquisition or retention of a discrimination between equimolar solutions of NaCl and LiCl in a forced-choice procedure and that this discrimination is not mediated by a conditioned taste aversion to the LiCl solution.}, } @article {pmid9259003, year = {1997}, author = {Lane, JR and Starbuck, EM and Fitts, DA}, title = {Ethanol preference, metabolism, blood pressure, and conditioned taste aversion in experimental cholestasis.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {57}, number = {4}, pages = {755-766}, doi = {10.1016/s0091-3057(96)00386-3}, pmid = {9259003}, issn = {0091-3057}, support = {AA-05390/AA/NIAAA NIH HHS/United States ; NS-22274/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Blood Pressure/drug effects/*physiology ; Body Weight/drug effects ; Cholestasis/blood/etiology/*physiopathology ; Conditioning, Psychological/physiology ; Drug Interactions ; Ethanol/*pharmacology ; Food Preferences/*physiology ; Male ; Organ Size/drug effects ; Rats ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*physiology ; }, abstract = {The effect of a ligation of the common bile duct (BDL) on the chronic free-selection intake of ethanol was investigated. Rats were given a choice between water and a solution of either 6% (v/v) ethanol, 0.06% (w/v) sodium saccharin, or a mixture of both ethanol and saccharin. In different experiments, solutions were first presented either 3 weeks before surgery, about the time of surgery, or 2 weeks after surgery. Reductions in ethanol or saccharin intake were observed in BDL rats whenever the solutions were first presented either 3 weeks before or shortly after the surgery. No differences attributable to BDL were seen when ethanol solutions were first presented 2 weeks after surgery. The contingent nature of the effect suggests that the reduction results from a conditioned taste aversion rather than from differences in ethanol metabolism, sensitivity, or neurohormones such as angiotensin. The findings urge caution in the monitoring of the dietary habits of patients with a rapidly developing biliary obstruction.}, } @article {pmid9272690, year = {1997}, author = {Kojima, S and Nanakamura, H and Nagayama, S and Fujito, Y and Ito, E}, title = {Enhancement of an inhibitory input to the feeding central pattern generator in Lymnaea stagnalis during conditioned taste-aversion learning.}, journal = {Neuroscience letters}, volume = {230}, number = {3}, pages = {179-182}, doi = {10.1016/s0304-3940(97)00507-7}, pmid = {9272690}, issn = {0304-3940}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Electrophysiology ; Feeding Behavior/physiology ; Lymnaea/*physiology ; Membrane Potentials/physiology ; Neural Inhibition/*physiology ; Taste/*physiology ; }, abstract = {To study the neuronal mechanism of a conditioned taste-aversion (CTA) learning in the pond snail Lymnaea stagnalis, we examined the synaptic connection between the neuron 1 medial (N1M) cell and the cerebral giant cell (CGC), the former is an interneuron in central pattern generator for the feeding response and the latter is a regulatory neuron to the central pattern generator. Inhibitory postsynaptic potential (IPSP) which was evoked in the N1M cell by activation of the CGC was larger and lasted longer in the conditioned animal than that in the control animal. The electrical properties of the cell body of CGC and the responses of the CGC to the chemosensory inputs were not changed during the CTA learning. These results, together with the previous report indicating the existence of excitatory projection from the N1M cell to the feeding motoneuron, suggest that enhanced IPSP in the N1M cell may underlie the suppression of feeding responses in the Lymnaea CTA learning.}, } @article {pmid9243614, year = {1997}, author = {Sakai, N and Yamamoto, T}, title = {Conditioned taste aversion and c-fos expression in the rat brainstem after administration of various USs.}, journal = {Neuroreport}, volume = {8}, number = {9-10}, pages = {2215-2220}, doi = {10.1097/00001756-199707070-00025}, pmid = {9243614}, issn = {0959-4965}, mesh = {Animals ; Brain Stem/*metabolism ; Conditioning, Psychological/*drug effects/physiology ; Electroshock ; Emetics/administration & dosage/*pharmacology ; Ethanol/administration & dosage/pharmacology ; Lithium Chloride/administration & dosage/*pharmacology ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Radiation ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Strychnine/administration & dosage/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is a form of association learning established when an animal associates a conditioned stimulus (taste) with a subsequent unconditioned stimulus (US, illness). We have studied the relationship between the efficacy of inducing CTA to 0.1% saccharin and c-fos expression in the lower brain stem following administration of 13 different USs in rats. The effective USs were grouped into abdominal irritants, rewarding drugs and emetic agents. Regardless of the properties of USs, good correlation was detected between the strength of CTA and c-fos expression within the area postrema, caudal and intermediate subdivisions of nucleus tractus solitarius and the external lateral subnucleus of the parabrachial nucleus. Only hypertonic saline was exceptional because of the experimental procedure: it induced strong c-fos expression, but was not an effective US for CTA formation. Different dosages of the emetic LiCl induced CTA and c-fos expression in a dose-dependent manner.}, } @article {pmid9185550, year = {1997}, author = {Rosenblum, K and Berman, DE and Hazvi, S and Lamprecht, R and Dudai, Y}, title = {NMDA receptor and the tyrosine phosphorylation of its 2B subunit in taste learning in the rat insular cortex.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {17}, number = {13}, pages = {5129-5135}, pmid = {9185550}, issn = {0270-6474}, mesh = {Animals ; Avoidance Learning ; Cerebral Cortex/metabolism/*physiology ; Conditioning, Psychological ; Isomerism ; Learning/*physiology ; Male ; Mental Recall ; Phosphorylation ; RNA, Messenger/metabolism ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/genetics/*metabolism ; Taste/*physiology ; Tyrosine/*metabolism ; }, abstract = {We demonstrate that the NMDA receptor is involved in taste learning in the insular cortex of the behaving rat and describe two facets of this involvement. Blockage of the NMDA receptor in the insular cortex by the reversible antagonist APV during training in a conditioned taste aversion (CTA) paradigm impaired CTA memory, whereas blockage of the NMDA receptor in an adjacent cortex or before a retrieval test had no effect. When rats sampled an unfamiliar taste and hence learned about it, either incidentally or in the context of CTA training, the tyrosine phosphorylation of the NMDA receptor subunit 2B (NR2B) in the insular cortex was specifically increased. The level of tyrosine phosphorylation on NR2B was a function of the novelty of the taste stimulus and the quantity of the taste substance consumed, properties that also determined the efficacy of the taste stimulus as a conditioned stimulus in CTA; however, blockage of the NMDA receptor by APV during training did not prevent tyrosine phosphorylation of NR2B. We suggest that tyrosine phosphorylation of NR2B subserves encoding of saliency in the insular cortex during the first hours after an unfamiliar taste is sampled and that this encoding is independent of another, necessary role of NMDA receptors in triggering experience-dependent modifications in the insular cortex during taste learning. Because a substantial fraction of the NR2B protein in the insular cortex seems to be expressed in interneurons, saliency and the tyrosine phosphorylation of NR2B correlated with it may modulate inhibition in cortex.}, } @article {pmid9219872, year = {1997}, author = {Miranda, MI and Löpez-Colomé, AM and Bermúdez-Rattoni, F}, title = {Recovery of taste aversion learning induced by fetal neocortex grafts: correlation with in vivo extracellular acetylcholine.}, journal = {Brain research}, volume = {759}, number = {1}, pages = {141-148}, doi = {10.1016/s0006-8993(97)00240-0}, pmid = {9219872}, issn = {0006-8993}, mesh = {Acetylcholine/metabolism ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*embryology/metabolism/*physiology ; Conditioning, Psychological/physiology ; Extracellular Space/metabolism ; *Fetal Tissue Transplantation ; Glutamic Acid/metabolism ; Male ; Microdialysis ; Potassium Chloride/pharmacology ; Rats ; Rats, Wistar ; Taste/*physiology ; Transplantation, Heterotopic ; }, abstract = {Rats showing disrupted taste aversion due to insular cortex lesions, received either homotopic or heterotopic (occipital) cortical fetal brain grafts. Behavioral results showed that the recovery of the ability to acquire conditioned taste aversions induced by fetal grafts depended on post-graft time (45 but not at 15 days) and tissue specificity (homotopic but not heterotopic). In vivo analysis of acetylcholine (ACh) release revealed that only the group receiving homotopic grafts and tested 45 days post graft had a release of ACh after KCl stimulation similar to that in the control group. Furthermore, homotopic grafts and lesioned groups showed significantly weaker specific receptor binding of [3H]L-glutamate compared with controls. These results suggest that ACh is specifically involved in the process of behavioral recovery induced by homotopic cortical transplants.}, } @article {pmid9189278, year = {1997}, author = {Scalera, G and Grigson, PS and Norgren, R}, title = {Gustatory functions, sodium appetite, and conditioned taste aversion survive excitotoxic lesions of the thalamic taste area.}, journal = {Behavioral neuroscience}, volume = {111}, number = {3}, pages = {633-645}, pmid = {9189278}, issn = {0735-7044}, support = {DC 00240/DC/NIDCD NIH HHS/United States ; DC 02216/DC/NIDCD NIH HHS/United States ; MH 43787/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Appetite/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Dietary Sucrose/administration & dosage ; Dose-Response Relationship, Drug ; Drinking/*physiology ; Ibotenic Acid ; Lithium Chloride/toxicity ; Male ; Motivation ; Rats ; Rats, Sprague-Dawley ; Sodium, Dietary/*administration & dosage ; Taste/*physiology ; Thalamic Nuclei/*physiology ; Water-Electrolyte Balance/*physiology ; }, abstract = {Rats with bilateral, electrophysiologically guided, ibotenic acid lesions of the gustatory thalamus (THLX) were tested for their ability to perform a variety of taste-guided behaviors. First, in daily 30-min sessions, the rats were given repeated 10-s access periods to a range of concentrations of sucrose, NaCl, or QHCl, plus water. Both the control and the THLX rats exhibited similar concentration-response functions, regardless of hydrational state. Next, on 3 trials, the rats were given 15 min access to 0.3 M l-alanine and then injected with LiCl (0.15 M, 1.33 ml/100 g body weight ip). All rats learned a taste aversion following 1 pairing with LiCl. Finally, on 3 separate occasions, the rats were injected with furosemide, and Na(+)-appetite was evaluated 24 hr later. All rats expressed an equivalent sodium appetite after the first furosemide injection, but only the control rats increased intake of 0.51 M NaCl with repeated sodium depletions. These observations reinforce prior data implying that an intact gustatory thalamus is not necessary for the expression of some taste-guided behaviors.}, } @article {pmid9133398, year = {1997}, author = {Gutiérrez, H and Miranda, MI and Bermúdez-Rattoni, F}, title = {Learning impairment and cholinergic deafferentation after cortical nerve growth factor deprivation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {17}, number = {10}, pages = {3796-3803}, pmid = {9133398}, issn = {0270-6474}, mesh = {Age Factors ; Animals ; Antibodies, Monoclonal/pharmacology ; Avoidance Learning/drug effects/*physiology ; Binding, Competitive/immunology ; Cholinergic Fibers/drug effects/*physiology ; Conditioning, Psychological/drug effects/physiology ; Denervation ; Fluorescent Dyes ; Male ; Memory/physiology ; Microinjections ; Nerve Growth Factors/analysis/immunology/*pharmacology ; Prosencephalon/cytology ; Rats ; Rats, Wistar ; *Stilbamidines ; Taste/physiology ; Thalamus/chemistry/cytology/physiology ; }, abstract = {Cholinergic basal forebrain (CBF) neurons have been shown to respond in vivo to exogenous administration of NGF. Although neurotrophins and their receptors are widely expressed in the CNS, little data exist for the physiological significance of endogenous neurotrophin signaling in CNS neurons. To test directly whether cortically derived NGF is functionally required for the cholinergic functions mediated by the cerebral cortex, repeated injections of anti-NGF mAbs were locally applied into the insular cortex (IC) of rats. The biochemical results, using an in vivo microdialysis technique, showed a dramatic lack of extracellular release of acetylcholine after high potassium stimulation compared with controls. Furthermore, by using small injections of the neurotracer fluorogold, we found a corresponding disruption in the connectivity between the IC and the CBF. Behavioral experiments showed that the NGF antibodies applied into the IC produced a significant disruption on the acquisition of conditioned taste aversion and inhibitory avoidance learning. However, the same animals were able to recall the taste aversion when the conditioning trial was established before injections of NGF antibodies. Given these results, it seems that cortical cholinergic functions are actively dependent on locally derived NGF in the adult normal brain, and that the cholinergic activity from the CBF is not necessary for recalling aversive stimuli, but is necessary for the acquisition of aversively motivated conditionings.}, } @article {pmid9234048, year = {1997}, author = {Lamb, RJ and Järbe, TU}, title = {Multielemental stimulus control: effects of saccharin concentration on a discriminated morphine-saccharin taste aversion.}, journal = {Experimental and clinical psychopharmacology}, volume = {5}, number = {2}, pages = {123-129}, doi = {10.1037//1064-1297.5.2.123}, pmid = {9234048}, issn = {1064-1297}, support = {KO2 DA 00253/DA/NIDA NIH HHS/United States ; R01 DA 08395/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Discrimination Learning/drug effects ; Dose-Response Relationship, Drug ; Lithium/pharmacology ; Male ; Morphine/*pharmacology ; Narcotics/pharmacology ; Rats ; Rats, Sprague-Dawley ; Saccharin/*pharmacology ; Sweetening Agents/*pharmacology ; Taste/*drug effects ; }, abstract = {The effects of saccharin concentration on the stimulus control by a compound stimulus consisting of morphine, saccharin (0.01, 0.03, or 0.10%, wt/vol), and a ball bearing drinking nozzle in a discriminated taste aversion (DTA) procedure were examined in rats (Rattus norvegicus). In paired rats injections of lithium followed presentation of this compound stimulus, whereas in unpaired rats saline injections followed this stimulus. DTA acquisition was more rapid at higher saccharin concentrations. In testing with each individual stimulus element, stimulus control was clearly exerted by all 3 stimulus elements. When another stimulus element was presented jointly with saccharin, behavioral control was similar to that of saccharin alone. Behavioral control by saccharin increased with saccharin concentration. However, behavioral control by the 2 other stimulus elements was relatively unaffected when the saliency of the saccharin element was increased.}, } @article {pmid9200138, year = {1997}, author = {Opitz, B and Mothes, HK and Clausing, P}, title = {Effects of prenatal ethanol exposure and early experience on radial maze performance and conditioned taste aversion in mice.}, journal = {Neurotoxicology and teratology}, volume = {19}, number = {3}, pages = {185-190}, doi = {10.1016/s0892-0362(96)00225-5}, pmid = {9200138}, issn = {0892-0362}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*adverse effects ; Female ; Male ; Maze Learning/*drug effects ; Mice ; Mice, Inbred C57BL ; Pregnancy ; *Prenatal Exposure Delayed Effects ; }, abstract = {C57BL/6 mice were intubated on gestational days 14-18 twice daily with 1.58 g/kg ethanol, 4.2 g/kg sucrose, or remained untreated. Offspring of ethanol-treated or lab chow control groups were raised either by group-housed dams and weaned on postnatal day (PND) 28 (enriched condition), or by individually housed dams and weaned on PND 21 (standard condition). Offspring of the sucrose control group were raised by individually housed dams and weaned on PND 21. Groups did not differ in pup weight or litter size. Male and female offspring were assessed for performance in an unbaited radial maze (PND 45-52) and male offspring only were tested for conditioned taste aversion (PND 54-59). As hypothesized, mice prenatally exposed to ethanol and raised under standard conditions failed to develop the conditioned taste aversion response. In contrast, subjects with in utero ethanol exposure that were raised under enriched preweaning conditions developed the taste aversion response. Maze performance improved significantly over days, but no significant effects were detected for either prenatal treatment or preweaning rearing conditions. In conclusion, enriched preweaning rearing conditions abolished the detrimental effects of prenatal ethanol exposure on conditioned taste aversion, but radial maze performance remained unaffected by any treatment in this study.}, } @article {pmid9164593, year = {1997}, author = {Prendergast, MA and Buccafusco, JJ and Terry, AV}, title = {Nitric oxide synthase inhibition impairs spatial navigation learning and induces conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {57}, number = {1-2}, pages = {347-352}, doi = {10.1016/s0091-3057(96)00313-9}, pmid = {9164593}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/*pharmacology ; Male ; Maze Learning/*drug effects ; Mental Recall/drug effects ; Motor Activity/drug effects ; NG-Nitroarginine Methyl Ester/*pharmacology ; Nitric Oxide Synthase/*antagonists & inhibitors ; Rats ; Rats, Wistar ; Reproducibility of Results ; Swimming ; Visual Acuity/drug effects ; }, abstract = {The free radical gas nitric oxide (NO) is formed from the amino acid precursor L-arginine in brain regions which are associated with learning and the formation of memory. We have previously reported that administration of the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-Name) impairs delayed recall in non-human primates but that, at higher doses, impairment is associated with aversive gastrointestinal side effects. The purpose of the present study was to examine the effects of L-Name on learning in a rat spatial navigation task and to assess the ability of L-Name to induce a conditioned taste aversion (CTA) to a novel sucrose solution in a two-bottle choice paradigm. In the Morris water maze. L-Name (5, 20, and 50 mg/kg) markedly impaired cued spatial learning required to locate a hidden platform on three consecutive days of testing, but did not affect general activity levels. These data also demonstrated the ability of L-Name to induce a potent CTA, though only with the 20 and 50 mg/kg doses. Both the impairment of learning and CTA were blocked by administration of a mole equivalent dose of L-arginine, indicating that attenuated NO activity was associated with both behavioral effects. These data demonstrate that inhibition of NO activity by L-Name induces significant and selective impairment of cognitive performance at low pharmacologic doses (< 20 mg/kg). However, with higher doses of NOS inhibitors, impairment may be a secondary effect of drug-induced malaise, possibly related to peristaltic dysregulation of gastrointestinal musculature. Therefore, conclusions as to the mediation of learning and memory processes by CNS NO may be difficult to interpret without the use of selective, centrally-acting compounds.}, } @article {pmid9159506, year = {1997}, author = {Yamamoto, T and Sako, N and Sakai, N and Iwafune, A}, title = {Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c-fos-like immunoreactivity.}, journal = {Neuroscience letters}, volume = {226}, number = {2}, pages = {127-130}, doi = {10.1016/s0304-3940(97)00265-6}, pmid = {9159506}, issn = {0304-3940}, mesh = {Administration, Oral ; Amygdala/cytology/*physiology ; Animals ; *Avoidance Learning ; Conditioning, Psychological/*physiology ; Enteral Nutrition ; Gene Expression ; Genes, fos ; Lithium Chloride/*pharmacology ; Male ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/analysis/*biosynthesis ; Rats ; Rats, Wistar ; Saccharin/administration & dosage/pharmacology ; Sucrose/administration & dosage/pharmacology ; Sweetening Agents/administration & dosage/pharmacology ; Taste/*physiology ; }, abstract = {Expression of proto-oncogene c-fos was immunohistochemically examined in the central and basolateral amygdaloid nuclei in rats after ingestion of taste solutions (0.5 M sucrose or 0.005 M saccharin), intragastric infusion of these solutions, or an intraperitoneal injection of malaise-inducing lithium chloride (LiCl). C-Fos-like immunoreactive neurons were distributed most densely in the central nucleus in response to the LiCl injection, followed by the ingestion and intragastric infusion of sucrose. The intraoral infusion of sucrose, but not of saccharin, elicited intense c-fos expression in the central nucleus after establishment of conditioned taste aversion to these taste stimuli. The results are discussed in terms of post-ingestional factors and the conditioned illness reaction after taste aversion learning.}, } @article {pmid9172136, year = {1997}, author = {Yasoshima, Y and Yamamoto, T}, title = {Rat gustatory memory requires protein kinase C activity in the amygdala and cortical gustatory area.}, journal = {Neuroreport}, volume = {8}, number = {6}, pages = {1363-1367}, doi = {10.1097/00001756-199704140-00009}, pmid = {9172136}, issn = {0959-4965}, mesh = {Amygdala/*enzymology ; Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*enzymology ; Conditioning, Operant/physiology ; Enzyme Inhibitors/pharmacology ; Male ; Memory/*physiology ; Microinjections ; Protein Kinase C/*metabolism ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {We have studied the physiological involvement of protein kinase C (PKC) in the formation of conditioned taste aversion (CTA) by means of microinjections of PKC inhibitors into the gustatory cortex (GC), amygdala (AMY) and thalamic gustatory area at various time-windows of the CTA paradigm. Rats injected between the CS-US interval with PKC inhibitors into the GC and AMY, but not into the thalamic gustatory area, failed to acquire CTA. Injections of PKC inhibitors 4 h after the US presentation or just before the retention test elicited no disruptive effect. Injections of PKC inhibitor into the AMY, but not into the GC, 30 min after the CS-US pairing impaired CTA formation. These results show that PKC activity in the GC and AMY has a key role in the acquisition phase of CTA, but not in the retrieval phase. The findings also suggest that the GC is concerned with information processing of the CS, and that the AMY is involved in the CS-US association.}, } @article {pmid9225288, year = {1997}, author = {Mokler, DJ and Abbruzzese, S and Trumble, V and Whitten, B}, title = {Effects of ketanserin on the discrimination of electrical stimulation of the dorsal raphé nucleus in rats.}, journal = {Neuropharmacology}, volume = {36}, number = {4-5}, pages = {631-636}, doi = {10.1016/s0028-3908(97)00053-1}, pmid = {9225288}, issn = {0028-3908}, support = {DA07316/DA/NIDA NIH HHS/United States ; }, mesh = {Amphetamines/pharmacology ; Animals ; Cues ; Discrimination, Psychological/*drug effects ; Electric Stimulation ; Generalization, Stimulus/drug effects ; Ketanserin/*pharmacology ; Male ; Raphe Nuclei/drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Serotonin Antagonists/*pharmacology ; Serotonin Receptor Agonists/pharmacology ; Sweetening Agents/pharmacology ; Taste/drug effects ; }, abstract = {The electrical stimulation of the dorsal raphé nucleus was used as a training cue in a discrimination paradigm. Sprague-Dawley rats were trained to discriminate between electrical stimulation (ES; 200 microA) of the dorsal raphé nucleus (DRN) and non-stimulation. This was accomplished by associating ES with intraperitoneal (i.p.) injection of lithium chloride (LiCl), following the session with electrical stimulation. This made the drinking of saccharin during ES aversive by conditioned taste aversion. Following training, rats decreased saccharin consumption in ES sessions. This discrimination was learned within three pairings of the ES with LiCl. Lowering the ES current to 50-100 microA resulted in levels of saccharin consumption similar to non-stimulation levels, whereas 150 microA showed a response intermediate between the stimulation response at 200 microA and non-stimulation. The discrimination of ES of the DRN (200 microA) was not affected by prior administration of the 5-HT2 antagonist ketanserin (1 or 2 mg/kg, i.p.), suggesting that activation of 5-HT2 receptors is not the primary discriminative cue generated by ES. However, the 5-HT2A/2C agonist DOI (0.25-0.5 mg/kg, i.p.), substituted for ES of the DRN, i.e. animals reduced saccharin consumption following DOI administration. This substitution of DOI for ES was antagonized by the administration of ketanserin (1 mg/kg, i.p.). These results suggest that ES of the DRN has properties that are similar to the activation of 5-HT2A/2C receptors by DOI. However, other stimuli such as activation of other 5-HT receptors are also involved, given that the discriminative cues of ES are not blocked by the 5-HT2A/2C antagonist ketanserin.}, } @article {pmid9332167, year = {1997}, author = {Mukherjee, SK and Goel, HC and Pant, K and Jain, V}, title = {Prevention of radiation induced taste aversion in rats.}, journal = {Indian journal of experimental biology}, volume = {35}, number = {3}, pages = {232-235}, pmid = {9332167}, issn = {0019-5189}, mesh = {Animals ; Avoidance Learning/*radiation effects ; Female ; *Gamma Rays ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {Diltiazem, a calcium channel blocker, and a cardiovascular therapeutic agent offers significant protection to mice against lethal dose of ionizing radiation. Considering the potential efficacy of diltiazem as a radioprotector for human use, it was deemed necessary to investigate its influence on radiation-induced behavioural changes like nausea, vomiting, learning, memory and performance. In the present studies, conditioned taste aversion (CTA) test based on consumption of saccharin solution, was used as a marker of behavioural changes. Significant CTA (97 +/- 2%) was observed in rats irradiated with Co-60 gamma rays (absorbed dose 1 Gy). Administration of diltiazem at doses greater than 10 mg/kg, body wt, evoked CTA in a dose-dependent manner and that was found to be further aggravated on irradiation. At a lower dose of 5 mg/kg, body wt, diltiazem did not evoke CTA and protected against radiation induced aversion significantly (62 +/- 3%). The results suggest that diltiazem at concentrations lower than 10 mg/kg, body wt, in rats may be useful in preventing radiation induced behavioural changes. This observation could be of particular significance in clinical radiotherapy where radiation induced nausea and vomiting are of great concern.}, } @article {pmid9106906, year = {1997}, author = {Gaiardi, M and Bartoletti, M and Bacchi, A and Gubellini, C and Babbini, M}, title = {Motivational properties of buprenorphine as assessed by place and taste conditioning in rats.}, journal = {Psychopharmacology}, volume = {130}, number = {2}, pages = {104-108}, doi = {10.1007/s002130050216}, pmid = {9106906}, issn = {0033-3158}, mesh = {Analgesics, Opioid/*pharmacology ; Animals ; Buprenorphine/*pharmacology ; Conditioning, Operant/*drug effects ; Male ; *Motivation ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; Reward ; Taste/*drug effects ; }, abstract = {Buprenorphine, a mixed agonist-antagonist opioid with considerable analgesic activity, is currently indicated as a therapeutic agent with low abuse potential. Nevertheless, buprenorphine abuse has been recently reported from some countries. Thus the present experiments were performed to characterize further the motivational properties of buprenorphine in rats. Rewarding and aversive effects were assessed by place preference and taste aversion conditioning, respectively. It was found that buprenorphine (0.025, 0.050, 0.100 mg/kg s.c.) causes a significant increase in the amount of time spent on the conditioned side, but no significant decrease in saccharin consumption. Therefore buprenorphine data are not consistent with the general finding that psychoactive drugs cause rewarding and aversive effects within a similar dose range.}, } @article {pmid9089764, year = {1997}, author = {Batsell, WR}, title = {Retention of context blocking in taste-aversion learning.}, journal = {Physiology & behavior}, volume = {61}, number = {3}, pages = {437-446}, doi = {10.1016/s0031-9384(96)00458-1}, pmid = {9089764}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Male ; Rats ; Retention, Psychology/*physiology ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {A series of experiments examined recovery from context blocking across a retention interval. In two flavor-aversion studies, rats received 0, 2, or 4 context + US pairings in Phase 1, a flavor + US pairing in Phase 2, and flavor testing after a 3-day or a 14-day retention interval. The procedures in Experimental 1 were performed in a novel context, whereas Experiment 2 was conducted in a moderately familiar context. In Experiment 1, the effects of 2 context + US pairing dissipated over the retention interval (i.e., the taste aversion increased in strength), but the effects of 4 context + US pairings did not change. In Experiment 2, no context blocking was observed after 2 context + US pairings, but the effects of 4 context + US pairings decreased across the retention interval. These studies are the first to show recovery from context blocking across a retention interval following single-element conditioning. Furthermore, Experiment 3 demonstrated that extinction of the context prior to taste conditioning eliminated context blocking, and Experiment 4 showed that weak taste aversions do not increase in strength across a retention interval. It is proposed that forgetting of the context-US association across an extended retention interval is the mechanism underlying recovery from context blocking.}, } @article {pmid9089755, year = {1997}, author = {McCaughey, SA and Giza, BK and Nolan, LJ and Scott, TR}, title = {Extinction of a conditioned taste aversion in rats: II. Neural effects in the nucleus of the solitary tract.}, journal = {Physiology & behavior}, volume = {61}, number = {3}, pages = {373-379}, doi = {10.1016/s0031-9384(96)00412-x}, pmid = {9089755}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Evoked Potentials ; Extinction, Psychological/*physiology ; Female ; Neurons/physiology ; Rats ; Rats, Wistar ; Solitary Nucleus/*physiology ; Taste/*physiology ; }, abstract = {The formation of a conditioned taste aversion (CTA) in rats results in neural changes at several levels of the gustatory system. In the nucleus of the solitary tract (NTS), the outstanding feature of the response to a CS is a brief burst of activity that is absent in unconditioned animals. The burst occurs about 1 s after stimulus onset and is seen only in neurons that respond well to sugars and the CS (0.0025 M NaSaccharin). We recorded single neuron activity in response to 12 stimuli from taste cells in the NTS of 8 rats, in which a CTA to NaSaccharin had been created and fully extinguished, and in 8 unconditioned controls. The issue was if the neural effects of the CTA in NTS were reversed with extinction. We recorded the activity of 41 neurons in controls and 55 in CTA-extinguished rats. Responses measured across all neurons were not significantly different in spontaneous activity, breadth of tuning, overall response magnitude to each of the 12 stimuli, relationship among stimuli in taste spaces, or time-course. However, cells in the sugar-sensitive subgroup showed a clear vestige of the conditioning experience. They gave a well-defined burst of activity to the CS, though of reduced amplitude and slightly longer latency than in fully conditioned rats. This burst was no longer associated with the conditioned behavior-which was fully extinguished-though it may be a permanent marker for the once-salient CS that can influence subsequent reacquisition of the aversion.}, } @article {pmid9124501, year = {1997}, author = {Thiele, TE and Van Dijk, G and Campfield, LA and Smith, FJ and Burn, P and Woods, SC and Bernstein, IL and Seeley, RJ}, title = {Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats.}, journal = {The American journal of physiology}, volume = {272}, number = {2 Pt 2}, pages = {R726-30}, doi = {10.1152/ajpregu.1997.272.2.R726}, pmid = {9124501}, issn = {0002-9513}, support = {AA-07455/AA/NIAAA NIH HHS/United States ; DK-17844/DK/NIDDK NIH HHS/United States ; DK-35816/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning ; Body Weight/drug effects ; Brain/*physiology ; *Conditioning, Psychological ; Eating/drug effects ; Glucagon-Like Peptide 1 ; Injections, Intraventricular ; Leptin ; Male ; Peptides/*administration & dosage/pharmacology ; Proteins/*administration & dosage/pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin ; Solutions ; *Taste ; }, abstract = {Leptin (ob protein) and glucagon-like peptide-1-(7-36) amide (GLP-1) are peptides recently proposed to be involved in the regulation of food intake. Although the ability of exogenous leptin and GLP-1 to modulate consummatory behavior is consistent with the suggestion that these peptides are endogenous regulatory agents, central administration of these peptides may have aversive side effects, which could explain the anorexia. In the present experiment, exposure to a saccharine taste was immediately followed by central administration of leptin or GLP-1 to determine if these drugs could produce a conditioned taste aversion (CTA) in rats. At doses equated for producing comparable reductions in short-term food intake, GLP-1, but not leptin, generated a robust CTA. Although leptin caused no aversion, this peptide was the only drug to cause relatively long-term reductions in food consumption (16 h) and body weight (24 h). Hence, the results indicate that central GLP-1 produces aversive side effects, and it is argued that these nonspecific effects may explain the anorectic actions of GLP-1.}, } @article {pmid9109637, year = {1997}, author = {St John, SJ and Markison, S and Spector, AC}, title = {Chorda tympani nerve transection disrupts taste aversion learning to potassium chloride, but not sodium chloride.}, journal = {Behavioral neuroscience}, volume = {111}, number = {1}, pages = {188-194}, doi = {10.1037//0735-7044.111.1.188}, pmid = {9109637}, issn = {0735-7044}, support = {K04-DC-00104/DC/NIDCD NIH HHS/United States ; R01-DC-01628/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Chorda Tympani Nerve/*physiology ; Discrimination Learning/*physiology ; Generalization, Stimulus/physiology ; Male ; Mental Recall/*physiology ; *Potassium Chloride/administration & dosage ; Rats ; Rats, Sprague-Dawley ; *Saline Solution, Hypertonic/administration & dosage ; Taste/*physiology ; Taste Buds/physiology ; Taste Threshold/physiology ; }, abstract = {In Experiment 1, rats with chorda tympani nerve transection (CTX) acquired a LiCl-conditioned taste aversion to 0.1 M NaCl at the same rate as controls. After 3 conditioning trials, the aversion generalized to 0.03 and 0.3 M NaCl, but did not generalize to KCI (0.03, 0.1, and 0.3 M), in either the sham or CTX group. In Experiment 2, the sham group, but not the CTX group, formed an aversion to 0.1 M KCI after 1 trial. The CTX rats did form a moderate aversion after 2 conditioning trials. Following the 3rd trial, the CTX group did not suppress licking to 0.03 or 0.3 M KCI or any concentration of NaCl in relation to controls. Although there is strong evidence that CTX affects NaCl taste perception, these findings indicate that, under certain conditions, rats can nonetheless distinguish NaCl from KCI after such neurotomy. Moreover, CTX appears to have a substantial effect on the perceived intensity of KCl.}, } @article {pmid9109636, year = {1997}, author = {Grigson, PS and Shimura, T and Norgren, R}, title = {Brainstem lesions and gustatory function: III. The role of the nucleus of the solitary tract and the parabrachial nucleus in retention of a conditioned taste aversion in rats.}, journal = {Behavioral neuroscience}, volume = {111}, number = {1}, pages = {180-187}, pmid = {9109636}, issn = {0735-7044}, support = {DC-00240/DC/NIDCD NIH HHS/United States ; DC-02016/DC/NIDCD NIH HHS/United States ; DC-02216/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Brain Stem/*physiology ; Conditioning, Classical/*physiology ; Dominance, Cerebral/physiology ; Extinction, Psychological/physiology ; Lithium Chloride/toxicity ; Male ; Mental Recall/physiology ; Neural Pathways/physiology ; Pons/*physiology ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology/*physiology ; Solitary Nucleus/*physiology ; Taste/*physiology ; }, abstract = {Bilateral electrolytic lesions of the nucleus of the solitary tract (NST) or ibotenic acid lesions of the pontine parabrachial nuclei (PBN) failed to disrupt retention of a preoperatively acquired conditioned taste aversion (CTA) to 0.3 M alanine. For both sham- and NST-lesioned rats, the CTA persisted following 3 nonreinforced conditioned stimulus (CS) presentations. For PBN-lesioned rats, retention was more labile. The preoperatively acquired CTA was extinguished by the 3rd nonreinforced CS exposure. When assessed postoperatively using a novel CS, NST-lesioned rats acquired a new CTA, although they were rendered anosmic with zinc sulfate (P. S. Grigson, T. Shimura, & R. Norgren, 1997). Rats with PBN lesions, however, failed to acquire a second CTA postoperatively. Thus, the PBN is essential for the acquisition of a CTA, but neither of the brainstem gustatory nuclei need be intact for the retention of a preoperatively acquired CTA.}, } @article {pmid9109635, year = {1997}, author = {Grigson, PS and Shimura, T and Norgren, R}, title = {Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na+ appetite, conditioned taste aversion, and conditioned odor aversion in rats.}, journal = {Behavioral neuroscience}, volume = {111}, number = {1}, pages = {169-179}, pmid = {9109635}, issn = {0735-7044}, support = {DC-00240/DC/NIDCD NIH HHS/United States ; DC-02016/DC/NIDCD NIH HHS/United States ; DC-02216/DC/NIDCD NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Appetite/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Brain Stem/*physiology ; Conditioning, Classical/*physiology ; Male ; Motivation ; Rats ; Rats, Sprague-Dawley ; Saline Solution, Hypertonic/administration & dosage ; Smell/*physiology ; Solitary Nucleus/*physiology ; Taste/*physiology ; Taste Buds/physiology ; Water-Electrolyte Balance/physiology ; }, abstract = {Rats with lesions of the nucleus of the solitary tract (NST) that demonstrated flat concentration-response functions for NaCl and sucrose (T. Shimura, P. S. Grigson, & R. Norgren, 1997) expressed a significant (albeit reduced) salt appetite following sodium depletion, and a normal conditioned taste aversion (CTA) for alanine when paired with lithium chloride-induced toxicosis. Rats with lesions of the NST also could acquire a conditioned odor aversion, but the CTA to alanine was not mediated by odor cues because other rats with NST lesions also demonstrated normal CTA learning even when made anosmic with zinc sulfate. Together, the data suggest that the rostral NST is essential for responding appropriately to increasing concentrations of a tastant, but not for the chemical identification necessary for sodium appetite and CTA learning.}, } @article {pmid9109632, year = {1997}, author = {Hernadi, I and Karadi, Z and Faludi, B and Lenard, L}, title = {Disturbances of neophobia and taste-aversion learning after bilateral kainate microlesions in the rat pallidum.}, journal = {Behavioral neuroscience}, volume = {111}, number = {1}, pages = {137-146}, pmid = {9109632}, issn = {0735-7044}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Dominance, Cerebral/*physiology ; Excitatory Amino Acid Agonists ; Fear/*physiology ; Globus Pallidus/*physiology ; Kainic Acid ; Male ; Rats ; Rats, Inbred Strains ; Retention, Psychology/physiology ; Taste/*physiology ; }, abstract = {These experiments aimed to elucidate feeding-associated behavioral roles of globus pallidus (GP) neurons in gustatory functions: The effects of bilateral microiontophoretic kainate (KA) lesions of the ventromedial pallidal (vmGP) region on neophobia and conditioned taste aversion (CTA) were studied. Lesioned rats displayed strong and persistent neophobia to a mild citric acid solution. Neuron-specific damage to the vmGP also prevented rats from proper acquisition of CTA. Rats that previously showed normal neophobia and successfully learned CTA demonstrated difficulties in CTA retention after GP lesions. KA-lesioned rats, in addition, exhibited deficits in orientation reactions but did not have aphagia, adipsia, or motor disturbances seen after larger pallidal lesions. These findings suggest that neurons of the GP are significant in acquisition, memory storage, and retrieval mechanisms of feeding-associated taste information.}, } @article {pmid9109631, year = {1997}, author = {Grigson, PS}, title = {Conditioned taste aversions and drugs of abuse: a reinterpretation.}, journal = {Behavioral neuroscience}, volume = {111}, number = {1}, pages = {129-136}, pmid = {9109631}, issn = {0735-7044}, support = {DA 09815/DA/NIDA NIH HHS/United States ; DC 00240/DC/NIDCD NIH HHS/United States ; DC 02016/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Illicit Drugs/*pharmacology ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Lithium Chloride/pharmacology ; Male ; Morphine/*pharmacology ; Motivation ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {A new hypothesis (and supporting data) provides a solution to the 25-year-old paradox whereby positively reinforcing drugs of abuse also support a conditioned taste aversion (CTA). The results show that unlike LiCl-induced CTAs, morphine- and cocaine-induced suppression of conditioned stimulus (CS) intake depends on the rewarding properties of the gustatory CS. This finding argues against the long-standing CTA interpretation in favor of a new reward comparison account. That is, rats decrease intake of a gustatory CS following taste-drug pairings because the value of the CS is outweighed by that of a highly reinforcing psychoactive drug. Suppression of CS intake, then, is a consequence of the well-documented positive reinforcing, rather than the hypothetical aversive, properties of drugs of abuse.}, } @article {pmid9035264, year = {1997}, author = {Nolan, LJ and McCaughey, SA and Giza, BK and Rhinehart-Doty, JA and Smith, JC and Scott, TR}, title = {Extinction of a conditioned taste aversion in rats: I. Behavioral effects.}, journal = {Physiology & behavior}, volume = {61}, number = {2}, pages = {319-323}, doi = {10.1016/s0031-9384(96)00411-8}, pmid = {9035264}, issn = {0031-9384}, mesh = {Animals ; Association Learning/physiology ; *Avoidance Learning ; *Conditioning, Classical ; Drinking/physiology ; *Extinction, Psychological ; Female ; Lithium Chloride/toxicity ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {The literature is divided over whether a conditioned taste aversion (CTA) can be fully extinguished. In Experiment 1, we created a powerful aversion in 54 rats by pairing the taste of 0.0025 M NaSaccharin (CS) with intraperitoneal injections of 127 mg/kg LiCl (US) on 3 occasions. We then offered 23-h deprived rats NaSaccharin for 10 min/day to observe the course of recovery. Extinction occurred in three phases: static, dynamic, and asymptotic. During the static phase (mean = 9.6 days), rats consumed the CS at < 10% of their preconditioned rate. With dynamic recovery (6.0 days), they increased acceptance to > 80% of preconditioning levels. Finally, they achieved asymptote (3.1 days) at 100% acceptance. In Experiment 2, we used 8 additional conditioned rats and 8 unconditioned controls. We followed the same 1-bottle extinction procedure and, again, obtained 100% acceptance. Then we offered both NaSaccharin and water for 8 days at 23 h/day and monitored lick patterns every 6 s to determine taste preferences. The conditioned animals consumed less NaSaccharin than controls on Day 1, and less NaSaccharin as a percentage of total fluid as late as Day 3. For the last 5 days of 2-bottle preference testing, there were no significant differences between the groups with regard to 1. volume of NaSaccharin or water consumed, 2. percentage of total fluid taken as NaSaccharin, 3. consumption of each fluid associated with a meal or taken spontaneously, 4. intake during the light or dark periods, or 5. the characteristics of ingestion, including number of drinking bouts, duration of bouts, number of licks/bout, and rate of licking. Therefore, a robust CTA is subject to complete behavioral extinction.}, } @article {pmid9035251, year = {1997}, author = {Misanin, JR and Hoefel, TD and Riedy, CA and Hinderliter, CF}, title = {Remote and proximal US preexposure and aging effects in taste aversion learning in rats.}, journal = {Physiology & behavior}, volume = {61}, number = {2}, pages = {221-224}, doi = {10.1016/s0031-9384(96)00371-x}, pmid = {9035251}, issn = {0031-9384}, support = {HD 21161/HD/NICHD NIH HHS/United States ; }, mesh = {Aging/*psychology ; Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Injections, Intraperitoneal ; Lithium Chloride/toxicity ; *Mental Recall ; Rats ; Rats, Wistar ; *Taste ; }, abstract = {Age as a factor in the effect of proximal and remote unconditioned stimulus (US) preexposure on conditioned taste aversion in weanling, young adult, and old rats was studied in 2 experiments. In Experiment 1, 6 daily US preconditioning exposures attenuated conditioning in weanlings and young adults, but not in old rats. In Experiment 2, exposure to a single US 1 h before the conditioning trial curtailed conditioning at all age levels. These results are explained in terms of age differences in familiarity with the conditioning context and Wagner's information-processing model for self- and retrieval-generated disruption of conditioning.}, } @article {pmid9042531, year = {1997}, author = {Houpt, TA and Berlin, R and Smith, GP}, title = {Subdiaphragmatic vagotomy does not attenuate c-Fos induction in the nucleus of the solitary tract after conditioned taste aversion expression.}, journal = {Brain research}, volume = {747}, number = {1}, pages = {85-91}, doi = {10.1016/s0006-8993(96)01221-8}, pmid = {9042531}, issn = {0006-8993}, support = {MH00149/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Immunohistochemistry ; Male ; Neurons, Afferent/drug effects/physiology ; Proto-Oncogene Proteins c-fos/*biosynthesis ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/*metabolism ; Sucrose/pharmacology ; Taste/*physiology ; *Vagotomy ; Weight Gain/physiology ; }, abstract = {After acquisition of a conditioned taste aversion (CTA) against sucrose, intraoral infusions of sucrose induce c-Fos-like immunoreactivity (c-FLI) in the medial intermediate nucleus of the solitary tract (iNTS) of the rat. In order to determine if c-FLI expression in the iNTS depends on subdiaphragmatic vagal afferent input to the NTS secondary to gastrointestinal symptoms during CTA expression (e.g. diarrhea), we quantified the induction of c-FLI in the iNTS by sucrose infusions after total subdiaphragmatic vagotomy in rats with a previously acquired CTA against sucrose. Rats were conditioned against infusions of sucrose by pairing sucrose infusions with toxic LiCl injections. After CTA acquisition, rats underwent bilateral subdiaphragmatic vagotomy or were sham-vagotomized. One week after surgery, rats received an intraoral infusion of sucrose. One hour after the test infusion, rats were perfused and processed for c-FLI. Vagotomy had no apparent effect on the behavioral expression of the previously acquired CTA, because both vagotomized and sham-vagotomized rats rejected all of the test intraoral infusion of sucrose. There was also no significant difference between vagotomized and sham-vagotomized rats in the number of c-FLI-positive cells in the iNTS after CTA expression. We conclude that c-FLI induction correlated with CTA expression is not dependent on subdiaphragmatic vagal efferent output or afferent input.}, } @article {pmid9353173, year = {1997}, author = {Risinger, FO}, title = {Fluoxetine's effects on ethanol's rewarding, aversive and stimulus properties.}, journal = {Life sciences}, volume = {61}, number = {16}, pages = {PL 235-42}, doi = {10.1016/s0024-3205(97)00743-1}, pmid = {9353173}, issn = {0024-3205}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Discrimination, Psychological/*drug effects ; Drug Interactions ; Ethanol/administration & dosage/*pharmacology ; Fluoxetine/*pharmacology ; Male ; Mice ; Motor Activity/drug effects ; Serotonin Uptake Inhibitors/*pharmacology ; Sodium Chloride/administration & dosage ; Sucrose/administration & dosage ; Taste/*drug effects ; }, abstract = {These experiments examined the influence of fluoxetine on ethanol-induced conditioned place preference, ethanol-induced conditioned taste aversion, and ethanol discrimination. In the place conditioning experiment, male Swiss-Webster mice received 4 pairings of a distinctive floor cue with 2 g/kg ethanol, 10 mg/kg fluoxetine + ethanol, or fluoxetine alone. A different floor was paired with saline. During conditioning ethanol produced locomotor stimulation. Fluoxetine + ethanol resulted in greater levels of locomotor activity during conditioning trials 2-4. Fluoxetine alone also caused increases in activity. Floor preference testing revealed conditioned place preference in groups receiving ethanol. Fluoxetine did not change the magnitude of ethanol-induced conditioned place preference nor produced place conditioning alone. In the taste conditioning procedure, mice received 1-h access to 0.2 M NaCl solution followed by injections of 0, 5 or 10 mg/kg fluoxetine and 0 or 2.5 g/kg ethanol. Ethanol produced reductions in NaCl intake. Fluoxetine (10 mg/kg) enhanced the development of ethanol-conditioned taste aversion but did not cause taste aversion alone. In the ethanol discrimination experiment, mice were trained to respond for 10% sucrose on an FR20 schedule following injections of either 1 g/kg ethanol or saline. Following acquisition, 10 mg/kg fluoxetine pretreatment enhanced ethanol-appropriate responding at a dose of ethanol (0.5 g/kg) below the training dose. These results indicate enhancement of serotonergic activity influences ethanol aversion and discrimination but not ethanol reward.}, } @article {pmid9352586, year = {1997}, author = {Kelly, JP and Wrynn, AS and Leonard, BE}, title = {The olfactory bulbectomized rat as a model of depression: an update.}, journal = {Pharmacology & therapeutics}, volume = {74}, number = {3}, pages = {299-316}, doi = {10.1016/s0163-7258(97)00004-1}, pmid = {9352586}, issn = {0163-7258}, mesh = {Animals ; Antidepressive Agents/therapeutic use ; *Behavior, Animal ; Depression/drug therapy/*etiology/physiopathology ; *Disease Models, Animal ; Neurotransmitter Agents/pharmacology ; Olfactory Bulb/*physiology/*surgery ; Olfactory Pathways/anatomy & histology ; Rats ; }, abstract = {The olfactory bulbectomized (OB) rat has been proposed as an animal model of depression. The following behavioural changes have been observed following bilateral olfactory bulbectomy: hyperactivity in an enclosed arena, such as the open-field; enhanced nocturnal hyperactivity in a 24-hr home cage activity monitor; deficits in memory, as shown by passive avoidance behaviour and in the Morris maze and the 8-arm radial maze; increased open arm entries in the elevated plus-maze; and changes in food motivated and conditioned taste aversion behaviour. Alterations in the noradrenergic, serotonergic, cholinergic, gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmitter systems are also associated with olfactory bulbectomy. The variety of immune changes following olfactory bulbectomy includes reduced neutrophil phagocytosis, lymphocyte mitogenesis, lymphocyte number and negative acute phase proteins, increased leucocyte adhesiveness/aggregation, monocyte phagocytosis, neutrophil number and positive acute phase proteins. An enhanced nocturnal secretion of corticosterone is observed in OB rats, which is normally suppressed by dexamethasone. The most commonly employed behavioural indicator of antidepressant activity is attenuation of the OB-related hyperactivity in the open-field. However, many of the other behavioural, neurotransmitter and immune changes have been shown to be attenuated by chronic (but not acute) antidepressant treatment. Tricyclic antidepressants (amitriptyline, desipramine), atypical agents (mianserin), selective serotonin reuptake inhibitors (paroxetine, sertraline, fluvoxamine), reversible inhibitors of monoamine oxidase A (moclobemide), as well as putative antidepressants such as 5-hydroxytryptamine1A agonists (zalospirone, ipsapirone), noncompetitive N-methyl-D-aspartate antagonists (MK-801) and triazolobenzodiazepines (alprazolam, adinazolam), have demonstrated antidepressant-like activity in this model. As many of the changes exhibited by the OB rat are qualitatively similar to those observed in depressed patients, it may be concluded that the OB rat is a model of depression and not just a means whereby putative antidepressants may be tested.}, } @article {pmid9040116, year = {1997}, author = {Ellenbroek, BA and Knobbout, DA and Cools, AR}, title = {The role of mesolimbic and nigrostriatal dopamine in latent inhibition as measured with the conditioned taste aversion paradigm.}, journal = {Psychopharmacology}, volume = {129}, number = {2}, pages = {112-120}, doi = {10.1007/s002130050170}, pmid = {9040116}, issn = {0033-3158}, mesh = {Amphetamine/administration & dosage/*pharmacology ; Animals ; Dopamine/*physiology ; Dopamine Uptake Inhibitors/*pharmacology ; Drinking ; Food Preferences ; *Inhibition, Psychological ; Injections, Intraventricular ; Learning/*drug effects ; Lithium Chloride ; Male ; Neostriatum/drug effects/*physiology ; Nucleus Accumbens/drug effects/*physiology ; Rats ; Rats, Wistar ; Taste ; }, abstract = {Repeatedly presenting a non-reinforced stimulus normally retards conditioning to this stimulus when it is coupled to a reinforcer. This phenomenon is called latent inhibition. Since latent inhibition is disturbed after systemic administration of amphetamine, the present study investigated the role of the mesolimbic and nigrostriatal dopamine terminal fields in latent inhibition using a conditioned taste aversion (CTA) paradigm. In this paradigm, a 5% sucrose solution was used as the test stimulus and lithium chloride (LiCl) as the CTA inducing drug. The degree of CTA was assessed by measuring the sucrose preference in a two-bottle sucrose/water choice paradigm 24 h after the LiCl injection. Since conditioned taste aversion has so far not been used to evaluate the role of dopamine in latent inhibition, we first studied the effects of systemic application of amphetamine. The results show that intraperitoneal injections of 0.25 or 0.5 mg/kg d-amphetamine sulphate (given at preexposure and conditioning) significantly disrupted latent inhibition, by selectively reducing sucrose preference in the preexposed group. This could not be attributed to a reduced sucrose intake during preexposure or to a conditioned taste aversion effect of amphetamine itself. In experiment 2 local bilateral administration of 10 micrograms/0.5 microliter amphetamine into the nucleus accumbens or the dorsal striatum was given in the pre-exposed and the conditioning phase, after which the rats were allowed to drink for a fixed period of time. The results show a significant reduction in latent inhibition after intrastriatal, but not after intra-accumbens injections of amphetamine. Intra-accumbens injections of amphetamine, however, significantly reduced fluid intake during preexposure and conditioning. In experiment 3, we therefore repeated this experiment, but allowed the animals to drink only a restricted amount of liquid during preexposure and conditioning. Again the results show a disruption of latent inhibition after intrastriatal, but not intra-accumbens injection of amphetamine. These experiments emphasize the importance of the nigrostriatal dopamine system in the disruption of latent inhibition, at least when using the conditioned taste aversion paradigm. A possible mechanism by which the dorsal striatum might influence latent inhibition is discussed.}, } @article {pmid9014026, year = {1997}, author = {Bienkowski, P and Kuca, P and Piasecki, J and Kostowski, W}, title = {5-HT3 receptor antagonist, tropisetron, does not influence ethanol-induced conditioned taste aversion and conditioned place aversion.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {14}, number = {1}, pages = {63-69}, doi = {10.1016/s0741-8329(96)00108-5}, pmid = {9014026}, issn = {0741-8329}, mesh = {Animals ; Avoidance Learning/drug effects ; Central Nervous System Depressants/*pharmacology ; Conditioning, Operant/*drug effects ; Ethanol/*pharmacology ; Indoles/*pharmacology ; Male ; Morphine/pharmacology ; Narcotics/pharmacology ; Rats ; Rats, Wistar ; Receptors, Serotonin/*drug effects/physiology ; Serotonin Antagonists/*pharmacology ; Taste/*drug effects ; Tropisetron ; }, abstract = {Numerous works have demonstrated an interaction between 5-HT3 receptor antagonists and some of the effects of ethanol (EtOH) using biochemical, electrophysiological, and behavioral techniques. Thus 5-HT3 antagonists are capable of reducing EtOH-induced release of dopamine in the nucleus accumbens, EtOH-induced hyperlocomotion, and voluntary EtOH consumption in laboratory animals. In addition to its rewarding effect, EtOH possesses aversive properties as demonstrated in the conditioned taste aversion (CTA) and conditioned place aversion (CPA) paradigms. The role of 5-HT3 receptors in aversive effects of EtOH remains, however, unknown. We decided to study the effect of 5-HT3 antagonist, tropisetron, on aversive properties of EtOH (1.5 g/kg i.p.) in rats using the CTA and CPA models. In addition, effect of tropisetron on morphine (Mf)-induced CTA (10.0 mg/kg SC) was investigated. Tropisetron (0.001-0.5 mg/kg) did not influence CTA produced by EtOH and Mf. When given alone, it failed to produce any taste conditioning. Furthermore, tropisetron did not modify CPA induced by EtOH. Our results suggest that 5-HT3 receptors are not involved in aversive effects of acute doses of EtOH.}, } @article {pmid9008862, year = {1997}, author = {Boakes, RA and Westbrook, RF and Elliott, M and Swinbourne, AL}, title = {Context dependency of conditioned aversions to water and sweet tastes.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {23}, number = {1}, pages = {56-67}, doi = {10.1037//0097-7403.23.1.56}, pmid = {9008862}, issn = {0097-7403}, mesh = {Animals ; Conditioning, Psychological/*physiology ; Discrimination, Psychological/*physiology ; Drinking/*physiology ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {Three experiments exposed rats (Rattus norvegicus) to a discriminative conditioning procedure whereby a specific fluid was followed by lithium in one environment but not in another. This produced context-specific aversion to water, as detected by 2-bottle tests in Experiment 1, and a context-dependent saccharin aversion, which was unaffected by context extinction, in Experiment 2. Experiment 3 found that sucrose preexposure increased contextual control over the aversion established by sucrose-lithium pairings but had no effect on the target context. By contrast, target context exposure during conditioning reduced aversion to this context but did not affect contextual control of the sucrose aversion. In conclusion, depending on the conditioning procedures, contextual control of a taste aversion can be independent of the context's Pavlovian properties.}, } @article {pmid8981619, year = {1997}, author = {Morley, JE and Suarez, MD and Mattamal, M and Flood, JF}, title = {Amylin and food intake in mice: effects on motivation to eat and mechanism of action.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {56}, number = {1}, pages = {123-129}, doi = {10.1016/S0091-3057(96)00168-2}, pmid = {8981619}, issn = {0091-3057}, mesh = {Amyloid/*pharmacology ; Animals ; Appetite Depressants/*pharmacology ; Arginine/pharmacology ; Avoidance Learning/drug effects ; Conditioning, Operant/drug effects ; Drinking/drug effects ; Eating/*drug effects ; Gastric Fundus/drug effects/enzymology ; Islet Amyloid Polypeptide ; Male ; Mice ; Mice, Inbred Strains ; Milk ; *Motivation ; Nitric Oxide Synthase/metabolism ; Taste/drug effects ; Water ; }, abstract = {Amylin is a hormone produced by the pancreatic islets of Langerhans. Amylin decreased food pellet consumption. Amylin also decreased lever pressing for milk solution whether or not the mice were prefed. Amylin did not produce a conditioned taste aversion in a two bottle test, whereas lithium chloride did. In addition, L-arginine, a precursor for nitric oxide synthesis, was demonstrated to inhibit the ability of amylin to decrease food intake. Amylin did not alter nitric oxide synthase activity in the fundus of the stomach. These studies demonstrated that amylin inhibits food intake at a higher range of doses than is typical of anorectic agents such as cholecystokinin. Amylin does not appear to decrease food intake by reducing the release of nitric oxide but may affect appetite by modulating serum glucose levels when co-released with insulin.}, } @article {pmid8976526, year = {1997}, author = {Perks, SM and Clifton, PG}, title = {Reinforcer revaluation and conditioned place preference.}, journal = {Physiology & behavior}, volume = {61}, number = {1}, pages = {1-5}, doi = {10.1016/s0031-9384(96)00243-0}, pmid = {8976526}, issn = {0031-9384}, mesh = {Animals ; *Association Learning ; Avoidance Learning ; *Conditioning, Classical ; Hunger ; Lithium Chloride/toxicity ; Male ; Mental Recall ; *Motivation ; Rats ; *Social Environment ; Taste ; Thirst ; }, abstract = {Conditioned place preference (CPP) tests provide a novel way of testing an animal's ability to respond to direct manipulation of its motivational state. In the first of two studies, rats exhibited an appropriate preference for a place previously paired with either food or fluid, depending on their current motivational state (hungry or thirsty). Preference was independent of the animal's prior exposure to the relevant reinforcer in that motivational state. In the second experiment, a sucrose solution was used to generate a place preference and was subsequently devalued using a LiCl taste aversion procedure. One group (B) received two CTA sessions and two further groups received a single CTA session either with (R), or without (N), a further nonreinforced opportunity to drink sucrose. Group B exhibited a substantial place aversion and a considerable reduction in sucrose consumption in a test following assessment of place preference. A weak place aversion was found in group N and a weak place preference was shown by group R; sucrose consumption in a test following measurement of place preference followed a similar pattern. These two studies indicate that performance on a place preference task is directly sensitive to both shifts in motivational state and reduction in reinforcer value.}, } @article {pmid8986351, year = {1996}, author = {Nader, K and Bechara, A and van der Kooy, D}, title = {Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discriminative properties.}, journal = {Behavioral neuroscience}, volume = {110}, number = {6}, pages = {1496-1502}, doi = {10.1037//0735-7044.110.6.1496}, pmid = {8986351}, issn = {0735-7044}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal/drug effects/physiology ; Brain Stem/*drug effects/*physiology ; Conditioning, Classical/drug effects/physiology ; Male ; Morphine/*adverse effects/*pharmacology ; Motivation ; Pons/drug effects/physiology ; Rats ; Rats, Wistar ; *Substance Withdrawal Syndrome/etiology/physiopathology ; Taste/physiology ; }, abstract = {This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task.}, } @article {pmid8946502, year = {1996}, author = {Houpt, TA and Philopena, JM and Joh, TH and Smith, GP}, title = {c-Fos induction in the rat nucleus of the solitary tract by intraoral quinine infusion depends on prior contingent pairing of quinine and lithium chloride.}, journal = {Physiology & behavior}, volume = {60}, number = {6}, pages = {1535-1541}, doi = {10.1016/s0031-9384(96)00326-5}, pmid = {8946502}, issn = {0031-9384}, support = {MH00149/MH/NIMH NIH HHS/United States ; MH44043/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Count/drug effects ; Conditioning, Psychological/*drug effects ; Lithium Chloride/*pharmacology ; Male ; Proto-Oncogene Proteins c-fos/*drug effects ; Quinine/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/*drug effects ; }, abstract = {Intraoral infusions of sucrose or saccharin induce c-Fos-like immunoreactivity (c-FLI) in the intermediate nucleus of the solitary tract (iNTS) of rats after acquisition of a conditioned taste aversion (CTA). The induction of c-FLI in the iNTS may be a consequence of the shift in behavioral response from ingestive to aversive behaviors that characterize acquisition and expression of a CTA. To test this hypothesis, rats were intraorally infused with 0.3 mM quinine sulfate, an aversive taste, 1. prior to conditioning, 2. after 3 noncontingent (unpaired) infusions of quinine and toxic lithium chloride (LiCl) injections, 3. after conditioning with 3 contingent pairings of quinine and LiCl, and 4. after extinction with repeated unpaired infusions of quinine. Intraoral infusions of quinine induced c-FLI in the iNTS only after acquisition of a CTA against quinine; quinine failed to induce c-FLI in the iNTS of unconditioned, noncontingently treated, or extinguished rats. The pattern of c-FLI in the iNTS induced by expression of a CTA against quinine was quantitatively and anatomically similar to that elicited by sucrose in rats expressing a CTA against sucrose. We conclude that aversive responses per se are not sufficient to induce c-FLI in the iNTS. Furthermore, contingent pairing of quinine and LiCl does not cause a shift in behavioral response from palatable, ingestive behaviors to aversive behaviors as in acquisition of a CTA against sucrose. Thus, we also conclude that a shift in behavior from ingestive to aversive responses is not required for increased c-FLI expression in the iNTS during CTA expression. Therefore, the induction of c-FLI in the iNTS during expression of a CTA may be correlated with neuronal processes specific to acquisition and expression of a CTA.}, } @article {pmid8946491, year = {1996}, author = {Batsell, WR and George, JW}, title = {Unconditioned stimulus intensity and retention interval effects.}, journal = {Physiology & behavior}, volume = {60}, number = {6}, pages = {1463-1467}, doi = {10.1016/s0031-9384(96)00310-1}, pmid = {8946491}, issn = {0031-9384}, mesh = {Animals ; Conditioning, Psychological/*physiology ; Dose-Response Relationship, Drug ; Eating/*physiology ; Learning/*physiology ; Male ; Rats ; Retention, Psychology/*physiology ; Saccharin/*pharmacology ; Taste/*physiology ; }, abstract = {In single-element taste-aversion learning, retention interval effects are seen if taste aversions are paradoxically weak when they are tested 1 day after conditioning than when they are tested 3 or more days after conditioning. One explanation of this phenomenon is that weaker taste aversions may increase in strength across a retention interval. To test this possibility, rats were given saccharin followed by an unconditioned stimulus (US) of weak, medium, or high intensity; testing occurred after a 1-day or a 5-day retention interval. The results showed retention-interval effects only at medium and high dosage levels, but not following a weak-intensity US. Furthermore, at the 5-day retention interval, aversion strength increased as the intensity of the US increased. However, at the 1-day retention interval, there were no significant differences due to US intensity. In accordance with previous experiments, this outcome suggests that nonassociative factors, such as US novelty, and not associative factors (e.g., US intensity), modulate taste aversion performance on a 1-day test.}, } @article {pmid9001712, year = {1996}, author = {Schafe, GE and Bernstein, IL}, title = {Forebrain contribution to the induction of a brainstem correlate of conditioned taste aversion: I. The amygdala.}, journal = {Brain research}, volume = {741}, number = {1-2}, pages = {109-116}, doi = {10.1016/s0006-8993(96)00906-7}, pmid = {9001712}, issn = {0006-8993}, support = {DC00248/DC/NIDCD NIH HHS/United States ; }, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Stem/anatomy & histology/*physiology ; Cell Nucleus/metabolism ; Immunohistochemistry ; Male ; Prosencephalon/anatomy & histology/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Solitary Nucleus/cytology/physiology ; Taste/*physiology ; }, abstract = {The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) has been shown to be a reliable cellular correlate of the acquisition and/or behavioral expression of a conditioned taste aversion (CTA). To begin to define neuroanatomical structures and pathways that contribute to this cellular response and to CTA learning in general, electrolytic lesions of the amygdala were combined with immunostaining for c-FLI. Rats were given either unilateral or bilateral electrolytic lesions of the amygdala or "sham' operations. Following surgery "paired' animals were given a single conditioning trial consisting of intraoral infusion of 5 ml 0.15% sodium-saccharin followed by injection with LiCl (0.15 M, 20 ml/kg, i.p.) while "unpaired' controls received a non-contingent saccharin-LiCl presentation. When tested, unilateral-lesioned rats displayed a CTA by rejecting the saccharin, but increases in c-FLI were evident only on the side of the iNTS contralateral to the lesion. Rats with bilateral lesions showed no evidence of having acquired a CTA and no increase in c-FLI in iNTS relative to unpaired controls. These findings support involvement of amygdala in CTA learning and suggest that a lateralized connection between amygdala and iNTS is necessary for the conditioned c-FLI which is induced by exposure to a conditioned aversive taste.}, } @article {pmid8979936, year = {1996}, author = {Calton, JL and Mitchell, KG and Schachtman, TR}, title = {Conditioned Inhibition Produced by Extinction of a Conditioned Stimulus.}, journal = {Learning and motivation}, volume = {27}, number = {4}, pages = {335-361}, doi = {10.1006/lmot.1996.0020}, pmid = {8979936}, issn = {0023-9690}, abstract = {Four experiments used a conditioned taste aversion procedure to examine the potential for CS-alone extinction treatment to produce a conditioned stimulus that possesses inhibitory properties. In Experiment 1, saccharin was paired with LiCl, and then saccharin was presented alone for several trials to produce extensive behavioral extinction. Animals receiving this treatment were retarded in reacquiring conditioned responding to saccharin relative to control subjects receiving conditioning to the flavor for the first time. In Experiment 2, the extinguished saccharin stimulus was shown to decrease conditioned responding to a known excitor when the two stimuli were presented in compound as a summation test. Experiments 3A and 3B replicated the findings of Experiments 1 and 2 while providing evidence that the effects were not due to the differential effects of neophobia during testing. These three experiments revealed that an extinguished conditioned excitor passes retardation and summation tests for conditioned inhibition. Experiment 4 found that extinction of a known excitor was slowed when the excitor was extinguished in compound with a previously extinguished conditioned stimulus. That is, an extinguished CS provided protection from extinction to another CS, a finding also consistent with the view that extinction produces conditioned inhibition.}, } @article {pmid8956099, year = {1996}, author = {Gonda, Z and Lehotzky, K}, title = {Effect of prenatal aluminium lactate exposure on conditioned taste aversion and passive avoidance task in the rat.}, journal = {Journal of applied toxicology : JAT}, volume = {16}, number = {6}, pages = {529-532}, doi = {10.1002/(SICI)1099-1263(199611)16:6<529::AID-JAT392>3.0.CO;2-S}, pmid = {8956099}, issn = {0260-437X}, mesh = {Aluminum/*toxicity ; Aluminum Compounds/*toxicity ; Animals ; Aversive Therapy ; Avoidance Learning/*drug effects ; Conditioning, Psychological ; Female ; Lactates/*toxicity ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Pregnant SPRD rats were injected s.c. daily with 2.45, 4.9 and 9.8 mg kg-1 aluminium lactate or distilled water on gestational days 7-15. Gestational aluminium treatment had no effect either on litter size or the body weight of pups on postnatal day 1 but it decreased postnatal weight gain resulting in significantly lower body weight at weaning (postnatal day 22). It had no effect on the acquisition of a conditioned taste aversion, but in a passive avoidance task the learning ability of pups of dams given the top dose of aluminium was impaired.}, } @article {pmid8949998, year = {1996}, author = {Bielavska, E and Roldan, G}, title = {Ipsilateral connections between the gustatory cortex, amygdala and parabrachial nucleus are necessary for acquisition and retrieval of conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {81}, number = {1-2}, pages = {25-31}, doi = {10.1016/s0166-4328(96)00039-3}, pmid = {8949998}, issn = {0166-4328}, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/*physiology ; Functional Laterality/*physiology ; Male ; Memory/physiology ; Neural Pathways/anatomy & histology/physiology ; Pons/anatomy & histology/*physiology ; Rats ; Somatosensory Cortex/anatomy & histology/*physiology ; Taste/*physiology ; Tetrodotoxin/pharmacology ; }, abstract = {Acquisition and retrieval of conditioned taste aversion (CTA) is implemented by the interaction of several brain structures. In order to clarify the role of 3 important gustatory and visceral relays, gustatory neocortex (GC), amygdala (AM) and parabrachial nucleus (PB), two experimental series were carried out. In Expt. 1 reversible unilateral lesions of the PB and AM or of AM and GC were induced by 10 ng of tetrodotoxin (TTX) either in the same hemisphere or in the opposite hemispheres during CTA acquisition. It was found that contralateral TTX injections into the above structures caused a complete blockade of CTA acquisition which was not affected by ipsilateral TTX administration. In Expt. 2, retrieval of CTA acquired during unilateral blockade of the PB or AM in one hemisphere has been examined during unilateral TTX blockade of GC alone, AM alone or during combined GC and AM inactivation either in the same or in the contralateral hemispheres. A clear CTA retrieval impairment was found only when structures in the opposite hemispheres were blocked. These results indicate a complete lateralization of CTA acquisition and retrieval processes and suggest that the long-term CTA engram can be formed in each hemisphere separately without participation of the contralateral hemisphere.}, } @article {pmid8947316, year = {1996}, author = {Risinger, FO and Bormann, NM and Oakes, RA}, title = {Reduced sensitivity to ethanol reward, but not ethanol aversion, in mice lacking 5-HT1B receptors.}, journal = {Alcoholism, clinical and experimental research}, volume = {20}, number = {8}, pages = {1401-1405}, doi = {10.1111/j.1530-0277.1996.tb01140.x}, pmid = {8947316}, issn = {0145-6008}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA10520/AA/NIAAA NIH HHS/United States ; AA10760/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholism/*genetics/physiopathology ; Animals ; Association Learning/physiology ; Avoidance Learning/physiology ; Conditioning, Classical/physiology ; Ethanol/administration & dosage ; Injections, Intraperitoneal ; Mice ; Mice, Knockout ; *Motivation ; Motor Activity/physiology ; Receptors, Serotonin/*genetics/physiology ; Social Environment ; Taste/genetics/physiology ; }, abstract = {Various serotonergic receptor systems are thought to influence the motivational effects of ethanol. This experiment characterized the acquisition of ethanol-induced conditioned taste aversion and ethanol-induced conditioned place reference in mutant knockout mice lacking 5-HT1b receptors. In the taste conditioning procedure, adult homozygous knockout mice (-/-) and homozygous wild-type mice (+/+) received access to 0.2 M NaCl solution, followed immediately by intraperitoneal injection of 0 to 4 g/kg of ethanol. Ethanol produced dose-dependent conditioned taste aversion that was the same in both genotypes. In the place conditioning procedure, knockout and wild-type mice received six pairings of a tactile stimulus with ethanol (2 g/kg, i.p.). A different tactile stimulus was paired with saline. Ethanol produced increases in locomotor activity, with wild-type mice showing higher levels of ethanol-stimulated activity than knockout mice during conditioning trials 5 and 6. Wild-type mice demonstrated conditioned place preference for the ethanol-paired stimulus. In contrast, knockout mice showed no evidence of place conditioning. These results are generally consistent with an important role for serotonergic systems in ethanol reward and specifically indicate that 5-HT1b receptors are important for ethanol's rewarding effects but not for ethanol's aversive effects.}, } @article {pmid8931016, year = {1996}, author = {Ellenbroek, BA and Budde, S and Cools, AR}, title = {Prepulse inhibition and latent inhibition: the role of dopamine in the medial prefrontal cortex.}, journal = {Neuroscience}, volume = {75}, number = {2}, pages = {535-542}, doi = {10.1016/0306-4522(96)00307-7}, pmid = {8931016}, issn = {0306-4522}, mesh = {Animals ; Avoidance Learning/drug effects ; Benzazepines/administration & dosage/pharmacology ; Dopamine/*physiology ; Dopamine Antagonists/pharmacology ; Dopamine D2 Receptor Antagonists ; Drinking Behavior/drug effects ; Evoked Potentials/physiology ; Injections ; Male ; Prefrontal Cortex/drug effects/*physiology ; Rats ; Rats, Wistar ; Receptors, Dopamine D1/antagonists & inhibitors ; Reflex, Startle/drug effects/*physiology ; Sulpiride/administration & dosage/pharmacology ; Synaptic Transmission/drug effects ; Taste/drug effects ; }, abstract = {The prefrontal cortex has often been implicated in the pathophysiology of schizophrenia. Schizophrenic patients are known to suffer from certain information processing deficits, which can be detected, among others, in the prepulse inhibition and the latent inhibition paradigm. The present study was designed to investigate the role of dopamine receptors in the medial prefrontal cortex in prepulse inhibition and latent inhibition. The results show that the local application of the selective antagonist of the dopamine D1-like receptor family, SCH 39166, into the medial prefrontal cortex dose-dependently reduced prepulse inhibition. Likewise, the selective antagonist of the dopamine D2-like receptor family, sulpiride, injected into the medial prefrontal cortex dose-dependently reduced prepulse inhibition. Neither of these antagonists, however, influenced latent inhibition as measured with the conditioned taste aversion paradigm. These data further indicate that the neuronal substrates of latent inhibition and prepulse inhibition are clearly different. Since the prefrontal cortex is intimately related to subcortical dopamine, the possible differential involvement of subcortical dopaminergic terminal fields in prepulse inhibition and latent inhibition is discussed.}, } @article {pmid8959041, year = {1996}, author = {Benson, KA and Ali, SF and Wilson, MC}, title = {The effects of prenatal cocaine exposure on dopaminergic challenge and receptor binding in Wistar rats.}, journal = {Annals of the New York Academy of Sciences}, volume = {801}, number = {}, pages = {289-300}, doi = {10.1111/j.1749-6632.1996.tb17449.x}, pmid = {8959041}, issn = {0077-8923}, mesh = {Animals ; Avoidance Learning/drug effects ; Benzazepines/metabolism/pharmacology ; Cocaine/*pharmacology ; Dopamine/*metabolism ; Dopamine Agonists/pharmacology ; Female ; Male ; Motor Activity/drug effects ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Protein Binding ; Rats ; Rats, Wistar ; Receptors, Dopamine/*drug effects/metabolism ; Spiperone/metabolism/pharmacology ; Tritium ; }, abstract = {The behavioral teratogenic effects of prenatal cocaine administration in Wistar rats were assessed in dams treated throughout gestation via oral gavage with either 0 or 80 mg/kg of cocaine. A pair-fed (PF) cohort group for the 80-mg/kg dose was used to control for an anorexic effect of cocaine. Alterations in the dopaminergic system at maturity were evaluated using pharmacological challenges with amphetamine and cocaine and by measuring D1 and D2 receptor binding in the nucleus accumbens and caudate nucleus. No significant difference among the offspring of the treatment groups was found in amphetamine-induced locomotion. A cocaine-based conditioned taste aversion was established in all offspring, but no significant effect of prenatal cocaine treatment was seen. Dopamine receptor binding was not significantly influenced by prenatal treatment, although a decreased D1 binding in the caudate nucleus of the prenatal cocaine rats approached significance.}, } @article {pmid8930332, year = {1996}, author = {Dougherty, KD and Salat, D and Walsh, TJ}, title = {Intraseptal injection of the cholinergic immunotoxin 192-IgG saporin fails to disrupt latent inhibition in a conditioned taste aversion paradigm.}, journal = {Brain research}, volume = {736}, number = {1-2}, pages = {260-269}, doi = {10.1016/0006-8993(96)00712-3}, pmid = {8930332}, issn = {0006-8993}, mesh = {Analysis of Variance ; Animals ; Antibodies, Monoclonal/administration & dosage/*pharmacology ; Biogenic Monoamines/metabolism ; Brain/drug effects/*physiology ; Choline O-Acetyltransferase/metabolism ; Cholinergic Agents/administration & dosage/*pharmacology ; Conditioning, Operant/*drug effects ; Drinking Behavior/drug effects ; Immunotoxins/administration & dosage/*pharmacology ; Male ; Microinjections ; N-Glycosyl Hydrolases ; Rats ; Rats, Sprague-Dawley ; Ribosome Inactivating Proteins, Type 1 ; Saccharin ; Saporins ; *Taste ; Water Deprivation ; }, abstract = {Male Sprague-Dawley rats received injections of 100 or 375 ng 192-IgG saporin (SAP) or artificial CSF (C) into the medial septum/diagonal band complex (MSDB). SAP treated rats exhibited brief increases in daily water consumption which recovered to control levels by twenty one days following surgical treatment. Half of all subjects were preexposed to a 0.2% saccharin solution (CS) for 4 consecutive days prior to the establishment of a conditioned taste aversion (CTA) to saccharin. SAP was not found to alter acquisition of a normal CTA nor CS preexposure effects. All subjects which experienced CS/US pairing displayed aversions to saccharin when given a two bottle choice test. However, those subjects which were preexposed to saccharin prior to CS/US pairing displayed significantly weaker aversions than non-preexposed subjects. These subjects consumed a higher percent saccharin on test day and their CTAs extinguished more rapidly relative to non-preexposed subjects. While these behavioral measures remained undisrupted, intraseptal SAP treatment dose-dependently decreased hippocampal levels of high affinity choline transport as well as significantly decreasing HAChT in cingulate and frontal cortices. No such changes in HAChT were observed in striatum or entorhina cortex. These data suggest that the MSDB cholinergic cell population is not critical to selective attentional processes believed to underlie latent inhibition.}, } @article {pmid8897973, year = {1996}, author = {Tang-Christensen, M and Larsen, PJ and Göke, R and Fink-Jensen, A and Jessop, DS and Møller, M and Sheikh, SP}, title = {Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats.}, journal = {The American journal of physiology}, volume = {271}, number = {4 Pt 2}, pages = {R848-56}, doi = {10.1152/ajpregu.1996.271.4.R848}, pmid = {8897973}, issn = {0002-9513}, mesh = {Animals ; Behavior, Animal/drug effects ; Brain/*physiology ; Drinking/*drug effects ; Eating/*drug effects ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptides ; Injections, Intraventricular ; Male ; Natriuresis/drug effects ; Peptide Fragments/*pharmacology ; Rats ; Rats, Wistar ; }, abstract = {Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.}, } @article {pmid9000221, year = {1996}, author = {Serova, ON and Solov'ea, NA and Lagutina, LV and Obukhova, MF}, title = {Formation of taste aversion and preference in protein synthesis inhibition in rats.}, journal = {Neuroscience and behavioral physiology}, volume = {26}, number = {5}, pages = {477-481}, pmid = {9000221}, issn = {0097-0549}, mesh = {Animals ; Azaguanine/pharmacology ; Cycloheximide/pharmacology ; Drinking ; Male ; *Protein Biosynthesis ; Protein Synthesis Inhibitors/pharmacology ; Rats ; Saccharin/administration & dosage/pharmacokinetics ; Taste/drug effects/*physiology ; }, abstract = {The investigation was devoted to the role of the synthesis of protein and peptide factors during the formation of chemosensory memory in rats. Two models of gustatory memorization were used: conditioned taste aversion (CTA), induced by the association of the taste of saccharine with a toxic injection of lithium chloride, and enhanced taste preference (ETP), induced by the influence of preliminary drinking of a saccharine solution on its repeat consumption. It was found that, under conditions of the inhibition of protein synthesis in the brain of 43% by cycloheximide and of 59% by 8-azaguanine, CTA does not form. ETP does not form under the influence of cycloheximide, but not [sic] of 8-azaguanine. A hypothesis was advanced regarding the participation of a varied spectrum of protein and peptide substances in the formation of taste aversion and preference. An influence of protein synthesis blockers on the process of retrieval of gustatory memory was not found.}, } @article {pmid8892522, year = {1996}, author = {Thiele, TE and Roitman, MF and Bernstein, IL}, title = {c-Fos induction in rat brainstem in response to ethanol- and lithium chloride-induced conditioned taste aversions.}, journal = {Alcoholism, clinical and experimental research}, volume = {20}, number = {6}, pages = {1023-1028}, doi = {10.1111/j.1530-0277.1996.tb01941.x}, pmid = {8892522}, issn = {0145-6008}, support = {AA07455/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects ; Brain Mapping ; Brain Stem/*drug effects/pathology ; Conditioning, Classical/*drug effects ; Ethanol/*toxicity ; Gene Expression/drug effects ; Immunoenzyme Techniques ; Lithium Chloride/*toxicity ; Male ; Proto-Oncogene Proteins c-fos/*genetics ; Rats ; Taste/*drug effects ; }, abstract = {When consumption of a novel taste (conditioned stimulus; CS) is followed by exposure to a toxin, organisms will avoid consumption of that taste in the future. This learned response, known as a conditioned taste aversion (CTA), can be demonstrated using a variety of drugs, including lithium chloride (LiCl) and ethanol. c-Fos immunohistochemistry was used to examine neural activation in the rat brainstem associated with drug administration and with a CS taste previously paired with these drugs. Relative to saline controls, animals injected with either LiCl (76 mg/kg) or ethanol (3.5 g/kg) displayed greater c-Fos expression in area postrema, nucleus of the solitary tract (NTS), and lateral parabrachial nucleus. At these doses, LiCl- and ethanol-injected groups did not differ from each other. For establishing a CTA, intraoral infusion of a 0.15% saccharin solution was followed by injection of either LiCl or ethanol. Both LiCl and ethanol produced quantitatively similar CTAs. Relative to unpaired control groups, saccharin paired with either drug induced significant c-Fos expression in NTS. Thus, like LiCl, ethanol and tastes that have become aversive by virtue of their association with ethanol activate brainstem regions hypothesized to play a role in CTA learning.}, } @article {pmid8883817, year = {1996}, author = {Naor, C and Dudai, Y}, title = {Transient impairment of cholinergic function in the rat insular cortex disrupts the encoding of taste in conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {79}, number = {1-2}, pages = {61-67}, doi = {10.1016/0166-4328(95)00262-6}, pmid = {8883817}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Carbachol/administration & dosage/pharmacology ; Cerebral Cortex/drug effects/*physiology ; Dose-Response Relationship, Drug ; Male ; Memory/drug effects ; Microinjections ; Muscarinic Agonists/administration & dosage/pharmacology ; Muscarinic Antagonists/administration & dosage/pharmacology ; Parasympathetic Nervous System/drug effects/*physiology ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Scopolamine/administration & dosage/pharmacology ; Sweetening Agents/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {The muscarinic antagonist scopolamine blocks conditioned taste aversion (CTA) when microinjected bilaterally into the rat insular cortex shortly before the exposure of the rat to a novel taste (the conditioned stimulus, CS) in CTA training. Scopolamine has no effect when microinjected shortly after the exposure to the novel taste or shortly before the application of the malaise-inducing agent (unconditioned stimulus, UCS). Scopolamine does not affect sensory, motor and retrieval mechanisms required for performing the CTA task, and does not block CTA when injected into another cortical area. The effect of scopolamine is independent of the taste used as CS. Furthermore, microinjection of scopolamine into the insular cortex shortly before the pre-exposure to a new taste in a latent inhibition paradigm, impairs the attenuation of CTA by that pre-exposure. Other muscarinic antagonists, pirenzepine and AF DX-116, have an effect similar to that of scopolamine. Comparison of the dose-dependency curves of the muscarinic antagonists suggests a predominant role in CTA for M2 subtype receptors. Carbachol, a muscarinic agonist, also impairs the encoding of taste in the insular cortex, but the results are confounded by the ability of that ligand to induce seizures. Our findings suggest that cholinergic neuromodulation participates in processing the CS in the gustatory cortex in CTA, either by encoding novelty at the cellular level, or by instructing the neural circuits to store the novel taste representation.}, } @article {pmid8876993, year = {1996}, author = {Caulliez, R and Meile, MJ and Nicolaidis, S}, title = {A lateral hypothalamic D1 dopaminergic mechanism in conditioned taste aversion.}, journal = {Brain research}, volume = {729}, number = {2}, pages = {234-245}, pmid = {8876993}, issn = {0006-8993}, mesh = {Animals ; Conditioning, Psychological/*physiology ; Drinking/drug effects ; Hypothalamus/*physiology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Dopamine D1/*physiology ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {The aim of this study was to elucidate the role of the neuropil located in the LHA in the acquisition of the association between a taste (conditioned stimulus = saccharin) and a visceral distress (unconditioned stimulus = lithium chloride) leading to long delayed learning of a conditioned taste aversion (CTA). In 82 male rats guide-cannulae were directed bilaterally into the basolateral LHA where bilateral microinjections were made after the conditioned stimulus and before the unconditioned stimulus. We found that: (1) tetrodotoxin, a non-specific blocker of neuronal activity disrupted the acquisition of the CTA; (2) SCH 23390, a specific D1 receptor blocker also disrupted learning of the CTA, while sulpiride, a D2 receptor blocker, did not; (3) neither the specific blockade of D1 nor of D2 receptors could prevent the visceral distress-induced decrease in water intake, showing that the visceral distress was actually experienced; and (4) the sham taste aversion learning (i.e. without visceral distress) revealed that neither the D1 nor the D2 receptors blockade induced by themselves either a taste preference or a taste aversion towards saccharin, indicating that the impaired acquisition of the CTA was not due to a superimposed taste preference that could have been induced by the intra-LHA D1 receptors blockade. It is concluded that the neuropil in the LHA is necessary in the process of the acquisition of long delayed learning and that it uses a D1 receptor specific mechanism.}, } @article {pmid11224428, year = {1996}, author = {de Beun, R and Lohmann, A and Kuhl, E and Dalmus, M and Schreiber, R and De Vry, J}, title = {Stimulus properties of the L-type calcium channel agonist BAY k 8644 in rats.}, journal = {Behavioural pharmacology}, volume = {7}, number = {4}, pages = {346-354}, doi = {10.1097/00008877-199608000-00006}, pmid = {11224428}, issn = {1473-5849}, abstract = {Calcium (Ca(2+)) channels appear to be involved in the regulation of ethanol (EtOH) intake, as indicated by the effectiveness of both L-type Ca(2+) channel antagonists and agonists in reducing EtOH intake in animals. The present study was aimed to investigate rewarding/aversive and discriminative stimulus effects of the Ca(2+) channel agonist BAY k 8644, a compound showing pronounced anti-alcohol effects in rats. Therefore, a series of conditioned taste aversion (CTA), conditioned place preference (CPP) and two-lever drug discrimination (DD) experiments were conducted in Wistar rats, with (+/-)-BAY k 8644 and its enantiomers. After i.p. application, (+/-)-BAY k 8644 (0.0625-1mg/kg), (-)-BAY k 8644 (0.125-1mg/kg) and (+)-BAY k 8644 (2.5-20mg/kg) all induced a dose-dependent CTA. The minimal effective doses (MED) for (+/-)-, (-)- and (+)-BAY k 8644 were 0.25, 0.25 and 10mg/kg, respectively. In a CPP study, however, (+/-)-BAY k 8644 (0.25-2mg/kg, i.p.) showed neither aversive nor rewarding stimulus properties. Rats were trained to discriminate (-)-BAY k 8644 (0.3mg/kg, i.p.), the enantiomer acting as a high potency Ca(2+) channel agonist, from vehicle, in a two-lever DD procedure (ED(50)) value: 0.05mg/kg); full generalisation: 0.1mg/kg). The (-)-BAY k 8644 cue dose-dependently generalized to (+/-)-BAY k 8644 and (+)-BAY k 8644, the enantiomer acting as a low potency Ca(2+) channel antagonist, with ED(50) values of 0.06 and 0.28mg/kg, respectively. Both (+/-)- and (+)-BAY k 8644 produced full generalization at 1mg/kg, the latter compound showing an inverted U-shaped curve (i.e., this was the only dose showing >80% drug lever selection). The stimulus patterns of BAY k 8644 and its enantiomers appear to resemble the anti-alcohol profiles of these compounds. Therefore, commonalities between the stimulus properties of the agonistic and antagonistic enantiomers might provide a clue for the mechanism underlying the anti-alcohol effects of L-type Ca(2+) channel antagonists and agonists.}, } @article {pmid8864276, year = {1996}, author = {Schafe, GE and Stein, PL and Park, CR and Bernstein, IL}, title = {Taste aversion learning in fyn mutant mice.}, journal = {Behavioral neuroscience}, volume = {110}, number = {4}, pages = {845-848}, pmid = {8864276}, issn = {0735-7044}, support = {5 RO1 DC 00248-10/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Female ; *Genotype ; Lithium Chloride/toxicity ; Male ; Mental Recall/*physiology ; Mice ; Mice, Neurologic Mutants ; Mice, Transgenic ; *Neoplasm Proteins ; Protein-Tyrosine Kinases/*genetics ; Taste/*genetics ; src-Family Kinases ; }, abstract = {Conditioned taste aversion (CTA) learning is a robust form of classical conditioning in which animals rapidly associate a flavor with aversive internal symptoms. The present study assessed CTA learning in transgenic mice deficient in a specific nonreceptor tyrosine kinase (the fyn mutant). Fyn mutants show impaired long-term potentiation and marked deficits in acquisition of spatial learning tasks. To assess whether they are also impaired in CTA learning, fyn mutant and wild-type mice received 2 conditioning trials consisting of access to a flavored solution followed by administration of LiCl. Fyn mutant mice acquired significant CTAs following a single conditioning trial and these aversions were comparable to those seen in wild-type mice. These results indicate that the fyn mutation does not interfere with the acquisition of CTAs and hence that this mutation is not associated with a global learning deficit.}, } @article {pmid8853186, year = {1996}, author = {De Beun, R and Lohmann, A and De Vry, J}, title = {Conditioned taste aversion and place preference induced by the calcium channel antagonist nimodipine in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {54}, number = {4}, pages = {657-663}, doi = {10.1016/0091-3057(95)02232-5}, pmid = {8853186}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Male ; Nimodipine/*pharmacology ; Rats ; Rats, Wistar ; Task Performance and Analysis ; Taste/*drug effects ; }, abstract = {It has become clear that various calcium channel antagonists are able to suppress excessive intake of ethanol in rats. With respect to these findings, it has become of interest whether these drugs can act as rewarding and/or aversive stimulus. Therefore, such affective stimulus effects of the L-type calcium channel antagonist nimodipine and its enantiomers were studied in Wistar rats in a series of conditioned taste aversion (CTA; two-bottle choice procedure) and conditioned place preference (CPP; two-compartment procedure) experiments. Racemic nimodipine (0.95-15 mg/kg IP) was found to induce a dose-dependent CTA, 7.5 mg/kg being the lowest effective dose. Subsequent studies with both enantiomers revealed that the CTA effects of nimodipine are completely dependent on the activity of (-)-nimodipine. With (+)-nimodipine (0.25-90 mg/kg IP), none of the doses tested induced a significant CTA, whereas with (-)-nimodipine clear and dose-dependent CTA effects were noted (0.5-30 mg/kg IP). For this enantiomer, the lowest effective dose was 15 mg/kg. In additional CPP experiments, it was confirmed that (+/-)-nimodipine and (-)-nimodipine have affective stimulus properties, whereas (+)-nimodipine was again an ineffective stimulus (dose used for all drugs: 15 mg/kg IP). Interestingly, the affective stimulus effects as measured with CPP of (+/-)- and (-)-nimodipine turned out to be rewarding, as it was found that both drugs produced a significant place preference. It is concluded from these studies that nimodipine possesses intrinsic affective stimulus effects which are rewarding in nature. Furthermore, these stimulus effects are mediated by the activity of the (-)-enantiomer. Possibly, these rewarding effects of nimodipine may play a role in the reported attenuating effects of this drug on voluntary ethanol intake in rats.}, } @article {pmid8840909, year = {1996}, author = {Blair-West, JR and Denton, DA and McBurnie, MI and Weisinger, RS}, title = {The dipsogen angiotensin II does not stimulate ethanol intake in mice.}, journal = {Physiology & behavior}, volume = {60}, number = {2}, pages = {481-487}, doi = {10.1016/s0031-9384(96)80022-9}, pmid = {8840909}, issn = {0031-9384}, mesh = {Alcohol Drinking/*psychology ; Angiotensin II/administration & dosage/*pharmacology ; Animals ; Avoidance Learning/drug effects ; Body Weight/drug effects ; Drinking Behavior/*drug effects ; Eating/drug effects ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred BALB C ; Potassium Chloride/pharmacology ; Quinine/pharmacology ; Taste/drug effects ; }, abstract = {Mice that were habituated to drinking ethanol solution and mice that had drunk water only (naive mice) were given an ICV infusion of angiotensin II (Ang II) at 2.9 ng/h for 8 days to determine the effect of chronic ethanol intake on the ingestive response to this potent dipsogen. Ang II infusion in alcohol-naive mice increased daily water intake from 3.7 +/- 0.2 ml (mean +/- SE, n = 6) to 11.0 +/- 1.5 ml on day 4 (p < 0.001) and to 18.3 +/- 2.6 ml on day 8 (p < 0.001). In subsequent experiments, mice had access to 4% ethanol solution up to day 4 and then to water for 4 days during the Ang II infusion. Alcohol-naive mice did not increase daily fluid intake until the water was provided on day 5; intake increased to 17.5 +/- 2.3 ml on day 8 (p < 0.001, n = 7). Mice accustomed to drinking 4% ethanol (4.3 +/- 0.3 ml/day) also did not increase intake until the water was provided; intake reached 22.9 +/- 3.0 ml of water on day 8 (p < 0.001, n = 7). Mice accustomed to drinking 10% ethanol behaved similarly (n = 4). Thus, alcohol-naive or -habituated mice did not respond to this dipsogenic stimulus until water was available; the thirst for water was unimpaired. Preference-aversion tests showed that mice drank little or no 4% ethanol (or even 2% ethanol) when water was also available. Taste aversion, plus previous experience from ingestion of ethanol in habituated mice, may explain the rejection of ethanol to quench Ang II-induced thirst. Experimental results obtained using other aversive solutions, 3 mM quinine and 300 mM KCl, suggest that postingestional, metabolic effects of solutes may also contribute to such rejection.}, } @article {pmid8840888, year = {1996}, author = {von Kluge, S and Perkey, T and Peregord, J}, title = {An ear for quality: differential associative characteristics of taste-potentiated auditory and odor avoidance.}, journal = {Physiology & behavior}, volume = {60}, number = {2}, pages = {331-339}, doi = {10.1016/0031-9384(96)00032-7}, pmid = {8840888}, issn = {0031-9384}, mesh = {Acoustic Stimulation ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Eating ; Extinction, Psychological/physiology ; Generalization, Stimulus ; Hearing/*physiology ; Male ; Odorants ; Rats ; Rats, Sprague-Dawley ; Smell/*physiology ; Taste/*physiology ; }, abstract = {This research compared the avoidance behavior of rats exposed to either a taste-tone (NaCl-70 dB, 1800 Hz) or a taste-odor (NaCl-almond) compound that had been paired with LiCl-induced illness. When tested in the presence of either the odor or the auditory cue presented alone it was found that taste potentiated both cues, but stronger initial avoidance and resistance to extinction was shown to the odor cue. A second experiment examined the generalization of potentiated odor and auditory aversions to a novel environment. Rats were exposed to either a taste-odor or taste-tone compound, again followed by illness. Half of each group was tested in the conditioning chamber and half in a novel chamber. Odor aversions were not affected by location, whereas auditory aversions were significantly stronger in the conditioning chamber. Experiment 3 showed that taste-potentiated odor and auditory aversions showed different patterns of extinction when the taste aversion on which they were based was gradually extinguished. These experiments provide evidence that while the taste potentiation of auditory cues is a reliable phenomena, the pattern of effects is different from that of taste-potentiated odor aversions.}, } @article {pmid8840011, year = {1996}, author = {Wang, Y and Cummings, SL and Gietzen, DW}, title = {Temporal-spatial pattern of c-Fos expression in the rat brain in response to indispensable amino acid deficiency. II. The learned taste aversion.}, journal = {Brain research. Molecular brain research}, volume = {40}, number = {1}, pages = {35-41}, doi = {10.1016/0169-328x(96)00033-2}, pmid = {8840011}, issn = {0169-328X}, support = {DK 35747/DK/NIDDK NIH HHS/United States ; DK 42274/DK/NIDDK NIH HHS/United States ; NS 33347/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/physiology ; Analysis of Variance ; Animals ; Brain/metabolism/*physiology ; Diet ; *Genes, fos ; Immunohistochemistry ; *Learning ; Male ; Neurons/metabolism ; Organ Specificity ; Proto-Oncogene Proteins c-fos/*biosynthesis ; Rats ; Rats, Sprague-Dawley ; *Taste ; Threonine/*deficiency ; Time Factors ; }, abstract = {Rats rapidly become anorectic when eating an amino acid-imbalanced diet that induces a deficiency of an indispensable amino acid. Recognition of amino acid deficiency is thought to be a function of the anterior piriform cortex. However, the neuronal circuitry underlying the secondary learned aversion to such diets may involve the amygdala. In this study, Fos immunohistochemistry was employed to identify regions of the brain activated during the learned aversion phase of the response to an amino acid-imbalanced diet. c-Fos expression was examined in the brains of rats at intervals from 1 to 6 h after introduction of a diet imbalanced in threonine, a corrected (amino acid-balanced) diet or a basal (low protein) diet. The study has revealed that, within the time frame associated with the learned aversive response, Fos-immunoreactive (Fos-IR) neurons increased selectively in the central nucleus of the amygdala in animals fed a threonine-imbalanced diet. These results suggest a temporal relationship between changes in neuronal activity in the central nucleus of the amygdala and the learned aversion associated with acute amino acid deficiency.}, } @article {pmid8905682, year = {1996}, author = {Swank, MW and Ellis, AE and Cochran, BN}, title = {c-Fos antisense blocks acquisition and extinction of conditioned taste aversion in mice.}, journal = {Neuroreport}, volume = {7}, number = {11}, pages = {1866-1870}, doi = {10.1097/00001756-199607290-00036}, pmid = {8905682}, issn = {0959-4965}, support = {HD33138-01/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain Stem/*drug effects ; Learning/*drug effects ; Male ; Mice ; Mice, Inbred Strains ; Proto-Oncogene Proteins c-fos/*pharmacology ; Taste/*drug effects ; }, abstract = {Conditioned taste aversion is an unusual form of associative learning in which long delays between conditional stimulus taste (CS) and unconditioned stimulus illness (US) suggest stimulus encoding by novel mechanisms. Recent data suggest that stimulus inputs are encoded by inducible bZIP proteins, the kinetics of which match the temporal features of the CS and US in taste aversion learning. Blockade of US-induced c-Fos translation in the brain stem by antisense oligonucleotides specifically blocks both acquisition and extinction of a learned taste aversion, but does not impair sensory processing of either CS or US, suggesting that c-Fos antisense blocks associative events within NTS necessary to support taste aversion learning.}, } @article {pmid10456074, year = {1996}, author = {Lamprecht, R and Dudai, Y}, title = {Transient expression of c-Fos in rat amygdala during training is required for encoding conditioned taste aversion memory.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {3}, number = {1}, pages = {31-41}, doi = {10.1101/lm.3.1.31}, pmid = {10456074}, issn = {1072-0502}, mesh = {Amygdala/drug effects/*metabolism ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Drug Administration Schedule ; Male ; Memory/drug effects/*physiology ; Microinjections ; Oligonucleotides, Antisense/administration & dosage/pharmacology ; Proto-Oncogene Proteins c-fos/genetics/*metabolism ; Rats ; Rats, Wistar ; Time Factors ; }, abstract = {Local microinjection into rat amygdala of phosphorothioate modified oligodeoxynucleotides (ODNs) antisense to c-fos several hours before conditioned taste aversion (CTA) training impaired taste aversion memory tested 3-5 days after conditioning. In contrast, injection of the antisense ODNs several days before training, before testing, or into the basal ganglia, or injection of c-fos sense ODNs, had no effect on CTA memory. Inhibition of translation by local microinjection of anisomycin into the amygdala shortly before as well as during CTA training, but not several days before training or shortly before testing, also impaired CTA memory. We conclude that translation in general, and c-Fos translation in particular, in the amygdala during or immediately after CTA training is essential for encoding taste aversion memory.}, } @article {pmid10456073, year = {1996}, author = {Houpt, TA and Philopena, JM and Joh, TH and Smith, GP}, title = {c-Fos induction in the rat nucleus of the solitary tract correlates with the retention and forgetting of a conditioned taste aversion.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {3}, number = {1}, pages = {25-30}, doi = {10.1101/lm.3.1.25}, pmid = {10456073}, issn = {1072-0502}, support = {MH00149/MH/NIMH NIH HHS/United States ; MH15455/MH/NIMH NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal/drug effects ; Conditioning, Psychological/*physiology ; Drug Administration Schedule ; Male ; Neurons/metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology/*physiology ; Solitary Nucleus/cytology/drug effects/*metabolism ; Sucrose/administration & dosage/pharmacology ; Taste/*physiology ; }, abstract = {Recently, we have described a potential neuronal correlate of the behavioral expression of a conditioned taste aversion (CTA) against sucrose at the level of c-Fos expression. Intraoral infusions of sucrose induce c-Fos-like immunoreactivity (c-FLI) in the intermediate nucleus of the solitary tract (iNTS) after a CTA has been acquired for sucrose. Sucrose infusions do not induce c-FLI in the iNTS of unconditioned rats or in conditioned rats after extinction of the CTA. Here, we describe persistence of altered responsiveness of the iNTS in rats with CTAs against sucrose by intraorally infusing sucrose 2 days, 3 months, or 6 months after acquisition of the CTA. Sucrose infusions induced c-FLI in the iNTS 6 months after conditioning. The behavioral expression of the CTA was attenuated at 6 months but not at 3 months; the number of c-FLI positive cells in the iNTS was proportional to the magnitude of the expression of the CTA. This evidence strengthens our hypothesis that c-FLI in the iNTS is a neuronal correlate of the expression of a CTA.}, } @article {pmid8856834, year = {1996}, author = {Broadbent, J and Linder, HV and Cunningham, CL}, title = {Genetic differences in naloxone enhancement of ethanol-induced conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {126}, number = {2}, pages = {147-155}, pmid = {8856834}, issn = {0033-3158}, support = {AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; AA08621/AA/NIAAA NIH HHS/United States ; P60 AA010760/AA/NIAAA NIH HHS/United States ; R01 AA007702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/drug effects ; Ethanol/*pharmacology ; Genetics, Behavioral ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Naloxone/*pharmacology ; Taste/*drug effects/genetics ; }, abstract = {The influence of the opioid system on acquisition of an ethanol-induced conditioned taste aversion was examined in alcohol-preferring and avoiding inbred strains of mice (C57BL/6J and DBA/2J). Fluid-deprived mice from each strain received either ethanol alone, naloxone alone, or both ethanol and naloxone immediately after access to a novel tasting fluid. Naloxone alone (1 or 3 mg/kg) did not induce a conditioned taste aversion in either strain of mice. Administration of ethanol (1.5 g/kg) to DBA/2J mice produced a moderate taste aversion that was not affected by co-administration of naloxone. Although ethanol administered alone (3 g/kg) did not cause a taste aversion in C57BL/6J mice, the combination of ethanol and the higher dose of naloxone produced a significant taste aversion that increased across trials. A second experiment addressed the possibility that naloxone failed to enhance the ethanol-induced condition taste aversion in DBA/2J mice due to a "floor" effect on consumption. A lower ethanol dose (1 g/kg) was given alone or in combination with naloxone (1 or 3 mg/kg). Again, ethanol produced a moderate conditioned taste aversion that was not potentiated by naloxone. Subsequent conditioning with a high ethanol dose produced further suppression of intake, confirming that naloxone's failure to enhance aversion on earlier trials was not due to a "floor" effect. These data demonstrate a strain specific interaction between the aversive effect of ethanol and naloxone. More specifically, the results indicate that blockade of opioid receptors enhances the aversive effect of ethanol in C57BL/6J but not DBA/2J mice, suggesting that genetically determined differences in the endogenous opioid system of alcohol-preferring mice may mitigate ethanol's aversive effect.}, } @article {pmid8804682, year = {1996}, author = {Prendergast, MA and Hendricks, SE and Yells, DP and Balogh, S}, title = {Conditioned taste aversion induced by fluoxetine.}, journal = {Physiology & behavior}, volume = {60}, number = {1}, pages = {311-315}, doi = {10.1016/0031-9384(95)02234-1}, pmid = {8804682}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Fluoxetine/*pharmacology ; Lithium Chloride/pharmacology ; Male ; Rats ; Serotonin Uptake Inhibitors/*pharmacology ; Sucrose ; Taste/*drug effects ; }, abstract = {The present study assessed the ability of the serotonin reuptake inhibitor fluoxetine (FLX) and lithium chloride (LiCl) to induce conditioned taste aversion (CTA) to a novel 20% sucrose solution. FLX (2, 5, or 8 mg/kg) or LiCl (10 mg/kg) was administered 30 min after an initial exposure to the solution. A single-bottle test of CTA 24 h after the initial exposure indicated that rats that received FLX, at any dose, or LiCl consumed significantly less solution than did those that received a vehicle treatment following the initial exposure. To examine the possibility that decreased consumption during the CTA test exposure was associated with lasting hypophagia and/or hypodipsia induced by FLX, separate groups of rats, without any prior exposure to the solution, were administered FLX (2, 5, or 8 mg/kg) and given access 24 h later to a 20% sucrose solution. FLX failed to suppress consumption of the solution at any dose. These data suggest that FLX induces an aversive drug state in rats, similar to that induced by LiCl, which serves as a potent conditioned stimulus in CTA. In addition, this CTA is independent of FLX-induced hypophagia and/or hypodipsia. The relevance of these results to the study of hypophagia induced by FLX administration is discussed.}, } @article {pmid8804645, year = {1996}, author = {Amaro, S and Monda, M and De Luca, B}, title = {EEG arousal, sympathetic activity, and brown adipose tissue thermogenesis after conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {60}, number = {1}, pages = {71-75}, doi = {10.1016/0031-9384(95)02250-3}, pmid = {8804645}, issn = {0031-9384}, mesh = {Adipose Tissue, Brown/*innervation ; Animals ; Arousal/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Body Temperature Regulation/*physiology ; Conditioning, Classical/*physiology ; Cortical Synchronization ; *Electroencephalography ; Female ; Lithium Chloride/toxicity ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic/physiology ; Saccharin ; Sympathetic Nervous System/*physiology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion was induced in rats by pairing saccharin with intraperitoneal LiCl injection. Animals injected with NaCl served as controls. After evaluating the preference levels for saccharin in rats of both groups, the animals were anesthetized with urethane and the duration of EEG desynchronization, firing rate of sympathetic nerves innervating interscapular brown adipose tissue (BAT), and temperature of the same tissues were recorded, before and after oral stimulation with saccharin or water. The EEG desynchronization was longer in conditioned rats after stimulation with saccharin. Firing rate of sympathetic nerves was higher in conditioned rats after presentation of saccharin. BAT temperature, decreased in conditioned rats after saccharin stimulus, was unchanged in the three other conditions. In a second experiment temperature and firing rate of sympathetic nerves of BAT were recorded after oral presentation of water or saccharin in rats treated as in the first experiment and injected with the alpha 1-adrenergic blocker prazosin. As in the first experiment, saccharin presentation in conditioned animals enhanced the neural sympathetic activity, whereas differently from the first experiment it increased BAT temperature. No changes were found in the same measurements in the three other conditions. The drop in interscapular BAT temperature found in the first experiment, an unexpected finding, probably depends on the use of lithium as unconditioned stimulus, because LiCl interacting with adrenergic receptors changes the two-phase response, normally seen in interscapular BAT after increased sympathetic activity, in a single-phase response.}, } @article {pmid8804644, year = {1996}, author = {Sollars, SI and Tracy, CJ and Bernstein, IL}, title = {Retention of conditioned taste aversion to NaCl after chorda tympani transection in Fischer 344 and Wistar rats.}, journal = {Physiology & behavior}, volume = {60}, number = {1}, pages = {65-69}, doi = {10.1016/0031-9384(95)02235-x}, pmid = {8804644}, issn = {0031-9384}, support = {DC00248/DC/NIDCD NIH HHS/United States ; T32HD07391/HD/NICHD NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Chorda Tympani Nerve/*physiology ; Conditioning, Classical/*physiology ; Drinking/physiology ; Functional Laterality/physiology ; Male ; Rats ; Rats, Inbred F344 ; Rats, Wistar ; Retention, Psychology/*physiology ; Sodium Chloride ; Species Specificity ; Taste/*physiology ; Taste Threshold/physiology ; }, abstract = {Fischer 344 (F344) rats fail to prefer sodium chloride (NaCl) solution to water, and this behavior is dramatically altered by bilateral transection of the chorda tympani nerve (CTX). Tests of retention and generalization of a conditioned taste aversion (CTA) to 0.15 M NaCl were used to assess alterations in salt taste perception after CTX. A CTA was established to 0.15 M NaCl in groups of F344 and Wistar rats after two pairings with LiCl (IP, 2% body weight; 0.15 M). After conditioning, animals received bilateral CTX or sham operations. Approximately 2 weeks after surgery animals were tested for retention of the CTA. Aversion to 0.15 M NaCl was evident in CTX and SHAM rats that had been conditioned prior to surgery, with no apparent difference in magnitude as a function of surgical condition. Thus, although CTX profoundly alters F344 rats' hedonic response to NaCl, it does not alter perceptual characteristics so markedly that NaCl is no longer recognized as the stimulus presented during aversion conditioning. Rather these studies suggest that in both the F344 and Wistar strains the chorda tympani nerve is not necessary for retention of a presurgical CTA to NaCl. These studies, therefore, do not provide evidence of changes in NaCl perceptual "quality" as a consequence of CTX either in F344 rats, where such changes were indicated by the preference data, or in the Wistar rat, where they were not.}, } @article {pmid8691155, year = {1996}, author = {Davey, VA and Biederman, GB}, title = {Conditioned antisickness: heat as an internal stimulus in conditioning taste aversion and aversion failure in rats.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {22}, number = {3}, pages = {235-243}, doi = {10.1037//0097-7403.22.3.235}, pmid = {8691155}, issn = {0097-7403}, mesh = {Animals ; Association Learning ; *Attention ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Food Preferences/*psychology ; *Hot Temperature ; Lithium Chloride/toxicity ; Mental Recall ; Rats ; Thermosensing ; }, abstract = {Heat was found to be effective as a conditional stimulus in the aversion failure procedure (S. Revusky, H. K. Taukulis, L. A. Parker, & S. Coombes, 1979) and was also found to be effective as an unconditional stimulus using a taste aversion procedure in which rats exposed to high ambient temperature following saccharin consumption showed robust saccharin aversions relative to unpaired and unheated controls. The antisickness and taste aversion conditioning evidence force reexamination of the view that toxic heat effects are referred to the external environment. Together with other recent evidence from this laboratory, these data support the hypothetical antisickness mechanism of aversion failure, which requires that toxic heat serve as an internal stimulus.}, } @article {pmid8661250, year = {1996}, author = {Nerad, L and Ramírez-Amaya, V and Ormsby, CE and Bermúdez-Rattoni, F}, title = {Differential effects of anterior and posterior insular cortex lesions on the acquisition of conditioned taste aversion and spatial learning.}, journal = {Neurobiology of learning and memory}, volume = {66}, number = {1}, pages = {44-50}, doi = {10.1006/nlme.1996.0042}, pmid = {8661250}, issn = {1074-7427}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Cortex/*physiology ; Conditioning, Classical/*physiology ; Dominance, Cerebral/physiology ; Escape Reaction/physiology ; Male ; Maze Learning/physiology ; Mental Recall/*physiology ; Rats ; Rats, Wistar ; Reaction Time/physiology ; Receptors, N-Methyl-D-Aspartate/*physiology ; Taste/*physiology ; }, abstract = {In this study, we evaluated the effects of NMDA-induced lesions in different sites of the insular cortex of the rat on the acquisition of conditioned taste aversion and spatial learning in the Morris water maze. The lesions were produced by bilateral microinjections of NMDA in the insular cortex at +3.7 mm (Anterior group), +1.7 mm (Central group), and -0.3 mm (Posterior group) anteroposterior from bregma. The results showed that the central and posterior, but not the anterior, lesions disrupted the acquisition of water maze learning as measured by the high latency to reach the target. In contrast, the conditioned taste aversion learning was disrupted by lesions in the central but not in the anterior or posterior insular cortex. These data confirm functional heterogeneity of the insular cortex and demonstrate that the more caudal parts are only necessary for acquisition of the water maze task, while the central insular cortex is crucial for the acquisition of both the conditioned taste aversion learning and the Morris water maze.}, } @article {pmid8813609, year = {1996}, author = {De Beun, R and Lohmann, A and Schneider, R and De Vry, J}, title = {Comparison of the stimulus properties of ethanol and the Ca2+ channel antagonist nimodipine in rats.}, journal = {European journal of pharmacology}, volume = {306}, number = {1-3}, pages = {5-13}, doi = {10.1016/0014-2999(96)00198-7}, pmid = {8813609}, issn = {0014-2999}, mesh = {Analysis of Variance ; Animals ; *Avoidance Learning ; Behavior, Animal/*drug effects ; Calcium Channel Blockers/*pharmacology ; Central Nervous System Depressants/*administration & dosage/antagonists & inhibitors ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage/antagonists & inhibitors ; Male ; Nimodipine/*pharmacology ; Rats ; Rats, Wistar ; Taste ; }, abstract = {A variety of L-type Ca2+ channel antagonists, including the dihydropyridine derivative nimodipine, have been shown to be effective in reducing ethanol intake and preference in animal models of alcoholism. The behavioral mechanism involved in the anti-alcohol effects of nimodipine are, however, not clear yet. The aim of the present study was to investigate the possibility that the effects of nimodipine on ethanol intake are based on stimulus substitution. Therefore, rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg i.p.) from saline in a two-lever food-reinforced drug discrimination procedure (dose range of ethanol tested: 125-1000 mg/kg i.p., ED50 value: 488 mg/kg). In cross-generalization tests with nimodipine (0.15-15 mg/kg i.p.), stimulus substitution was not noted. In addition, a cross-familiarization conditioned taste aversion paradigm was utilized. In rats, 1000 mg/kg i.p. ethanol was used as the reference drug producing a conditioned taste aversion. Effects of preexposure to ethanol (500-1500 mg/kg i.p.) and nimodipine (7.5-30 mg/kg i.p.) on the magnitude of the ethanol-induced conditioned taste aversion were investigated as an index for stimulus similarity between preexposure and reference drug. Preexposure to both ethanol and nimodipine prevented the development of a conditioned taste aversion. Contrary to the drug discrimination results, these latter findings suggest that there may be similarities between the stimulus properties of nimodipine and ethanol. Moreover, the apparent discrepancy between the results obtained in drug discrimination and cross-familiarization conditioned taste aversion suggests that different stimulus properties of ethanol control behavior in both procedures. The finding that, under particular conditions, ethanol and nimodipine appear to share common stimulus properties needs to be further evaluated, as this may be related to the reported anti-alcohol effects of nimodipine and other Ca2+ channel antagonists.}, } @article {pmid8889000, year = {1996}, author = {Sollars, SI and Bernstein, IL}, title = {Neonatal chorda tympani transection alters adult preference for ammonium chloride in the rat.}, journal = {Behavioral neuroscience}, volume = {110}, number = {3}, pages = {551-558}, doi = {10.1037//0735-7044.110.3.551}, pmid = {8889000}, issn = {0735-7044}, support = {DC00248/DC/NIDCD NIH HHS/United States ; T32HD07391/HD/NICHD NIH HHS/United States ; }, mesh = {*Ammonium Chloride ; Animals ; Animals, Newborn ; Avoidance Learning/physiology ; Chorda Tympani Nerve/*physiology ; Conditioning, Psychological/physiology ; Male ; Nerve Regeneration ; Rats ; Sodium Chloride ; Taste/*physiology ; Taste Buds/cytology/physiology ; }, abstract = {The immature gustatory system of the neonatal rat is characterized by sensitivity to disruption by early interventions such as receptor or nerve damage. The present studies examined the effect of chorda tympani transection (neoCTX) of neonates on adult preference for salt and nonsalt stimuli. NeoCTX at 10 days of age led to a striking change in adult rats' preference for NH4Cl solutions but little change in preference for other solutions, including NaCl and KCl. Permanent anatomical effects of neoCTX included failure of the nerve to regenerate and a loss of all fungiform taste buds. Preference for NH4Cl was not due to an inability to discriminate it from NaCl. Following taste aversion conditioning to NaCl, neoCTX rats clearly distinguished between NaCl and NH4Cl. The effects on NH4Cl preference reflect a sensitive period during development because adult rats receiving similar surgery did not show any change in NH4Cl preference.}, } @article {pmid8888989, year = {1996}, author = {Ferry, B and Oberling, P and Jarrard, LE and Di Scala, G}, title = {Facilitation of conditioned odor aversion by entorhinal cortex lesions in the rat.}, journal = {Behavioral neuroscience}, volume = {110}, number = {3}, pages = {443-450}, doi = {10.1037//0735-7044.110.3.443}, pmid = {8888989}, issn = {0735-7044}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; Conditioning, Psychological ; Entorhinal Cortex/anatomy & histology/*physiology ; Male ; *Odorants ; Rats ; }, abstract = {This study examined the role of the entorhinal cortex (EC) in conditioned odor aversion learning (COA). Lateral EC lesions did not impair but rather facilitated COA. In the experiments the delay separating the odor cue presentation from the subsequent toxicosis was varied during acquisition. EC-lesioned rats demonstrated COA for delays up to 2 hr, whereas sham-operated rats displayed COA only if toxicosis immediately followed the odor cue. This facilitation was not dependent on the intensity of the odor and corresponded to a facilitated long-delay learning. EC lesion did not affect conditioned taste aversion, confirming that the facilitation effect does not correspond to a general facilitation of conditioned aversion learning. Taken together, these results indicate that the removal of the EC may allow odor-toxicosis associations across longer delays by extending the duration of the olfactory trace.}, } @article {pmid8811934, year = {1996}, author = {Ramírez-Amaya, V and Alvarez-Borda, B and Ormsby, CE and Martínez, RD and Pérez-Montfort, R and Bermúdez-Rattoni, F}, title = {Insular cortex lesions impair the acquisition of conditioned immunosuppression.}, journal = {Brain, behavior, and immunity}, volume = {10}, number = {2}, pages = {103-114}, doi = {10.1006/brbi.1996.0011}, pmid = {8811934}, issn = {0889-1591}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Operant/*physiology ; Cyclophosphamide/*pharmacology ; Hemagglutinins/biosynthesis ; Immunization ; Immunoglobulin M/biosynthesis ; *Immunosuppression Therapy ; Immunosuppressive Agents/*pharmacology ; Male ; N-Methylaspartate/*toxicity ; Neuroimmunomodulation/*physiology ; Neurotoxins/*toxicity ; Ovalbumin/immunology ; Parietal Lobe/drug effects/*physiology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/drug effects/physiology ; Saccharin/*pharmacology ; Sheep/blood ; Taste ; }, abstract = {Conditioned immunosuppression can be readily obtained in animals by associating a taste with an immunosuppressive drug. On subsequent exposure to the conditioned taste, the animals show an attenuated immune response and also exhibit a conditioned taste aversion. It has been established that insular cortex lesions disrupt the acquisition of conditioned taste aversion. The effect of NMDA-induced lesions in either the insular cortex or the parietal cortex of male Wistar rats was evaluated in the acquisition of conditioned immunosuppression in two experiments. Unlesioned control rats showed the conditioned immunosuppressive response after reexposure to the taste, as indicated by lower hemagglutinating titers to sheep red blood cells in the first experiment and by a decreased IgM production to ovalbumin, measured by ELISA, in the second experiment. Insular cortex-lesioned rats did not show the conditioned immunosuppression in either experiment, while parietal cortex lesions and the sham-lesioned animals presented a clear decrease of hemagglutinating titer and a low IgM production. The insular cortex lesions did not affect the normal immune response, showing normal hemagglutinating titers and IgM production when compared to nonconditioned controls. The immunosuppressive action of cyclophosphamide also remained unaltered. In conclusion, these results show that the insular cortex is essential for the acquisition of conditioned immunosuppression.}, } @article {pmid8800385, year = {1996}, author = {McKinzie, DL and Eha, R and Murphy, JM and McBride, WJ and Lumeng, L and Li, TK}, title = {Effects of taste aversion training on the acquisition of alcohol drinking in adolescent P and HAD rat lines.}, journal = {Alcoholism, clinical and experimental research}, volume = {20}, number = {4}, pages = {682-687}, doi = {10.1111/j.1530-0277.1996.tb01672.x}, pmid = {8800385}, issn = {0145-6008}, support = {AA07462/AA/NIAAA NIH HHS/United States ; AA07611/AA/NIAAA NIH HHS/United States ; AA10256/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Alcohol Drinking/*genetics/psychology ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; Extinction, Psychological ; Female ; Lithium Chloride/toxicity ; Male ; Motivation ; Pregnancy ; Rats ; Species Specificity ; Taste/*genetics ; }, abstract = {Early alcohol drinking has been hypothesized to cause alcohol-related problems in adulthood. In addition, a potential role for genetic factors exist in the etiology of some types of alcoholism. The objective of the present study was to determine if taste aversion training to ethanol during adolescence in previously ethanol-naive, alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats would retard or prevent the onset of high alcohol drinking. Taste aversion training began at 30 days of age. Male and female rat pups were fluid deprived for 24 hr before 30 min access to a 10% [v/v] ethanol solution, followed by an intraperitoneal injection of either saline or 0.15 M LiCl (10 ml/kg). A total of five training sessions were administered every other day with unrestricted access to water on intervening training days. Twenty-four hours after the last training trial, rats were given continuous free-choice between water and 10% ethanol for 4 weeks with food available and libitum. There were no obvious gender or line differences to the effects of taste aversion training. All LiCl-treated subjects avoided the usually preferred ethanol solution for the entire 4-week test period, whereas saline-treated rats steadily increased their alcohol intake to over 6.0 g/kg/day by week 4. Rats in the saline and LiCl-treated groups gained weight at comparable rates, and the groups did not differ in total fluid intake. The findings demonstrate that early environmental intervention can prevent the onset of high alcohol drinking in the selectively bred alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats.}, } @article {pmid8800382, year = {1996}, author = {Davidson, D and Amit, Z}, title = {Effects of naloxone on limited-access ethanol drinking in rats.}, journal = {Alcoholism, clinical and experimental research}, volume = {20}, number = {4}, pages = {664-669}, doi = {10.1111/j.1530-0277.1996.tb01669.x}, pmid = {8800382}, issn = {0145-6008}, mesh = {Alcohol Drinking/*psychology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Injections, Intraperitoneal ; Male ; Motivation ; Naloxone/*pharmacology ; Narcotic Antagonists/*pharmacology ; Rats ; Reinforcement Schedule ; Taste/*drug effects ; }, abstract = {The hypothesis that naloxone (NAL) decreases oral ethanol intake in rats by inducing a conditioned taste aversion (CTA) to ethanol was investigated. Rats were trained to drink 8% ethanol (v/v) on a 1-hr limited-access schedule. They received 4 days of intraperitoneal injections of 10 mg/kg of NAL, 10 min before limited-access (-10MIN group), immediately after limited-access (1HR group), or 3 hr after limited-access (3HR). Ethanol intake decreased in the -10MIN and 1HR groups during the injection period and on the postinjection day. In experiment 2, rats received 4 days of NAL injections when ethanol was not available (pre-exposure), and then the paradigm was repeated. In this experiment, there was no suppression of ethanol intake for any group on the postinjection day. The decrease in ethanol intake during injections observed for the 1HR in experiment 1 and the sustained suppression postinjection was interpreted as a CTA. Pre-exposure in experiment 2 abolished the CTA. Differences in the pattern ethanol intake for the -10MIN and 3HR groups during the experiments, however, suggest that a CTA is not the sole mechanism underlying NAL's suppressant effects on ethanol intake. In conclusion, in rats both the dose of NAL and the relative timing of NAL injections and ethanol drinking effect subsequent NAL suppression of ethanol intake.}, } @article {pmid8774022, year = {1996}, author = {Hu, S and Willoughby, LM and Lagomarsino, JJ and Jaeger, HA}, title = {Optokinetic rotation-induced taste aversions correlate with over-all symptoms of motion sickness in humans.}, journal = {Perceptual and motor skills}, volume = {82}, number = {3 Pt 1}, pages = {859-864}, doi = {10.2466/pms.1996.82.3.859}, pmid = {8774022}, issn = {0031-5125}, mesh = {Adolescent ; Adult ; Association Learning/physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking/physiology ; Female ; Humans ; Male ; Motion Sickness/*physiopathology/psychology ; Nystagmus, Physiologic/*physiology ; Psychophysiology ; Rotation ; Taste/*physiology ; }, abstract = {51 subjects were divided into Familiar- and Unfamiliar-drink groups based on whether they had tasted soybean milk before the experiment. Each subject then viewed an optokinetic rotating drum for 10 min. Subjective assessments of nausea and over-all symptoms of motion sickness were measured during the drum rotation. Two hours later subjects drank the soybean milk again. The consumed volume and rating of likeableness of the drink were subsequently measured. Analysis showed that the subjects in the Unfamiliar-drink group reported significantly higher taste aversion and consumed significantly less soybean milk after rotation than those in the Familiar-drink group. Correlation for the Unfamiliar-drink group indicated that the rated taste aversion was positively correlated with ratings of over-all symptoms of motion sickness and that the consumed volume of soybean milk was negatively correlated with ratings of over-all symptoms of motion sickness. We concluded that the magnitude of acquired conditioned taste aversion was dependent upon the severity of over-all symptoms of visually induced motion sickness when subjects were unfamiliar with the flavor of the target drink.}, } @article {pmid8737899, year = {1996}, author = {Janz, LJ and Green-Johnson, J and Murray, L and Vriend, CY and Nance, DM and Greenberg, AH and Dyck, DG}, title = {Pavlovian conditioning of LPS-induced responses: effects on corticosterone, splenic NE, and IL-2 production.}, journal = {Physiology & behavior}, volume = {59}, number = {6}, pages = {1103-1109}, doi = {10.1016/0031-9384(95)02171-x}, pmid = {8737899}, issn = {0031-9384}, mesh = {Animals ; Conditioning, Classical/*physiology ; Corticosterone/*biosynthesis ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Interleukin-2/*biosynthesis ; Lipopolysaccharides/*pharmacology ; Male ; Norepinephrine/*biosynthesis ; Radioimmunoassay ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Spleen/drug effects/*metabolism ; Sweetening Agents/pharmacology ; Taste/drug effects ; }, abstract = {The present study used a taste aversion paradigm to condition lipopolysaccharide (LPS)-induced suppression of splenic lymphocyte interleukin-2 (IL-2) production, with concurrent measurement of corticosterone production and splenic norepinephrine (NE) content). In training, two groups of rats received saccharin and IP LPS in a paired (P) manner and a third group in a specifically unpaired (U) manner. In the test, the unpaired group (group U) and one of the paired (group P) groups were re-exposed (R) to the cue and the other not (NR). An additional group controlled for the effects of cues (conditional stimulus) and fluid deprivation (negative control; NC). A robust taste aversion in the P-R group was accompanied by suppression of IL-2 production, reduced splenic NE content, and elevated corticosterone production, relative to combined controls (i.e., groups U-R, P-NR, and NC). The conditioned modulation of IL-2 secretion, along with the concomitant alteration of adrenocortical and sympathetic mediators, supports the involvement of bidirectional central nervous-immune system pathways in this paradigm.}, } @article {pmid8843492, year = {1996}, author = {Rabin, BM}, title = {Free radicals and taste aversion learning in the rat: nitric oxide, radiation and dopamine.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {20}, number = {4}, pages = {691-707}, doi = {10.1016/0278-5846(96)00041-3}, pmid = {8843492}, issn = {0278-5846}, mesh = {Animals ; Avoidance Learning/*physiology/radiation effects ; Brain Chemistry/drug effects ; Cyclic N-Oxides ; Dopamine/metabolism/*physiology ; Dopamine Antagonists/pharmacology ; Enzyme Inhibitors/pharmacology ; Free Radicals/metabolism ; Haloperidol/pharmacology ; Male ; Microscopy, Electron, Scanning ; Nitric Oxide/metabolism/*physiology ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitroarginine/pharmacology ; Nitrogen Oxides/pharmacology ; Nitroprusside/pharmacology ; Rats ; Rats, Wistar ; Taste/*physiology/radiation effects ; }, abstract = {1. Injection of sodium nitroprusside (SNP) or N-tert-butyl-alpha-phenyl nitrone (PBN) produces a conditioned taste aversion (CTA) in rats. The CTA can be prevented by pretreatment with N omega-nitro-L-arginine (L-NArg), indicating that nitric oxide (NO) is a behaviorally toxic compound. 2. Radiation-induced CTA learning is not affect by pretreatment with L-NArg or by preexposure to PBN, indicating that a radiation-stimulated formation of NO does not mediate the toxic effects of radiation on behavior. 4. Pretreating rats with the dopamine antagonist haloperidol prevented the acquisition of the CTA produced by SNP and attenuated, but did not eliminate, the PBN-induced CTA. Preexposure to the dopamine agonist amphetamine, attenuated a PBN-induced CTA, although PBN preexposure did not affect an amphetamine-induced CTA. 5. The results are interpreted as supporting a role for NO-stimulated dopamine release in the acquisition of taste aversions following injection of SNP or PBN.}, } @article {pmid8616593, year = {1996}, author = {Ninomiya, Y and Nomura, T}, title = {Effects of cerebroventricle administration of acidic fibroblast growth factor on conditioned taste aversion learning in rats.}, journal = {Neurobiology of learning and memory}, volume = {65}, number = {3}, pages = {283-286}, doi = {10.1006/nlme.1996.0034}, pmid = {8616593}, issn = {1074-7427}, mesh = {Animals ; Dose-Response Relationship, Drug ; Fibroblast Growth Factors/*pharmacology ; Injections, Spinal ; Learning/*drug effects ; Male ; Rats ; Rats, Wistar ; Task Performance and Analysis ; }, abstract = {Wistar strain rats were given acidic fibroblast growth factor (aFGF) or denatured aFGF into their cerebroventricle before taste aversion conditioning for saccharin solution. Animals administered with aFGF showed significantly lower aversion threshold for saccharin at the 1st day and preference ratios for saccharin vs distilled water at the 4th, 6th, and 7th day after the conditioning than those administered with denatured aFGF. These results suggests that aFGF in the cerebrospinal fluid facilitates acquisition of the conditioned taste aversion learning.}, } @article {pmid8801594, year = {1996}, author = {De Beun, R and Lohmann, A and Schneider, R and De Vry, J}, title = {Ethanol intake-reducing effects of ipsapirone in rats are not due to simple stimulus substitution.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {53}, number = {4}, pages = {891-898}, doi = {10.1016/0091-3057(95)02119-1}, pmid = {8801594}, issn = {0091-3057}, mesh = {Alcohol Deterrents/*pharmacology ; Alcohol Drinking/*psychology ; Animals ; Avoidance Learning/drug effects ; Discrimination, Psychological/drug effects ; Dose-Response Relationship, Drug ; Food ; Generalization, Stimulus/drug effects ; Male ; Pyrimidines/*pharmacology ; Rats ; Rats, Wistar ; Serotonin Receptor Agonists/*pharmacology ; Taste/drug effects ; }, abstract = {The present series of experiments was conducted to investigate whether the previously reported ethanol intake reducing effects of the 5-HT1A receptor agonist ipsapirone could be based on possible stimulus similarities between both compounds. Rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg, IP) from saline in a two-lever food-reinforced drug discrimination (DD) procedure. Discrimination criterion was reached after a mean number of training sessions of 42. In subsequent generalization sessions, a dose-response curve was established for ethanol (125-1000 mg/kg, IP, ED50 value: 355 mg/kg). In additional cross-generalization tests with ipsapirone (1-30 mg/kg, IP), stimulus substitution for the ethanol cue was not noted (maximal degree of generalization: 33%, at 10 and 30 mg/kg). To confirm the DD findings that ipsapirone does not substitute for ethanol, an alternative cross-familiarization conditioned taste aversion paradigm (CF-CTA) was utilized. In rats, 1000 mg/kg IP ethanol was used as the reference drug producing a conditioned taste aversion (CTA). It was found that preexposure to ethanol (500-1500 mg/kg, IP) dose-dependently attenuates the CTA produced by this same drug. Full familiarization was noted with 1000 and 1500 mg/kg. In contrast with this, ipsapirone (1-30 mg/kg, IP) failed to abolish ethanol-induced CTA, suggesting again that the ipsapirone stimulus complex is dissimilar to that produced by ethanol. Because the present findings indicate that, in rats, ipsapirone does not substitute for ethanol, it is suggested that the reported ethanol intake-reducing effects of ipsapirone in animal models of alcoholism are not due to simple stimulus substitution.}, } @article {pmid8801586, year = {1996}, author = {Del Prete, E and Lutz, TA and Scharrer, E}, title = {Inhibition of food intake in rats by the K+ channel opener cromakalim.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {53}, number = {4}, pages = {839-842}, doi = {10.1016/0091-3057(95)02090-x}, pmid = {8801586}, issn = {0091-3057}, mesh = {Animals ; Benzopyrans/*pharmacology ; Cromakalim ; Depression, Chemical ; Diet ; Eating/*drug effects ; Gastric Emptying/drug effects ; Male ; Potassium Channels/drug effects/*metabolism ; Pyrroles/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; Vagotomy ; }, abstract = {We studied the effect of the K+ channel opener cromakalim, which exhibits antihypertensive properties, on food intake in rats. Intraperitoneally injected cromakalim induced a dose-dependent (0.1, 0.5, and 1.0 mg/kg body wt.) reduction in food intake, which was associated with an inhibition of gastric emptying. The anorectic effect was not influenced by subdiaphragmatic vagotomy. Cromakalim's anorectic effect did not appear to be due to a learned taste aversion. Therefore, an intact abdominal vagus is not a prerequisite for cromakalim's anorectic effect.}, } @article {pmid8778854, year = {1996}, author = {Lett, BT and Grant, VL}, title = {Wheel running induces conditioned taste aversion in rats trained while hungry and thirsty.}, journal = {Physiology & behavior}, volume = {59}, number = {4-5}, pages = {699-702}, doi = {10.1016/0031-9384(95)02139-6}, pmid = {8778854}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Hunger/*physiology ; Male ; Motor Activity/*physiology ; Physical Exertion/physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; Thirst/*physiology ; }, abstract = {Rats while both hungry and thirsty were given three exposures to either a salt solution or a sour solution followed by a brief period of wheel running. On other occasions, these rats while hungry and thirsty were exposed to the alternate solution without wheel running. Conditioned aversion to the flavor paired with wheel running was evident after two pairings. During final tests with each solution, the rats were thirsty but not hungry. As expected, conditioned aversion to the particular flavor paired with wheel running was still observed despite a change in deprivation state from training to test. These results indicate that wheel running can induce sickness. Because sickness suppresses eating, activity anorexia in rats and some forms of anorexia nervosa in humans may be caused, at least in part, by sickness.}, } @article {pmid8705295, year = {1996}, author = {Edmonds, BK and Edwards, GL}, title = {The area postrema is involved in paraquat-induced conditioned aversion behavior and neuroendocrine activation of the hypothalamic-pituitary-adrenal axis.}, journal = {Brain research}, volume = {712}, number = {1}, pages = {127-133}, doi = {10.1016/0006-8993(95)01419-5}, pmid = {8705295}, issn = {0006-8993}, support = {DK 42533/DK/NIDDK NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Conditioning, Operant/*drug effects ; Corticosterone/blood ; Dose-Response Relationship, Drug ; Herbicides/*pharmacology ; Hypothalamo-Hypophyseal System/drug effects ; Male ; Neurosecretory Systems/*drug effects ; Paraquat/*pharmacology ; Pituitary-Adrenal System/drug effects ; Rats ; Rats, Sprague-Dawley ; Rhombencephalon/*physiology ; Taste/drug effects ; }, abstract = {Paraquat is a herbicide capable of eliciting conditioned taste aversion (CTA), a behavioral response characteristic of toxicosis. The area postrema (AP) is a hindbrain circumventricular organ previously shown to be important in mediating signs of paraquat-induced toxicity, namely CTA and weight loss. The relationship between neural substrates for paraquat-induced CTA and activation of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in Sprague-Dawley rats with lesions centered on the AP (APX) and sham-operated (SHM) rats administered paraquat (25 mumol/kg) or saline (1 ml/kg). Injection of paraquat at a dose sufficient to condition taste aversion, but produce no other signs of overt toxicity, significantly increased plasma corticosterone concentrations in SHM rats up to 4 h after administration. Paraquat-induced activation of the HPA axis was significantly attenuated in AP-lesioned rats as compared to sham-operated controls. These findings suggest the area postrema is a common neural substrate for the behavioral and neuroendocrine responses to paraquat.}, } @article {pmid8963318, year = {1996}, author = {Kassil', VG and Bondarenko, MIu and Mikhaĭlenko, VA}, title = {[The conditioned-reflex reaction of the sympathoadrenal system to an aversive taste stimulus].}, journal = {Fiziologicheskii zhurnal imeni I.M. Sechenova}, volume = {82}, number = {3}, pages = {57-65}, pmid = {8963318}, issn = {1027-3646}, mesh = {Adrenal Glands/*physiology ; Animals ; Avoidance Learning/*physiology ; Catecholamines/urine ; Conditioning, Classical/*physiology ; Female ; Male ; Rats ; Rats, Wistar ; Sex Characteristics ; Sympathetic Nervous System/*physiology ; Taste/*physiology ; Time Factors ; Water Deprivation/physiology ; }, abstract = {A non-reinforced taste stimulus with aversive properties was found to increase the level of excretion of adrenaline, noradrenaline and dopamine, thus reflecting occurring anxiety. The dopamine increase seems to be due to unspecific reasons of the experimental procedure. Catecholamines increase more in males rather than in females. The conditioned taste aversion seems to be preserved for a longer period of time in activating of the sympathetic-adrenal system.}, } @article {pmid8866974, year = {1996}, author = {Bevins, RA and Delzer, TA and Bardo, MT}, title = {Characterization of the conditioned taste aversion produced by 7-OH-DPAT in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {53}, number = {3}, pages = {695-699}, doi = {10.1016/0091-3057(95)02071-3}, pmid = {8866974}, issn = {0091-3057}, support = {DA05312/DA/NIDA NIH HHS/United States ; DA05623/DA/NIDA NIH HHS/United States ; DA07746/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Feeding Behavior/drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; Tetrahydronaphthalenes/*pharmacology ; }, abstract = {Using the conditioned taste aversion preparation, we described the dose-effect curve for the reputed dopamine D3 agonist (+/-)7-OH-DPAT (0, 0.001, 0.01, 0.1, 1.0, or 10 mg/kg). Rats received a 0.1% saccharin taste paired on repeated occasions with one of the 7-OH-DPAT doses. The 0.1, 1.0, and 10.0 mg/kg doses of 7-OH-DPAT produced a significant conditioned saccharin aversion. This aversion was evident regardless of whether saccharin intake of 7-OH-DPAT-treated rats was compared to their own water consumption or to saccharin intake by saline-treated rats.}, } @article {pmid8833104, year = {1996}, author = {Krivanek, J}, title = {Conditioned taste aversion and protein kinase C in the parabrachial nucleus of rats.}, journal = {Neurobiology of learning and memory}, volume = {65}, number = {2}, pages = {154-162}, doi = {10.1006/nlme.1996.0017}, pmid = {8833104}, issn = {1074-7427}, mesh = {Animals ; Behavior, Animal/drug effects ; Brain/*enzymology ; *Conditioning, Psychological ; Cytosol/*metabolism ; Drinking Behavior/drug effects ; Lithium Chloride/pharmacology ; Male ; Memory/*drug effects ; Protein Kinase C/*metabolism ; Rats ; Saccharin/pharmacology ; *Taste ; }, abstract = {The enzymatic activity of protein kinase C (PKC) was measured in the cytosol and particulate fraction of parabrachial nucleus, the presumed site of conditioned taste aversion (CTA) engrams. At various time intervals after acquisition of the task (pairing saccharin consumption with subsequent LiCl poisoning) the nucleus was dissected from the frozen coronal sections. An increase (+40%) in the cytosol PKC activity was found 48 h after that pairing in comparison with controls (saline injection instead of LiCl). Particulate enzyme activity virtual did not change (-5%). Thus the total PKC activity increased significantly (21%). Qualitatively similar but less markedly expressed PKC shifts (+18% in cytosol) ere found 24 h following CTA. Twelve hours and 5 days after CTA acquisition the activity and distribution of PKC was similar to that seen in normal rats. The control experiments revealed that 6 h after LiCl injection alone (without previous saccharin consumption) translocation of PKC from the cytosol to the membrane fraction (found previously 1 h after LiCl injection alone) still persisted but did not differ from that found 6 h after its pairing with saccharin drinking (CTA). It is concluded that acquisition of conditioned taste aversion may be followed by synthesis of PKC rather than by its translocation or downregulation.}, } @article {pmid8814657, year = {1996}, author = {Thiele, TE and Kiefer, SW and Badia-Elder, NE}, title = {Delayed generalization testing produces enhanced alcohol aversions in rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {13}, number = {2}, pages = {201-207}, doi = {10.1016/0741-8329(95)02048-9}, pmid = {8814657}, issn = {0741-8329}, support = {AA05397/AA/NIAAA NIH HHS/United States ; T32 MH 19547/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Central Nervous System Depressants/*pharmacology ; Conditioning, Operant/*drug effects ; Ethanol/*pharmacology ; Extinction, Psychological ; Generalization, Psychological/*drug effects ; Male ; Rats ; Reinforcement, Psychology ; Water Deprivation ; }, abstract = {Three experiments examined the effects of the training-to-testing interval on alcohol aversions. In Experiments 1 and 2, rats learned a taste aversion to a 4% (v/v) alcohol solution using lithium chloride as the illness agent. With a between-groups design, subjects were tested with 1%, 4%, or 7% alcohol, beginning either 2 or 21 days after training. In both experiments, results showed that rats learned aversions to the trained 4% alcohol that generalized to the nontrained 1% and 7% concentrations. Furthermore, in Experiment 1 aversions to 1% and 7% alcohol were stronger in groups tested 21 days after training relative to groups tested 2 days after training. When the strength of the illness agent was reduced in Experiment 2, aversions to all concentrations of alcohol were stronger at the delayed testing interval. Experiment 3 ruled out the possibility that enhanced alcohol avoidance at delayed testing was the result of spontaneous recovery of neophobia. The results suggest that taste aversions to alcohol become stronger with time. Possible mechanisms for this "incubation effect" are discussed. The present findings have implications for improving emetic therapy as a treatment for human alcoholics.}, } @article {pmid8814653, year = {1996}, author = {Shoaib, M and Almeida, OF}, title = {Absence of tolerance to the aversive stimulus properties of ethanol following oral ethanol self-administration.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {13}, number = {2}, pages = {175-180}, doi = {10.1016/0741-8329(95)02039-x}, pmid = {8814653}, issn = {0741-8329}, mesh = {Alcohol Drinking/*psychology ; Animals ; Central Nervous System Depressants/administration & dosage/*pharmacology ; Conditioning, Operant/drug effects ; Drug Tolerance ; Ethanol/administration & dosage/*pharmacology ; Male ; Rats ; Rats, Wistar ; Reinforcement, Psychology ; Self Administration ; Taste/drug effects ; }, abstract = {Depending on the situation, ethanol can serve as a reinforcer in one paradigm and an aversive stimulus in another. The relationships between the two stimuli are not clear, particularly the behavioural adaptation following chronic ethanol exposure. We report on two experiments using an oral-self administration (OSA) paradigm and a conditioned taste aversion (CTA) paradigm. Male Wistar rats were exposed to ethanol using either the OSA or the CTA paradigm, and the consequences were examined in the same groups of rats by performing the other corresponding experiment. Thus, sensitisation or tolerance to the respective stimulus properties of ethanol would be detectable. For OSA experiments, rats were presented, under a free-choice setting, tap water and an ascending series of ethanol concentrations (2-10%) for up to 4 days per concentration. The amounts of ethanol and water consumed in 23-h sessions were measured. For CTA, a two-bottle procedure was employed. Distinctively flavoured solutions (saccharin or saline) were paired with IP injections of either ethanol (1.5 g/kg) or saline (1 ml/kg). Tests for aversion were made after two pairings, when both solutions were presented simultaneously for 10 min. At low concentrations of ethanol, drinking solution consumption was high, decreasing gradually with increasing concentrations; however, daily intake of orally self-administered ethanol remained stable. No significant differences could be established between the two groups tested. Ethanol preference [EtOH/EtOH + H2O] was attenuated in rats experienced with the CTA procedure before the OSA experiment. Injections of ethanol produced marked CTAs, even in rats that had consumed ethanol in the OSA experiment. The absence of tolerance to the aversive stimulus effects suggests that this stimulus property may not play a significant role in the consumption of ethanol.}, } @article {pmid8838612, year = {1996}, author = {Pucilowski, O and Rezvani, AH and Overstreet, DH}, title = {Role of taste aversion in calcium channel inhibitor-induced suppression of saccharin and alcohol drinking in rats.}, journal = {Physiology & behavior}, volume = {59}, number = {2}, pages = {319-324}, doi = {10.1016/0031-9384(95)02097-7}, pmid = {8838612}, issn = {0031-9384}, mesh = {Alcohol Drinking/*physiopathology/psychology ; Animals ; Avoidance Learning/*drug effects ; Calcium Channel Blockers/*pharmacology ; Conditioning, Classical/*drug effects ; Diltiazem/pharmacology ; Dose-Response Relationship, Drug ; Drinking/*drug effects ; Isradipine/pharmacology ; Male ; Nicardipine/pharmacology ; Rats ; Rats, Sprague-Dawley ; *Saccharin ; Taste/*drug effects ; }, abstract = {L-type calcium (Ca2+) channel inhibitors suppress drinking of highly preferred solutions of simple carbohydrates, saccharin, or alcohol. The present study was designed to examine whether this decrease in drinking behavior can be explained by the development of consummatory aversion. In the first experiment, the propensity of Ca2+ channel inhibitors to induce conditioned taste aversion (CTA) to 0.1% saccharin was examined using two saccharin/drug injection pairings in saccharin-naive rats. We compared three chemically different drugs: diltiazem, isradipine, and nicardipine. A dose-dependent CTA was observed after both conditioning sessions for all three drugs tested. Interestingly, the lowest dose of nicardipine (i.e., 1.25 mumol/kg), significantly increased saccharin intake. A nonsignificant trend to increase saccharin intake was also observed with the lowest dose of isradipine. We then examined whether nicardipine could similarly induce CTA to a novel taste of alcohol (6%, v/v). The drug failed to produce a significant effect. In the third experiment, we found that nicardipine did not induce CTA (or preference) if the saccharin taste was familar to rats. In the final experiment, the interaction of nicardipine (1.25 and 2.5 mumol/kg) with the ethanol (1.5 g/kg)-induced CTA to saccharin was investigated. The higher dose of nicardipine potentiated the aversive effect of ethanol in the test. Overall, the present results suggest that CTA does not play a major role in Ca2+ channel inhibitor-induced suppression of drinking behavior.}, } @article {pmid8808127, year = {1996}, author = {Pizzi, WJ and Cook, DF}, title = {Conditioned taste aversion is a confound in behavioral studies that report a reduction in the reinforcing effects of drugs.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {53}, number = {2}, pages = {243-247}, doi = {10.1016/0091-3057(95)00203-0}, pmid = {8808127}, issn = {0091-3057}, support = {1#R15#NS26131/NS/NINDS NIH HHS/United States ; }, mesh = {Analgesics, Non-Narcotic/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Calcium Channel Blockers/pharmacology ; Carbamazepine/pharmacology ; Consummatory Behavior/drug effects ; Dose-Response Relationship, Drug ; Female ; Glucose/pharmacology ; Isradipine/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {Pharmacologic agents with a potential to attenuate the reinforcing properties of drugs of abuse may have an important role in the treatment of drug addiction. The reduction of drug self-administration and sweet solution intake are two common animal models employed to screen for promising therapeutic agents. When these agents are effective in suppressing the behavior maintained by drugs of abuse, the cause is usually attributed to a neuronal mechanism such as the modification of neurotransmitters that subserve reinforcement. These experiments present data for an alternate interpretation which suggest that some of these agents produce a conditioned taste aversion (CTA) that acts as a confounding variable in the screening of potential therapeutic agents. Both carbamazepine and isradipine were shown to establish a CTA at doses reported to attenuate the reinforcing properties of drugs of abuse. It is concluded that CTA represents a potential experimental confound in studies of pharmacologic agents that appear to attenuate the reinforcing properties of drugs. These results suggest that screening for a CTA is necessary in any paradigm that measures the suppression of consummatory behavior in response to pharmacologic intervention.}, } @article {pmid8652067, year = {1996}, author = {Eckel, LA and Ossenkopp, KP}, title = {Area postrema mediates the formation of rapid, conditioned palatability shifts in lithium-treated rats.}, journal = {Behavioral neuroscience}, volume = {110}, number = {1}, pages = {202-212}, pmid = {8652067}, issn = {0735-7044}, mesh = {Animals ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Brain Mapping ; Brain Stem/*drug effects ; Conditioning, Classical/*drug effects ; Food Preferences/*drug effects ; Lithium Chloride/*toxicity ; Male ; Motivation ; Paraventricular Hypothalamic Nucleus/*drug effects ; Rats ; Retention, Psychology/*drug effects ; Taste/*drug effects ; }, abstract = {The rapid acquisition and subsequent retention of lithium-induced conditioned changes in taste reactivity responses to sucrose were examined in rats with the area postrema (AP) either ablated or intact. On 2 conditioning days, a series of brief intraoral sucrose infusions was paired with the effects of LiCl or NaCl injections. Repeated associations of the sucrose taste with the effects of lithium significantly reduced ingestive responses and increased aversive responses only in the AP-intact group. AP-ablated rats treated with LiCl and rats injected with NaCl displayed an ingestive pattern of responses. Only the AP-intact rats, previously injected with LiCl, subsequently displayed evidence of a conditioned taste aversion. We conclude that toxin activation of the AP is required to produce the conditioned shift in taste reactivity responses and subsequent expression of a taste aversion in rats treated with lithium.}, } @article {pmid8811717, year = {1996}, author = {Bernardis, LL and Bellinger, LL}, title = {The lateral hypothalamic area revisited: ingestive behavior.}, journal = {Neuroscience and biobehavioral reviews}, volume = {20}, number = {2}, pages = {189-287}, doi = {10.1016/0149-7634(95)00015-1}, pmid = {8811717}, issn = {0149-7634}, mesh = {Animals ; Drinking Behavior/*physiology ; Feeding Behavior/*physiology ; Humans ; Hypothalamic Area, Lateral/*physiology ; Hypothalamic Hormones/physiology ; }, abstract = {This article discusses the role of the lateral hypothalamic area (LHA) in feeding and drinking and draws on data obtained from lesion and stimulation studies and neurochemical and electrophysiological manipulations of the area. The LHA is involved in catecholaminergic and serotonergic feeding systems and plays a role in circadian feeding, sex differences in feeding and spontaneous activity. This article discusses the LHA regarding dietary self-selection, responses to high-protein diets, amino acid imbalances, liquid and cafeteria diets, placentophagia, "stress eating," finickiness, diet texture, consistency and taste, aversion learning, olfaction and the effects of post-operative period manipulations by hormonal and other means. Glucose-sensitive neurons have been identified in the LHA and their manipulation by insulin and 2-deoxy-D-glucose is discussed. The effects on feeding of numerous transmitters, hormones and appetite depressants are described, as is the role of the LHA in salivation, lacrimation, gastric motility and secretion, and sensorimotor deficits. The LHA is also illuminated as regards temperature and feeding, circumventricular organs and thirst and electrolyte dynamics. A discussion of its role in the ischymetric hypothesis as an integrative Gestalt concept concludes the review.}, } @article {pmid8786704, year = {1996}, author = {Risinger, FO and Brown, MM}, title = {Genetic differences in nicotine-induced conditioned taste aversion.}, journal = {Life sciences}, volume = {58}, number = {12}, pages = {223-229}, doi = {10.1016/0024-3205(96)00051-3}, pmid = {8786704}, issn = {0024-3205}, support = {P60 AA010760/AA/NIAAA NIH HHS/United States ; AA 09612/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Male ; Mice ; Mice, Inbred C57BL ; Nicotine/*pharmacology ; Taste/*drug effects/*genetics ; }, abstract = {Genetic differences in nicotine-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J, DBA/2J, BALB/cJ and C3H/heJ mice were adapted to a 2-h per day water access regimen. Subsequently, mice received nicotine injections (0.5, 1.0 or 2.0 mg/kg) immediately after 1-h access to a NaCl flavored solution. DBA and C3H mice developed dose-dependent aversions to the nicotine-paired flavor. BALB mice showed only minor reductions in intake with no difference between the nicotine dose groups. C57BL mice did not show development of nicotine-induced conditioned taste aversion. These results demonstrate that nicotine's aversion motivational effect is strongly influenced by genotype. Further, genetic sensitivity (DBA mice) or insensitivity (C57BL mice) to nicotine-induced conditioned taste aversion was similar to reports of genetic sensitivity to ethanol's aversive effect measured in this design.}, } @article {pmid8741936, year = {1996}, author = {Josselyn, SA and Franco, VP and Vaccarino, FJ}, title = {Devazepide, a CCKA receptor antagonist, impairs the acquisition of conditioned reward and conditioned activity.}, journal = {Psychopharmacology}, volume = {123}, number = {2}, pages = {131-143}, pmid = {8741936}, issn = {0033-3158}, mesh = {Animals ; Benzodiazepinones/*pharmacology ; Conditioning, Operant/*drug effects ; Devazepide ; Dose-Response Relationship, Drug ; Eating/drug effects ; Hormone Antagonists/*pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Cholecystokinin/*antagonists & inhibitors ; Time Factors ; }, abstract = {Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions of the mesolimbic system, where it may facilitate the function of DA through the CCKA receptor subtype. DA has been implicated in the acquisition of conditioned incentive learning, raising the possibility of a role for endogenous CCK in this learning process. This hypothesis was tested using two complementary behavioral paradigms. Experiment 1 examined the effects of systemic administration of the CCKA receptor selective antagonist, devazepide (0, 0.001, 0.01, 0.1 mg/kg), on the acquisition of conditioned reward. Two novel levers were presented to drug-free animals in a test session; depression of the conditioned reward (CR) lever produced a light-tone stimulus previously paired with food availability while depression of the non-CR lever produced no programmed consequence. Animals receiving vehicle pretreatment in the food-CS conditioning sessions responded more frequently on the CR lever during the test session. However, pre-treatment with devazepide (0.1 mg/kg but not 0.001 or 0.01 mg/kg) in the conditioning sessions blocked the acquisition of conditioned reward. In contrast, experiment 2 showed that the development of conditioned reward was not affected by similar administration of the CCKB selective antagonist, L-365,260 (0, 0.001, 0.01, or 0.1 mg/kg). The possibilities that devazepide (0.1 mg/kg) impaired the development of conditioned reward by decreasing the amount of food consumed or by inducing a conditioned taste aversion to the food were ruled out in experiments 3 and 4. The effects of devazepide on the acquisition of conditioned activity induced by amphetamine were assessed in experiment 5. During four conditioning sessions, rats received devazepide (0, 0.001, 0.01, 0.1 or 1.0 mg/kg) treatment prior to amphetamine-environment pairings. The conditioned activity effect was demonstrated if on the subsequent drug-free test day the environment alone elicited increased locomotion. Devazepide (0.1 or 1.0 mg/kg) attenuated the development of conditioned activity. Together, these results provide converging evidence that intact CCKA function may be necessary for the development of conditioned incentive learning.}, } @article {pmid8735976, year = {1996}, author = {Mosher, JT and Johnson, MF and Birkemo, LS and Ervin, GN}, title = {Several roles of CCKA and CCKB receptor subtypes in CCK-8-induced and LiCl-induced taste aversion conditioning.}, journal = {Peptides}, volume = {17}, number = {3}, pages = {483-488}, doi = {10.1016/0196-9781(96)00028-9}, pmid = {8735976}, issn = {0196-9781}, mesh = {Animals ; Benzodiazepinones/pharmacology ; Chlordiazepoxide/pharmacology ; Conditioning, Psychological/*drug effects ; Devazepide ; Dose-Response Relationship, Drug ; Hormone Antagonists/pharmacology ; Indoles/pharmacology ; Lithium Chloride/*pharmacology ; Male ; Meglumine/analogs & derivatives/pharmacology ; *Phenylurea Compounds ; Rats ; Rats, Inbred Strains ; Receptor, Cholecystokinin A ; Receptor, Cholecystokinin B ; Receptors, Cholecystokinin/antagonists & inhibitors/classification/*metabolism ; Sincalide/*pharmacology ; Taste/*drug effects ; }, abstract = {Administration of a relatively large IP dose of sulfated cholecystokinin (26-33) (CCK-8; 1.0 mumol/kg) consistently induced moderate taste aversion conditioning (TAC) using a 20-min, one-bottle test in Long-Evans rats. Because CCK-8 has affinity for both CCKA and CCKB receptor subtypes, we wanted to determine the subtype involved in CCK-8-induced TAC. Pretreatment with the selective CCKA antagonist MK-329 (L-364, 718 or devazepide), at doses of 0.1, 1.0, or 10.0 mumol/kg, markedly antagonized (> 70%) CCK-8-induced TAC. Pretreatment with the selective CCKB antagonist L-365,260, at doses of 0.1 or 1.0 mumol/kg, partially antagonized (approximately 50%) CCK-8-induced TAC, although the highest dose of L-365,260. 10.0 mumol/kg, did not. These partial antagonistic effects of L-365,260 on CCK-8-induced TAC were replicated in our second study. In our third study, we observed that another CCKB antagonist, the dipeptoid CI-988, also partially antagonized CCK-8-induced TAC at a dose of 0.1, but not 1.0 or 10.0, mumol/kg. In our final study, pretreatments with a single dose (i.e., 10.0, but not 0.1 or 1.0, mumol/kg) of either MK-329 or L-365,260 were also shown to partially antagonize the formation of moderate TAC induced by treatment with LiCl at 708 mumol/kg. Marked antagonism of LiCl-induced TAC was also observed following pretreatment with the known anxiolytic chlordiazepoxide HCl at 7.4 mumol/kg. Considering the existing data on the induction of TAC by various CCK analogues, we consider an action of CCK-8 on peripheral CCKA, but not CCKB, receptors necessary for the induction of TAC. Our results of partial antagonism of CCK-8- and LiCl-induced TAC by L-365,260, CI-988, or MK-329 suggest, but do not prove, that both CCKA and CCKB mechanisms may be operative during TAC. Because the CCK antagonists affected TAC like chlordiazepoxide, blockade of CCKA and CCKB mechanisms may produce a mild anxiolytic effect.}, } @article {pmid8693799, year = {1996}, author = {Kassil', VG and Bondarenko, MIu}, title = {[Sex dimorphism in the patterns of conditioned-reflex taste aversion and orienting-exploratory and passive-defensive behaviors].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {46}, number = {1}, pages = {63-72}, pmid = {8693799}, issn = {0044-4677}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Escape Reaction/*physiology ; Exploratory Behavior/*physiology ; Extinction, Psychological/physiology ; Female ; Higher Nervous Activity/physiology ; Male ; Maze Learning/physiology ; Rats ; Rats, Wistar ; *Sex Characteristics ; Taste/*physiology ; }, abstract = {The patterns of conditioned taste aversion (CTA) and of some other types of behaviour were compared in adult male and female Wistar rats. Correlations between the CTA variables, on the one hand, and those of the exploratory and defensive behaviours, on the other, were shown. Females displayed initially less expressed CTA and more rapid its extinction than males. While tested in the open field, in a six-arm radial maze and in a special enclosed cubic chamber with holes in its vertical walls the females demonstrated higher levels of exploratory and locomotor activities with lower levels of emotionality and defensive behaviour than males. Sex differences were revealed in correlations between variables of CTA and behavioural responses under study. Thus, CTA patterns appear to be one of the manifestations of sexual dimorphism in non-reproductive behaviour.}, } @article {pmid8636062, year = {1996}, author = {de Boer, T}, title = {The pharmacologic profile of mirtazapine.}, journal = {The Journal of clinical psychiatry}, volume = {57 Suppl 4}, number = {}, pages = {19-25}, pmid = {8636062}, issn = {0160-6689}, mesh = {Adrenergic alpha-Antagonists/pharmacology/therapeutic use ; Animals ; Antidepressive Agents, Tricyclic/*pharmacology/therapeutic use ; Autoreceptors/drug effects ; Behavior, Animal/drug effects ; Depressive Disorder/*drug therapy ; Dioxanes/pharmacology/therapeutic use ; Drug Evaluation, Preclinical ; Humans ; Idazoxan ; Imidazoles/pharmacology/therapeutic use ; Mianserin/*analogs & derivatives/pharmacology/therapeutic use ; Mirtazapine ; Rats ; Receptors, Neurotransmitter/*drug effects ; Receptors, Serotonin/*drug effects ; Serotonin Antagonists/pharmacology ; Synaptic Transmission/drug effects ; }, abstract = {Mirtazapine (Org 3770) is a new antidepressant with prominent alpha 2-adrenergic auto- and heteroreceptor antagonistic properties and no effect on monoamine reuptake. Mirtazapine increases noradrenergic and serotonergic transmission, as measured by on-line microdialysis and by enhancement of noradrenergic locus ceruleus and serotonergic raphe nucleus cell firing. Mirtazapine has a low affinity for 5-HT1A receptors but shows 5-HT1A-agonistic-like effects in a conditioned taste aversion test and by causing lower lip retraction in rats. Mirtazapine therefore causes enhancement of 5-HT1-mediated transmission. Other studies show that both 5-HT2 and 5-HT3 receptors are specifically blocked. The enhancement of both noradrenergic and serotonergic transmission probably underlies the therapeutic activity of mirtazapine. Blockade of 5-HT2 and 5-HT3 receptors possibly prevents side effects associated with nonselective 5-HT activation and may also contribute to the anxiolytic and sleep-improving properties of mirtazapine.}, } @article {pmid8627931, year = {1996}, author = {Boston, S and Wobeser, G and Gillespie, M}, title = {Consumption of deoxynivalenol-contaminated wheat by mallard ducks under experimental conditions.}, journal = {Journal of wildlife diseases}, volume = {32}, number = {1}, pages = {17-22}, doi = {10.7589/0090-3558-32.1.17}, pmid = {8627931}, issn = {0090-3558}, mesh = {Analysis of Variance ; Animals ; Aspartate Aminotransferases/blood ; Blood Proteins/analysis ; Body Weight/drug effects ; Creatine Kinase/blood ; *Ducks ; Eating/drug effects ; Female ; *Food Contamination ; Male ; Random Allocation ; Taste ; Trichothecenes/administration & dosage/*toxicity ; *Triticum ; }, abstract = {Captive mallards (Anas platyrhynchos) were fed wheat containing 5.8 ppm deoxynivalenol (DON, vomitoxin) from an outbreak of Fusarium graminearium head-blight that occurred on grain crops in Manitoba, Canada, during 1993. There was no evidence of taste aversion to this grain during a 10-day palatability trial. No significant differences were detected in serum protein, calcium, glucose, creatinine kinase, aspartate aminotransferase or uric acid levels, blood packed cell volume, or body or organ weight, between ducks fed contaminated wheat and those fed uncontaminated wheat during a 14-day feeding trial. No gross or microscopic lesions were detected in birds fed contaminated wheat for 14 days. Based on these results, ducks will consume grain containing moderate levels of DON and short-term exposure to this grain will not result in obvious adverse effects.}, } @article {pmid8611314, year = {1996}, author = {La Noce, A and Danieli, A and Bertani, F and Tirone, P and de Haën, C}, title = {Conditioned taste aversion in rats following intrathecal administration of contrast media.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {37}, number = {1}, pages = {116-120}, doi = {10.1177/02841851960371P122}, pmid = {8611314}, issn = {0284-1851}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Contrast Media/*administration & dosage/toxicity ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Injections, Spinal ; Iopamidol/administration & dosage/analogs & derivatives/toxicity ; Rats ; Rats, Sprague-Dawley ; Statistics, Nonparametric ; Taste/*drug effects ; Time Factors ; Triiodobenzoic Acids/administration & dosage/toxicity ; }, abstract = {PURPOSE: The occurrence of side-effects such as visceral malaise after intrathecal administration of the non-ionic radiography contrast media iomeprol, iopamidol, and iotrolan was assessed in rats by the conditioned tasted aversion procedure.

METHODS: Reduced preference towards a saccharose solution compared with normal water following intraventricular administration of a contrast medium was used as a measure of the aversive response.

RESULTS: At a dose of 100 mg I/kg none of the tested contrast media induced aversion. At 200 and 300 mg I/kg, both iopamidol and iomeprol induced significant aversive responses with respect to control, although the response of the iomeprol group appeared milder than that of the iopamidol group at a dose of 200 mg I/kg. Iotrolan could be tested only at the lowest dose since the high doses caused excessive mortality.

CONCLUSION: Intrathecally administered iomeprol appeared to be well tolerated in rats at doses higher than those suggested for clinical use.}, } @article {pmid8742472, year = {1995}, author = {Lamprecht, R and Dudai, Y}, title = {Differential modulation of brain immediate early genes by intraperitoneal LiCl.}, journal = {Neuroreport}, volume = {7}, number = {1}, pages = {289-293}, pmid = {8742472}, issn = {0959-4965}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping/*methods ; Conditioning, Classical/*physiology ; Gene Expression Regulation/*physiology ; *Genes, Immediate-Early ; Genes, fos ; Injections, Intraperitoneal ; Lithium Chloride/*pharmacology ; Male ; Rats ; Rats, Wistar ; }, abstract = {We have used in situ hybridization to investigate the modulation of expression of the immediate early genes (IEGs) c-fos, fos-B, zif/268 and CREM in rat brain following oral administration of saccharin, i.p. injection of LiCl, and conditioned taste aversion (CTA) training in which these stimuli are used as the conditioned stimulus (CS) and the unconditioned stimulus (UCS), respectively. Modulation of c-fos, zif/268 and CREM was detected in the NTS, PBN, hypothalamic PVN and central nucleus of the amygdala after the administration of the UCS but not the CS. Our data are consonant with the hypothesis that differential and combinatorial expression of IEGs plays a role in encoding the representation of LiCl-induced malaise in the brain.}, } @article {pmid8623020, year = {1995}, author = {Lutz, TA and Geary, N and Szabady, MM and Del Prete, E and Scharrer, E}, title = {Amylin decreases meal size in rats.}, journal = {Physiology & behavior}, volume = {58}, number = {6}, pages = {1197-1202}, doi = {10.1016/0031-9384(95)02067-5}, pmid = {8623020}, issn = {0031-9384}, mesh = {Amyloid/*pharmacology ; Animals ; Behavior, Animal/drug effects ; Diet ; Eating/*drug effects ; Injections, Intraperitoneal ; Islet Amyloid Polypeptide ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors ; }, abstract = {Adult male rats were intraperitoneally (i.p.) injected with 1.0 microgram/kg amylin at the beginning of the dark phase in 24 h food deprived or undeprived rats, and a computerized system measured feeding behavior. In food deprived rats, amylin reduced the size of the first postdeprivation meal without affecting intrameal feeding rate or the size or timing of subsequent meals. The same pattern was observed in undeprived rats, but amylin also increased the latency to the first postinjection meal. In a conditioned taste aversion test, i.p. amylin (1 microgram/kg) injection just prior to rats' first access to a saccharine-flavored version of their maintenance diet, failed to affect their subsequent selection of that diet relative to the maintenance diet 2 d later. Finally, 2-min meal-contingent hepatic portal infusions of amylin (1-3.2 microgram/rat) during nocturnal spontaneous meals in undisturbed, ad lib fed rats reduced the meal size and meal duration, and increased the postprandial satiety ratio. Again, feeding rate and the size and duration of subsequent meals were not affected. These results suggest that amylin inhibits feeding by facilitating meal-ending satiety processes.}, } @article {pmid8747167, year = {1995}, author = {Yasoshima, Y and Shimura, T and Yamamoto, T}, title = {Single unit responses of the amygdala after conditioned taste aversion in conscious rats.}, journal = {Neuroreport}, volume = {6}, number = {17}, pages = {2424-2428}, doi = {10.1097/00001756-199511270-00034}, pmid = {8747167}, issn = {0959-4965}, mesh = {Amygdala/cytology/drug effects/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Drinking Behavior/drug effects/physiology ; Electrodes, Implanted ; Electrophysiology ; Hydrochloric Acid/pharmacology ; Male ; Neurons, Afferent/drug effects/*physiology ; Quinine/pharmacology ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Sodium Chloride/pharmacology ; Sucrose/pharmacology ; Sweetening Agents/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Amygdalar neuronal responses to sodium saccharin used as the conditioned stimulus (CS) and to other taste stimuli including sucrose, NaCl, HCl and quinine hydrochloride were recorded before and after the acquisition of conditioned taste aversion (CTA) in freely behaving rats. Of 73 units recorded from the basolateral nucleus of the amygdala (BLA), 17 (23%) and 1 (1%) exhibited facilitatory and inhibitory responses, respectively, to both the CS and sucrose after aversive conditioning to the CS. On the other hand, 3 (5%) and 11 (17%) of 64 units recorded from the central nucleus of the amygdala (Ce) exhibited facilitatory and inhibitory responses, respectively. The responsiveness of these BLA and Ce units to other taste stimuli did not change significantly. These findings that the facilitatory effect was dominant in the BLA, while the inhibitory effect was more frequent in the Ce suggest that the BLA and Ce are differentially involved in CTA.}, } @article {pmid8590615, year = {1995}, author = {Risinger, FO and Cunningham, CL}, title = {Genetic differences in ethanol-induced conditioned taste aversion after ethanol preexposure.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {12}, number = {6}, pages = {535-539}, doi = {10.1016/0741-8329(95)00040-2}, pmid = {8590615}, issn = {0741-8329}, support = {AA07468/AA/NIAAA NIH HHS/United States ; AA08621/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Central Nervous System Depressants/*pharmacology ; Conditioning, Psychological/*drug effects ; Drinking Behavior ; Ethanol/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Inbred Strains ; Sodium Chloride/pharmacology ; Species Specificity ; Taste/*drug effects/*genetics ; }, abstract = {The present studies examined the development of ethanol-induced conditioned taste aversion in C57BL/6J (B6) and DBA/2J (D2) mice with a history of ethanol preexposure. In Experiment 1, adult male B6 and D2 mice received four preexposure injections of either saline or 4 g/kg ethanol over an 8-day period. After preexposure, all mice were given five conditioning trials consisting of 1-h access to 0.15% w/v saccharin solution followed immediately by ethanol injections (4 g/kg, IP) on all but the last trial. Drug-naive D2 mice showed greater reductions in saccharin intake. Ethanol preexposure reduced the development of ethanol-induced taste aversion in each strain. However, B6 mice showed little taste aversion overall, hindering the characterization of genetic differences in ethanol's preexposure effect. To address this problem, the parameters for taste conditioning were changed in Experiment 2 to more closely match degree of taste aversion in drug-naive mice across both strains. B6 and D2 mice received four preexposure injections of either saline, 2 g/kg ethanol, or 4 g/kg ethanol, or 4 g/kg ethanol. Subsequently, mice received five conditioning trials consisting of 1-h access to 0.2 M NaCl flavor followed by 4 g/kg ethanol (B6 mice) or 2 g/kg ethanol (D2 mice) on trials 1-4. Ethanol-naive mice of each strain developed similar levels of conditioned taste aversion. Ethanol preexposure produced greater retardation of conditioned aversion in B6 mice than in D2 mice. These results demonstrate genetic differences in the ability of ethanol preexposure to reduce the development of ethanol-induced conditioned taste aversion.}, } @article {pmid8577895, year = {1995}, author = {Stock, HS and Rosellini, RA and Abrahamsen, GC and McCaffrey, RJ and Ruckdeschel, JC}, title = {Methotrexate does not interfere with an appetitive Pavlovian conditioning task in Sprague-Dawley rats.}, journal = {Physiology & behavior}, volume = {58}, number = {5}, pages = {969-973}, doi = {10.1016/0031-9384(95)00147-b}, pmid = {8577895}, issn = {0031-9384}, mesh = {Animals ; Antimetabolites, Antineoplastic/*pharmacology ; Appetitive Behavior/*drug effects ; Avoidance Learning/drug effects ; Conditioning, Classical/*drug effects ; Discrimination, Psychological/drug effects ; Female ; Male ; Methotrexate/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects ; }, abstract = {There has been considerable interest in developing an animal model of the neuropsychological toxicity of chemotherapeutic agents used in the treatment of patients with cancer, especially children, since these agents often cause significant, long-term neuropsychological deficits. Yanovski, Packer, Levine, Davidson, Micalizzi, D'Angio (13) recently proposed such a model based on their finding that methotrexate retarded the formation of aversive Pavlovian excitatory associations. The present experiment examined the generality of methotrexate induced cognitive impairments by testing rats in Appetitive Pavlovian Conditioning tasks and a Conditioned Taste Aversion paradigm. The results of our study revealed no impairment following methotrexate exposure on the Appetitive Pavlovian tasks or on the Taste Aversion task, relative to two control conditions. While there were a number of methodological differences between the present experiment and those conducted by Yanovski et al. (13), the present results question the robustness and generality of Yanovski's et al. (13) animal model.}, } @article {pmid7472511, year = {1995}, author = {Ellenbroek, BA and Geyer, MA and Cools, AR}, title = {The behavior of APO-SUS rats in animal models with construct validity for schizophrenia.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {15}, number = {11}, pages = {7604-7611}, doi = {10.1523/JNEUROSCI.15-11-07604.1995}, pmid = {7472511}, issn = {0270-6474}, support = {F6TW01813/TW/FIC NIH HHS/United States ; KO5-MH01223/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Apomorphine/*pharmacology ; Avoidance Learning ; Behavior, Animal/*physiology ; Conditioning, Psychological ; *Disease Models, Animal ; Exploratory Behavior/*physiology ; Male ; Mastication ; Neural Inhibition ; Rats ; Rats, Wistar ; Reaction Time ; Reflex, Startle ; *Schizophrenic Psychology ; Stereotyped Behavior ; Taste ; }, abstract = {Schizophrenic patients are known to suffer from a number of information processing disturbances, including deficits in both prepulse inhibition of startle and latent inhibition. Since these behavioral phenomena can also be observed in animals, they represent an ideal starting point for developing animal models having construct validity for specific deficits observed in schizophrenia. The principal question is how to induce a condition in animals most similar to the schizophrenic deficit. In the present study, we have selected rats on the basis of their response to an open filed or to the dopaminergic agonist apomorphine, and evaluated their prepulse inhibition and latent inhibition. We used three different selection procedures (open field selection for novelty response, gnawing cage selection for apomorphine response, and pharmacogenetic selection for apomorphine response). The results show that, irrespective of the selection procedure used, rats with a high response to novelty or apomorphine susceptible (collectively called APO-SUS rats) show diminished prepulse inhibition of the acoustic startle response as compared to rats with a low response to novelty or apomorphine unsusceptible (collectively called APO-UNSUS rats). This difference was apparent only at low prepulse intensities. Moreover, these APO-SUS rats show diminished latent inhibition in a conditioned taste aversion paradigm as compared to APO-UNSUS rats. Given the fact that the pharmacogenetically bred APO-SUS rats show several central nervous, endocrinological, and immunological similarities to schizophrenic patients, they are hypothesised to represent an interesting nonpharmacological animal model for schizophrenia-prone patients.}, } @article {pmid8584756, year = {1995}, author = {Hulsey, MG and Pless, CM and White, BD and Martin, RJ}, title = {ICV administration of anti-NPY antisense oligonucleotide: effects on feeding behavior, body weight, peptide content and peptide release.}, journal = {Regulatory peptides}, volume = {59}, number = {2}, pages = {207-214}, doi = {10.1016/0167-0115(95)00110-w}, pmid = {8584756}, issn = {0167-0115}, mesh = {Animals ; Avoidance Learning/drug effects ; Base Sequence ; Body Weight/*drug effects ; Drug Evaluation, Preclinical ; Feeding Behavior/*drug effects ; Injections, Intraventricular ; Male ; Molecular Sequence Data ; Neuropeptide Y/*genetics/metabolism ; Oligonucleotides, Antisense/*pharmacology ; Paraventricular Hypothalamic Nucleus/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Taste/physiology ; Thionucleotides/*pharmacology ; }, abstract = {Neuropeptide-Y (NPY) is a potent stimulator of feeding, and chronic administration of the peptide has been shown to increase body weight. This study determined the chronic effects of repeated daily injections of an antisense phosphorothioate oligonucleotide complementary to the rat mRNA for NPY (aNPY) on food intake, feeding behavior and body weight change in rats. Five micrograms of the aNPY oligonucleotide in ten microliters of vehicle or a missense control oligonucleotide were administered intracerebroventricularly (ICV) for seven consecutive days. Cumulative food intake, meal size and meal duration were significantly lowered in aNPY-treated animals. Body weight change of aNPY-injected animals was significantly lower than controls, and the effect was reversed after treatments ceased. A two-bottle taste aversion paradigm was employed to determine the behavioral specificity of the anorectic effect, and the phosphorothioate oligonucleotide was found not to be aversive at the dosage used. Following an additional five day injection period, animals were killed and paraventricular nuclei (PVN) were dissected. In vitro release and tissue content of NPY from this brain area were evaluated by heterologous radioimmunoassay. Content of NPY was unchanged in this brain area. Paradoxically, in vitro release of NPY was increased in aNPY-treated animals.}, } @article {pmid8577801, year = {1995}, author = {Exton, MS and Bull, DF and King, MG and Husband, AJ}, title = {Paradoxical conditioning of the plasma copper and corticosterone responses to bacterial endotoxin.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {52}, number = {2}, pages = {347-354}, doi = {10.1016/0091-3057(95)00109-a}, pmid = {8577801}, issn = {0091-3057}, mesh = {Acute-Phase Reaction/psychology ; Animals ; Conditioning, Classical/*drug effects ; Copper/*blood ; Corticosterone/*blood ; Endotoxins/*pharmacology ; Feeding Behavior/drug effects ; Interleukin-1/biosynthesis ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Stress, Psychological/psychology ; Sweetening Agents/pharmacology ; }, abstract = {The cascade of physiologic mechanisms in response to infection, the acute phase response, is recognized as having a major role in host defense. Two such responses are an increase in plasma copper and activation of the hypothalamic-pituitary-adrenal axis, which are consistently reported to occur during bacterial infection. We aimed to determine whether the alterations in plasma copper and corticosterone were conditionable using the conditioned taste aversion paradigm. The regime involved the pairing of a novel-tasting saccharine solution (the conditioned stimulus) with lipopolysaccharide (the unconditioned stimulus). Seven days after the initial pairing of these stimuli (the test day), the saccharine solution was represented. Animals exposed to this condition displayed a significant decrease in plasma copper levels. In addition, these rats experienced a reduction in plasma corticosterone that was time dependent. Paradoxically, the conditioned response of both these variables were in a direction contrary to that reported during bacterial infection. These results suggest that some acute phase responses may condition as a rebound response, or in an opposing trend to that occurring as the initial reaction.}, } @article {pmid8564430, year = {1995}, author = {Markison, S and Spector, AC}, title = {Amiloride is an ineffective conditioned stimulus in taste aversion learning.}, journal = {Chemical senses}, volume = {20}, number = {5}, pages = {559-563}, doi = {10.1093/chemse/20.5.559}, pmid = {8564430}, issn = {0379-864X}, support = {DC-01628/DC/NIDCD NIH HHS/United States ; K04-DC00104/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Cues ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Taste/*drug effects ; Thirst/physiology ; Water Deprivation/physiology ; }, abstract = {The present study demonstrated that 100 microM amiloride serves as an ineffective conditioned taste stimulus in a taste aversion paradigm. Even if amiloride has a detectable taste, it's unlikely that its behavioral effects in salt mixture experiments are due to its inherent taste quality.}, } @article {pmid8559797, year = {1995}, author = {Batsell, WR and Pritchett, KP}, title = {Retention of rotationally induced taste aversions.}, journal = {Physiology & behavior}, volume = {58}, number = {4}, pages = {815-818}, doi = {10.1016/0031-9384(95)00133-4}, pmid = {8559797}, issn = {0031-9384}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Drinking ; *Kinesthesis ; Lithium Chloride/toxicity ; Male ; Rats ; *Retention, Psychology ; Rotation ; *Taste ; }, abstract = {Retention interval effects are seen in single-element taste-aversion learning when taste aversions are significantly weaker if testing occurs 1 day after conditioning compared to tests conducted 3 or more days after conditioning. Since all previous demonstrations of this phenomenon have occurred following conditioning with the drug lithium chloride (LiCl), it was necessary to determine if the increased drinking at the 1-day interval was due to the aftereffects of LiCl. The present experiment explored the presence of retention interval differences following the use of a nonpharmacological unconditioned stimulus (US), rotational stimulation. Following a saccharin-rotation pairing, a saccharin aversion was seen at a 5-day testing interval, and this aversion was significantly stronger than the aversion observed at a 1-day test. Thus, these results are clear in showing that the retention interval effect occurs following conditioning with a nonpharmacological US, and this outcome allows for the refutation of an aftereffects of LiCl hypothesis.}, } @article {pmid8554723, year = {1995}, author = {Scalera, G and Spector, AC and Norgren, R}, title = {Excitotoxic lesions of the parabrachial nuclei prevent conditioned taste aversions and sodium appetite in rats.}, journal = {Behavioral neuroscience}, volume = {109}, number = {5}, pages = {997-1008}, pmid = {8554723}, issn = {0735-7044}, support = {DC 00161/DC/NIDCD NIH HHS/United States ; DC 00240/DC/NIDCD NIH HHS/United States ; MH 43787/MH/NIMH NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Appetite Regulation/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Axons/physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Ibotenic Acid ; Lithium Chloride/toxicity ; Neurons/physiology ; Prosencephalon/*physiology ; Rats ; Rats, Sprague-Dawley ; Viscera/innervation ; Water-Electrolyte Balance/*physiology ; }, abstract = {Electrolytic lesions of the parabrachial nuclei (PBN) disrupt conditioned taste aversion (CTA) in the rat, but it is not known whether this effect is due to damaging axons of passage or to destruction of intrinsic neurons. We tested 10 rats with electrophysiologically guided, ibotenic acid lesions of the PBN (PBNx) to determine whether they could acquire a LiCl-induced CTA to l-alanine (0.3 M) or demonstrate a sodium appetite following furosemide treatment and overnight access to sodium deficient chow. Vehicle-treated and nonsurgical controls were included in the design. PBNx rats failed to develop a CTA, even after 3 conditioning trials. Moreover, more than 8 months later, a subset of the PBNx rats were again unable to learn a CTA using NaCl as the conditional stimulus (CS). After the furosemide treatment, the control rats drank an average of 20.3 ml of strong salt in 24 hr. The PBNx rats drank virtually no NaCl during the first 2 hr and averaged only 4.0 ml in 24 hr. In the PBN, damage to neuronal somata is more critical than interrupting fibers of passage for producing deficits in taste-guided behaviors.}, } @article {pmid8554717, year = {1995}, author = {Spector, AC and Scalera, G and Grill, HJ and Norgren, R}, title = {Gustatory detection thresholds after parabrachial nuclei lesions in rats.}, journal = {Behavioral neuroscience}, volume = {109}, number = {5}, pages = {939-954}, pmid = {8554717}, issn = {0735-7044}, support = {DC-00104/DC/NIDCD NIH HHS/United States ; DC-00161/DC/NIDCD NIH HHS/United States ; DC-00240/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Appetite Regulation/physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Lithium Chloride/toxicity ; Mental Recall/physiology ; Motivation ; Neural Pathways/physiology ; Prosencephalon/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste Threshold/*physiology ; Water-Electrolyte Balance/*physiology ; }, abstract = {Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment 2) that had been electrophysiologically centered in the gustatory zone of the parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection thresholds in a conditioned avoidance task. With 1 exception, all of these rats had previously shown severe deficits in acquiring an LiCl-based conditioned taste aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions also had failed to express a depletion-induced sodium appetite. Despite the uniformity of these deficits, the rats with lesions exhibited varied performance in the detectability task. Roughly 1/3 of the rats did not perform competently, 1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in taste detectability. These findings demonstrate that the elimination of CTA following PBN lesions is not necessarily linked to an impairment in taste signal detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely correspond with impairments on another.}, } @article {pmid7472437, year = {1995}, author = {Schafe, GE and Seeley, RJ and Bernstein, IL}, title = {Forebrain contribution to the induction of a cellular correlate of conditioned taste aversion in the nucleus of the solitary tract.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {15}, number = {10}, pages = {6789-6796}, doi = {10.1523/JNEUROSCI.15-10-06789.1995}, pmid = {7472437}, issn = {0270-6474}, support = {AA07455/AA/NIAAA NIH HHS/United States ; DC00248/DC/NIDCD NIH HHS/United States ; DK17844/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Decerebrate State ; Immunohistochemistry ; Lithium Chloride/pharmacology ; Male ; Neurons/*physiology ; Prosencephalon/pathology/*physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Solitary Nucleus/cytology/*physiology ; Solutions ; Taste/*physiology ; }, abstract = {A conditioned taste aversion (CTA) is a form of classical conditioning in which animals avoid a taste (conditioned stimulus; CS) which has been previously paired with a treatment (unconditioned stimulus; US) that produces transient illness. Recently, a reliable cellular correlate of the behavioral expression of a CTA was identified using c-Fos immunostaining as a marker of neuronal activation. Exposure to a saccharin solution (CS) which had previously been paired with lithium chloride (LiCl; US) induced significant c-Fos-like immunoreactivity (c-FLI) in the intermediate zone of the nucleus of the solitary tract (NTS), a response that was quite similar to that displayed following administration of LiCl alone. The present studies employed a variant of the chronic decerebrate rat preparation to explore whether circuitry intrinsic to the brainstem is sufficient for the induction of c-FLI in both as an unconditioned response to the LiCl and as a conditioned response to the saccharin. Using chronic hemidecerebrate rats, which have a unilateral brain transection at the level of the superior colliculus, we found that the unconditioned c-FLI to LiCI was unaltered by the transection, while the conditioned expression of c-FLI to the CS taste was evident only on the side of the NTS which retained neural connections with the forebrain. These findings strongly implicate forebrain input in this cellular correlate of CTA learning and also indicate that the pathways mediating the response to the US (LiCl) and the CS (saccharin) differ.}, } @article {pmid8548298, year = {1995}, author = {Lipinski, WJ and Rusiniak, KW and Hilliard, M and Davis, RE}, title = {Nerve growth factor facilitates conditioned taste aversion learning in normal rats.}, journal = {Brain research}, volume = {692}, number = {1-2}, pages = {143-153}, doi = {10.1016/0006-8993(95)00673-e}, pmid = {8548298}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*drug effects ; Choline O-Acetyltransferase/metabolism ; Food Preferences/drug effects ; Injections, Intraventricular ; Lithium Chloride/pharmacology ; Memory/drug effects ; Neostriatum/drug effects/enzymology ; Nerve Growth Factors/administration & dosage/*pharmacology ; Prosencephalon/drug effects/enzymology ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Sweetening Agents/pharmacology ; Taste/*drug effects ; }, abstract = {Chronic intracerebroventricular (i.c.v.) infusion of 3.2 micrograms/day of nerve growth factor (NGF) in normal rats elevated choline acetyltransferase (ChAT) activity of the striatum, medial septum, and basal forebrain and improved performance of a conditioned taste aversion (CTA) task. Relative to bovine serum albumin (BSA) or Cytochrome C treatments, NGF treatment facilitated acquisition and prolonged extinction of a lithium chloride (LiCl)-induced saccharin aversion. This facilitation was evident at saccharin/LiCl intervals ranging up to 1 h. Also, NGF treatment did not increase reactivity to LiCl-induced illness and neither shifted detection thresholds nor altered hedonic reactions to taste stimuli, indicating that NGF did not produce simple changes in sensory function. NGF treatments that elevate ChAT also facilitate memory of CTA in normal, adult rats.}, } @article {pmid8552000, year = {1995}, author = {Clausing, P and Ferguson, SA and Holson, RR and Allen, RR and Paule, MG}, title = {Prenatal ethanol exposure in rats: long-lasting effects on learning.}, journal = {Neurotoxicology and teratology}, volume = {17}, number = {5}, pages = {545-552}, doi = {10.1016/0892-0362(95)00014-i}, pmid = {8552000}, issn = {0892-0362}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Conditioning, Operant/*drug effects ; Ethanol/*toxicity ; Female ; Male ; Maze Learning/*drug effects ; Predictive Value of Tests ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Sensitivity and Specificity ; Time Factors ; }, abstract = {Pregnant Sprague-Dawley rats were fed a liquid diet containing either 0% (group C), 18% (group L), or 36% (group H) ethanol-derived calories (EDC) from gestational day 1 to 20. Male offspring were assessed under a conditioned taste aversion paradigm (PND 35-45), in a complex maze (PND 68-80), and for operant behavior (temporal response differentiation and motivation to work for food, PND 140-198). Although conditioned taste aversion was fully acquired by all groups, retention of the conditioned taste aversion response was impaired in group H animals. Importantly, deficits in the acquisition of timing behavior were found in group H (group L not tested), confirming that this operant task is quite sensitive in detecting prenatal drug effects and demonstrating that neurological effects of prenatal ethanol exposure persist into late adulthood.}, } @article {pmid7582825, year = {1995}, author = {Ferry, B and Sandner, G and Di Scala, G}, title = {Neuroanatomical and functional specificity of the basolateral amygdaloid nucleus in taste-potentiated odor aversion.}, journal = {Neurobiology of learning and memory}, volume = {64}, number = {2}, pages = {169-180}, doi = {10.1006/nlme.1995.1056}, pmid = {7582825}, issn = {1074-7427}, mesh = {Amygdala/*physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Caudate Nucleus/physiology ; Conditioning, Classical/*physiology ; Entorhinal Cortex/physiology ; Lithium Chloride/toxicity ; Male ; Memory, Short-Term/physiology ; Putamen/physiology ; Rats ; Smell/*physiology ; Taste/*physiology ; Temporal Lobe/physiology ; gamma-Aminobutyric Acid/physiology ; }, abstract = {The present study aimed at documenting the neurobiological substrate of taste-potentiated odor aversion (TPOA) in the rat. The role of several temporal lobe structures in discriminative TPOA learning was questioned. The effects of excitotoxic lesions (ibotenate) of the basolateral amygdaloid nucleus, the central amygdaloid nucleus, the caudate putamen nucleus, and aspirative lesion of the entorhinal cortex were studied. The results show that only basolateral amygdaloid nucleus (ABL) damage impaired TPOA. This effect was selective of TPOA, since it spared conditioned taste aversion (CTA) and olfactory perception. In order to find out which process in TPOA requires normal functioning of the ABL, the effects of microinjections of a GABAA agonist (muscimol) into the ABL at various stages of the experiment were examined. The results show that application of muscimol during the acquisition, before or after the presentation of the odor-taste stimulus, impaired TPOA without affecting CTA. Contrastingly, application of muscimol before the test impaired neither TPOA nor CTA. These results suggest that ABL is involved in the acquisition but not in the retrieval of TPOA. The efficacy of muscimol microinjected after the presentation of the odor-taste stimulus further suggests that the deficit is not due to a sensory impairment but rather to the disruption of a memory process, critical for TPOA.}, } @article {pmid7582820, year = {1995}, author = {De la Casa, G and Lubow, RE}, title = {Latent inhibition in conditioned taste aversion: the roles of stimulus frequency and duration and the amount of fluid ingested during preexposure.}, journal = {Neurobiology of learning and memory}, volume = {64}, number = {2}, pages = {125-132}, doi = {10.1006/nlme.1995.1051}, pmid = {7582820}, issn = {1074-7427}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; *Drinking ; Female ; Male ; *Mental Recall ; Rats ; Rats, Wistar ; Retention, Psychology ; Saccharin ; *Taste ; Thirst ; }, abstract = {Two experiments examined the effects of total stimulus preexposure on latent inhibition (LI) in a conditioned taste aversion procedure with rats. Experiment 1 varied the frequency and duration of saccharin preexposures. LI was an increasing function of the product of frequency x duration. Experiment 2 kept saccharin exposure time constant but varied the amount of saccharin consumed by manipulating number of hours of fluid deprivation prior to exposure. Deprivation schedule conditions affected the amounts consumed which, in turn, modulated LI magnitude, at least with a 1-day acquisition-test interval, as in Experiment 1. The data clearly indicate that LI is a function of total amount of contact with the preexposed saccharin solution. In addition, half of the subjects in Experiment 2 were tested 21 days after the conditioning event. LI was not present in any group tested at this interval. These data were discussed in regard to the controversy regarding whether LI represents a failure to acquire the CS-US association or a failure to retrieve that association.}, } @article {pmid8542305, year = {1995}, author = {Mark, GP and Weinberg, JB and Rada, PV and Hoebel, BG}, title = {Extracellular acetylcholine is increased in the nucleus accumbens following the presentation of an aversively conditioned taste stimulus.}, journal = {Brain research}, volume = {688}, number = {1-2}, pages = {184-188}, doi = {10.1016/0006-8993(95)00401-b}, pmid = {8542305}, issn = {0006-8993}, support = {DA 03597/DA/NIDA NIH HHS/United States ; NS 30697/NS/NINDS NIH HHS/United States ; }, mesh = {Acetylcholine/*metabolism ; Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/*physiology ; Male ; Nucleus Accumbens/*metabolism ; Rats ; Rats, Sprague-Dawley ; Stimulation, Chemical ; Taste/*physiology ; }, abstract = {To determine if acetylcholine (ACh) is released in the nucleus accumbens in response to a conditioned stimulus (CS) that reminds the animal of an aversive event, in vivo microdialysis was used to monitor extracellular ACh during conditioned taste aversion. Saccharin flavored water (2.5 mM saccharin) was paired twice with nausea induced by i.p. lithium chloride (100 mg/kg). This is normally sufficient to create an aversion to the taste of saccharin, but instead of a preference test, the saccharin solution was squirted directly into the rat's mouth via a cheek catheter during nucleus accumbens microdialysis. The result was a 40% increase in extracellular ACh. We reported earlier that dopamine changes in the opposite direction; it decreases. This suggests that high synaptic ACh and low DA are correlated with an aversive state and cessation of behavior.}, } @article {pmid7576224, year = {1995}, author = {Schafe, GE and Sollars, SI and Bernstein, IL}, title = {The CS-US interval and taste aversion learning: a brief look.}, journal = {Behavioral neuroscience}, volume = {109}, number = {4}, pages = {799-802}, pmid = {7576224}, issn = {0735-7044}, support = {DC00248/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Apomorphine/toxicity ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Male ; *Mental Recall ; Rats ; Retention, Psychology ; Time Factors ; }, abstract = {Temporal parameters of taste aversion learning are known to differ markedly from other learning paradigms in that acquisition occurs despite lengthy delays between exposure to conditioned (CS) and unconditioned stimulus (US). Far less consideration has been paid to very brief CS-US intervals and the possibility that this learning may also be distinguished by an ineffectiveness of close temporal contiguity between CS and US. The effectiveness of a very brief CS-US interval (10 s) was compared with that of 2 lengthier intervals (15 and 30 min). Temporal control of CS delivery (0.15% saccharin solution) into the oral cavity and US delivery (7.5 mg/kg apomorphine hydrochloride) into circulation involved infusion pumps and indwelling catheters. Using a 1-trial learning paradigm, CS-US delays of 15 and 30 min led to significant aversions whereas the 10-s CS-US interval did not, suggesting that close temporal contiguity between CS and US is neither necessary nor sufficient for conditioned taste aversion acquisition.}, } @article {pmid7576210, year = {1995}, author = {Hatfield, T and Gallagher, M}, title = {Taste-potentiated odor conditioning: impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala.}, journal = {Behavioral neuroscience}, volume = {109}, number = {4}, pages = {663-668}, doi = {10.1037//0735-7044.109.4.663}, pmid = {7576210}, issn = {0735-7044}, support = {MH35554/MH/NIMH NIH HHS/United States ; RSA K05 MH01149/MH/NIMH NIH HHS/United States ; }, mesh = {2-Amino-5-phosphonovalerate/*pharmacology ; Amygdala/*drug effects ; Animals ; Association Learning/drug effects ; Avoidance Learning/drug effects ; Brain Mapping ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists/*pharmacology ; Injections, Intraventricular ; Long-Term Potentiation/drug effects ; Male ; Mental Recall/drug effects ; Rats ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Smell/*drug effects ; Taste/*drug effects ; }, abstract = {Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated odor conditioning: a form of learning that is dependent on information processing in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired in their acquisition of the potentiated learning to an odor cue. Expression of this learning and acquisition of a simple taste aversion remained intact following drug treatment. In Experiment 2, dose dependence and stereoselectivity were demonstrated for the antagonist compound. These results are consistent with previous studies demonstrating that either basolateral amygdala lesions, or treatment with NMDA antagonists, by other routes (systemic or intraventricular) produce selective deficits in taste-potentiated odor conditioning.}, } @article {pmid7568998, year = {1995}, author = {Balleine, B and Gerner, C and Dickinson, A}, title = {Instrumental outcome devaluation is attenuated by the anti-emetic ondansetron.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {48}, number = {3}, pages = {235-251}, pmid = {7568998}, issn = {0272-4995}, mesh = {Animals ; Antiemetics/*pharmacology ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Lithium Chloride/toxicity ; Male ; Mental Recall/drug effects ; *Motivation ; Ondansetron/*pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {In three experiments we assessed the effect of an anti-emetic, the selective 5-HT antagonist ondansetron, on (1) the conditioning of a taste aversion using lithium chloride (LiCl); (2) the expression of that aversion; and (3) instrumental outcome-devaluation effects. In Experiment 1 it was found that ondansetron reduced the aversion induced by LiCl when administered prior to the LiCl injection and also attenuated the expression of that aversion when administered prior to test sessions. In Experiments 2 and 3, thirsty rats were trained, in a single session, to lever press and chain pull for sucrose and saline solutions concurrently before being injected with LiCl. They were then re-exposed to both solutions, one after injection of vehicle and the other after injection of ondansetron. In a choice extinction test on the levers and chains, animals performed more of the action whose training outcome was re-exposed under ondansetron than the other action, whether the test was conducted after an injection of vehicle or after one of ondansetron.}, } @article {pmid7485843, year = {1995}, author = {Kulkosky, PJ and Carr, BA and Flores, RK and LaHeist, AF and Hopkins, LM}, title = {Conditioned taste aversions induced by alcohol and lithium in rats selectively bred for ethanol neurosensitivity.}, journal = {Alcoholism, clinical and experimental research}, volume = {19}, number = {4}, pages = {945-950}, doi = {10.1111/j.1530-0277.1995.tb00971.x}, pmid = {7485843}, issn = {0145-6008}, support = {2S06 GM-08197-12/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain/drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Ethanol/*toxicity ; Lithium Chloride/*toxicity ; Male ; Rats ; Rats, Inbred Strains ; Sleep Stages/drug effects ; Taste/*drug effects ; }, abstract = {Rats that were selectively bred for differences in alcohol-induced sleep time (alcohol neurosensitivity) were tested for differences in formation and extinction of alcohol- and LiCl-induced conditioned taste aversions. Male rats bred for high, control, or low alcohol sensitivity (HAS, CAS, and LAS rats, respectively) were deprived of water and given daily 30 min access to water for a baseline period of 7 days. Rats were then given a novel 0.125% sodium saccharin solution, followed by an intraperitoneal injection of either saline, 2 g/kg of ethanol (at 10% w/v), or 50.9 mg/kg of LiCl (0.15 M) on 3 conditioning days. Each saccharin exposure was followed by a recovery day of access to water. The ethanol-induced saccharin aversion extinguished more rapidly in LAS rats than in CAS or HAS rats (p < 0.05), but LiCl conditioned equivalent aversions in each group. Also, ethanol injection results in large differences in observed resting behavior in these rats (HAS > CAS > LAS), but LiCl injection produced no reliable group differences in resting. The weaker alcohol-induced taste aversion in LAS rats accords with their previously measured higher oral consumption of alcohol (Kulkosky et al., Alcoholism 17:545-551, 1993) and the idea that alcohol intake is limited by an expectancy of postingestive consequences. The weaker ethanol-induced aversion in LAS rats reflects selective breeding of an alcohol-specific trait and not a general difference in aversive conditioning or chemical neurosensitivity.}, } @article {pmid8540258, year = {1995}, author = {Serova, ON and Solov'eva, NA and Lagutina, LV and Obukhova, MF}, title = {[The formation of taste aversion and preference under conditions of protein synthesis inhibition in rats].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {45}, number = {4}, pages = {742-747}, pmid = {8540258}, issn = {0044-4677}, mesh = {Animals ; Azaguanine/pharmacology ; Conditioning, Classical/drug effects/physiology ; Cycloheximide/pharmacology ; Lithium Chloride/pharmacology ; Male ; Protein Biosynthesis ; Protein Synthesis Inhibitors/pharmacology ; Proteins/*antagonists & inhibitors/drug effects ; Rats ; Saccharin ; Taste/drug effects/*physiology ; }, abstract = {The study is devoted to the role of protein synthesis in formation of chemosensory memory in rats. Two experimental models of taste memorizing were used, i.e., conditioned taste aversion (CTA) caused by association of succharin intake with being poisoned by lithium chloride, and increased taste preference (ITP) caused by the influence of primary consumption of succharin solution on its repeated intake. It was found out that CTA was not formed under conditions both of 43% inhibition of brain protein synthesis by cycloheximide and of 59% its inhibition by 8-azaguanine. Cycloheximide but not 8-azaguanine prevented formation of ITP. A proposal was made about participation of different spectra of protein and peptide molecules in formation of taste aversion and preference. The effect of protein synthesis inhibitors on the process of taste memory retrieval was not found.}, } @article {pmid7587968, year = {1995}, author = {Mucha, RF and Fassos, FF and Perl, FM}, title = {Withdrawal-like effects of pentylenetetrazol and valproate in the naive organism: a model of motivation produced by opiate withdrawal?.}, journal = {Drug and alcohol dependence}, volume = {39}, number = {1}, pages = {1-6}, doi = {10.1016/0376-8716(95)01116-g}, pmid = {7587968}, issn = {0376-8716}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; *Disease Models, Animal ; Dose-Response Relationship, Drug ; Male ; Morphine Dependence/psychology ; *Motivation ; Naloxone/pharmacology ; Neurologic Examination/drug effects ; Opioid-Related Disorders/*psychology ; Pentylenetetrazole/*toxicity ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome/*psychology ; Taste/drug effects ; Valproic Acid/*toxicity ; }, abstract = {Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive rat various behavioural effects resembling signs of opiate withdrawal in the morphine-treated subject. Suggestions in the literature that these substances may activate directly some of the neural consequences of opiate and drug withdrawal prompted us to look for and examine possible aversive effects of these substances at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion procedure, relatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do indeed have aversive effects. The maximum aversions were produced by 10 and 20 mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of morphine withdrawal precipitated by 0.01-0.03 mg/kg naloxone in a morphine pellet-implanted animal. Moreover, the maximum aversions with PTZ and VPA were significantly higher than the maximum aversions seen with naloxone in the drug-naive animal under the same training conditions. Thus, the data from the present study confirmed the notion that low doses of PTZ and VPA in the naive animal may activate processes activated by drug withdrawal, including those important for the motivational effect of withdrawal. However, it was also pointed out that the lowest dose VPA producing aversion was higher than that found here to produce writhes and ataxia (80 mg/kg) but the same as that required for shaking (160 mg/kg), while the PTZ aversion was at a dose lower than that known to produce a PTZ cue. Implications were discussed for using withdrawal-like phenomena as a model in the non-treated organism of clinically-relevant withdrawal effects.}, } @article {pmid11224346, year = {1995}, author = {Shoaib, M and Stolerman, IP}, title = {Conditioned taste aversions in rats after intracerebral administration of nicotine.}, journal = {Behavioural pharmacology}, volume = {6}, number = {4}, pages = {375-385}, pmid = {11224346}, issn = {1473-5849}, abstract = {Previous studies suggested that the conditioned taste aversion (CTA) produced by nicotine was of central origin. The aims of the present work were to identify neural substrates that mediate nicotine-induced CTA, and to examine the relationship between the CTA and locomotor depressant effects of nicotine. After two conditioning trials with 0.1 or 0.4mg/kg nicotine (s.c.), significant CTA was apparent. In contrast, CTA was absent when nicotine (4 or 32µg) was administered into a lateral ventricle or when nicotine (4µg) was administered into the fourth ventricle, but decreases in locomotor activity were apparent during the conditioning phase. Nicotine (8µg) produced CTA when administered bilaterally into the nucleus accumbens. This finding was confirmed in a second experiment, but was not found in rats pretreated with the nicotine antagonist mecamylamine (2mg/kg s.c.). Bilateral administration of nicotine into the striatum, ventral tegmental area, dorsal hippocampus or the mesopontine tegmentum failed to produce CTA, and administration of nicotine into the interpeduncular nucleus produced CTA in one of two experiments only. It was concluded that the aversive effects produced by systemically administered nicotine may be mediated in part through nicotinic receptors located in the nucleus accumbens. The locomotor depression associated with intraventricular administration of nicotine could be dissociated from the aversive effect as measured by the CTA procedure.}, } @article {pmid11224343, year = {1995}, author = {Sobel, BF and Wetherington, CL and Riley, AL}, title = {The contribution of within-session averaging of drug- and vehicle-appropriate responding to the graded dose-response function in drug discrimination learning.}, journal = {Behavioural pharmacology}, volume = {6}, number = {4}, pages = {348-358}, pmid = {11224343}, issn = {1473-5849}, abstract = {Prior work within the taste aversion baseline of drug discrimination learning has demonstrated that the generalization function for individual rats is graded in nature. In such work, intermediate doses of the training drug produced intermediate levels of drug-appropriate responding. Under some conditions, such graded responding has been reported to be due to an averaging of quantal drug- and vehicle-appropriate responding at different periods within the session. The present experiment assessed the contribution of such averaging to the graded responding within the aversion design. Rats were first trained to discriminate either 1mg/kg naloxone or 10mg/kg pentobarbital from distilled water. They were then administered various doses of the training drug (or a different drug), and the within-session pattern of licking was monitored minute by minute over the 20min session. Responding within the session was primarily either drug- or vehicle-appropriate. The specific pattern of drug- or vehicle-appropriate responding was presumably dependent upon the onset and/or offset of the drug stimulus. Thus, for the aversion baseline the graded response function for individual rats appears to be a function of the within session averaging of quantal (either drug- or vehicle-appropriate) responding.}, } @article {pmid7791092, year = {1995}, author = {Ervin, GN and Birkemo, LS and Johnson, MF and Conger, LK and Mosher, JT and Menius, JA}, title = {The effects of anorectic and aversive agents on deprivation-induced feeding and taste aversion conditioning in rats.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {273}, number = {3}, pages = {1203-1210}, pmid = {7791092}, issn = {0022-3565}, mesh = {Animals ; Appetite Depressants/*pharmacology ; Avoidance Learning/*drug effects ; Bombesin/pharmacology ; Dextroamphetamine/pharmacology ; Fenfluramine/pharmacology ; *Food Deprivation ; Lithium Chloride/pharmacology ; Male ; Rats ; Sincalide/pharmacology ; Taste/*drug effects ; }, abstract = {We compared the effects of intraperitoneally administered LiCl (0.5-2830 mumol/kg), sulfated cholecystokinin26-33 (10-1000 nmol/kg; CCK-8), nonsulfated CCK-8 (500 and 1000 nmol/kg), sulfated CCK26-29 (500 and 1000 nmol/kg), CCK30-33 (10-1000 nmol/kg) bombesin (10-1000 nmol/kg; BOM), (dl) fenfluramine HCl (0.9-37.3 mumol/kg; fenfluramine), fluoxetine HCl (2.9-86.7 mumol/kg; fluoxetine), and d-amphetamine sulfate (0.27-10.9 mumol/kg; AMPH) on both 18-hr deprivation-induced feeding and one-bottle, taste aversion conditioning in male, Long-Evans rats. Doses of LiCl > or = 177 mumol/kg (or 7.5 mg/kg) induced significant, dose-related taste aversions, but only doses of LiCl > or = 2123 mumol/kg (90 and 120 mg/kg) induced significant anorexia. CCK-8 induced marked anorexia (at doses > or = 25-50 nmol/kg), but only relatively mild taste aversions which were only statistically significant at the highest dose (1000 nmol/kg). The anorectic effects of CCK-8 at 500 and 1000 nmol/kg, but not at lower doses, lasted at least 3 hr. Sulfated CCK26-29, CCK30-33 and nonsulfated CCK-8 induced neither anorexia nor taste aversion. BOM induced marked anorexia at all doses tested, but did not induce statistically significant taste aversions. The nonpeptidal anorectic compounds, fenfluramine, fluoxetine, and AMPH, induced both dose-related anorexia and taste aversion conditioning. We focus on several issues concerning the interpretation of taste aversion conditioning. Our results challenge any simple relationship between the ability of a compound to induce taste aversion and to decrease feeding.}, } @article {pmid7662164, year = {1995}, author = {Chavez, M and Seeley, RJ and Woods, SC}, title = {A comparison between effects of intraventricular insulin and intraperitoneal lithium chloride on three measures sensitive to emetic agents.}, journal = {Behavioral neuroscience}, volume = {109}, number = {3}, pages = {547-550}, pmid = {7662164}, issn = {0735-7044}, support = {AA-07247/AA/NIAAA NIH HHS/United States ; DK-17844/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/drug effects ; Avoidance Learning/drug effects ; Body Weight/*drug effects ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Injections, Intraperitoneal ; Injections, Intraventricular ; Insulin/*pharmacology ; Lithium Chloride/*pharmacology ; Male ; Oxytocin/blood ; Rats ; Taste/drug effects ; Viscera/innervation ; Water-Electrolyte Balance/drug effects ; }, abstract = {When low doses of insulin are infused directly into the third ventricle, rats reduce their food intake and lose weight. To determine whether these effects could be due to malaise induced by the treatment, the effects of intraventricular insulin were compared to the effects of the emetic agent lithium chloride to condition a taste aversion, to stimulate oxytocin secretion, and to reduce sodium appetite in response to furosemide treatment. For all three of these measures, lithium chloride treatment had a predictable effect compared to controls. Specifically, lithium caused a significant taste aversion, elevated plasma oxytocin, and attenuated sodium appetite. However, lithium did not produce a significant change in food intake or body weight. On the other hand, intraventricular insulin treatment did cause a significant reduction in body weight yet had no effect on these indices of malaise in the rat. These data are consistent with the hypothesis that intraventricular insulin does not reduce food intake and body weight by producing malaise but rather serves as a negative feedback signal of body adiposity to the central nervous system.}, } @article {pmid7662152, year = {1995}, author = {Gallo, M and Cándido, A}, title = {Dorsal hippocampal lesions impair blocking but not latent inhibition of taste aversion learning in rats.}, journal = {Behavioral neuroscience}, volume = {109}, number = {3}, pages = {413-425}, doi = {10.1037//0735-7044.109.3.413}, pmid = {7662152}, issn = {0735-7044}, mesh = {Animals ; Association Learning ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Hippocampus/*physiology ; Lithium Chloride/toxicity ; Male ; Mental Recall/physiology ; Neural Inhibition/*physiology ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {The aim of the present experiments was to study the effect of nonselective electrolytic lesions of the rat dorsal hippocampus on 2 learning phenomena: the L.J. Kamin (1969) blocking effect and latent inhibition of taste aversion learning. Bilateral dorsal hippocampal lesions selectively impaired blocking induced by 1 saccharin-lithium chloride pairing previous to 1 serial compound (saccharin-cider vinegar)-lithium pairing, but lesions had no effect on latent inhibition of a saline aversion, induced by 6 saline preexposures, in the same group of animals. Moreover, dorsal hippocampal lesions did not affect latent inhibition of saccharin-conditioned aversion induced by 1 or 6 preexposures. It is argued that blocking and latent inhibition of taste aversion learning do not share a common neural mechanism.}, } @article {pmid7574574, year = {1995}, author = {Houpt, TA}, title = {Molecular approaches to conditioned taste aversion.}, journal = {Appetite}, volume = {24}, number = {3}, pages = {259}, doi = {10.1016/s0195-6663(95)99823-3}, pmid = {7574574}, issn = {0195-6663}, mesh = {Animals ; Association Learning/*physiology ; Immunohistochemistry ; Lithium Chloride/pharmacology ; Proto-Oncogene Proteins c-fos/analysis/physiology ; Quinine/adverse effects/pharmacology ; Rats ; Solitary Nucleus/chemistry/drug effects/physiology ; Sucrose/pharmacology ; Taste/drug effects/*physiology ; }, } @article {pmid7567421, year = {1995}, author = {Brosvic, GM and Hartsell, P and Spruill, J and Correia, M and Long, P and McEntegart, B}, title = {Conditioned taste aversions and latent inhibition in Egyptian spiny mice and Long-Evans rats.}, journal = {Perceptual and motor skills}, volume = {80}, number = {3 Pt 1}, pages = {995-998}, doi = {10.2466/pms.1995.80.3.995}, pmid = {7567421}, issn = {0031-5125}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Male ; Muridae ; Rats ; Rats, Inbred Strains ; *Reaction Time ; Species Specificity ; *Taste ; }, abstract = {The acquisition and extinction of a conditioned taste aversion in Egyptian spiny mice and Long-Evans rats was compared during 20 posttest sessions using a cross-over design and double-blind control procedures. Spiny mice preexposed to a sucrose CS demonstrated more latent inhibition and a faster rate of extinction than did Long-Evans rats preexposed to the same CS. Preference indices did not differ between control animals or as a function of gender. The present results are the first report of the effects of latent inhibition on learning taste aversion in Egyptian spiny mice.}, } @article {pmid7771580, year = {1995}, author = {Terry-Nathan, VR and Gietzen, DW and Rogers, QR}, title = {Serotonin3 antagonists block aversion to saccharin in an amino acid-imbalanced diet.}, journal = {The American journal of physiology}, volume = {268}, number = {5 Pt 2}, pages = {R1203-8}, doi = {10.1152/ajpregu.1995.268.5.R1203}, pmid = {7771580}, issn = {0002-9513}, support = {DK-35747/DK/NIDDK NIH HHS/United States ; DK-42274/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acids/*administration & dosage ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological ; Diet ; Eating ; Food Preferences ; Indoles/pharmacology ; Male ; Ondansetron/pharmacology ; Rats ; Rats, Sprague-Dawley ; *Saccharin ; Serotonin Antagonists/*pharmacology ; Tropanes/pharmacology ; Tropisetron ; }, abstract = {Conditioned taste aversion presumably plays a role in the anorectic responses to amino acid-imbalanced diets that induce acute amino acid deficiency. The serotonin3 (5-HT3) receptor antagonists, tropisetron (Trop), MDL-72222 (MDL), and ondansetron, increase intake of imbalanced amino acid diets. Therefore, we tested whether 5-HT3 receptor antagonists would block an aversion to powdered saccharin after it was included in an amino acid-imbalanced diet. Rats were given an intraperitoneal injection of Trop, MDL, or vehicle (Veh), just before introducing one of four diets: imbalanced amino acid diet +/- saccharin (Imb or ImbSac) or a balanced (corrected) diet +/- saccharin (Cor or CorSac). Subsequent aversion to saccharin was shown in preference tests using Cor and CorSac. Saccharin preference was significantly decreased (8.3% on test day 1) in the Veh/ImbSac group, but the Trop/ImbSac group's saccharin preference (57.8%) was similar to controls (49.6-70.3%); MDL also blocked the aversion to saccharin after ImbSac. This confirms previous reports of conditioned taste aversions with amino acid limitation and suggests a role for the 5-HT3 receptor in the development of these aversions.}, } @article {pmid7659769, year = {1995}, author = {Arnold, B and Allison, K and Ivanová, S and Paetsch, PR and Paslawski, T and Greenshaw, AJ}, title = {5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats.}, journal = {Psychopharmacology}, volume = {119}, number = {2}, pages = {213-221}, pmid = {7659769}, issn = {0033-3158}, mesh = {Animals ; Behavior, Animal/*drug effects ; Dose-Response Relationship, Drug ; Granisetron/pharmacology ; Haloperidol/pharmacology ; Indoles/pharmacology ; Male ; Motor Activity/*drug effects ; Nicotine/*pharmacology ; Ondansetron/pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin Antagonists/*pharmacology ; Time Factors ; Tropanes/pharmacology ; Tropisetron ; }, abstract = {The effects of 5-HT3 receptor antagonists (ondansetron 0.1 mg kg-1 SC 30 min; bemesetron 0.03 mg kg-1 SC 45 min) on nicotine-induced increases in locomotor activity were measured in male Sprague-Dawley rats. Intermittent daily injections of nicotine (0.3-1.2 mg kg-1 SC 30 min) resulted in increased locomotor activity as measured by photocell counts. The effect of nicotine was not affected by administration of the 5-HT3 receptor antagonists at doses that are reported to block nicotine- and morphine-induced place-preference conditioning. Neither of the 5-HT3 receptor antagonists tested affected activity counts in vehicle treated animals. Nicotine-induced hyperactivity was blocked by the dopamine antagonist haloperidol (0.03 mg kg-1 SC 2 h) and by the nicotinic antagonist mecamylamine (1 mg kg-1 SC 1 min). The effects of a range of doses (0-1 mg kg-1) of the 5-HT3 receptor antagonists ondansetron, bemesetron, granisetron and tropisetron on hyperactivity induced by 0.6 mg kg-1 nicotine were then assessed. Only tropisetron at 1 mg kg-1 attenuated nicotine-induced hyperactivity. To demonstrate the efficacy of the present range of doses of the 5-HT3 receptor antagonists in this study, conditioned taste aversion experiments were conducted. Ondansetron (0.1 mg kg-1) failed to attenuate a conditioned taste aversion to saccharin induced by nicotine (0.6 mg kg-1), but did induce a reduction in saccharin preference in choice tests following three saccharin-ondansetron pairings.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8564025, year = {1995}, author = {Spector, AC}, title = {Gustatory function in the parabrachial nuclei: implications from lesion studies in rats.}, journal = {Reviews in the neurosciences}, volume = {6}, number = {2}, pages = {143-175}, doi = {10.1515/revneuro.1995.6.2.143}, pmid = {8564025}, issn = {0334-1763}, support = {DC-00161/DC/NIDCD NIH HHS/United States ; K04-DC00104/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Electrophysiology ; Neural Pathways/anatomy & histology/physiology ; Pons/anatomy & histology/*physiology ; Rats ; Taste/*physiology ; }, abstract = {In rodents, third order gustatory neurons reside in the parabrachial nuclei of the dorsal pons. Lesions in this area of the brain have a variety of consequences on taste-related behaviors. Some behaviors are severely impaired, such as the expression of either conditioned taste aversion or depletion-induced sodium appetite. Other taste-based behaviors are less affected or not influenced at all. Although the lesion-behavior approach possesses serious methodological limitations, the constellation of findings from studies employing this experimental strategy in the PBN has promising implications. Foremost among these is the suggestion that the neural circuitry subserving performance in some of these taste-guided behavioral paradigms is dissociable. This paper critically reviews this body of behavioral research and discusses the conceptual ramifications of the results.}, } @article {pmid7675599, year = {1995}, author = {Misanin, JR and Hinderliter, CF}, title = {Lack of age differences in context-illness associations in the long-delay taste-aversion conditioning of rats.}, journal = {Perceptual and motor skills}, volume = {80}, number = {2}, pages = {595-598}, doi = {10.2466/pms.1995.80.2.595}, pmid = {7675599}, issn = {0031-5125}, support = {HD 21161/HD/NICHD NIH HHS/United States ; }, mesh = {Aging/*psychology ; Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Lithium Chloride ; Rats ; Rats, Wistar ; *Retention, Psychology ; Social Environment ; *Taste ; }, abstract = {To evaluate whether previously observed age differences in long-delay taste aversion were due to age-related differences in the shared association of contextual cues and CS with the US, weanling, young-adult, and old-adult rats were given a NaCl or LiCl US immediately after or a LiCl US 3 hr. after a saccharin CS presentation in a black or white context. They were then given a context-preference test in a chamber which was half black and half white. Analysis showed rats, irrespective of age or conditioning context, spent a significantly smaller percentage of time on the white side than on the black side of the test chamber. These results suggest that age differences in long-delay taste-aversion conditioning are not due to age-related differences in the shared association of contextual cues and CS with the US.}, } @article {pmid7667477, year = {1995}, author = {Hinderliter, CF and Misanin, JR}, title = {Age differences and the interstimulus interval context in long-delay taste-aversion conditioning of rats.}, journal = {Psychological reports}, volume = {76}, number = {2}, pages = {636-638}, doi = {10.2466/pr0.1995.76.2.636}, pmid = {7667477}, issn = {0033-2941}, mesh = {Aging/*psychology ; Animals ; Association Learning ; Attention ; *Avoidance Learning ; *Conditioning, Classical ; Cues ; Female ; Rats ; Rats, Wistar ; *Retention, Psychology ; Social Environment ; *Taste ; }, abstract = {Young-adult and old-adult rats were allowed to remain in the conditioning context or were returned to their home cages during a 3-hr. interval to assess whether previously observed age differences in long-delay taste-aversion conditioning may be due to age differences in the use of home-cage cues to mediate the CS-US association over a long delay. The old adults but not the young adults showed an aversion irrespective of the context in which they were detained during the interstimulus interval. These results suggest that young-adult rats do not use the interstimulus context cues to mediate the association over a delay interval. They suggest, rather, that context cues, which are more contiguous with the US than taste cues in long-delay conditioning, may be more effective in overshadowing taste cues in young adults than in old adults.}, } @article {pmid7617718, year = {1995}, author = {Exton, MS and Bull, DF and King, MG and Husband, AJ}, title = {Behavioral conditioning of endotoxin-induced plasma iron alterations.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {50}, number = {4}, pages = {675-679}, doi = {10.1016/0091-3057(94)00353-x}, pmid = {7617718}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Classical/*drug effects ; Endotoxins/*pharmacology ; Iron/*blood ; Lipopolysaccharides/*pharmacology ; Male ; Rats ; Rats, Wistar ; }, abstract = {The cascade of physiologic mechanisms in response to infection, the acute-phase response, is recognized as playing a major role in host defence. One such response is the hypoferremia that is consistently reported to occur during bacterial infection. This study aimed to determine whether the alterations in plasma iron were conditionable using the conditioned taste aversion (CTA) paradigm. The regime involved the pairing of a novel-tasting saccharin solution with bacterial endotoxin. Seven days after the initial pairing of these stimuli (the test day), the saccharin solution was represented. Animals exposed to this condition displayed a significant reduction in the level of plasma iron. Animals treated with an intraperitoneal dose of 400 micrograms/Kg lipopolysaccharide (LPS) displayed lower conditioned iron levels than rats infused with 100 micrograms/Kg LPS; however, this difference was not significant. These results showed that in addition to other acute-phase responses (fever and anorexia), plasma iron alterations are able to be manipulated through behavioral manipulations.}, } @article {pmid7781158, year = {1995}, author = {Mickley, GA and Lovelace, JD and Farrell, ST and Chang, KS}, title = {The intensity of a fetal taste aversion is modulated by the anesthesia used during conditioning.}, journal = {Brain research. Developmental brain research}, volume = {85}, number = {1}, pages = {119-127}, doi = {10.1016/0165-3806(94)00202-b}, pmid = {7781158}, issn = {0165-3806}, mesh = {Anesthetics/*pharmacology ; Animals ; Animals, Suckling ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Embryonic and Fetal Development/*drug effects ; Female ; Ketamine/pharmacology ; Lithium Chloride/pharmacology ; Male ; Pentobarbital/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {Rat fetuses (E18) can learn a taste aversion in utero if experience with a sweet flavor (saccharin = Sac) is followed by a malaise-producing injection of lithium chloride (LiCl). Here we report that this phenomenon can be significantly modulated by the type of anesthesia administered to the pregnant dam before the conditioning procedure. Dams were anesthetized with one of the following drugs or drug combinations: (1) sodium pentobarbital; (2) ketamine hydrochloride and xylazine; or (3) sodium pentobarbital and ketamine hydrochloride. While under the influence of these anesthetics, rat fetuses received pairings of Sac + LiCl or one of the following sets of oral and systemic (i.p.) control injections: Sac + Saline, H2O + LiCl; H2O + Saline. At age 15 days neonatal rats were given a taste preference test by allowing them to select nipples painted with either saccharin or vehicle (H2O). After weaning, rats were given an additional taste preference test where they were allowed to drink from bottles filled with either 0.30% saccharin or water. Neonates that received Sac + LiCl injections avoided saccharin-painted nipples while neonates that received control injections in utero preferred saccharin-painted nipples. Rats that acquired the taste aversion under the influence of ketamine showed a significantly stronger conditioned taste aversion on the nipple preference test than did those from dams injected with sodium pentobarbital. The conditioned taste aversion was not detectable later during the bottle preference test. Since ketamine blocks N-methyl-D-aspartate (NMDA) glutamate receptors, and these receptors have been implicated in neural plasticity during development, our data suggest that NMDA antagonism can potentiate fetal learning. Ketamine has been used as an obstetrical and pediatric anesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7606439, year = {1995}, author = {Swank, MW and Schafe, GE and Bernstein, IL}, title = {c-Fos induction in response to taste stimuli previously paired with amphetamine or LiCl during taste aversion learning.}, journal = {Brain research}, volume = {673}, number = {2}, pages = {251-261}, doi = {10.1016/0006-8993(94)01421-d}, pmid = {7606439}, issn = {0006-8993}, support = {DC00248/DC/NIDCD NIH HHS/United States ; }, mesh = {Amphetamine/*pharmacology ; Animals ; Learning/drug effects ; Lithium Compounds/*pharmacology ; Male ; Proto-Oncogene Proteins c-fos/*genetics ; Rats ; Sodium Chloride ; Taste/*drug effects ; Taste Threshold ; }, abstract = {Amphetamine and lithium chloride (LiCl) are both effective unconditioned stimuli (USs) in the establishment of conditioned taste aversions (CTA) in the rat. However, the mechanism of action of these drugs is quite different with the area postrema and related emetic circuitry critical to the response to LiCl but not amphetamine. c-Fos immunohistochemistry was used to define brain regions activated during drug administration and during expression of a CTA using either amphetamine or LiCl as the US drug. Administration of LiCl induced dense c-Fos-like immunoreactivity (c-FLI) in the nucleus of the solitary tract (NTS) while amphetamine induced only light staining in this area. A conditioned stimulus (CS) saccharin solution paired with amphetamine, however, was associated with c-FLI in NTS in a pattern quite similar to that seen to a LiCl-paired CS. This suggests that the pattern of c-Fos expression to a taste CS after conditioning is characteristic of aversion conditioning, in general, and appears not to represent a matching of the conditioned response to specific unconditioned effects of the drug. To examine this conditioned response further, c-FLI to the aversive saccharin CS was compared to the response to quinine hydrochloride, which is innately aversive. Although behaviorally the animals' ingestive responses were quite similar, the saccharin CS induced significant elevations of c-FLI in NTS whereas the quinine did not. Thus, a taste which had become aversive by virtue of conditioning induced c-FLI expression in NTS while a taste which was inherently aversive did not.}, } @article {pmid11224322, year = {1995}, author = {Järbe, TU and Lamb, RJ}, title = {Discriminated conditioned taste aversion for studying multi-element stimulus control.}, journal = {Behavioural pharmacology}, volume = {6}, number = {2}, pages = {149-155}, pmid = {11224322}, issn = {1473-5849}, abstract = {The effects of morphine pre-treatment interval on the stimulus control exerted by a multi-element stimulus consisting of morphine (5.6mg/kg), saccharin (0.2%, w/v), and a ball-bearing drinking nozzle in a discriminated taste aversion procedure were examined. In this discriminated aversion procedure, rats received injections of LiCI following presentation of this multielement stimulus, and injections of saline following the saline, water, and non-ball-bearing nozzle composite stimulus. These paired rats were compared to unpaired rats that received saline injections rather than LiCI injections following presentation of the multi-element stimulus. Morphine pre-treatment times of 5, 10, and 20min were examined in groups of 12 paired and 6 unpaired rats. The discrimination was rapidly learned under all three pre-treatment intervals. In subsequent testing with each individual stimulus element and combinations of two stimulus elements, stimulus control was clearly exerted by both morphine and saccharin. Paired rats drank less saccharin than unpaired rats, and less saccharin than water. Similarly, paired rats drank less fluid following morphine administration than following saline administration, and less fluid than unpaired rats following morphine administration. Control by the nozzle type was also apparent in significant interactions between the nozzle and morphine or saccharin and pairing with LiCI. In general, pre-treatment time did not influence the stimulus control that developed. However, at the two shorter pre-treatment times there was some indication that a conditioned taste aversion to morphine was developing in the unpaired rats. These experiments indicate that such discriminated taste aversion procedures may be viable methods for studying the contextual control of how drugs function as discriminative stimuli, and that longer drug pre-treatment times may be desirable in such procedures.}, } @article {pmid8521145, year = {1995}, author = {Blom, JM and Tamarkin, L and Shiber, JR and Nelson, RJ}, title = {Learned immunosuppression is associated with an increased risk of chemically-induced tumors.}, journal = {Neuroimmunomodulation}, volume = {2}, number = {2}, pages = {92-99}, doi = {10.1159/000096877}, pmid = {8521145}, issn = {1021-7401}, support = {CA58168/CA/NCI NIH HHS/United States ; S07RR07041/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; *Conditioning, Psychological ; Cyclophosphamide/pharmacology ; Female ; *Immunosuppression Therapy ; Learning ; Mice ; Mice, Inbred Strains ; Neoplasms, Experimental/*chemically induced ; Risk Factors ; }, abstract = {Based on the hypothesis that certain aspects of the CNS and immune system interact and that altered immune function affects carcinogenesis, an animal model was developed to examine the effects of learned immunosuppression on the development of a chemically induced tumor. In two experiments, we evaluated whether mice, for which immunosuppression was associated with a neutral (conditioned) stimulus, would exhibit an increased susceptibility to tumor development upon reexposure to the conditioned stimulus, as compared to nonconditioned and control animals. A taste aversion conditioning paradigm, based on classical conditioning techniques, was employed to suppress immune function using the cytotoxic and immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus and consequently increase the risk of chemically induced tumorigenesis. CY (100 mg/kg, intraperitoneal) was paired with saccharin in the drinking water (0.1%) of adult female mice (CF-1). Conditioned mice were exposed to saccharin twice in the absence of CY, on days 4 and 7 after the first exposure (day 1). All mice were injected with the chemical carcinogen 9,10-dimethylbenzanthracene (DMBA, 50 mg/kg, subcutaneous) on day 4 of conditioning. Two subsequent exposures to saccharin alone substantially increased the risk of developing DMBA-induced tumors (ranging from 83-91%), as compared to control animals (36%) that had not received this pairing. Mice that received all agents (i.e., CY, DMBA, and saccharin) in a slightly different order did not display elevated tumor incidence. Three separate exposures to CY also significantly increased the number of animals developing tumors in response to the carcinogen (75%). Mice were observed for at least 8 weeks after conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7900910, year = {1995}, author = {Grill, HJ and Friedman, MI and Norgren, R and Scalera, G and Seeley, R}, title = {Parabrachial nucleus lesions impair feeding response elicited by 2,5-anhydro-D-mannitol.}, journal = {The American journal of physiology}, volume = {268}, number = {3 Pt 2}, pages = {R676-82}, doi = {10.1152/ajpregu.1995.268.3.R676}, pmid = {7900910}, issn = {0002-9513}, support = {DK-21397/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antimetabolites/pharmacology ; Deoxyglucose/pharmacology ; Feeding Behavior/*drug effects/*physiology ; Genes, fos/genetics ; Ibotenic Acid/toxicity ; Male ; Mannitol/*analogs & derivatives/pharmacology ; Pons/drug effects/pathology/*physiology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Systemic injection of the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits a feeding response and induces c-fos activity in the parabrachial nuclei (PBN). We used bilateral ibotenic acid lesions of PBN to determine whether the activation inferred from c-fos activity was causally related to the feeding response. The relationship between the PBN lesion and feeding behavior was also examined with the glucose analogue 2-deoxy-D-glucose (2-DG). The PBN lesions interfered with the feeding response to 2,5-AM but spared the feeding response to 2-DG. Rats were also tested in a conditioned taste-aversion paradigm. Differences were observed in the relationship between lesion extent and behavioral deficit for feeding responses to 2,5-AM and taste-guided intake after taste-aversion conditioning. These data provide the first demonstration that central lesions can disrupt feeding responses to peripherally acting 2,5-AM. The results suggest that the neural substrate for this response differs from that mediating taste-aversion conditioning and from that involved in the feeding response to 2-DG.}, } @article {pmid7792081, year = {1995}, author = {Yamamoto, T and Fujimoto, Y and Shimura, T and Sakai, N}, title = {Conditioned taste aversion in rats with excitotoxic brain lesions.}, journal = {Neuroscience research}, volume = {22}, number = {1}, pages = {31-49}, doi = {10.1016/0168-0102(95)00875-t}, pmid = {7792081}, issn = {0168-0102}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/pathology ; Brain Diseases/*chemically induced/pathology/*psychology ; Ibotenic Acid/toxicity ; Lithium Chloride/pharmacology ; Male ; Memory/drug effects ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is well known to be a robust and long-lasting learning after a single conditioned stimulus (CS) (taste)--unconditioned stimulus (US) (malaise) pairing. The neural mechanisms of this taste aversion learning still remain to be resolved. To elucidate the basic brain mechanisms of the taste aversion learning, we examined the effects of lesions of various sites of the rat brain on the acquisition and retention of CTAs. Confined brain lesions were made by injections of a small amount of excitotoxic drug, ibotenic acid. CTAs were established to saccharin (CS) by pairing its ingestion with an i.p. injection of LiCl (US). Rats lacking the parabrachial nucleus (PBN) almost completely failed to acquire CTAs. The second most effective lesion was in the medial thalamus including the parvocellular part of the ventral posteromedial nucleus of the thalamus (VPMpc) and the midline part, followed by the damage of the lateral nuclear group of the amygdala including the basolateral amygdaloid nucleus. Lesions of the gustatory cortex (GC) and hippocampus induced moderate effects, but lesions in the other subnuclei of the amygdala, such as the medial and central amygdaloid nuclei, entorhinal cortex, lateral hypothalamic area, and ventromedial hypothalamic nucleus induced slight or no effects. On the other hand, paired lesions among the amygdala, medial thalamus and GC caused severe impairment of CTAs; in particular, lesions of amygdala and VPMpc completely disrupted acquisition of CTAs. These results suggest that the PBN, medial thalamus and the lateral nuclear group of the amygdala play an essential role in the formation of taste aversion learning.}, } @article {pmid7782058, year = {1995}, author = {Arzuffi, R and Racotta, IS and Angeles, TP and Racotta, R}, title = {The role of conditioned taste aversion in the hypophagia induced by intraperitoneal epinephrine and glucose.}, journal = {Hormones and behavior}, volume = {29}, number = {1}, pages = {1-11}, doi = {10.1006/hbeh.1995.1001}, pmid = {7782058}, issn = {0018-506X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Copper/pharmacology ; Copper Sulfate ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Epinephrine/*pharmacology ; Glucose Solution, Hypertonic/*pharmacology ; Injections, Intraperitoneal ; Male ; Prazosin/pharmacology ; Propranolol/pharmacology ; Rats ; Rats, Wistar ; Saccharin ; Taste/*drug effects ; }, abstract = {It has been repeatedly shown that relatively high doses of epinephrine (E) and glucose (G) injected intraperitoneally (ip) produce hypophagia in fasted rats. In the present work we used a conditioned taste aversion (CTA) paradigm in order to test whether this effect could be due to "malaise." We determined the effect on food intake and saccharin preference with the following treatments: (a) E ip 100 and 250 micrograms/kg; (b) E ip 250 micrograms/kg with or without previous alpha 1 plus beta adrenergic blockade; (c) G ip 3.5 and 4 g/kg. Both doses of E significantly reduced food intake more than 75% but only the high dose produced a significant (50%) reduction in saccharin preference. Blockade of alpha 1 and beta adrenergic receptors completely suppressed the E-induced hypophagia but attenuated only slightly the taste aversivon effect. Both doses of G decreased food intake but only the high dose reduced saccharin preference; part of these effects would appear to be due to the high osmolarity of the solution. The present results indicate that E and G may induce CTA in our experimental conditions. However, their hypophagic and aversive effects seem to be elicited by different mechanisms.}, } @article {pmid7783940, year = {1995}, author = {Gallo, M and Cándido, A}, title = {Reversible inactivation of dorsal hippocampus by tetrodotoxin impairs blocking of taste aversion selectively during the acquisition but not the retrieval in rats.}, journal = {Neuroscience letters}, volume = {186}, number = {1}, pages = {1-4}, doi = {10.1016/0304-3940(94)11265-k}, pmid = {7783940}, issn = {0304-3940}, mesh = {Acetates/pharmacology ; Acetic Acid ; Animals ; Conditioning, Operant/*drug effects ; Hippocampus/*drug effects ; Lithium/pharmacology ; Male ; Memory/*drug effects ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; Taste/*drug effects ; Tetrodotoxin/*toxicity ; }, abstract = {The role of the dorsal hippocampus in the different stages of blocking was examined in a taste aversion learning task. Blocking is a learning effect in which one previously conditioned element of a compound makes the conditioning of the added element difficult. An effective blocking procedure with one trial in each stage was tested in unoperated rats. In the first stage, rats drank saccharin and later received lithium chloride by i.p. injection. In the second stage, they were presented with a serial compound saccharin-cider vinegar before lithium injection. In a one-bottle, test a reduced aversion to cider vinegar was observed in this group compared to control groups with no previous saccharin aversion. Bilateral tetrodotoxin (TTX) injection (10 ng/microliters) in the dorsal hippocampus attenuated blocking if this was applied before drinking the compound stimulus during the second stage, but it produced no effect applied either before drinking saccharin in the first stage or before testing. Non-specific retrieval deficit produced by TTX injection applied before testing was ruled out in a control group subjected to a conventional cider vinegar aversion learning which showed complete retrieval of the aversion under TTX. It is concluded that the hippocampal function relevant for blocking takes place during the compound phase.}, } @article {pmid7862652, year = {1995}, author = {Rosenblum, K and Schul, R and Meiri, N and Hadari, YR and Zick, Y and Dudai, Y}, title = {Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {92}, number = {4}, pages = {1157-1161}, pmid = {7862652}, issn = {0027-8424}, mesh = {Animals ; *Avoidance Learning ; Cerebral Cortex/*metabolism ; Conditioning, Classical ; Male ; Membrane Proteins/metabolism ; Nerve Tissue Proteins/*metabolism ; Phosphorylation ; Rats ; Rats, Wistar ; *Taste ; Tyrosine/*metabolism ; }, abstract = {Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation. Recent data indicate that tyrosine phosphorylation also plays a role in neuronal plasticity. We are using conditioned taste aversion, a fast and robust associative learning paradigm subserved among other brain areas by the insular cortex, to investigate molecular correlates of learning and memory in the rat cortex. In conditioned taste aversion, rats learn to associate a novel taste (e.g., saccharin) with delayed poisoning (e.g., by LiCl injection). Here we report that after conditioned taste aversion training, there is a rapid and marked increase in tyrosine phosphorylation of a set of proteins in the insular cortex but not in other brain areas. A major protein so modulated, of 180 kDa, is abundant in a membrane fraction and remains modulated for more than an hour after training. Exposure of the rats to the novel taste alone results in only a small modulation of the aforementioned proteins whereas administration of the malaise-inducing agent per se has no effect. To the best of our knowledge, this is the first demonstration of modulation of protein tyrosine phosphorylation in the brain after a behavioral experience.}, } @article {pmid7753482, year = {1995}, author = {Goehler, LE and Busch, CR and Tartaglia, N and Relton, J and Sisk, D and Maier, SF and Watkins, LR}, title = {Blockade of cytokine induced conditioned taste aversion by subdiaphragmatic vagotomy: further evidence for vagal mediation of immune-brain communication.}, journal = {Neuroscience letters}, volume = {185}, number = {3}, pages = {163-166}, doi = {10.1016/0304-3940(95)11251-q}, pmid = {7753482}, issn = {0304-3940}, support = {MH45045/MH/NIMH NIH HHS/United States ; NS31569/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Brain/*immunology ; Cytokines/pharmacology ; Interleukin-1/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin ; *Taste ; Tumor Necrosis Factor-alpha/pharmacology ; Vagotomy ; Vagus Nerve/immunology/*physiology ; }, abstract = {Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are cytokines released by activated immune cells. IL-1 beta and TNF-alpha elicit various illness symptoms including avoidance of novel tastes with which they have been paired (conditioned taste aversion). Previous hypotheses to account for these actions have focused on blood-borne IL-1 beta and TNF-alpha exerting their effects directly at the brain. However, recent evidence suggests that these cytokines may activate subdiaphragmatic vagal afferents. The present experiments demonstrate that subdiaphragmatic vagal transection both attenuates acquisition and facilitates extinction of conditioned taste aversions induced by i.p. administration of either IL-1 beta or TNF-alpha.}, } @article {pmid7896975, year = {1995}, author = {Jacobsen, PB and Bovbjerg, DH and Schwartz, MD and Hudis, CA and Gilewski, TA and Norton, L}, title = {Conditioned emotional distress in women receiving chemotherapy for breast cancer.}, journal = {Journal of consulting and clinical psychology}, volume = {63}, number = {1}, pages = {108-114}, doi = {10.1037//0022-006x.63.1.108}, pmid = {7896975}, issn = {0022-006X}, support = {45157//PHS HHS/United States ; 58178//PHS HHS/United States ; }, mesh = {Adolescent ; Adult ; Breast Neoplasms/*psychology/*therapy ; *Conditioning, Psychological ; Drinking Behavior ; *Drug Therapy ; *Emotions ; Female ; Humans ; Middle Aged ; }, abstract = {This study investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Women scheduled to begin chemotherapy were randomly assigned either to an experimental group (exposed to a distinctive stimulus before each chemotherapy infusion) or a control group. After repeated infusions of chemotherapy, patients' responses to the distinctive stimulus were assessed in a location not associated with chemotherapy administration. At the test trial, experimental group patients showed evidence of increased emotional distress (self-reported on a visual analog scale) after the presentation of the distinctive stimulus, whereas control group patients did not. Post hoc analyses indicated that these increases in distress were not secondary to other conditioned responses (e.g., nausea, taste aversion). Thus, results supported the hypothesis that the pairing of a distinctive stimulus with chemotherapy would result in the development of a conditioned emotional response.}, } @article {pmid7734083, year = {1995}, author = {Spector, AC}, title = {Gustatory parabrachial lesions disrupt taste-guided quinine responsiveness in rats.}, journal = {Behavioral neuroscience}, volume = {109}, number = {1}, pages = {79-90}, doi = {10.1037//0735-7044.109.1.79}, pmid = {7734083}, issn = {0735-7044}, support = {DC-00161/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Dominance, Cerebral/physiology ; Dose-Response Relationship, Drug ; Lithium Chloride/toxicity ; Male ; Pons/*physiology ; *Quinine ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; Taste Threshold/physiology ; }, abstract = {This study examined the effects of electrophysiologically placed electrolytic lesions in the gustatory zone of the parabrachial nuclei (PBN) on the rat's taste-guided unconditioned licking of quinine hydrochloride during repeated 10-s trials. Concentration-response functions measured in water-deprived rats before and after surgery significantly shifted to the right as a result of the bilaterally placed lesions. These same rats were tested on their ability to acquire a lithium chloride (LiCl)-based conditioned taste aversion (CTA) to 0.1 M sucrose. Although the largest lesions severely affected performance in both tasks, there was only a modest correlation (r = -.447) between the extent of the lesion-induced shift in the quinine concentration-response curves and the degree of sucrose intake suppression after the first CTA conditioning trial. Thus, PBN lesions can disrupt performance on both tasks, but it appears that the neural processes governing unconditioned responsiveness to quinine may be to some extent dissociable from those subserving acquisition of a sucrose LiCl-based CTA.}, } @article {pmid7716224, year = {1995}, author = {Exton, MS and Bull, DF and King, MG}, title = {Behavioral conditioning of lipopolysaccharide-induced anorexia.}, journal = {Physiology & behavior}, volume = {57}, number = {2}, pages = {401-405}, doi = {10.1016/0031-9384(94)00249-5}, pmid = {7716224}, issn = {0031-9384}, mesh = {Animals ; Anorexia/chemically induced/*psychology ; Body Weight/drug effects ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Eating/drug effects ; *Escherichia coli ; Lipopolysaccharides/*pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; }, abstract = {One manifestation of the acute phase response, sickness behavior, is now considered an important response in the organism's overall attempt to reinstate homeostasis. This report aimed to determine whether the sickness behavior of anorexia was conditionable using the conditioned taste aversion paradigm. To investigate this phenomenon, lipopolysaccharide (LPS) (100 micrograms/kg) was used as the unconditioned stimulus, and was paired with a novel 1% saccharin solution (conditioned stimulus). Upon conditioned stimulus representation, the anorectic effects of LPS were observed. These data are consistent with recent literature showing acute phase events to be conditionable.}, } @article {pmid8554631, year = {1995}, author = {Creim, JA and Lovely, RH and Weigel, RJ and Forsythe, WC and Anderson, LE}, title = {Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions.}, journal = {Bioelectromagnetics}, volume = {16}, number = {5}, pages = {301-306}, doi = {10.1002/bem.2250160506}, pmid = {8554631}, issn = {0197-8462}, mesh = {Air ; Analysis of Variance ; Animals ; Association Learning/*radiation effects ; Avoidance Learning/*radiation effects ; Conditioning, Classical ; Cyclophosphamide/administration & dosage/pharmacology ; Drinking/drug effects ; *Electricity ; *Electromagnetic Fields ; Injections, Intraperitoneal ; Ions ; Male ; Mental Recall ; Rats ; Reproducibility of Results ; Saccharin/administration & dosage/pharmacology ; Specific Pathogen-Free Organisms ; *Taste/drug effects ; }, abstract = {Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one group to +75 kV/m (+2 x 10(5) air ions/cm3) and the other group to -75 kV/m (-2 x 10(5) air ions/cm3). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: This group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water "recovery" sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol. No saccharin-flavored water was consumed in the two-bottle preference test by the cyclophosphamide-injected, sham-exposed group compared to 74% consumed by the saline-injected sham-exposed controls (P < .0001). Saccharin-preference data for the static field-exposed groups showed no TA learning compared to data for sham-exposed controls. In summary, exposure to intense static electric fields and air ions did not produce TA learning as assessed by this particular design.}, } @article {pmid7878104, year = {1995}, author = {Hamilton, J and Cabanac, M and Lafrance, L and Nagy, J}, title = {Ingestive response shows absence of taste aversion after bovine satietin in rats.}, journal = {Physiology & behavior}, volume = {57}, number = {1}, pages = {125-128}, doi = {10.1016/0031-9384(94)00213-o}, pmid = {7878104}, issn = {0031-9384}, mesh = {Animals ; Appetite Depressants/*pharmacology ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Cocos ; Eating/drug effects ; Fruit ; Glycopeptides/*pharmacology ; Infusions, Parenteral ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; }, abstract = {Six adult male rats (409 +/- 16 g) were equipped with chronically implanted oral catheters. Facial consummatory responses to gustatory stimuli, of 50 microliters 2.0 mol.1-1 banana or coconut flavoring, were recorded on a +4/-4 scale for 30 s. The new flavors were paired with IP injections on three different days. The rats were injected with either saline or 1 mg.kg-1 bovine serum satietin (bs-SAT). Food intake and body weight were reduced (p < 0.005) after satietin but not after saline. Both coconut and banana flavors aroused mild ingestive responses in the naive rats. Five days after the beginning of the pairing with IP injections, the rats' response to coconut and banana remained unchanged. The results show that satietin was able to reduce food intake and body weight but did not arouse taste aversion.}, } @article {pmid7770194, year = {1995}, author = {Parker, LA}, title = {Rewarding drugs produce taste avoidance, but not taste aversion.}, journal = {Neuroscience and biobehavioral reviews}, volume = {19}, number = {1}, pages = {143-157}, doi = {10.1016/0149-7634(94)00028-y}, pmid = {7770194}, issn = {0149-7634}, support = {NIDA 06659/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Lithium/pharmacology ; Male ; Psychotropic Drugs/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; Reward ; Taste/*drug effects ; }, abstract = {Paradoxically, drugs that animals will self-administer also produce conditioned taste avoidance at similar dosage levels. The present review presents evidence that the taste avoidance produced by these rewarding drugs differs qualitatively from the taste avoidance produced by the nonrewarding, emetic drug, lithium chloride. An analysis of data pooled across 6 experiments compares the nature of flavor-drug associations produced by various rewarding drugs (amphetamine, cocaine, methamphetamine, methylphenidate, morphine, nicotine and phencyclidine) with that produced by lithium. The data from the groups conditioned with the rewarding drugs and with lithium were combined into the two categories of low/moderate and high doses. When assessed by the CTA test, the rewarding drugs did not differ from lithium in the strength of the CTA at low/moderate or at high doses. However, when assessed by the TR test, lithium produced more prominent aversive taste reactions than did the rewarding drugs. These findings suggest that the flavor-drug association produced by lithium and rewarding drugs differs qualitatively. With the large pooled data set we also assessed the relationship among the various TR categories, resulting in two factors of "Ingestion" and "Aversion" accounting for 55% of the total variability within the data.}, } @article {pmid7670890, year = {1995}, author = {Marfaing-Jallat, P and Portha, B and Pénicaud, L}, title = {Altered conditioned taste aversion and glucose utilization in related brain nuclei of diabetic GK rats.}, journal = {Brain research bulletin}, volume = {37}, number = {6}, pages = {639-643}, doi = {10.1016/0361-9230(95)00060-r}, pmid = {7670890}, issn = {0361-9230}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Chemistry/*physiology ; Brain Stem/metabolism ; Deoxyglucose/metabolism ; Diabetes Mellitus, Type 2/genetics/*metabolism/*psychology ; Drinking/physiology ; Eating ; Energy Metabolism/physiology ; Female ; Glucose/*metabolism ; Hypothalamus/metabolism ; Insulin/metabolism ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {The impact of diabetes and especially hyperglycemia on brain glucose utilization and insulin binding are still not clear. This is probably due to the fact that most studies have been performed in streptozotocin treated rats that are highly hyperglycemia and that could have an effect per se on the brain. The aim of the present work was to measure, in vivo, glucose utilization and insulin binding in different areas of the brain of the spontaneously diabetic GK rats that present a moderate hyperglycemia. Brain insulin receptors number was not changed in the brain of GK rats. By contrast, an increased glucose utilization was present in the external plexiform and the intergranular layers of the olfactory bulbs, as well as in the amygdaloid of the GK rats. These structures are involved in conditioned taste aversion, which was found to be greatly altered in the diabetic rats. These results sustain the hypothesis of impaired neuropsychological functions in diabetic patients particularly in term of learning and memory.}, } @article {pmid7651910, year = {1995}, author = {Ervin, GN and Mosher, JT and Birkemo, LS and Johnson, MF}, title = {Multiple, small doses of cholecystokinin octapeptide are more efficacious at inducing taste aversion conditioning than single, large doses.}, journal = {Peptides}, volume = {16}, number = {3}, pages = {539-545}, doi = {10.1016/0196-9781(95)00001-z}, pmid = {7651910}, issn = {0196-9781}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Lithium Chloride/administration & dosage ; Male ; Rats ; Sincalide/*administration & dosage ; Statistics as Topic ; Taste/*drug effects ; Tetragastrin/*administration & dosage ; }, abstract = {Using a one-bottle taste aversion conditioning paradigm, sulfated cholecystokinin(26-33) (CCK-8) has again been shown to induce taste aversion conditioning in rats. Even though the effective doses of CCK-8 are relatively high, they do not induce as strong an aversion as has been demonstrated with LiCl. This pharmacodynamic profile of CCK-8 (i.e., relatively moderate, but not strong, taste aversion induction) may result, in part, from its unusual pharmacokinetic profile. CCK-8 seems to have a plasma half-life of just several minutes, whereas LiCl has a plasma half-life of 6 h in rats. In the present study, CCK-8, CCK-4, or LiCl was administered either as single, large doses immediately following consumption of 0.2% sodium saccharin (SACC), or as 10 half-hourly injections of one-tenth the large dose. Presumably, multiple small doses extended the time CCK-8 and CCK-4 were acting in the body, even though the peak plasma concentrations were quantitatively lower than after the large, single doses. Ten injections of CCK-8 of 10 or 100 nmol/kg (11.4 or 114.3 micrograms/kg) induced significantly stronger taste aversions than single injections of the same total dose of 100 or 1000 nmol/kg (114.3 or 1143.3 micrograms/kg), whereas multiple injections of LiCl of 70.8 mumol/kg (3.0 mg/kg x 10) did not induce stronger taste aversions than single injections of 708 mumol/kg (30.0 mg/kg). Neither single nor multiple injections of CCK-4 of 1000 nmol/kg (596.7 micrograms/kg) x 1, or 100 or 1000 nmol/kg (59.7 or 596.7 micrograms/kg) x 10 induced any sign of taste aversion conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7718154, year = {1994}, author = {Roldan, G and Bures, J}, title = {Tetrodotoxin blockade of amygdala overlapping with poisoning impairs acquisition of conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {65}, number = {2}, pages = {213-219}, doi = {10.1016/0166-4328(94)90107-4}, pmid = {7718154}, issn = {0166-4328}, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Lithium Chloride/pharmacology ; Male ; Memory, Short-Term/drug effects ; Pons/physiology ; Prosencephalon/physiology ; Rats ; Saccharin/pharmacology ; Taste/*drug effects ; Tetrodotoxin/*pharmacology/*toxicity ; }, abstract = {The role of several forebrain structures in the association of the short-term gustatory memory (GSTM) of the conditioned stimulus (CS; 0.1% sodium saccharin) with the visceral unconditioned stimulus (US; 0.15 M LiCl, 2% b.wt.) in acquisition of conditioned taste aversion (CTA) was investigated. Experiment 1 examined the effects of bilateral reversible inactivation of amygdala (Amy), hippocampus (Hipp), gustatory cortex (GC), bed nucleus of stria terminalis (BNST), lateral hypothalamic area (LHA), ventral thalamus (VT) or LHA+VT, induced by intracerebral injection of tetrodotoxin (TTX; 10 ng/microliters per site) applied before i.p. injection of LiCl to rats anesthetized by pentobarbital (50 mg/kg) immediately after saccharin drinking. Amy blockade resulted in a complete disruption of learning, while the inactivation of the remaining areas examined produced mild or no impairments. The dose-related effects of TTX injection into Amy were investigated in Experiment 2. Doses of 3 and 1 ng TTX were as effective as the 10 ng dose used in Expt. 1. However, 0.3 ng or saline did not interfere with CTA acquisition. Analysis of the retrograde amnesic effect produced by transient amygdalectomy (Experiment 3), showed that TTX (10 ng) injected immediately or 1.5 h after LiCl application induced a marked learning disruption, whereas no amnesia was elicited at 6 and 24 h post-acquisition intervals. It is suggested that Amy plays an essential role in the associative phase of acquisition, but not in the consolidation of the permanent taste aversion engram.}, } @article {pmid7718144, year = {1994}, author = {Yamamoto, T and Shimura, T and Sako, N and Yasoshima, Y and Sakai, N}, title = {Neural substrates for conditioned taste aversion in the rat.}, journal = {Behavioural brain research}, volume = {65}, number = {2}, pages = {123-137}, doi = {10.1016/0166-4328(94)90097-3}, pmid = {7718144}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Models, Neurological ; *Nervous System Physiological Phenomena ; Rats ; Taste/drug effects/*physiology ; }, abstract = {Conditioned taste aversions (CTAs) are well known to be robust and long-lasting instances of learning induced by a single CS (taste)-US (malaise) pairing. CTA can be taken as a general model to search for neural mechanisms of learning and memory. In spite of extensive research on CTAs using a variety of approaches during the last three decades, the neural mechanisms of taste aversion learning still remain unsolved. In this article we propose a model of neural substrates of CTAs on the basis of our recent studies incorporating previous findings by other workers. Our studies mainly included experiments using ibotenic acid injections into various parts of the rat brain as a lesion technique, and c-fos immunohistochemistry in naive and CTA trained rats. CTAs were established by pairing the ingestion of saccharin (CS) with an ip injection of LiCl (US). Behavioral studies have shown that the parabrachial nucleus (PBN), medial thalamus, and basolateral nucleus of the amygdala are essential for both acquisition and retention of CTAs. C-fos studies suggested that association between gustatory CS and visceral US takes place in the PBN. The gustatory cortex (GC) may modify the strength of this association depending on the nature of the CS, viz., novel or familiar. The amygdala is indispensable for the expressions of CTAs. Tastes with hedonic values are stored in the GC in a long-term manner.}, } @article {pmid7715818, year = {1994}, author = {Bielavska, E and Krivanek, J}, title = {Intracerebral injection of polymyxin B blocks the acquisition of conditioned taste aversion in rats.}, journal = {Neuroscience letters}, volume = {182}, number = {2}, pages = {239-242}, doi = {10.1016/0304-3940(94)90806-0}, pmid = {7715818}, issn = {0304-3940}, mesh = {Alkaloids/pharmacology ; Animals ; Conditioning, Operant ; Drinking ; Male ; Piperazine ; Piperazines/pharmacology ; Polymyxin B/*pharmacology ; Protein Kinase C/*antagonists & inhibitors ; Rats ; Staurosporine ; Taste ; Visual Cortex ; }, abstract = {The contribution of protein kinase C (PKC) to the acquisition of conditioned taste aversion (CTA) was tested by injection of three PKC inhibitors--polymyxin B, H7 and staurosporine--into the parabrachial nucleus (PBN). From the tested drugs only polymyxin B (20 mM) prevented CTA acquisition. Application of H7 (10 mM) and staurosporine (100 and 500 microM) into the PBN did not impair CTA learning. The blocking effect of polymyxin B is dose dependent (5 and 10 mM concentration did not disrupt CTA formation) and site specific (application of polymyxin B into the visual cortex did not elicit CTA blockade). The ability of polymyxin B to disrupt CTA learning is not due to irreversible damage of PBN. These results suggest that polymyxin B blocks acquisition of CTA in some nonspecific way not necessarily involving inhibition of PKC. This conclusion is supported by failure of two other more specific PKC inhibitors to affect CTA learning.}, } @article {pmid7880455, year = {1994}, author = {Schalomon, PM and Robertson, AM and Laferriere, A}, title = {Prefrontal cortex and the relative associability of taste and place cues in rats.}, journal = {Behavioural brain research}, volume = {65}, number = {1}, pages = {57-65}, doi = {10.1016/0166-4328(94)90073-6}, pmid = {7880455}, issn = {0166-4328}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Corpus Callosum/physiology ; Cues ; Dominance, Cerebral/*physiology ; Lithium Chloride/toxicity ; Male ; Mental Recall/*physiology ; Orientation/*physiology ; Prefrontal Cortex/*physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; }, abstract = {The effects of cutting the corticocortical connections between medial and sulcal prefrontal areas on the conditioning of taste and place cues were examined. In Experiment 1, rats were simultaneously exposed to taste and place cues before injection of 0.15 M LiCl. In controls, a significant conditioned taste aversion (CTA) but no conditioned place aversion (CPA) was observed. In contrast, rats with bilateral knife cuts showed a significant CPA but a weaker CTA. To test whether these results could have been due to the effects of simultaneously exposing the rats to taste and place cues during conditioning, rats were trained independently in either CTA or CPA paradigms in Experiment 2. In the CTA test, rats both in operated and control groups showed a CTA when first tested. Rats with bilateral knife cuts, however, showed a weaker CTA than those in the control group. In the CPA test, rats in the control group did not exhibit a CPA, whereas the knife cut group did. Rats with sham lesions tested in Experiment 2 did not differ from control subjects on either the CPA or the CTA test. Thus, bilateral cuts increased the CPA and decreased the CTA even when tested independently. These results indicate that the relative ease of association of place and taste stimuli may be accounted for in part by the organization of the intrinsic connections of the prefrontal cortex in the rat.}, } @article {pmid7857239, year = {1994}, author = {Witt, ED}, title = {Mechanisms of alcohol abuse and alcoholism in adolescents: a case for developing animal models.}, journal = {Behavioral and neural biology}, volume = {62}, number = {3}, pages = {168-177}, doi = {10.1016/s0163-1047(05)80015-9}, pmid = {7857239}, issn = {0163-1047}, mesh = {Adolescent ; Age Factors ; Alcoholism/*physiopathology/psychology ; Animals ; Avoidance Learning/physiology ; Brain/*physiopathology ; *Disease Models, Animal ; Fetal Alcohol Spectrum Disorders/physiopathology ; Humans ; Neurotransmitter Agents/*physiology ; Rats ; Risk Factors ; Species Specificity ; Taste/physiology ; }, abstract = {This paper reviews the ontogeny of neurotransmitter systems and neuropharmacological challenge within transmitter systems and discusses the actions of alcohol on such systems during the juvenile through adolescent periods. To place the animal research within the context of human development, an attempt is made to first examine some fundamental principles of developmental research as they relate to the adolescent period. Evidence presented from animal studies indicates that unique neurochemical and behavioral changes are occurring during postnatal development, including adolescence, that could mediate the response to alcohol. The limited number of studies on the neurochemical and behavioral response to alcohol during adolescence has employed rats and has been restricted by the relatively brief adolescent period in that species. While one alternative is to use primates, it is suggested that innovative behavioral paradigms be developed for adolescent animals in other species to study behaviors such as alcohol self-administration or alcohol stimulus discrimination. It is also suggested that existing behavioral models that are more easily adapted to younger age ranges (e.g., conditioned place preference, conditioned taste aversion, thermal response to ethanol) be extended to make ontogenetic comparisons through adolescence and adulthood. This may further our understanding of alcohol's immediate consequences during each maturational stage and, more important, the contribution of early alcohol exposure to excessive drinking and abnormal cognitive and social functioning during subsequent stages of development.}, } @article {pmid11539983, year = {1994}, author = {Rabin, BM and Joseph, JA and Hunt, WA and Dalton, TB and Kandasamy, SB and Harris, AH and Ludewigt, B}, title = {Behavioral endpoints for radiation injury.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {14}, number = {10}, pages = {457-466}, doi = {10.1016/0273-1177(94)90500-2}, pmid = {11539983}, issn = {0273-1177}, mesh = {Amphetamine/pharmacology ; Animals ; Argon ; Avoidance Learning/drug effects/*radiation effects ; Behavior, Animal/*drug effects/*radiation effects ; Central Nervous System Stimulants/pharmacology ; *Cosmic Radiation ; Dopamine/metabolism ; Dopamine Antagonists/pharmacology ; Dopamine Uptake Inhibitors/pharmacology ; Dose-Response Relationship, Radiation ; Ferrets ; Gamma Rays ; Haloperidol/pharmacology ; Helium ; *Iron ; Linear Energy Transfer ; Lithium Chloride/pharmacology ; Neon ; Neutrons ; Niobium ; Particle Accelerators ; Rats ; Relative Biological Effectiveness ; Taste ; Vomiting ; }, abstract = {The relative behavioral effectiveness of heavy particles was evaluated. Using the taste aversion paradigm in rats, the behavioral toxicity of most types of radiation (including 20Ne and 40Ar) was similar to that of 60Co photons. Only 56Fe and 93Nb particles and fission neutrons were significantly more effective. Using emesis in ferrets as the behavioral endpoint, 56Fe particles and neutrons were again the most effective; however, 60Co photons were significantly more effective than 18 MeV electrons. These results suggest that LET does not completely predict behavioral effectiveness. Additionally, exposing rats to 10 cGy of 56Fe particles attenuated amphetamine-induced taste aversion learning. This behavior is one of a broad class of behaviors which depends on the integrity of the dopaminergic system and suggests the possibility of alterations in these behaviors following exposure to heavy particles in a space radiation environment.}, } @article {pmid11539981, year = {1994}, author = {Switzer RC 3rd, and Bogo, V and Mickley, GA}, title = {Histologic effects of high energy electron and proton irradiation of rat brain detected with a silver-degeneration stain.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {14}, number = {10}, pages = {443-451}, doi = {10.1016/0273-1177(94)90498-7}, pmid = {11539981}, issn = {0273-1177}, mesh = {Animals ; Astrocytes/pathology/*radiation effects ; Behavior, Animal/radiation effects ; Brain/*pathology/*radiation effects ; Dose-Response Relationship, Radiation ; *Electrons ; Male ; *Protons ; Radiation Dosage ; Radiation, Ionizing ; Rats ; Rats, Sprague-Dawley ; Silver Staining/methods ; }, abstract = {Application of the degeneration sensitive, cupric-silver staining method to brain sections of male Sprague-Dawley rats irradiated 4 days before sacrifice with 155 Mev protons, 2-8 Gy at 1 Gy/min (N=6) or 22-l0lGy at 20 Gy/min (N=16) or with 18.6 Mev electrons, 32-67 Gy at 20 Gy/min (N=20), doses which elicit behavioral changes (accelerod or conditioned taste aversion), resulted in a display of degeneration of astrocyte-like cell profiles which were not uniformly distributed. Plots of 'degeneration scores' (counts of profiles in 29 areas) vs. dose for the proton and electron irradiations displayed a linear dose response for protons in the range of 2-8 Gy. In the 20-100 Gy range, for both electrons and protons the points were distributed in a broad band suggesting a saturation curve. The dose range in which these astrocyte-like profiles becomes maximal corresponds well with the dose range for the X-ray eradication of a subtype of astrocytes, 'beta astrocytes'.}, } @article {pmid7862950, year = {1994}, author = {Risinger, FO and Malott, DH and Prather, LK and Niehus, DR and Cunningham, CL}, title = {Motivational properties of ethanol in mice selectively bred for ethanol-induced locomotor differences.}, journal = {Psychopharmacology}, volume = {116}, number = {2}, pages = {207-216}, pmid = {7862950}, issn = {0033-3158}, support = {R01 AA007702/AA/NIAAA NIH HHS/United States ; AA05828/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/psychology ; Animals ; Cues ; Drinking/drug effects ; Ethanol/blood/*pharmacology ; Male ; Mice ; *Motivation ; Motor Activity/*drug effects ; Taste/drug effects ; }, abstract = {Ethanol-induced locomotor stimulation has been proposed to be positively correlated with the rewarding effects of ethanol (Wise and Bozarth 1987). The present experiments provided a test of this hypothesis using a genetic model. Three behavioral indices of the motivational effects of ethanol (drinking, taste conditioning, place conditioning) were examined in mice from two independent FAST lines, selectively bred for sensitivity to ethanol-induced locomotor stimulation, and mice from two independent SLOW lines, selectively bred for insensitivity to ethanol-induced locomotor stimulation. In a single-bottle procedure, mice were allowed access to drinking tubes containing ethanol in a concentration (1-12% v/v) that increased over 24 consecutive days. FAST mice consumed greater amounts of ethanol solution. In a two-bottle procedure, mice were allowed access to tubes containing water or various concentrations of ethanol (2-8% v/v) over 6 days. FAST mice generally showed greater preference for ethanol solutions than SLOW mice. In a conditioned taste aversion procedure, mice received access to saccharin solution followed by injection of 2.5 g/kg ethanol (IP). SLOW mice developed aversion to the saccharin flavor more readily than FAST mice. In a series of place conditioning experiments, tactile stimuli were paired with various doses of ethanol (0.8-2.0 g/kg). During conditioning, FAST mice showed locomotor stimulation after 1.0, 1.2 and 2.0 g/kg ethanol while SLOW mice did not. During testing, mice conditioned with 1.2 g/kg and 2.0 g/kg ethanol showed conditioned place preference, but there were no line differences in magnitude of preference. These results indicate that genetic selection for sensitivity to ethanol-stimulated activity has resulted in genetic differences in ethanol drinking and ethanol-induced conditioned taste aversion but not ethanol-induced conditioned place preference. Overall, these data provide mixed support for the psychomotor stimulant theory of addiction.}, } @article {pmid7800742, year = {1994}, author = {Sako, N and Shimura, T and Komure, M and Mochizuki, R and Matsuo, R and Yamamoto, T}, title = {Differences in taste responses to Polycose and common sugars in the rat as revealed by behavioral and electrophysiological studies.}, journal = {Physiology & behavior}, volume = {56}, number = {4}, pages = {741-745}, doi = {10.1016/0031-9384(94)90236-4}, pmid = {7800742}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; *Carbohydrates ; Chorda Tympani Nerve/drug effects/physiology ; Conditioning, Classical/drug effects/*physiology ; Food Preferences/drug effects/*physiology ; Generalization, Stimulus/drug effects/physiology ; *Glucans ; Male ; Plant Proteins/pharmacology ; Rats ; Rats, Wistar ; Taste/drug effects/*physiology ; Taste Buds/drug effects/*physiology ; }, abstract = {Behavioral and electrophysiological experiments were performed to examine the suggestion that rats have two types of carbohydrate taste receptors, one for polysaccharides (e.g., Polycose) and one for common sugars (e.g., sucrose). Qualitative difference between the tastes of Polycose and sugars including sucrose, maltose, glucose, and fructose was surveyed by means of a conditioned taste aversion paradigm in which the number of licks for 20 s to each taste stimulus was measured. Aversive conditioning to Polycose did not generalize to sugars, while aversive conditioning to sucrose generalized to other sugars, but not to Polycose. In the electrophysiological study, taste responses of the whole chorda tympani were recorded. A proteolytic enzyme, pronase E, suppressed nerve responses to both Polycose and sugars to less than 50%. A novel anti-sweet peptide, gurmarin, strongly suppressed responses to sugars, but had essentially no effect on Polycose responses. On the other hand, KHCO3 enhanced responses to sugars to about 300%, but had little effect on Polycose responses. These results have confirmed the notion that rats can differentiate the tastes between Polycose and common sugars and that rats have two types of carbohydrate receptors.}, } @article {pmid7972395, year = {1994}, author = {Amaro, S and Monda, M and Pellicano, MP and Cioffi, LA and de Luca, B}, title = {Postprandial thermogenesis and conditioned taste aversion or preference.}, journal = {Physiology & behavior}, volume = {56}, number = {3}, pages = {463-469}, doi = {10.1016/0031-9384(94)90288-7}, pmid = {7972395}, issn = {0031-9384}, mesh = {Adipose Tissue, Brown/drug effects/physiology ; Animals ; Association Learning/drug effects/physiology ; Autonomic Nervous System/drug effects/physiology ; Avoidance Learning/drug effects/*physiology ; Body Temperature Regulation/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Eating/drug effects/*physiology ; Food Preferences/drug effects/*physiology ; Male ; Oxygen/physiology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/*physiology ; Thiamine/administration & dosage ; }, abstract = {Postprandial thermogenesis is under the control of the autonomic nervous system and alimentary conditioned stimuli change sympathetic and parasympathetic activity. Here we studied the effect of conditioned taste aversion on postprandial thermogenesis in rats. Two groups of animals were used, rats of the first group were controls, these were placed on a standard diet and, for some days, on two other different diets: one thiamine-free and the other thiamine-rich. Each diet had a different taste. The treated animals belonged to the second group, these were fed with the same three diets but for different lengths of times: thiamine-free diet for the first 5 wk afterwards, with thiamine-rich diet for 3 wk, and finally with laboratory standard diet for a few days. After a preference test with the three familiar diets, oxygen consumption rate and brown adipose tissue temperature were evaluated three times in both groups after ingestion of a test meal, each time with one of the three different diets. The preference test was unvaried for the three different familiar foods in controls, while the treated animals showed a lower preference for thiamine-free food than for the other two. Treated rats had a significantly higher increase in O2 consumption rate than controls. In this group intake of thiamine-free food induced a significantly lower increase in O2 consumption than the other two. The increase in brown adipose tissue temperature was also higher in treated than in control animals but in treated rats this was lower after intake of thiamine-free food than after the intake of the other two.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7924258, year = {1994}, author = {Smith, P and Inglis, IR and Cowan, DP and Kerins, GM and Bull, DS}, title = {Symptom-dependent taste aversion induced by an anticoagulant rodenticide in the brown rat (Rattus norvegicus).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {108}, number = {3}, pages = {282-290}, doi = {10.1037/0735-7036.108.3.282}, pmid = {7924258}, issn = {0735-7036}, mesh = {4-Hydroxycoumarins/*pharmacology ; Animals ; Behavior, Animal/drug effects ; Feeding Behavior/drug effects ; Food Preferences/drug effects ; Male ; *Rats ; Rodenticides/*pharmacology ; Taste/*drug effects ; }, abstract = {In a series of 3 experiments with different experimental paradigms, feeding patterns of laboratory rats (Rattus norvegicus) were monitored in 2-choice feeding tests after intubation with a sublethal dose of an anticoagulant rodenticide. We report for the first time that contrary to accepted wisdom, anticoagulants can induce taste aversions. Furthermore, we report behavioral symptoms within the 1st day after dosing. Our data suggest that the taste aversion is induced through an inhibition of the vitamin K cycle and is transient, attenuating over the same period as the levels of vitamin K-dependent proteins return to normal. Because the taste aversion is expressed most strongly when symptoms are most pronounced and is not expressed after symptoms have disappeared, we term this novel form of control symptom-dependent taste aversion.}, } @article {pmid7818451, year = {1994}, author = {Ossenkopp, KP and Rabi, YJ and Eckel, LA}, title = {Alcohol-induced conditioned taste aversions in chemically labyrinthectomized rats.}, journal = {Aviation, space, and environmental medicine}, volume = {65}, number = {9}, pages = {824-828}, pmid = {7818451}, issn = {0095-6562}, mesh = {Animals ; Arsanilic Acid ; Conditioning, Classical/*drug effects ; Ear, Inner/*physiology ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Time Factors ; }, abstract = {Male rats were chemically labyrinthectomized (n = 22) by intratympanic injections of sodium arsanilate, and control rats (n = 15) received intratympanic injections of isotonic saline. All rats were tested for labyrinthine integrity and then adjusted to a 23 h.d-1 water deprivation schedule. Both labyrinthectomized and control rats were exposed to a conditioned taste aversion (CTA) procedure or a control procedure. The CTA technique involved pairing a novel saccharin taste with subsequent intraperitoneal injection of ethanol (1.5 g.kg-1; 15% solution). The control CTA procedure paired a novel saccharin taste with injections of isotonic saline. Following two conditioning trials and 3 d of water only, saccharin preference ratios were obtained in two-bottle choice tests (saccharin vs. water) over 4 consecutive days. Control rats conditioned with ethanol exhibited a strong CTA (p < 0.01) relative to control rats injected with saline. Labyrinthectomized rats drinking saccharin followed by ethanol injections showed a strong CTA (p < 0.01) if conditioning occurred 29-30 d post-labyrinthectomy. However, CTA's were not apparent in labyrinthectomized rats conditioned with ethanol 19 d post-labyrinthectomy. Thus, ethanol-induced CTA formation varied across the post-labyrinthectomy time period.}, } @article {pmid7805467, year = {1994}, author = {Wang, Z and Liu, L and Jiang, B}, title = {Motion sickness in mice and conditioned taste aversion.}, journal = {Chinese medical journal}, volume = {107}, number = {9}, pages = {712-714}, pmid = {7805467}, issn = {0366-6999}, mesh = {Animals ; Conditioning, Classical/*physiology ; Male ; Mice ; *Motion Sickness ; Random Allocation ; Taste ; Visual Fields ; }, abstract = {Forty-eight male mice in 6 groups were studied. Conditioned taste aversion (CTA) in mice was produced by various motions including cross-coupled acceleration, rotation to two directions (with or without visual field) and linear acceleration. Deprived of water for 24 hours, the mice were exposed to motion immediately after drinking a novel solution, 0.15% saccharin. All groups received two pairings of CTA training related to motion. The results showed that both of cross-coupled and rotation produced frank CTA and former was far more obvious than the latter. In addition, motion with visual field had a trend to intensify sickness response.}, } @article {pmid7984736, year = {1994}, author = {Misanin, JR and Hinderliter, CF}, title = {Efficacy of lithium chloride in the taste-aversion conditioning of young-adult and old-age rats.}, journal = {Psychological reports}, volume = {75}, number = {1 Pt 1}, pages = {267-271}, doi = {10.2466/pr0.1994.75.1.267}, pmid = {7984736}, issn = {0033-2941}, support = {HD 21161/HD/NICHD NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Association Learning/*drug effects ; Conditioning, Classical/*drug effects ; Female ; Generalization, Psychological/drug effects ; Lithium Chloride/*toxicity ; Mental Recall/*drug effects ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {An absolute amount of a LiCl US was administered to 24 young-adult and 24 old-age rats during taste-aversion conditioning to determine whether the superior performance of old-age rats, when a 1% body-weight injection of a LiCl US is administered 3 hr. after a saccharin CS, is due to age-related differences in US intensity or the efficacy of LiCl. The aversion conditioned in old-age rats with a 3-hr. CS-US interval and an absolute amount of LiCl was still significantly greater than that in young adults suggesting that age-related differences in US intensity or the efficacy of LiCl cannot explain the superior performance of old-age rats. Possibly, old-age rats forget the specifics of the CS more than young adults and, thus, older animals show greater stimulus generalization to the substantially different test stimuli.}, } @article {pmid7972283, year = {1994}, author = {Mokler, DJ and Dixon, M and Stambaugh, L}, title = {Electrical stimulation of the dorsal raphe nucleus as a discriminative stimulus: generalization to (+/-)-DOI.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {48}, number = {4}, pages = {1041-1045}, doi = {10.1016/0091-3057(94)90218-6}, pmid = {7972283}, issn = {0091-3057}, mesh = {Amphetamines/*pharmacology ; Animals ; Cues ; Discrimination Learning/*drug effects ; Electric Stimulation ; Generalization, Stimulus/*drug effects ; Lithium Chloride/pharmacology ; Male ; Raphe Nuclei/*physiology ; Rats ; Rats, Sprague-Dawley ; Serotonin Receptor Agonists/*pharmacology ; Taste/drug effects ; }, abstract = {Electrical stimulation of the dorsal raphe nucleus of Sprague-Dawley rats was used as the cue for discrimination using a taste aversion paradigm. Rats were trained to associate saccharin drinking during electrical stimulation of the dorsal raphe nucleus with LiCl injection after the session as the aversive unconditioned stimulus. In sessions without stimulation, rats were allowed to consume saccharin and received a saline injection after the session. Suppression of saccharin consumption during electrical stimulation was learned within 12 trials. Rats trained in the reverse discrimination, i.e., sessions with no electrical stimulation paired with LiCl injection, showed a similar learning curve. Animals injected prior to the session with the hallucinogenic 5-HT2 agonist (+/-)-DOI associated DOI with electrical stimulation of the dorsal raphe nucleus. Thus, animals may be trained to discriminate electrical stimulation of the dorsal raphe nucleus. Furthermore, animals generalize from activation of 5-HT2 receptors to electrical stimulation of the dorsal raphe nucleus.}, } @article {pmid7938231, year = {1994}, author = {Persinger, MA and Bureau, YR and Peredery, O}, title = {Dissociation between conditioned taste aversion and radial maze learning following seizure-induced multifocal brain damage: quantitative tests of serial vs. parallel circuit models of memory.}, journal = {Physiology & behavior}, volume = {56}, number = {2}, pages = {225-235}, doi = {10.1016/0031-9384(94)90188-0}, pmid = {7938231}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Brain Damage, Chronic/chemically induced/*physiopathology ; Brain Mapping ; Conditioning, Classical/drug effects/*physiology ; Dose-Response Relationship, Drug ; Evoked Potentials/drug effects/physiology ; Lithium Chloride ; Male ; Maze Learning/drug effects/*physiology ; Mental Recall/drug effects/*physiology ; Nerve Degeneration/drug effects/physiology ; Nerve Net/drug effects/*physiopathology ; Pilocarpine ; Rats ; Rats, Wistar ; Seizures/chemically induced/*physiopathology ; Synaptic Transmission/drug effects/*physiology ; Taste/drug effects/*physiology ; Telencephalon/drug effects/physiopathology ; Thalamic Nuclei/drug effects/physiopathology ; }, abstract = {Multivariate analyses between conditioned taste aversion (CTA) and radial maze acquisition (RMA) scores and percentages of neuronal dropout within thalamic and telencephalic structures were completed for rats in which overt seizures had been evoked following a single systemic injection of lithium/pilocarpine. Despite multifocal damage, only the amount of damage within the hippocampus (CA1) and the basolateral amygdala was most strongly associated with attenuated CTA, whereas damage within the mediodorsal thalamus was primarily associated with RMA. There was no significant correlation between CTA or RMA. Multiple regression analyses for specific Paxinos and Watson structures and their traditional aggregates supported more precise delineation of neuronal substrates of learning/memory and a multimodal (parallel) model for these processes.}, } @article {pmid8084893, year = {1994}, author = {Bull, DF and Exton, MS and Husband, AJ}, title = {Acute-phase immune response: lipopolysaccharide-induced fever and sleep alterations are not simultaneously conditionable in the rat during the inactive (light) phase.}, journal = {Physiology & behavior}, volume = {56}, number = {1}, pages = {143-149}, doi = {10.1016/0031-9384(94)90272-0}, pmid = {8084893}, issn = {0031-9384}, mesh = {Acute-Phase Reaction/*immunology ; Animals ; Avoidance Learning/physiology ; Body Temperature Regulation/immunology ; Circadian Rhythm/*physiology ; Conditioning, Classical/*physiology ; Endotoxins/immunology ; Escherichia coli/immunology ; Fever/*immunology ; Food Preferences/physiology ; Interleukin-1/physiology ; Lipopolysaccharides/*immunology ; Male ; Mental Recall/physiology ; Motor Activity/*physiology ; Rats ; Rats, Wistar ; Sleep Stages/*immunology ; Sleep, REM/immunology ; Taste/physiology ; }, abstract = {Recent research has demonstrated that specific parameters of the immune system can be augmented by behavioral conditioning. These physiological alterations have been largely achieved by implementation of the conditioned taste aversion paradigm. Fever and sleep alterations are early occurrences within the acute-phase immune response to infection. The present study attempted to concurrently condition these two simultaneous, yet independent, responses. Lipopolysaccharide (LPS) was used as an unconditioned stimulus. When paired with a novel-tasting saccharin solution, a conditioned febrile response was observed. However, the somnogenic effects of LPS were not simultaneously conditionable. The conditioning of fever, as well as other interleukin-1-mediated responses, offers promise in both clinical and experimental applications.}, } @article {pmid7938116, year = {1994}, author = {Smurthwaite, ST and Riley, AL}, title = {Nalorphine as a stimulus in drug discrimination learning: assessment of the role of mu- and kappa-receptor subtypes.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {48}, number = {3}, pages = {635-642}, doi = {10.1016/0091-3057(94)90325-5}, pmid = {7938116}, issn = {0091-3057}, mesh = {3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; Analgesics/pharmacology ; Animals ; Diprenorphine/pharmacology ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Female ; Generalization, Stimulus/drug effects ; Nalorphine/*pharmacology ; Naloxone/pharmacology ; Naltrexone/pharmacology ; Pyrrolidines/pharmacology ; Rats ; Receptors, Opioid, kappa/*drug effects ; Receptors, Opioid, mu/*drug effects ; }, abstract = {Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate nalorphine from distilled water. In subsequent generalization tests, the mu-opiate agonist morphine substituted for the nalorphine stimulus in a dose-dependent manner, while the kappa-opiate agonist U50,488H and the mu-opiate antagonists naloxone and naltrexone failed to do so. That the mu-agonist morphine substituted for the nalorphine stimulus while a kappa-agonist and mu-antagonists failed to substitute indicate that the discriminative control that was established with nalorphine in the present study was mu-agonist receptor-mediated. The basis for this selective control by the mu-receptor subtype may be related to the relative salience of receptor activity in opiate-naive animals. The present results suggest that discriminative control by compounds with activity at multiple receptor sites is not uniformly mediated by specific activity at all of those sites. The specific site mediating discriminative control appears to be a function of the specific training drug.}, } @article {pmid7938112, year = {1994}, author = {McMahon, LR and Morien, A and Davies, BT and Wellman, PJ}, title = {Conditioned taste aversion in rats induced by the alpha 1-adrenoceptor agonist cirazoline.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {48}, number = {3}, pages = {601-604}, doi = {10.1016/0091-3057(94)90320-4}, pmid = {7938112}, issn = {0091-3057}, mesh = {*Adrenergic alpha-1 Receptor Agonists ; Adrenergic alpha-Agonists/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects ; Imidazoles/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Recent studies have indicated that alpha 1-adrenoceptor agonists such as phenylpropanolamine (PPA), cirazoline, amidephrine, and SK&F-89748 suppress food intake in rats. These compounds activate alpha 1-adrenoceptors within the paraventricular hypothalamic nucleus (PVN) and may excite efferent fibers that inhibit feeding. Studies of the effects of alpha 1-agonists suggest a specificity for feeding behavior, but no study to date has evaluated whether these agonists may suppress feeding behavior by the induction of malaise. Accordingly, the present experiment examined the ability of systemically administered cirazoline (0.1, 0.2, and 0.4 mg/kg, IP) to induce conditioned taste aversion (CTA) to a saccharin solution. Significant CTA was noted for 0.2 and 0.4 mg/kg cirazoline but not for 0.1 mg/kg cirazoline, compared to a vehicle treatment. The ED50 for cirazoline-induced aversion was computed to be 0.3 mg/kg, which contrasts with an ED50 value of 0.09 mg/kg for the effect of cirazoline on food intake (computed in other studies). More importantly, a 0.1 mg/kg dose of cirazoline, which is slightly greater than that of the ED50 value for suppression of feeding, did not induce significant CTA in the present study. These results suggest that malaise is not a prominent factor in the suppressive activity of cirazoline on food intake and advocate the use of cirazoline as an effective appetite suppressant.}, } @article {pmid8055271, year = {1994}, author = {Yamamoto, T and Shimura, T and Sako, N and Yasoshima, Y and Sakai, N}, title = {Some critical factors involved in formation of conditioned taste aversion to sodium chloride in rats.}, journal = {Chemical senses}, volume = {19}, number = {3}, pages = {209-217}, doi = {10.1093/chemse/19.3.209}, pmid = {8055271}, issn = {0379-864X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chorda Tympani Nerve/drug effects/physiology ; Denervation ; Feeding Behavior/drug effects/physiology ; Glossopharyngeal Nerve/drug effects/physiology ; Male ; Neurons, Afferent/drug effects/physiology ; Rats ; Rats, Wistar ; Sodium Chloride/*pharmacology ; Taste/*drug effects ; }, abstract = {Some factors concerning acquisition and retention of conditioned taste aversions (CTAs) were behaviorally examined in the rat. In the CTA paradigm, aqueous solution of 0.1 M NaCl was used as the conditioned stimulus (CS) and an intraperitoneal (i.p.) injection of 0.15 M LiCl was employed as the unconditioned stimulus (US). In experiment 1, CTAs to 0.1 M NaCl were examined in both forward (CS-US) and backward (US-CS) conditioning paradigms. Reliable CTAs were produced in the US-CS conditioning paradigm when the US-CS interval was less than 10 min, as well as in the CS-US conditioning paradigm. In experiment 2, strong CTAs to 0.1 M NaCl were established when water-deprived rats made at least 500 continuous licks, corresponding to 2.5 ml intake and 2 min of drinking time. In experiment 3, effects of gustatory deafferentation on CTA formation were studied. Only the chorda tympani played an important role in acquisition and retention of CTAs to NaCl solutions. These results indicate that strong CTAs can be acquired to 0.1 M NaCl, if its taste information which is conveyed via the chorda tympani during the 500 continuous licks is followed by LiCl-induced sickness.}, } @article {pmid8043508, year = {1994}, author = {Peeters, BW and Broekkamp, CL}, title = {Involvement of corticosteroids in the processing of stressful life-events. A possible implication for the development of depression.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {49}, number = {4-6}, pages = {417-427}, doi = {10.1016/0960-0760(94)90288-7}, pmid = {8043508}, issn = {0960-0760}, mesh = {Adrenal Cortex Hormones/*physiology ; Adrenalectomy ; Amphetamines/administration & dosage ; Animals ; Avoidance Learning ; Conditioning, Classical ; Cortisone/pharmacology ; Depression/*etiology/metabolism ; Dexamethasone/pharmacology ; Lithium Chloride ; Male ; Mice ; Mice, Inbred ICR ; Stress, Psychological/*metabolism ; Taste ; }, abstract = {In a sub-population of endogenously depressed patients, disturbances of the hypothalamic-pituitary-adrenal axis can be observed. Increased cortisol and CRH levels combined with normal ACTH concentrations have often been reported. Corticosteroids appear to play a role in the mood changes, in depressed subjects. However, their mechanism of action is unknown. In animal experiments, the involvement of corticosteroids in stressor-induced learning was investigated. Three paradigms were used. In the Porsolt swimtest an animal had to learn to adapt to an inescapable situation. In the lithium chloride conditioned taste aversion an animal learned to avoid sugar water. In the amphetamine sensitization a second injection of amphetamine caused a potentiated response, because of conditioning. All three conditions appeared to be stressful because they induced a corticosterone release. When adrenalectomized (ADX) mice were compared to control animals it appeared that, in all three paradigms, their memory function was disturbed. The data indicated that this was a specific glucocorticoid-mediated effect since corticosterone and dexamethasone injections were able to reverse the ADX-induced deficit. The ADX-induced disturbances were only observable at moderate stress levels. More severe stressors (lower water temperature in the Porsolt swimtest, higher lithium chloride and amphetamine doses) also made ADX mice remember their previous experiences. The results suggest that corticosteroids are involved in the consolidation of stressful events and the corresponding coping responses. They play, however, only a role in the case of moderate stressors. In ADX animals no stressor-induced corticosterone increase can occur and therefore these animals only remember severe stressors. In a depressed patient basal steroid levels are increased and consequently very mild stressors, which induce only a small extra steroid release, will be remembered. The remembering of all these negative experiences might be of importance for the development and maintenance of the depression.}, } @article {pmid8084508, year = {1994}, author = {Houpt, TA and Philopena, JM and Wessel, TC and Joh, TH and Smith, GP}, title = {Increased c-fos expression in nucleus of the solitary tract correlated with conditioned taste aversion to sucrose in rats.}, journal = {Neuroscience letters}, volume = {172}, number = {1-2}, pages = {1-5}, doi = {10.1016/0304-3940(94)90648-3}, pmid = {8084508}, issn = {0304-3940}, support = {MH00149/MH/NIMH NIH HHS/United States ; MH05455/MH/NIMH NIH HHS/United States ; MH44043/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Gene Expression/*drug effects ; Genes, fos/*drug effects ; Lithium Chloride/pharmacology ; Male ; Medulla Oblongata/physiology ; Rats ; Solitary Nucleus/drug effects/*physiology ; Sucrose/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {The pattern of neuronal activation in the rat nucleus of the solitary tract (NTS) in response to a standard gustatory stimulus was examined using c-Fos-like immunoreactivity (c-FLI) before and after conditioned taste aversion (CTA) formation. While unconditioned oral infusions of sucrose solution did not induce c-FLI in the NTS, after three pairings of sucrose with lithium chloride injections, sucrose induced c-FLI in the medial intermediate NTS 1 h after oral infusion. Extinction of the CTA by repeated infusions of sucrose alone reversed the induction of c-FLI.}, } @article {pmid8029299, year = {1994}, author = {Melton, PM and Riley, AL}, title = {Receptor mediation of the stimulus properties of cholecystokinin.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {48}, number = {1}, pages = {275-279}, doi = {10.1016/0091-3057(94)90527-4}, pmid = {8029299}, issn = {0091-3057}, mesh = {Animals ; Benzodiazepinones/pharmacology ; Cholecystokinin/antagonists & inhibitors/*pharmacology ; Devazepide ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Female ; *Phenylurea Compounds ; Rats ; Receptors, Cholecystokinin/antagonists & inhibitors/drug effects/*physiology ; Saccharin/pharmacology ; Taste/drug effects ; }, abstract = {Recently, Melton, Kopman, and Riley (20) reported the rapid acquisition of drug discrimination learning using the sulfated form of cholecystokinin (CCK) within the conditioned taste aversion baseline of drug discrimination learning. The present study was designed to explore the receptor mediation of the stimulus properties of CCK within this procedure. Every fourth day, experimental subjects were given CCK-saccharin-LiCl pairings, and on the intervening recovery days, saccharin alone. Once discriminative control was established, doses of the CCK receptor antagonists devazepide (CCK-type A receptor subtype) and L-365,260 (CCK-type B receptor subtype) were administered in combination with the training dose of CCK. Unlike L-365,260 (1-1000 micrograms/kg), devazepide (1 microgram/kg) blocked the CCK stimulus, suggesting that within this design CCK's stimulus properties are mediated by the CCK-type A receptor subtype.}, } @article {pmid8029278, year = {1994}, author = {Higgins, GA and Sellers, EM}, title = {Antagonist-precipitated opioid withdrawal in rats: evidence for dissociations between physical and motivational signs.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {48}, number = {1}, pages = {1-8}, doi = {10.1016/0091-3057(94)90489-8}, pmid = {8029278}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Drug Implants ; Eating/drug effects ; Food ; Food Deprivation/physiology ; Male ; Morphine/administration & dosage ; Morphine Dependence/*physiopathology/*psychology ; *Motivation ; Naloxone/*pharmacology ; Rats ; Rats, Wistar ; Reinforcement Schedule ; Substance Withdrawal Syndrome/*physiopathology/*psychology ; Taste/drug effects ; }, abstract = {In rats made opioid dependent by the implantation of a single morphine 75 mg base pellet, an attempt was made to determine whether any correlational existed between physical and motivational withdrawal signs by adjusting the dose of naloxone used to precipitate withdrawal. The models used to study motivational signs were taste (one- and two-bottle) conditioning and operant responding for food under an FR15 schedule of reinforcement. Naloxone at doses of 0.01 mg/kg and above produced both a conditioned taste aversion (two-bottle test only) and reduced food responding in morphine pellet, but not placebo pellet, implanted animals. No physical withdrawal signs, e.g., wet dog shakes, diarrhoea, were noted until naloxone doses of 0.05 mg/kg and above were used. It is concluded that the difference in naloxone doses required to elicit physical and motivational withdrawal components provides further support for their dissociation.}, } @article {pmid8159723, year = {1994}, author = {Meiri, N and Masos, T and Rosenblum, K and Miskin, R and Dudai, Y}, title = {Overexpression of urokinase-type plasminogen activator in transgenic mice is correlated with impaired learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {91}, number = {8}, pages = {3196-3200}, pmid = {8159723}, issn = {0027-8424}, mesh = {Animals ; Behavior, Animal/physiology ; Brain/*enzymology ; Gene Expression ; Learning Disabilities/*genetics ; Memory/physiology ; Mice ; Mice, Transgenic ; RNA, Messenger/genetics ; Urokinase-Type Plasminogen Activator/genetics/*metabolism ; }, abstract = {Transgenic mice designated alpha MUPA overproduce in the brain murine urokinase-type plasminogen activator (uPA), an extracellular protease implicated in tissue remodeling. We have now localized, by in situ hybridization, extensive signal of uPA mRNA in the alpha MUPA cortex, hippocampus, and amygdala, sites that were not labeled in counterpart wild-type mice. Furthermore, biochemical measurements reveal a remarkably high level of enzymatic activity of uPA in the cortex and hippocampus of alpha MUPA compared with wild-type mice. We have used the alpha MUPA mice to examine whether the abnormal level of uPA in the cortex and the limbic system affects learning ability. We report that alpha MUPA mice perform poorly in tasks of spatial, olfactory, and taste-aversion learning, while displaying normal sensory and motor capabilities. Our results suggest that uPA is involved in neural processes subserving a variety of learning types.}, } @article {pmid8169817, year = {1994}, author = {Kosten, TA and Miserendino, MJ and Chi, S and Nestler, EJ}, title = {Fischer and Lewis rat strains show differential cocaine effects in conditioned place preference and behavioral sensitization but not in locomotor activity or conditioned taste aversion.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {269}, number = {1}, pages = {137-144}, pmid = {8169817}, issn = {0022-3565}, support = {P50-DA04060/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*drug effects ; Cocaine/*pharmacology/toxicity ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Male ; Models, Biological ; Motor Activity/*drug effects ; Rats ; Rats, Inbred F344/*physiology ; Rats, Inbred Lew/*physiology ; Taste/*drug effects/physiology ; }, abstract = {Current research suggests there are genetic differences in susceptibility to drug abuse. One way to examine this relationship is to study inbred strains, such as Lewis (LEW) and Fischer 344 (F344) rats, that show differential biochemical and behavioral effects in response to psychoactive drugs. In the present study several behavioral effects of cocaine were compared in these strains, including conditioned place preference (CPP), conditioned taste aversion and locomotor activity. Cocaine CPP was greater in LEW rats than in F344 rats. In contrast, cocaine conditioned taste aversion did not differ between LEW and F344 rats, or did the locomotor activity levels seen after the first cocaine administration. LEW rats, however, showed enhanced locomotor activity to repeated cocaine administrations at all doses tested, an effect not seen in F344 rats. These data suggest that differences in the development of cocaine CPP in LEW and F344 rats are not due to differences in detection of or in inability to condition to cocaine. Rather, these differences in CPP may reflect strain differences in the response to repeated cocaine administrations and may be related to previously observed biochemical differences between the two rat strains.}, } @article {pmid8029247, year = {1994}, author = {Cannon, DS and Leeka, JK and Block, AK}, title = {Ethanol self-administration patterns and taste aversion learning across inbred rat strains.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {47}, number = {4}, pages = {795-802}, doi = {10.1016/0091-3057(94)90279-8}, pmid = {8029247}, issn = {0091-3057}, mesh = {Alcohol Drinking/*psychology/therapy ; Animals ; Aversive Therapy ; Conditioning, Psychological ; Ethanol/*administration & dosage ; Learning ; Male ; Rats ; Rats, Inbred Strains ; Self Administration/*psychology ; Species Specificity ; Taste ; }, abstract = {Initial self-administration of high doses of EtOH is shown to be associated in some inbred rat strains with the eventual development of a low preference for EtOH, presumably as a consequence of taste aversion learning occurring during initial intake. Only modest support was obtained for the hypothesis that strain differences in the aversiveness of EtOH affects taste aversion learning. The instrinsic palatability of EtOH and the salience of EtOH as a conditioned stimulus may also affect EtOH preference, but there do not appear to be differences among strains in their general ability to form taste-toxicosis associations.}, } @article {pmid8208786, year = {1994}, author = {Bellinger, LL and Nagy, J and Hamilton, J}, title = {HPLC-purified bovine satietin suppresses food intake and weight without causing conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {47}, number = {3}, pages = {659-666}, doi = {10.1016/0091-3057(94)90171-6}, pmid = {8208786}, issn = {0091-3057}, support = {DK42635/DK/NIDDK NIH HHS/United States ; }, mesh = {Angiotensin II/administration & dosage/pharmacology ; Animals ; Appetite Depressants/isolation & purification/*pharmacology ; Body Weight/*drug effects ; Brain Chemistry/*physiology ; Cattle ; Chromatography, High Pressure Liquid ; Conditioning, Operant/*drug effects ; Drinking/drug effects ; Eating/*drug effects ; Glycopeptides/isolation & purification/*pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {Satietin (SAT) is a putative satiety agent found in a variety of species including man and the rat. In the present study, satietin was extracted from bovine plasma (b-SAT) and further high-pressure liquid chromatography (HPLC)-purified. Rats were given chronic third ventricle cannulas and patency was verified. In experiment 1, rats were divided into three groups and ICV infused with artificial cerebrospinal fluid (a-CSF) or b-SAT: group 1, a-CSF (n = 11); group 2, 20 micrograms/rat, b-SAT (n = 11); and group 3, 40 micrograms/rat, b-SAT (n = 9). Infusions were repeated thrice three days apart. Compared to a-CSF, the high b-SAT dose suppressed food intake for 24-h after each successive infusion. The low dose significantly decreased food intake only after the first infusion. Water intake was suppressed only after the first injection of the high dose. Body weight was decreased after the first and second infusions of both doses and following the third infusion of the high dose. In experiment 2, rats were trained to drink fluid for 1 h/day while food was ad lib. On day 1, both groups received no infusions and were given tap water. On day 2, the groups were ICV infused with a-CSF, but group 1 (n = 12) was given banana-flavored fluid (BFF) and group 2 (n = 12) almond-flavored fluid (AFF). On day 3, group 1 was again a-CSF-infused but given AFF, whereas group 2 received 40 micrograms/rat b-SAT and was given BFF.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7838919, year = {1994}, author = {Bardo, MT and Valone, JM}, title = {Morphine-conditioned analgesia using a taste cue: dissociation of taste aversion and analgesia.}, journal = {Psychopharmacology}, volume = {114}, number = {2}, pages = {269-274}, pmid = {7838919}, issn = {0033-3158}, support = {DA05312/DA/NIDA NIH HHS/United States ; DA07746/DA/NIDA NIH HHS/United States ; }, mesh = {*Analgesia ; Animals ; Avoidance Learning/*drug effects ; *Cues ; Dose-Response Relationship, Drug ; Lithium/pharmacology ; Male ; Morphine/*pharmacology ; Pain Measurement/drug effects ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {The present study examined the ability of a taste cue to serve as a conditioned stimulus (CS) for conditioning the analgesic effect of morphine. Rats were given three pairings of a taste CS with a morphine unconditioned stimulus (US). As expected, there was a decrease in CS intake across repeated pairings, indicating that a conditioned taste aversion was obtained. More important, presentation of the CS alone also increased paw-lick latencies on a hot plate test (either 50 degrees C or 54 degrees C hot plate), suggesting that an analgesic conditioned response (CR) was obtained. The dose of morphine required to produce conditioned analgesia was higher than the dose of morphine required to produce conditioned taste aversion. Using 15 mg/kg morphine, however, both conditioned taste aversion and conditioned analgesia were present when the morphine US was given immediately following CS intake, but not when given 6 h following CS intake. In contrast to morphine, pairing a taste CS with lithium produced a conditioned taste aversion without any conditioned analgesic response. These results indicate that acquisition of an analgesic CR is not the result of stress induced by an aversion to the taste CS.}, } @article {pmid7838912, year = {1994}, author = {Glowa, JR and Shaw, AE and Riley, AL}, title = {Cocaine-induced conditioned taste aversions: comparisons between effects in LEW/N and F344/N rat strains.}, journal = {Psychopharmacology}, volume = {114}, number = {2}, pages = {229-232}, pmid = {7838912}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/*pharmacology ; Dose-Response Relationship, Drug ; Female ; Habituation, Psychophysiologic/drug effects ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Saccharin ; Species Specificity ; Taste/*drug effects ; }, abstract = {Recent studies have found the LEW/N rat self-administers drugs of abuse at higher rates than the F344/N rat, suggesting a genetic predisposition toward the abuse potential of drugs. The current study compared the acquisition of a conditioned taste aversion (CTA) to cocaine in these strains. During an initial 20-min daily session a 0.1% saccharin solution was available and a dose (0-50 mg/kg, SC) of cocaine was given immediately after that session. Water was available during sessions on the following 3 days. Fluid consumption was assessed over three saccharin/water cycles, and a final saccharin session. Vehicle injections (0 mg/kg) that followed exposure to saccharin had no effect on subsequent saccharin consumption. In contrast, when cocaine followed exposure to saccharin, rates of saccharin consumption decreased over successive saccharin sessions in a dose-related manner in both strains. The lowest dose (18 mg/kg) decreased consumption in LEW/N rats but not in F344/N rats. An intermediate dose (32 mg/kg) decreased consumption maximally in LEW/N rats and only marginally in F344/N rats. The highest dose (50 mg/kg) decreased consumption completely in LEW/N rats and almost completely in F344/N rats. These findings demonstrate that significant differences in sensitivity to stimuli paired with cocaine occur between these strains. These differences are consistent with previous reports that the LEW/N rat is uniquely sensitive to both behavioral and biochemical effects of drugs of abuse. The current report extends this sensitivity to the noxious effects of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8013551, year = {1994}, author = {Berendsen, HH and Broekkamp, CL}, title = {Comparison of stimulus properties of fluoxetine and 5-HT receptor agonists in a conditioned taste aversion procedure.}, journal = {European journal of pharmacology}, volume = {253}, number = {1-2}, pages = {83-89}, doi = {10.1016/0014-2999(94)90760-9}, pmid = {8013551}, issn = {0014-2999}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Amphetamines/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Fluoxetine/*pharmacology ; Male ; Mice ; Paroxetine/pharmacology ; Pyrazines/pharmacology ; Serotonin Receptor Agonists/*pharmacology ; *Taste ; }, abstract = {Pre-exposure to 5-hydroxytryptamine (5-HT) receptor agonists in conditioned taste aversion experiments was used to characterize the stimulus properties of fluoxetine. The taste aversion induced by fluoxetine (10 mg/kg) was completely prevented when mice were pre-exposed to fluoxetine or when they were pre-exposed to the preferential 5-HT1C receptor agonist MK 212. Pre-exposure to MK 212 also prevented the conditioned taste aversion induced by another serotonin uptake inhibitor, paroxetine. A partial attenuation of fluoxetine-induced conditioned taste aversion was seen after pre-exposure to a high dose of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 1 mg/kg), but not to lower doses. No familiarization for the fluoxetine stimulus was obtained by pre-exposure to treatments with the mixed 5-HT1C/2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). With the reversed sequence, pre-exposure to fluoxetine prevented the conditioned taste aversion induced by MK 212 or 8-OH-DPAT and reduced that induced by DOI. It is concluded that the acute stimulus properties of fluoxetine mostly resemble those of a 5-HT1C receptor agonist. This supports the suggestion that the 5-HT1C receptor can play an important role in the therapeutic effect of 5-HT reuptake inhibitors.}, } @article {pmid8012803, year = {1994}, author = {Swank, MW and Bernstein, IL}, title = {c-Fos induction in response to a conditioned stimulus after single trial taste aversion learning.}, journal = {Brain research}, volume = {636}, number = {2}, pages = {202-208}, doi = {10.1016/0006-8993(94)91018-9}, pmid = {8012803}, issn = {0006-8993}, support = {DC00248/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Chemistry/physiology ; Cell Nucleus/metabolism ; Hypoglossal Nerve/anatomy & histology/metabolism ; Immunohistochemistry ; Lithium Chloride/pharmacology ; Male ; Pons/anatomy & histology/metabolism ; Proto-Oncogene Proteins c-fos/*biosynthesis ; Rats ; Solitary Nucleus/anatomy & histology/metabolism ; Taste/*physiology ; }, abstract = {Taste aversion conditioning is characterized by its prompt acquisition despite the introduction of long delays between CS (taste) and UCS (toxic drug). Although the dramatic changes in behavioral response to a taste after this conditioning are well documented, relatively little is known about the changes in neural activity that accompany this learning. c-Fos immunohistochemical staining was employed to define brain regions activated during the expression of a conditioned taste aversion (CTA). The present studies examined c-Fos immunoreactivity in the brains of rats after i.p. injection of LiCl or NaCl or after intraoral infusion of a saccharin CS. LiCl administration, a common unconditioned stimulus (UCS) in CTA experiments, was found to induce c-Fos protein in a number of brainstem regions, including the nucleus of the solitary tract (NTS), medial and lateral pontine parabrachial nucleus (PBN), and hypoglossal nucleus. Conditioned animals received a single pairing of the CS saccharin with the UCS LiCl, while controls were exposed to the CS saccharin but received non-contingent LiCl 24 h after saccharin exposure. Following saccharin re-exposure, conditioned animals showed patterns of neuronal activation to a taste which were similar to those activated by the UCS drug. Specifically, the pattern of c-Fos expression in conditioned animals was confined to the same region of the NTS which showed the most activation following the UCS LiCl. This pattern of activation was not evident in controls re-exposed to saccharin.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8153166, year = {1994}, author = {Ganesan, R}, title = {The aversive and hypophagic effects of estradiol.}, journal = {Physiology & behavior}, volume = {55}, number = {2}, pages = {279-285}, doi = {10.1016/0031-9384(94)90134-1}, pmid = {8153166}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Diet ; Eating/*drug effects ; Estradiol/*pharmacology ; Ethamoxytriphetol/pharmacology ; Female ; Food Preferences/drug effects ; Gerbillinae ; Male ; Mice ; Ovariectomy ; Progesterone/pharmacology ; Receptors, Estradiol/antagonists & inhibitors ; Species Specificity ; Taste/drug effects ; }, abstract = {Estradiol is known to reduce food intake in many species. Recent studies have also shown that estradiol can function as an unconditioned stimulus in taste aversion paradigms, suggesting that it induces nausea and malaise in rats and mice. The experiments reported here compared the hypophagic and aversive effects of estradiol. Using mice as subjects, the first investigation examined the taste aversion properties of the estradiol receptor antagonist MER-25, which is estrogenic with respect to feeding. MER-25 induced a strong taste aversion, contrary to a previous report. Second, progesterone, which counteracts the hypophagic effects of estradiol, did not disrupt the taste aversion induced by estradiol in mice. The third investigation used the Mongolian gerbil, a species in which estradiol increases food intake, in contrast to other species. Despite increasing food intake, estradiol induced a conditioned taste aversion in the gerbil similar to that seen in rats and mice. Taken together, these results indicate that the feeding and aversive effects of estrogen are mediated by different mechanisms.}, } @article {pmid8153165, year = {1994}, author = {Brownson, EA and Sengstake, CB and Chambers, KC}, title = {The role of serum testosterone in the accelerated extinction of a conditioned taste aversion in fluid deprived male rats.}, journal = {Physiology & behavior}, volume = {55}, number = {2}, pages = {273-278}, doi = {10.1016/0031-9384(94)90133-3}, pmid = {8153165}, issn = {0031-9384}, support = {HD18185/HD/NICHD NIH HHS/United States ; RR-00163/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Dihydrotestosterone/blood ; Extinction, Psychological/*physiology ; Lithium Chloride/pharmacology ; Male ; Rats ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; Species Specificity ; Taste/*physiology ; Testosterone/blood/*physiology ; Water Deprivation/*physiology ; }, abstract = {Fluid deprivation decreases serum testosterone (T) levels and increases the rate of extinction of a conditioned taste aversion in Sprague-Dawley male rats. It has been suggested that the decreased serum levels may be the primary factor responsible for the accelerated extinction rates during fluid deprivation. To test the generality of this hypothesis, the effect of fluid deprivation on T levels and extinction rate was investigated in Fischer 344 male rats. Extinction rates were accelerated in Fischer 344 rats but T levels were not decreased. In a second study, the behavioral and hormonal responses of Fischer 344 and Sprague-Dawley males to fluid deprivation were compared. Extinction rates were increased in both strains of rat by fluid deprivation, but serum T levels were decreased in fluid-deprived Sprague-Dawley males and not Fischer 344 males. It was suggested that the accelerated extinction in fluid-deprived Sprague-Dawley males was primarily due to decreases in serum T levels, while the faster extinction in deprived Fisher 344 males could be accounted for by decreases in sensitivity to T.}, } @article {pmid8153159, year = {1994}, author = {Wright, BE and Abadie, J and Svec, F and Porter, JR}, title = {Does taste aversion play a role in the effect of dehydroepiandrosterone in Zucker rats?.}, journal = {Physiology & behavior}, volume = {55}, number = {2}, pages = {225-229}, doi = {10.1016/0031-9384(94)90127-9}, pmid = {8153159}, issn = {0031-9384}, mesh = {Administration, Oral ; Animals ; Avoidance Learning/*drug effects ; Dehydroepiandrosterone/administration & dosage/*pharmacology ; Diet ; Eating/drug effects ; Female ; Food Preferences/drug effects ; Injections, Intraperitoneal ; Obesity/psychology ; Rats ; Rats, Zucker ; Taste/*drug effects ; }, abstract = {Dehydroepiandrosterone (DHEA) reduces food intake in obese Zucker rats. To study the role of taste aversion on this process, we used two approaches. First, we presented increasing concentrations of DHEA in chow to lean and obese Zucker rats, either in competition with unadulterated chow, or alone. Second, we examined energy intake following parenteral DHEA administration. Both lean and obese rats always preferred nonadulterated chow to DHEA-supplemented chow. However, lean rats required a higher DHEA concentration (0.06%) than obese rats (0.015%) to achieve the same degree of aversion. When DHEA-supplemented chow was presented alone, only high concentrations (0.3 and 0.6% DHEA) decreased food intake. Rats given DHEA by IP injection (200 mg/kg/day) also decreased their energy intakes. The results demonstrate that although DHEA can cause taste aversion at low concentrations in Zucker rats, it does not alter energy intake until high concentrations are given. In addition, nonoral DHEA also decreases energy intake in these animals. These results suggest that DHEA's antiobesity effect is not mediated by taste aversion.}, } @article {pmid8146218, year = {1994}, author = {Pohjanvirta, R and Unkila, M and Tuomisto, J}, title = {TCDD-induced hypophagia is not explained by nausea.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {47}, number = {2}, pages = {273-282}, doi = {10.1016/0091-3057(94)90010-8}, pmid = {8146218}, issn = {0091-3057}, mesh = {Animals ; Antiemetics/pharmacology ; Benzamides/pharmacology ; Body Weight/drug effects ; Eating/*drug effects ; Energy Metabolism/drug effects ; Female ; Kaolin ; Male ; Metoclopramide/pharmacology ; Nausea/*chemically induced/psychology ; Oxytocin/blood ; Polychlorinated Dibenzodioxins/*pharmacology ; Rats ; Rats, Inbred Strains ; Rats, Wistar ; Taste/drug effects ; }, abstract = {2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent known anorexigens with an unestablished mechanism of action. In the present study, the role of nausea in TCDD-induced hypophagia was assessed by a battery of behavioral (conditioned taste aversion [CTA], kaolin consumption, protein selection), biochemical (plasma oxytocin), and antiemetic drug intervention (trimethobenzamine, metoclopramide) approaches. Moreover, both the most TCDD-susceptible (Long-Evans [L-E]; IP LD50 approximately 10 micrograms/kg) and the most TCDD-resistant (Han/Wistar [H/W]; IP LD50 > 3000 micrograms/kg) rat strains were employed in the experiments. L-E rats were exposed to a lethal dose of TCDD (50 micrograms/kg), whereas H/W rats were treated with high but nonlethal doses (50 or 1000 micrograms/kg). TCDD produced a positive CTA response in H/W rats alone. These animals also increased their kaolin consumption more than L-E rats of either gender after TCDD exposure. TCDD decreased the proportional intake of energy from high-protein diet in female L-E rats, but tended to increase it in male L-E and H/W rats. TCDD did not affect plasma oxytocin concentration by itself, but potentiated the elevation caused by the positive control compound, LiCl, in L-E rats on day 8. Neither antiemetic tested had any detectable influence on TCDD-induced wasting. These findings imply that the degree of nausea elicited by TCDD in the rat depends on strain and gender. However, nausea has only a minor, if at all, causal role in the lethal wasting syndrome characteristic of this compound.}, } @article {pmid8146216, year = {1994}, author = {Bellinger, LL and Mendel, VE}, title = {Effects of components derived from HPLC purification of human satietin on ingestion, body weight, and taste aversion in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {47}, number = {2}, pages = {255-263}, doi = {10.1016/0091-3057(94)90008-6}, pmid = {8146216}, issn = {0091-3057}, support = {DK42635/DK/NIDDK NIH HHS/United States ; }, mesh = {Angiotensin II/pharmacology ; Animals ; Appetite Depressants/administration & dosage/chemistry/*pharmacology ; Body Weight/*drug effects ; Chromatography, High Pressure Liquid ; Drinking/drug effects ; Eating/*drug effects ; Glycopeptides/administration & dosage/chemistry/*pharmacology ; Humans ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects ; }, abstract = {The putative satiety agent human satietin (h-SAT) once thought to be homogenous has been separated by high-performance liquid chromatography (HPLC) into components designated peak A (P-A, 53%/w) and Peak B (P-B, 47%/w); P-B contains a putative satiety agent. In Experiment 1, male Sprague-Dawley rats were divided into six (n = 9-11) groups (Grps) and ICV infused: Grp 1, artificial cerebrospinal fluid (a-CSF), 10 microliters/rat; Grp 2, albumin (ALB), 53 micrograms/rat; Grp 3, semipurified (sp) h-SAT (parent compound), 100 micrograms/rat; Grp 4, P-A, 53 micrograms/rat; Grp 5, P-B, 47 micrograms/rat; and Grp 6, P-A+B, 53+47 micrograms/rat, respectively. Compared to Grp 1, food intake, the first day postinfusion, was suppressed in Grp 3 (p < 0.01) and equally attenuated (p < 0.06) in Grps 5 and 6. Body weight remained suppressed (p < 0.05) in Grps 3, 5, and 6 for 3 days and in Grps 3 and 6 (p < 0.05) for an additional 3 days; Grps 2 and 4 did not differ from Grp 1. These data show P-B suppresses food intake comparably to P-A+B and causes a prolonged weight loss. In Experiment 2, sph-SAT and a recombination of P-A and P-B was tested for aversiveness using the two-bottle test. Both sph-SAT and P-A+B significantly suppressed food intake, but only sph-SAT was found to be aversive. These data show that most likely during HPLC processing of sph-SAT an aversive component was lost.}, } @article {pmid8008412, year = {1994}, author = {Wicrtelak, EP and Smith, KP and Furness, L and Mooney-Heiberger, K and Mayr, T and Maier, SF and Watkins, LR}, title = {Acute and conditioned hyperalgesic responses to illness.}, journal = {Pain}, volume = {56}, number = {2}, pages = {227-234}, doi = {10.1016/0304-3959(94)90098-1}, pmid = {8008412}, issn = {0304-3959}, support = {MH45045/MH/NIMH NIH HHS/United States ; NIMH MH14617/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Disease/*psychology ; Formaldehyde ; Hot Temperature ; Hyperalgesia/chemically induced/*psychology ; Injections, Intraperitoneal ; Lipopolysaccharides/administration & dosage/pharmacology ; Lithium Chloride/administration & dosage/pharmacology ; Male ; Nociceptors/*physiology ; Pain Measurement/drug effects ; Rats ; Rats, Sprague-Dawley ; Reaction Time/drug effects ; Skin Temperature/drug effects ; Taste/drug effects ; }, abstract = {It has been argued that pain functions to facilitate recovery from injury and/or illness by stimulating recuperative behaviors. If this is the case, then hyperalgesia might be expected to be part of the constellation of adaptations that occur during sickness. The present series of studies tested two agents that induce illness (lithium chloride and bacterial cell-wall endotoxin (lipopolysaccharide)) to determine their acute effects on pain responsivity in rats. Both agents produced hyperalgesia as measured by the tail-flick and formalin tests. This enhanced responsivity appears to be specific to pain since (a) no enhanced response was observed to a non-painful stimulus (6 g von Frey hairs), and (b) the effect could not be accounted for by changes in tail skin temperature. In addition, a conditioned taste aversion paradigm was used to examine the possibility that illness-induced hyperalgesia could be conditioned to a novel taste (saccharine). This procedure was successful in producing a conditioned hyperalgesia which was comparable in magnitude and duration to acute illness induced pain facilitation. Taken together, this series of studies suggests that such pain facilitation might have adaptive functions similar to those ascribed to other illness-induced behaviors.}, } @article {pmid7908448, year = {1994}, author = {Lin, HQ and McGregor, IS and Atrens, DM and Christie, MJ and Jackson, DM}, title = {Contrasting effects of dopaminergic blockade on MDMA and d-amphetamine conditioned taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {47}, number = {2}, pages = {369-374}, doi = {10.1016/0091-3057(94)90025-6}, pmid = {7908448}, issn = {0091-3057}, mesh = {3,4-Methylenedioxyamphetamine/*analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Benzazepines/pharmacology ; Dextroamphetamine/*pharmacology ; *Dopamine Antagonists ; Dopamine D2 Receptor Antagonists ; Haloperidol/pharmacology ; Male ; N-Methyl-3,4-methylenedioxyamphetamine ; Raclopride ; Rats ; Rats, Wistar ; Receptors, Dopamine D1/antagonists & inhibitors ; Salicylamides/pharmacology ; Taste/*drug effects ; }, abstract = {A series of experiments examined the role of dopamine in the conditioned taste aversion (CTA) produced by 3,4-methylenedioxymethamphetamine (MDMA) and d-amphetamine in rats. The CTA induced by MDMA (1.0 mg/kg) was unaffected by the D1 dopamine receptor antagonist SCH23390 (0.3 or 0.6 mg/kg), the D2 receptor antagonist raclopride (0.3 or 0.6 mg/kg), SCH23390 and raclopride combined (both 0.3 or 0.6 mg/kg), or the D1/D2 receptor antagonist haloperidol (0.4 mg/kg). In contrast, the CTA produced by d-amphetamine (0.5 mg/kg) was attenuated by SCH23390 and raclopride combined (both 0.3 mg/kg) as well as haloperidol (0.4 mg/kg), but not by SCH23390 (0.3 or 0.6 mg/kg) or raclopride (0.3 or 0.6 mg/kg) alone. These results suggest that dopamine plays different roles in MDMA and amphetamine CTAs, and that the D1 and D2 receptors independently mediate the aversive effect of amphetamine in CTA.}, } @article {pmid8185850, year = {1994}, author = {Bielavska, E and Bures, J}, title = {Universality of parabrachial mediation of conditioned taste aversion.}, journal = {Behavioural brain research}, volume = {60}, number = {1}, pages = {35-42}, doi = {10.1016/0166-4328(94)90060-4}, pmid = {8185850}, issn = {0166-4328}, mesh = {Afferent Pathways/physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Drinking/physiology ; Food Preferences/physiology ; Lithium Chloride/toxicity ; Male ; Mental Recall/physiology ; Mesencephalon/*physiology ; Rats ; Smell/physiology ; Taste/*physiology ; Taste Buds/physiology ; }, abstract = {Disruption of conditioned taste aversion (CTA) by tetrodotoxin (TTX) blockade of parabrachial nuclei elicited after ingestion of the gustatory CS and before administration of the visceral US is revealed by unchanged CS preference in retrieval test performed two days after acquisition. The universality of the above amnesia was examined in rats. In Experiment 1, parabrachial TTX disrupted CTAs when sodium saccharin (0.1%), quinine hydrochloride (0.0072%), sodium chloride (0.9%) or a garlic extract were used as the CS and i.p. LiCl (0.15 M, 2% body weight) as the US. In Experiment 2, parabrachial TTX disrupted CTAs when 0.9% NaCl was used as the CS and i.p. injection of LiCl (0.15 M, 2% body weight), D-amphetamine (3 mg/kg) or carbachol (0.15 mg/kg) served as the US. Experiment 3 showed that post-drinking parabrachial TTX blocked also CTA induced by LiCl drinking, i.e. under conditions of CS-US identity. Experiments 4 and 5 demonstrated that the amnesia is not confounded by TTX-induced reduction of fluid intake because the CTA disruption was well expressed even when tested after recovery of normal fluid intake 3 days after TTX injection and in animals receiving 12 days of preacquisition adaptation to limited fluid access. It is concluded that parabrachial nuclei represent an important point of convergence for various classes of CTA eliciting stimuli.}, } @article {pmid8183185, year = {1994}, author = {Ferrari, CM and Riley, AL}, title = {Effect of prenatal cocaine on the acquisition of cocaine-induced taste aversions.}, journal = {Neurotoxicology and teratology}, volume = {16}, number = {1}, pages = {17-23}, doi = {10.1016/0892-0362(94)90004-3}, pmid = {8183185}, issn = {0892-0362}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/administration & dosage/*toxicity ; Dose-Response Relationship, Drug ; Female ; Injections, Subcutaneous ; Male ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Saccharin/pharmacology ; Sex Characteristics ; Taste/*drug effects ; Weight Gain/drug effects ; }, abstract = {Pregnant Long-Evans rats were injected SC twice daily with 20 mg/kg cocaine from gestational days (GD) 7-19. Vehicle controls were administered distilled water on these days. Pair-fed controls were similarly treated but allowed the same amount of food as consumed by the cocaine-exposed mothers. On postnatal day 1 (PND 1), pups of the mothers exposed to cocaine were surrogate-fostered. On PND 41, all subjects were grouped according to their history (cocaine, vehicle, and pair-fed) and were tested for their behavioral sensitivity to the aversive effects of cocaine by assessing their ability to acquire a cocaine-induced taste aversion. Rats from all three conditions were given saccharin to drink and then injected SC with either 0, 18, 32, or 50 mg/kg cocaine. Prenatal exposure to cocaine had no effect on the acquisition of aversions. Specifically, the prenatally exposed animals acquired the taste aversion in a dose-dependent manner similar to that of the controls. These data indicate that changes in sensitivity to cocaine are not necessary consequences of prenatal cocaine exposure.}, } @article {pmid8170624, year = {1994}, author = {Lucki, I and Singh, A and Kreiss, DS}, title = {Antidepressant-like behavioral effects of serotonin receptor agonists.}, journal = {Neuroscience and biobehavioral reviews}, volume = {18}, number = {1}, pages = {85-95}, doi = {10.1016/0149-7634(94)90039-6}, pmid = {8170624}, issn = {0149-7634}, support = {MH 36262/MH/NIMH NIH HHS/United States ; MH 48125/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Antidepressive Agents/*pharmacology ; Behavior, Animal/*drug effects ; Humans ; Serotonin Receptor Agonists/*pharmacology ; }, abstract = {The clinical discoveries that drugs that stimulate 5-HT neurotransmission, either by inhibiting 5-HT uptake or by stimulating postsynaptic receptors directly, have antidepressant properties has stimulated interest in defining the role of the 5-HT receptor system in the clinical effects of antidepressant drugs. Two approaches are reviewed in this paper that address the neurochemical mediation of the therapeutic effects of antidepressant drugs from the standpoint of animal behavior. The first approach utilizes a behavioral response in rats, the forced swimming test, that correlates well with predicting antidepressant drugs in humans. Studies are reviewed that examined serotonergic compounds in the forced swimming test, from the standpoint of identifying better serotonergic mechanisms involved in the antidepressant response. Both 5-HT uptake inhibitors and 5-HT1A receptor agonists produce effects in the forced swimming test that are similar to those of other classes of antidepressant drugs. In contrast, agonists at other 5-HT receptors or 5-HT receptor antagonists do not produce antidepressant-like behavioral effects. Evidence for an important role of 5-HT1A receptors in the antidepressant response is supported by findings that antagonists of 5HT1A receptors prevent the ability of 5-HT1A receptor agonists to reduce immobility in the forced swimming test. The results of studies interfering with 5-HT neurotransmission, either by inhibition of 5-HT synthesis or by the destruction of 5-HT neurons, favor the idea that the effects of 5-HT1A receptor agonists are produced by the stimulation of postsynaptic 5-HT1A receptors. The second approach for studying the behavioral effects of antidepressant drugs employs drug discrimination studies, conducted using a discriminated taste aversion procedure, to provide a method for studying the discriminative stimulus effects of the antidepressant 5-HT uptake inhibitor sertraline. Rats were trained to discriminate the effects of sertraline (10 mg/kg) from saline. Other 5-HT uptake inhibitors, such as fluoxetine, fluvoxamine and paroxetine, substituted for the sertraline stimulus. High doses of norepinephrine uptake inhibitors, such as desipramine or maprotiline, were required to produce similar effects. These two behavioral approaches promise to be useful for defining the important pharmacological effects associated with the behavioral effects of antidepressant drugs.}, } @article {pmid8140166, year = {1994}, author = {Merwin, A and Doty, RL}, title = {Early exposure to low levels of estradiol (E2) mitigates E2-induced conditioned taste aversions in prepubertally ovariectomized female rats.}, journal = {Physiology & behavior}, volume = {55}, number = {1}, pages = {185-187}, doi = {10.1016/0031-9384(94)90029-9}, pmid = {8140166}, issn = {0031-9384}, support = {DC 00161/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Estradiol/*analogs & derivatives/pharmacology ; Female ; Hypothalamus/drug effects ; Premedication ; Rats ; Rats, Sprague-Dawley ; Saccharin/administration & dosage ; Sexual Maturation/*drug effects ; Taste/*drug effects ; }, abstract = {17 beta-Estradiol (E2) can serve as a potent unconditioned stimulus in producing a conditioned taste aversion to saccharin in rats, with the effect being greater in males than in females. To determine whether the female's lower susceptibility to such conditioning is due, in part, to early experience with estrogen, we performed the following experiment. First, we pretreated groups of prepubertally ovariectomized female rats with either sesame oil (control group) or low doses of E2 (0.3, 0.75, or 1.50 microgram). Second, in subsequent conditioning sessions, we presented a 0.2% saccharin solution to the rats prior to the injection of 100 micrograms of E2 (the unconditioned stimulus). Third, we tested the magnitude of the conditioned aversion to the saccharin solution and its tendency to extinguish during the following week. The E2-pretreated animals evidenced significantly weaker taste aversions and extinguished them more rapidly than did the oil-pretreated controls, even at the lowest E2 pretreatment dose, suggesting that prior experience with low levels of estrogen can significantly mitigate, in female rats, the magnitude of a conditioned taste aversion produced by a high dose of estrogen.}, } @article {pmid8129688, year = {1994}, author = {Escobar, ML and Russell, RW and Booth, RA and Bermúdez-Rattoni, F}, title = {Accelerating behavioral recovery after cortical lesions. I. Homotopic implants plus NGF.}, journal = {Behavioral and neural biology}, volume = {61}, number = {1}, pages = {73-80}, doi = {10.1016/s0163-1047(05)80046-9}, pmid = {8129688}, issn = {0163-1047}, support = {MH 17691/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/*physiology ; Cerebral Cortex/embryology/*physiology/transplantation ; Conditioning, Psychological/physiology ; *Fetal Tissue Transplantation ; Lithium Chloride/pharmacology ; Male ; Nerve Growth Factors/administration & dosage/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Taste/drug effects/physiology ; }, abstract = {We recently demonstrated that fetal brain implants produced a significant recovery in the ability of insular cortex (IC)-lesioned rats to learn a conditioned taste aversion (CTA). We now report effects on the recovery of CTA and of a second measure of learning, inhibitory avoidance (IA), of supplementing the implants with nerve growth factor (NGF). Four groups of male Sprague-Dawley animals showing disrupted taste aversion following IC lesions, plus two control groups, received different experimental treatments: Group 1, unlesioned control; Group 2, homotopic IC implants without NGF; Groups 3 and 4, IC implants + NGF; Group 5, heterotopic occipital cortical implants + NGF; and Group 6, without an implant as a lesioned control. All groups except Group 4 were trained pre- and postimplant in the CTA paradigm. Two days after CTA testing postimplant, all groups received IA training. Behavioral results showed that insular cortex implants with NGF promoted recovery to control levels of the ability to learn both tasks at 15 days postimplant. Those animals that received occipital implants with NGF or insular cortex with vehicle or remained without implants did not show any significant behavioral recovery at 15 days postimplant. These findings suggest that NGF associated with homotopic implants facilitates recovery of learning abilities in insular cortex-lesioned rats and suggest that similar treatments with NTFs may have analogous effects when lesions involve other brain areas.}, } @article {pmid8015970, year = {1994}, author = {Bull, DF and Husband, AJ and Munro, KI and Exton, MS and Pfister, HP and King, MG}, title = {Inhibition of endotoxin-induced temperature change by behavioral conditioning using alpha-melanocyte-stimulating hormone as an unconditioned stimulus.}, journal = {Peptides}, volume = {15}, number = {1}, pages = {139-142}, doi = {10.1016/0196-9781(94)90182-1}, pmid = {8015970}, issn = {0196-9781}, mesh = {Animals ; Body Temperature Regulation/*drug effects ; Conditioning, Classical/*physiology ; Lipopolysaccharides/*pharmacology ; Male ; Rats ; Rats, Wistar ; Saccharin/pharmacology ; alpha-MSH/*pharmacology ; }, abstract = {The experiments reported here investigate the conditionability, using taste aversion conditioning, of the antagonistic effects of alpha-MSH on the thermoregulatory changes associated with injection of bacterial endotoxin lipopolysaccharide (LPS) in rats. Animals were administered LPS and then given alpha-MSH, as an unconditioned stimulus (UCS), in association with the novel taste of saccharin, the conditioned stimulus (CS). The temperature response at this time in alpha-MSH-treated rats was similar to that observed in control animals. However, 7 days later, when these animals were again injected with LPS but re-exposed to saccharin alone, there was a significant reduction in the temperature response profile compared to controls. These results demonstrate that in male rats the conditioned antipyretic effect following conditioning with alpha-MSH as the UCS is sufficiently robust to counteract the acute effects on body temperature of an LPS injection at the time of CS reexposure. This complements previous experiments demonstrating that thermoregulation may be influenced by cognitive association.}, } @article {pmid7953770, year = {1994}, author = {Niijima, A and Yamamoto, T}, title = {The effects of lithium chloride on the activity of the afferent nerve fibers from the abdominal visceral organs in the rat.}, journal = {Brain research bulletin}, volume = {35}, number = {2}, pages = {141-145}, doi = {10.1016/0361-9230(94)90094-9}, pmid = {7953770}, issn = {0361-9230}, mesh = {Abdomen/innervation ; Afferent Pathways/drug effects/*physiology ; Animals ; Lithium Chloride/*pharmacology ; Male ; Nerve Fibers/drug effects/*physiology ; Rats ; Rats, Wistar ; Splanchnic Nerves/drug effects/*physiology ; Time Factors ; Vagus Nerve/drug effects/*physiology ; Viscera/innervation ; }, abstract = {The effect of lithium chloride on the activity of the afferent nerve fibers from the abdominal organs was studied in anesthetized rats. The administration of the lithium chloride solution (0.15 M) over the mesentery increased afferent discharge rate of the splanchnic and vagal gastric nerve. Injection of the same solution into the portal vein caused an increase in afferent activity of the vagal hepatic nerve. Further, infusion of the same solution into the duodenum resulted in facilitation of the afferent activity of the splanchnic as well as vagal celiac nerves. The results may explain the mechanism played by lithium chloride as unconditioned stimulus in the conditioned taste aversion paradigm.}, } @article {pmid7862845, year = {1994}, author = {Kirby, LG and Rowan, GA and Smith, RL and Lucki, I}, title = {Discriminative stimulus properties of the benzodiazepine receptor inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM).}, journal = {Psychopharmacology}, volume = {113}, number = {3-4}, pages = {351-360}, pmid = {7862845}, issn = {0033-3158}, support = {DA 05186/DA/NIDA NIH HHS/United States ; DA 05367/DA/NIDA NIH HHS/United States ; DA 05413/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Carbolines/antagonists & inhibitors/*pharmacology ; Convulsants/antagonists & inhibitors/*pharmacology ; Discrimination, Psychological/*drug effects ; Flumazenil/pharmacology ; *GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; Generalization, Stimulus/drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharin/pharmacology ; Taste/drug effects ; }, abstract = {The purpose of this study was to determine whether rats could be trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor inverse agonist DMCM from saline in a conditioned taste aversion paradigm. On a drug trial, water-deprived rats were injected with DMCM (0.55-0.6 mg/kg IP), allowed access to a 0.25% saccharin solution for 30 min, and then injected with LiCl. On non-drug trials, saline injections bracketed the drinking period. Conditioned controls were treated similarly with DMCM and saline on drug and non-drug trials, but received injections of saline instead of LiCl. At the completion of training, CMCM produced a 69% reduction of saccharin consumption on drug trials, compared with 23% for conditioned controls. The stimulus properties of DMCM were then measured by its ability to reduce the preference for saccharin over water in a two-bottle choice test. DMCM reduced saccharin preference in rats that received discrimination training from 68% to 19%, but did not alter saccharin preference in conditioned controls. Other compounds with varying activity at BZ receptors were evaluated for their ability to substitute for the discriminative stimulus effects of DMCM. Two BZ receptor inverse agonists, beta-CCE (10-18 mg/kg) and FG 7142 (3.2-18 mg/kg), substituted completely for DMCM. Partial substitution for DMCM was shown by the BZ receptor antagonist CGS 8216 (3.2-10 mg/kg) and the non-BZ convulsant pentylenetetrazol (10-20 mg/kg). The BZ receptor agonists chlordiazepoxide (0.32-5.0 mg/kg), diazepam (0.32-10 mg/kg), and alprazolam (0.1-3.2 mg/kg) and the BZ receptor antagonist flumazenil (1.0-32 mg/kg) failed to substitute for the DMCM stimulus. Pretreatment with flumazenil (1.0 mg/kg) blocked the stimulus effects of the training dose of DMCM and produced a shift to the right of the DMCM generalization curve. The pattern of compounds that substituted for the DMCM stimulus and the blockade of that stimulus by flumazenil indicate that the stimulus properties of DMCM are associated with its effects as a BZ receptor inverse agonist.}, } @article {pmid8155277, year = {1993}, author = {Galaverna, OG and Seeley, RJ and Berridge, KC and Grill, HJ and Epstein, AN and Schulkin, J}, title = {Lesions of the central nucleus of the amygdala. I: Effects on taste reactivity, taste aversion learning and sodium appetite.}, journal = {Behavioural brain research}, volume = {59}, number = {1-2}, pages = {11-17}, doi = {10.1016/0166-4328(93)90146-h}, pmid = {8155277}, issn = {0166-4328}, support = {NIMH MH 455787/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Appetite/*drug effects ; Avoidance Learning/*physiology ; Lithium Chloride/pharmacology ; Male ; Mouth/physiology ; Movement/physiology ; Neural Pathways/physiology ; Pons/physiology ; Rats ; Rats, Sprague-Dawley ; Sodium, Dietary/*pharmacology ; Taste/*physiology ; }, abstract = {Bilateral damage to the central nucleus of the amygdala (CeAX) in the rat blunts need-induced NaCl intake and abolishes daily need-free NaCl intake when measured with a two-bottle test. Such a deficit could be the result of impaired taste function. To assess the taste function of the CeAX rat various taste stimuli were introduced directly into the oral cavity and taste-elicited oral motor responses were measured. Oral motor responses elicited by 0.62 M and 0.13 M sodium chloride, 0.3 M sucrose and 0.01 M citric acid, were similar in control and CeAX rats. Additionally CeAX and control rats acquired a taste aversion for fructose or maltose when either was paired with LiCl. Finally, in CeAX rats, like in control rats, the pattern of oral motor responses to 0.5 M NaCl was dependent on internal state; sodium depletion dramatically altered taste-elicited oral motor behavior. These results suggest that, in the rat, the deficits in NaCl intake behavior that follow CeAX do not appear to be a result of dramatic changes in gustatory function.}, } @article {pmid8111635, year = {1993}, author = {Krivanek, J}, title = {Protein kinase C in nucleus parabrachialis: effect of drugs inducing conditioned taste aversion.}, journal = {Brain research}, volume = {629}, number = {2}, pages = {327-330}, doi = {10.1016/0006-8993(93)91340-x}, pmid = {8111635}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Operant/drug effects/*physiology ; Copper/pharmacology ; Copper Sulfate ; Cytosol/drug effects/metabolism ; Lithium Chloride/pharmacology ; Male ; Pons/drug effects/*enzymology/physiology ; Protein Kinase C/*metabolism ; Rats ; Saccharin/pharmacology ; Taste/*drug effects ; Visual Cortex/drug effects/metabolism ; }, abstract = {A method for the dissection of the nucleus parabrachialis (NPB) from the coronal sections of frozen rat brain is described. The protein kinase C (PKC) activity was determined in the cytosol and particulate fractions of the pooled samples of the nucleus. The effect of the i.p. administration of the conditioned taste aversion-inducing agents LiCl and CuSO4 on PKC in the NPB and visual cortex (VC) was tested. 1 h after the LiCl injection, the portion of the membrane-bound PKC was increased by 23% (P < 0.01) above the level found after the saline injection. CuSO4 produced a 19% increase. Since the PKC activity in the cytosol declined, it is likely that the translocation of the enzyme took place. No changes in the PKC distribution in the VC samples could be detected. The results support the idea that the PKC translocation is not directly induced by the tested substances but that it rather reflects changes in the activity of the visceral system.}, } @article {pmid8170797, year = {1993}, author = {Hinderliter, CF and Misanin, JR}, title = {Context familiarity and delayed conditioned taste aversion in young-adult and old-age rats.}, journal = {Perceptual and motor skills}, volume = {77}, number = {3 Pt 2}, pages = {1403-1406}, doi = {10.2466/pms.1993.77.3f.1403}, pmid = {8170797}, issn = {0031-5125}, support = {HD 21161/HD/NICHD NIH HHS/United States ; }, mesh = {Aging/*psychology ; Animals ; *Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Lithium Chloride/toxicity ; Memory, Short-Term ; *Mental Recall ; Rats ; Retention, Psychology ; Social Environment ; *Taste ; }, abstract = {Familiarity with a conditioning context different from the home-cage environment was examined in immediate and delayed (3-hr.) conditioned taste aversion (CTA) learning for young-adult (90-120 days) and old-age (680-750 days) female Wistar albino rats. Context familiarity increased CTA for young adults at the 3-hr. delay. Old-age rats showed no aversion at 3-hr. delays. Results suggest that home-cage cues may be used in mediating long-delay CTA and that the role of these cues may differ with age.}, } @article {pmid8136075, year = {1993}, author = {Reilly, S and Harley, C and Revusky, S}, title = {Ibotenate lesions of the hippocampus enhance latent inhibition in conditioned taste aversion and increase resistance to extinction in conditioned taste preference.}, journal = {Behavioral neuroscience}, volume = {107}, number = {6}, pages = {996-1004}, doi = {10.1037//0735-7044.107.6.996}, pmid = {8136075}, issn = {0735-7044}, mesh = {Animals ; Appetitive Behavior/drug effects/physiology ; Association Learning/drug effects/physiology ; Avoidance Learning/*drug effects/physiology ; Axons/drug effects/physiology ; Brain Mapping ; Conditioning, Classical/*drug effects/physiology ; Extinction, Psychological/*drug effects/physiology ; Food Preferences/drug effects/physiology ; Hippocampus/*drug effects/physiology ; Ibotenic Acid/*pharmacology ; Male ; Neural Inhibition/*drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; }, abstract = {In 2 experiments, the effects of axon-sparing lesions of the hippocampus on performance in aversive and appetitive taste conditioning tasks were investigated. In Experiment 1, hippocampally lesioned rats showed no impairment of conditioned taste aversion learning relative to control subjects, but they did display an increased sensitivity to latent inhibition (LI). In Experiment 2, the same hippocampectomized rats acquired a conditioned taste preference but failed to show any evidence of extinction. The influence of the neurotoxic lesion on LI is in the opposite direction to the effect typically found following hippocampal damage induced by traditional methods. Accordingly, the data present challenges for most current theories of hippocampal function.}, } @article {pmid8136054, year = {1993}, author = {Reilly, S and Grigson, PS and Norgren, R}, title = {Parabrachial nucleus lesions and conditioned taste aversion: evidence supporting an associative deficit.}, journal = {Behavioral neuroscience}, volume = {107}, number = {6}, pages = {1005-1017}, doi = {10.1037//0735-7044.107.6.1005}, pmid = {8136054}, issn = {0735-7044}, support = {DC-00047-02/DC/NIDCD NIH HHS/United States ; DC-00240/DC/NIDCD NIH HHS/United States ; MH 00653/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Dominance, Cerebral/physiology ; Lithium Chloride/toxicity ; Male ; Mental Recall/*physiology ; Neural Pathways/physiology ; Orientation/physiology ; Pons/*physiology ; Rats ; Rats, Sprague-Dawley ; Smell/physiology ; Social Environment ; Taste/*physiology ; }, abstract = {Three experiments examined the conditioned taste aversion (CTA) deficit that occurs following electrolytic lesions of the parabrachial nucleus (PBN). In Experiment 1, lesioned rats failed to avoid either a gustatory or an olfactory stimulus that had been paired with lithium chloride-induced toxicosis. In Experiment 2, however, all rats learned a conditioned flavor preference. Finally, in Experiment 3, all controls and 7 of the 12 lesioned rats learned a conditioned place aversion. Together, these results demonstrate that the disruption of CTA in lesioned rats cannot be ascribed to an inability to process either gustatory or visceral afferent information per se. Rather, the data suggest that PBN-lesioned rats are unable to form a specific association between gustatory and visceral cues.}, } @article {pmid8297323, year = {1993}, author = {Cole, KC and Bakner, L and Vernon, A and Riccio, DC}, title = {The effect of US preexposure on conditioned taste aversion: lack of postconditioning recovery of the aversion.}, journal = {Behavioral and neural biology}, volume = {60}, number = {3}, pages = {271-273}, doi = {10.1016/0163-1047(93)90523-k}, pmid = {8297323}, issn = {0163-1047}, support = {NIMH 37535/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; *Conditioning, Classical ; Discrimination Learning ; Drinking Behavior ; Male ; Rats ; Retention, Psychology ; Sucrose/administration & dosage ; *Taste ; Water Deprivation ; }, abstract = {Although the CS preexposure effect in CTA was once viewed exclusively as an acquisition failure, recent studies have suggested that the latent inhibition phenomenon is the result of retrieval impairment. This interpretive challenge is based on the unexpected finding that recovery of the aversion occurs over a long retention interval following conditioning (Kraemer, Lariviere, & Spear, Animal Learning and Behavior, 16, 185-190, 1988; Bakner, Strohen, Nordeen, & Riccio, Physiology & Behavior, 50, 1269-1272, 1991). This study examined whether a similar recovery occurs after US preexposure. Following preexposure to the US (LiCl), rats received a sucrose-illness pairing and were subsequently tested after either short or long training-to-test intervals. In contrast to the findings with the CS preexposure effect, US-preexposed subjects did not show a spontaneous increase in CTA following the long retention interval.}, } @article {pmid8297313, year = {1993}, author = {Fernandez-Ruiz, J and Miranda, MI and Bermúdez-Rattoni, F and Drucker-Colín, R}, title = {Effects of catecholaminergic depletion of the amygdala and insular cortex on the potentiation of odor by taste aversions.}, journal = {Behavioral and neural biology}, volume = {60}, number = {3}, pages = {189-191}, doi = {10.1016/0163-1047(93)90314-8}, pmid = {8297313}, issn = {0163-1047}, mesh = {Amygdala/*drug effects/*metabolism ; Animals ; Behavior, Animal/drug effects ; Biogenic Monoamines/metabolism ; Catecholamines/*deficiency/metabolism ; Male ; Oxidopamine/*pharmacology ; Rats ; Rats, Wistar ; Receptors, Dopamine/drug effects/metabolism ; Smell/*drug effects ; Taste/*drug effects ; }, abstract = {This experiment examined the effects of catecholamine depletion of the amygdala or insular cortex on the acquisition of olfactory and gustatory learning tasks. Bilateral lesions with 6-hydroxydopamine (4 micrograms/0.5 microliters) were done in either amygdala or insular cortex of Wistar male rats, with two groups receiving sham lesions. All four groups of animals were trained and tested in the potentiation of odor by taste aversion paradigm. The results showed that the amygdala-lesioned group acquired the taste, but not hte odor aversion, while the insular cortex-lesioned group acquired odor, but not taste aversion. Both sham groups showed strong taste and odor aversions. Catecholamine levels in both lesioned groups were significantly lower than those in the sham groups. These results suggest that catecholamines are necessary in the insular cortex for the acquisition of taste and in the amygdala for the acquisition of odor aversion in the potentiation of odor by taste aversion paradigm.}, } @article {pmid8278436, year = {1993}, author = {Pournaghash, S and Riley, AL}, title = {Buprenorphine as a stimulus in drug discrimination learning: an assessment of mu and kappa receptor activity.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {46}, number = {3}, pages = {593-604}, doi = {10.1016/0091-3057(93)90549-9}, pmid = {8278436}, issn = {0091-3057}, mesh = {Animals ; Benzomorphans/pharmacology ; Buprenorphine/antagonists & inhibitors/*pharmacology ; Diprenorphine/antagonists & inhibitors/pharmacology ; Discrimination Learning/*drug effects ; Female ; Generalization, Stimulus/drug effects ; Morphine/pharmacology ; Narcotic Antagonists/pharmacology ; Rats ; Receptors, Opioid, kappa/antagonists & inhibitors/*drug effects ; Receptors, Opioid, mu/antagonists & inhibitors/*drug effects ; Taste/drug effects ; }, abstract = {Using the conditioned taste aversion baseline of drug discrimination learning, different groups of animals were trained to discriminate either buprenorphine or morphine from distilled water. Specifically, animals were injected with buprenorphine or morphine prior to a saccharin-LiCl pairing and the drug vehicle prior to saccharin alone. By the fifth conditioning trial, animals differentially consumed saccharin on the basis of administration of the drug or its vehicle. In subsequent generalization tests, buprenorphine stimulus control generalized completely to the mu agonist morphine in four of the five subjects tested, while morphine stimulus control completely generalized to buprenorphine in two of five subjects and partially generalized in the remaining three. Buprenorphine failed to generalize to the relatively selective kappa antagonist MR2266 and the broad-based antagonist diprenorphine. Morphine also failed to generalize to MR2266, but did generalize to diprenorphine. That morphine and buprenorphine displayed some degree of cross-generalization suggests that these compounds share some stimulus property, presumably their agonist activity at the mu receptor, and that the mu activity of these compounds was used in the establishment of the discrimination, a conclusion supported by the fact that compounds with mu antagonist activity (e.g., naloxone, MR2266) blocked both buprenorphine and morphine stimulus control. That buprenorphine failed to generalize to compounds with kappa antagonist activity suggests that animals trained to discriminate buprenorphine from its vehicle do not use the kappa antagonist activity of the drug in the establishment of the discrimination. The basis for the differential ability of various receptor subtypes to mediate the discriminative properties of compounds with mixed receptor activity was discussed.}, } @article {pmid8248390, year = {1993}, author = {Weingarten, S and Senn, M and Langhans, W}, title = {Does a learned taste aversion contribute to the anorectic effect of bacterial lipopolysaccharide?.}, journal = {Physiology & behavior}, volume = {54}, number = {5}, pages = {961-966}, doi = {10.1016/0031-9384(93)90309-4}, pmid = {8248390}, issn = {0031-9384}, mesh = {Animals ; Antiemetics/pharmacology ; Appetite/*drug effects ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Bacterial Proteins ; Benzamides/pharmacology ; Chemoreceptor Cells/drug effects ; Conditioning, Classical/*drug effects ; Eating/drug effects ; Indomethacin/pharmacology ; Lipopolysaccharides/*pharmacology ; Male ; Neural Pathways/drug effects ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus/*drug effects ; Taste/*drug effects ; }, abstract = {The present study addressed the possible role of a conditioned taste aversion in the anorectic effect of bacterial lipopolysaccharide (LPS) in the rat. Pairing an intraperitoneal (IP) injection of LPS (100 micrograms/kg b.wt.) with the subsequent presentation of a familiar diet (FD) or of a novel-tasting saccharin diet (SD) for several hours did not affect FD or SD intake when the same diet was offered several days later after 12 h of food deprivation. However, food intake during the second presentation of SD was reduced when food was not withheld prior to the test. In a similarly designed experiment, the antipyretic and antiinflammatory drug indomethacin (5 mg/kg b.wt., IP) attenuated the anorectic effect of LPS during the initial pairing, but did not affect the inhibition of SD intake in LPS-pretreated rats during the second feeding test. The antiemetic trimethobenzamide (5 mg/kg b.wt., IP) failed to influence the anorectic effect of LPS. Lesion of the area postrema (AP) and the adjacent nucleus of the solitary tract (NST) was found to enhance the anorectic effect of LPS, but the development of tolerance to this effect remained unchanged in AP/NST-lesioned animals. In spite of the ability of LPS to induce a taste aversion that inhibits feeding under certain conditions (novel-tasting diet, no food deprivation prior to the feeding test), the findings indicate that a learned taste aversion is not the only contributor to the anorectic effect of LPS.}, } @article {pmid7948179, year = {1993}, author = {Fernández-Ruiz, J and Guzmán, R and Martínez, MD and Miranda, MI and Bermúdez-Rattoni, F and Drucker-Colín, R}, title = {Adrenal medullary grafts restore olfactory deficits and catecholamine levels of 6-OHDA amygdala lesioned animals.}, journal = {Journal of neural transplantation & plasticity}, volume = {4}, number = {4}, pages = {289-297}, doi = {10.1155/NP.1993.289}, pmid = {7948179}, issn = {0792-8483}, mesh = {Adrenal Medulla/*transplantation ; Amygdala/*drug effects/pathology ; Animals ; Biogenic Monoamines/metabolism ; Catecholamines/*metabolism ; Male ; Olfactory Pathways/*physiology ; Oxidopamine/*pharmacology ; Rats ; Rats, Wistar ; Smell/physiology ; Taste/physiology ; }, abstract = {Aside from motor and cognitive deficits, Parkinson patients also manifest a little-studied olfactory deficit. Since in Parkinson's disease there is a dopamine depletion of the amygdala due to mesocorticolimbic system degeneration, we decided to test olfactory and taste performance of 6-OHDA amygdala lesioned rats, as well as the possible restoration of either function with adrenal medullary transplants. Two 6-OHDA lesioned groups and one control group were tested in the potentiation of odor by taste aversion paradigm. On taste aversion none of the groups showed any impairment. In contrast, the 6-OHDA lesioned rats showed a marked impairment in olfactory aversion. At this point, one of the lesioned groups received a bilateral adrenal medullary graft within the lesioned area. After two months, all groups were submitted again to the behavioral paradigm. Taste remained unaffected, but the lesioned only group did not recover either olfactory aversion or normal catecholamine levels. The grafted group, on the other hand, restored olfactory aversion and catecholamine levels. It can be concluded from this study that catecholamine depletion of the amygdala is sufficient to produce a selective olfactory deficit, not accompanied by taste impairments, and that such a deficit can be reversed by adrenal medullary transplants, which in turn restore catecholamine levels.}, } @article {pmid8255917, year = {1993}, author = {Melton, PM and Riley, AL}, title = {An assessment of the interaction between cholecystokinin and the opiates within a drug discrimination procedure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {46}, number = {1}, pages = {237-242}, doi = {10.1016/0091-3057(93)90347-v}, pmid = {8255917}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Cholecystokinin/antagonists & inhibitors/*pharmacology ; Diprenorphine/pharmacology ; Discrimination, Psychological/*drug effects ; Drug Interactions ; Female ; Generalization, Psychological/drug effects ; Lithium Chloride/pharmacology ; Morphine/pharmacology ; Naloxone/pharmacology ; Narcotic Antagonists/pharmacology ; Narcotics/*pharmacology ; Rats ; }, abstract = {Recently, cholecystokinin (CCK) has been reported to antagonize a variety of opiate-induced effects, including nociception, body shaking, thermoregulation, and locomotion. Consistent with these results, a number of CCK antagonists potentiate the opiates in a range of behavioral and physiological assessments. The present study further examined the interaction between CCK and the opiates within the conditioned taste aversion baseline of drug discrimination learning, a design that utilizes the stimulus properties of the drug to control consummatory behavior. Specifically, animals injected with CCK prior to saccharin-LiCl pairings and the CCK vehicle prior to saccharin alone rapidly acquired the CCK-vehicle discrimination, avoiding saccharin consumption following the administration of CCK and consuming the same saccharin solution following the vehicle. Although the stimulus properties of CCK did not generalize to either naloxone or diprenorphine, morphine blocked and naloxone potentiated CCK's stimulus effects. These data are thus consistent with a physiological (rather than a pharmacological) interaction between CCK and the opiates.}, } @article {pmid7902981, year = {1993}, author = {Lin, HQ and Atrens, DM and Christie, MJ and Jackson, DM and McGregor, IS}, title = {Comparison of conditioned taste aversions produced by MDMA and d-amphetamine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {46}, number = {1}, pages = {153-156}, doi = {10.1016/0091-3057(93)90333-o}, pmid = {7902981}, issn = {0091-3057}, mesh = {3,4-Methylenedioxyamphetamine/*analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Designer Drugs/*pharmacology ; Dextroamphetamine/*pharmacology ; Dose-Response Relationship, Drug ; Male ; N-Methyl-3,4-methylenedioxyamphetamine ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Many drugs of abuse such as d-amphetamine support the development of taste aversion in a conditioned taste aversion paradigm. However, it has yet to be established whether methylenedioxymethamphetamine (MDMA), an amphetamine-like stimulant, has this property. A direct comparison was made between MDMA and d-amphetamine over a dose range of 0.125-2.0 mg/kg (SC). Two pairings of either drug with saccharin produced dose-related taste aversions to saccharin that were retained for at least three successive testing trials. The minimally effective dose was 1 mg/kg for MDMA and 0.5 mg/kg for d-amphetamine. The relative potency of MDMA to amphetamine was 4.5, similar to that previously reported for drug discrimination and self-stimulation.}, } @article {pmid8415839, year = {1993}, author = {Agüero, A and Arnedo, M and Gallo, M and Puerto, A}, title = {The functional relevance of the lateral parabrachial nucleus in lithium chloride-induced aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {45}, number = {4}, pages = {973-978}, doi = {10.1016/0091-3057(93)90150-r}, pmid = {8415839}, issn = {0091-3057}, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*drug effects ; Cerebral Ventricles/physiology ; Lithium Chloride/*pharmacology ; Male ; Medulla Oblongata/physiology ; Pons/anatomy & histology/*physiology ; Rats ; Rats, Wistar ; Stereotaxic Techniques ; Taste/drug effects ; }, abstract = {Lesions to the lateral parabrachial nucleus (PBN), one of the subnuclei that make up the pontine parabrachial complex, impairs the acquisition of taste aversion learning (TAL) with LiCl as the toxic stimulus. In this experiment, PBNl-lesioned and control rats were trained to learn a delayed task with a 15-min interval between presentation of the gustatory and the aversive stimulus. The impairment in learning observed after lesions of the PBNl is discussed in terms of disruption of the transmission of toxic stimuli (LiCl) processed by the humoral pathway and the area postrema (AP).}, } @article {pmid8234143, year = {1993}, author = {Sala, M and Braida, D and Calcaterra, P and Leone, MP and Gori, E}, title = {Possibility of spontaneous drug abuse tested in rat.}, journal = {Pharmacological research}, volume = {28}, number = {1}, pages = {21-34}, doi = {10.1006/phrs.1993.1106}, pmid = {8234143}, issn = {1043-6618}, mesh = {Animals ; *Avoidance Learning ; Brain/physiology ; Choice Behavior ; Cocaine ; *Conditioning, Operant ; Disease Models, Animal ; Haloperidol ; Hypnotics and Sedatives ; Rats ; Rats, Wistar ; Saccharin/administration & dosage ; Substance-Related Disorders/diagnosis/*physiopathology/psychology ; }, abstract = {Given that a number of the techniques used to test drug abuse liability are not free from criticism, a series of oral free-choice experimental procedures was adopted. When simultaneously offered as alternatives to glucose using the classical polydipsic procedure, no preference for buprenorphine (0.025 mg/ml), morphine (0.5 mg/ml) or fentanyl (0.005 mg/ml) solutions was shown by premedicated rats. The same result was obtained when the two-bottle procedure was used for at least one month to offer etonitazene (10 micrograms/ml), buprenorphine (60 micrograms/ml), cocaine (300 micrograms/ml) and haloperidol (25 micrograms/ml) solutions as simultaneous alternatives to aspartame. This absence of preference was maintained even when the rats showed evident pharmacological effects and, in the case of the opiates, tolerance and withdrawal syndrome. However, when a gustatory marker (quinine) was introduced into one of the two solutions, preference was always shown for the other. Finally, in a conditioned taste aversion (CTA) test, etonitazene (5 or 40 micrograms/kg, i.p.) and haloperidol (0.5 or 2 mg/kg, i.p.) did not induce any reduction in saccharin consumption, while morphine (40 mg/kg) did. Pretreatment with naloxone (120 micrograms/kg, i.c.v.) did not antagonize morphine-induced CTA, while it did antagonize morphine-induced analgesia.}, } @article {pmid8511200, year = {1993}, author = {Persinger, MA and Bureau, YR and Kostakos, M and Peredery, O and Falter, H}, title = {Behaviors of rats with insidious, multifocal brain damage induced by seizures following single peripheral injections of lithium and pilocarpine.}, journal = {Physiology & behavior}, volume = {53}, number = {5}, pages = {849-866}, doi = {10.1016/0031-9384(93)90261-d}, pmid = {8511200}, issn = {0031-9384}, mesh = {Acetylcholine/physiology ; Aggression/drug effects/physiology ; Animals ; Association Learning/drug effects/physiology ; Avoidance Learning/drug effects/physiology ; Brain/drug effects/pathology/*physiopathology ; Brain Damage, Chronic/chemically induced/pathology/*physiopathology ; Calcium/metabolism ; Conditioning, Classical/drug effects/physiology ; Discrimination Learning/drug effects/physiology ; Drug Synergism ; Electroencephalography/drug effects ; Female ; Glycosaminoglycans/metabolism ; Limbic System/drug effects/pathology/physiopathology ; Lithium/*pharmacology ; Male ; Mental Recall/drug effects/physiology ; Necrosis ; Nerve Degeneration/drug effects/physiology ; Orientation/drug effects/physiology ; Pain Threshold/drug effects/physiology ; Pilocarpine/*pharmacology ; Rats ; Rats, Wistar ; Reaction Time/drug effects/physiology ; Seizures/chemically induced/pathology/*physiopathology ; Taste/drug effects/physiology ; }, abstract = {Several domains of behavior were measured in rats (n = 465) 10 days to 100 days after induction of limbic seizures by a single subcutaneous injection of lithium and pilocarpine. These rats displayed enhanced intragroup aggression but normal muricide; gustatory neophobia and conditioned taste aversion were virtually eliminated. Severe working and reference memory deficits were evident within the radial arm maze. Both state-dependent memory and possible situation-dependent precipitation of spontaneous seizures were suggested. The behavioral changes were considered commensurate with the multifocal pattern of thalamic, hippocampal/amygdaloid, and limbic cortical damage.}, } @article {pmid8390061, year = {1993}, author = {Shaw, NA}, title = {Impairment of the gustatory engram by generalised seizure activity without associated loss of conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {53}, number = {5}, pages = {839-843}, doi = {10.1016/0031-9384(93)90259-i}, pmid = {8390061}, issn = {0031-9384}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Cerebral Cortex/physiopathology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Electroshock ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/*physiology ; Rats ; Seizures/*physiopathology ; Taste/*physiology ; Taste Threshold/physiology ; }, abstract = {Three experiments are reported concerning the disruption of conditioned taste aversion (CTA) by generalised seizure activity (GSA) induced by electroconvulsive shock (ECS). Rats were taught CTAs by pairing either strong or weak taste cues (10% or 2.5% sucrose solutions) with either strong (0.15 M) or weak (0.05 M) doses of LiCl. In Experiment 1 it is shown that a 2.5% sucrose cue combined with a weak dose of LiCl will reproduce the disruptive effect of GSA when the CTA is established using a 10% sucrose cue. Likewise, a CTA acquired using a 2.5% sucrose cue paired with a strong dose of LiCl will simulate the failure of GSA to disrupt a CTA which has been established with a 10% sucrose cue. These findings support the theory that GSA acts to disrupt CTA by weakening the gustatory engram and an apparent inability to disrupt CTA by GSA does not necessarily signify that the gustatory engram itself remains intact. In Experiment 2, a CTA was established to a 2.5% sucrose cue using the more toxic dose of LiCl. It is shown that GSA will cause a substantial learning loss irrespective of whether it is interpolated within the taste-illness interval, or after the aversion has been acquired. It is concluded that the gustatory engram continues to reside in an active labile state even after the CTA has been established. In Experiment 3 it was estimated that the memory of the 2.5% sucrose cue must have been reduced to just over half of its original strength in order to create the learning loss reported in Experiment 2.}, } @article {pmid8261127, year = {1993}, author = {Sziklas, V and Petrides, M}, title = {Memory impairments following lesions to the mammillary region of the rat.}, journal = {The European journal of neuroscience}, volume = {5}, number = {5}, pages = {525-540}, doi = {10.1111/j.1460-9568.1993.tb00518.x}, pmid = {8261127}, issn = {0953-816X}, mesh = {Animals ; Hippocampus/physiology ; Learning/physiology ; Male ; Mammillary Bodies/*physiology ; Memory/*physiology ; Motor Activity/physiology ; Rats ; Retention, Psychology/physiology ; Space Perception/physiology ; Time Factors ; }, abstract = {The contribution of the mammillary region to learning and memory was investigated. It was demonstrated that lesions of this region impair performance on tasks that require memory for spatial information but that the deficit depends both on the amount of damage within the region and the difficulty of the task. A dissociation in the effect of such lesions on performance of comparable spatial and non-spatial memory tasks was shown. In contrast to the deficits observed on spatial memory tasks, the acquisition and retention of a complex non-spatial memory task was not impaired after extensive damage to the mammillary region. Such lesions also did not impair performance in a conditioned taste aversion task. These experiments suggest that the mammillary region may be selectively involved in spatial learning and memory.}, } @article {pmid8100072, year = {1993}, author = {López-García, JC and Fernández-Ruiz, J and Escobar, ML and Bermúdez-Rattoni, F and Tapia, R}, title = {Effects of excitotoxic lesions of the nucleus basalis magnocellularis on conditioned taste aversion and inhibitory avoidance in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {45}, number = {1}, pages = {147-152}, doi = {10.1016/0091-3057(93)90098-e}, pmid = {8100072}, issn = {0091-3057}, mesh = {Acetylcholinesterase/metabolism ; Animals ; Avoidance Learning/*drug effects ; Basal Ganglia/anatomy & histology/drug effects/*physiology ; Cerebral Cortex/anatomy & histology/drug effects/physiology ; Choline O-Acetyltransferase/metabolism ; Fluorescent Dyes ; Histocytochemistry ; Male ; Neural Pathways/drug effects/physiology ; Neurotransmitter Agents/physiology ; Parasympathetic Nervous System/anatomy & histology/drug effects/physiology ; Rats ; Rats, Wistar ; *Stilbamidines ; Taste/*drug effects ; }, abstract = {The role of the nucleus basalis magnocellularis (NBM) in a variety of learning tasks is well known. Lesions of this nucleus result in a reduction of cholinergic transmission throughout a vast portion of the cortex. Because cholinergic transmission in the insular cortex seems to be important for the acquisition of conditioned taste aversion, the aim of the present work was to study the effects of bilateral chemically induced lesions of the NBM on this conditioning, as correlated with some cholinergic markers in the insular cortex. The effect on inhibitory avoidance was also studied. Lesions prevented the acquisition of the aversion and disrupted retention of the task in previously trained animals. Learning in the inhibitory avoidance paradigm was also notably affected. Postlesion reductions of choline acetyltransferase and acetylcholinesterase activities and of K(+)-stimulated [3H]acetylcholine release were found in the insular cortex. Further, in intact rats labeling of NBM neurons was observed by retrograde tracing after injection of Fluoro-Gold into the insular cortex. These findings indicate that the NBM is involved in the neural integration of feeding behavior and that its cholinergic projection to the insular cortex is one of the implicated neurotransmitter systems.}, } @article {pmid8484895, year = {1993}, author = {Chambers, KC and Sengstake, CB and Brownson, EA and Westfahl, PK}, title = {Decreased testosterone levels and accelerated extinction of a conditioned taste aversion in fluid-deprived male rats.}, journal = {Behavioral neuroscience}, volume = {107}, number = {2}, pages = {299-305}, doi = {10.1037//0735-7044.107.2.299}, pmid = {8484895}, issn = {0735-7044}, support = {HD18185/HD/NICHD NIH HHS/United States ; RR-00163/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Male ; Motivation ; Rats ; Rats, Sprague-Dawley ; Taste/*physiology ; Testosterone/*blood ; Water Deprivation/*physiology ; Water-Electrolyte Balance/*physiology ; }, abstract = {The hypothesis that fluid deprivation accelerates extinction of a conditioned taste aversion in male Sprague-Dawley-derived rats by reducing serum testosterone levels was tested. Serum testosterone levels were found to be lower in fluid-deprived males than in nondeprived males (Experiments 1 and 2). Exogenous testosterone treatment that results in high physiological levels of serum testosterone slowed the extinction of fluid-deprived gonadectomized males to rates comparable with those of nondeprived sham males (Experiment 3). It was noted, however, that testosterone treatment was less effective in slowing extinction in fluid-deprived gonadectomized males than in nondeprived gonadectomized males even though the serum testosterone levels were the same (Experiments 3 and 4). These results provide strong support for the original hypothesis, but they suggest that fluid deprivation also reduces sensitivity to testosterone.}, } @article {pmid8469710, year = {1993}, author = {Grupp, LA and Chow, SY}, title = {Angiotensin II mediates a conditioned taste aversion in water-replete rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {44}, number = {4}, pages = {985-988}, doi = {10.1016/0091-3057(93)90036-s}, pmid = {8469710}, issn = {0091-3057}, mesh = {Angiotensin II/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Body Water/*physiology ; Male ; Rats ; Rats, Wistar ; Taste/*drug effects ; }, abstract = {Many compounds that exert an influence on behavioral processes will, under the unique conditions of the conditioned taste aversion (CTA) procedure, cause animals to avoid consuming an otherwise preferred fluid. While angiotensin II (ANG II) is a peptide with a number of behavioral and physiological actions, previous research did not support its role as an agent capable of inducing a CTA. Those studies used fluid deprivation to induce fluid intake and only a single conditioning trial. Fluid deprivation can elevate endogenous ANG II levels that may have interfered with or masked the ability of ANG II injections to exert an effect as a CTA-inducing agent. The present study reassessed the ability of ANG II to induce a CTA using fully hydrated animals and a number of conditioning trials. ANG II was able to induce a significant taste aversion at a dose five times lower than that used in previous studies.}, } @article {pmid8463862, year = {1993}, author = {Gietzen, DW}, title = {Neural mechanisms in the responses to amino acid deficiency.}, journal = {The Journal of nutrition}, volume = {123}, number = {4}, pages = {610-625}, doi = {10.1093/jn/123.4.610}, pmid = {8463862}, issn = {0022-3166}, support = {DK35747/DK/NIDDK NIH HHS/United States ; DK42274/DK/NIDDK NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Amino Acids, Essential/*deficiency/metabolism ; Animals ; Brain/*metabolism ; *Diet ; Eating ; Food Preferences ; Liver/metabolism ; Scopolamine/pharmacology ; Vagotomy ; }, abstract = {Food intake is rapidly and reliably reduced when animals are offered diets that result in an essential amino acid deficiency, such as those used in the imbalanced amino acid diet (IMB) paradigm. There seem to be at least three phases in the responses of rats to IMB: 1) In order to respond to a dietary challenge, the animals must first recognize that challenge. The available data suggest that before the behavioral effects occur, a decline in the concentration of an essential amino acid is sensed in a specific brain area, the prepyriform cortex. This recognition phase is associated with localized decreases in the concentrations of the limiting amino acid, norepinephrine and cyclic AMP and with altered protein synthesis. 2) Subsequent to recognition of the deficiency, a conditioned taste aversion develops, mediated in part by serotonin at the level of the vagus. 3) Finally, in the absence of a choice, the animals adapt to an IMB (but not a diet devoid of one or more essential amino acids) in approximately 1 wk. Damage to certain extrahypothalamic brain areas or liver denervation accelerates adaptation to IMB, suggesting both central and peripheral control in the adaptation phase. The resulting behavioral responses provide adaptive advantage to an animal in the selection of a diet with an appropriate balance of amino acids.}, } @article {pmid8390057, year = {1993}, author = {De Beun, R and Peeters, BW and Broekkamp, CL}, title = {Stimulus characterization of estradiol applying a crossfamiliarization taste aversion procedure in female mice.}, journal = {Physiology & behavior}, volume = {53}, number = {4}, pages = {715-719}, doi = {10.1016/0031-9384(93)90178-i}, pmid = {8390057}, issn = {0031-9384}, mesh = {Animals ; Apomorphine/toxicity ; Avoidance Learning/*drug effects ; Chlorides/toxicity ; Conditioning, Classical/*drug effects ; Discrimination Learning/drug effects ; Dose-Response Relationship, Drug ; Estradiol/*pharmacology ; Female ; Lithium/toxicity ; Lithium Chloride ; Mental Recall/drug effects ; Mice ; Progesterone/pharmacology ; Taste/*drug effects ; Testosterone/pharmacology ; }, abstract = {In female mice (n = 240), the estradiol stimulus was characterized by studying preexposure effects of sex steroids and sickness-inducing drugs on estradiol-induced (50 micrograms/kg SC) conditioned taste aversion (CTA). It was established that preexposure to estradiol itself (2-50 micrograms/kg SC) attenuates the development of CTA produced by the hormone. Only partial crossfamiliarization effects were found with progesterone (50-200 micrograms/kg SC) and testosterone (250-1000 micrograms/kg SC), steroids that induce CTA themselves. Preexposure to the sickness-inducing drugs lithium chloride (22 mg/kg SC) and apomorphine (0.1-0.2 mg/kg SC) prevented or substantially reduced the development of estradiol-induced CTA, respectively. It was concluded that only a low degree of stimulus resemblance exists between estradiol and the other principal sex steroids, progesterone and testosterone. In addition, it was concluded that the estradiol stimulus resembles the stimuli produced by sickness-inducing drugs.}, } @article {pmid8110867, year = {1993}, author = {Escobar, ML and Jiménez, N and López-García, JC and Tapia, R and Bermúdez-Rattoni, F}, title = {Nerve growth factor with insular cortical grafts induces recovery of learning and reestablishes graft choline acetyltransferase activity.}, journal = {Journal of neural transplantation & plasticity}, volume = {4}, number = {2}, pages = {167-172}, doi = {10.1155/NP.1993.167}, pmid = {8110867}, issn = {0792-8483}, mesh = {Animals ; Avoidance Learning/*physiology ; *Brain Tissue Transplantation ; Cerebral Cortex/embryology/injuries/physiopathology/*transplantation ; Choline O-Acetyltransferase/*biosynthesis ; *Fetal Tissue Transplantation ; Graft Survival ; Lithium Chloride ; Male ; Nerve Growth Factors/pharmacology/*therapeutic use ; Nerve Tissue Proteins/*biosynthesis ; Rats ; Rats, Wistar ; Taste/*physiology ; }, abstract = {Rats showing disrupted taste aversion due to insular cortex (IC)-lesions received either IC-grafts with NGF, grafts without NGF, or NGF alone. An additional group served as lesioned controls. Only those animals that received IC-grafts with NGF recovered the ability to learn the conditioned taste aversion task, at 15 days post-graft. Choline acetyltransferase (ChAT) activity in the IC-grafts with, but not without NGF, was similar to the IC activity of unoperated controls. In contrast, glutamate decarboxylase activity was similar in all the groups. These findings suggest that IC-grafts associated with NGF induce recovery of learning abilities in IC-lesioned rats, which correlates with reestablishment of ChAT activity in the grafts at 15 days post-implantation.}, } @article {pmid8451314, year = {1993}, author = {Orr, TE and Walters, PA and Carl, GF and Elkins, RL}, title = {Brain levels of amines and amino acids in taste aversion-prone and -resistant rats.}, journal = {Physiology & behavior}, volume = {53}, number = {3}, pages = {495-500}, doi = {10.1016/0031-9384(93)90143-4}, pmid = {8451314}, issn = {0031-9384}, mesh = {Amines/*metabolism ; Amino Acids/*metabolism ; Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Conditioning, Classical/*physiology ; Female ; Male ; Rats ; Rats, Inbred Strains ; Selection, Genetic ; Species Specificity ; Taste/genetics/*physiology ; }, abstract = {Possible biological contributions to taste aversion (TA) conditionability were explored by comparing whole-brain levels of five neurotransmitter amines and 14 common amino acids within TA-prone (TAP) and TA-resistant (TAR) rats. The selectively bred strains had been developed via 22 generations of bidirectional nonsibling matings based on susceptibility to cyclophosphamide-induced conditioned TAs. The target substances were separated by HPLC and were measured by electrochemical or fluorometric procedures. The TAP brains had higher levels of serotonin (5-HT) and lower levels of norepinephrine (NE) than TAR brains. No strain differences were found with respect to dihydroxyphenylalanine (DOPAC), dopamine (DA), or 5-hydroxyindoleacetic acid (5-HIAA). Among amino acids, TAP rats had lower levels of lysine than TARs: no other differences were detected. Therefore, higher levels of 5-HT and lower levels of NE and lysine were associated with enhanced TA conditionability. The 5-HT and NE results extend prior indications of their central neurotransmitter TA involvements. The functional role of lysine in TA or other brain functions remains obscure.}, } @article {pmid8450478, year = {1993}, author = {Higgins, GA and Joharchi, N and Sellers, EM}, title = {Behavioral effects of the 5-hydroxytryptamine3 receptor agonists 1-phenylbiguanide and m-chlorophenylbiguanide in rats.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {264}, number = {3}, pages = {1440-1449}, pmid = {8450478}, issn = {0022-3565}, mesh = {Animals ; Behavior, Animal/*drug effects ; Biguanides/administration & dosage/*pharmacology ; Conditioning, Psychological/drug effects ; Dopamine/metabolism ; Haloperidol/pharmacology ; Indoles/pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Wistar ; Receptors, Serotonin/*drug effects ; Serotonin Receptor Agonists/*pharmacology ; Tropisetron ; }, abstract = {We have investigated the behavioral effect of the 5-hydroxytryptamine3 (5-HT3) receptor agonists 1-phenylbiguanide (PBG) and m-chlorophenylbiguanide (mCPBG) in rats after i.p. and i.c.v. injection. It was hoped that this approach may provide an alternative means of studying the role of 5-HT3 receptors on animal behavior, for the majority of related studies have used antagonists at this subtype. Both PBG (3-60 mg/kg, i.p.) and mCPBG (1-30 mg/kg i.p.) produced abdominal constrictions, writhing and salivation in some, but not all, rats. The most marked behaviors were seen after mCPBG (30 mg/kg, i.p.), where paw shakes and chin rubbing was also recorded. Almost certainly as a consequence of these behaviors, PBG (3-30 mg/kg, i.p.) and mCPBG (0.3-10 mg/kg, i.p.) produced a conditioned place aversion. Pretreatment with the 5-HT3 antagonists ondansetron (0.01-0.1 mg/kg, s.c.), ICS205-930 and quaternized ICS205-930 (both 0.1 mg/kg, i.p.) blocked the PBG (30 mg/kg, i.p.)-induced place aversion. PBG (30 mg/kg, i.p.) and mCPBG (10 mg/kg, i.p.) also produced a conditioned taste aversion. The central administration of PBG (1-30 micrograms, i.c.v.) and mCPBG (0.1-10 micrograms, i.c.v.) enhanced locomotor- and gnawing-related behavior, although the effects with PBG seemed more consistent. These PBG (10 micrograms, i.c.v.)-induced behaviors were completely blocked by haloperidol (0.01-0.1 mg/kg, s.c.). In contrast, ondansetron (0.0001-1 mg/kg, s.c.) and ICS205-930 (0.1 mg/kg, i.p.) produced only a mild and inconsistent attenuation of these responses. PBG (1-30 micrograms, i.c.v.) failed to produce any place conditioning (i.e., neither a preference nor aversion was found). It is concluded that activation of peripheral 5-HT3 receptors leads to aversive-type behaviors, which may be related to gastrointestinal discomfort or malaise. In contrast, central injection of PBG and mCPBG produced a range of dopamine-related behaviors; however, a 5-HT3 receptor involvement is unclear. Because both PBG and mCPBG have dopamine releasing properties, the use of 5-HT3 agonists lacking such effects and/or the use of more discrete microinjection studies are needed to more clearly elucidate the roles of 5-HT3 receptors in the central nervous system.}, } @article {pmid8387656, year = {1993}, author = {Yamamoto, T}, title = {Neural mechanisms of taste aversion learning.}, journal = {Neuroscience research}, volume = {16}, number = {3}, pages = {181-185}, doi = {10.1016/0168-0102(93)90122-7}, pmid = {8387656}, issn = {0168-0102}, mesh = {Animals ; Avoidance Learning/*physiology ; Humans ; Neurons, Afferent/*physiology ; Taste/*physiology ; }, abstract = {When ingestion of a taste stimulus is paired with internal malaise the animal remembers the taste and rejects its ingestion thereafter. A model of neural substrate for this conditioned taste aversion (CTA) is presented on the basis of our recent experiments. To establish the CTA in rats, 0.01 M saccharin was paired with i.p. injection of 0.15 M LiCl. Behavioral lesion experiments by means of ibotenic acid showed that the parabrachial nucleus (PBN), medial thalamus (MT), and lateral part of the amygdala (LPA) were crucial to establish the CTA. c-fos immunoreactivity studies showed that ingestion of saccharin induced a remarkable activation of the central lateral (cl) subnucleus of the PBN in normal rats, however, rats with the CTA to saccharin showed c-fos neurons in the ventral lateral (vl) subnucleus of the PBN. These findings suggest that the recipient zone for saccharin taste switches from the cl to vl subnuclei after acquisition of a CTA. The taste pathway from the vl subnucleus to the LPA through the MT may be a neural substrate for taste aversion learning. The switching may result from a plastic change involving long-term potentiation and depression due to a convergence of the taste input of saccharin and general visceral information of LiCl injection.}, } @article {pmid8097409, year = {1993}, author = {Goudie, AJ and Harrison, AA and Leathley, MJ}, title = {Evidence for a dissociation between benzodiazepine withdrawal signs.}, journal = {Neuroreport}, volume = {4}, number = {3}, pages = {295-298}, doi = {10.1097/00001756-199303000-00017}, pmid = {8097409}, issn = {0959-4965}, mesh = {Animals ; Anti-Anxiety Agents/*pharmacology ; Avoidance Learning/drug effects ; Body Weight/drug effects ; Chlordiazepoxide/pharmacology ; Male ; Rats ; Rats, Wistar ; Substance Withdrawal Syndrome/*psychology ; Taste/physiology ; }, abstract = {The relationship between benzodiazepine-withdrawal induced weight loss and conditioned taste aversion was studied. Rats were treated with chlordiazepoxide (CDP) for 10 days (n = 37) or with vehicle (n = 39). Significant withdrawal-induced weight loss was observed. On day 11 all animals received an intra-oral infusion of saccharin. In a subsequent saccharin vs water choice test significant withdrawal-induced conditioned taste aversion was observed, as CDP pretreated animals drank less saccharin than controls. The two withdrawal indices were not correlated in the CDP pretreated animals [r = + 0.05], despite the fact that we studied a large group of rats. These data are in agreement with suggestions that drug withdrawal syndromes may be heterogeneous phenomena with a number of different underlying neural mechanisms.}, } @article {pmid8452374, year = {1993}, author = {Ganesan, R and Rosellini, RA and Svare, B}, title = {Investigation of anabolic steroids in two taste aversion paradigms.}, journal = {Appetite}, volume = {20}, number = {1}, pages = {1-11}, doi = {10.1006/appe.1993.1001}, pmid = {8452374}, issn = {0195-6663}, support = {5RO3 DA0647202/DA/NIDA NIH HHS/United States ; }, mesh = {Anabolic Agents/*pharmacology ; Animals ; Estradiol/pharmacology ; Food Preferences/drug effects ; Male ; Mice ; Nandrolone/pharmacology ; Saccharin ; Taste/*drug effects ; Testosterone/analogs & derivatives/pharmacology ; }, abstract = {The aversive effects of estradiol have been studied in two different taste aversion paradigms. A similar investigation was undertaken for the anabolic-androgenic steroids, nandralone and testosterone cypionate, using Rockland-Swiss mice. Experiments 1 and 2 used the brief exposure of a novel saccharin solution as the conditioned stimulus for taste aversion learning, and showed that anabolic steroids (1 mg) do not induce taste aversions. Instead, these hormones induced a small non-contingent increase in saccharin preference. Experiment 3 showed that daily nandralone administration (1 mg/day) had a greater anabolic effect than the same dose of testosterone cypionate. Experiment 4 paired the continuous exposure to a novel diet with daily nandralone injections, and showed that steroid treatment increased intake of the novel diet. When the novel diet was subsequently presented with the familiar diet in a two-choice preference test, there was no indication that an aversion was conditioned to the novel target diet. On the contrary, nandralone treatment significantly increased the preference for the novel diet. These experiments show that anabolic-androgenic steroids do not have aversive effects in mice, and that they may have positive consequences.}, } @article {pmid8446690, year = {1993}, author = {Spector, AC and Grill, HJ and Norgren, R}, title = {Concentration-dependent licking of sucrose and sodium chloride in rats with parabrachial gustatory lesions.}, journal = {Physiology & behavior}, volume = {53}, number = {2}, pages = {277-283}, doi = {10.1016/0031-9384(93)90205-t}, pmid = {8446690}, issn = {0031-9384}, support = {DC-00161/DC/NIDCD NIH HHS/United States ; DC-00240/DC/NIDCD NIH HHS/United States ; MH-43787/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Dose-Response Relationship, Drug ; Drinking/*physiology ; Male ; Pons/*physiology ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; Sucrose ; Taste/*physiology ; Thirst/physiology ; }, abstract = {The medial zone of parabrachial nuclei (PBN) serves as an obligatory synapse in the central gustatory system in rodents. Lesions in the PBN impair taste aversion learning and depletion-induced sodium appetite in rats, and also alter the ingestion of sapid stimuli. Interpretation of these lesion-induced behavioral deficits requires an evaluation of whether taste function is compromised. The present study examined whether rats with PBN lesions could show normal concentration-dependent changes in licking behavior to very small volumes of NaCl and sucrose. Physiological state was also varied; taste responsivity was examined in water-deprived and nondeprived rats. In a specially designed gustometer, nine rats with electrophysiologically guided lesions in the PBN and five surgical controls were trained to lick a drinking spout to receive 10-s access to various concentrations of NaCl (0.03-1.0 M) and sucrose (0.01-1.0 M) during 30-min sessions. Water-deprived control rats progressively decreased their responses compared with water as the concentration of NaCl was raised. In contrast, water-deprived PBNX rats did not decrease their licking responses to NaCl relative to water until the concentration reached 1.0 M. In the nondeprived state, control and PBNX rats decreased their responsiveness as a function of NaCl concentration, and the two groups did not differ. The licking responses of water-deprived PBNX rats did not differ from control rats when sucrose was the stimulus. In the nondeprived condition, both groups monotonically increased their licking to sucrose as a function of concentration, but PBNX rats were significantly less responsive than controls.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8446659, year = {1993}, author = {Aragon, CM and Amit, Z}, title = {Taurine and ethanol-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {44}, number = {2}, pages = {263-266}, doi = {10.1016/0091-3057(93)90460-b}, pmid = {8446659}, issn = {0091-3057}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Drug Interactions ; Ethanol/blood/*pharmacology ; Male ; Rats ; Taste/drug effects ; Taurine/*pharmacology ; }, abstract = {It has been reported that acute, simultaneous injections of taurine and ethanol were effective in reducing ethanol-induced locomotor activity and sleep time. The possible involvement of taurine administration in ethanol-induced conditioned taste aversion (CTA) was investigated. The results obtained in the present study following simultaneous administration of taurine (45 mg/kg) and ethanol (0.8, 1.2, and 1.6 g/kg) demonstrate a significant interaction between taurine and ethanol in their effect on ethanol-induced CTA in rats. This interaction was biphasic in nature and dependent upon the specific dose of ethanol. At the lowest ethanol dose (0.8 g/kg), which in itself resulted in a marginal CTA, taurine significantly enhanced the CTA induced by this dose. The intermediate ethanol dose of 1.2 g/kg produced a significant CTA. This CTA was blocked by administration of taurine. Finally, the CTA produced by the high dose of ethanol (1.6 g/kg) was not affected by administration of taurine. Taurine by itself does not produce a CTA. Peripheral levels of ethanol were ethanol dose dependent and the same in all animals regardless of treatment, indicating taurine had no effects on plasma ethanol levels. These data are similar to those obtained by earlier studies on the effects of taurine on ethanol-induced motor activity in mice. The present results support the findings reported by other investigators that taurine administration exerts a significant effect on ethanol-induced behaviors.}, } @article {pmid8383501, year = {1993}, author = {Biederman, GB and Davey, VA}, title = {Antisickness conditioning using a nausea-producing nondrug cue.}, journal = {Behavioral neuroscience}, volume = {107}, number = {1}, pages = {215-217}, doi = {10.1037//0735-7044.107.1.215}, pmid = {8383501}, issn = {0735-7044}, mesh = {Animals ; *Association Learning/drug effects ; *Avoidance Learning/drug effects ; Chlorides/pharmacology ; *Conditioning, Classical/drug effects ; *Cues ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Sprague-Dawley ; Rotation ; *Taste/drug effects ; }, abstract = {Most drugs induce conditioned taste aversions and are therefore commonly supposed to produce nausea or sickness. Paradoxically, some drugs appear to lose induction capability when made to serve as a cue for a second drug that produces more severe sickness, perhaps through selective association with a hypothetical homeostatic or antisickness aftereffect of sickness. Using drug-drug pairings had made antisickness conditioning theory difficult to validate. We report here that rotation serves in lieu of a drug cue in rats. Rotation-drug pairings eliminate drug interactions and enable the sorts of parametric manipulations required to validate the theory. By postulating a common sickness mechanism to explain both taste aversion and aversion failure, the theory places the phenomenon within an adaptive evolutionary framework. Successful application could yield a direct countermeasure to severe nausea in clinical settings.}, } @article {pmid8383500, year = {1993}, author = {Bechara, A and Martin, GM and Pridgar, A and van der Kooy, D}, title = {The parabrachial nucleus: a brain stem substrate critical for mediating the aversive motivational effects of morphine.}, journal = {Behavioral neuroscience}, volume = {107}, number = {1}, pages = {147-160}, doi = {10.1037//0735-7044.107.1.147}, pmid = {8383500}, issn = {0735-7044}, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Brain Mapping ; Brain Stem/*drug effects ; Conditioning, Classical/*drug effects ; Male ; Medulla Oblongata/drug effects ; Mesencephalon/drug effects ; Morphine/*pharmacology ; *Motivation ; Neural Pathways/drug effects ; Rats ; Rats, Wistar ; Receptors, Opioid/drug effects ; Social Environment ; Taste/*drug effects ; }, abstract = {Bilateral ibotenic acid lesions of the lateral, but not the medial, parabrachial nucleus (PBN) blocked conditioned taste aversion (CTA) induced by morphine but not conditioned place preference induced by morphine. The same lateral PBN lesions also blocked conditioned place aversion produced by low intraperitoneal doses of morphine (shown to produce aversion, instead of preference, due to a restricted action on gut opiate receptors). Lateral PBN lesions did not block CTA produced by LiCl. Cerebral peduncle lesions that destroyed the direct descending projections from the visceral cortex to the PBN did not block CTA induced by morphine, nor did ibotenic acid lesions of the tegmental pedunculopontine nuclei (shown to block place preference produced by even high morphine doses). It is suggested that the lateral PBN is a critical link in the neural pathway carrying the aversive motivational effects of opiates from the gut into the central nervous system, independent of the neural pathway carrying the rewarding motivational effects of morphine.}, } @article {pmid8383337, year = {1993}, author = {Melton, PM and Kopman, JA and Riley, AL}, title = {Cholecystokinin as a stimulus in drug discrimination learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {44}, number = {2}, pages = {249-252}, doi = {10.1016/0091-3057(93)90458-6}, pmid = {8383337}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/administration & dosage ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Female ; *Generalization, Stimulus ; Lithium/administration & dosage ; Lithium Chloride ; Rats ; Saccharin/administration & dosage ; Sincalide/*administration & dosage ; Taste ; }, abstract = {Animals were trained to discriminate a relatively low dose of the octapeptide cholecystokinin (CCK) from distilled water within the conditioned taste aversion baseline of drug discrimination learning. Specifically, rats were injected with CCK (5.6 micrograms/kg) prior to the presentation of saccharin-LiCl pairings and with the CCK vehicle prior to the presentation of saccharin alone. After 10 conditioning trials (40 days), subjects acquired the discrimination, avoiding saccharin consumption following administration of CCK and consuming the same saccharin solution following the drug vehicle. Once the discrimination was acquired, a generalization function was determined for doses above and below that of the training stimulus. At doses below the training dose of CCK (i.e., 0, 3.2, and 4.2 micrograms/kg), subjects drank at control levels, whereas at the training dose and above (10 micrograms/kg) subjects significantly reduced consumption. That a relatively low dose of CCK can be used as a discriminative stimulus within a drug discrimination design may be important in that the procedure can now be used in the assessment of the pharmacological characteristics of CCK at a dose similar to that used in other behavioral assessments of the compound.}, } @article {pmid8457907, year = {1993}, author = {Agüero, A and Arnedo, M and Gallo, M and Puerto, A}, title = {Lesions of the lateral parabrachial nuclei disrupt aversion learning induced by electrical stimulation of the area postrema.}, journal = {Brain research bulletin}, volume = {30}, number = {5-6}, pages = {585-592}, doi = {10.1016/0361-9230(93)90086-q}, pmid = {8457907}, issn = {0361-9230}, mesh = {Animals ; Electric Stimulation ; Electrodes, Implanted ; Learning/*physiology ; Male ; Pons/anatomy & histology/*physiology ; Rats ; Rats, Wistar ; Reinforcement, Psychology ; Taste/physiology ; }, abstract = {The research about the neural basis of taste aversion learning (TAL) has pointed out the area postrema (AP) as a fundamental structure implied in the processing of certain toxic stimuli. Likewise, recent studies demonstrated that electric stimulation of the AP is an efficient substitute of the aversive stimulus. The lateral parabrachial nucleus (PBN1), one of the subnuclei of the parabrachial complex, is the main anatomic rostral connection of the AP. In the experiment presented here, we demonstrate that TAL induced by electric stimulation of the AP is interrupted when the PBN1 is lesioned, thus giving support to the functional role of this anatomic system (AP-PBN1) in the codification of aversive stimuli processed by the AP.}, } @article {pmid8442735, year = {1993}, author = {Arnedo, M and Gallo, M and Agüero, A and Molina, F and Puerto, A}, title = {Medullary afferent vagal axotomy disrupts NaCl-induced short-term taste aversion learning.}, journal = {Behavioral and neural biology}, volume = {59}, number = {1}, pages = {69-75}, doi = {10.1016/0163-1047(93)91187-r}, pmid = {8442735}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Male ; Medulla Oblongata/physiology ; Models, Neurological ; Rats ; Rats, Wistar ; *Sodium Chloride/pharmacology ; Taste/drug effects/*physiology ; Vagotomy ; Vagus Nerve/*physiology ; }, abstract = {The effect of medullary afferent vagal axotomy on NaCl-induced short-term and long-term taste aversion learning (TAL) was examined to assess the relevance of the vagus nerve in drug-induced TAL. The results show that medullary afferent vagal axotomy disrupts NaCl-induced short-term (nondelayed) TAL, while having no effect on learning acquired with the same product in long-term (delayed) TAL protocols. Acquisition of learning in delayed discrimination tasks may be mediated by alternative mechanisms of nonvagal nature, e.g., the humoral system. The possibility that short-term and long-term TAL may be mediated by different neurobiological substrates is discussed.}, } @article {pmid8442732, year = {1993}, author = {Rosenblum, K and Meiri, N and Dudai, Y}, title = {Taste memory: the role of protein synthesis in gustatory cortex.}, journal = {Behavioral and neural biology}, volume = {59}, number = {1}, pages = {49-56}, doi = {10.1016/0163-1047(93)91145-d}, pmid = {8442732}, issn = {0163-1047}, mesh = {Animals ; Anisomycin/pharmacology ; Avoidance Learning/drug effects ; Cerebral Cortex/drug effects/*metabolism ; Conditioning, Psychological/drug effects ; Male ; Memory/drug effects/*physiology ; Nerve Tissue Proteins/*biosynthesis ; Rats ; Rats, Wistar ; Saccharin/administration & dosage/pharmacology ; Taste/drug effects/*physiology ; }, abstract = {Application of the protein synthesis inhibitor anisomycin to the rat gustatory cortex before and during training impairs conditioned taste aversion (CTA) to saccharin. No behavioral impairment is observed if the inhibitor is applied to an adjacent cortical area or to one cortical hemisphere only. The consumption of saccharin and of total fluid, as well as behavioral recognition of saccharin, is not affected. Preexposure of rats to saccharin several days before training markedly inhibits CTA to that taste. Injection of anisomycin to the gustatory cortex immediately prior to the preexposure period attenuates the latent inhibition. These results suggest that protein synthesis in the gustatory cortex is required for normal acquisition of the memory of taste.}, } @article {pmid8434072, year = {1993}, author = {Barry, MA and Larson, DC and Frank, ME}, title = {Loss and recovery of sodium-salt taste following bilateral chorda tympani nerve crush.}, journal = {Physiology & behavior}, volume = {53}, number = {1}, pages = {75-80}, doi = {10.1016/0031-9384(93)90013-6}, pmid = {8434072}, issn = {0031-9384}, support = {5P01-DC00168-11/DC/NIDCD NIH HHS/United States ; DC00058/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Chorda Tympani Nerve/*physiology ; Conditioning, Classical/physiology ; Cricetinae ; Functional Laterality/*physiology ; Humans ; Male ; Mesocricetus ; Middle Aged ; Nerve Regeneration/*physiology ; *Sodium Chloride ; Taste/*physiology ; Taste Buds/physiology ; }, abstract = {The ability of the gustatory system to recover following peripheral nerve injury was investigated in adult hamsters. A conditioned taste aversion paradigm was utilized to test sodium salt-taste function after bilateral crush of the chorda tympani nerve and after nerve regeneration. Bilateral chorda tympani crush abolished expression of a previously learned conditioned taste aversion to 0.1 M NaCl. At 10 to 16 weeks following surgery, the hamsters were reconditioned three times to 0.1 M NaCl. The hamsters were able to relearn the conditioned taste aversion and by 16 weeks, the crush and sham groups showed equally strong and specific aversions to 0.1 M NaCl. A second surgery to cut the regenerated chorda tympani nerves resulted, again, in the loss of expression of the conditioned taste aversion. Thus, regenerated chorda tympani nerves are capable of carrying the information needed to form a conditioned taste aversion specific for sodium salts in the adult hamster.}, } @article {pmid8249660, year = {1993}, author = {Mogensen, J and Divac, I}, title = {Behavioural changes after ablation of subdivisions of the rat prefrontal cortex.}, journal = {Acta neurobiologiae experimentalis}, volume = {53}, number = {3}, pages = {439-449}, pmid = {8249660}, issn = {0065-1400}, mesh = {Animals ; Behavior, Animal/*physiology ; Male ; Prefrontal Cortex/*physiology ; Rats ; Rats, Wistar ; }, abstract = {Sham operated controls and four groups of rats subjected to ablation of various parts of their frontal cortex were compared in food and water intake and four behavioural tasks. The ablations were aimed at removing (1) the ventral prefrontal cortex, (2) the dorsal part of the medial prefrontal cortex, (3) the total medial prefrontal cortex, and (4) the anterior dorsolateral (non-prefrontal) cortex. Only two groups had a significantly impaired food and water intake: the ventral prefrontal and the non-prefrontal anterolateral. The latter group was not adipsic. Two variants of spontaneous alternation were administered in a T-maze: a non-cued version in which both arms were grey and a cued version in which one arm was white and the other black. While all ablated groups behaved like the control group on the non-cued test, the number of perseverative responses of the total anteromedial group was significantly increased in the cued version of the test. Significant group differences could be seen neither in a test of conditioned taste aversion nor in extinction of operantly conditioned bar presses. Finally, in a vertical hole-board exploration test the only significant group difference was a prolongation of the mean visit duration of the ventrally lesioned animals in comparison with all other groups. The results of the present study further indicate functional differentiation within the prefrontal cortex of the rat.}, } @article {pmid7904976, year = {1993}, author = {Simiand, J and Keane, PE and Barnouin, MC and Keane, M and Soubrié, P and Le Fur, G}, title = {Neuropsychopharmacological profile in rodents of SR 57746A, a new, potent 5-HT1A receptor agonist.}, journal = {Fundamental & clinical pharmacology}, volume = {7}, number = {8}, pages = {413-427}, pmid = {7904976}, issn = {0767-3981}, mesh = {Aggression/drug effects ; Animals ; Anti-Anxiety Agents/pharmacology ; Antidepressive Agents/pharmacology ; Behavior, Animal/drug effects ; Male ; Mice ; Naphthalenes/*pharmacology ; Nervous System/*drug effects ; Pyridines/*pharmacology ; Radiation-Protective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin/drug effects/physiology ; Serotonin Receptor Agonists/*pharmacology ; Stimulation, Chemical ; }, abstract = {The effect of the 5-HT1A agonist SR 57746A (1-[2-(naphth-2-yl) ethyl]-4-(3-trifluoromethylphenyl))-1,2,5,6 tetrahydropyridine hydrochloride), was evaluated in a variety of psychopharmacological tests in rodents. In the approach-avoidance conflict test in rats, orally administered SR 57746A significantly increased punished responding at doses as low as 3 mg/kg, while unpunished responding was only reduced at 30 mg/kg. SR 57746A was active for at least 4 hours in this test. SR 57746A significantly antagonised the lithium-induced taste aversion in rats at doses of 3 and 10 mg/kg po. In staircase test in mice, SR 57746A reduced rearing at doses which did not reduce the number of steps climbed. In the two-compartment exploratory model in mice, SR 57746A increased the latency to the first entry into the dark compartment (at 2 to 8 mg/kg po), and reduced the time spent in the dark compartment (at 8 mg/kg po), but had no effect on the total number of transitions. SR 57746A potently reduced aggressive behaviour in isolated mice, the dose of 1 mg/kg po produced over 80% inhibition of fighting in this test. SR 57746A was also active in the behavioural despair test of depression in mice and rats, and reversed learned helpless behaviour in rats. SR 57746A was also active in the behavioural despair test of depression in mice and rats, and reversed learned helpless behaviour in rats. SR 57746A dose-dependently generalised to the cue produced by 8-OH-DPAT in rats, but produced only a very weak serotonergic syndrome. Like 8-OH-DPAT and ipsapirone, SR 57746A reduced body temperature in mice, but only at a high dose (10 mg/kg po). SR 57746A reversed haloperidol-induced catalepsy in rats with an ED50 of 3.85 mg/kg po, but was unable to antagonise the stereotypy induced by apomorphine in this species. SR 57746A was inactive or only very weakly active in a series of tests typical of benzodiazepine-like activity, including antagonism of pentetrazol-induced seizures, reduction of muscle tone and locomotor activity, impairment of motor co-ordination, and potentiation of the effects of centrally-acting sedative-hypnotics. SR 57746A was also inactive as an analgesic in the PBQ writhing test. Thus, SR 57746A is active in a number of tests indicative of 5-HT1A receptor stimulation in vivo, and, more particularly, in a number of tests predictive of anxiolytic, anti-aggressive and antidepressant activities. SR 57746A is as potent as diazepam in anxiolytic tests, and more potent than imipramine in antidepressant tests, whereas it is devoid of neuroleptic potential. In view of this profile of activity, SR 57746A merits evaluation as a potential anxiolytic and antidepressant in humans.}, } @article {pmid7871000, year = {1993}, author = {De Beun, R and Rijk, HW and Broekkamp, CL}, title = {Cross-familiarisation conditioned taste aversion procedure as a method to reveal stimulus resemblance between drugs: studies on the 5-HT1A agonist 8-OHDPAT.}, journal = {Psychopharmacology}, volume = {112}, number = {1}, pages = {121-128}, pmid = {7871000}, issn = {0033-3158}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacokinetics/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Discrimination, Psychological/drug effects ; Dose-Response Relationship, Drug ; Glucose/metabolism ; Male ; Mice ; Receptors, Serotonin/metabolism ; Serotonin Receptor Agonists/pharmacokinetics/*pharmacology ; Taste/*drug effects ; }, abstract = {In the present study a cross-familiarisation conditioned taste aversion (CTA) paradigm was utilized to reveal stimulus resemblance between the selective 5-HT1A agonist 8-OHDPAT and a variety of serotonergic and non-serotonergic drugs. In male mice, a 0.22 mg/kg dose of 8-OHDPAT was used as the reference compound inducing CTA. Dose-dependent effects of pre-exposure to 24 different test drugs on the magnitude of the 8-OHDPAT-induced CTA were tested as a measure for stimulus similarity between these test drugs and 8-OH-DPAT (the reference compound). Pre-exposure to 8-OH-DPAT itself, ipsapirone, buspirone, RU 24969, sertraline, d-amphetamine, LSD, metergoline and idazoxan effectively prevented the development of CTA induced by 8-OHDPAT. Pre-exposure to apomorphine, diazepam, SCH 23390, LiCl, spiperone, DOI, spiroxatrine, umespirone, pindolol, mCPP, haloperidol, MK 212, clonidine, quipazine and also 5-MeODMT was not effective in completely abolishing the CTA produced by 8-OHDPAT. It is concluded from these results that the relatively simple and fast cross-familiarisation taste aversion method is a suitable paradigm to study similarities in stimulus properties of different drugs.}, } @article {pmid7870902, year = {1993}, author = {Jaeger, TV and van der Kooy, D}, title = {Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects.}, journal = {Psychopharmacology}, volume = {110}, number = {1-2}, pages = {76-84}, pmid = {7870902}, issn = {0033-3158}, mesh = {Animals ; Brain/anatomy & histology ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Generalization, Stimulus/drug effects ; Male ; Microinjections ; Morphine/administration & dosage/*pharmacology ; Nucleus Accumbens/physiology ; Pons/anatomy & histology/*drug effects ; Rats ; Rats, Wistar ; Reinforcement, Psychology ; Saccharin/pharmacology ; }, abstract = {Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 micrograms) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid11224122, year = {1992}, author = {Gauvin, DV and Sannerud, CA and Holloway, FA}, title = {Second-order (environmental) conditioning of a taste aversion in rats.}, journal = {Behavioural pharmacology}, volume = {3}, number = {3}, pages = {249-254}, pmid = {11224122}, issn = {1473-5849}, abstract = {Four groups of rats (n = 10/group) were conditioned in a taste aversion task using a second-order reinforcer associated with precipitated morphine withdrawal. Rats in CS+, CS- and CS(random) groups were exposed to a chronic morphine (morphine sulfate, MS) dosing regimen. A control group received equivalent volumes of saline. All rats then received daily i.p. injections of naloxone HCI (1.0-3.2mg/kg), inducing precipitated morphine withdrawal in group-dependent unique environments. The 4-h withdrawal trials were terminated by a 20mg/kg MS injection (MS treatment groups only) and returned to their home cage. After a 1-week wash-out was imposed, all subjects were exposed to a conditioned taste aversion (CTA) task using environmental stimuli (CSI) from Phase 1 paired with saccharin (CS2) in a second-order conditioning procedure. The CS+ group developed a significant CTA; the CS- and CS(random) groups increased their consumption of saccharin. The saline group was unaffected by the treatment conditions. The data demonstrate the salience and importance of environmental stimuli and suggest a role for such conditioning in drug relapse phenomena.}, } @article {pmid11224086, year = {1991}, author = {de Beun, R and Heinsbroek, RP and Slangen, JL and van De Poll, NE}, title = {Discriminative stimulus properties of estradiol in male and female rats revealed by a taste-aversion procedure.}, journal = {Behavioural pharmacology}, volume = {2}, number = {6}, pages = {439-445}, pmid = {11224086}, issn = {1473-5849}, abstract = {Gonadectomized male and female rats were trained to discriminate 50µg/kg estradiol-17B(E(2)) from its vehicle in a one-bottle forced-drinking discriminative taste-aversion procedure. The animals were injected SC with E(2) or arachidic oil, 60min prior to daily training sessions during which they had access to a saccharin (Sac) solution for 10min. Animals injected with E(2) prior to Sac-LiCl pairings and with arachidic oil prior to Sac-NaCl pairings acquired hormone discrimination, only suppressing Sac intake following the administration of E(2) and not following the administration of arachidic oil. Both males and females reliably discriminated E(2) from arachidic oil within 28 training sessions. Subsequent generalization tests revealed dose-dependent stimulus control of Sac intake by E(2) in both sexes (range of substitution doses: 0.4-250µg/kg). The results show that E(2) may act as a discriminative stimulus in male and female rats.}, } @article {pmid11224077, year = {1991}, author = {Lucki, I and Marcoccia, JM}, title = {Discriminated taste aversion with a 5-HT(1A) agonist measured using saccharin preference.}, journal = {Behavioural pharmacology}, volume = {2}, number = {4 And 5}, pages = {335-344}, pmid = {11224077}, issn = {1473-5849}, abstract = {Rats were trained to discriminate the stimulus properties of the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.4mg/kg i.p.) versus saline, using a discriminated taste aversion procedure. Tests of stimulus generalization and drug substitution were conducted using two-bottle choice tests between saccharin and water. Rats that received pairings of 8-OH-DPAT with LiCl demonstrated significant reductions of saccharin preference when administered 8-OH-DPAT at doses of 0.1mg/kg or higher. 8-OH-DPAT did not alter saccharin preference significantly in controls that did not receive LiCl injections. Other drugs with high affinity for 5-HT(1A) receptors, such as the azapirones gepirone, ipsapirone and buspirone, produced selective reductions of saccharin preference in rats trained to discriminate 8-OH-DPAT from saline but not in controls. Three drugs with low affinity for 5-HT(1A) receptors, the benzodiazepine anxiolytic diazepam, d-amphetamine, and a common metabolite of the azapirones 1-(2-pyrimidinyl) piperazine (1-PP) altered fluid intake significantly but failed to produce significant changes in saccharin preference in either the discrimination or control groups. This study indicates that two-bottle preference tests can be used to measure the stimulus properties of 8-OH-DPAT trained using a discriminated taste aversion procedure, because the stimulus effects of drugs, measured using saccharin preference, can be separated from the nonspecific effects of drugs on fluid consumption.}, } @article {pmid11224076, year = {1991}, author = {Riley, AL and Kautz, MA and Geter, B and Smurthwaite, ST and Pournaghash, S and Melton, PM and Ferrari, CM}, title = {A demonstration of the graded nature of the generalization function of drug discrimination learning within the conditioned taste aversion procedure.}, journal = {Behavioural pharmacology}, volume = {2}, number = {4 And 5}, pages = {323-334}, pmid = {11224076}, issn = {1473-5849}, abstract = {Although control of discriminative performance will often generalize to different doses of the training drug or to drugs from the same class as the training drug, the nature of this generalization is unknown. Prior work has suggested that the generalization is primarily quantal in nature with animals displaying either vehicle-appropriate or drug-appropriate responding, depending upon their detection of the drug stimulus. It has been questioned whether this quantal nature of generalization reflects a characteristic response to drug stimuli or whether such responding is a function of the specific training and testing procedures used to establish and measure drug discrimination learning. The present paper evaluated this issue by analyzing the generalization functions of individual subjects trained and tested within one specific drug discrimination procedure, i.e. the conditioned taste aversion design. Responding within this design was generally graded. It is clear that quantal responding is not a necessary outcome of drug generalization assessments and that the nature of generalization in drug discrimination learning is a function of the specific procedure utilized in training and testing the discrimination. The results of the present analysis are discussed in terms of other recent work reporting graded functions.}, } @article {pmid11537313, year = {1989}, author = {Hunt, WA and Joseph, JA and Rabin, BM}, title = {Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {9}, number = {10}, pages = {333-336}, doi = {10.1016/0273-1177(89)90456-0}, pmid = {11537313}, issn = {0273-1177}, mesh = {Animals ; Avoidance Learning/*radiation effects ; Behavior, Animal/*radiation effects ; Caudate Nucleus/metabolism ; Dopamine/metabolism ; Dose-Response Relationship, Radiation ; *Heavy Ions ; Iron ; Male ; Motor Activity/radiation effects ; Muscarinic Agonists/pharmacology ; Oxotremorine/pharmacology ; Particle Accelerators ; Potassium/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine/*radiation effects ; *Solar Activity ; Taste/radiation effects ; }, abstract = {Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.}, } @article {pmid3824381, year = {1987}, author = {Dey, MS and Krieger, RI and Ritter, RC}, title = {Paraquat-induced, dose-dependent conditioned taste aversions and weight loss mediated by the area postrema.}, journal = {Toxicology and applied pharmacology}, volume = {87}, number = {2}, pages = {212-221}, doi = {10.1016/0041-008x(87)90283-3}, pmid = {3824381}, issn = {0041-008X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/*drug effects ; Dose-Response Relationship, Drug ; Feeding Behavior/drug effects ; Male ; Paraquat/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Time Factors ; }, abstract = {Paraquat's (PQ) effect on feeding behavior in the rat was examined using a conditioned taste aversion (CTA) paradigm. CTA is a learned avoidance of tastes closely associated with prior illness. Male Sprague-Dawley rats trained to drink an instant breakfast solution were subsequently offered a novel-flavored solution and consumption was measured over 30 min. Following consumption of the novel solution, PQ (0.48-48.0 mumol/kg) was injected subcutaneously. Peak blood PQ concentrations were measured by serially sampling blood (0.15 ml) from an indwelling jugular cannula between 10 and 35 min after injection. Two days later, the rats were offered the same novel-flavored solution. Paraquat produced dose-dependent avoidance of the novel solution when injected subcutaneously. A PQ dosage of 2.7 mumol/kg or less did not alter consumption. The ED50 for CTA production of 13.0 mumol/kg was determined by log-probit analysis. The minimum effective dosage was 4.2 micron/kg. The doses examined did not produce overt clinical or histological signs of toxicity. Peak blood paraquat concentration was linearly related (r = 0.995) to dosage. Additionally when administered by gavage CTAs occurred only with a much larger PQ dosage (480 mumol/kg). Thermal lesions of a hindbrain circumventricular organ, the area postrema (AP), prevented PQ-induced CTAs despite repeated PQ injections. Additionally, weight loss following PQ exposure was also attenuated by AP lesions. CTAs were induced in these same AP-lesioned rats by oral administration of copper sulfate. This substance conditions taste aversions by activating vagal afferent neurons. The fact that copper sulfate-induced aversions were not blocked by lesions of the area posterema indicates that the lesioned rats are capable of forming CTAs when treated with a toxicant which does not act via the AP. These data indicate that PQ produces CTAs in a dose-dependent manner. Furthermore, PQ-induced CTAs and weight loss are mediated by the AP. The AP may contain receptors which detect xenobiotics, enabling animals to avoid future contact with these compounds.}, } @article {pmid3815078, year = {1987}, author = {Yamamoto, T and Yuyama, N}, title = {On a neural mechanism for cortical processing of taste quality in the rat.}, journal = {Brain research}, volume = {400}, number = {2}, pages = {312-320}, doi = {10.1016/0006-8993(87)90630-5}, pmid = {3815078}, issn = {0006-8993}, mesh = {Animals ; Behavior, Animal ; Biomechanical Phenomena ; Cerebral Cortex/*physiology ; Chorda Tympani Nerve/physiology ; Electrophysiology ; Male ; Rats ; Rats, Inbred Strains ; Sodium Chloride ; Taste/*physiology ; }, abstract = {The responses of 31 chorda tympani fibers and 47 cortical neurons were recorded in response to 6 concentrations of NaCl, and single concentrations of sucrose, HCl, and quinine hydrochloride solutions applied to the anterior portion of the tongue in rats. The neural responses were analyzed in terms of the two hypotheses of quality coding: across-neuron response pattern and across-region response pattern notions. In a behavioral experiment, animals were given a conditioned taste aversion to one of 5 concentrations of NaCl solution by pairing it with a gastrointestinal illness caused by i.p. injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of drinking, which indicates the extent of generalization of aversion to each of the 4 basic taste stimuli. Among the two neural analyses employed for the chorda tympani and cortical units, across-region correlation coefficients for cortical neurons that were derived from the across-region response pattern theory showed the highest correlation (r = 0.89) with the behavioral suppression rates. Across-neuron correlation coefficients in the chorda tympani fibers also showed a good correlation (r = 0.81) with the behavioral data. However, the taste profile for 1.0 M NaCl in chorda tympani fibers was very similar to that for the lower concentrations of NaCl, in spite of the suggestion from the behavioral experiment and the neural analyses of cortical responses that 1.0 M NaCl has HCl and quinine components besides the NaCl component. The present result confirmed the idea that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons.}, } @article {pmid3828060, year = {1987}, author = {Sirota, P and Boland, FJ}, title = {A role for taste aversion learning in FLA-57 induced reductions of voluntary alcohol intake.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {4}, number = {1}, pages = {21-24}, doi = {10.1016/0741-8329(87)90055-3}, pmid = {3828060}, issn = {0741-8329}, mesh = {Alcohol Drinking/*drug effects ; Animals ; *Avoidance Learning ; Azepines/*pharmacology ; Brain/physiology ; *Conditioning, Classical ; Male ; Norepinephrine/physiology ; Rats ; Rats, Inbred Strains ; Saccharin ; *Taste ; }, abstract = {It has been proposed by Amit, Brown and colleagues that the reduction in voluntary alcohol intake observed after the administration of FLA-57 in rats can be attributed to decreased NE levels produced by FLA-57. Our studies investigated whether a conditioned taste aversion could better explain this phenomenon. In the key study, two groups of rats were injected with FLA-57 or Ringers before drinking alcohol for five days, while a third group was injected with FLA-57 before exposure to intragastrically intubated (untasted) alcohol in amounts identical to those in the tasted group. Results showed that only the FLA-57 group that tasted alcohol reduced subsequent voluntary alcohol intake. When a CTA was precluded, allowing only for an effect due to reduced NE, no reduction was observed. This suggests that FLA-57 reduces VAI, not via reduced NE levels, but by a conditioned taste aversion. A second study, utilizing saccharin instead of alcohol, generally supported this conclusion. While these results support a CTA explanation, it is possible that under other conditions FLA-57 might produce a central pharmacological effect.}, } @article {pmid3823162, year = {1986}, author = {Bermúdez-Rattoni, F and Grijalva, CV and Kiefer, SW and Garcia, J}, title = {Flavor-illness aversions: the role of the amygdala in the acquisition of taste-potentiated odor aversions.}, journal = {Physiology & behavior}, volume = {38}, number = {4}, pages = {503-508}, doi = {10.1016/0031-9384(86)90417-8}, pmid = {3823162}, issn = {0031-9384}, support = {HO5958/HO/NHLBI NIH HHS/United States ; NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/drug effects/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Male ; *Odorants ; Procaine/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {In the present experiments the role of the amygdaloid complex and its specific nuclei were tested in the conditioning of taste potentiated odor aversions. In the first experiment two groups of rats were given either large electrolytic lesions in the amygdala (AMX) or sham operations (SH). Postoperatively, these rats were trained to avoid either a taste, an odor, or a taste-odor compound using LiCl illness. Subsequent tests with odor and taste alone showed that the SH group developed strong taste and odor aversions; however, the AMX group failed to display either an odor or taste aversion. In the second experiment, another four groups of rats received either lesions in the medial and basomedial nuclei (M), central nuclei (C), lateral and basolateral (L), or sham operations (SH). The results from postoperative conditioning showed that all groups had strong taste and odor aversions, except group L which displayed a significant disruption of odor aversion learning. In conclusion, these data indicate that the amygdala is involved in the acquisition of taste, odor and potentiated odor aversions learning. Moreover, it is demonstrated that the lateral and/or basolateral nuclei are particularly involved in the development of potentiated odor aversions learning.}, } @article {pmid3954875, year = {1986}, author = {Elkins, RL}, title = {Separation of taste-aversion-prone and taste-aversion-resistant rats through selective breeding: implications for individual differences in conditionability and aversion-therapy alcoholism treatment.}, journal = {Behavioral neuroscience}, volume = {100}, number = {1}, pages = {121-124}, doi = {10.1037//0735-7044.100.1.121}, pmid = {3954875}, issn = {0735-7044}, support = {1 R01 AA06465-01/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholism/genetics/*therapy ; Animals ; *Avoidance Learning ; Crosses, Genetic ; Female ; *Individuality ; Male ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {Both rats and alcoholic humans display considerable variability in acquisition of illness-induced consummatory aversions. Differential conditionability may be a significant modulator of outcome in alcoholics who elect taste aversion (TA) approaches to abstinence facilitation. This is a report of the ongoing development of rat strains suitable for studies of biological bases of individual differences in TA conditionability. Sprague-Dawley-derived rats have been selectively bred over seven generations as strong or weak learners of a cyclophosphamide-induced saccharin aversion. Efficiency of aversion acquisition is a selectable propensity, as indicated by progressively divergent strain separation that attained significance in the second selected generation. Subjects have also been studied with respect to shock-motivated environmental avoidance (SMEA), but efficiency of SMEA performance has not been a selection factor. Results have produced an unexpected trend across generations indicative of a within-strain reversal of TA and SMEA learning efficiency. Continuation of this reversal in subsequent generations could have important implications for studies of genetic contributions to different learning capacities and for the selection of biologically appropriate noxious stimuli for aversive therapy treatments of various target problems.}, } @article {pmid3941594, year = {1986}, author = {Mucha, RF and Herz, A}, title = {Preference conditioning produced by opioid active and inactive isomers of levorphanol and morphine in rat.}, journal = {Life sciences}, volume = {38}, number = {3}, pages = {241-249}, doi = {10.1016/0024-3205(86)90309-7}, pmid = {3941594}, issn = {0024-3205}, mesh = {Animals ; Dextrorphan/*pharmacology ; Food Preferences/*drug effects ; Isomerism ; Levorphanol/*pharmacology ; Male ; Morphinans/*pharmacology ; Morphine/*pharmacology ; Motivation/drug effects ; Rats ; Rats, Inbred Strains ; Spatial Behavior/*drug effects ; Structure-Activity Relationship ; }, abstract = {Using taste and place preference conditioning, the present study examined the motivational properties produced in adult rats by systemic administration of (-) and (+) morphine, levorphanol, and dextrorphan. Conditioned place preference was stereospecific; it was only produced by the opioid receptor active isomers, levorphanol and (-) morphine. Similarly, a conditioned taste preference produced by a low dose of morphine was only seen with the active isomer. Conditioned taste aversion, however, was produced in a comparable dose range by both the active and the inactive isomers. In addition injections of inactive isomers also produced tolerance to the taste aversion produced by (-) morphine. Therefore, administration of both opioid active and inactive isomers of opioid agonists are unconditioned stimuli for the production of preference behaviors. In addition, it was concluded that the appetitive reinforcing properties of these drugs, seen as taste and place preferences, appear to require activation of specific opioid receptors, whereas the aversive effects, seen as taste aversion may also involve other mechanisms.}, } @article {pmid3964438, year = {1986}, author = {Di Lorenzo, PM and Kiefer, SW and Rice, AG and Garcia, J}, title = {Neural and behavioral responsivity to ethyl alcohol as a tastant.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {3}, number = {1}, pages = {55-61}, doi = {10.1016/0741-8329(86)90071-6}, pmid = {3964438}, issn = {0741-8329}, support = {AA03513/AA/NIAAA NIH HHS/United States ; HD05958/HD/NICHD NIH HHS/United States ; NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Ethanol/*pharmacology ; Generalization, Stimulus ; Male ; Nervous System/*drug effects ; Quinine/pharmacology ; Rats ; Rats, Inbred Strains ; Sodium Chloride/pharmacology ; Taste/*drug effects ; }, abstract = {Three experiments were designed to study the sensory properties of ethyl alcohol (EtOH) in the rat. In Experiment 1, a conditioned taste aversion (CTA) was produced to 3%, 6% or 9% EtOH. None of these aversions generalized to any of the 4 basic tastants. However, rats in the 6% and 9% EtOH groups did generalize the CTA to a mixture of sucrose-QHCl but not to a mixture of NaCl-HCl. In Experiment 2, a CTA was produced to 6% EtOH and animals were then tested with all 6 combinations of the basic tastants. The CTA was found to generalize significantly to sucrose-QHCl and marginally to sucrose-HCl. In Experiment 3, single unit responses to gustatory stimuli were recorded in the nucleus of the tractus solitarius. Solutions of NaCl, HCl, sucrose, QHCl, 6% and 9% EtOH were bathed over the rostral tongue through a plastic flow chamber. Approximately half of the units responded to 9% EtOH. Analysis of the across-unit patterns of response revealed a weak relationship between responses to EtOh and sucrose in the first 1.0 sec of response.}, } @article {pmid3951679, year = {1986}, author = {Aragon, CM and Abitbol, M and Amit, Z}, title = {Acetaldehyde may mediate reinforcement and aversion produced by ethanol. An examination using a conditioned taste-aversion paradigm.}, journal = {Neuropharmacology}, volume = {25}, number = {1}, pages = {79-83}, doi = {10.1016/0028-3908(86)90062-6}, pmid = {3951679}, issn = {0028-3908}, mesh = {Acetaldehyde/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cues ; Ethanol/*pharmacology ; Male ; Rats ; Saccharin/*pharmacology ; Taste/*drug effects ; }, abstract = {Groups of water-deprived rats were exposed to acetaldehyde, ethanol or vehicle control. On the conditioning day, the animals were first presented with a solution of saccharin after which the animals that were exposed to acetaldehyde received ethanol and those exposed to ethanol received acetaldehyde. Saccharin was again presented on three more occasions (testing days) without injection of drug. Using the percentage change in saccharin consumed from the first presentation as a measure of aversion, it was found that exposure to acetaldehyde blocked the taste aversion conditioned by ethanol. Animals exposed to ethanol showed no aversion to the saccharin which was paired with a small dose of acetaldehyde, indicating a symmetrical relationship between ethanol and acetaldehyde at this dose. However, exposure with ethanol did not block the aversion produced by conditioning with larger doses of acetaldehyde. These results suggest that the mechanism underlying the smaller dose of the taste aversion conditioned with acetaldehyde may be central while the mechanism underlying the larger dose is probably peripheral.}, } @article {pmid3945668, year = {1986}, author = {Mackey, WB and Keller, J and van der Kooy, D}, title = {Visceral cortex lesions block conditioned taste aversions induced by morphine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {24}, number = {1}, pages = {71-78}, doi = {10.1016/0091-3057(86)90047-x}, pmid = {3945668}, issn = {0091-3057}, mesh = {Animals ; Cerebral Cortex/anatomy & histology/*drug effects ; Conditioning, Operant/*drug effects ; Ibotenic Acid/pharmacology ; Lithium/pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Reinforcement, Psychology ; Taste/*drug effects ; }, abstract = {Rats with bilateral ibotenic acid or sham lesions of the visceral (agranular insular) cortex were tested for a conditioned taste aversion (CTA) to saccharin after five pairings of morphine sulphate injections (15 mg/kg IP) with consumption of a novel solution (0.1% saccharin). Lesioned animals demonstrated no evidence of the morphine-induced CTA that was seen in the sham operated animals. A third group of rats received ibotenic acid lesions but had saccharin consumption paired with saline vehicle injections. This group had the normal preference (seen in naive rats) for saccharin on testing, showing that the visceral cortex lesion had no effect on the ability of the rats to discriminate saccharin from water. In order to test if visceral cortex lesions abolish specifically the CTA induced by morphine, we ran a similar set of CTA experiments using two new novel flavours and either 15 or 75 mg/kg IP lithium chloride (LiCl) as the unconditioned stimuli. Dose dependent CTA's to the LiCl were established in all groups indicating that the visceral cortex plays no role in mediating the aversive effect of LiCl. Using the condition place preference paradigm we investigated the role of the visceral cortex in the expression of morphine's rewarding aspects. Identical place preferences were found in groups of rats with or without visceral cortex lesions suggesting that this cortical region plays no role in either the perception of morphine's rewarding effects or the association of morphine's rewarding properties with sensory stimuli. Visceral cortex lesions also had no effect on the establishment of a conditioned place aversion to a high dose of LiCl (75 mg/kg IP). Thus, visceral cortex appears critical for the establishment of a morphine-induced CTA, but is not crucial for mediating gross taste discrimination, the aversive aspects of LiCl nor the rewarding properties of morphine.}, } @article {pmid3810078, year = {1986}, author = {Archer, T and Mohammed, AK and Järbe, TU}, title = {Context-dependent latent inhibition in taste aversion learning.}, journal = {Scandinavian journal of psychology}, volume = {27}, number = {3}, pages = {277-284}, doi = {10.1111/j.1467-9450.1986.tb01205.x}, pmid = {3810078}, issn = {0036-5564}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; *Inhibition, Psychological ; Male ; Rats ; Rats, Inbred Strains ; *Taste ; }, } @article {pmid4092889, year = {1985}, author = {Bignami, G and Giardini, V and Scorrano, M}, title = {Behaviorally augmented versus other components in organophosphate tolerance: the role of reinforcement and response factors.}, journal = {Fundamental and applied toxicology : official journal of the Society of Toxicology}, volume = {5}, number = {6 Pt 2}, pages = {S213-24}, doi = {10.1016/0272-0590(85)90131-9}, pmid = {4092889}, issn = {0272-0590}, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Body Weight/drug effects ; Drug Tolerance ; Male ; Organophosphorus Compounds/*toxicity ; Paraoxon/toxicity ; Rats ; Rats, Inbred Strains ; Reinforcement, Psychology ; Taste/drug effects ; Time Factors ; }, abstract = {Male Wistar-derived rats were used to assess the behaviorally augmented component of tolerance to paraoxon depression of a feeding response. Separate groups of animals were treated daily by 0.125 mg/kg of the compound given sc either 1 hr before the start or 45 min after the end of a 90-min feeding session. However, the dose was reduced to 0.0625 mg/kg from Day 9 to Day 12 of the treatment series if animals showed too severe a reduction in food consumption. After development of tolerance by the presession treatment group, the animals treated after feeding were shifted to treatment before feeding. This shift produced a marked depression in food consumption. This confirms similar data previously obtained by a different test (two-way avoidance), and indicates that behaviorally augmented tolerance to paraoxon related to practice factors may be a fairly general phenomenon. Other experiments were to assess the effects of paraoxon in the conditioned taste aversion (CTA) paradigm. These showed the development of an aversion only at high dosage levels (two pairings between the flavor cue and 0.25 mg/kg sc, or four pairings with a 0.17-mg/kg dose). However, the failure of lower doses to produce CTA may have depended on the relatively slow onset of the intoxication, producing an extended interval between the end of cue exposure and the development of malaise or illness. Two pretreatments given 6 and 3 days before the first conditioning session in an experiment using the 2 X 0.25-mg/kg schedule did not affect the development of CTA as measured by a conventional double-bottle test. However, a typical interference effect produced by prior exposure was shown by a substantial acceleration of subsequent CTA extinction in pretreated animals.}, } @article {pmid4084182, year = {1985}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Intragastric copper sulfate produces a more reliable conditioned taste aversion in vagotomized rats than in intact rats.}, journal = {Behavioral and neural biology}, volume = {44}, number = {3}, pages = {364-373}, doi = {10.1016/s0163-1047(85)90664-8}, pmid = {4084182}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical ; Copper/*pharmacology ; Copper Sulfate ; Gastric Emptying ; Male ; Rats ; Rats, Inbred Strains ; Stomach/*drug effects ; Taste/*physiology ; Vagotomy ; Vagus Nerve/*physiology ; }, abstract = {Although copper sulfate is an emetic stimulus, preliminary experiments failed to obtain a taste aversion in intact rats following intragastric administration as had been previously reported in the literature. Several experiments were therefore run to further investigate the capacity of intragastric copper sulfate to function as an unconditioned stimulus for taste aversion learning and the role of the vagus in mediating that learning. The results of the first series of experiments showed that intragastric administration of copper sulfate (5 mg/kg X 5H2O) was more effective in reliably producing a taste aversion in vagotomized rats than in sham-operated control rats. The second experiment examined the effects of area postrema lesions on the acquisition of a taste aversion produced by intragastrically administered copper sulfate in vagotomized rats. The results indicated that the taste aversion observed following treatment with intragastric copper sulfate in vagotomized rats could be prevented by lesions of the area postrema. The present results indicate that intragastric administration of copper sulfate is a more reliable unconditioned stimulus for taste aversion learning in vagotomized rats than in intact rats. It is not certain what factors might account for the discrepant results between the present experiments and previously published research.}, } @article {pmid3909169, year = {1985}, author = {Stolerman, IP}, title = {Motivational effects of opioids: evidence on the role of endorphins in mediating reward or aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {23}, number = {5}, pages = {877-881}, doi = {10.1016/0091-3057(85)90086-3}, pmid = {3909169}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Operant/drug effects ; Endorphins/*pharmacology/*physiology ; Morphine/pharmacology ; Motivation/*drug effects ; Naloxone/pharmacology ; *Reinforcement, Psychology ; *Reward ; Taste/drug effects ; }, abstract = {It has been suggested that endogenous peptides with opiate-like effects may contribute to the mediation of reward or aversion. One line of evidence relating to these hypotheses derives from studies of the motivational effects of opioids. The ability of opioid agonists and antagonists to serve as positively reinforcing or aversive stimuli is reviewed, with results compared across several different behavioural procedures. The results for rewarding effects are consistent and independent of procedure: in self-administration, conditioned place preference and conditioned taste preference studies, opioid agonists are consistently effective whereas antagonists are inactive. Results for indices of aversive effects are more difficult to interpret because they are, to some extent, dependent on the procedure used. Neither agonists nor antagonists seem able to support operant escape/avoidance conditioning. Agonists can support taste aversion and place aversion conditioning to some extent, whereas antagonists are clearly active in both procedures. The results provide some support for the involvement of enkephalins or endorphins in reward and aversion, but there are significant gaps and contradictions in the evidence.}, } @article {pmid4080251, year = {1985}, author = {Ng Cheong Ton, JM and Amit, Z}, title = {Acetaldehyde and morphine interaction in the preexposure conditioned taste aversion paradigm in the rat.}, journal = {Neuroscience letters}, volume = {61}, number = {1-2}, pages = {131-134}, doi = {10.1016/0304-3940(85)90413-6}, pmid = {4080251}, issn = {0304-3940}, mesh = {Acetaldehyde/*administration & dosage ; Animals ; Avoidance Learning/*drug effects ; Drug Interactions ; Ethanol/pharmacology ; Male ; Morphine/*administration & dosage ; Rats ; Rats, Inbred Strains ; Reward ; Saccharin ; Taste/*drug effects ; }, abstract = {The interaction between acetaldehyde, the primary metabolite of ethanol, and morphine was examined in the preexposure conditioned taste aversion (CTA) paradigm. Rats that were preexposed to acetaldehyde did not display a CTA to morphine. While acetaldehyde at the dose tested did not induce a strong CTA, morphine preexposure, however, reversed the decrease in saccharin associated with acetaldehyde injection thus reflecting a symmetrical interaction between acetaldehyde and morphine. Implications for a mechanism of ethanol-opiates interaction are discussed.}, } @article {pmid4091954, year = {1985}, author = {Bluthé, RM and Dantzer, R and Le Moal, M}, title = {Peripheral injections of vasopressin control behavior by way of interoceptive signals for hypertension.}, journal = {Behavioural brain research}, volume = {18}, number = {1}, pages = {31-39}, doi = {10.1016/0166-4328(85)90166-4}, pmid = {4091954}, issn = {0166-4328}, mesh = {Angiotensin II/pharmacology ; Animals ; Apomorphine/pharmacology ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/*drug effects ; Conditioning, Psychological/drug effects/physiology ; Dose-Response Relationship, Drug ; Hypertension/*physiopathology ; Injections, Subcutaneous ; Male ; Rats ; Rats, Inbred Strains ; Sensory Receptor Cells/drug effects/*physiology ; Taste/drug effects/physiology ; Vasopressins/*administration & dosage/pharmacology ; }, abstract = {The stimulus properties of peripheral injections of vasopressin were assessed using conditioned taste aversion techniques. Conditioned taste aversion induced by vasopressin was blocked by prior exposure to vasopressin but not to another aversive agent, apomorphine. Prior exposure to behaviorally equivalent doses of another hypertensive agent, angiotensin II, blocked also conditioned taste aversion induced by vasopressin and this effect was fully reciprocal, since prior exposure to AVP blocked the aversive effect of angiotensin II. The protection offered by prior exposure to angiotensin II was not due to an endogenous release of AVP since the aversive properties of angiotensin II were not blocked by administration of a specific antagonist of the vasopressor effects of vasopressin. These data suggest that the interoceptive cues which are responsible for the conditioned taste aversion induced by vasopressin are related to the hypertensive action of this peptide.}, } @article {pmid4070333, year = {1985}, author = {Bellinger, LL and Mendel, VE}, title = {The effect of intracerebroventricularly infused satietin on conditioned taste aversion and feeding in rats fasted different lengths.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {23}, number = {4}, pages = {559-566}, doi = {10.1016/0091-3057(85)90419-8}, pmid = {4070333}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Conditioning, Operant/*drug effects ; Drinking/drug effects ; Eating/drug effects ; Fasting ; Glycopeptides/administration & dosage/*pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Time Factors ; }, abstract = {Satietin is a glycoprotein (50,000-70,000 daltons MW) found in human serum (greater than 2 micrograms/ml) that is reported to be a strong anorexigenic agent when infused (10-100 micrograms/rat) intracerebroventricularly (ICV) into rats. The initial three experiments presented here explored whether satietin suppresses food intake by making the animals ill or causing them to experience malaise. A two-bottle taste aversion paradigm was used for this testing. In all experiments the rats were fitted with chronic third ventricle cannulas. After recovery from surgery the rats were trained for at least 6 days to drink their water in one hour a day, 1100-1200-hr (LD12:12-hr, lights out 12:00-hr). In Experiment 1 and 3 satietin (100 or 25 micrograms/rat) or vehicle was infused ICV 30 minutes prior to exposure to a novel neutral preference fluid flavor (banana or almond flavoring in water). Three days later the rats were given a choice of the two flavors to consume; this was repeated the next day. In both experiments satietin treated rats showed strong aversion to the flavor paired with satietin infusion, while saline infused controls showed no aversion. A similar paradigm was used during the second experiment, except satietin or vehicle infusion was paired with a highly preferred saccharin-water solution. Three days later the rats were given a choice between water and the saccharin-water solution. The satietin (50 micrograms/rat) treated rats exhibited a marked aversion to the saccharin-water solution. These data suggest that satietin may be an aversive substance.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid4070328, year = {1985}, author = {White, BC and Mason, FD}, title = {Caffeine-induced taste aversion and mimetic responses.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {23}, number = {4}, pages = {515-518}, doi = {10.1016/0091-3057(85)90411-3}, pmid = {4070328}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Caffeine/*pharmacology ; Female ; Motor Activity/drug effects ; Rats ; Taste/*drug effects ; Time Factors ; }, abstract = {Novel tastes preceded a range of caffeine doses (10-80 mg/kg) in a taste aversion training trial. One week later rats which had doses of 30 mg or higher showed strong aversions as measured by a single bottle consumption test. The 10 and 20 mg dose produced the most hyperactivity and apparently enhanced intake of the taste paired with caffeine. During the training trial, rats receiving the 80 mg dose exhibited copious gapes and chin-rubs, mimetic responses to noxious tastes. Gapes also occurred in these subjects during the aversion test. Consumption was more sensitive than mimetic responding as a measure of the aversive effects of caffeine. Only the 80 mg dose produced neophobia. Tests with isotonic injections indicated that tonicity was not the source of the aversions.}, } @article {pmid4080064, year = {1985}, author = {Liu, WF and Beaton, JM}, title = {The neurobehavioral effects of pralidoxime mesylate in the rat.}, journal = {Neurobehavioral toxicology and teratology}, volume = {7}, number = {5}, pages = {449-452}, pmid = {4080064}, issn = {0275-1380}, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Conditioning, Operant/drug effects ; Male ; Motor Activity/drug effects ; Nervous System/*drug effects ; Pralidoxime Compounds/*pharmacology/toxicity ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; }, abstract = {The neurobehavioral effects of pralidoxime mesylate (P2S) were characterized in the rat by comparing standard measures such as conditioned taste aversion, operant behavior and spontaneous locomotor activity. Male albino Sprague-Dawley rats were injected IP with either saline, 25, 50, or 100 mg/kg of P2S. None of these doses produced any overt toxic effects. P2S produced a conditioned taste aversion at the highest dose (100 mg/kg) using a single conditioning trial with sucrose in a one-bottle test. Acute administration of 100 mg/kg did not disrupt fixed ratio responding on a water reinforced schedule. All three doses, 25, 50, and 100 mg/kg, decreased spontaneous locomotor activity in a dose-dependent manner. The results of these studies support the findings that a single injection of P2S at the therapeutic levels would not disrupt the normal working performance in man.}, } @article {pmid4065427, year = {1985}, author = {Melcer, T and Alberts, JR and Gubernick, DJ}, title = {Early weaning does not accelerate the expression of nursing-related taste aversions.}, journal = {Developmental psychobiology}, volume = {18}, number = {5}, pages = {375-381}, doi = {10.1002/dev.420180503}, pmid = {4065427}, issn = {0012-1630}, support = {MH-00222/MH/NIMH NIH HHS/United States ; MH-28355/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Female ; *Food Preferences ; Lactation ; *Milk ; Pregnancy ; Rats ; Rats, Inbred Strains ; Taste ; *Weaning ; }, abstract = {Preweanling rat pups do not display an aversion to a flavor conditioned stimulus (CS) paired with illness if the CS is presented during the act of suckling. In contrast, 20-day-old pups do form such a conditioned taste aversion while suckling (Martin & Alberts, 1979). The dissolution of the nursing-related "blockade" of toxiphobia correlates with the onset of solid food intake. Moreover, prevention of weaning prolongs the blockade; ingestive experience with solid food is necessary for the expression of nursing-related taste aversions in 26-day-old "food naive" pups (Gubernick & Alberts, 1984). The present experiments tested the possibility that premature weaning to solid food might accelerate the onset of nursing-related toxiphobia. Pups were weaned at 13 days of age and ingested only food and water. These prematurely weaned pups received taste aversion conditioning while suckling on Day 16, but showed no aversion to the CS flavor during a later food test. Thus, conditions that lead to early weaning (ingestion of solid food) do not accelerate the onset of taste aversions to mother's milk.}, } @article {pmid4048231, year = {1985}, author = {Goudie, AJ}, title = {Comparative effects of cathinone and amphetamine on fixed-interval operant responding: a rate-dependency analysis.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {23}, number = {3}, pages = {355-365}, doi = {10.1016/0091-3057(85)90006-1}, pmid = {4048231}, issn = {0091-3057}, mesh = {Alkaloids/*pharmacology ; Amphetamine/*pharmacology ; Animals ; Conditioning, Operant/*drug effects ; Dextroamphetamine/pharmacology ; Dose-Response Relationship, Drug ; Male ; Rats ; Reinforcement Schedule ; Taste/drug effects ; Time Factors ; }, abstract = {The actions of dl-cathinone and d-amphetamine on operant responding were compared in rats. The effects of both drugs were predominantly suppressive on behaviour maintained by a Fixed Interval 2 minutes schedule of reward. Both drugs had equivalent durations of action in suppressing responding. The actions of the two compounds could be described as rate-dependent, although their rate-dependent actions could most parsimoniously be attributed to drug-induced rate constancy. Methysergide (10 mg/kg) had no significant differential effect on the response suppressant effects of the two compounds, even though in vitro studies have indicated that cathinone and amphetamine differ in their serotonin receptor affinity. The actions of cathinone were qualitatively similar to those of amphetamine in this behavioural test. Furthermore the observed potency ratio for dl-cathinone to d-amphetamine (1:3) was similar to that reported elsewhere in a range of other behavioural tests (anorexia, adipsia, drug-induced rotation, lethality) for this pair of isomers. The only major difference reported to date between the behavioural actions of cathinone and amphetamine relates to the unexpectedly weak potency of cathinone in the conditioned taste aversion procedure. Cathinone, the major active constituent of the Khat plant, is therefore a psychostimulant drug which may possess potent reinforcing properties by virtue of its amphetamine-like stimulant actions coupled with its very weak aversive properties.}, } @article {pmid4048227, year = {1985}, author = {Kolakowska, L and Larue-Achagiotis, C and Le Magnen, J}, title = {Effect of amygdaloid lesions on ethanol intake in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {23}, number = {3}, pages = {333-338}, doi = {10.1016/0091-3057(85)90002-4}, pmid = {4048227}, issn = {0091-3057}, mesh = {*Alcohol Drinking ; Amygdala/anatomy & histology/*physiology ; Animals ; Male ; Rats ; Rats, Inbred Strains ; Time Factors ; }, abstract = {The effect of electrolytic lesions of the amygdala on ethanol intake in ethanol naïve rats has been studied. Rats with basolateral nuclei and lateral nuclei lesions showed a reduced neophobic response to an ethanol solution. However, the ethanol intake was too small in normal and lesioned rats to augment aversion through conditioning. Oral intake of ethanol supplemented by intraperitoneal ethanol injection to reach 2 g/kg indeed enhanced the initial sensory aversion to ethanol. This induced aversion was attenuated after basolateral lesions. An initial aversion to a mixed ethanol-sucrose solution was abolished after basolateral lesions, while the lateral lesions induced an initial preference for this solution. The initial oral intake of ethanol-sucrose in normal rats was again too small to induce the conditioned taste aversion (C.T.A.). Despite the high oral intake of this solution, rats with basolateral lesions did not show a conditioned aversion while laterally lesioned rats exhibited a strong conditioned aversion to the ethanol-sucrose mixture. The results which confirm the suppression of the C.T.A. by basolateral amygdala lesions are discussed in relation to the role of toxicophobia in ethanol intake by rats.}, } @article {pmid4070397, year = {1985}, author = {Lasiter, PS and Deems, DA and Oetting, RL and Garcia, J}, title = {Taste discriminations in rats lacking anterior insular gustatory neocortex.}, journal = {Physiology & behavior}, volume = {35}, number = {2}, pages = {277-285}, doi = {10.1016/0031-9384(85)90350-6}, pmid = {4070397}, issn = {0031-9384}, support = {R01-11618//PHS HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Conditioning, Psychological ; Discrimination, Psychological/*physiology ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {Previous neurobehavioral investigations have demonstrated that the anterior insular gustatory neocortex (AIGN) mediates taste-illness learning. The present experiment evaluated taste discriminations in rats lacking AIGN. Two groups of rats received distinct surgical treatments. One-half of the animals received bilateral electrolytic lesion placements in the AIGN: Remaining animals received anesthesia and scalp incisions only. Following postoperative recovery animals received standard two-bottle preference tests with various concentrations of sucrose to evaluate gustatory reactivity. Animals thereafter received two-bottle discrimination tests with selected sucrose concentrations. At the conclusion of preference tests and discrimination tests with sucrose, preference tests and discrimination tests were conducted with sodium chloride. Following those tests animals received taste aversion conditioning to determine whether or not AIGN lesions impaired taste-illness learning. Results of two-bottle taste tests indicated that AIGN lesions do not obviously alter taste reactivity nor taste discriminations to preferred concentrations of sucrose and NaCl. Anterior insular lesions did, however, impair normal taste aversion learning. These results, in combination with those of previous investigators, provide further evidence that the AIGN preferentially contributes to taste learning functions.}, } @article {pmid3834924, year = {1985}, author = {Hunt, T and Spivak, K and Amit, Z}, title = {Further evaluation of morphine aversion: maintenance of a taste aversion using a low, nonaversive morphine dose.}, journal = {Behavioral and neural biology}, volume = {44}, number = {1}, pages = {74-79}, doi = {10.1016/s0163-1047(85)91196-3}, pmid = {3834924}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Dose-Response Relationship, Drug ; Generalization, Stimulus/drug effects ; Male ; Morphine/*administration & dosage ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Time Factors ; }, abstract = {Previously, in an investigation of morphine-conditioned taste aversion (CTA), we found that limited preexposure to a low, nonaversive (non-CTA-inducing) dose of morphine (2.5 mg/kg) was as effective as preexposure to a higher, CTA-inducing dose (15 mg/kg) in blocking the formation of a subsequent morphine CTA. In the present study, we examined the capacity of this low, 2.5-mg/kg morphine dose to maintain a CTA initially induced by the 15-mg/kg dose. A standard CTA procedure was used. Results indicated that rats given three initial taste-drug pairings with 15 mg/kg morphine followed on subsequent pairing days by treatment with the low, non-CTA-inducing, 2.5-mg/kg dose continued to exhibit a strong CTA over 8 pairing days. A similar pattern was observed for animals continuing to receive taste-drug pairings with the 15-mg/kg dose. Animals receiving only one taste-drug pairing with the 15-mg/kg dose, followed on subsequent pairing days by 2.5-mg/kg conditioning, failed to show such a pattern of CTA. An intermediate CTA pattern was seen with animals conditioned with 15, 10, 5, and repeated 2.5-mg/kg doses over consecutive pairing days. These data suggest that exposure to a low dose of morphine, with no apparent CTA-inducing properties, is sufficient to maintain a previously established morphine taste aversion. Potential implications for understanding the apparent discriminative complexity of morphine's motivational properties are discussed.}, } @article {pmid3834923, year = {1985}, author = {Hunt, T and Spivak, K and Amit, Z}, title = {Aversive stimulus properties of morphine: evaluation using the drug preexposure conditioned taste aversion paradigm.}, journal = {Behavioral and neural biology}, volume = {44}, number = {1}, pages = {60-73}, doi = {10.1016/s0163-1047(85)91181-1}, pmid = {3834923}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Discrimination Learning/drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Generalization, Stimulus/drug effects ; Male ; Morphine/*administration & dosage/pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Taste/*drug effects ; Time Factors ; }, abstract = {Interpretation of the finding that positive-reinforcing drugs such as morphine also possess possible aversive properties, as revealed by their ability to induce a conditioned taste aversion (CTA), remains problematic. This issue was addressed in the present study using the drug preexposure CTA paradigm. Water-deprived rats were given noncontingent preexposure to one of three doses of morphine (2.5, 5.0, or 15.0 mg/kg) or drug vehicle. Subsequently, animals in each of these preexposure groups were presented with a novel 0.1% saccharin-flavored solution followed immediately by injection with one of the same three morphine doses or drug vehicle. This procedure was repeated at 5-day intervals until six saccharin presentations had been performed. Results indicated that while the three morphine doses were differentially potent as taste aversion-conditioning agents, they were equipotent as preexposure agents serving to disrupt CTA. These data suggest that preexposure to morphine's predominantly positive-reinforcing (and non-CTA-inducing) properties is sufficient for preexposure disruption of subsequent morphine CTA. A second experiment indicated that the minimal effective preexposure dose is between 0.3 and 1.25 mg/kg of morphine. It is suggested that an important commonality may exist between the discriminative stimulus properties of morphine as a CTA-inducing agent and as a positive reinforcer.}, } @article {pmid3924347, year = {1985}, author = {Tam, FW and Chen, C and Alpert, JE and Iversen, SD}, title = {Aversive effects of subcutaneously injected vasopressin in the rat: independence of the ascending dorsal noradrenergic bundle.}, journal = {Brain research}, volume = {337}, number = {1}, pages = {133-137}, doi = {10.1016/0006-8993(85)91617-8}, pmid = {3924347}, issn = {0006-8993}, mesh = {Animals ; Arginine Vasopressin/administration & dosage/*pharmacology ; Avoidance Learning/*drug effects ; Brain Chemistry/drug effects ; Conditioning, Classical/drug effects ; Hydroxydopamines/pharmacology ; Injections, Subcutaneous ; Male ; Norepinephrine/*physiology ; Oxidopamine ; Rats ; Rats, Inbred Strains ; *Taste/physiology ; }, abstract = {The unconditioned stimulus properties of subcutaneously administered arginine vasopressin (AVP) were examined using place and taste conditioning paradigms. Evidence for an aversive effect of the peptide was found, in general agreement with a previous report, although a high dose of AVP (10 micrograms) was required. Also investigated was the possible role of the dorsal noradrenergic bundle (DNAB) in conditioned taste aversion established by AVP. Although the DNAB has been proposed as one of the central pathways through which AVP exerts a facilitatory effect on conditioned behaviour, destruction of this pontine-forebrain projection with 6-hydroxydopamine did not appear to alter the aversiveness of the drug in the present study. These results replicate the finding that AVP can serve as an aversive stimulus but also indicate that the aversive properties of the peptide may prove to be dissociable from its ability to enhance the retention of learned behaviour.}, } @article {pmid4009224, year = {1985}, author = {Yamamoto, T and Yuyama, N and Kato, T and Kawamura, Y}, title = {Gustatory responses of cortical neurons in rats. III. Neural and behavioral measures compared.}, journal = {Journal of neurophysiology}, volume = {53}, number = {6}, pages = {1370-1386}, doi = {10.1152/jn.1985.53.6.1370}, pmid = {4009224}, issn = {0022-3077}, mesh = {Animals ; Behavior, Animal/*physiology ; Cerebral Cortex/cytology/*physiology ; Electrophysiology ; Male ; Neurons/physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {The responses of 39 cortical neurons to 13 kinds of taste stimuli including the four putative basic taste solutions (sucrose, NaCl, HCl, and quinine HCl) applied to the anterior portion of the tongue were recorded extracellularly in lightly anesthetized rats. The neural responses were analyzed in terms of the four hypotheses of quality coding: across-neuron response pattern, labeled-line, matrix pattern, and across-region response pattern notions. Animals were given a conditioned taste aversion to one of the 11 stimuli by pairing it with a gastrointestinal illness caused by intraperitoneal injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of rate of drinking, which indicates the extent of generalization of aversion to each of the four basic taste stimuli. Neural taste profiles of each taste stimulus, which indicate the relation of the taste of a stimulus to each taste of the four basic stimuli, differed more or less depending on the kind of quality-coding notions employed. Among the four analyses, across-region correlation coefficients that were derived from an across-region response-pattern theory showed the highest correlation with the behavioral suppression rates. Therefore we conclude that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons. Fluid intake per day of each of the 12 taste solutions was measured by the single-bottle preference method. When the amount of intake was described in terms of an hedonic index (HI), which indicates the hedonic aspect of the taste of each solution, HI's for sucrose, NaCl, HCl, and quinine were 1.17, 0.43, -0.49, and -0.89, respectively. These values represent the degree of deviation of solution intake above (i.e., preferable) or below (aversive) the standard water intake. Then, HI's were calculated for each of the 12 taste stimuli based on the neural taste profiles and actual HI's for each of the four basic taste stimuli. The correlations between the calculated and the actual (or behaviorally obtained) HI's were very high (ranging from 0.832 to 0.941). This result suggests that the hedonic dimension of taste can be matched well by any one of the four proposed hypotheses.}, } @article {pmid3843722, year = {1985}, author = {Lasiter, PS and Deems, DA and Glanzman, DL}, title = {Thalamocortical relations in taste aversion learning: I. Involvement of gustatory thalamocortical projections in taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {99}, number = {3}, pages = {454-476}, doi = {10.1037//0735-7044.99.3.454}, pmid = {3843722}, issn = {0735-7044}, support = {NS-11618/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Cortex/*physiology ; Corpus Striatum/physiology ; Male ; Olfactory Bulb/physiology ; Rats ; Taste/*physiology ; Thalamic Nuclei/*physiology ; }, abstract = {The anterior insular gustatory neocortex (AIGN) has been implicated as a functional substrate of conditioned taste aversion (CTA) learning. Results of previous neuroanatomical and neurobehavioral experiments indicate that projections from gustatory-responsive neurons in the posterior ventromedial thalamic nuclei (parvicellular division; VPMpc) may provide relevant input to the AIGN during CTA learning. In rat, gustatory thalamocortical projections from VPMpc thalamus traverse the ventrolateral neostriatum (VLS) enroute to the AIGN. In these experiments, various neuroanatomical and neurobehavioral manipulations in the VLS were used to examine the contribution of presumed gustatory thalamocortical projections to CTA learning. These experiments demonstrate that projections from VPMpc thalamus to the AIGN are essential for normal CTA learning. Because both VPMpc thalamus and the AIGN each have been implicated as functional substrates of CTA learning, the present results suggest that the gustatory thalamocortical relay per se is necessary for normal taste-illness learning.}, } @article {pmid4034711, year = {1985}, author = {Sclafani, A and Kramer, TH}, title = {Aversive effects of vagotomy in the rat: a conditioned taste aversion analysis.}, journal = {Physiology & behavior}, volume = {34}, number = {5}, pages = {721-725}, doi = {10.1016/0031-9384(85)90370-1}, pmid = {4034711}, issn = {0031-9384}, support = {AM-23064/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Anorexia/physiopathology ; Avoidance Learning/*physiology ; Drinking Behavior/physiology ; Female ; Ileum/surgery ; Jejunum/surgery ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; *Vagotomy ; Vagus Nerve/physiology ; }, abstract = {Subdiaphragmatic vagotomy suppresses food intake and water intake in normal rats. Since human patients report some nausea and discomfort following vagotomy, the present study assessed the aversive consequences of vagotomy in rats using a conditioned taste aversion paradigm. Rats were given a total subdiaphragmatic vagotomy or sham vagotomy, and were then maintained on either plain water (Vag-Water and Sham-Water groups) or a novel cherry solution (Vag-Cherry and Sham-Cherry groups). When subsequently tested for their water vs. cherry preferences on postoperative days 6, 16, and 26, the Vag-Cherry group displayed a greater aversion to the cherry solution than did the remaining three groups. This result suggests that vagotomy produces visceral malaise in rats which may contribute to the feeding and drinking suppressive effects of the surgery.}, } @article {pmid4034710, year = {1985}, author = {Sclafani, A and Kramer, TH and Koopmans, HS}, title = {Aversive consequences of jejunoileal bypass in the rat: a conditioned taste aversion analysis.}, journal = {Physiology & behavior}, volume = {34}, number = {5}, pages = {709-719}, doi = {10.1016/0031-9384(85)90369-5}, pmid = {4034710}, issn = {0031-9384}, support = {AM-23064/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Anorexia/physiopathology ; Avoidance Learning/*physiology ; Body Weight ; Drinking Behavior/physiology ; Feeding Behavior/physiology ; Female ; Ileum/*surgery ; Jejunum/*surgery ; Obesity/physiopathology/therapy ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {Jejunoileal bypass (JIB) surgery reduces food intake and body weight in obese humans and rats. Human bypass patients report visceral discomfort following surgery, and the present study assessed the aversive consequences of JIB in rats using a conditioned taste aversion paradigm. In Experiment 1 rats given a cherry-flavored solution immediately after JIB surgery subsequently displayed a strong aversion to the cherry flavor compared to Bypass and Sham-Bypass control groups. Rats in Experiment 2 were familiarized with cherry solution prior to surgery and they did not display an aversion to the solution after receiving a JIB. In Experiment 3, Bypass rats who developed a cherry flavor aversion after JIB subsequently lost this aversion following reconnection of their intestinal tract. The rats in Experiment 4 displayed an aversion to a saccharin-flavored chow that was eaten shortly after JIB surgery, although the aversion was not as pronounced as that obtained with the cherry solution. The results suggest that JIB produces a persisting malaise in rats that may contribute to the feeding and weight inhibitory effects of the operation.}, } @article {pmid4033865, year = {1985}, author = {Romano, JA and King, JM and Penetar, DM}, title = {A comparison of physostigmine and soman using taste aversion and nociception.}, journal = {Neurobehavioral toxicology and teratology}, volume = {7}, number = {3}, pages = {243-249}, pmid = {4033865}, issn = {0275-1380}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Food Preferences/drug effects ; Male ; Nociceptors/*drug effects ; Organophosphorus Compounds/*pharmacology ; Physostigmine/*pharmacology/toxicity ; Rats ; Rats, Inbred Strains ; Reaction Time/drug effects ; Saccharin ; Soman/*pharmacology/toxicity ; Taste/*drug effects ; }, abstract = {The effects of a reversible (physostigmine) and an irreversible (soman) acetylcholinesterase inhibitor were compared in terms of nociception using the rat tail flick (TF), and hot plate (HP) tests. The conditioned taste aversion (CTA) procedure was employed to evaluate the stimulus properties of these drugs. In all procedures physostigmine salicylate was administered at doses of 0.20, 0.32, 0.45, or 0.65 mg/kg, IM. Soman was administered at doses ranging from 40 to 80 microgram/kg, IM. Using either TF or HP, physostigmine and soman were evaluated at 40 min following injection. Both physostigmine and soman produced dose-related effects on each measure of nociception. The median effective dose of physostigmine was 0.27 mg/kg on TF and 0.55 mg/kg on HP. For soman, the median effective dose was 54 micrograms/kg on TF and 52 micrograms/kg on HP. In the CTA procedure, a novel, saccharin sweetened solution was paired with either physostigmine or soman. Three days later rats were offered a choice of saccharin or tap water. Both soman and physostigmine produced dose-related CTAs over the range of doses studied. Whereas the ED50 for soman was 59 micrograms/kg with significant effects at doses of 60 micrograms/kg or more, physostigmine produced effects at doses of 0.45 mg/kg or greater (ED50 = 0.05 mg/kg) with no additional changes in saccharin preference beyond 0.45 mg/kg. The data suggest that these experimental procedures, TF, HP, and conditioned taste aversion may be employed to evaluate the behavioral toxicity of physostigmine and soman.}, } @article {pmid3998395, year = {1985}, author = {Hermann, GE and Rogers, RC}, title = {Convergence of vagal and gustatory afferent input within the parabrachial nucleus of the rat.}, journal = {Journal of the autonomic nervous system}, volume = {13}, number = {1}, pages = {1-17}, doi = {10.1016/0165-1838(85)90002-5}, pmid = {3998395}, issn = {0165-1838}, mesh = {Animals ; Brain Mapping ; Evoked Potentials, Somatosensory ; Locus Coeruleus/physiology ; Neural Inhibition ; Pons/*physiology ; Rats ; Reaction Time/physiology ; Taste/*physiology ; Vagus Nerve/*physiology ; }, abstract = {Our previous anatomical and electrophysiological studies demonstrated that first-order hepatic and gustatory afferents project to separate regions of the solitary nucleus (NST) and no intra-NST interaction of these two sensory systems could be demonstrated. However, iontophoretic injections of horseradish peroxidase into physiologically identified zones of the NST revealed that both of these regions send overlapping projections to the immediately subjacent parvocellular reticular formation as well as the postero-medial parabrachial nucleus (PBN). The present electrophysiological studies demonstrate that an interstitial zone of neurons in the caudal, medial PBN, indeed, receive convergent input from second-order gustatory and vagal afferents. Co-activation of these PBN units by the simultaneous arrival of both input sources frequently resulted in an additive interaction of evoked activity. PBN units lateral and caudal to this zone responded to vagal stimulation only, while units in the anterior and extreme medial portion of the PBN only responded to gustatory stimulation. By virtue of the efferent projections of the PBN, one might speculate that the convergence of information at this locus may, eventually, play a role in directing long term feeding behavior patterns such as learned taste aversion as well as the more transient changes in taste preference with visceral loading.}, } @article {pmid3843711, year = {1985}, author = {Lasiter, PS and Glanzman, DL}, title = {Cortical substrates of taste aversion learning: involvement of dorsolateral amygdaloid nuclei and temporal neocortex in taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {99}, number = {2}, pages = {257-276}, doi = {10.1037//0735-7044.99.2.257}, pmid = {3843711}, issn = {0735-7044}, support = {NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Conditioning, Classical/physiology ; Diencephalon/physiology ; Male ; Neural Pathways/physiology ; Olfactory Bulb/physiology ; Pons/physiology ; Rats ; Taste/*physiology ; Temporal Lobe/*physiology ; }, abstract = {The amygdaloid complex is functionally implicated in conditioned taste aversion (CTA) learning. Results of previous neurobehavioral studies have provided equivocal evidence concerning the involvement of specific amygdaloid nuclei in CTA learning. The present study was conducted to examine the involvement of the central (CE), lateral (LA), and basolateral (BL) amygdaloid nuclei and the temporal neocortices (area 20) in CTA learning. To that end, distinct groups of rats received bilateral electrolytic lesion placements in the CE, LA, BL, or the temporal neocortices. Control animals received scalp and meningeal incisions only. Following recovery, animals were habituated to a restricted drinking schedule with distilled water. Animals then received CTA conditioning, with LiCl used both as the conditioned stimulus and as the unconditioned stimulus. Anterograde degeneration histologies were performed on all brain tissue to evaluate relations between CTA learning deficits and axonal pathology induced by lesion placements. Results of behavioral manipulations indicated that destruction of the CE, LA, or temporal neocortex impaired CTA acquisition, but damage induced to the basolateral amygdaloid nucleus did not. Anatomical observations indicated that degeneration of amygdalofugal and/or corticofugal projections to the convolutions of the olfactory tubercle (medial), subthalamic nucleus, and the parabrachial complex is correlated with CTA learning deficits. These results indicate that destruction of the dorsolateral amygdaloid nuclei and/or the temporal neocortices may produce CTA learning deficits by affecting olfactory, gustatory, and/or gastrointestinal processing in various portions of the forebrain.}, } @article {pmid4040378, year = {1985}, author = {Driscoll, CD and Riley, EP and Meyer, LS}, title = {Delayed taste aversion learning in preweanling rats exposed to alcohol prenatally.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {2}, number = {2}, pages = {277-280}, doi = {10.1016/0741-8329(85)90059-x}, pmid = {4040378}, issn = {0741-8329}, support = {AA00077/AA/NIAAA NIH HHS/United States ; AA03249/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Female ; Fetal Alcohol Spectrum Disorders/*physiopathology ; Hippocampus/*physiopathology ; Humans ; Learning Disabilities/*physiopathology ; Male ; Pregnancy ; Rats ; Taste/physiology ; }, abstract = {Parallels between the behavioral profiles of rats exposed to alcohol prenatally and those with hippocampal damage suggest that hippocampal dysfunction may underlie some of the behavioral abnormalities resulting from prenatal alcohol exposure. Because of possible hippocampal involvement in the acquisition of a delayed conditioned taste aversion, this task was assessed in rat pups exposed to alcohol prenatally. Long-Evans rats were maintained on liquid diets containing either 35% or 0% ethanol derived calories from Days 6-20 of gestation. Pair-feeding procedures and an ad lib Lab Chow (LC) group were included. Fifteen-day-old offspring from these three groups were given access to saccharin and then injected immediately (0 hr) or 2 hr later with either lithium chloride (LiCl) or sodium chloride (NaCl). Immediate pairing of saccharin with LiCl produced a marked taste aversion, although this effect was less pronounced in 35% EDC pups. In the 2 hr condition, weaker aversions were exhibited and again the 35% EDC group showed the least aversion. However, prenatal treatment did not interact with the injection interval.}, } @article {pmid4034846, year = {1985}, author = {Klosterhalfen, S and Klosterhalfen, W}, title = {Conditioned taste aversion and traditional learning.}, journal = {Psychological research}, volume = {47}, number = {2}, pages = {71-94}, pmid = {4034846}, issn = {0340-0727}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Extinction, Psychological ; Generalization, Stimulus ; Rats ; *Taste ; }, } @article {pmid4034697, year = {1985}, author = {Lasiter, PS and Deems, DA and Garcia, J}, title = {Involvement of the anterior insular gustatory neocortex in taste-potentiated odor aversion learning.}, journal = {Physiology & behavior}, volume = {34}, number = {1}, pages = {71-77}, doi = {10.1016/0031-9384(85)90080-0}, pmid = {4034697}, issn = {0031-9384}, support = {HD 05958/HD/NICHD NIH HHS/United States ; NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Male ; Models, Neurological ; Rats ; Smell/*physiology ; Taste/*physiology ; }, abstract = {When an odor conditioned stimulus (CS) precedes illness (unconditioned stimulus; UCS), rats acquire relatively weak odor aversions. Conversely, when a compound odor-taste (flavor) CS precedes illness, rats acquire robust aversions both to the odor and to the taste components of a compound flavor CS. Thus, tastes potentiate odor-illness aversions during toxiphobic conditioning. Such conditioning effects have been referred to as taste-potentiated odor aversion learning (POA). Previous neurobehavioral experiments have shown that the anterior insular gustatory neocortex contributes to conditioned taste aversion (CTA) learning. The present experiment examined the involvement of the anterior insular gustatory neocortex in CTA learning and POA learning. To that end, four distinct groups of rats received bilateral electrolytic lesion placements in the orbitofrontal neocortex, the "somatic" gustatory neocortex, the anterior insular gustatory neocortex or the posterior insular neocortex. Control animals received anesthesia only. Subgroups of animals thereafter received aversion conditioning using either an odor (almond) CS or a compound odor-taste (almond-saccharin) CS. Aversions to the almond odorant and/or saccharin tastant were evaluated during extinction. Results indicated that animals lacking orbitofrontal neocortex or posterior insular neocortex acquired normal CTAs and POAs. Animals lacking somatic gustatory neocortex exhibited impaired CTA learning, yet those animals showed normal POA learning. Lesions centered in the anterior insular neocortex impaired both CTA learning and POA learning. These results demonstrate that the insular gustatory neocortex is uniquely involved in the higher-order integration of odors, tastes and illness.}, } @article {pmid4023657, year = {1985}, author = {Archer, T and Järbe, TU and Mohammed, AK and Priedite, G}, title = {The effect of stimulus preexposure upon the context effect in taste-aversion learning in noradrenaline-depleted rats.}, journal = {Scandinavian journal of psychology}, volume = {26}, number = {2}, pages = {158-169}, doi = {10.1111/j.1467-9450.1985.tb01151.x}, pmid = {4023657}, issn = {0036-5564}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Cues ; Male ; Memory/*physiology ; Mental Recall/*physiology ; Norepinephrine/*physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, } @article {pmid3936088, year = {1985}, author = {Goudie, AJ and Newton, T}, title = {The puzzle of drug-induced conditioned taste aversion: comparative studies with cathinone and amphetamine.}, journal = {Psychopharmacology}, volume = {87}, number = {3}, pages = {328-333}, pmid = {3936088}, issn = {0033-3158}, mesh = {Alkaloids/*pharmacology ; Animals ; *Avoidance Learning ; Behavior, Animal/drug effects ; *Conditioning, Classical ; Dextroamphetamine/*pharmacology ; Drinking Behavior/drug effects ; Female ; Rats ; Reinforcement, Psychology ; Saccharin ; Self Administration ; *Taste ; }, abstract = {The potency of dl-cathinone (the active constituent of the Khat plant) was compared with that of d-amphetamine in the conditioned taste aversion (C.T.A.) procedure and in a test of drug-induced adipsia in rats. Both drugs induced C.T.A., the potency ratio being 1:17 (amphetamine was more potent). Both drugs induced adipsia in deprived rats given access to water for 120 min. The potency ratio in this procedure was 1:4. Potency in the C.T.A. procedure did not therefore correlate with potency in inducing adipsia; consequently drug-induced C.T.A. cannot be attributed to conditioned adipsia. In the adipsia test the drugs had similar durations of action, thus factors related to duration of drug action (cf Cappell and Le Blanc 1977) cannot account for the surprisingly low potency of cathinone in the C.T.A. procedure. These data, obtained with stimulant drugs with similar structures and similar actions in a variety of conventional in vivo and in vitro pharmacological tests, illustrate the unpredictable nature of drug actions in the C.T.A. procedure. The low potency of cathinone in inducing C.T.A. could not be predicted from knowledge of the potency of this compound in tests of adipsia (as shown here) or (as reported elsewhere) in tests of anorexia, locomotor stimulation, stereotypy, suppression of operant responding, drug discrimination, release and inhibition of reuptake of dopamine and noradrenaline, lethality and actions on the cardiovascular system. All of these studies have reported potency ratios considerably lower than 1:17, which were nevertheless similar to the 1:4 ratio observed in the adipsia test.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3931152, year = {1985}, author = {Bluthé, RM and Dantzer, R and Mormède, P and Le Moal, M}, title = {Specificity of aversive stimulus properties of vasopressin.}, journal = {Psychopharmacology}, volume = {87}, number = {2}, pages = {238-241}, pmid = {3931152}, issn = {0033-3158}, mesh = {Animals ; Arginine Vasopressin/analogs & derivatives/pharmacology ; Avoidance Learning/*drug effects ; Deamino Arginine Vasopressin/pharmacology ; Dose-Response Relationship, Drug ; Male ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; Vasopressins/antagonists & inhibitors/*pharmacology ; }, abstract = {Rats injected SC with arginine vasopressin (AVP) following consumption of a milk solution developed a marked aversion to the taste of this solution. An analog of vasopressin devoid of pressor activity, dDAVP, was unable to induce conditioned taste aversion. The aversive stimulus properties of AVP were blocked by the vasopressor antagonist dPTyr(Me)AVP. This antagonist did not block apomorphine-mediated conditioned taste aversion. These results demonstrate that AVP induces conditioned taste aversion by interacting with vasopressor-like receptors.}, } @article {pmid3927372, year = {1985}, author = {Giardini, V}, title = {Influence of housing conditions and state of partner on conditioning and extinction of taste aversion to lithium and chlorpromazine.}, journal = {Psychopharmacology}, volume = {86}, number = {1-2}, pages = {96-101}, pmid = {3927372}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning ; Chlorpromazine/*pharmacology ; *Conditioning, Classical ; Extinction, Psychological ; Lithium/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; *Social Isolation ; Taste ; }, abstract = {Rats were used in two experiments to investigate the influence of social variables on the acquisition of Conditioned Taste Aversion (CTA) to either lithium chloride (10 ml/kg IP of a 0.3-M solution given twice) or chlorpromazine (8 mg/kg IP given four times) and on subsequent extinction. CTA acquisition was not affected by original housing assignment (isolation or paired housing for 15-23 days prior to conditioning), by the shifted social assignment during conditioning, or by the drugged state of the paired animals' partners on drug-scheduled days. However, for both drugs, permanently isolated animals extinguished CTA more slowly than rats housed permanently in pairs. Shifts from isolation to pairing or vice versa failed to alter CTA extinction in the case of lithium, but affected it significantly in chlorpromazine-treated rats. Shifts from isolation to paired housing with an undrugged partner produced faster extinction for lithium than the corresponding group with a drugged partner. For chlorpromazine, the effect of the same shift was exactly the opposite. Overall, the results show that changes in CTA extinction can be a function of social variables.}, } @article {pmid3927369, year = {1985}, author = {Giardini, V}, title = {Conditioned taste aversion to chlorpromazine, but not to haloperidol.}, journal = {Psychopharmacology}, volume = {86}, number = {1-2}, pages = {81-83}, pmid = {3927369}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning ; Basal Ganglia Diseases/chemically induced ; Chlorpromazine/adverse effects/*pharmacology ; Conditioning, Classical ; Haloperidol/adverse effects/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Receptors, Dopamine/drug effects ; Taste ; }, abstract = {Using in rats a Conditioned Taste Aversion (CTA) procedure, chlorpromazine was shown to possess significant US properties at the highest dose tested (8 mg/kg IP repeated four times). In contrast, haloperidol failed to exert a similar effect at a dosage (1.6 mg/kg IP X 4) at least twice as high, in terms of pharmacological activity, as the effective chlorpromazine dosage. These data suggest that the induction of neuroleptic extrapyramidal side effects and the antidopaminergic properties shared by the two drugs may not be responsible for the aversive effect of chlorpromazine. However, it cannot be excluded than haloperidol produces an aversion which is antagonized by some action of the drug not shared by chlorpromazine.}, } @article {pmid6549259, year = {1984}, author = {Ettenberg, A}, title = {Intracerebroventricular application of a vasopressin antagonist peptide prevents the behavioral actions of vasopressin.}, journal = {Behavioural brain research}, volume = {14}, number = {3}, pages = {201-211}, doi = {10.1016/0166-4328(84)90189-x}, pmid = {6549259}, issn = {0166-4328}, mesh = {Animals ; Arginine Vasopressin/*analogs & derivatives/*pharmacology ; Arousal/drug effects ; Injections, Spinal ; Male ; Memory/*drug effects ; Rats ; Rats, Inbred Strains ; Reaction Time/drug effects ; Stimulation, Chemical ; }, abstract = {Three experiments were conducted to test the hypothesis that the memory-improving properties of peripherally-applied vasopressin (AVP) were related to its aversive (i.e. arousing) actions. The memory effects of AVP were observed in a one-trial food-finding task where non-deprived rats were briefly exposed to a large open field that contained an alcove in which a high-incentive familiar food reward (sweetened milk) was freely available. AVP injections immediately upon removal from the open-field produced faster latencies to refind the alcove (compared to vehicle controls) when tested 48 h later. The aversive actions of AVP were demonstrated in two behavioral assays: (1) a conditioned taste aversion test in which rats learned to avoid a preferred saccharin solution after it had been paired with injections of AVP; and (2) a conditioned place test in which rats learned to avoid a distinctive environment associated with AVP administration. Both the memory and aversive responses to AVP were prevented, in a dose-dependent manner, by immediate pretreatment with intracerebroventricular infusions of the pressor antagonist analog 1-deaminopenicillamine-2-(O-methyl)-tyrosine AVP. The large antagonist doses required to block AVP's behavioral effects suggest that the critical site of action may be far removed from the lateral ventricles. The possibility that AVP-induced improvements in memory result from peripheral arousing actions is discussed.}, } @article {pmid6542029, year = {1984}, author = {Borison, HL and Borison, R and McCarthy, LE}, title = {Role of the area postrema in vomiting and related functions.}, journal = {Federation proceedings}, volume = {43}, number = {15}, pages = {2955-2958}, pmid = {6542029}, issn = {0014-9446}, mesh = {Animals ; Artiodactyla/physiology ; Cats ; Cerebral Ventricles/*physiopathology ; Chemoreceptor Cells/physiology ; Defecation/drug effects ; Dogs ; Emetics/pharmacology ; Gastric Emptying ; Humans ; Medulla Oblongata/*physiopathology ; Pica/physiopathology ; Taste/physiology ; Vomiting/chemically induced/*physiopathology ; }, abstract = {Before 1949, the vomiting center was said to be located in the dorsal vagal nuclei of the medulla, but it was uncertain whether two centers existed separately for the control of direct and reflex actions of emetic agents. Borison and Wang then used a stereotaxic technique with electrical stimulation to localize the vomiting center in the reticular formation at a measurable distance from the dorsal vagal nuclei. They also formulated the concept of a separate emetic chemoreceptor trigger zone (CTZ) so that the vomiting center itself is not sensitive to emetic agents and serves solely to coordinate the reflex process. The CTZ was soon identified with the area postrema (AP), but the question remains unanswered whether the CTZ constitutes part or all of tht circumventricular organ. Furthermore, different chemosensory functions, as for defecation and certain forms of autonomic expression, may be represented regionally within the AP. Species that are unable to vomit, e.g., rodents, show other postrema-mediated effects as radiation-induced gastric stasis and drug-induced conditioned taste aversion. In sheep, digitalis-induced arrest of rumination is prevented by postremectomy. It is suggested that these behavioral end points in nonvomiting species may serve for biological assay of antinauseant drugs. Finally, a tabular summary is given of known causes of vomiting in which the AP has been implicated.}, } @article {pmid6537525, year = {1984}, author = {Canbeyli, RS and Koopmans, HS}, title = {Comparison of gastric, duodenal and jejunal contributions to the inhibition of food intake in the rat.}, journal = {Physiology & behavior}, volume = {33}, number = {6}, pages = {951-957}, doi = {10.1016/0031-9384(84)90235-x}, pmid = {6537525}, issn = {0031-9384}, support = {AM 17926/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Duodenum/*physiology ; *Eating ; Feeding Behavior ; Jejunum/*physiology ; Rats ; Rats, Inbred Strains ; Satiety Response ; Stomach/*physiology ; Time Factors ; }, abstract = {Rats equipped with tubes leading to their stomach, duodenum or jejunum were infused with a liquid diet for 9 hr (4 ml/hr) and were allowed to eat during the last 8 hr of infusion. All rats ate significantly less on diet infusion days than on saline or no infusion days. A second study showed that a taste aversion could not be conditioned to flavored water associated with diet infusion. Apparently, intrajejunal injection of nutrients produces satiety and not discomfort. Infusion of the diet for 5 consecutive days into the stomach, duodenum or jejunum consistently and significantly lowered food intake by reducing meal size, not meal frequency. Results suggest that the small intestine below the infusion site contributes to normal satiety.}, } @article {pmid6500070, year = {1984}, author = {Contreras, RJ and Kosten, T and Bird, E}, title = {Area postrema: part of the autonomic circuitry of caloric homeostasis.}, journal = {Federation proceedings}, volume = {43}, number = {15}, pages = {2966-2968}, pmid = {6500070}, issn = {0014-9446}, support = {HL-28952/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; *Body Weight ; Cerebral Ventricles/*physiology ; Feeding Behavior/physiology ; Homeostasis ; Medulla Oblongata/*physiology ; Rats ; Taste/*physiology ; }, abstract = {Investigations in which lesion techniques are used suggest a role for the area postrema (AP) in caloric homeostasis. Ablations of the AP in rat are associated with temporary hypophagia, hypodipsia, and rapid body weight loss. This is followed by a steady period of relatively normal eating and drinking and body weight gain. This steady period is characterized specifically by lowered body weight maintenance levels, overingestion of palatable foods, and attenuated taste aversion learning and glucoprivic feeding. These effects cannot be attributed simply to lesions of central terminations of gustatory and visceral afferents. The AP may be involved in feeding behaviors that are triggered by chemical signals in the blood or cerebrospinal fluid. In addition, the AP along with the adjacent nucleus tractus solitarii (NTS) seems to be part of the central autonomic system subserving caloric homeostasis; this system includes the lateral hypothalamus, which has a well-documented role in energy balance. The contribution of the AP along with the NTS must be considered with respect to their relationship to other structures within this system.}, } @article {pmid6096189, year = {1984}, author = {Gubernick, DJ and Alberts, JR}, title = {A specialization of taste aversion learning during suckling and its weaning-associated transformation.}, journal = {Developmental psychobiology}, volume = {17}, number = {6}, pages = {613-628}, doi = {10.1002/dev.420170605}, pmid = {6096189}, issn = {0012-1630}, support = {MH-00222/MH/NIMH NIH HHS/United States ; MH-28355/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects ; *Avoidance Learning/drug effects ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Feeding Behavior/drug effects ; Lithium/toxicity ; Lithium Chloride ; Rats ; Rats, Inbred Strains ; *Sucking Behavior/drug effects ; *Taste/drug effects ; *Weaning ; }, abstract = {During ontogenesis, altricial mammals advance through different ecological niches which require correspondingly different adaptive strategies. We view learning as an important feature of ontogenetic adaptations and consider the acquisition and expression of taste aversion learning during nursing within this framework. Fifteen-day-old preweanling rat pups fail to acquire conditioned taste aversions while nursing, whereas 20-day-old weanlings readily learn flavor aversions while suckling (Martin & Alberts, 1979). The developmental emergence of taste aversion learning while nursing coincides with reduction in maternal milk supply and the rat pup's transition to a solid food diet. We considered the ontogenetic transformation of learning while nursing as a feeding-related adaptive strategy of the weanling rat and tested two predictions derived from this view: (1) delayed weaning might postpone acquisition or expression of suckling-related taste aversions and (2) conditions that permit weaning (e.g., access to alternate food sources) might induce acquisition or expression of such taste aversions. Both predictions were confirmed.}, } @article {pmid6096188, year = {1984}, author = {Vogt, MB and Rudy, JW}, title = {Ontogenesis of learning: IV. Dissociation of memory and perceptual-altering processes mediating taste neophobia in the rat.}, journal = {Developmental psychobiology}, volume = {17}, number = {6}, pages = {601-611}, doi = {10.1002/dev.420170604}, pmid = {6096188}, issn = {0012-1630}, support = {RR07013-1980/RR/NCRR NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Animals, Newborn ; *Arousal/drug effects ; Avoidance Learning/drug effects ; Chlorides/toxicity ; Conditioning, Classical/drug effects ; Female ; Lithium/toxicity ; Lithium Chloride ; Male ; *Memory/drug effects ; *Mental Recall/drug effects ; Rats ; *Taste/drug effects ; }, abstract = {The rat's neophobic response to tastes can be conceptualized as depending on two processes: memory processes that store a representation of an experienced taste so that it can be recognized as familiar on subsequent encounters, and perceptual-altering processes that respond differentially to novel versus familiar tastes. We investigated the ontogeny of these processes by studying the preweanling rat's behavioral reaction to a 10% sucrose solution. Experiments I and II suggest that the memory processes mature earlier (by 7-8 days of age) than the perceptual-altering processes (about 11 days of age). Experiment III suggests that pups do not acquire an aversion to sucrose paired with illness until they are 12-days-old, implying a close correspondence between the maturation of processes mediating neophobia and taste aversion learning. These findings are consistent with our previous work (Vogt & Rudy, 1984), and our view that ontogenetic dissociations in taste-guided behavior reflect caudal-to-rostral maturation in the ascending gustatory system.}, } @article {pmid6571596, year = {1984}, author = {Liu, WF and Hu, NW and Chian, TF and Ma, C and Lin, CH and Liu, CY and Wu, MT}, title = {Adverse behavioral effects of the anticholinesterase poisoning protector pralidoxime methanesulfonate.}, journal = {Proceedings of the National Science Council, Republic of China. Part B, Life sciences}, volume = {8}, number = {4}, pages = {341-346}, pmid = {6571596}, issn = {0255-6596}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cholinesterase Inhibitors/*antagonists & inhibitors ; Drinking Behavior/*drug effects ; Exploratory Behavior/*drug effects ; Gastrointestinal Diseases/chemically induced/physiopathology ; Male ; Nausea/chemically induced/physiopathology ; Pralidoxime Compounds/pharmacology/*toxicity ; Rats ; Rats, Inbred Strains ; Taste ; }, abstract = {Pralidoxime methanesulfonate (P2S) has anticholinesterase protective properties, but it also has an array of gastrointestinal (GI) symptoms. Because such a symptom would be disadvantageous to occupational workers who handled and used organophosphorus anticholinesterase continuously, and to soldiers who have had oral pretreatment in a situation where anticholinesterase agent poisoning is a possibility, this question was investigated in rats using three behavioral paradigms to evaluate the feasibility of the oral prophylactic regimen. These are: (1) conditioned taste aversion (CTA), (2) operant behavior and (3) spontaneous locomotor activity (SMA); these three behavioral parameters are analogous to toxicant-induced gastrointestinal (GI) disturbances, performance of learned tasks and behavioral arousal, respectively. Dose-response studies of P2S in dose levels of 0.2, 0.4, 0.8 and 1.6 gm/kg (P.O.) were evaluated. The results consistently demonstrated that only the highest dose significantly produced marked decreases in consumption of flavored solution associated with its ingestion, suppressed keypress response maintained under a 20-response fixed-ratio schedule of water presentation, and inhibited SMA. By inference, if CTA, operant behavior and SMA are appropriate paradigms, P2S, on an acute single oral high dose level, would cause GI disturbances, impair task performance and induce sedation in man.}, } @article {pmid6525595, year = {1984}, author = {Smith, JC and Blumsack, JT and Bilek, FS and Spector, AC and Hollander, GR and Baker, DL}, title = {Radiation-induced taste aversion as a factor in cancer therapy.}, journal = {Cancer treatment reports}, volume = {68}, number = {10}, pages = {1219-1227}, pmid = {6525595}, issn = {0361-5960}, support = {CA-22768/CA/NCI NIH HHS/United States ; }, mesh = {Abdomen/radiation effects ; Ageusia/*etiology ; Animals ; Conditioning, Classical ; Drinking Behavior ; Food ; Humans ; Male ; Neoplasms/radiotherapy ; Pelvis/radiation effects ; Radiotherapy/*adverse effects ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste Disorders/*etiology ; }, } @article {pmid6504950, year = {1984}, author = {Iwamoto, ET and Williamson, EC}, title = {Nicotine-induced taste aversion: characterization and preexposure effects in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {21}, number = {4}, pages = {527-532}, doi = {10.1016/s0091-3057(84)80034-9}, pmid = {6504950}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Hexamethonium Compounds/pharmacology ; Male ; Mecamylamine/pharmacology ; Nicotine/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Rats were trained to drink their 24 hr water intake during a single daily 30 min period. After stabilization, rats were presented with 0.1% (w/v) of sodium saccharin for 30 min. Immediately after removal of the saccharin solution, the animals were injected with saline, mecamylamine hydrochloride or hexamethonium hydrobromide; thirty minutes later, saline or nicotine, 0.05, 0.16, or 0.50 mg/kg were administered. Twenty-four hr later, rats were allowed access to both water and saccharin. Nicotine caused a dose-related decrease in the proportion of fluid consumed as saccharin solution during the 30 min testing situation. Neither mecamylamine nor hexamethonium alone decreased saccharin preference; however, 3 mg/kg of mecamylamine blocked the decrease of saccharin preference induced by nicotine. Preexposure of drug-naive rats to 0.5 mg/kg of nicotine for 2 or 4 days abolished the nicotine-induced taste aversions to saccharin when tested one day, or one week, after conditioning.}, } @article {pmid6487414, year = {1984}, author = {Kiefer, SW and Cabral, RJ and Garcia, J}, title = {Neonatal ablations of the gustatory neocortex in the rat: taste aversion learning and taste reactivity.}, journal = {Behavioral neuroscience}, volume = {98}, number = {5}, pages = {804-812}, doi = {10.1037//0735-7044.98.5.804}, pmid = {6487414}, issn = {0735-7044}, support = {HD 05958/HD/NICHD NIH HHS/United States ; NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Animals, Newborn ; Avoidance Learning/*physiology ; Extinction, Psychological/physiology ; Female ; Food Preferences ; Male ; Rats ; Sodium Chloride ; Somatosensory Cortex/*physiology ; Taste/*physiology ; }, abstract = {Rats sustaining ablations of gustatory neocortex (GN) at 2, 10, 20, or 60 days of age were compared with control rats in the acquisition and extinction of a learned taste aversion; in addition, these rats were tested for taste preference across five concentrations of sodium chloride solution. Results indicated that GN ablation disrupted aversion acquisition and extinction regardless of age at surgery. Taste response functions for the sodium chloride solutions shown by all GN groups of rats mirrored those of control rats: preference (relative to water baseline) for middle concentrations and rejection of the strongest salt concentration. There was a suggestion that the 20- and 60-day-old GN rats were hyperresponsive to the suprathreshold concentrations of NaCl (except the strongest concentration). The increased response to salt solutions in the 20- and 60-day GN rats may have been related to the significant decreases in water consumption relative to that of normal rats. Water consumption of control rats and GN rats in the 2-day and 10-day groups was essentially equal. It is concluded that infant ablation of the GN does not spare normal taste aversion learning and that rats with GN ablations, regardless of age at surgery, respond in a normal manner to the hedonic aspects of sodium chloride solutions.}, } @article {pmid6441178, year = {1984}, author = {Bardos, G and Laszy, J}, title = {Learned aversion to mannitol in water-deprived rats.}, journal = {Physiology & behavior}, volume = {33}, number = {4}, pages = {533-536}, doi = {10.1016/0031-9384(84)90366-4}, pmid = {6441178}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Digestive System/*drug effects ; Digestive System Physiological Phenomena ; Drinking Behavior/*drug effects ; Male ; Mannitol/*pharmacology ; Rats ; Satiation/*drug effects ; Satiety Response/*drug effects/physiology ; Stimulation, Chemical ; Taste ; Water Deprivation ; }, abstract = {Mannitol, a non-absorbent compound may suppress free drinking in rats. It was suggested that the osmotic accumulation of water in the intestine produced a satiety signal by distending the wall of the gut, which resulted in the reduction of intake. However, we never obtained this suppression during the first exposure to mannitol in water deprived rats, while subsequent administration of this compound significantly reduced the amount of the consumed fluid. Moreover, mannitol preloaded intragastrically increased and not decreased fluid intake. Results show that in water-deprived rats the accumulation of the fluid in the intestine did not result in satiety. The subsequent reduction of the fluid intake might be associated with the development of a taste aversion in the rats.}, } @article {pmid6095324, year = {1984}, author = {Bardo, MT and Miller, JS and Risner, ME}, title = {Opiate receptor supersensitivity produced by chronic naloxone treatment: dissociation of morphine-induced antinociception and conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {21}, number = {4}, pages = {591-597}, doi = {10.1016/s0091-3057(84)80044-1}, pmid = {6095324}, issn = {0091-3057}, support = {RR07114-14/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain/metabolism ; Drug Implants ; Male ; Morphine/*pharmacology ; Naloxone/administration & dosage/*pharmacology ; Nociceptors/*drug effects ; Rats ; Rats, Inbred Strains ; Reaction Time/drug effects ; Receptors, Opioid/*drug effects ; Spinal Cord/metabolism ; Taste/drug effects ; }, abstract = {In three separate experiments, rats were used to assess the effects of chronic administration of naloxone on specific binding of 3H-naloxone in various regions of the central nervous system (CNS) and on the efficacy of morphine to produce antinociception and a conditioned taste aversion. Chronic naloxone treatment increased opiate binding in medulla-pons, midbrain, hypothalamus, hippocampus, striatum, and prefrontal cortex, but not in either spinal cord or cerebellum. In those CNS regions exhibiting increased opiate binding, the duration of increased binding following termination of the naloxone treatment differed between regions. In conjunction with the increase in opiate binding, the efficacy of morphine to produce antinociception was potentiated, while the efficacy to produce a conditioned taste aversion was unchanged. Moreover, the administration of naloxone during behavioral testing blocked completely the antinociceptive effect, but not the aversive effect, of morphine. These results indicate that morphine-induced antinociception and conditioned taste aversion may be dissociated neuropharmacologically.}, } @article {pmid6090055, year = {1984}, author = {Gemberling, GA}, title = {Ingestion of a novel flavor before exposure to pups injected with lithium chloride produces a taste aversion in mother rats (Rattus norvegicus).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {98}, number = {3}, pages = {285-301}, pmid = {6090055}, issn = {0735-7036}, mesh = {Animals ; Animals, Newborn ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Chlorides/*toxicity ; Conditioning, Classical/drug effects ; Cues ; Female ; Lithium/*toxicity ; Lithium Chloride ; Male ; *Maternal Behavior ; Pregnancy ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Vocalization, Animal/drug effects ; }, abstract = {In a series of experiments, the ability of a mother rat to learn aversions to novel flavors ingested prior to the illness of her pups was investigated. In Experiment 1, mother rats learned to avoid a novel flavored solution ingested prior to the illness of their nursing litters. Experiment 2 was designed to investigate the extent to which any adult rat is capable of such learning: Nonlactating multiparous female rats learned aversions to novel flavors ingested prior to exposure to pups injected with lithium chloride, whereas nonlactating nulliparous female and male rats did not learn these aversions. Several possible reasons for differences in this learning ability are discussed. In Experiments 3 and 4, the nature of the unconditioned stimulus for these aversions was investigated. Visual, auditory, and taste cues associated with the lithium-injected pups did not mediate the aversions (Experiments 3A-C). The evidence suggests that olfactory characteristics of the lithium-injected pups mediate the flavor aversions in the present experiments (Experiment 3D). Finally, these olfactory cues did not appear to be general stress signals but instead were likely specific cues for gastrointestinal discomfort (Experiment 4). The results of the experiments are discussed in terms of classical conditioning and also of their adaptive significance for both mother and offspring.}, } @article {pmid6540588, year = {1984}, author = {Kiefer, SW and Leach, LR and Braun, JJ}, title = {Taste agnosia following gustatory neocortex ablation: dissociation from odor and generality across taste qualities.}, journal = {Behavioral neuroscience}, volume = {98}, number = {4}, pages = {590-608}, doi = {10.1037//0735-7044.98.4.590}, pmid = {6540588}, issn = {0735-7044}, support = {NS-16616/NS/NINDS NIH HHS/United States ; }, mesh = {Agnosia/physiopathology ; Animals ; Avoidance Learning/physiology ; Brain Mapping ; Humans ; Male ; Memory/*physiology ; Odorants ; Olfactory Bulb/physiology ; Rats ; Smell/physiology ; Somatosensory Cortex/*physiology ; Taste/*physiology ; }, abstract = {In Experiment 1, rats trained to avoid drinking in the presence of a compound odor (benzyl acetate) and taste (sucrose) conditional stimulus (CS) lost the taste habit but retained the odor habit following gustatory neocortex (GN) ablation. Conversely, olfactory bulb ablation resulted in loss of the odor habit but retention of the taste habit. In Experiment 2, rats lacking GN did not retain preoperatively instated learned aversions to a suprathreshold quinine hydrochloride (bitter) taste solution which had been employed as a CS. However, rats with GN lesions that were virtually identical to those of the bitter-trained group retained a preoperatively learned aversion to a hydrochloric acid (sour) CS. Experiment 3 demonstrated that reliable agnosia for an acid CS could be produced by lesions that extended more deeply into perirhinal areas near the claustrum at the level of the GN. It is concluded that the agnosia following GN ablation is relatively specific to gustation and that agnosia for preoperatively acquired taste aversion habits occurs for all four basic gustatory stimuli following anterolateral cortex ablations centered on the GN.}, } @article {pmid6090995, year = {1984}, author = {Ng Cheong Ton, JM and Amit, Z}, title = {Attenuation of ethanol-induced conditioned taste aversion by naloxazone: behavioral evidence for an opiate receptor-mediated morphine-ethanol interaction.}, journal = {Neuroscience letters}, volume = {48}, number = {2}, pages = {127-132}, doi = {10.1016/0304-3940(84)90007-7}, pmid = {6090995}, issn = {0304-3940}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Ethanol/*pharmacology ; Morphine/*pharmacology ; Naloxone/*analogs & derivatives/pharmacology ; Rats ; Receptors, Opioid/drug effects/*physiology ; Saccharin ; Taste/*physiology ; }, abstract = {When rats are presented with a novel saccharin solution and immediately injected with either morphine or ethanol, they subsequently develop a conditioned taste aversion (CTA) to the saccharin solution which reflects the aversive component of the conditioning drug. The present study provides evidence which suggests that both morphine-induced and ethanol-induced CTAs can be blocked by the specific high-affinity binding opiate antagonist, naloxazone.}, } @article {pmid6466259, year = {1984}, author = {Fox, RA and Lauber, AH and Daunton, NG and Phillips, M and Diaz, L}, title = {Off-vertical rotation produces conditioned taste aversion and suppressed drinking in mice.}, journal = {Aviation, space, and environmental medicine}, volume = {55}, number = {7}, pages = {632-635}, pmid = {6466259}, issn = {0095-6562}, support = {S06RR08192-02/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Psychological/physiology ; *Drinking ; Male ; Mice ; Motion Sickness/*etiology ; Rotation/*adverse effects ; Taste/*physiology ; }, abstract = {The effects of off-vertical rotation upon the intake of tap water immediately after rotation, and upon conditioned taste aversion, were assessed in mice with the tilt of the rotation axis varying from 5 to 20 degrees from the earth-vertical. Conditioned taste aversion occurred in all mice that were rotated, but the intake of tap water was suppressed only in mice that were rotated at 15 or 20 degrees of tilt. The greater suppression of tap water intake and the stronger conditioned aversion in the mouse as the angle of tilt was increased in this experiment are consistent with predictions from similar experiments with human subjects where motion sickness develops more rapidly as the angle of tilt is increased. It was suggested that off-vertical rotation may be a useful procedure for insuring experimental control over vestibular stimulation in animal studies of motion sickness.}, } @article {pmid6095345, year = {1984}, author = {Borsini, F and Rolls, ET}, title = {Role of noradrenaline and serotonin in the basolateral region of the amygdala in food preferences and learned taste aversions in the rat.}, journal = {Physiology & behavior}, volume = {33}, number = {1}, pages = {37-43}, doi = {10.1016/0031-9384(84)90010-6}, pmid = {6095345}, issn = {0031-9384}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Chlorides/poisoning ; Eating/drug effects ; *Food Preferences/drug effects ; Grooming/physiology ; Lithium/poisoning ; Lithium Chloride ; Male ; Norepinephrine/*physiology ; Rats ; Serotonin/*physiology ; Taste/*physiology ; }, abstract = {First, it was confirmed that bilateral lesions in the basolateral region of the amygdala (ABL) of the rat increased the time spent eating novel as compared to familiar food in a food preference test, and that the lesions impaired learned taste aversion to a sucrose solution which had been paired with lithium chloride. Then the roles of noradrenaline and serotonin in the amygdala in these aspects of food intake were investigated. In Experiment 2, it was shown that injections of 10 and 20 nmoles of noradrenaline (NA) into the ABL increased the time spent eating familiar food in the food preference test. Higher doses of NA (50 and 100 nmoles) increased the total time spent eating without changing the preference of the rats for familiar or novel food, and produced behavioral side effects. Serotonin (5HT) injected into the ABL in doses of 10, 50 and 100 nmoles did not modify the pattern of choice of the foods. In Experiment 3, it was shown that depletion of NA in the ABL with 10 micrograms 6-hydroxydopamine did not alter the level of feeding of novel and familiar foods, but did impair taste aversion Depletion of 5HT in the ABL with 10 micrograms 5,7 dihydroxytryptamine did not alter food preferences or impair the taste aversion learning. The depletions of NA and 5HT were confirmed biochemically. These results provide further evidence for a role of the amygdala in preferences for novel as compared to familiar foods and in learning that the ingestion of a food is associated with sickness, and suggest that noradrenaline but not serotonin in the amygdala is involved in these types of control of food intake.}, } @article {pmid6093405, year = {1984}, author = {Vavilova, NM and Kassil', VG}, title = {[Conditioned reflex taste aversion during dog ontogeny].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {34}, number = {4}, pages = {662-668}, pmid = {6093405}, issn = {0044-4677}, mesh = {Age Factors ; Animals ; Animals, Suckling ; Avoidance Learning/*physiology ; Chlorides ; Conditioning, Classical/*physiology ; Dogs ; Extinction, Psychological/physiology ; Lithium ; Lithium Chloride ; Memory/physiology ; Sucrose ; Taste/*physiology ; }, abstract = {The conditioned taste aversion (CTA) in dogs of different age including suckling puppies, is elaborated in one combination of conditioned stimulus (taste of 30% sucrose solution) with discomfort, elicited by parenteral injection of 0.28 M of LiCl solution. CTA persists up to a week and a half in mother-fed puppies, whose long-term memory for exteroceptive signals is not yet formed. In elaboration of CTA participation of not only intero- but also exteroceptive signals has been revealed even at early stages of ontogenesis. The longest preservation of CTA is common to animals of exaltative period of development. However, here two subperiods may be singled out characterised by different ability to CTA extinction depending on presence or absence of previous acquaintance with conditioned stimulus (2-2.5 and 3-4 months). The time of CTA extinction in suckling puppies does not depend on the degree of previous acquaintance with conditioned stimulus.}, } @article {pmid6494312, year = {1984}, author = {Smith, DV and Theodore, RM}, title = {Conditioned taste aversions: generalization to taste mixtures.}, journal = {Physiology & behavior}, volume = {32}, number = {6}, pages = {983-989}, doi = {10.1016/0031-9384(84)90289-0}, pmid = {6494312}, issn = {0031-9384}, support = {NS-00168/NS/NINDS NIH HHS/United States ; NS-10211/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cyclophosphamide/*toxicity ; Drinking/drug effects ; Generalization, Stimulus/*drug effects ; Rats ; Taste/*drug effects ; }, abstract = {Rats were trained to take their daily water ration within a 30-min session, during which the number of licks per 10-sec presentation of a drinking tube could be recorded. During one of these sessions, one of three stimuli (sucrose, NaCl or HCl) was presented, followed by the administration of cyclophosphamide to produce a conditioned taste aversion. When tested with mixtures of the conditioned stimulus (CS) with the other two stimuli and also with quinine hydrochloride, the animals avoided mixtures containing the CS in proportion to its concentration in the mixture. Although the natural preferences and aversions for these stimuli interacted somewhat with the learned taste aversions, rats responded to the presence of a CS in a mixture and did not generalize to other stimuli not containing the CS. Thus, the generalization of conditioned taste aversions provides a good measure of the behavioral similarities among gustatory stimuli.}, } @article {pmid6463070, year = {1984}, author = {Fletcher, PJ and Burton, MJ}, title = {Effects of manipulations of peripheral serotonin on feeding and drinking in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {20}, number = {6}, pages = {835-840}, doi = {10.1016/0091-3057(84)90002-9}, pmid = {6463070}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Drinking/*drug effects ; Feeding Behavior/*drug effects ; Fenfluramine/pharmacology ; Male ; Metergoline/pharmacology ; Methysergide/pharmacology ; Rats ; Serotonin/*physiology ; Taste/drug effects ; Time Factors ; }, abstract = {Rats injected peripherally with serotonin showed a dose dependent increase in water intake which was maximal at 2-hours. This effect, along with a dose dependent anorexia was also observed in animals eighteen hour food deprived overnight. In rats maintained on a 6-hour feeding schedule there was a significant anorectic effect of 5-HT that could be reversed by pretreatment with methysergide but not metergoline. However the hyperdipsia was not apparent in these animals due to prandial drinking by control animals. The optimal dose of 5-HT for producing an anorexic response produced only a transient conditioned taste aversion to a novel solution in a sensitive 2-bottle choice test. On the other hand a high dose of 5-HT, and 3 mg/kg fenfluramine produced sustained aversions. These results are discussed with regard to a possible peripheral role for 5-HT in the control of food intake.}, } @article {pmid6329244, year = {1984}, author = {Babine, AM and Smotherman, WP}, title = {Uterine position and conditioned taste aversion.}, journal = {Behavioral neuroscience}, volume = {98}, number = {3}, pages = {461-466}, doi = {10.1037//0735-7044.98.3.461}, pmid = {6329244}, issn = {0735-7044}, support = {HD 16102/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Extinction, Psychological/physiology ; Female ; Lithium/poisoning ; Lithium Chloride ; Male ; Pregnancy ; Rats ; Rats, Inbred Strains ; Sex Differentiation ; Taste/*physiology ; Testosterone/blood ; Uterus/*physiology ; }, abstract = {Three experiments were designed to determine the influence of uterine position on the performance of female rats in a conditioned taste aversion paradigm. The first and second experiments confirmed a differential behavioral response by males and females during acquisition and extinction of the conditioned taste aversion. However, no differences were found between females that had caudal male littermates in utero (MF) and females that had no caudal male littermates (FF). In the third experiment, in which testosterone was administered to females throughout testing, MF females showed an increased sensitivity to testosterone and a more prolonged rate of extinction than FF females. Exposure to testosterone during prenatal development heightened postnatal responsiveness to testosterone in female rats. The results are discussed in terms of the organizational and activational effects of testosterone on behavior in a conditioned taste aversion situation.}, } @article {pmid6093168, year = {1984}, author = {Mikulka, PJ and Freeman, FG}, title = {The effect of amygdala-kindled seizures on the acquisition of taste and odor aversions.}, journal = {Physiology & behavior}, volume = {32}, number = {6}, pages = {967-972}, doi = {10.1016/0031-9384(84)90287-7}, pmid = {6093168}, issn = {0031-9384}, mesh = {Amygdala/*physiology ; Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Cues ; Drinking ; *Kindling, Neurologic/drug effects ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/physiology ; Rats ; Smell/*physiology ; Taste/*physiology ; }, abstract = {Two experiments were conducted to investigate the effect of amygdala-kindled seizures on the acquisition of fluid aversions using taste, odor, and compound taste-odor cues. In Experiment 1 all subjects were poisoned with lithium chloride 30 minutes after ingesting a novel taste. Experimental subjects were either kindled 15 minutes following ingestion or 15 minutes following LiCl injection. The strength of the taste aversion in the kindled animals was significantly attenuated compared to nonkindled controls. There was a tendency for kindling within the CS-US interval to be more disruptive than kindling that occurred after LiCl injection. The second study explored the effect of kindling after the CS on the development of aversions to an odor cue or a compound taste-odor cue. This study found that kindling after drinking effectively blocked the acquisition of both odor and taste aversions and compounding did not affect the strength of the odor aversion.}, } @article {pmid6093167, year = {1984}, author = {Stewart, CN and Reidinger, RF}, title = {Disparity between formation of conditioned flavor aversions and neophobia during grooming in rats and mice.}, journal = {Physiology & behavior}, volume = {32}, number = {6}, pages = {955-959}, doi = {10.1016/0031-9384(84)90285-3}, pmid = {6093167}, issn = {0031-9384}, mesh = {Animals ; Arousal/drug effects ; Attention/drug effects ; Avoidance Learning/*drug effects ; Chlorides/*toxicity ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Grooming/*drug effects ; Lithium/*toxicity ; Lithium Chloride ; Male ; Mice ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Mice (Mus musculus) allowed to groom a paste containing saccharin from their fur before injection with lithium chloride displayed a saccharin aversion in subsequent drinking preference tests. No attenuation of neophobia was observed in mice grooming saccharin because the animals failed to display a neophobia towards saccharin in drinking tests. Rattus norvegicus displayed neophobia towards saccharin in two- and single-bottle drinking tests but this neophobia was not attenuated by grooming experience with the saccharin paste. Rats apparently learn that if a taste is hazardous in the grooming context it is also likely hazardous in an appetitive context. Learned safety in grooming, however, does not generalize into the appetitive context. The results support the view that neophobia and learned taste aversion depend upon different mechanisms.}, } @article {pmid6087485, year = {1984}, author = {Riley, EP and Barron, S and Driscoll, CD and Chen, JS}, title = {Taste aversion learning in preweanling rats exposed to alcohol prenatally.}, journal = {Teratology}, volume = {29}, number = {3}, pages = {325-331}, doi = {10.1002/tera.1420290303}, pmid = {6087485}, issn = {0040-3709}, support = {AA03249/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; *Animals, Newborn ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; *Conditioning, Psychological ; Ethanol/*pharmacology ; Female ; Lithium/pharmacology ; Lithium Chloride ; Male ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {The effects of prenatal alcohol exposure on the development of a conditioned taste aversion were examined in preweanling rat pups. Mothers of these pups were fed isocaloric liquid diets containing either 35 or 0% ethanol-derived calories (EDC) from gestation days 6 through 20. A pair-feeding procedure was employed, and an ad lib lab chow control group was also included. At 5, 10, or 15 days of age, pups were infused with a saccharin solution through a cannula implanted in the oral cavity. Half of the pups in each group were then injected with lithium chloride (LiCl), which served as the poisoning agent, and the other half with sodium chloride (NaCl) as a control. Animals were subsequently tested for a conditioned aversion to the saccharin solution. At 15 days of age, all of the pups in the LiCl-poisoned group demonstrated a conditioned taste aversion to the saccharin solution, but the degree of this aversion was less in alcohol-exposed offspring. At 10 days of age, a taste aversion was learned, although it was not as strong as that shown by 15-day-old pups, and it appeared to be learned equally well by all of the prenatal treatment groups. At 5 days of age, there was marginal support for taste aversion learning. Again, it did not interact with prenatal treatment. The ontogenic differences in taste aversion learning exhibited by alcohol-exposed offspring relative to controls are discussed in terms of altered hippocampal development.}, } @article {pmid6610880, year = {1984}, author = {Ervin, GN and Carter, RB and Webster, EL and Moore, SI and Cooper, BR}, title = {Evidence that taste aversion learning induced by l-5-hydroxytryptophan is mediated peripherally.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {20}, number = {5}, pages = {799-802}, doi = {10.1016/0091-3057(84)90202-8}, pmid = {6610880}, issn = {0091-3057}, support = {MS-14269//PHS HHS/United States ; }, mesh = {5-Hydroxytryptophan/*pharmacology ; Animals ; Avoidance Learning/*physiology ; Benserazide/pharmacology ; Brain Chemistry/drug effects ; Conditioning, Operant/drug effects ; Drinking Behavior/drug effects ; Male ; Mesentery/metabolism ; Peripheral Nerves/*physiology ; Rats ; Serotonin/metabolism ; Taste/*physiology ; }, abstract = {Rats learned to avoid a saccharin solution if their initial consumption of it was followed by intraperitoneal (IP) administration of 25 mg/kg l-5-hydroxytryptophan (l-5-HTP); this taste aversion learning did not occur in rats pretreated with 50 mg/kg (IP) of the aromatic l-amino acid decarboxylase inhibitor RO 4-4602 (benserazide). RO 4-4602 antagonized the l-5-HTP-induced elevation of 5-hydroxytryptamine (5-HT) in the mesentery but significantly increased the l-5-HTP-induced elevation of 5-HT in the brain. These results indicate that l-5-HTP-induced taste aversion is correlated with peripheral, but not central, elevation of 5-HT.}, } @article {pmid6536288, year = {1984}, author = {Sinclair, JD}, title = {Ethanol-induced conditioned taste aversion to ethanol.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {1}, number = {3}, pages = {223-227}, doi = {10.1016/0741-8329(84)90102-2}, pmid = {6536288}, issn = {0741-8329}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Temperature/drug effects ; Ethanol/*pharmacology ; Male ; Rats ; Saccharin/pharmacology ; Taste ; }, abstract = {A single injection of 2.5 g/kg ethanol one hr after drinking a 10% ethanol-0.05% saccharin solution produced a persistent conditioned taste aversion to the ethanol-saccharin solution. Twelve pairings produced a still stronger aversion that generalized to an aversion to a 10% ethanol solution without saccharin. Unpaired presentations of ethanol-saccharin solution and ethanol injections prevented the subsequent development of an aversion from a single pairing. Twelve pairings of access to saccharin solution with ethanol injections produced an aversion that generalized to an ethanol-saccharin solution. All groups receiving 12 alternate-day ethanol injections developed tolerance to the hypothermic effect of ethanol, but the tolerance was not conditioned to the drinking fluids previously paired with ethanol injections and it was unrelated to the subsequent drinking behaviors.}, } @article {pmid6087788, year = {1984}, author = {Richardson, R and Williams, C and Riccio, DC}, title = {Stimulus generalization of conditioned taste aversion in rats.}, journal = {Behavioral and neural biology}, volume = {41}, number = {1}, pages = {41-53}, doi = {10.1016/s0163-1047(84)90706-4}, pmid = {6087788}, issn = {0163-1047}, support = {MH437535/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/drug effects ; *Avoidance Learning/drug effects ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Cues ; Drinking/drug effects ; *Generalization, Stimulus/drug effects ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; Retention, Psychology/drug effects ; *Taste/drug effects ; }, abstract = {Relatively little information is available regarding the intradimensional stimulus generalization of conditioned taste aversion (CTA). Experiment 1 employed a between-groups generalization test to examine the extent to which conditioned flavor aversion to one sucrose solution generalized to other concentrations of sucrose in adult rats. Evidence of a gradient of aversion was obtained. Because generalization gradients in other tasks have been found to flatten over a retention interval, Experiment 2 investigated the effects of delayed testing (2, 7, or 21 days) upon the slope of the generalization gradient. The generalization gradient flattened at the intervals, suggesting that subjects forgot the specific attributes of the conditioning concentration and avoided generalized stimuli as if they were the original CS. Experiment 3 used a long delay between taste and toxicosis to degrade the associative contingency and found no evidence that the generalization gradients found in the first two experiments could be explained in terms of enhanced neophobia due to poisoning. These findings provide further evidence (cf. A. W. Logue, 1979, Psychological Bulletin, 86, 276-296; M. Domjan, 1980, in J. S. Rosenblatt, R. A. Hinde, C. Beer, & M. Busnel (Eds.), Advances in the study of behavior, Vol. 11, New York: Academic Press) that CTA shares a number of similarities with other learning processes. Further, they illustrate that stimulus forgetting can be detected in a paradigm considered relatively immune to retention loss.}, } @article {pmid6087787, year = {1984}, author = {Misanin, JR and Kniss, DA and Yoder, SD and Yazujian, DL and Hinderliter, CF}, title = {The effect of electroconvulsive shock on the attenuation of taste-aversion conditioning produced by flavor preexposure.}, journal = {Behavioral and neural biology}, volume = {41}, number = {1}, pages = {30-40}, doi = {10.1016/s0163-1047(84)90693-9}, pmid = {6087787}, issn = {0163-1047}, mesh = {Animals ; *Association Learning/drug effects ; Attention/drug effects ; *Avoidance Learning/drug effects ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Drinking/drug effects ; Electroshock ; *Learning/drug effects ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/drug effects ; Rats ; Rats, Inbred Strains ; *Taste/drug effects ; }, abstract = {The effect of electroconvulsive shock on the attenuation of taste-aversion conditioning produced by preexposure to the flavor conditioned stimulus (CS) was examined in three experiments. Electroconvulsive shock administered immediately after flavor preexposure attenuated the flavor-preexposure effect whereas delayed electroconvulsive shock did not. Attenuation of the flavor-preexposure effect resulted even though memory for the flavor CS remained intact, suggesting that electroconvulsive shock interfered with associative processes.}, } @article {pmid6728868, year = {1984}, author = {Pratt, JA and Stolerman, IP}, title = {Pharmacologically specific pretreatment effects on apomorphine-mediated conditioned taste aversions in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {20}, number = {4}, pages = {507-511}, doi = {10.1016/0091-3057(84)90296-x}, pmid = {6728868}, issn = {0091-3057}, mesh = {Animals ; Apomorphine/*pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Domperidone/pharmacology ; Dopamine Antagonists ; Drug Interactions ; Male ; Nicotine/pharmacology ; Pimozide/pharmacology ; Rats ; Taste/*drug effects ; Time Factors ; }, abstract = {Pretreatment with pimozide (0.2-1.2 mg/kg) reduced a conditioned taste aversion produced by apomorphine (0.4 mg/kg) in a dose-related manner. This pretreatment effect was pharmacologically specific as shown by the inability of pimozide to prevent a conditioned taste aversion produced by nicotine (0.4 mg/kg). The results argue against the hypothesis that "proximal pre-exposure" effects are always non-specific and indicate that further pharmacological characterisation of drug-induced conditioned taste aversion may be possible. Pretreatment with a peripherally-acting antiemetic compound, domperidone, did not prevent apomorphine producing conditioned taste aversions. These data suggest that conditioned taste aversions produced by apomorphine are mediated through central dopamine receptors unrelated to the emetic properties of apomorphine and are not a result of conditioned nausea.}, } @article {pmid6328544, year = {1984}, author = {Ford, KA and Riley, AL}, title = {The effects of LiCl preexposure on amphetamine-induced taste aversions: an assessment of blocking.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {20}, number = {4}, pages = {643-645}, doi = {10.1016/0091-3057(84)90318-6}, pmid = {6328544}, issn = {0091-3057}, mesh = {Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Chlorides/*pharmacology ; Conditioning, Psychological/*drug effects ; Drug Interactions ; Female ; Lithium/*pharmacology ; Lithium Chloride ; Rats ; Saccharin ; Taste/*drug effects ; Time Factors ; }, abstract = {Preexposure to lithium chloride attenuated the subsequent acquisition of amphetamine-induced taste aversions. This attenuation was independent of the similarity of the preexposure and conditioning environments, an effect inconsistent with an associative interpretation of the effects of LiCl preexposure. These results were discussed in terms of the mechanism underlying the effects of drug preexposure on taste aversion learning.}, } @article {pmid6091162, year = {1984}, author = {Kolakowska, L and Larue-Achagiotis, C and Le Magnen, J}, title = {[Comparative effects of lesion of the basolateral nucleus and lateral nucleus of the amygdaloid body on neophobia and conditioned taste aversion in the rat].}, journal = {Physiology & behavior}, volume = {32}, number = {4}, pages = {647-651}, doi = {10.1016/0031-9384(84)90320-2}, pmid = {6091162}, issn = {0031-9384}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {The effects of bilateral lesions of the basolateral and lateral nuclei of the amygdala on the neophobic response and LiCl-conditioned taste aversion to a saccharin solution were studied in rats. Compared to intact animals, rats with basolateral lesions did not exhibit neophobia to the novel stimulus, while rats with lateral lesions demonstrated an initial preference to the sweet solution over water. The LiCl-induced aversion was suppressed after basolateral lesions and was unchanged after lateral lesions. It is concluded that these two amygdaloid nuclei play an important but distinct role in neophobia and conditioned taste aversion.}, } @article {pmid6709677, year = {1984}, author = {Lynch, MR and Porter, JH and Rosecrans, JA}, title = {Latent inhibition in the aversion to oral methadone.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {20}, number = {3}, pages = {467-472}, doi = {10.1016/0091-3057(84)90287-9}, pmid = {6709677}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Extinction, Psychological/drug effects ; Female ; Male ; Methadone/*pharmacology ; Naltrexone/pharmacology ; Quinine/pharmacology ; Rats ; Rats, Inbred Strains ; Time Factors ; }, abstract = {Fourteen adult Sprague-Dawley rats received daily 3 mg/kg naltrexone (Group One, n = 7) or saline (Group Two, n = 7) injections for 24 days. During this time they underwent forced choice testing with 0.125 mg/ml methadone (the unconditioned stimulus, UCS) versus taste-balanced 0.04 mg/ml quinine placebo solutions. The handling, injection ritual, and taste cues served as a conditioned stimulus (CS)-complex. While Group Two (CS-UCS paired) animals showed pronounced pharmacological methadone aversions, those in Group One (CS pre-exposed rats in which the effects of methadone were blocked by the naltrexone) maintained a moderate intake of the opiate solution. When the injection conditions were reversed for 10 days, no change in percent methadone solution occurred for either group; thus, Group One displayed a latent inhibition effect after the CS pre-exposure, while Group Two maintained its previously acquired aversion. Testing after a 3-month drug free period, however, revealed the acquisition of a comparable methadone aversion by Group One (hence, recovery from the latent inhibition observed in the first reversal phase). Parallels with latent inhibition and retention in conditioned taste aversion studies were drawn, and further support for generality in the laws of learning, suggested.}, } @article {pmid6472556, year = {1984}, author = {Liu, WF and Hu, NW and Beaton, JM}, title = {Behavioral toxicological assessment of oral pralidoxime methanesulfonate in the rat.}, journal = {Neurobehavioral toxicology and teratology}, volume = {6}, number = {2}, pages = {121-127}, pmid = {6472556}, issn = {0275-1380}, mesh = {Administration, Oral ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Cholinesterase Reactivators/*toxicity ; Cimetidine/pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Male ; Pralidoxime Compounds/antagonists & inhibitors/*toxicity ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {The behavioral toxicity of pralidoxime methanesulfonate (P2S) was examined in the rat by comparing standard measures such as conditioned taste aversion (CTA), drinking behavior and acute oral toxicity. P2S produced a weak CTA at doses of 0.4 and 0.8 g/kg (PO) and a profound CTA at the highest dose (1.6 g/kg) using a single sucrose-flavored conditioning trial with a one bottle test. The CTA produced by the highest dose of P2S was blocked by a specific, and exclusively peripheral, histamine-H2blocker, cimetidine (30 mg/kg, IP), which also has a cytoprotecting effect on gastric mucosal lesions. These data suggest that the H2 receptors may be involved in inducing the aversive effects of P2S through the inherent local irritating property of P2S on the rat gastric mucosa. There was no disruption of water drinking in thirsty rats with P2S at doses ranging from 0.2 to 1.6 g/kg. The survival time after an acute oral lethal dose of P2S (8-15 g/kg) was prolonged in non-fasted rats (16.5-38.5 min) compared to fasted ones (3.5-14.5 min), however the LD50's were identical (8.7 +/- 1.0 and 7.5 +/- 0.5 g/kg; respectively); indicating that P2S taken with food delays the lethal effects, but does not affect its lethal potency.}, } @article {pmid6463131, year = {1984}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Recall of a previously acquired conditioned taste aversion in rats following lesions of the area postrema.}, journal = {Physiology & behavior}, volume = {32}, number = {3}, pages = {503-506}, doi = {10.1016/0031-9384(84)90270-1}, pmid = {6463131}, issn = {0031-9384}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*physiology ; Cerebral Ventricles/*physiology ; *Conditioning, Psychological ; Male ; *Memory ; *Mental Recall ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {A conditioned taste aversion was produced by pairing a novel sucrose solution with either 3 mEq lithium chloride or with 100 rad gamma radiation in rats with the area postrema intact. Lesions of the area postrema were then made in half of the rats exposed to each treatment and in rats that were not treated with the unconditioned stimulus. When tested for a conditioned taste aversion, all treated rats showed a significant aversion to the sucrose solution compared to the untreated control rats. There were no significant differences between rats with area postrema lesions and those with the area postrema intact, indicating that the lesions had no effect on the recall of the previously acquired aversion. The results are interpreted as being consistent with the hypothesis that the role of the area postrema in taste aversion learning is to monitor blood and cerebrospinal fluid for potential toxins and to transmit that information to the central nervous system.}, } @article {pmid6331023, year = {1984}, author = {Perkova, EO}, title = {[Formation of taste aversions in the rat].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {34}, number = {2}, pages = {237-242}, pmid = {6331023}, issn = {0044-4677}, mesh = {Animals ; *Avoidance Learning ; Chlorides ; *Food Preferences ; Lithium ; Lithium Chloride ; Male ; Rats ; Saccharin ; *Taste ; Thirst ; }, abstract = {The presence of correlation between the initial attitude of animals to a certain taste agent and the intensity of conditioned taste aversion (CTA) after LiCl poisoning was studied in nonlineal male white rats. 4 types of behavioural reactions were revealed: 1) the nonspecific inhibitory reaction to the situation in which CTA was elaborated; 2) specific associative-adaptive connection of CTA with the taste agent used (0,1% saccharine solution); 3) complex reaction consisting of the two first ones; 4) the same drinking behaviour as that before CTA elaboration. Moreover, a correlation was found between the initial attitude of animals to certain taste agent and the intensity of CTA after pairing of this agent with subsequent poisoning.}, } @article {pmid6725017, year = {1984}, author = {Shimai, S and Satoh, H and Yasuda, N}, title = {Taste aversion learning and perinatal methylmercury exposure in mice.}, journal = {Industrial health}, volume = {22}, number = {1}, pages = {41-44}, doi = {10.2486/indhealth.22.41}, pmid = {6725017}, issn = {0019-8366}, mesh = {Animals ; Avoidance Learning/*drug effects ; Female ; Methylmercury Compounds/*adverse effects ; Mice ; Pregnancy ; *Prenatal Exposure Delayed Effects ; *Taste ; }, } @article {pmid6718522, year = {1984}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Effects of dose and of partial body ionizing radiation on taste aversion learning in rats with lesions of the area postrema.}, journal = {Physiology & behavior}, volume = {32}, number = {1}, pages = {119-122}, doi = {10.1016/0031-9384(84)90081-7}, pmid = {6718522}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*radiation effects ; Cerebral Ventricles/*physiology ; Conditioning, Psychological ; Dose-Response Relationship, Radiation ; Male ; Rats ; Rats, Inbred Strains ; Taste/*radiation effects ; }, abstract = {The effect of area postrema lesions on the acquisition of a conditioned taste aversion following partial body exposure to ionizing radiation was investigated in rats exposed to head-only irradiation at 100, 200 and 300 rad or to body-only irradiation at 100 and 200 rad. Following head-only irradiation area postrema lesions produced a significant attenuation of the radiation-induced taste aversion at all dose levels, although the rats still showed a significant reduction in sucrose preference. Following body-only exposure, area postrema lesions completely disrupted the acquisition of the conditioned taste aversion. The results are interpreted as indicating that: (a) the acquisition of a conditioned taste aversion following body-only exposure is mediated by the area postrema; and (b) taste aversion learning following radiation exposure to the head-only is mediated by both the area postrema and a mechanism which is independent of the area postrema.}, } @article {pmid6606662, year = {1984}, author = {Bovbjerg, D and Ader, R and Cohen, N}, title = {Acquisition and extinction of conditioned suppression of a graft-vs-host response in the rat.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {132}, number = {1}, pages = {111-113}, pmid = {6606662}, issn = {0022-1767}, support = {K05 MH06318/MH/NIMH NIH HHS/United States ; NS-15071/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Classical/*physiology ; Cyclophosphamide/administration & dosage ; Extinction, Psychological/*physiology ; Female ; Graft vs Host Reaction/*drug effects ; *Immunosuppression Therapy ; Rats ; Rats, Inbred Lew ; Saccharin/administration & dosage ; Taste/drug effects ; }, abstract = {Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution results in a conditioned aversion to saccharin and a conditioned suppression of immune responses. In this study, female Lewis X Brown Norwegian F1 rats were conditioned by pairing saccharin with 50 mg/kg CY. Seven weeks later (day 0), a graft-vs-host response (GvHR) was induced in these animals by injecting splenic leukocytes from Lewis donors into a rear footpad. At this time, some conditioned animals were reexposed to saccharin, the conditioned stimulus. During the 7-wk interval between conditioning and immunization, subgroups of conditioned rats were given 0, 4, 9, or 18 extinction trials (saccharin followed by saline injections). Animals receiving 4, 9, or 18 extinction trials showed a greater preference for saccharin on day 0 than did animals receiving no extinction trials, but these groups did not differ among themselves; all conditioned groups showed a lower preference for saccharin than placebo-treated animals. There was a clear effect of number of extinction trials on the GvHR. Animals receiving 9 or 18 extinction trials did not differ from controls, whereas animals receiving 0 or 4 trials had a milder GvHR than did conditioned rats that were not reexposed to saccharin at the time of immunization. These results confirm a previous report of conditioned suppression of a GvHR, demonstrate that conditioned immunopharmacologic responses are subject to experimental extinction, and indicate that conditioned immunosuppression can be dissociated from conditioned taste aversion.}, } @article {pmid6542191, year = {1984}, author = {Wellman, PJ and Watkins, PA and Nation, JR and Clark, DE}, title = {Conditioned taste aversion in the adult rat induced by dietary ingestion of cadmium or cobalt.}, journal = {Neurotoxicology}, volume = {5}, number = {2}, pages = {81-90}, pmid = {6542191}, issn = {0161-813X}, mesh = {Animals ; *Avoidance Learning ; Body Weight ; *Cadmium ; *Cobalt ; Conditioning, Operant ; *Diet ; Extinction, Psychological ; Food Preferences ; Male ; Rats ; *Taste ; }, abstract = {The potential aversive qualities of dietary cadmium chloride (10, 100 mg/kg) or cobalt chloride (20, 100, 200 mg/kg) were evaluated in a conditioned saccharin aversion task. Male Long-Evans hooded rats (n = 42) were trained to drink tap water and ingest 10 grams of chow during daily 60 minute access tests. During the aversion-acquisition phase, a second bottle containing 0.1% sodium saccharin was introduced and the various metal-adulterated diets (10 grams, dose calculated as mg metal base/kg body weight) offered in place of plain chow. During extinction testing, all rats were fed the plain chow. Diets adulterated with cadmium (10 or 100 mg/kg) or cobalt (100, 200 mg/kg) induced marked conditioned saccharin aversions after 2-3 days of exposure and were found to be profoundly resistant to extinction. Both cadmium (100 mg/kg) and cobalt (100, 200 mg/kg) induced a corresponding suppression of intake of adulterated food and significant weight losses. The relation of these aversive effects to the influence of cadmium and cobalt on operant responding for food reward is discussed.}, } @article {pmid6539488, year = {1984}, author = {Unwin, JW and Taberner, PV}, title = {Ethanol preference in mice following acute or chronic ethanol administration.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {8}, number = {1}, pages = {179-183}, doi = {10.1016/0278-5846(84)90148-9}, pmid = {6539488}, issn = {0278-5846}, mesh = {*Alcohol Drinking ; Animals ; Ethanol/*administration & dosage ; Injections, Subcutaneous ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Species Specificity ; Taste ; }, abstract = {C57Bl mice, unlike LACG or BALB mice, show a significant preference for 12% (w/v) ethanol solution compared to water. C57Bl mice which have been rendered tolerant to but not dependent upon ethanol by a programme of enforced ethanol drinking lose this preference on withdrawal of compulsory ethanol. Loss of preference also occurs following one or more acute injections of ethanol (4ml /kg) and persists in mice 12 weeks following withdrawal. It is suggested that this long-lasting loss of preference has a CNS basis and is not due merely to taste aversion.}, } @article {pmid6538786, year = {1984}, author = {Elkins, RL}, title = {Taste-aversion retention: an animal experiment with implications for consummatory-aversion alcoholism treatments.}, journal = {Behaviour research and therapy}, volume = {22}, number = {2}, pages = {179-186}, doi = {10.1016/0005-7967(84)90106-2}, pmid = {6538786}, issn = {0005-7967}, mesh = {Alcoholism/*therapy ; Animals ; Aversive Therapy/*methods ; Avoidance Learning ; Disease Models, Animal ; Humans ; Male ; Rats ; Rats, Inbred Strains ; Retention, Psychology ; *Taste ; }, } @article {pmid6468568, year = {1984}, author = {Yamamoto, T and Azuma, S and Kawamura, Y}, title = {Functional relations between the cortical gustatory area and the amygdala: electrophysiological and behavioral studies in rats.}, journal = {Experimental brain research}, volume = {56}, number = {1}, pages = {23-31}, pmid = {6468568}, issn = {0014-4819}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/physiology ; Electric Stimulation ; Evoked Potentials, Somatosensory ; Male ; Neural Inhibition ; Neural Pathways/physiology ; Rats ; Rats, Inbred Strains ; Retention, Psychology/physiology ; Somatosensory Cortex/*physiology ; Taste/*physiology ; }, abstract = {The functional interconnections between the cortical gustatory area (CGA) and the amygdala were examined by electrophysiological and behavioral experiments in rats. The cortical neurons responsive to taste stimuli applied to the anterior part of the tongue were located in the Vth layer of the agranular insular cortex. Of a total of 27 cortical neurons recorded, 10 showed facilitatory and/or inhibitory responses with the mean onset latency of about 20 msec to electrical stimulation of the ipsilateral amygdala. On the other hand, of 18 amygdaloid neurons responsive to taste stimuli, 13 showed facilitatory and/or inhibitory responses to electrical shocks to the ipsilateral CGA, with a mean latency of about 16 ms. No cortical and amygdaloid neurons sampled responded antidromically to the electrical stimulation. These results suggest the existence of mutual polysynaptic fiber connections between the CGA and the amygdala. The behavioral experiment was performed by means of a conditioned taste aversion (CTA) technique. After acquisition of CTA to sucrose solution by pairing it with an i.p. injection of LiCl which produces sickness, bilateral small knife cuts between the CGA and the amygdala in the perirhinal region disrupted retention of CTA. Thus, these interconnections may play some role in association of taste-related cognitive processes with feeding behavior.}, } @article {pmid6436871, year = {1984}, author = {Buresová, O and Bures, J}, title = {Central mediation of the conditioned taste aversion induced in rats by harmaline.}, journal = {Psychopharmacology}, volume = {83}, number = {4}, pages = {384-389}, pmid = {6436871}, issn = {0033-3158}, mesh = {Alkaloids/*pharmacology ; Anesthesia ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Harmaline/administration & dosage/*pharmacology ; Injections ; Injections, Intraperitoneal ; Injections, Intraventricular ; Male ; Olivary Nucleus ; Rats ; Taste/*drug effects ; }, abstract = {The assumption that drugs used as unconditioned stimuli in conditioned taste aversion (CTA) studies act centrally was tested by comparing the effects of systemic and intracerebral injections of harmaline hydrochloride (H) in 340 rats. Intraperitoneal injection of 5-20 mg/kg but not of 2.5 mg/kg H administered 5 min after 15-min saccharin (0.1%) drinking decreased saccharin-water preference in a two-choice retention test, performed 48 h later, from 55% to 20%. Since CTA was not diminished when H (10 mg/kg) was injected into rats anesthetised immediately after saccharin drinking by pentobarbital (40 mg/kg), H (1.7-50 micrograms) was administered intracerebrally to anesthetised rats fixed in the stereotaxic apparatus. Injection of 3-6 micrograms H into the inferior olive elicited CTA comparable to that of systemic injection of 10 mg/kg H. Injections of 6 and 50 micrograms H into cerebellum and bulbar reticular formation elicited weaker CTA while neocortical, hypothalamic and mesencephalic applications were ineffective. CTA could also be elicited when 50 micrograms but not 6 micrograms H was injected into the inferior olive 1 or 2 h after saccharin drinking. This delay-dependent effect and failure of non-contingent H administration to change saccharin preference indicates that the H-induced CTA is not contaminated by a non-specific increase in neophobia. It is concluded that H probably elicits CTA by activation of caudal bulbar structures, including the nucleus of the solitary tract, area postrema and lateral reticular formation.}, } @article {pmid6427822, year = {1984}, author = {Rodgers, RJ and Richards, C and Precious, JI}, title = {Naloxone administration following brief exposure to novelty reduces activity and rearing in mice upon 24-h retest: a conditioned aversion?.}, journal = {Psychopharmacology}, volume = {82}, number = {4}, pages = {322-326}, pmid = {6427822}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Defecation/drug effects ; Drinking Behavior/drug effects ; Exploratory Behavior/*drug effects ; Male ; Mice ; Naloxone/*pharmacology ; Time Factors ; }, abstract = {It has recently been reported that naloxone treatment, prior to initial exposure to a novel arena, results in significant behavioural change when animals are retested 24 h later. In an attempt to clarify the nature of this delayed action of the opiate antagonist, three further studies have been performed. In the first experiment, male mice were injected with naloxone hydrochloride (0-10 mg/kg, IP) immediately after their initial experience of the test arena. When retested 24 h later, all groups that had previously received naloxone exhibited greatly reduced activity and rearing, with no evidence of a dose-response relationship. In the second experiment, naloxone (0-10 mg/kg) failed to induce a conditioned place aversion when administered according to the above regimen. In the final experiment, no evidence for a naloxone-induced taste aversion to saccharin was observed. It is concluded that the behavioural changes observed in the open-field study may reflect either (a) subtle aversive properties of naloxone which are insensitive to traditional one-trial paradigms or (b) opioid modulation of memory for non-painful experiences.}, } @article {pmid6425899, year = {1984}, author = {Greenshaw, AJ and Dourish, CT}, title = {Differential aversive stimulus properties of beta-phenylethylamine and of d-amphetamine.}, journal = {Psychopharmacology}, volume = {82}, number = {3}, pages = {189-193}, pmid = {6425899}, issn = {0033-3158}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dextroamphetamine/*pharmacology ; Male ; Motor Activity/drug effects ; Phenethylamines/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste/*drug effects ; }, abstract = {In a conditioned taste-aversion experiment with male Wistar rats (two-bottle test, single pairing), the effects of beta-phenylethylamine (PEA 12.5, 25.0, 50.0, 100.0 mg/kg IP) and of d-amphetamine (2.5 mg/kg IP) were compared with the effect of the saline vehicle. The amphetamine-treated group exhibited a marked aversion to saccharin on each of four retention trials. A decrease in saccharin intake after PEA was limited to the highest dose group (100 mg/kg) and the first retention trial for that group. Doses of up to 50 mg/kg of PEA were also ineffective with a single-bottle conditioned taste-aversion procedure involving multiple conditioning trials, although doses of 25 and 50 mg/kg of PEA induced marked changes in spontaneous motor activity. These data demonstrate that behaviourally active doses of PEA are ineffective in inducing a conditioned taste aversion to saccharin. This result extends previous reports that structurally similar compounds may have different potencies in this paradigm. It is proposed that further studies of structure-activity relationships may help to reveal the features of drug action that are necessary for the induction of a conditioned taste aversion.}, } @article {pmid6420822, year = {1984}, author = {Leshem, M}, title = {Suppression of feeding by naloxone in rat: a dose-response comparison of anorexia and conditioned taste aversion suggesting a specific anorexic effect.}, journal = {Psychopharmacology}, volume = {82}, number = {1-2}, pages = {127-130}, pmid = {6420822}, issn = {0033-3158}, mesh = {Analysis of Variance ; Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Feeding Behavior/*drug effects ; Male ; Naloxone/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste ; }, abstract = {The dose-related suppression of feeding by naloxone (0.25-15.0 mg/kg), either by injection before feeding, or by conditioning taste aversion (CTA), was compared. The weaker suppression found for CTA at low (below 0.75 mg/kg) and high (above 5.0 mg/kg) doses suggests that the aversive sequelae of naloxone injection cannot account fully for its suppressive effects. In turn, this suggests that naloxone exerts a specific anorexic effect. Comprehensive dose-response curves for naloxone anorexia (15 doses) and CTA (nine doses) are presented.}, } @article {pmid6398454, year = {1984}, author = {Yamamoto, T}, title = {Taste responses of cortical neurons.}, journal = {Progress in neurobiology}, volume = {23}, number = {4}, pages = {273-315}, doi = {10.1016/0301-0082(84)90007-8}, pmid = {6398454}, issn = {0301-0082}, mesh = {Afferent Pathways/physiology ; Animals ; Biophysical Phenomena ; Biophysics ; Brain Mapping ; Cats ; Cerebral Cortex/*physiology ; Dogs ; Efferent Pathways/physiology ; Evoked Potentials, Somatosensory ; Humans ; Macaca ; Medulla Oblongata/physiology ; Pons/physiology ; Rabbits ; Rats ; Reaction Time/physiology ; Saimiri ; Taste/*physiology ; Thalamic Nuclei/physiology ; }, abstract = {Branches of the facial, glossopharyngeal and vagus nerves which synapse with the receptor cells in the taste buds convey taste messages to the rostral part of the nucleus of the solitary tract. The second relay nucleus for ascending taste input is the parabrachial nucleus of the pons. The third relay nucleus is the medial parvocellular component of the ventrobasal complex of the thalamus. This thalamic nucleus projects to the cortical taste area. Another ascending projection site of the parabrachial nucleus is to the lateral hypothalamus, amygdala and bed nucleus of the stria terminalis. In monkeys, neurons from the gustatory area of the solitary nucleus directly reach the thalamic taste area, bypassing the parabrachial nucleus. Taste-elicited reflex activities are based on a hedonic (acceptable or rejective) aspect of taste, and are basically determined in the brain stem without activation of cortical neurons. The cerebral cortical taste area is located dorsal to the rhinal sulcus in or near the insular cortex in different species of animals. Besides this taste area, taste inputs also project to the tongue tactile area of the SI in monkeys, cats and rats. Taste-responsive neurons in SI area are also responsive to light tactile stimulation of the tongue. Human clinical case reports suggest that discrimination or recognition of taste quality are processed in the cortical taste area. In animal experiments, it is difficult to determine the functional significance of this area. However, recent behavioral studies using the conditioned taste aversion technique in rats suggest that the cortical taste area plays an important role in cognitive (learning, memorial, associative and discriminative) processes of taste sensation. Summated cortical evoked potentials have been recorded in human and rats to electrical and taste stimulations applied to the tongue surface. Recording of gustatory primary evoked potentials is unsuccessful in human subjects. The responses to taste stimulation are composed of an early component, which is induced by mechanical stimulation of a test solution poured on the tongue surface and a slow component, which is assumed to be the gustatory response. Essentially similar results are obtained for cortical summated responses to taste stimuli in rats. Besides these averaged evoked potentials, arousal changes of EEG occur in response to taste stimulation. There is a possibility that the arousal response can be used an objective indicator for intensity and hedonics of perceived taste sensation.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid6329158, year = {1984}, author = {Kucharski, D and Spear, NE}, title = {Potentiation of a conditioned taste aversion in preweanling and adult rats.}, journal = {Behavioral and neural biology}, volume = {40}, number = {1}, pages = {44-57}, doi = {10.1016/s0163-1047(84)90158-4}, pmid = {6329158}, issn = {0163-1047}, support = {1 RO1 MH35219/MH/NIMH NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Animals, Newborn ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Extinction, Psychological/drug effects ; Lithium/poisoning ; Lithium Chloride ; Rats ; Rats, Inbred Strains ; Saccharin ; Saline Solution, Hypertonic ; *Taste/drug effects ; }, abstract = {Preweanling (18 days old) and adult rats were made ill with LiCl either 2 min or 1 hr after tasting controlled amounts of either one of two single flavors (saccharin or NaCl) or a compound mixture of the two. Conditioning was assessed with a single test 4 days later relative to explicitly unpaired control conditions. Generally, potentiation of the aversions to either flavor occurred for animals conditioned to the compound. The potentiation effect was decreased or eliminated by nonreinforced exposure to the alternative flavor of the compound. These effects tended to be stronger for the younger rats. Specifically, adult animals did not express potentiation of the saccharin aversion whereas preweanlings expressed potentiated salt aversions. Nonreinforced exposure to the alternative element eliminated the potentiation effect. Conditions conducive to potentiation are discussed in light of investigators who have not observed this effect in similar studies with compound stimuli.}, } @article {pmid6325971, year = {1984}, author = {Dacanay, RJ and Mastropaolo, JP and Olin, DA and Riley, AL}, title = {Sex differences in taste aversion learning: an analysis of the minimal effective dose.}, journal = {Neurobehavioral toxicology and teratology}, volume = {6}, number = {1}, pages = {9-11}, pmid = {6325971}, issn = {0275-1380}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Dose-Response Relationship, Drug ; Female ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Saccharin/pharmacology ; Sex Factors ; Taste/*physiology ; }, abstract = {Male and female rats injected with various doses of LiCl following the consumption of a novel saccharin solution subsequently avoided consumption of saccharin, with the degree of the aversion directly related to the dose of LiCl. Although this dose-response relationship was evident for both males and females, the minimal effective dose for inducing an aversion was lower for males, an effect consistent with previous work examining sex differences in taste aversion learning. The necessity of considering sex as a variable when comparing the relative sensitivity of behavioral measures of toxicity was discussed.}, } @article {pmid6325970, year = {1984}, author = {Rappold, VA and Porter, JH and Llewellyn, GC}, title = {Evaluation of the toxic effects of aflatoxin B1 with a taste aversion paradigm in rats.}, journal = {Neurobehavioral toxicology and teratology}, volume = {6}, number = {1}, pages = {51-58}, pmid = {6325970}, issn = {0275-1380}, mesh = {Aflatoxin B1 ; Aflatoxins/*toxicity ; Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Chlorides/pharmacology ; Choice Behavior/drug effects ; Dose-Response Relationship, Drug ; Lithium/pharmacology ; Lithium Chloride ; Liver/pathology ; Male ; Rats ; Taste ; Time Factors ; Water Deprivation ; }, abstract = {A taste aversion test was used to evaluate the toxic effects of aflatoxin (AF) B1 which is considered to be one of the most potent hepatocarcinogens known. Sixty male Fisher rats were randomly assigned to six treatment (injection) groups: Water (H2O); Dimethyl Sulphoxide (DMSO); Lithium Chloride (LiCl); 0.125 mg/kg AFB1 (AF-Low); 0.250 mg/kg AFB1 (AF-Medium) and 0.500 mg/kg AFB1 (AF-High). After adaption to a water-deprivation schedule which permitted 10-min access to water each day, the rats were given 10-min access to 0.1% saccharin solution which was followed by intraperitoneal injections of either H2O, DMSO, LiCl, or AF of varying doses according to group assignment. After a five-day recovery period, the rats were initially tested for a conditional taste aversion to the saccharin solution with a two-bottle test during the 10-min access period. Then, a series of two-bottle taste aversion tests were conducted in which H2O and saccharin solutions were available on an ad lib basis. The LiCl, AF-Low, AF-Medium, and AF-High groups developed strong aversions to the saccharin solution; whereas, the H2O and DMSO control groups did not. In addition, there was a dose-response relationship between the doses of aflatoxin and the level of aversion with the AF-High group demonstrating the most marked aversion throughout all saccharin tests. Retention tests showed that the taste aversion was still evident 30 days after the initial pairing of saccharin with AF.}, } @article {pmid6325968, year = {1984}, author = {Miyagawa, M and Honma, T and Sato, M and Hasegawa, H}, title = {Conditioned taste aversion induced by toluene administration in rats.}, journal = {Neurobehavioral toxicology and teratology}, volume = {6}, number = {1}, pages = {33-37}, pmid = {6325968}, issn = {0275-1380}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Conditioning, Psychological/*drug effects ; Gases ; Injections, Intraperitoneal ; Injections, Intravenous ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste ; Time Factors ; Toluene/administration & dosage/*pharmacology ; }, abstract = {Effect of toluene as unconditioned stimulus in the conditioned taste aversion (CTA) learning in rats was investigated for a behavioral assessment of toluene toxicity. Intraperitoneal (200-800 mg/kg B.W.) and intravenous (20-40 mg/kg B.W.) administration of toluene induced dose-dependent CTA. Inhalation exposure to toluene at 1650-3300 ppm for 4 hr also induced moderate CTA. These results suggest that toluene functions as a "behaviorally aversive" stimulus and that the required dose for the conditioning varies with the route of administration. In addition, the interference effect of toluene vapor odor on the taste stimulus, which would reduce the strength of CTA, was examined but not revealed.}, } @article {pmid6233984, year = {1984}, author = {Creim, JA and Lovely, RH and Kaune, WT and Phillips, RD}, title = {Attempts to produce taste-aversion learning in rats exposed to 60-Hz electric fields.}, journal = {Bioelectromagnetics}, volume = {5}, number = {2}, pages = {271-282}, doi = {10.1002/bem.2250050214}, pmid = {6233984}, issn = {0197-8462}, mesh = {Animals ; *Avoidance Learning ; *Electromagnetic Fields ; *Electromagnetic Phenomena ; Male ; Rats ; Rats, Inbred Strains ; Specific Pathogen-Free Organisms ; *Taste ; }, abstract = {A measure of taste-aversion (TA) learning was used in three experiments to 1) determine whether exposure to intense 60-Hz electric fields can produce TA learning in male Sprague-Dawley rats, and 2) establish a dose-response function for the behavior in question. In Experiment 1, four groups of eight rats each were distributed into one of two exposures (69 +/- 5 kV/m or 133 +/- 10 kV/m) or into one of two sham-exposure groups. Conditioning trials paired 0.1% sodium saccharin in water with 3 h of exposure to a 60-Hz electric field. Following five conditioning trials, a 20-min, two-bottle preference test between water and saccharin-flavored water failed to reveal TA conditioning in exposed groups. In Experiment 2, four groups of eight rats each (34 +/- 2 kV/m or 133 +/- 10 kV/m and two sham-exposed groups) were treated as before. Electric-field exposure had no effect on TA learning. Experiment 3 tested for a possible synergy between a minimal dose (for TA learning) of cyclophosphamide (6 mg/kg) and 5 h of exposure to 133 +/- 10 kV/m electric fields in a dark environment under conditions otherwise similar to those of Experiments 1 and 2. The results indicated no TA learning as reflected in the relative consumption of saccharin.}, } @article {pmid6095442, year = {1984}, author = {Archer, T and Sjödén, PO and Nilsson, LG}, title = {The importance of contextual elements in taste-aversion learning.}, journal = {Scandinavian journal of psychology}, volume = {25}, number = {3}, pages = {251-257}, doi = {10.1111/j.1467-9450.1984.tb01016.x}, pmid = {6095442}, issn = {0036-5564}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/*toxicity ; *Cues ; Lithium/*toxicity ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, } @article {pmid6095144, year = {1984}, author = {Riley, AL and Dacanay, RJ and Mastropaolo, JP}, title = {The effects of trimethyltin chloride on the acquisition of long delay conditioned taste aversion learning in the rat.}, journal = {Neurotoxicology}, volume = {5}, number = {2}, pages = {291-295}, pmid = {6095144}, issn = {0161-813X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides ; Conditioning, Classical/drug effects ; Lithium ; Lithium Chloride ; Male ; Memory/drug effects ; Rats ; Saccharin ; Taste/*drug effects ; Trialkyltin Compounds/*pharmacology ; Trimethyltin Compounds/*pharmacology ; }, abstract = {Naive rats injected with LiCl at various times following consumption of a novel saccharin solution subsequently avoided the ingestion of saccharin with the degree of the aversion related to the interval between ingestion and LiCl administration. Although a similar relationship was also evident in animals which had received a single intragastric administration of trimethyltin chloride 21 days prior to the pairing of saccharin and LiCl, the trimethyltin-pretreated subjects receiving delayed injections of LiCl displayed weaker taste aversions than those not exposed to trimethyltin. This disruption in the acquisition of taste aversions over long delays is consistent with other work suggesting that trimethyltin disrupts tasks involving short-term memory. The utility of the conditioned taste aversion paradigm in detecting and characterizing drug toxicity was discussed.}, } @article {pmid6092021, year = {1984}, author = {Kassil', VG and Makukhina, GV}, title = {[Effect of experimental conditions on the acquisition and retention of conditioned taste aversion in white rats].}, journal = {Doklady Akademii nauk SSSR}, volume = {277}, number = {3}, pages = {746-748}, pmid = {6092021}, issn = {0002-3264}, mesh = {Animals ; Avoidance Learning/*physiology ; Chlorides/pharmacology ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Extinction, Psychological/*physiology ; Female ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; *Set, Psychology ; Taste/*physiology ; Time Factors ; }, } @article {pmid6088007, year = {1984}, author = {Kelley, KW and Dantzer, R and Mormède, P and Salmon, H and Aynaud, JM}, title = {[Induction of immunosuppression by dietary aversion acquired in the absence of immunosuppressive treatment].}, journal = {Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie}, volume = {299}, number = {5}, pages = {123-126}, pmid = {6088007}, issn = {0764-4469}, mesh = {Animals ; Avoidance Learning/physiology ; Chlorides/pharmacology ; Conditioning, Psychological/*physiology ; Cyclophosphamide/pharmacology ; Female ; *Immune Tolerance ; Immunity, Cellular ; Immunosuppressive Agents/pharmacology ; Lithium/pharmacology ; Lithium Chloride ; Mice ; Mice, Inbred BALB C ; Taste ; }, abstract = {Conditioned taste aversion induced by either an immunosuppressive (cyclophosphamide) or non immunosuppressive (lithium chloride) drug reduced expression of a T cell mediated immune response that is highly susceptible to stress hormones. These results demonstrate that the proposed concept of conditioned immunosuppression really represents another example of how stress can alter normal regulation of cell mediated immune events.}, } @article {pmid6317281, year = {1983}, author = {Galef, BG and Wigmore, SW and Kennett, DJ}, title = {A failure to find socially mediated taste aversion learning in Norway rats (R. norvegicus).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {97}, number = {4}, pages = {358-363}, pmid = {6317281}, issn = {0735-7036}, mesh = {Animals ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Cues ; Eating/drug effects ; Lithium/poisoning ; Lithium Chloride ; Rats ; *Social Environment ; *Taste/drug effects ; }, abstract = {Observer rats interacted with conspecific demonstrators immediately after demonstrators ate a novel diet and were made ill by LiCl injection. Following their interaction with demonstrators, observers were tested for aversion to their ill demonstrator's diet. Previous research has shown that (a) an observer can extract information from a demonstrator sufficient to permit identification of the demonstrator's diet (Galef & Wigmore, 1983) and (b) a rat ill from LiCl toxicosis is an adequate unconditioned stimulus in a taste aversion learning paradigm (Lavin, Freise, & Coombes, 1980). Further, two of the present experiments demonstrated that cues emitted by a rat, reflecting the particular diet it has eaten, are an adequate conditional stimulus in a toxicosis-induced aversion learning situation. Observer avoidance of a diet previously ingested by an ill demonstrator was, however, not demonstrated. The implications of the failure to find socially mediated aversion learning are discussed.}, } @article {pmid6670971, year = {1983}, author = {Martinez, JL and Rigter, H}, title = {Assessment of retention capacities in old rats.}, journal = {Behavioral and neural biology}, volume = {39}, number = {2}, pages = {181-191}, doi = {10.1016/s0163-1047(83)90825-7}, pmid = {6670971}, issn = {0163-1047}, support = {AG00538/AG/NIA NIH HHS/United States ; }, mesh = {*Aging ; Animals ; *Avoidance Learning ; Conditioning, Classical ; Electroshock ; Male ; *Memory ; Motor Activity ; Rats ; Rats, Inbred Strains ; Reaction Time ; *Retention, Psychology ; Taste ; }, abstract = {Young (3-6 month) and old (24-27 month) barrier reared Wistar rats were tested for their ability to retain an inhibitory (passive) avoidance, acquired immobility, and a conditioned taste aversion response as a function of time. Old rats exhibited accelerated forgetting of both the inhibitory avoidance and acquired immobility response in comparison to young rats. In contrast, old rats displayed good retention of the conditioned taste aversion response at all time intervals tested. It appears that the dynamic aspects of retention are altered in aged rats depending on the task, and in some instances may be expressed as accelerated forgetting.}, } @article {pmid6359178, year = {1983}, author = {Gosnell, BA and Morley, JE and Levine, AS}, title = {A comparison of the effects of corticotropin releasing factor and sauvagine on food intake.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {19}, number = {5}, pages = {771-775}, doi = {10.1016/0091-3057(83)90078-3}, pmid = {6359178}, issn = {0091-3057}, mesh = {Amphibian Proteins ; Animals ; Corticotropin-Releasing Hormone/*pharmacology ; Cyclazocine/analogs & derivatives/pharmacology ; Ethylketocyclazocine ; Feeding Behavior/*drug effects ; Food Deprivation ; Male ; Peptide Hormones ; Peptides/*pharmacology ; Rats ; Rats, Inbred Strains ; }, abstract = {Corticotropin releasing factor (CRF) and sauvagine (SVG) when administered ICV both reduced spontaneous feeding as well as feeding induced by deprivation or the administration of ethylketocyclazocine (EKC). For spontaneous- and EKC-induced feeding, SVG produced a larger and longer-lasting suppressive effect than did CRF. Both peptides produced a conditioned taste aversion when paired with a novel saccharin taste. As the feeding effects, SVG produced a stronger aversion than CRF. These studies further establish the similarity between CRF and SVG and suggest that they may have a disruptive effect on feeding.}, } @article {pmid6322739, year = {1983}, author = {Rusiniak, KW and Garcia, J and Palmerino, CC and Cabral, RJ}, title = {Developmental flavor experience affects utilization of odor, not taste in toxiphobic conditioning.}, journal = {Behavioral and neural biology}, volume = {39}, number = {2}, pages = {160-180}, doi = {10.1016/s0163-1047(83)90808-7}, pmid = {6322739}, issn = {0163-1047}, support = {AA-03513/AA/NIAAA NIH HHS/United States ; HD-05958/HD/NICHD NIH HHS/United States ; NS-11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Cues ; Drinking/drug effects ; Extinction, Psychological/drug effects ; Female ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; *Smell/drug effects ; Social Environment ; *Taste/drug effects ; }, abstract = {Feeding experiences were varied in developing rats and the effects upon flavor neophobia and lithium chloride-induced flavor aversions were observed. In Experiment 1, nursing experience of neonate rats was reduced by artificial feeding via intragastric cannula; the rats then were tested with apple juice paired with lithium chloride injection at weaning or maturity. Conditioned aversions were not affected, but neophobia to novel apple juice was attenuated in artificially-reared rats tested at maturity. In Experiment 2, rats received enriched feeding experience after weaning, which consisted of (a) obtaining many complex flavors, a few of which were paired with poisoning, effortlessly in the home cage, or (b) foraging for various foods on an elevated maze. No dramatic effects on neophobia or conditioned taste aversion for saccharin water were apparent. In Experiment 3, rats were given experience after weaning with vanilla-scented water either paired or unpaired with quinine water, and then tested with the odor of almond or that odor compounded with saccharin water for neophobia and lithium-induced aversions. Flavor-experienced rats exhibited more pronounced odor conditioning and more resistance to extinction of the odor aversion after both simple and compound conditioning. In contrast, saccharin taste aversions were relatively unchanged. Apparently, enriched feeding and drinking experience facilitates the utilization of odor more than taste cues.}, } @article {pmid6634898, year = {1983}, author = {Dourish, CT and Greenshaw, AJ and Boulton, AA}, title = {Deuterium substitution enhances the effects of beta-phenylethylamine on spontaneous motor activity in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {19}, number = {3}, pages = {471-475}, doi = {10.1016/0091-3057(83)90122-3}, pmid = {6634898}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Conditioning, Classical/*drug effects ; Deuterium/*pharmacology ; Male ; Motor Activity/*drug effects ; Phenethylamines/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste ; Time Factors ; }, abstract = {The effects of beta-phenylethylamine (PEA) and alpha, alpha, beta, beta-tetradeutero-beta-phenylethylamine (deuterated PEA) on spontaneous motor activity and conditioned taste aversion learning in the rat were examined. The intensity and duration of certain behavioural components elicited by PEA, namely, sniffing, headweaving, splayed hindlimbs and hyperreactivity, were significantly increased by deuterium substitution. In contrast, deuteration had no effect on the ability of PEA to elicit a conditioned taste aversion. The potentiation of the amine's effects on activity seemed to be directly related to the longer persistence of PEA in the brain due to the kinetic isotope effect since it appears that tetra-deuterated PEA is a poorer substrate for monoamine oxidase than the protonated amine.}, } @article {pmid6318718, year = {1983}, author = {Lasiter, PS}, title = {Gastrointestinal reactivity in rats lacking anterior insular neocortex.}, journal = {Behavioral and neural biology}, volume = {39}, number = {1}, pages = {149-154}, doi = {10.1016/s0163-1047(83)90790-2}, pmid = {6318718}, issn = {0163-1047}, support = {NS 11618/NS/NINDS NIH HHS/United States ; S07 RR07112/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Chlorides/poisoning ; Conditioning, Classical/physiology ; Digestive System/*innervation ; Lithium/poisoning ; Lithium Chloride ; Male ; Muridae ; Taste/*physiology ; }, abstract = {Behavioral and physiological studies have shown that the insular neocortex participates in a wide variety of special visceral processes, in particular, the higher-order integration of taste stimuli and the regulation of autonomic activity. The present experiment examined the involvement of the anterior insular (gustatory) neocortex (AIGN) in gastrointestinal reactivity and taste learning in rats by the use of a modified taste aversion training procedure. Normal rats and rats lacking AIGN demonstrated similar "illness thresholds" to the early onset symptoms of ingested LiCl. Conversely, animals lacking AIGN showed significant impairments in taste aversion learning ability. From a consideration of several research findings it is concluded that animals lacking AIGN can normally perceive tastes and illness, but these animals experience reliable impairments in taste aversion learning ability.}, } @article {pmid6888188, year = {1983}, author = {Mickley, GA and Stevens, KE and White, GA and Gibbs, GL}, title = {Changes in morphine self-administration after exposure to ionizing radiation: evidence for the involvement of endorphins.}, journal = {Life sciences}, volume = {33}, number = {8}, pages = {711-718}, doi = {10.1016/0024-3205(83)90775-0}, pmid = {6888188}, issn = {0024-3205}, mesh = {Animals ; Cobalt Radioisotopes ; Drinking Behavior/drug effects/*radiation effects ; Endorphins/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Morphine/*administration & dosage ; Naloxone/*pharmacology ; Saccharin ; Solutions ; }, abstract = {Recent findings have implicated endogenous opiates in radiation-induced behavioral change. The present experiment further investigated this hypothesis by observing alterations in morphine self-administration after irradiation. Under the presumption that the release of endogenous opiates would decrease the need for exogenously supplied morphine, we hypothesized that after radiation exposure morphine-experienced mice would self-administer less of the opiate. C57BL/6J mice had continuous access to two drinking flasks which contained either water or morphine in saccharine water. Irradiated mice drank significantly less morphine than did sham-irradiated controls. This decrease was naloxone-reversible and could not be entirely attributed to a generalized radiogenic hypodipsia or taste aversion. These results are consistent with the hypothesis that radiation-induced behavioral changes may be due, in part, to the fluctuations of endogenous opiates.}, } @article {pmid6877038, year = {1983}, author = {Ton, JM and Amit, Z}, title = {Symmetrical effect of pre-exposure between alcohol and morphine on conditioned taste aversion.}, journal = {Life sciences}, volume = {33}, number = {7}, pages = {665-670}, doi = {10.1016/0024-3205(83)90255-2}, pmid = {6877038}, issn = {0024-3205}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Ethanol/*pharmacology ; Kinetics ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin ; *Taste ; Water Deprivation ; }, abstract = {It has previously been reported that pre-exposure to a psychoactive drug can block the conditioned taste aversion associated with that drug. This study was an attempt to investigate alcohol-morphine interactions using this pre-exposure paradigm. After two weeks of adaptation to a schedule of daily 30-minute access to water, rats were pre-exposed to morphine, ethanol, or the respective vehicle control every second day for three days before (Days 1, 3, 5) and after the first conditioning day (Days 8, 10, 12). On conditioning days (Days 7, 14), animals were first presented with a saccharin solution for 30 minutes following which animals that were pre-exposed to morphine were injected with ethanol while those pre-exposed to ethanol were administered with morphine. Saccharin was again presented on three more occasions (Days 21, 28, 35) without drug injection. Using the percent change in saccharin consumed from the first presentation as a measure of aversion, it was found that pre-exposure to morphine blocked ethanol conditioned taste aversion. Similarly, animals pre-exposed to ethanol showed less aversion to the saccharin paired with morphine. This is the first demonstration of a symmetrical relationship between alcohol and the opiates.}, } @article {pmid6357186, year = {1983}, author = {Langhans, W and Scharrer, E}, title = {Changes in food intake and meal patterns following injection of D-mannoheptulose in rats.}, journal = {Behavioral and neural biology}, volume = {38}, number = {2}, pages = {269-286}, doi = {10.1016/s0163-1047(83)90282-0}, pmid = {6357186}, issn = {0163-1047}, mesh = {Animals ; Blood Glucose/metabolism ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Eating/*drug effects ; Feeding Behavior/*drug effects ; Heptoses/*pharmacology ; Insulin/blood ; Male ; Mannoheptulose/*pharmacology ; Rats ; Rats, Inbred Strains ; Satiety Response/drug effects ; }, abstract = {Behavioral and metabolic effects of intraperitoneal D-mannoheptulose (MH) injections were investigated in rats fed a high carbohydrate (HC) or a high fat (HF) diet. Injection of 125 or 250 mg/kg body weight (body wt) MH did not affect food intake in HC rats. Injection of 400 mg/kg body wt MH inhibited feeding in HC rats by primarily reducing meal size. In contrast, none of the MH doses tested (125, 250, 400, 800 mg/kg body wt) affected food intake or meal patterns in HF rats. The hyperglycemia following MH injection (400 mg/kg body wt) was more pronounced in HC compared to HF rats. MH injection (400 mg/kg body wt) induced a strong taste aversion in HC rats, but had only weak aversive consequences in HF rats. The data throw some doubt on the hypothetical role of insulin in the production of satiety. In addition, the results suggest that a hedonic shift takes place following MH injection in HC rats. The strong dislike for the HC diet after MH injection might be triggered by the severe disturbance of glucose homeostasis and might contribute to the transient hypophagia in HC rats by primarily reducing meal size.}, } @article {pmid6316290, year = {1983}, author = {Crawley, JN}, title = {Divergent effects of cholecystokinin, bombesin, and lithium on rat exploratory behaviors.}, journal = {Peptides}, volume = {4}, number = {4}, pages = {405-410}, doi = {10.1016/0196-9781(83)90040-2}, pmid = {6316290}, issn = {0196-9781}, mesh = {Animals ; Bombesin/*pharmacology ; Chlorides/*pharmacology ; Eating ; Exploratory Behavior/*drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Peptides/*pharmacology ; Rats ; Rats, Inbred Strains ; Sincalide/*pharmacology ; }, abstract = {Cholecystokinin induces a reduction in exploratory behaviors which could reflect an underlying behavioral state of either satiety or malaise. To investigate these alternative hypotheses, the effects of CCK were compared to the effects of (a) consumption of an extra quantity of palatable food, of (b) bombesin at doses known to inhibit food consumption, and of (c) lithium chloride, at doses known to produce taste aversion. Parameters of exploration of a novel arena surface and investigation of a novel object placed in the center of the arena were analyzed by an automated video-tracking computer-assisted animal behavior monitor. Cholecystokinin reduced all parameters of exploration. Ingestion of at least one gram of chocolate chip cookie also reduced all exploratory parameters. Bombesin reduced only parameters of approach to the novel object and the center of the arena. Lithium chloride reduced only parameters of approach to the novel object and the center of the arena. CCK may influence exploratory behaviors through mechanisms similar to those produced by ingestion of palatable food, but somewhat different from those produced by lithium and bombesin.}, } @article {pmid6314989, year = {1983}, author = {Shaw, N}, title = {Taste aversion learning: simulation of interference with the gustatory cue during conditioning.}, journal = {Behavioral and neural biology}, volume = {38}, number = {2}, pages = {307-312}, doi = {10.1016/s0163-1047(83)90310-2}, pmid = {6314989}, issn = {0163-1047}, mesh = {Animals ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Discrimination Learning/drug effects ; Drinking/drug effects ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Retention, Psychology/drug effects ; *Taste/drug effects ; *Taste Threshold/drug effects ; }, abstract = {Rats were taught an aversion to a sucrose taste cue of varying strengths. The concentration of the sucrose solution was either, 10, 7.5, 5, 2.5, 1, 0.5, or 0.25% which the animals drank for 5 min. Thirty minutes later they were poisoned with lithium chloride. On the test day all animals had access to a 10% sucrose solution regardless of the concentration they had drunk on the conditioning day. Animals conditioned with a 10, 7.5, or 5% sucrose cue subsequently displayed an identically strong aversion to the 10% cue. Only those animals conditioned with a sucrose cue which was 1% or less displayed a significantly weaker aversion to the 10% cue. The results are discussed in terms of the theory that interference with taste aversion learning by such agents as pentylenetetrazol and electroconvulsive shock may have their effect by disrupting the gustatory engram. If this assumption is correct then it suggests that the memory of the gustatory cue may be stored, at least prior to poisoning, in a quite labile state and an apparently limited disruption of taste aversion learning may in fact represent a substantial amnesic effect.}, } @article {pmid6314988, year = {1983}, author = {Archer, T and Mohammed, AK and Järbe, TU}, title = {Latent inhibition following systemic DSP4: effects due to presence and absence of contextual cues in taste-aversion learning.}, journal = {Behavioral and neural biology}, volume = {38}, number = {2}, pages = {287-306}, doi = {10.1016/s0163-1047(83)90296-0}, pmid = {6314988}, issn = {0163-1047}, mesh = {Amines/*pharmacology ; Animals ; Association Learning/drug effects ; Attention/drug effects ; Avoidance Learning/*drug effects ; Benzylamines/*pharmacology ; Chlorides/poisoning ; Conditioning, Classical/drug effects ; Drinking/drug effects ; Hippocampus/drug effects ; Lithium/poisoning ; Lithium Chloride ; Male ; Norepinephrine/*metabolism ; Rats ; Rats, Inbred Strains ; Serotonin/metabolism ; Social Environment ; Taste/*drug effects ; }, abstract = {Three taste-aversion experiments were performed to test the effect of noradrenaline (NA) depletion, following systemic administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), upon the Lubow "latent inhibition" effect in rats. DSP4-treated rats did not demonstrate any attenuation of latent inhibition, the conditioned stimulus (CS) preexposure effect. Instead, when the contextual conditions (provided by a noise-producing bottle) were so arranged that there was a "mismatch" from the saccharin preexposure to the saccharin-aversion conditioning phase, the DSP4 rats showed some considerable enhancement of latent inhibition. This disruption of the contextual control of the degree of latent inhibition evinced by the NA-depleted rats was found to bear a striking resemblance to the attenuated contextual control of extinction in taste aversion by DSP4 treated rats demonstrated earlier. Biochemical analysis of noradrenaline and serotonin accumulation performed after Experiment 1, and postdecapitation reflex analysis after each experiment, confirmed the selective NA depletion. These results are compared to earlier findings concerning noradrenaline and latent inhibition and the effects are discussed with reference to selective attentional and retrieval-based models of noradrenaline function in learning and memory.}, } @article {pmid6877871, year = {1983}, author = {Keymer, A and Crompton, DW and Sahakian, BJ}, title = {Parasite-induced learned taste aversion involving Nippostrongylus in rats.}, journal = {Parasitology}, volume = {86 (Pt 3)}, number = {}, pages = {455-460}, doi = {10.1017/s0031182000050642}, pmid = {6877871}, issn = {0031-1820}, mesh = {Animals ; Eating ; Female ; Nematode Infections/*psychology/veterinary ; Nippostrongylus ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {After demonstrating that rats were capable of discriminating between the same diet treated with either flavour 1 or flavour 2 and that the 2 flavours of diet were equipreferred, an experiment was carried out to see whether learned taste aversion might play a role in the reduction of food intake that is commonly observed during the course of a parasitic infection. The results showed that rats, given a subcutaneous inoculation of approximately 6000 third-stage larvae of Nippostrongylus brasiliensis (Nematoda) while feeding on a diet containing flavour 2, strongly preferred to eat diet containing flavour 1 when given simultaneous choice conditions. Uninfected rats showed no preference and ate equal amounts of both flavoured diets. This effect is interpreted as the first experimental demonstration of learned taste aversion using a eukaryotic parasite as the inductive agent.}, } @article {pmid6310659, year = {1983}, author = {Misanin, JR and Guanowsky, V and Riccio, DC}, title = {The effect of CS-preexposure on conditioned taste aversion in young and adult rats.}, journal = {Physiology & behavior}, volume = {30}, number = {6}, pages = {859-862}, doi = {10.1016/0031-9384(83)90248-2}, pmid = {6310659}, issn = {0031-9384}, support = {MH 30223/MH/NIMH NIH HHS/United States ; MH 37235/MH/NIMH NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Chlorides ; *Conditioning, Psychological ; Female ; Lithium ; Lithium Chloride ; Rats ; Rats, Inbred Strains ; Saccharin ; *Taste ; }, abstract = {Young and adult rats were given nonreinforced exposures to the flavor-CS prior to a taste aversion conditioning session. CS-preexposure prevented the conditioning of a taste aversion in young rats but only attenuated conditioning in adults. These results suggest that an enhanced CS-preexposure effect may account for the previously reported weaker conditioned taste aversion observed in young rats, as compared to adults, when there is a protracted interstimulus interval.}, } @article {pmid6307325, year = {1983}, author = {Kurz, EM and Levitsky, DA}, title = {Lithium chloride and avoidance of novel places.}, journal = {Behavioral neuroscience}, volume = {97}, number = {3}, pages = {445-451}, doi = {10.1037//0735-7044.97.3.445}, pmid = {6307325}, issn = {0735-7044}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/*poisoning ; Conditioning, Classical/*drug effects ; Exploratory Behavior/drug effects ; Lithium/*poisoning ; Lithium Chloride ; Male ; Muridae ; Orientation/drug effects ; *Social Environment ; Taste/drug effects ; }, abstract = {Rats were exposed to a distinctive chamber (chamber A, part of a two-chamber apparatus), which was novel for half of the rats but familiar for the other half. Each rat was subsequently injected with lithium chloride or saline. In a test trial conducted 24 hr later, all rats were given a choice between chamber A and a second chamber (B), which was novel for all rats. The main result was that the group made familiar with chamber A and then given lithium showed a significant preference for that side or an avoidance of the novel side, a "spatial neophobia." A second experiment confirmed the spatial neophobia effect and demonstrated that it was not dependent on the particular conditioning procedure used in the first experiment. The spatial neophobia effect was related to similar effects in the taste aversion literature, and to the results of research on lithium-induced decreases in exploratory behavior.}, } @article {pmid6871671, year = {1983}, author = {Davis, JL and Pico, RM and Cherkin, A}, title = {Dose-dependent and time-dependent action of oxytocin on chick memory.}, journal = {Brain research}, volume = {266}, number = {2}, pages = {355-358}, doi = {10.1016/0006-8993(83)90669-8}, pmid = {6871671}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/drug effects ; Chickens ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Kinetics ; Male ; Memory/*drug effects ; Oxytocin/*pharmacology ; Time Factors ; }, abstract = {Experiments were conducted to investigate the dose-related and time-dependent effects of oxytocin on memory for a one-trial conditioned taste aversion task using two-day old chicks. Oxytocin was administered intracerebrally 1 min posttraining to 5 groups of chicks in dose levels differing by a factor of 10 and ranging from 5.0 pg to 50 ng. A second experiment tested the time-dependent nature of the neuropeptide's action. In this experiment the oxytocin (5.0 ng) was administered at either 1 min, 9 min or 59 min posttraining. In both experiments saline-injected control groups were included. The taste aversion training for all experiments consisted of presenting an attractive lure, coated with an aversive liquid (EtOH), to each chick for a 10-s training trial. Most chicks pecked 1 or 2 times at the lure before inhibiting any further response. The retention testing took place 24 h after the training and consisted of presenting the dry, uncoated lure to each chick for an additional 10 s. Chicks that avoided pecking at the lure were considered to have exhibited enhanced retention. The groups of chicks receiving 50 pg to 50 ng of oxytocin exhibited enhancement of retention, as did the 1 min group of the time-dependent experiment. These results are compared to the effects on memory consolidation in chicks induced by vasopressin and L-prolyl-L-leucyl-glycineamide. The apparent conflict between these results and those obtained in mammalian studies with oxytocin are discussed.}, } @article {pmid6685096, year = {1983}, author = {Suzuki, T and Masukawa, Y and Yoshii, T and Kawai, T and Yanaura, S}, title = {[Effect of methamphetamine on morphine preference].}, journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica}, volume = {81}, number = {5}, pages = {459-468}, pmid = {6685096}, issn = {0015-5691}, mesh = {Animals ; Caffeine/pharmacology ; Choice Behavior/*drug effects ; Cocaine/pharmacology ; Drug Combinations ; Humans ; Male ; Methamphetamine/*pharmacology/toxicity ; *Morphine/toxicity ; Morphine Dependence ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; }, abstract = {The effect of methamphetamine on preference for morphine was studied in rats by the drug-admixed food (DAF) method. The preference rates for morphine-admixed food gradually increased by the repetition of choice and forced trials and then became stable at the level of 70%. On the other hand, the preference rates for morphine-admixed food combined with methamphetamine did not so increase compared with the case of morphine alone. From the taste aversion test, it was assumed that combination of morphine and methamphetamine did not enhance taste aversion, although methamphetamine suppressed development of preference for morphine. In the case of combination of morphine and cocaine or caffeine, preference rates for these drugs increased like the case of morphine. This result indicated that the suppression of the preference for morphine which was induced by methamphetamine was not produced by the general effect of CNS stimulants. We found that methamphetamine suppressed the development of the preference for morphine. These findings suggest that the suppression resulted from neither taste aversion nor the general effect of CNS stimulants. Furthermore, acute toxicity and other effects were enhanced by the combination of morphine and methamphetamine, and it might participate with the suppression.}, } @article {pmid6626102, year = {1983}, author = {Ossenkopp, KP}, title = {Area postrema lesions in rats enhance the magnitude of body rotation-induced conditioned taste aversions.}, journal = {Behavioral and neural biology}, volume = {38}, number = {1}, pages = {82-96}, doi = {10.1016/s0163-1047(83)90414-4}, pmid = {6626102}, issn = {0163-1047}, mesh = {Animals ; Cerebral Ventricles/*physiology ; *Conditioning, Classical ; Male ; Motion Sickness ; N-Methylscopolamine ; Rats ; Rats, Inbred Strains ; *Rotation ; Saccharin/administration & dosage ; Scopolamine Derivatives/pharmacology ; *Taste ; }, abstract = {The role of the area postrema, a circumventricular organ located on the dorsal medulla in the fourth ventricle, in body rotation-induced conditioned taste aversions was examined in male hooded rats. One group of rats received lesions of the area postrema, another group was given sham lesions, and two other groups received no surgery. Three groups of rats, those with area postrema lesions, those with sham lesions, and one unoperated group, were given pairings of 1-hr access to a 0.1% sodium saccharin solution with 30 min of body rotation at 70 rpm (on a schedule of 15-sec on--5-sec off). A fourth group of unoperated rats was given pairings of access to the saccharin solution with 30 min of sham rotation. The three rotated groups all developed a taste aversion to the saccharin solution whereas the sham-rotated group did not. The group with lesions of the area postrema exhibited a greater aversion to the saccharin taste than the other two rotated groups. In a second phase of the experiment all rats were given pairing of 1-hr access to chocolate milk with injections of scopolamine methyl nitrate (1 mg/kg). The area postrema-lesioned group failed to exhibit a taste aversion to the chocolate milk whereas the other groups all showed very strong aversions. It was concluded that area postrema lesions abolish taste aversions induced by blood-borne toxins such as scopolamine methyl nitrate, but enhance taste aversions induced by motion sickness. Some speculations concerning the enhanced taste aversions induced by motion sickness in area postrema lesioned rats, are provided.}, } @article {pmid6407035, year = {1983}, author = {Miller, DB and Miller, LL}, title = {Bupropion, d-amphetamine, and amitriptyline-induced conditioned taste aversion in rats: dose effects.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {18}, number = {5}, pages = {737-740}, doi = {10.1016/0091-3057(83)90016-3}, pmid = {6407035}, issn = {0091-3057}, mesh = {Amitriptyline/*pharmacology ; Analysis of Variance ; Animals ; Antidepressive Agents/*pharmacology ; Avoidance Learning/*drug effects ; Bupropion ; Dextroamphetamine/*pharmacology ; Dose-Response Relationship, Drug ; Female ; Male ; Propiophenones/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Nine groups of rats (n = 6 per group) were adapted to a daily one-half hour period of water availability. When intake had stabilized, they were allowed access to a 0.1% (w/v) solution of saccharin, and immediately afterward were given IP injections of isotonic saline; bupropion HCl (10.0, 20.0, or 40.0 mg/kg); d-amphetamine-sulfate (0.5, 1.0, 2.0 mg/kg); or amitriptyline HCl (5.0, 10.0, or 20.0 mg/kg) in a volume of 1 ml. The lowest dose of each compound as chosen to be equipotent in screening tests used to identify potential antidepressants. Following 2 days of access to water alone, all groups were given a choice between water and saccharin for 3 consecutive days. All compounds induced taste aversions in a dose-related manner, but amitriptyline induced greater and longer-lasting aversions than either bupropion or d-amphetamine which were equipotent over the dose range studied. As such, this is the first demonstration that bupropion and amitriptyline, two clinically effective antidepressants, can induce taste aversions and replicates as well the common finding that d-amphetamine has substantial taste aversion-inducing properties. The ability of these compounds to induce taste aversions could be mediated through their effects on central catecholaminergic processes although amitriptyline has significant peripheral anticholinergic effects.}, } @article {pmid6304784, year = {1983}, author = {Zabik, JE and Roache, JD}, title = {5-hydroxytryptophan-induced conditioned taste aversion to ethanol in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {18}, number = {5}, pages = {785-790}, doi = {10.1016/0091-3057(83)90023-0}, pmid = {6304784}, issn = {0091-3057}, support = {GM 07095/GM/NIGMS NIH HHS/United States ; RR 0558613/RR/NCRR NIH HHS/United States ; }, mesh = {5-Hydroxytryptophan/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Conditioning, Psychological/drug effects ; *Ethanol ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Taste/*drug effects ; Time Factors ; }, abstract = {This experiment was conducted to determine the efficacy of 5-HTP in producing conditioned taste aversions (CTAs) to ethanol in rats restricted to a one-hour daily access to fluid. Administration of 100 mg/kg of DL-5-HTP immediately following novel exposure to ethanol resulted in an aversion of such magnitude that some rats refused to consume the ethanol solution. Since ethanol was the only fluid available to these rats, they eventually died, presumably of dehydration. By comparison, LiCl administration also produced a CTA to ethanol, but no such persistent rejection was observed. Both 5-HTP and LiCl also produced CTAs when saccharin and tartaric acid solutions were used as novel fluids, but these aversions were short-lived and all rats resumed drinking. The causative factor(s) in the persistent ethanol rejection until death observed in rats treated with 5-HTP remain undetermined but the results have indicated that simple CS-UCS associative learning mechanisms are probably not a primary causative factor.}, } @article {pmid6220081, year = {1983}, author = {Kusnecov, AW and Sivyer, M and King, MG and Husband, AJ and Cripps, AW and Clancy, RL}, title = {Behaviorally conditioned suppression of the immune response by antilymphocyte serum.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {130}, number = {5}, pages = {2117-2120}, pmid = {6220081}, issn = {0022-1767}, mesh = {Animals ; Antilymphocyte Serum/*administration & dosage ; Conditioning, Classical/*physiology ; Female ; *Immune Tolerance ; Immunity, Cellular ; Lymphocyte Culture Test, Mixed ; Male ; Rabbits ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Taste/drug effects ; }, abstract = {Previous studies have shown that cyclophosphamide, a drug with a broad spectrum of cytotoxic activity and one that produces noxious gastrointestinal side effects, can elicit taste aversion conditioning when paired with a non-immunosuppressive oral stimulus (saccharin) resulting in immunosuppression after subsequent exposure to the paired stimulus (1). The study reported here indicates that rabbit anti-rat lymphocyte serum (ALS) which is selectively cytotoxic for lymphocytes and does not produce sensory side effects can similarly induce taste aversion conditioning of the immune response. Rats were exposed to oral saccharin paired with ALS injection. Upon subsequent reexposure to saccharin alone the immunosuppressive effects of ALS were reenlisted and the primary mixed lymphocyte culture response of conditioned rats to allogeneic lymphocytes was suppressed by 35% compared to controls. The demonstrated influence of psychologic factors on the immune response has far reaching implications, especially to human medicine, and their role in the course of disease and recovery in man demands further investigation.}, } @article {pmid6135477, year = {1983}, author = {Kumar, R and Pratt, JA and Stolerman, IP}, title = {Characteristics of conditioned taste aversion produced by nicotine in rats.}, journal = {British journal of pharmacology}, volume = {79}, number = {1}, pages = {245-253}, pmid = {6135477}, issn = {0007-1188}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Ganglionic Blockers/pharmacology ; Male ; Mecamylamine/pharmacology ; Nicotine/*pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {1 Nicotine produced conditioned taste aversions in rats which were directly related to the dose of nicotine and to the number of conditioning trials. 2 The tobacco alkaloid (-)-nicotine was four to five times as potent as its stereoisomer, (+)-nicotine. 3 Mecamylamine but not hexamethonium blocked the development of taste aversions produced by nicotine. 4 Mecamylamine did not block the development of taste aversions produced by apomorphine. 5 Prolonged treatment with mecamylamine prior to conditioning did not produce supersensitivity to nicotine.}, } @article {pmid6878467, year = {1983}, author = {Spector, AC and Smith, JC and Hollander, GR}, title = {The effect of postconditioning CS experience on recovery from radiation-induced taste aversion.}, journal = {Physiology & behavior}, volume = {30}, number = {4}, pages = {647-649}, doi = {10.1016/0031-9384(83)90236-6}, pmid = {6878467}, issn = {0031-9384}, support = {CA22768/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Cues ; *Food Preferences ; Gamma Rays ; Male ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste/*physiology ; }, abstract = {Seventy-two hours after saccharin (CS) was paired with either a 100R or sham radiation exposure, rats received a 0-, 3-, 6-, 12-, 24-, or 46-hour saccharin-alone presentation followed by a 23-hour two-bottle preference test. Generally, faster recovery from the aversion was observed in animals receiving longer CS-alone presentations. The present procedure differs from previous work done with other toxins in that animals were not fluid-deprived during the postconditioning period. This enabled animals to constantly control the volume, duration, and inter-bout interval of the saccharin drinking episodes independent of any experimentally imposed drinking schedule. In addition, the two-bottle test provided a sensitive measure of the status of the saccharin aversion following the saccharin-alone presentation.}, } @article {pmid6405760, year = {1983}, author = {Corcoran, ME and Lewis, J and Fibiger, HC}, title = {Forebrain noradrenaline and oral self-administration of ethanol by rats.}, journal = {Behavioural brain research}, volume = {8}, number = {1}, pages = {1-21}, doi = {10.1016/0166-4328(83)90168-7}, pmid = {6405760}, issn = {0166-4328}, mesh = {Alcohol Drinking ; Animals ; *Brain Chemistry ; Conditioning, Psychological/physiology ; Ethanol/*administration & dosage ; Hydroxydopamines/pharmacology ; Male ; Norepinephrine/metabolism/*physiology ; Oxidopamine ; Quinine/administration & dosage ; Rats ; Rats, Inbred Strains ; Self Administration ; }, abstract = {The effects of 6-hydroxydopamine-induced depletion of forebrain noradrenaline (NA) on oral intake of ethanol were studied in male Wistar rats. Prior depletion of NA produced a smaller and significantly less variable intake of a concentrated solution of ethanol than that of control rats, and this effect was not accompanied by hyperreactivity to aversive solutions of quinine. NA-depleted rats also displayed rejection 'thresholds' for ethanol solutions that were significantly lower than those of controls. Depletion of forebrain NA did not, however, affect the punishing effects of ethanol injections measured in the conditioned taste aversion paradigm. In contrast to these effects of NA depletion on initiation of ethanol intake, depletion of forebrain NA after a preference for ethanol had been established failed to affect subsequent intake of ethanol. These results suggest that forebrain NA is involved in the initiation of ethanol intake by naive rats but not in the maintenance of established patterns of intake by experienced rats. Possible mechanisms for this differential involvement of NA are discussed.}, } @article {pmid6306696, year = {1983}, author = {Rabin, BM and Hunt, WA}, title = {Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {18}, number = {4}, pages = {629-635}, doi = {10.1016/0091-3057(83)90292-7}, pmid = {6306696}, issn = {0091-3057}, mesh = {Animals ; Antiemetics/*pharmacology ; Avoidance Learning/*drug effects/radiation effects ; Benzamides/pharmacology ; Chlorides/pharmacology ; Cyclizine/pharmacology ; Lithium/pharmacology ; Lithium Chloride ; Male ; Prochlorperazine/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.}, } @article {pmid6306695, year = {1983}, author = {Smith, DF}, title = {Lithium and carbamazepine: effects on learned taste aversion and open field behavior in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {18}, number = {4}, pages = {483-488}, doi = {10.1016/0091-3057(83)90268-x}, pmid = {6306695}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Body Weight/drug effects ; Carbamazepine/blood/*pharmacology ; Chlorides/pharmacology ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Three experiments were done to compare effects of LiCl and carbamazepine (CBZ) on behaviors known to be influenced by LiCl in rats. The first experiment showed acute treatment with either LiCl (0.3-1.5 mmol/kg) or CBZ (0.13-0.42 mmol/kg) to produce a learned taste aversion to saccharin. The second experiment showed short-term treatment (once daily for 5 days) with LiCl (1.5 mmol/kg/day) to suppress open field activity in otherwise untreated rats and to cause a behavioral syndrome when given together with pargyline. In contrast, short-term treatment with CBZ (0.42 mmol/kg/day) failed to influence open field behavior. The third experiment compared effects of LiCl (1.5 mmol/kg) and CBZ given at a dose (1.68 mmol/kg) higher than that used in Experiments 1 and 2. LiCl or CBZ had similar suppressant effects on locomotor activity in otherwise untreated rats, but only LiCl led to a behavioral syndrome in rats given pargyline. The findings suggest that LiCl and CBZ may have some similar mechanisms of action on behavior, as well as some different ones.}, } @article {pmid6304804, year = {1983}, author = {Cairnie, AB}, title = {Adverse effects of radioprotector WR2721.}, journal = {Radiation research}, volume = {94}, number = {1}, pages = {221-226}, pmid = {6304804}, issn = {0033-7587}, mesh = {Amifostine/adverse effects/*toxicity ; Animals ; Conditioning, Psychological/*drug effects/radiation effects ; Diet ; Dose-Response Relationship, Drug ; Male ; Nausea/*etiology ; Organothiophosphorus Compounds/*toxicity ; Radiotherapy/*adverse effects ; Rats ; Rats, Inbred Strains ; Research Design ; Saccharin/pharmacology ; Taste/drug effects/radiation effects ; Vomiting/*etiology ; }, abstract = {S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic--in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy60Co gamma radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approximately 200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation.}, } @article {pmid6626092, year = {1983}, author = {Davis, JL and Buresova, O and Bures, J}, title = {Cortical spreading depression and conditioned taste aversion: an attempt to resolve a controversy.}, journal = {Behavioral and neural biology}, volume = {37}, number = {2}, pages = {338-343}, doi = {10.1016/s0163-1047(83)91444-9}, pmid = {6626092}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; *Cortical Spreading Depression ; Cues ; Male ; Rats ; Taste/*physiology ; }, abstract = {The claim (Winn, Todd, & Elias, Behav. Biol. 19, 55-63 (1977)) that cortical spreading depression (CSD) can serve as US in the conditioned taste-aversion (CTA) paradigm was experimentally examined. Rats given 15-min access to novel 0.1% sodium saccharin (CS) followed by ip NaCl and bilateral or unilateral CSD (US) displayed similar saccharin preference (54%) as the sham-CSD-treated controls in a multiple-bottle retention test. Rats receiving ip LiCl (0.15 M, 2% body weight) and sham CSD as the US showed marked saccharin aversion. It is concluded that CSD does not elicit CTA and that some claims to the contrary can perhaps be ascribed to CSD-induced disruption of attenuation of neophobia.}, } @article {pmid6300938, year = {1983}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Acquisition of lithium chloride- and radiation-induced taste aversions in hypophysectomized rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {18}, number = {3}, pages = {463-465}, doi = {10.1016/0091-3057(83)90470-7}, pmid = {6300938}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Dose-Response Relationship, Radiation ; Hypophysectomy ; Lithium/poisoning ; Lithium Chloride ; Pituitary-Adrenal System/*physiology ; Rats ; Taste/*physiology ; }, abstract = {The effects of hypophysectomy on the acquisition of conditioned taste aversions following injection of lithium chloride and following exposure to ionizing radiation were studied using a two-bottle preference test. Hypophysectomy did not disrupt the acquisition of a taste aversion following either treatment. The results are interpreted as: (a) suggesting that pituitary/adrenal hormones do not mediate the acquisition of a conditioned taste aversion following injections of lithium chloride or following exposure to ionizing radiation in a two-bottle preference test, and (b) consistent with other research suggesting that the involvement of pituitary/adrenal hormones in taste aversion learning may be related to the conflict induced by using a one-bottle test and not to the learning itself.}, } @article {pmid6302719, year = {1983}, author = {Fitzgerald, RE and Burton, MJ}, title = {Neophobia and conditioned taste aversion deficits in the rat produced by undercutting temporal cortex.}, journal = {Physiology & behavior}, volume = {30}, number = {2}, pages = {203-206}, doi = {10.1016/0031-9384(83)90006-9}, pmid = {6302719}, issn = {0031-9384}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Lithium/poisoning ; Lithium Chloride ; Muridae ; Neural Pathways/physiology ; Taste/*physiology ; Temporal Lobe/*physiology ; }, abstract = {Adult male hooded rats with parasagittal knife-cuts between the amygdala and temporal cortex (n = 8), with electrolytic basolateral amygdala lesions (n = 8), and sham-operated controls (n = 8), were tested for neophobia and LiCl-induced aversion to a 0.1% saccharin solution in a one-bottle forced choice paradigm. Both types of lesion produced equal deficits in neophobia and conditioned aversion. It was concluded that severing the connections between the amygdala and the temporal cortex produces the same deficits as basolateral amygdala damage. Possible anatomical substrates for these effects are discussed.}, } @article {pmid6301517, year = {1983}, author = {Peters, RH}, title = {Learned aversions to copulatory behaviors in male rats.}, journal = {Behavioral neuroscience}, volume = {97}, number = {1}, pages = {140-145}, doi = {10.1037//0735-7044.97.1.140}, pmid = {6301517}, issn = {0735-7044}, mesh = {Animals ; Chlorides/pharmacology ; *Conditioning, Classical ; *Copulation ; Environment ; Extinction, Psychological ; Female ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; }, abstract = {When male rats received an injection of lithium chloride immediately after an encounter with an estrous female, the vigor of subsequent copulatory responding was initially unaffected. After 5 to 10 such pairings, however, male rats displayed an aversion to copulatory behaviors; they ceased to copulate entirely. These aversions persisted when the rats were tested in a novel environment and extinguished after four nonreinforced trials. This multiple-trial adaptation of the conditioned taste aversion paradigm provides a new approach to the aversive control of sexual behavior.}, } @article {pmid6301516, year = {1983}, author = {Kramer, TH and Sclafani, A and Kindya, K and Pezner, M}, title = {Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts.}, journal = {Behavioral neuroscience}, volume = {97}, number = {1}, pages = {110-119}, doi = {10.1037//0735-7044.97.1.110}, pmid = {6301516}, issn = {0735-7044}, mesh = {Animals ; Body Weight ; Chlorides/administration & dosage ; Conditioning, Classical/*physiology ; Extinction, Psychological/physiology ; Female ; Hypothalamus, Middle/*physiology ; Lithium/administration & dosage ; Lithium Chloride ; Obesity/physiopathology ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Sodium Chloride/administration & dosage ; Taste/*physiology ; Water Deprivation ; }, abstract = {The development of a conditioned taste aversion (CTA) was assessed in rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). The animals were water deprived and presented with a .1% saccharin solution paired with injections of either lithium chloride or sodium chloride. In Experiment 1, VMH rats tested at a nonobese weight level did not differ from sham-operated control rats in the acquisition and extinction of the CTA. In Experiment 2, moderately obese VMH rats displayed a stronger CTA than did sham-operated control rats as evidenced by a slower rate of extinction. This effect was not due to the higher absolute dose of LiCl given to the obese VMH rats. A second group of obese VMH rats given an amount of LiCl equivalent to that given to the control rats also displayed retarded extinction of the CTA. The results of these experiments demonstrate that hyperphagia-inducing knife cuts do not alter aversive taste conditioning in rats but that hypothalamic obesity does enhance conditioned taste aversions. This may reflect an obesity-induced suppression in appetitive motivation.}, } @article {pmid6296913, year = {1983}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Attenuation of radiation- and drug-induced conditioned taste aversions following area postrema lesions in the rat.}, journal = {Radiation research}, volume = {93}, number = {2}, pages = {388-394}, pmid = {6296913}, issn = {0033-7587}, mesh = {Animals ; Avoidance Learning/drug effects/*radiation effects ; Brain Stem/drug effects/physiology/*radiation effects ; Chlorides/pharmacology ; Drinking ; Histamine/pharmacology ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/drug effects/*radiation effects ; Whole-Body Irradiation ; }, abstract = {The effects of lesions of the area postrema on the acquisition of radiation- and drug-induced (histamine and lithium chloride) conditioned taste aversions were investigated. The results indicated that area postrema lesions caused a significant attenuation of the aversion produced by pairing a novel sucrose solution with radiation (100 rad) or drug injection. Further, the area postrema lesions produced a similar level of attenuation of the taste aversion in all three treatment conditions. The results are discussed in terms of the implications of this finding for defining the mechanisms by which exposure to ionizing radiation can lead to the acquisition of a conditioned taste aversion.}, } @article {pmid6824923, year = {1983}, author = {van der Kooy, D and Swerdlow, NR and Koob, GF}, title = {Paradoxical reinforcing properties of apomorphine: effects of nucleus accumbens and area postrema lesions.}, journal = {Brain research}, volume = {259}, number = {1}, pages = {111-118}, doi = {10.1016/0006-8993(83)91071-5}, pmid = {6824923}, issn = {0006-8993}, mesh = {Animals ; Apomorphine/*pharmacology ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; Dose-Response Relationship, Drug ; Male ; Medulla Oblongata/*drug effects ; Nucleus Accumbens/*drug effects/physiology ; Rats ; *Reinforcement, Psychology ; Septal Nuclei/*drug effects ; Taste/drug effects ; }, abstract = {Apomorphine (0.01-10.0 mg/kg, subcutaneously) paradoxically produced both dose-dependent aversive and positive reinforcing effects, as measured in conditioned taste aversion and place preference paradigms, respectively. The conditioned taste aversions produced by apomorphine were not modified in rats with bilateral 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens (producing 92% depletion of dopamine in the nucleus accumbens) nor in rats with thermal lesions of the area postrema. Both types of lesions were behaviorally verified as effective in other paradigms; the 6-OHDA lesions potentiated the facilitatory effects to a novel flavor paired with scopolamine methylnitrate (1.0 mg/kg, intraperitoneally). However, 6-OHDA lesions of the nucleus accumbens did clearly potentiate the conditioned place preferences induced by apomorphine. These results suggest that both the positive reinforcing and locomotor effects of apomorphine may partially result from activation of post-synaptic dopamine receptors in the nucleus accumbens. Moreover, the dissociation of apomorphine's aversive and positive reinforcing properties revealed by the 6-OHDA lesions may provide the first step in attempts to pinpoint the different brain sites of action where apomorphine produces its opposite motivational effects.}, } @article {pmid6856006, year = {1983}, author = {Kallman, MJ and Lynch, MR and Landauer, MR}, title = {Taste aversions to several halogenated hydrocarbons.}, journal = {Neurobehavioral toxicology and teratology}, volume = {5}, number = {1}, pages = {23-27}, pmid = {6856006}, issn = {0275-1380}, mesh = {Animals ; Conditioning, Psychological/drug effects ; Dichloroethylenes/toxicity ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Hydrocarbons, Halogenated/*toxicity ; Male ; Mice ; Mice, Inbred Strains ; Saccharin ; Taste/*drug effects ; Trichloroethylene/toxicity ; }, abstract = {Five halogenated hydrocarbons (chloral; trichloroethylene; 1,2-dichloroethylene; 1,2-dichloroethane and 1,1,2-trichloroethane) were evaluated in the taste aversion paradigm to determine thresholds for producing aversion effects. Comparisons were made between threshold determination for acute and repetitive conditioning trials. All of the compounds produced saccharin aversions following one pairing of the chemical exposure with saccharin ingestion. Repetitive conditioning trials did not alter the thresholds for producing aversions with any of the five compounds evaluated. Potencies of the compounds in producing conditioned taste aversions were chloral greater than 1,1,2-trichloroethane greater than 1,2-dichloroethane greater than 1,2-dichloroethylene greater than trichloroethylene.}, } @article {pmid6647588, year = {1983}, author = {Buresová, O and Bures, J and Skopková, J}, title = {Specificity of the effect of desglycinamide (8-D-arginine) deaminovasopressin on short--term memory.}, journal = {Physiologia Bohemoslovaca}, volume = {32}, number = {5}, pages = {403-408}, pmid = {6647588}, issn = {0369-9463}, mesh = {Animals ; Arginine Vasopressin/*pharmacology ; Avoidance Learning/drug effects ; Deamino Arginine Vasopressin/*pharmacology ; Lypressin/pharmacology ; Male ; Memory, Short-Term/*drug effects ; Nerve Tissue Proteins/pharmacology ; Rats ; }, abstract = {The effect of desglycinamide (8-D-arginine) deaminovasopressin (desgly NH2 dDAVP) on learning was studied in rats using the conditioned taste aversion (CTA) paradigm. Desgly NH2 dDAVP (3 micrograms/kg) applied 40 min before presentation of the gustatory CS (0.1 % saccharin) did not affect CTA formation, when the visceral US (0.15 mol/l LiCl, 2 % body weight) was applied after a 1 h delay. With 2 h CS-US delay the same dosage of the peptide caused CTA impairment, manifested by weaker and faster decaying aversion to saccharin. The above effect of the peptide was blocked by post-CS anesthesia (pentobarbital 40 mg/kg). It is suggested that desgly NH2 dDAVP affects learning indirectly, by increased arousal interfering with the persistence of the short-term gustatory traces in the relatively long CS-US interval.}, } @article {pmid6309134, year = {1983}, author = {Bermudez-Rattoni, F and Rusiniak, KW and Garcia, J}, title = {Flavor-illness aversions: potentiation of odor by taste is disrupted by application of novocaine into amygdala.}, journal = {Behavioral and neural biology}, volume = {37}, number = {1}, pages = {61-75}, doi = {10.1016/s0163-1047(83)91075-0}, pmid = {6309134}, issn = {0163-1047}, support = {AA 03513/AA/NIAAA NIH HHS/United States ; HD 05958/HD/NICHD NIH HHS/United States ; NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/*drug effects ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Chlorides/poisoning ; Conditioning, Classical/drug effects ; Electroshock ; Lithium/poisoning ; Lithium Chloride ; Male ; Procaine/*pharmacology ; Rats ; Rats, Inbred Strains ; Smell/*drug effects ; Taste/*drug effects ; }, abstract = {Taste and odor have different properties in toxiphobic conditioning. When each is used alone, taste becomes aversive when followed by immediate or delayed poison, while odor becomes aversive only if followed by immediate poison. However, if odor and taste are presented as a compound and followed by delayed poison, then odor does become aversive when tested alone. It is as if taste has potentiated the odor signal. Several experiments assessed the role of the amygdala in this potentiation effect by anesthetizing the amygdala with 10% novocaine. Novocaine applied 30 min before presentation (Pre-CS) of an odor-taste compound disrupted the potentiated odor aversion but not the taste aversion. In contrast, novocaine applied 1 min after the compound odor-taste or 1 min prior to LiCl poison did not dissociate odor and taste aversions; both odor and taste aversions were facilitated. Novocaine applied 30 min before an odor alone also disrupted an odor aversion induced by immediate LiCl. But identical treatment did not disrupt odor avoidance conditioned by immediate foot-shock, suggesting that amygdala anesthesia does not simply produce anosmia. Pre-CS novocaine treatment also disrupted flavor neophobia prior to conditioning. The results suggest that novocaine applied to the amygdala disrupts the integration of odor with taste and illness during toxiphobic conditioning.}, } @article {pmid6309133, year = {1983}, author = {Guanowsky, V and Misanin, JR and Riccio, DC}, title = {Retention of conditioned taste aversion in weanling, adult, and old-age rats.}, journal = {Behavioral and neural biology}, volume = {37}, number = {1}, pages = {173-178}, doi = {10.1016/s0163-1047(83)91187-1}, pmid = {6309133}, issn = {0163-1047}, support = {MH 37235/MH/NIMH NIH HHS/United States ; }, mesh = {*Aging ; Animals ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Female ; Lithium/poisoning ; Lithium Chloride ; *Memory/drug effects ; Rats ; Rats, Inbred Strains ; *Retention, Psychology/drug effects ; *Taste/drug effects ; }, abstract = {Rats ranging in age from weanling to old age were given a single saccharin/lithium chloride pairing and were tested for saccharin aversion 1 or 28 days later. Weanling, adult, and old-age rats did not differ in their retention of the conditioned aversion at the 1-day retention interval, but weanling rats showed substantially less aversion than adult and old-age rats at the 28-day interval. The old-age rats did not differ from the adults at either retention interval. As old-age rats generally forget a passive avoidance task sooner than adults do, these results lend limited support to the hypothesis that retention of conditioned taste aversion may be mediated by a different memory system than the system that mediates retention of more conventional types of learning.}, } @article {pmid6188180, year = {1983}, author = {Langhans, W and Wiesenreiter, F and Scharrer, E}, title = {Plasma metabolites and food intake reduction following heparinoid injection in rats.}, journal = {Physiology & behavior}, volume = {30}, number = {1}, pages = {113-119}, doi = {10.1016/0031-9384(83)90046-x}, pmid = {6188180}, issn = {0031-9384}, mesh = {3-Hydroxybutyric Acid ; Animals ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Eating/*drug effects ; Fatty Acids, Nonesterified/*blood ; Glycerol/*blood ; Hydroxybutyrates/*blood ; Male ; Pentosan Sulfuric Polyester/*pharmacology ; Polysaccharides/*pharmacology ; Rats ; Rats, Inbred Strains ; Satiation/drug effects ; }, abstract = {Behavioral and physiological consequences of heparinoid injections, which increase plasma levels of nonesterified fatty acids (NEFA) by releasing lipoproteinlipase into the circulation, were studied in rats, because, according to the lipostatic hypothesis of food intake control, changes in plasma metabolite levels should influence food intake. Subcutaneously injected 55 mg/kg body wt. of the heparinoid Na-pentosanpolysulfate (PPS) significantly reduced feeding in rats with ad lib access to either a high carbohydrate (HC) or a high fat (HF) diet. However, the reduction of food intake in HF-rats exceeded that in HC-rats. Moreover, the food intake reduction following PPS-injections was associated with greater increases in plasma levels of NEFA and free glycerol in HF-rats, whereas PPS increased plasma levels of D-(-)-3-hydroxybutyrate only in HF-rats, and did not alter blood glucose concentrations. Although PPS inhibited blood coagulation, it did not affect the hematocrit. Furthermore, PPS-injections that reduced feeding, failed to produce a conditioned taste aversion in a two bottle preference test. The data therefore strongly suggest that elevated levels of plasma NEFA and/or free plasma glycerol decrease food intake in rats. These metabolites might contribute to a lipostatic mechanism of feeding control.}, } @article {pmid6295562, year = {1982}, author = {Pritchard, TC and Scott, TR}, title = {Amino acids as taste stimuli. II. Quality coding.}, journal = {Brain research}, volume = {253}, number = {1-2}, pages = {93-104}, doi = {10.1016/0006-8993(82)90676-x}, pmid = {6295562}, issn = {0006-8993}, support = {NS 10405/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Axons/physiology ; Chorda Tympani Nerve/*physiology ; Conditioning, Classical/physiology ; Evoked Potentials, Somatosensory ; Generalization, Stimulus/physiology ; Male ; Neural Inhibition ; Neurons/physiology ; Rats ; Rats, Inbred Strains ; Reaction Time/physiology ; Synaptic Transmission ; Taste/*physiology ; Taste Threshold/physiology ; }, abstract = {Two experiments were performed in rats to evaluate the relative taste qualities of 12 L-amino acids, each at a concentration which evoked half the maximum response for that chemical. The first study involved recording the activity of 40 individual chorda tympani fibers to the stimulus series. Only 34% of the evoked responses resembled the short latency phasic-tonic activity which characterizes gustatory responses to inorganic salts and acids. 32% had latencies exceeding 1 s; another 27% consisted of only a phasic burst lasting less than 1 s. The remaining 7% were inhibitory. Both long latency and purely phasic activity were stimulus selective: 61% of the former were in response to Gly or Pro while 69% of the latter were evoked by Cys-HCl, Lys-HCl or His. Response inhibition was not associated with either specific fibers or stimuli. Thus amino acids, which to humans represent a class of perceptually complex stimuli, show a corresponding complexity of evoked neural properties in the rat. The second study employed a conditioned taste aversion paradigm to assess the qualitative similarity of each amino acid to the others and to the 4 prototypical taste stimuli; NaCl, HCl, quinine-HCl and sucrose. Some amino acids showed strong generalization to a single gustatory prototype (Pro and Gly to sucrose; Cys-HCl to HCl); others generalized well to multiple prototypes (e.g. Arg to sucrose and NaCl). Several showed poor generalization to all 4 prototypical tastes, calling into question the assumption that these 4 totally encompass the gustatory domain.}, } @article {pmid7163346, year = {1982}, author = {Greenshaw, AJ and Buresová, O}, title = {Learned taste aversion to saccharin following intraventricular or intraperitoneal administration of d,l-amphetamine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {17}, number = {6}, pages = {1129-1133}, doi = {10.1016/0091-3057(82)90107-1}, pmid = {7163346}, issn = {0091-3057}, mesh = {Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Injections, Intraperitoneal ; Injections, Intraventricular ; Male ; Muridae ; Taste/*drug effects ; }, abstract = {The effects of intracerebroventricular (ICV--160, 250, 500 micrograms) and intraperitoneal (IP--3,5 mg/kg) administration of d,1-amphetamine were compared using a multiple-bottle CTA procedure. After one conditioning trial animals receiving IP amphetamine exhibited a marked aversion to saccharin. This effect was dose-dependent. With cannulated animals receiving ICV saline the effectiveness of amphetamine at 5 mg/kg IP was equivalent to that of 3 mg/kg IP with unoperated rats. After one conditioning trial amphetamine at 160 micrograms ICV was ineffective in inducing an aversion to saccharin. Animals receiving 250 or 500 micrograms ICV exhibited a marked aversion to saccharin after one trial. The 160 micrograms ICV dose was effective after two conditioning trials. This differential potency of centrally and peripherally administered amphetamine after one conditioning trial indicates that the aversive stimulus properties of amphetamine may not simply be centrally mediated. It is proposed that both central and peripheral amphetamine effects may be necessary for the induction of a CTA with this drug.}, } @article {pmid7151753, year = {1982}, author = {Balster, RL and Borzelleca, JF}, title = {Behavioral toxicity of trihalomethane contaminants of drinking water in mice.}, journal = {Environmental health perspectives}, volume = {46}, number = {}, pages = {127-136}, pmid = {7151753}, issn = {0091-6765}, mesh = {Administration, Oral ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Female ; Fetus/drug effects ; Hydrocarbons, Halogenated/*toxicity ; Mice ; Mice, Inbred ICR ; Physical Exertion ; Pregnancy ; Swimming ; Taste/drug effects ; Teratogens ; Water Pollutants/*toxicity ; Water Pollutants, Chemical/*toxicity ; Water Supply ; }, abstract = {The behavioral toxicity of trichloromethane (TCM), dichlorobromomethane (DCBM), dibromochloromethane (DBCM) and tribromomethane (TBM) was evaluated following oral administration in mice. A variety of dosage regimens and behavioral measures were used. Studies included acute dose effect, 14-and 90-day treatments at 300 and 3000 times the estimated average human daily intake of contaminated drinking water, 30 days of 100 mg/kg/day, and 60 days of 100 and 400 mg/kg/day. In addition, TCM was tested for the production of taste aversions with 10-day administration and for behavioral teratology in offspring following extensive perinatal exposure. The ED50 for acute effects on a screen test of motor performance was about 500 mg/kg for all four trihalomethanes. The 14-day treatments had no effect on swimming behavior and the 90-day treatments had no effect on bar clinging, a test of motor coordination, and a measure of exploratory behavior. None of the compounds produced effects on passive-avoidance learning following 100 mg/kg/day for 30 days. TCM, DBCM and TBM elicited clear effects at both 100 and 400 mg/kg/day on operant behavior when administered for 60 days. DBCM elicited clear effects at 400 mg/kg/day. These effects on operant behavior were seen following the first dose and tolerance tended to develop. Thus, there was no evidence from these studies for a progressive neurotoxicity from trihalomethanes in adult mice. A behavioral teratology study was also conducted with TCM. Both parents were treated with 31.1 mg/kg/day TCM, and treatment of the dam continued throughout gestation and lactation. No clear evidence for behavioral effects in the offspring were observed. The most sensitive measure for the effects of TCM was the taste aversion paradigm in which saccharin aversions were produced after a single treatment of 30 mg/kg.}, } @article {pmid6307252, year = {1982}, author = {Langley, WM and Knapp, K}, title = {Importance of olfaction to suppression of attack response through conditioned taste aversion in the grasshopper mouse.}, journal = {Behavioral and neural biology}, volume = {36}, number = {4}, pages = {368-378}, doi = {10.1016/s0163-1047(82)90772-5}, pmid = {6307252}, issn = {0163-1047}, mesh = {Animals ; *Appetitive Behavior/drug effects ; Arousal/drug effects ; Attention/drug effects ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Lithium/poisoning ; Lithium Chloride ; Muridae ; *Predatory Behavior/drug effects ; *Smell/drug effects ; *Taste/drug effects ; }, } @article {pmid6296894, year = {1982}, author = {Chambers, KC}, title = {Failure of ACTH to prolong extinction of a conditioned taste aversion in the absence of the testes.}, journal = {Physiology & behavior}, volume = {29}, number = {5}, pages = {915-919}, doi = {10.1016/0031-9384(82)90343-2}, pmid = {6296894}, issn = {0031-9384}, support = {RR-00163/RR/NCRR NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Castration ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Extinction, Psychological/*drug effects ; Female ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Testosterone/*blood ; Water Deprivation ; }, abstract = {Both corticotropin (ACTH) and testosterone prolong the extinction of a conditioned taste aversion in water-deprived intact male rats. An investigation was made to determine whether ACTH affects extinction in the absence of the testes and also to determine the effect of ACTH on serum testosterone levels. Water-deprived intact males showed prolonged extinction after ACTH injections; water-deprived gonadectomized males and intact females did not. All three of these groups showed elevated testosterone levels after ACTH administration, but testosterone levels were higher in the intact males than in the gonadectomized males or intact females. These results clearly show that in the absence of the testes ACTH is unable to prolong extinction. It is proposed that the increased level of testosterone following ACTH injection in water-deprived intact males is responsible for the prolonged extinction of a conditioned taste aversion. Although testosterone levels may increase in females and castrated males following ACTH injection, the increase is not sufficient to prolong extinction in these water-deprived animals.}, } @article {pmid6294700, year = {1982}, author = {Shaw, N and Webster, DM}, title = {Disruption of conditioned taste aversion by the combined effects of LiCl and ECS.}, journal = {Physiology & behavior}, volume = {29}, number = {4}, pages = {755-757}, doi = {10.1016/0031-9384(82)90252-9}, pmid = {6294700}, issn = {0031-9384}, mesh = {Animals ; Chlorides/*poisoning ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Electroshock ; Lithium/*poisoning ; Lithium Chloride ; Male ; Memory/*drug effects ; Mental Recall/*drug effects ; Rats ; Taste/*drug effects ; }, abstract = {Rats were taught a conditioned taste aversion by allowing them to drink sucrose (CS) for 5 min and 30 min later poisoning them with LiCl (UCS). Experimental animals were given ECS (80 mA for 250 msec) at 0, 15, 20, 25, 27.5, 30, 32.5, 35, 40, or 45 min after the CS. Only animals given ECS both within the CS-UCS interval and in close temporal proximity to the UCS (within 5 min) showed a significant, although limited, disruption of learning. At least two explanations are possible. The first is that apart from its toxicity, LiCl may also possess amnesic properties which interact with those of the ECS. Alternatively, ECS may have impaired the ability of the animals to fully experience the lithium-induced illness.}, } @article {pmid6292270, year = {1982}, author = {Schweitzer, L and Green, L}, title = {Acquisition and extended retention of a conditioned taste aversion in preweanling rats.}, journal = {Journal of comparative and physiological psychology}, volume = {96}, number = {5}, pages = {791-806}, doi = {10.1037/h0077916}, pmid = {6292270}, issn = {0021-9940}, support = {1-R01-AM21024-01/AM/NIADDK NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Animals, Newborn ; Association Learning/drug effects ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; Choice Behavior/drug effects ; *Conditioning, Classical/drug effects ; Drinking/drug effects ; Lithium/poisoning ; Lithium Chloride ; *Memory/drug effects ; Rats ; Rats, Inbred Strains ; *Retention, Psychology/drug effects ; *Taste/drug effects ; }, abstract = {The time course of memory decay for infant rats may shed light on the processes responsible for infantile amnesia. A taste aversion conditioning procedure appropriate for both neonatal and adult rats was employed in four experiments to investigate the ontogeny of extended retention. In Experiment 1, rats trained at 1, 10, 20, or 60 days of age were tested for retention of the taste aversion 25 days later. At testing, only those rats conditioned when 20 or 60 days old demonstrated significant taste aversions. Experiments 2 and 3 established that rats 14-15 days old and older were able to retain significant taste aversions following a 25-day retention interval. Younger rats did, however, acquire and retain the aversion for several days and showed a gradual retention loss over progressively longer retention intervals (Experiment 4). These findings suggest that preweanling rats demonstrate initial consolidation, storage, and retrieval of conditioned taste aversions. It is only after this initial period that retention deficits become evident.}, } @article {pmid6292269, year = {1982}, author = {Wilkin, LD and Cunningham, CL and Fitzgerald, RD}, title = {Pavlovian conditioning with ethanol and lithium: effects on heart rate and taste aversion in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {96}, number = {5}, pages = {781-790}, doi = {10.1037/h0077924}, pmid = {6292269}, issn = {0021-9940}, support = {AA07074/AA/NIAAA NIH HHS/United States ; HL07332/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Chlorides/*poisoning ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Ethanol/*administration & dosage ; Female ; Heart Rate/*drug effects ; Lithium/*poisoning ; Lithium Chloride ; Muridae ; Taste/*drug effects ; }, abstract = {Rats received paired injections of either ethanol or saline as the conditioned stimulus and lithium chloride as the unconditioned stimulus (US) in a Pavlovian differential conditioning paradigm. Lithium chloride evoked a large deceleration in heart rate (80-100 beats per minute) as an unconditioned response. As a result of 10 conditioning trials, the substance paired with LiCl elicited a lower average heart rate than that elicited by the unpaired substance. Moreover, animals that received ethanol-LiCl injections subsequently were more averse to the taste of ethanol than animals receiving saline-LiCl pairings. However, there were no differences in ethanol's ability to serve as the US to induce an aversion to a novel flavor solution (i.e., the Avfail phenomenon was not observed). The overall pattern of results underscores the value of using multiple indexes of learning in drug-drug conditioning paradigms.}, } @article {pmid7134954, year = {1982}, author = {Bircher, J and Bührer, M and Franz, K and van Velthuijsen, JA}, title = {[1st use of lactitol in the treatment of porto-systemic encephalopathy].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {112}, number = {38}, pages = {1306-1307}, pmid = {7134954}, issn = {0036-7672}, mesh = {Esophageal and Gastric Varices/surgery ; Hepatic Encephalopathy/*drug therapy ; Humans ; Lactulose/therapeutic use ; Liver Cirrhosis, Alcoholic/*complications ; Male ; Middle Aged ; *Portacaval Shunt, Surgical ; Postoperative Complications/drug therapy ; Sugar Alcohols/*therapeutic use ; }, abstract = {Lactitol (beta-galactosido-sorbitol) is not absorbed in the small bowel but metabolized by colonic bacteria, and should therefore be as effective in the treatment of portal-systemic encephalopathy as lactulose (beta-galactosido-fructose). This hypothesis was tested in a 61-year-old alcoholic with an end-to-side portacaval anastomosis and chronic portal-systemic encephalopathy. Under controlled conditions he was switched from optimized treatment with lactulose to several regimens with lactitol (40-68 g/day), after which he was maintained on the new treatment for 1 year. On lactitol his condition was at least as good as on lactulose, but lactitol produced no taste aversion because it is less sweet. In addition, the patient no longer had nausea after taking the drug because lactitol can be supplied in a nonhygroscopic, chemically pure, crystalline form and therefore is less hyperosmotic than lactulose, which is supplied with contaminations of galactose and lactose. Obviously the data in single case represent only a feasibility study. Nevertheless, the outcome in this patient, together with the advantages of the new sugar, justify the planning of controlled clinical trials.}, } @article {pmid6294541, year = {1982}, author = {Anderson, CE and Tilson, HA and Mitchell, CL}, title = {Conditioned taste aversion following acutely administered acrylamide.}, journal = {Neurobehavioral toxicology and teratology}, volume = {4}, number = {5}, pages = {497-499}, pmid = {6294541}, issn = {0275-1380}, mesh = {Acrylamides/*poisoning ; Animals ; Avoidance Learning/*drug effects ; Chlorides/*poisoning ; Conditioning, Classical/*drug effects ; Discrimination Learning/drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Lithium/*poisoning ; Lithium Chloride ; Male ; Rats ; Rats, Inbred F344 ; Taste/*drug effects ; }, abstract = {Fischer-344 rats were acclimated to a daily 15 min period of water availability. After water consumption had stabilized, the rats were permitted a 15 min access to 0.15% (w/v) solution of saccharin. One to two min following saccharin presentation, they were given various doses of acrylamide (10-50 mg/kg) or lithium chloride (LiCl; 3 mEq/kg) by gavage. Three days later, aversion to the saccharin solution was determined. Acrylamide, like LiCl, produced an aversion to saccharin. The effect of acrylamide appeared to be dose-related with the threshold dose being 10 mg/kg.}, } @article {pmid7119179, year = {1982}, author = {Wirsig, CR and Grill, HJ}, title = {Contribution of the rat's neocortex to ingestive control: I. Latent learning for the taste of sodium chloride.}, journal = {Journal of comparative and physiological psychology}, volume = {96}, number = {4}, pages = {615-627}, doi = {10.1037/h0077911}, pmid = {7119179}, issn = {0021-9940}, support = {AM-21397/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/physiology ; Association Learning/physiology ; Avoidance Learning/physiology ; Cerebral Cortex/*physiology ; Discrimination Learning/*physiology ; *Drinking ; Extinction, Psychological/physiology ; Male ; Rats ; Rats, Inbred Strains ; Retention, Psychology/physiology ; Sodium Chloride ; Taste/*physiology ; Water-Electrolyte Balance ; }, abstract = {Neocortical mechanisms do not directly contribute to the execution of taste discrimination, sodium appetite, or the acquisition of a taste aversion in the rat. Examination of previous studies led to the question of whether some permanent ingestive control deficit would be revealed if elements of these experimental paradigms were combined. A latent learning paradigm for the taste of salt was applied to decorticate rats. The ability of decorticate rats to associate how they obtained the taste of NaCl when sodium replete was assessed by examining bar presses during extinction when sodium depleted. Intact rats exposed to 4-6 hr of NaCl taste training retained the association after decortication; decorticate rats exposed to the same training acquired the association. What was most striking was that decorticate rats exposed to as little as 2 min of NaCl taste training demonstrated the ability to associate bar pressing with NaCl by their resistance to extinction. The association was specific to NaCl training; training with distilled water or KCl did not yield resistance to extinction during sodium depletion. Subcortical structures are therefore adequate for latent learning involving NaCl taste. Conversely, data of other investigators have revealed that the neocortex is required for the retention of taste aversion learning for the same taste.}, } @article {pmid6752964, year = {1982}, author = {Cairnie, AB and Leach, KE}, title = {Dexamethasone: a potent blocker for radiation-induced taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {17}, number = {2}, pages = {305-311}, doi = {10.1016/0091-3057(82)90085-5}, pmid = {6752964}, issn = {0091-3057}, mesh = {Animals ; Aspirin/pharmacology ; Avoidance Learning/drug effects/*radiation effects ; Cimetidine/pharmacology ; Conditioning, Classical/drug effects/*radiation effects ; Dexamethasone/*pharmacology ; Dimethyl Sulfoxide/pharmacology ; Domperidone/pharmacology ; Dose-Response Relationship, Radiation ; Gamma Rays ; Haloperidol/pharmacology ; Insulin/pharmacology ; Male ; Naloxone/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/drug effects/*radiation effects ; }, abstract = {Rats, trained to drink water during a single 30-min period each day, were then given 0.1% saccharin twice a week and water on other days for 30 min. If 20 rad of radiation (0.2 Gy) were given each time 30 to 40 min after the saccharin the rats developed a profound aversion to saccharin during the course of three weeks, whereas control groups failed to do so. This paradigm was then used to test the ability of drugs, given twice weekly immediately after the saccharin, to prevent the development during three weeks of an aversion when 20 rad was given, 30 to 40 min later. Insulin, domperidone, haloperidol, acetylsalicylic acid, naloxone, chlorpheniramine, cimetidine, and dimethyl sulphoxide were tested without notable success. However dexamethasone, at doses ranging from 0.013 mg/kg to 1.3 mg/kg, significantly attenuated the conditioned taste aversion by up to 60 percent. The results are discussed in terms of a search for an antinauseant and antiemetic drug effective against radiation in man.}, } @article {pmid6292967, year = {1982}, author = {Weinberg, J and Gunnar, MR and Brett, LP and Gonzalez, CA and Levine, S}, title = {Sex differences in biobehavioral responses to conflict in a taste aversion paradigm.}, journal = {Physiology & behavior}, volume = {29}, number = {2}, pages = {201-210}, doi = {10.1016/0031-9384(82)90004-x}, pmid = {6292967}, issn = {0031-9384}, support = {R01 AA007789/AA/NIAAA NIH HHS/United States ; HD-02881/HD/NICHD NIH HHS/United States ; MH-15147/MH/NIMH NIH HHS/United States ; MH-19936/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Arousal/physiology ; Avoidance Learning/*physiology ; Castration ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; *Conflict, Psychological ; Corticosterone/blood ; Extinction, Psychological/physiology ; Female ; Food Deprivation ; Lithium/poisoning ; Lithium Chloride ; Male ; Pituitary-Adrenal System/physiology ; Rats ; Rats, Inbred Strains ; Sex Factors ; Taste/*physiology ; Water Deprivation ; }, abstract = {A conditioned aversion to a novel milk solution was produced, and animals were then reexposed to milk while nondeprived (low conflict) or following a 72-hr food and water deprivation regimen (high conflict). No sex differences occurred if animals were nondeprived throughout testing. However, if deprived during the interval between conditioning and reexposure, sex differences in both behavior and adrenocortical responses occurred: (1) Presession corticoid levels of females were higher than those of males. (2) On the first reexposure day, females showed a suppression of plasma corticosterone below presession levels, while males maintained elevated or increased corticosterone levels. (3) On the second reexposure day, when no longer deprived, males showed a marked suppression of intake compared to females, and females subsequently recovered to pretoxicosis intake levels faster than males. (4) Gonadectomy eliminated these sex differences. While ovariectomized females continued to resemble intact females in both behavioral and hormonal responses, castrated males exhibited a corticoid suppression on the first reexposure day, and subsequently recovered to pretoxicosis intake levels at the same rate as females.}, } @article {pmid6288779, year = {1982}, author = {Kiefer, SW and Rusiniak, KW and Garcia, J}, title = {Flavor-illness aversions: gustatory neocortex ablations disrupt taste but not taste-potentiated odor cues.}, journal = {Journal of comparative and physiological psychology}, volume = {96}, number = {4}, pages = {540-548}, doi = {10.1037/h0077910}, pmid = {6288779}, issn = {0021-9940}, support = {AA 03513/AA/NIAAA NIH HHS/United States ; HD 05958/HD/NICHD NIH HHS/United States ; NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Chlorides/poisoning ; Cues ; Drinking/drug effects ; Learning/*physiology ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Retention, Psychology/physiology ; Smell/*physiology ; Taste/*physiology ; }, abstract = {Two experiments evaluated the contribution of the gustatory neocortex (GN) to the potentiation of odor by taste during illness-induced aversions in rats. In Experiment 1, rats lacking GN and control rats were given an odor, a taste, or an odor-taste compound cue followed by intragastric gavage of lithium chloride. Prior to conditioning, neophobia for flavored solutions was absent in rats with GN lesions. After pairing with LiCl, GN rats developed normal conditioned odor aversions (Experiment 1B), whereas conditioned taste aversions were attenuated (Experiment 1A) or totally blocked (Experiment 1B). Potentiation of odor by taste after compound conditioning was evident in both control and GN rats, although GN lesions attenuated the effect slightly in Experiment 1B. In Experiment 2, normal rats were given compound conditioning to induce potentiated odor aversions and then given GN lesions prior to tests with the odor and taste components. Taste aversion retention was disrupted totally by GN ablation; potentiated odor aversions were retained by both groups, although the GN group extinguished faster. Gustatory neocortex ablations produced differential effects on odor and taste, disrupting taste memorial and associative processes but leaving odor conditioning and the potentiation of odor by taste processes relatively unaffected. Integrity of the GN apparently is not necessary for the acquisition or retention of potentiation odor aversions.}, } @article {pmid6811292, year = {1982}, author = {Luttinger, D and King, RA and Sheppard, D and Strupp, J and Nemeroff, CB and Prange, AJ}, title = {The effect of neurotensin on food consumption in the rat.}, journal = {European journal of pharmacology}, volume = {81}, number = {3}, pages = {499-503}, doi = {10.1016/0014-2999(82)90116-9}, pmid = {6811292}, issn = {0014-2999}, support = {MH-22536/MH/NIMH NIH HHS/United States ; MH-33127/MH/NIMH NIH HHS/United States ; MH-34121/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Eating/*drug effects ; Food Deprivation/physiology ; Habituation, Psychophysiologic ; Injections, Intraventricular ; Lithium/pharmacology ; Male ; Neurotensin/administration & dosage/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; Thyrotropin-Releasing Hormone/pharmacology ; }, abstract = {The effect of neurotensin on feeding behavior were studied in rats. Intracerebroventricular administration of neurotensin (3.3-30 micrograms) produced a dose-related decrease in food intake in 24 h food deprived rats. Acute intracerebroventricular injection of neurotensin (30 micrograms) shortly after the ingestion of a novel flavor did not produce a flavor aversion during testing 48 h later, suggesting that reduction of food intake by low doses of centrally administered neurotensin is not related to a conditioned taste aversion. Intracerebroventricularly administered thyrotropin-releasing hormone (2.2 micrograms) also inhibited food intake and appeared to attenuate slightly the inhibition of food intake induced by 10 micrograms neurotensin.}, } @article {pmid7202221, year = {1982}, author = {Tucker, AR and Oei, TP}, title = {Protein synthesis inhibition and amnesia for saccharin aversion memory in rats after intra-cisternal administration of cycloheximide.}, journal = {Physiology & behavior}, volume = {28}, number = {6}, pages = {1025-1028}, doi = {10.1016/0031-9384(82)90170-6}, pmid = {7202221}, issn = {0031-9384}, mesh = {Amnesia/*metabolism ; Animals ; Avoidance Learning/*drug effects ; Brain/metabolism ; Cisterna Magna ; Cycloheximide/administration & dosage/*pharmacology ; Female ; Humans ; Injections ; Male ; Nerve Tissue Proteins/*biosynthesis ; Rats ; *Saccharin ; Time Factors ; }, abstract = {The series of experiments reported further investigated the time course relationship of the amnesia for saccharin aversion memory in rats and the inhibition of protein synthesis resulting from cycloheximide (CXM). The first experiment showed that intraventricular CXM injected rats which had been trained 7 hrs after injection had learned the contingency under a considerable inhibition of protein synthesis. However, 1 hr after CXM injection protein synthesis inhibition was 86% and yet there was no amnesia observed 24 hr after training. It was also apparent that there were no marked regional differences in the extent of protein synthesis inhibition after intraventricular CXM. Finally, intracisternal injection of CXM 1 hr before training resulted in amnesia 24 hrs after training although this effect was greater when the injection was performed 7 hr before training. The findings (1) are consistent with Day et al's [4] suggestion of maximal protein synthesis inhibition at 1 hr post CXM injection with an approximately linear decline thereafter, and (2) provide no support for the involvement of the brain stem nucleus solitarius in taste aversion learning.}, } @article {pmid7111450, year = {1982}, author = {Jakinovich, W}, title = {Taste aversion to sugars by the gerbil.}, journal = {Physiology & behavior}, volume = {28}, number = {6}, pages = {1065-1071}, doi = {10.1016/0031-9384(82)90176-7}, pmid = {7111450}, issn = {0031-9384}, support = {R01 NS16022-01/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning ; Carbohydrates/*pharmacology ; Disaccharides/pharmacology ; Female ; Gerbillinae/*physiology ; Male ; Monosaccharides/pharmacology ; Taste/*drug effects ; }, abstract = {Some conditioned taste aversion experiments were undertaken to determine how the gerbil responds to disaccharides, monosaccharides and polyols. We observed the following: animals taught an aversion to 0.1 M sucrose generalized the avoidance to most sugars, the exception being galactitol; animals taught to avoid 0.01 M hydrochloric acid generalized the avoidance towards lactose, cellobiose, maltitol, methyl alpha-D-galactopyranoside, methyl alpha-D-mannopyranoside, methyl beta-D-glucopyranoside, and glycerol; animals taught to avoid 0.001 M quinine . HCl generalized the avoidance towards methyl alpha-D-glucopyranoside, methyl-beta-D-glucopyranoside, glycerol, ethylene glycol and erythritol. In no case did animals taught to avoid 0.1 M sodium chloride avoid any of the sugars. Moreover, it was observed that the gerbil's behavior with most reducing sugars was different than with equivalent methyl glycosides. For example, animals that were taught to avoid sucrose generalized the avoidance towards reducing sugars, such as, D-galactose, D-glucose, and D-mannose. However, the methyl glycosides, such as methyl alpha-D-glucopyranoside, methyl beta-D-glucopyranoside, methyl alpha-D-galactopyranoside and methyl alpha-D-mannopyranoside, in addition to being avoided by animals taught to avoid sucrose, were also avoided by animals taught to avoid quinine . HCl or hydrochloric acid. In addition, we have observed that the control animals consumed differing amounts of sugars and have concluded, therefore, that the sugars were not equally pleasant despite our attempt to use concentrations which produced equally intense neural responses in the gerbil's chorda tympani nerve.}, } @article {pmid7089182, year = {1982}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {State-dependent interactions in the antihistamine-induced disruption of a radiation-induced conditioned taste aversion.}, journal = {Radiation research}, volume = {90}, number = {3}, pages = {621-627}, pmid = {7089182}, issn = {0033-7587}, mesh = {Animals ; Avoidance Learning/drug effects/*radiation effects ; Chlorpheniramine/analogs & derivatives/pharmacology ; Gamma Rays ; Histamine Antagonists/*pharmacology ; Male ; Rats ; Sucrose ; *Taste ; }, } @article {pmid7089181, year = {1982}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Studies on the role of central histamine in the acquisition of a radiation-induced conditioned taste aversion.}, journal = {Radiation research}, volume = {90}, number = {3}, pages = {609-620}, pmid = {7089181}, issn = {0033-7587}, mesh = {Animals ; Avoidance Learning/drug effects/physiology/*radiation effects ; Gamma Rays ; Histamine/pharmacology/*physiology ; Histamine Antagonists/pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Sucrose ; *Taste ; }, } @article {pmid6293453, year = {1982}, author = {Archer, T and Cotic, T and Järbe, TU}, title = {Attenuation of the context effect and lack of unconditioned stimulus-preexposure effect in taste-aversion learning following treatment with DSP4, the selective noradrenaline neurotoxin.}, journal = {Behavioral and neural biology}, volume = {35}, number = {2}, pages = {159-173}, doi = {10.1016/s0163-1047(82)91173-6}, pmid = {6293453}, issn = {0163-1047}, mesh = {Amines/*pharmacology ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Benzylamines/*pharmacology ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Cues ; Desipramine/pharmacology ; Dopamine beta-Hydroxylase/metabolism ; Frontal Lobe/drug effects ; Hippocampus/drug effects ; Lithium/poisoning ; Lithium Chloride ; Male ; Muscle Contraction/drug effects ; Neurotoxins/*pharmacology ; Norepinephrine/*metabolism ; Rats ; Rats, Inbred Strains ; Reflex/drug effects ; Taste/*drug effects ; }, } @article {pmid6293452, year = {1982}, author = {Dray, SM and Taylor, AN}, title = {ACTH4-10 enhances retention of conditioned taste aversion learning in infant rats.}, journal = {Behavioral and neural biology}, volume = {35}, number = {2}, pages = {147-158}, doi = {10.1016/s0163-1047(82)91163-3}, pmid = {6293452}, issn = {0163-1047}, support = {NS-09122/NS/NINDS NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/*pharmacology ; Animals ; Animals, Newborn ; Avoidance Learning/*drug effects ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Lithium/poisoning ; Lithium Chloride ; Memory/*drug effects ; Peptide Fragments/*pharmacology ; Rats ; Rats, Inbred Strains ; Retention, Psychology/*drug effects ; Taste/*drug effects ; }, } @article {pmid6284812, year = {1982}, author = {Lasiter, PS and Glanzman, DL}, title = {Cortical substrates of taste aversion learning: dorsal prepiriform (insular) lesions disrupt taste aversion learning.}, journal = {Journal of comparative and physiological psychology}, volume = {96}, number = {3}, pages = {376-392}, doi = {10.1037/h0077894}, pmid = {6284812}, issn = {0021-9940}, support = {935191//PHS HHS/United States ; 935306//PHS HHS/United States ; S07-RR07112/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Axons/physiology ; Brain Mapping ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Lithium/poisoning ; Lithium Chloride ; Male ; Muridae ; Nerve Degeneration ; Nerve Fibers/physiology ; Neural Pathways/physiology ; Somatosensory Cortex/*physiology ; Taste/*physiology ; }, abstract = {The functional relation between restricted damage to ventral primary somatosensory neocortex and the ability of rats to acquire conditioned taste aversion (CTA(was examined by a combination of behavioral and neurohistological techniques. Lesions confined exclusively to the established gustatory neocortex (GN) did not disrupt CTA acquisition, nor did lesions confined to suprarhinal cortical areas ventral to the GN. Lesions that encroached on dorsal prepiriform and insular cortices produced CTA acquisition deficits and damaged a large proportion of efferent projections to the prefrontal and precentral neocortex. In a second experiment, lesions of dorsal prepiriform and insular cortices did not modify taste preference-aversion threshold to any of the four taste modalities. It is concluded tha ventral somatosensory neocortical fields, including the established GN, do not mediate CTA acquisition and that rhinal cortices ventral and posterior to the GN are preferentially involved in associative learning for tastes and illness.}, } @article {pmid7169278, year = {1982}, author = {Scrima, L and Corey, DT and Choo, AF}, title = {Interanimal transferability of taste aversion learning for 0.1% saccharin.}, journal = {The International journal of neuroscience}, volume = {16}, number = {3-4}, pages = {135-142}, doi = {10.3109/00207458209147140}, pmid = {7169278}, issn = {0020-7454}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/physiology ; Conditioning, Classical/*physiology ; Drinking ; Extinction, Psychological/physiology ; Male ; Nerve Tissue Proteins/*physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Tissue Extracts ; }, abstract = {Three experiments were performed to assess the interanimal transferability of conditioned taste aversion to 0.1% saccharin. Two experiments used an intracerebrospinal fluid (subdural) route for administering brain extracts and a third used an intraperitoneal (IP) route. As assessed by repeated measurements ANOVA, saccharin consumption was significantly lower during extinction of conditioned aversion for experimental recipients (ER) receiving extracts from aversively conditioned donors, than that of control recipients (CR), receiving extracts from unconditioned donors in one subdural experiment, F(21, 189) = 1.61, p less than 0.05. In the IP experiment the results were in the same direction, though not significant, F(34, 238) = 1.39, p less than 0.1. Results of the other subdural experiment are discussed. It is concluded that these experiments with the conditioned taste aversion paradigm have potential as a model for investigations of behavioral interanimal transfer (BIT) and for neuromolecular research aimed at identification of associated putative neurochemical(s) and the elaboration of their mechanism of action.}, } @article {pmid7100293, year = {1982}, author = {Maggio, CA and Koopmans, HS}, title = {Food intake after intragastric meals of short-, medium, or long-chain triglyceride.}, journal = {Physiology & behavior}, volume = {28}, number = {5}, pages = {921-926}, doi = {10.1016/0031-9384(82)90215-3}, pmid = {7100293}, issn = {0031-9384}, support = {AM 17926/AM/NIADDK NIH HHS/United States ; HD07000/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Chemical Phenomena ; Chemistry ; Dietary Fats/*administration & dosage ; *Digestive System Physiological Phenomena ; Energy Intake ; Feeding Behavior/*physiology ; Food Preferences ; Male ; Rats ; Rats, Inbred Strains ; Satiation/*physiology ; Satiety Response/*physiology ; Triglycerides/*administration & dosage ; }, abstract = {Food-deprived Sprague-Dawley rats were given equicaloric intragastric infusions of mixed meals consisting largely of short- (SCT), medium- (MCT), or long-chain triglyceride (LCT). When animals were allowed to feed 20 min after infusion, there was an immediate reduction of food intake that was sustained over the 2 hr feeding period. During the first hour of feeding, the SCT, which is digested and absorbed more rapidly than the MCT or the LCT, was more effective per calorie in reducing food intake than these longer-chain triglycerides. However, during the second hour, cumulative intakes after the different triglyceride infusions were not significantly different. Equicaloric infusions of the MCT and the LCT resulted in equivalent reductions of food intake at all times. The satiety effects of these two triglycerides appear to be related to their caloric properties rather than to chain length. Since the LCT reduced food intake before the absorbed fat could have entered the blood to stimulate satiety signals, this satiety effect may be mediated by a gastroenteric signal. None of the triglyceride infusions resulted in a conditioned taste aversion suggesting that food intake was reduced through normal satiety rather than through discomfort.}, } @article {pmid7099349, year = {1982}, author = {Landauer, MR and Lynch, MR and Balster, RL and Kallman, MJ}, title = {Trichloromethane-induced taste aversions in mice.}, journal = {Neurobehavioral toxicology and teratology}, volume = {4}, number = {3}, pages = {305-309}, pmid = {7099349}, issn = {0275-1380}, support = {ES-07087/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Chloroform/*pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Male ; Muridae ; Taste/*drug effects ; }, abstract = {In Experiment 1 four groups (N = 10) of individually housed mice were given access to deionized water for 30 min daily. When fluid consumption stabilized, they were given 30-min access to a 0.3% saccharin solution. This was followed by oral doses of 3, 10 or 30 mg/kg trichloromethane (TCM) or the vehicle (Emulphor). Beginning 24 hr later the subjects were given a two-bottle choice test (saccharin vs water) followed by the appropriate injection in that group. This procedure continued for 10 days. A dose of 30 mg/kg produced a taste aversion on the first choice test and a reduction in total fluid intake which continued throughout the 10-day test period, while doses of 3 and 10 mg/kg TCM or vehicle did not affect either measure. To determine whether the aversion produced by 30 mg/kg TCM was specific to gavage, animals in Experiment 2 received IP injections of 10, 30 or 100 mg/kg TCM or vehicle. All TCM groups showed taste aversions which lasted for the 10-day test period. Although concomitant fluid reductions occurred for all doses on day one, only the 100 mg/kg group maintained this drop throughout the 10-day test period. Thus, TCM produces taste aversions when given at relatively low doses by both oral and IP routes of administration.}, } @article {pmid6284873, year = {1982}, author = {Ingram, DK}, title = {Lithium chloride-induced taste aversion in C57BL/6J and DBA/2J mice.}, journal = {The Journal of general psychology}, volume = {106}, number = {2d Half}, pages = {233-249}, pmid = {6284873}, issn = {0022-1309}, support = {AG 00250/AG/NIA NIH HHS/United States ; GM 21266/GM/NIGMS NIH HHS/United States ; MH 12126/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/*poisoning ; Conditioning, Classical/drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Lithium/*poisoning ; Lithium Chloride ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; *Species Specificity ; Taste/*drug effects ; }, abstract = {Male C57BL/6J and DBA/2J mice (Mus musculus) were tested in a one-bottle conditioned taste aversion paradigm with 15% sucrose as the conditioned stimulus and lithium chloride (LiCl) as the unconditioned stimulus. The results of a dose-response experiment yielded evidence that higher doses of LiCl than used in past studies were required to produce profound aversions in these mice, with a 6.0 mEq/kg dose appearing as optimal. When the mice were conditioned with the 6.0 mEq/kg dose in one-bottle tests, there was little evidence of a strain difference in the acquisition of a taste aversion. During extinction trials, however, DBA/2J mice exhibited stronger resistance to extinction than did C57BL/6J mice. Additional analyses of fluid consumption suggested that strain differences in drinking behavior were evident in the paradigm and that these must be considered in interpreting the strain differences observed in conditioned taste aversion.}, } @article {pmid6283577, year = {1982}, author = {Wellman, PJ}, title = {Pre-exposure to flavor and conditioned taste aversion: amphetamine and lithium reinforcers.}, journal = {Psychological reports}, volume = {50}, number = {2}, pages = {555-558}, doi = {10.2466/pr0.1982.50.2.555}, pmid = {6283577}, issn = {0033-2941}, mesh = {Animals ; *Avoidance Learning/drug effects ; Chlorides/*poisoning ; *Conditioning, Classical ; Dextroamphetamine/*poisoning ; Extinction, Psychological ; Female ; Lithium/*poisoning ; Lithium Chloride ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; *Taste/drug effects ; }, } @article {pmid6281830, year = {1982}, author = {Reidinger, RF and Beauchamp, GK and Barth, M}, title = {Conditioned aversion to a taste perceived while grooming.}, journal = {Physiology & behavior}, volume = {28}, number = {4}, pages = {715-723}, doi = {10.1016/0031-9384(82)90057-9}, pmid = {6281830}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects ; Chlorides/poisoning ; Choice Behavior/drug effects ; *Conditioning, Classical/drug effects ; Drinking/drug effects ; Generalization, Stimulus/drug effects ; *Grooming/drug effects ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; *Taste/drug effects ; }, abstract = {Four experiments were conducted to determine how the characteristics of conditioned taste aversion (CTA), as described from studies conducted in the drinking and feeding contexts, applied in the grooming context. In Experiment 1, sodium saccharin was mixed with a "neutral-tasting" jelly and applied to the fur of male Sprague-Dawley rats. Rats injected with LiCl after the applications strongly avoided saccharin solutions in subsequent 1-hr, 2-choice (Saccharin solution vs water) drinking tests, whereas rats injected with NaCl or given plain jelly on the fur showed only an initial neophobic response to the saccharin solution. Thus, the taste of saccharin was perceived while grooming and the CTA formed in the grooming context generalized to drinking. In experiments 2-4, we obtained evidence that: (a) rats discriminated between one intensity of saccharin applied to the fur and another used in the test solution; and (b) rats differentiated between qualities of the two tastants applied to the fur in that saccharin overshadowed NaCl; and (c) taste qualities were more important than toxic properties when two stimuli (Saccharin, LiCl) were used (saccharin overshadowed NaCl in subsequent drinking tests). We speculate that taste, while grooming might play a role in social communication in some vertebrates. Further, CTA and grooming might have uses in rodent control (e.g., in agricultural situations) not previously considered such as in delivering a non-attractive, low-salience toxin so that the taste of the crop overshadows that of the bait, and induces crop aversion.}, } @article {pmid6145489, year = {1982}, author = {Schoemaker, H and Nickolson, VJ and Kerbusch, S and Crabbe, JC}, title = {Synaptosomal uptake studies on recombinant inbred mice; neurotransmitter interaction and behavioral correlates.}, journal = {Brain research}, volume = {235}, number = {2}, pages = {253-264}, doi = {10.1016/0006-8993(82)91005-8}, pmid = {6145489}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*metabolism ; Choline/metabolism ; Crosses, Genetic ; Male ; Mice ; Mice, Inbred BALB C/metabolism ; Mice, Inbred C57BL/metabolism ; Mice, Inbred Strains/*physiology ; Neurotransmitter Agents/*metabolism ; Norepinephrine/metabolism ; Species Specificity ; Synaptosomes/metabolism ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {The uptake of noradrenaline, choline and GABA into whole brain synaptosomes from the mice inbred strains C57BL/6By, BALB/cBy, their reciprocal crosses and seven recombinant inbred strains derived from the F2 crosses was measured in order to study the relation between different neurotransmitter systems and their possible correlations with behavioral parameters. Analysis of variance demonstrated significant differences in both Vmax and Km for each substrate between the inbred strains studied. Only the Km for GABA uptake did not reach significance although a strong trend (P = 0.07) was apparent. For none of the uptake parameters clear strain distribution patterns were found. A positive phenotypic as well as genotypic correlation was found between the Vmax and Km for noradrenaline, choline and GABA uptake. A genetic analysis showed a positive correlation between the Vmax for noradrenaline and choline uptake. Since prior to these neurochemical studies, all subjects were tested in a variety of behavioral paradigms, phenotypic and genotypic correlations between behavioral and neurochemical parameters could be calculated. The most consistent correlations were found between noradrenaline and choline uptake and water consumption and the preference ratio as measured in a conditioned taste aversion test.}, } @article {pmid7089995, year = {1982}, author = {Miyagawa, M}, title = {Conditioned taste aversion induced by inhalation exposure to methyl bromide in rats.}, journal = {Toxicology letters}, volume = {10}, number = {4}, pages = {411-416}, doi = {10.1016/0378-4274(82)90239-9}, pmid = {7089995}, issn = {0378-4274}, mesh = {Animals ; Avoidance Learning/drug effects ; Brain/*drug effects ; Hydrocarbons, Brominated/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Taste/drug effects ; Water Deprivation ; }, abstract = {The toxic effect of methyl bromide vapor was assessed by a conditioned taste aversion regime. Rats kept under a water deprivation schedule for 7 days, were permitted access to 0.3% (w/v) sodium saccharin, and were exposed to methyl bromide at 0, 25, 50, and 100 ppm for 4 h. 3 days after the exposure, saccharin preference tests were carried out, revealing dose-dependent saccharin aversion in the exposure group. This result suggests that the conditioned taste aversion method is effective for assessing the toxicity of gaseous substances such as methyl bromide.}, } @article {pmid6279486, year = {1982}, author = {Caza, PA and Brown, L and Spear, NE}, title = {Epinephrine-induced conditioned taste aversion.}, journal = {Hormones and behavior}, volume = {16}, number = {1}, pages = {31-45}, doi = {10.1016/0018-506x(82)90004-6}, pmid = {6279486}, issn = {0018-506X}, support = {R MH35219-01/MH/NIMH NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Choice Behavior/drug effects ; Circadian Rhythm/drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Epinephrine/blood/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, } @article {pmid6277349, year = {1982}, author = {Crabbe, JC and Rigter, H and Kerbusch, S}, title = {Analysis of behavioural responses to an ACTH analog in CXB/By recombinant inbred mice.}, journal = {Behavioural brain research}, volume = {4}, number = {3}, pages = {289-314}, doi = {10.1016/0166-4328(82)90006-7}, pmid = {6277349}, issn = {0166-4328}, mesh = {Adrenocorticotropic Hormone/*analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Crosses, Genetic ; Discrimination Learning/drug effects ; Dose-Response Relationship, Drug ; Exploratory Behavior/drug effects ; Extinction, Psychological/drug effects ; Grooming/drug effects ; Hybridization, Genetic ; Male ; Mice ; Mice, Inbred Strains ; Motor Activity/drug effects ; Orientation/drug effects ; Peptide Fragments/*pharmacology ; *Recombination, Genetic ; Taste/drug effects ; }, abstract = {Male mice of the C57BL/6By and BALB/cBy inbred strains, their reciprocal F1 hybrids, and 7 recombinant inbred strains, were tested for open-field activity, a shock-motivated successive reversal position discrimination problem in a T-maze, and a toggle box exploration task. The test battery was repeated one month later. Finally, mice were tested for the acquisition and extinction of a taste aversion conditioned by ethanol injection. Mice of each strain were tested after injection with saline or one of 3 doses of an ACTH analogue. Highly significant genotypic differences were found for all measures, an expected result. The strain distribution pattern seen in the toggle box suggested single gene mediation of exploratory activity after habituation. One aspect of avoidance responding and extinction of conditioned taste aversion also yielded strain distribution pattern consistent with single gene control. Peptide treatment reduced internal field crossings in the open field. This effect was not strain dependent. Peptide treatment had no effect on T-maze learning, conditioned taste aversion, or toggle-box exploration.}, } @article {pmid7079345, year = {1982}, author = {Geary, N and Smith, GP}, title = {Pancreatic glucagon and postprandial satiety in the rat.}, journal = {Physiology & behavior}, volume = {28}, number = {2}, pages = {313-322}, doi = {10.1016/0031-9384(82)90081-6}, pmid = {7079345}, issn = {0031-9384}, support = {AM 17240/AM/NIADDK NIH HHS/United States ; MH 00149/MH/NIMH NIH HHS/United States ; MH 15455/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Body Temperature Regulation ; Conditioning, Classical/physiology ; Drinking ; *Eating ; Glucagon/*physiology ; Male ; Pancreas/*physiology ; Rats ; Rats, Inbred Strains ; Satiation/*physiology ; Satiety Response/*physiology ; Taste/physiology ; }, abstract = {The hypothesis that administration of pancreatic glucagon inhibits feeding by eliciting satiety for food was tested against several behavioral and physiological criteria of specificity. The effects of intraperitoneal glucagon injections on intake of a palatable milk diet were tested in rats maintained with ad lib access to pelleted diet. Injections of 25--800 micrograms/kg glucagon administered at meal onset inhibited meal size by 17--36%, but did not affect the normal postprandial behavioral satiety sequence or elicit any behavioral signs of toxicity. Latency to rest and intermeal interval were not affected. Glucagon decreased meal size by specifically inhibiting feeding during the terminal phase of the meal without affecting feeding earlier in the meal. This was also the case when glucagon was injected 4 min prior to meal onset. This range of glucagon doses did not affect water intake in water deprived rats consuming fluid volumes comparable to the milk intakes. They also did not affect body temperature. Finally, injection of 400 micrograms/kg glucagon after the initial exposure to a novel drinking fluid was not sufficient to form a conditioned taste aversion in a two bottle preference test. These data, together with reports that circulating pancreatic glucagon levels increase during meals, strongly suggest that pancreatic glucagon is involved in the production of postprandial satiety.}, } @article {pmid6291097, year = {1982}, author = {Archer, T and Sjödén, PO}, title = {Higher-order conditioning and sensory preconditioning of a taste aversion with an exteroceptive CSi.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {34 (Pt 1)}, number = {}, pages = {1-17}, doi = {10.1080/14640748208400886}, pmid = {6291097}, issn = {0272-4995}, mesh = {Animals ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Lithium/poisoning ; Lithium Chloride ; Male ; *Perception/drug effects ; Rats ; Rats, Inbred Strains ; *Taste/drug effects ; }, } @article {pmid6278398, year = {1982}, author = {Shimai, S and Hoshishima, K}, title = {Effects of bilateral amygdala lesions on neophobia and conditioned taste aversion in mice.}, journal = {Perceptual and motor skills}, volume = {54}, number = {1}, pages = {127-130}, doi = {10.2466/pms.1982.54.1.127}, pmid = {6278398}, issn = {0031-5125}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Fear/physiology ; Lithium/poisoning ; Lithium Chloride ; Male ; Muridae ; Taste/*physiology ; }, } @article {pmid7187775, year = {1982}, author = {Bures, J and Buresová, O}, title = {Ethological models in research into the neural mechanisms of short-term memory.}, journal = {Journal de physiologie}, volume = {78}, number = {9}, pages = {870-871}, pmid = {7187775}, issn = {0021-7948}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Foodborne Diseases/physiopathology ; Memory, Short-Term/*physiology ; Models, Neurological ; Models, Psychological ; Rats ; Taste/*physiology ; }, abstract = {Rats are protected against intake of toxic diets by specific evolutionary prepared behavioral adaptations. Intake of potentially dangerous novel food is reduced by neophobia. The taste signal is stored for several hours in a short-term memory file from which it gradually emerges in form of a permanent gustatory engram labeled as safe, when there are no adverse effects of feeding, or as aversive, when visceral symptoms of poisoning appear in the critical post-ingestion interval. The experimental evidence reviewed indicates that positive labeling (manifested by attenuation of neophobia) requires intact higher brain functions whereas the aversive experience (manifested by conditioned taste aversion) is recorded even under deep coma. The biological significance of the different neural mechanisms underlying the above forms of gustatory-visceral associations is discussed.}, } @article {pmid7180616, year = {1982}, author = {Baker, TB and Cannon, DS}, title = {Alcohol and taste-mediated learning.}, journal = {Addictive behaviors}, volume = {7}, number = {3}, pages = {211-230}, doi = {10.1016/0306-4603(82)90049-1}, pmid = {7180616}, issn = {0306-4603}, support = {191347//PHS HHS/United States ; }, mesh = {*Alcohol Drinking ; Alcoholism/*psychology ; Animals ; *Association Learning/drug effects ; Avoidance Learning/drug effects ; Conditioning, Classical/drug effects ; Disease Models, Animal ; Humans ; *Learning/drug effects ; Morphine/pharmacology ; *Taste/drug effects ; }, abstract = {Taste-mediated learning is relevant to the alcohol consumption patterns of animals. This review concludes that taste aversion learning has thus far prevented development of an animal model of alcoholism. The presence of a taste cue, lack of control over alcohol administration, and high alcohol concentrations or dosages all facilitate the development of alcohol aversions. There is little evidence that taste preference learning is involved in the development of alcohol dependence. Data from taste-mediated learning research with animals are consistent with drinking patterns of human alcoholics.}, } @article {pmid7180314, year = {1982}, author = {Buresová, O and Semenov, LV and Bures, J}, title = {Electrical stimulation of chemical blockade of vestibular nuclei can serve as the unconditioned stimulus in the conditioned taste aversion paradigm.}, journal = {Acta biologica Academiae Scientiarum Hungaricae}, volume = {33}, number = {2-3}, pages = {139-148}, pmid = {7180314}, issn = {0001-5288}, mesh = {Analysis of Variance ; Animals ; *Avoidance Learning ; *Conditioning, Psychological ; Ear, Inner/physiology ; Electric Stimulation ; Male ; Potassium Chloride/pharmacology ; Rats ; Rats, Inbred Strains ; Rotation ; *Taste ; Vestibular Nuclei/*physiology ; }, abstract = {Nausea of vestibular origin can be used instead of poisoning in the conditioned taste aversion (CTA) paradigm. In an attempt to establish the forms of vestibular stimulation best suited for inducing CTA in rats, effectiveness of 2 h rotation (Exp. 1) was compared with tonal asymmetry elicited by unilateral microinjection of 5.0 microliters of 25% KCl into the vestibular complex (Exp. 2), by unilateral electrical stimulation of vestibular nuclei (100 Hz, 1 ms, 100-200 microA, 15 min--Exp. 3) or by 10 min polarization of labyrinth through electrodes inserted in the external auditory meati (Exp. 4). Nystagmus, deviation of the head and leaning towards the blocked and away from the stimulated side were typical symptoms. When the above stimuli were applied within 10 min after saccharin drinking, galvanic stimulation was ineffective, but electrical stimulation or chemical blockade of vestibular nuclei elicited marked CTA to saccharin, considerably stronger than CTA induced by rotation. It is concluded that direct interference with the activity of vestibular nuclei elicits CTA more effectively than the stimulation of the labyrinth and is, therefore, well suited for the analytical research into the mechanisms of CTA.}, } @article {pmid6296903, year = {1982}, author = {Goudie, AJ and Stolerman, IP and Demellweek, C and D'Mello, GD}, title = {Does conditioned nausea mediate drug-induced conditioned taste aversion?.}, journal = {Psychopharmacology}, volume = {78}, number = {3}, pages = {277-281}, pmid = {6296903}, issn = {0033-3158}, mesh = {Amphetamine/poisoning ; Animals ; Avoidance Learning/*drug effects ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Extinction, Psychological/drug effects ; Female ; Lithium/poisoning ; Lithium Chloride ; Male ; Morphine/pharmacology ; Muridae ; Nausea/*chemically induced ; Prochlorperazine/pharmacology ; Scopolamine/pharmacology ; Taste/*drug effects ; }, abstract = {Two antiemetic drugs were tested on the expression of taste aversions previously conditioned in rats with lithium, amphetamine or morphine. Neither prochlorperazine nor scopolamine administered prior to testing attenuated established aversions, although both drugs are known to have antiemetic effects in other species. Negative findings were obtained with a range of dose of prochlorperazine and scopolamine, with strong and weak aversions, with one- and two-stimulus tests, in a repeated one-stimulus extinction procedure, with between- and within-group designs and with hooded, albino, male and female rats. The results do not support the widely accepted hypothesis that conditioned nausea mediates conditioned taste aversion.}, } @article {pmid6295072, year = {1982}, author = {Brozek, G}, title = {Electrophysiological analysis of conditioned taste aversion in rats.}, journal = {Acta neurobiologiae experimentalis}, volume = {42}, number = {1}, pages = {29-41}, pmid = {6295072}, issn = {0065-1400}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Evoked Potentials, Somatosensory/drug effects ; Lithium/poisoning ; Lithium Chloride ; Neurons/physiology ; Rats ; Taste/*physiology ; }, abstract = {The memory mechanisms of conditioned taste aversion (CTA) were examined using electrophysiological methods. Presentation of the aversive taste to CTA trained animals inhibited unit activity in gustatory cortex, amygdala and ventromedial hypothalamus and caused delayed excitation of neurons in lateral hypothalamus. Lick-triggered rewarding stimulation of medial forebrain bundle substituted the taste CS in CTA experiments. The same stimulation triggered by nose-poking failed to be associated with subsequent poisoning. Importance of specific brain areas for CTA retrieval was assessed by the effect of lick-triggered stimulation of the examined site on gustatory discrimination. The disruption threshold was lowest in amygdala and lateral hypothalamus. Stimulation of other brain structures did not interfere with gustatory discrimination at current intensities subthreshold for disruption of licking. Unilateral electrical stimulation of vestibular nuclei following ingestion of saccharin elicited marked aversion to this taste.}, } @article {pmid6281747, year = {1982}, author = {West, DB and Williams, RH and Braget, DJ and Woods, SC}, title = {Bombesin reduces food intake of normal and hypothalamically obese rats and lowers body weight when given chronically.}, journal = {Peptides}, volume = {3}, number = {1}, pages = {61-67}, doi = {10.1016/0196-9781(82)90143-7}, pmid = {6281747}, issn = {0196-9781}, support = {AM 17844/AM/NIADDK NIH HHS/United States ; GM-07108/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Weight/*drug effects ; Bombesin/*pharmacology ; Chlorides/pharmacology ; Cholecystokinin/pharmacology ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Female ; Hypothalamus/*physiology ; Hypothalamus, Middle/*physiology ; Lithium/pharmacology ; Lithium Chloride ; Obesity/etiology/*physiopathology ; Peptide Fragments/pharmacology ; Peptides/*pharmacology ; Rats ; Rats, Inbred Strains ; Sincalide ; }, abstract = {Bombesin is a peptide hormone reported to reduce meal size when administered in rats. In the first experiment, synthetic bombesin was injected subcutaneously into normal rats and obese rats with lesions of the ventromedial hypothalamus just prior to the presentation of food. A dose-dependent suppression of meal size occurred for both groups, showing that the peptide has this action in obese as well as normal animals. In a second experiment, a conditioned taste aversion was not formed with a dose of bombesin which suppressed meal size by approximately 50% while the animals did develop an aversion with a dose of LiCl reported to reduce meal size equivalently. In a third experiment, rats were placed on a feeding schedule where they received three 30-min meals each day. After weights had stabilized under this paradigm, bombesin was administered just prior to each meal for six days. The bombesin caused a consistent suppression of meal size when the animals were allowed 30-min meals such that the rats lost weight over the six-day period. When this experiment was repeated with 60-min meals apparent tolerance developed to these actions of bombesin.}, } @article {pmid7335800, year = {1981}, author = {Thompson, CI and Zagon, IS}, title = {2-Deoxy-D-glucose produces delayed hypophagia and conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {27}, number = {6}, pages = {1001-1004}, doi = {10.1016/0031-9384(81)90361-9}, pmid = {7335800}, issn = {0031-9384}, support = {DA 01618/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Choice Behavior/drug effects ; Conditioning, Classical/*drug effects ; Deoxy Sugars/*pharmacology ; Deoxyglucose/*pharmacology ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Eating/*drug effects ; Female ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, } @article {pmid7200583, year = {1981}, author = {Cory-Slechta, DA and Weiss, B}, title = {Aversiveness of cadmium in solution.}, journal = {Neurotoxicology}, volume = {2}, number = {4}, pages = {711-724}, pmid = {7200583}, issn = {0161-813X}, support = {ES-01247/ES/NIEHS NIH HHS/United States ; ES-01248/ES/NIEHS NIH HHS/United States ; ES-05177/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Body Weight/drug effects ; Cadmium/*administration & dosage/*toxicity ; Drinking/*drug effects ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Solutions ; *Taste ; }, abstract = {Weanling rats were given cadmium chloride solutions as drinking water (0, 25, 50 or 150 ppm Cd). Immediate decrements in fluid consumption and retarded weight gain were observed at the highest concentration. In addition, two of the 150 ppm rats died within four days. The rapid onset of these effects suggested taste aversion and sharply reduced water intake, not physiological impairment, as the cause. To test this possibility, rats were given a choice between two drinking water solutions. One contained distilled water, the other cadmium. Concentrations as low as 1 ppm were rejected by some rats. Additional studies showed that chronic cadmium exposure modified the intake pattern of saccharin solutions typical of rats, and that the addition of saccharin to the 150 ppm cadmium solution did not reduce its aversive properties. These data indicated that the taste of cadmium, at least in solution, is aversive to rats. Since taste aversion can reduce fluid and food consumption, and consequently body weight, properly designed experiments must include adequate control procedures such as pair-feeding and pair-watering to differentiate unique effects of cadmium from those produced by undernutrition.}, } @article {pmid6273206, year = {1981}, author = {Yamamoto, T and Azuma, S and Kawamura, Y}, title = {Significance of cortical-amygdalar-hypothalamic connections in retention of conditional taste aversion in rats.}, journal = {Experimental neurology}, volume = {74}, number = {3}, pages = {758-768}, doi = {10.1016/0014-4886(81)90249-1}, pmid = {6273206}, issn = {0014-4886}, mesh = {Amygdala/*physiology ; Animals ; *Avoidance Learning/drug effects ; Cerebral Cortex/*physiology ; Chlorides/pharmacology ; Electric Stimulation ; Hypothalamus/*physiology ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste ; }, } @article {pmid6271613, year = {1981}, author = {Franchina, JJ and Dietz, S}, title = {Taste aversion following backward conditioning procedures in preweanling and adult rats.}, journal = {Developmental psychobiology}, volume = {14}, number = {6}, pages = {499-505}, doi = {10.1002/dev.420140602}, pmid = {6271613}, issn = {0012-1630}, mesh = {Age Factors ; Animals ; Association Learning ; Chlorides ; *Conditioning, Psychological ; Female ; Lithium ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Sucrose ; *Taste ; Time Factors ; }, abstract = {Laboratory rats, 18 and 90 days old, received an intraperitoneal injection (2% body weight) of .15M lithium chloride or .9% saline 10 or 30 min before 15-min access to 12% sucrose. Additional control groups received LiCl injection followed by tap water access. Testing with a 2-bottle choice procedure revealed reliable aversion effects for both age groups at each toxicosis-flavor interval. Adult rats showed reliably greater persistence of aversion following training with the 10- than with the 30-min interval. Rat pups showed no reliable differences in aversion across training intervals. Reliably greater aversion effects occurred for adults than for pups following training at the 10-min interval. Following training at the 30-min interval a similar reliable age effect occurred on Test Trial 1; but from Trial 2 onward the magnitude of aversion was similar for pups and adult rats.}, } @article {pmid6172744, year = {1981}, author = {Jancsár, SM and Leonard, BE}, title = {The effects of antidepressant drugs on conditioned taste aversion learning of the olfactory bulbectomized rat.}, journal = {Neuropharmacology}, volume = {20}, number = {12B}, pages = {1341-1345}, pmid = {6172744}, issn = {0028-3908}, mesh = {Amygdala/metabolism ; Animals ; Antidepressive Agents/*pharmacology ; Avoidance Learning/*drug effects ; Hydroxyindoleacetic Acid/metabolism ; Lithium/pharmacology ; Male ; Olfactory Bulb/*physiology ; Rats ; Rats, Inbred Strains ; Serotonin/metabolism ; Taste/*drug effects ; }, } @article {pmid7323197, year = {1981}, author = {Spector, AC and Smith, JC and Hollander, GR}, title = {A comparison of dependent measures used to quantify radiation-induced taste aversion.}, journal = {Physiology & behavior}, volume = {27}, number = {5}, pages = {887-901}, doi = {10.1016/0031-9384(81)90059-7}, pmid = {7323197}, issn = {0031-9384}, support = {CA22768/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*radiation effects ; Conditioning, Classical/*radiation effects ; Dose-Response Relationship, Radiation ; Drinking/radiation effects ; Male ; Rats ; Rats, Inbred Strains ; Taste/*radiation effects ; }, } @article {pmid7312910, year = {1981}, author = {Switzman, L and Hunt, T and Amit, Z}, title = {Heroin and morphine: aversive and analgesic effects in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {15}, number = {5}, pages = {755-759}, doi = {10.1016/0091-3057(81)90018-6}, pmid = {7312910}, issn = {0091-3057}, mesh = {*Analgesics ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Heroin/*pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Reaction Time/drug effects ; Taste/drug effects ; }, abstract = {Although a number of studies demonstrate morphine-induced taste aversions, no such reports exist for heroin. In a conventional taste aversion paradigm, rats were injected with one of six heroin doses (0.5-12.0 mg/kg) after consuming a novel saccharin solution (Experiment 1). When the saccharin was reintroduced a second time no significant reduction in consumption occurred at any of the doses tested. It was therefore concluded that heroin does not readily induce a taste aversion. In Experiment 2, morphine was tested in an identical taste aversion paradigm and, as expected, a significant taste aversion did result at two of the doses tested. Experiment 3 demonstrated that heroin produced analgesia equal to or greater than morphine when comparing dosages of heroin which failed to induce a CTA with CTA-inducing morphine dosages. Thus, whereas heroin is more potent than morphine as an analgesic, heroin is less potent than morphine as a CTA-inducing agent.}, } @article {pmid7299491, year = {1981}, author = {Glick, Z}, title = {Modes of action of gallic acid in suppressing food intake of rats.}, journal = {The Journal of nutrition}, volume = {111}, number = {11}, pages = {1910-1916}, doi = {10.1093/jn/111.11.1910}, pmid = {7299491}, issn = {0022-3166}, support = {AM-15165/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Body Weight/drug effects ; Eating/*drug effects ; Female ; Gallic Acid/*pharmacology ; Intubation, Gastrointestinal ; Kinetics ; Male ; Methylation ; Propyl Gallate/pharmacology ; Rats ; Rats, Inbred Strains ; Structure-Activity Relationship ; Taste ; }, abstract = {Gallic acid (3,4,5,trihydroxybenzoic acid) is a naturally occurring polyphenol comprising the major hydrolytic product of tannic acid. Gallic acid and tannic acid were previously shown to suppress food intake of animals to a similar extent. However, the mechanism by which this effect takes place has not been previously reported. Reported here is that the effect of gallic acid on food intake is not mediated entirely through taste aversion or through other gastrointestinal factors, since a continuous daily infusion of a gallic acid solution (18 ml; 2%) resulted in a significant reduction of food intake. The catechol moiety of gallic acid plays an important role in its suppression of food intake since administration of tis 4-0 methyl derivative was significantly less effective is suppressing food intake (P less than 0.01). The effectiveness of gallic acid in suppressing food intake diminishes with time, indicating adaptation to the consumption of this polyphenol. Propyl gallate is a more potent suppressor of food intake than gallic acid. Adaptation to the consumption of this polyphenol, it it exists at all, is much slower than with gallic.}, } @article {pmid7323158, year = {1981}, author = {Smotherman, WP and Burt, G and Kimble, DP and Strickrod, G and BreMiller, R and Levine, S}, title = {Behavioral and corticosterone effects in conditioned taste aversion following hippocampal lesions.}, journal = {Physiology & behavior}, volume = {27}, number = {4}, pages = {569-574}, doi = {10.1016/0031-9384(81)90224-9}, pmid = {7323158}, issn = {0031-9384}, support = {1-RO1-NS15718-02/NS/NINDS NIH HHS/United States ; K5-MH19936/MH/NIMH NIH HHS/United States ; RR07079/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Behavior, Animal/*physiology ; Corticosterone/blood/*pharmacology ; Hippocampus/*physiology ; Male ; Memory/physiology ; Rats ; Rats, Inbred Strains ; Sympathetic Nervous System/physiology ; Taste/physiology ; }, } @article {pmid7296307, year = {1981}, author = {Royet, JP and Pager, J}, title = {Olfactory bulb responsiveness to an aversive or novel food odor in ;the unrestrained rat.}, journal = {Brain research bulletin}, volume = {7}, number = {4}, pages = {375-378}, doi = {10.1016/0361-9230(81)90032-0}, pmid = {7296307}, issn = {0361-9230}, mesh = {Animals ; Food ; Hunger ; Learning ; Male ; *Odorants ; Olfactory Bulb/*physiology ; Rats ; Rats, Inbred Strains ; Satiation ; *Smell ; }, abstract = {The mechanisms subserving neophobia and learned aversion have been investigated by recording multiunit olfactory bulb discharges either in hungry rats following food deprivation or in satiated rats. Under the two conditions, rats were stimulated with the smell of their familiar maintenance diet or that of a novel food or of control food-unrelated odor. Responses to the odor of the novel food were tested, following a pairing of the first or the second intake of that food with a LiCl injection, or following its first intake paired with a NaCl control injection. All rats exhibited enhanced level of discharges when they were stimulated in the hungry state with the smell of the familiar food and not when stimulated with the non-alimentary control odor. The hunger to satiety modulation of olfactory bulb discharges, also exhibited in rats tested with the smell of the novel food, previously paired with NaCl, was absent after a LiCl-induced taste aversion to this odor. The small, although significant, modulation observed when the conditioning of aversion occurred with the less novel food is consistent with the view that learned safety prevails upon learned harmfulness. Results are discussed in terms of relations of olfactory bulb electrical responses to odors with food palatability, neophobia and learned aversion.}, } @article {pmid7291268, year = {1981}, author = {Blair, R and Amit, Z}, title = {Morphine conditioned taste aversion reversed by periaqueductal gray lesions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {15}, number = {4}, pages = {651-653}, doi = {10.1016/0091-3057(81)90224-0}, pmid = {7291268}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain/*physiology ; Dextroamphetamine/pharmacology ; Ethanol/pharmacology ; Fenfluramine/pharmacology ; Lithium/pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {The role of the periaqueductal gray (PAG) in morphine conditioned taste aversion (CTA) was studied using male Wistar rats as subjects. Following the presentation of a novel saccharin solution, animals with or without a lesion of the PAG were intraperitoneally injected with either morphine, lithium, ethanol or fenfluramine. As evident by the amount of saccharin solution consumed on a subsequent presentation, a PAG lesion reversed a morphine CTA but not CTAs produced by the other drugs used. The results suggest that the PAG may in part mediate morphine CTA.}, } @article {pmid7288616, year = {1981}, author = {D'Mello, GD and Goldberg, DM and Goldberg, SR and Stolerman, IP}, title = {Conditioned taste aversion and operant behavior in rats: effects of cocaine, apomorphine and some long-acting derivatives.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {219}, number = {1}, pages = {60-68}, pmid = {7288616}, issn = {0022-3565}, support = {DA 00499/DA/NIDA NIH HHS/United States ; DA 01505/DA/NIDA NIH HHS/United States ; MH 07658/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Apomorphine/*analogs & derivatives/*pharmacology ; Avoidance Learning/*drug effects ; Cocaine/*analogs & derivatives/*pharmacology ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Male ; Rats ; Taste ; Time Factors ; }, abstract = {Apomorphine and cocaine and their long-acting derivatives, diisobutyrylapomorphine and Win 35,428 (a fluorine-substituted phenyltropane analog of cocaine), were compared for their effects in producing conditioned taste aversions and altering schedule-controlled behavior in rats. The drugs had qualitatively similar effects in both types of experiments; suitable doses of each drug produced marked decreases in consumption of flavored solutions associated with their injection and suppressed key-press responding maintained under a 30-response fixed-ratio scheduled of food presentation. Potency ratios for apomorphine and cocaine relative to their long-acting derivatives were similar in both experiments; Win 35,428 was approximately 34 times more potent than cocaine, whereas apomorphine and diisobutyrylapomorphine did not differ appreciably in potency. Extending the duration of action of cocaine by administering an initial dose of 53 micromol/kg of cocaine followed by two additional doses of 26.5 micromol/kg at 30-min intervals failed to produce a greater degree of taste aversion than administration of only a single dose of 53 micromol/kg of cocaine. The observations with Win 35,428 and diisobutyrylapomorphine confirm previous work with these compounds and extend its generally to other species of animal and types of behaviors. None of the findings support the view that the potency of a drug in producing conditioned taste aversions is correlated with its duration of action.}, } @article {pmid7335779, year = {1981}, author = {Aggleton, JP and Petrides, M and Iversen, SD}, title = {Differential effects of amygdaloid lesions on conditioned taste aversion learning by rats.}, journal = {Physiology & behavior}, volume = {27}, number = {3}, pages = {397-400}, doi = {10.1016/0031-9384(81)90322-x}, pmid = {7335779}, issn = {0031-9384}, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/*physiology ; Drinking Behavior ; Male ; Quinine ; Rats ; Rats, Inbred Strains ; Sucrose ; Taste/*physiology ; }, } @article {pmid7325935, year = {1981}, author = {Sjödén, PO and Archer, T}, title = {Associative and nonassociative effects of exteroceptive context in taste-aversion conditioning with rats.}, journal = {Behavioral and neural biology}, volume = {33}, number = {1}, pages = {74-92}, doi = {10.1016/s0163-1047(81)92254-8}, pmid = {7325935}, issn = {0163-1047}, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical ; Cues ; Extinction, Psychological/physiology ; Learning/*physiology ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, } @article {pmid7312891, year = {1981}, author = {Pollock, JD and Rowland, N}, title = {Peripherally administered serotonin decreases food intake in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {15}, number = {2}, pages = {179-183}, doi = {10.1016/0091-3057(81)90174-x}, pmid = {7312891}, issn = {0091-3057}, mesh = {Animals ; Arousal/drug effects ; Avoidance Learning/drug effects ; Depression, Chemical ; Drinking Behavior/drug effects ; Feeding Behavior/*drug effects ; Male ; Motor Activity/drug effects ; Rats ; Rats, Inbred Strains ; Serotonin/*pharmacology ; Taste/drug effects ; }, abstract = {We report that intraperitoneal injection of serotonin produces a dose-related decrease in the food intake of hungry rats. The efficacy of serotonin was increased by prior treatment with clorgyline, a type A monoamine oxidase inhibitor. Doses of serotonin which were anorectic did not significantly impair locomotor activity or sensorimotor performance. Further, 2 mg/kg serotonin (ED50 on food intake) did not produce a conditioned taste aversion when paired repeatedly with sucrose ingestion. We conclude that the anorectic effects of serotonin are not secondary to nonspecific effects of the agent, and suggest that peripheral serotonin may play a role in normal satiation.}, } @article {pmid7291421, year = {1981}, author = {Balcom, FW and Coleman, WR and Norman, JL}, title = {Taste aversion learning and long-term retention in juvenile rats.}, journal = {Psychological reports}, volume = {49}, number = {1}, pages = {266}, doi = {10.1177/003329418104900101}, pmid = {7291421}, issn = {0033-2941}, mesh = {Aging ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; *Memory ; Rats ; *Retention, Psychology ; *Taste ; }, } @article {pmid7276281, year = {1981}, author = {Schoenfeld, TA and Hamilton, LW}, title = {Disruption of appetite but not hunger or satiety following small lesions in the amygdala of rats.}, journal = {Journal of comparative and physiological psychology}, volume = {95}, number = {4}, pages = {565-587}, doi = {10.1037/h0077801}, pmid = {7276281}, issn = {0021-9940}, support = {MH 05403/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Appetite/*physiology ; Body Weight ; Corpus Striatum/physiology ; Drinking ; Eating ; Hunger/*physiology ; Male ; Rats ; Rats, Inbred Strains ; Satiation/*physiology ; Thalamic Nuclei/physiology ; }, abstract = {Discretely localized lesions were made in the amygdala to examine how specifically they might alter various measures of feeding behavior in male rats. Behavioral tests included spontaneous intake and body weight regulation, reactivity to saccharin and quinine solutions, conditioned taste aversion, the feeding response to food deprivation, the response to glucose gavage, and teh response to dietary amino acid imbalance. Lesions in virtually all regions of the amygdala disrupted feeding behavior in some respect, but alterations in specific tasks were associated only with highly circumscribed brain damage. Body weight regulation, spontaneous food and water intake, and the responses to glucose gavage and long-term food deprivation were not altered by lesions in the amygdala. The results provide evidence that, in the rat, the amygdala may play a greater role in appetite than in hunger or safety. In particular, amygdaloid nuclei may participate in maintaining a negative bias in the reactivity to all appetitive stimuli.}, } @article {pmid6947302, year = {1981}, author = {Kenney, NJ and Moe, KE and Skoog, KM}, title = {The antidipsogenic action of peripheral prostaglandin E2.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {15}, number = {2}, pages = {263-269}, doi = {10.1016/0091-3057(81)90186-6}, pmid = {6947302}, issn = {0091-3057}, support = {NIH AM22024/AM/NIADDK NIH HHS/United States ; }, mesh = {Angiotensin II/pharmacology ; Animals ; Dehydration/physiopathology ; Dinoprostone ; Drinking/*drug effects ; Injections, Intraventricular ; Male ; Polyethylene Glycols/pharmacology ; Prostaglandins E/*pharmacology ; Rats ; Time Factors ; Water Deprivation ; }, abstract = {Intraperitoneal (IP) injection of 50 micrograms/kg prostaglandin E2 (PGE2) suppresses water intake elicited by cellular dehydration, intracerebroventricular injection of angiotensin II (A II) and, for a shorter duration, water deprivation. At a dose of 100 micrograms/kg, IP PGE2 reduces drinking to all of these stimuli as well as to hypovolemia. A 10 microgram/kg dose of PGE2 has no effect on drinking under any of the conditions tested. Intraperitoneal PGE2, at either 50 or 100 micrograms/kg, does not support the formation of a conditioned taste aversion suggesting that PGE may act via specific inhibition of drinking rather than by producing a generalized malaise. Although both central and peripheral administration of PGE suppresses water intake, the findings that peripheral PGE2 reduces drinking to cellular dehydration but has minimal effects on drinking due to hypovolemia are in marked contrast to the actions reported for intracranial PGE. In addition, peripheral PGE2 reduces body temperature whereas centrally applied PGE induces thermogenesis. These data may indicate differential roles and/or mechanisms by which central and peripheral PGE may control water intake.}, } @article {pmid7291233, year = {1981}, author = {Kesner, RP and Hardy, JD and Calder, LD}, title = {Phencyclidine and behavior: I. Sensory-motor function, activity level, taste aversion and water intake.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {15}, number = {1}, pages = {7-13}, doi = {10.1016/0091-3057(81)90330-0}, pmid = {7291233}, issn = {0091-3057}, support = {RR07092-12/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Drinking Behavior/drug effects ; Male ; Motor Activity/drug effects ; Motor Skills/drug effects ; Phencyclidine/*pharmacology ; Rats ; Sensation/drug effects ; Taste/drug effects ; }, abstract = {Phencyclidine (PCP) injections in rats at doses of 4 mg/kh increased activity level, which might have been a function of impaired habituation. At doses of 8 mg/kg PCP produced a marked reduction in activity level. At doses of 12 mg/kg and above there were profound disruptive effects in detection of odors, visual square and touch measures, and performance of placing reflexes requiring visuo-motor coordination, righting, grasping reflexes, and equilibrium. Decreases in water intake occurred only at higher dose levels of PCP (16 and 24 mg/kg). On a qualitative basis the changes observed in rats are similar to changes described for humans.}, } @article {pmid7283919, year = {1981}, author = {Lasiter, PS and Braun, JJ}, title = {Shock facilitation of taste aversion learning.}, journal = {Behavioral and neural biology}, volume = {32}, number = {3}, pages = {277-281}, doi = {10.1016/s0163-1047(81)92320-7}, pmid = {7283919}, issn = {0163-1047}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Classical ; Electroshock ; Extinction, Psychological ; Male ; Muridae ; *Taste ; }, } @article {pmid6269526, year = {1981}, author = {Springer, AD and Fraley, SM}, title = {Extinction of a conditioned taste aversion in young, mid-aged, and aged C57/BL6 mice.}, journal = {Behavioral and neural biology}, volume = {32}, number = {3}, pages = {282-294}, doi = {10.1016/s0163-1047(81)92333-5}, pmid = {6269526}, issn = {0163-1047}, support = {AG02150/AG/NIA NIH HHS/United States ; }, mesh = {*Aging ; Animals ; *Avoidance Learning/drug effects ; Chlorides/poisoning ; *Conditioning, Classical/drug effects ; Drinking/drug effects ; *Extinction, Psychological/drug effects ; Lithium/poisoning ; Lithium Chloride ; Male ; Mice ; Mice, Inbred C57BL ; *Taste/drug effects ; }, } @article {pmid6267627, year = {1981}, author = {Chambers, KC and Sengstake, CB and Yoder, RL and Thornton, JE}, title = {Sexually dimorphic acquisition of a conditioned taste aversion in rats: effects of gonadectomy, testosterone replacement and water deprivation.}, journal = {Physiology & behavior}, volume = {27}, number = {1}, pages = {83-88}, doi = {10.1016/0031-9384(81)90303-6}, pmid = {6267627}, issn = {0031-9384}, support = {RR-00163/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; *Castration ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Extinction, Psychological/drug effects ; Female ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Sex Factors ; Taste/*drug effects ; Testosterone/*pharmacology ; Water Deprivation ; }, } @article {pmid7196046, year = {1981}, author = {Jacobs, WJ and Zellner, DA and LoLordo, VM and Riley, AL}, title = {The effect of post-conditioning exposure to morphine on the retention of a morphine-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {14}, number = {6}, pages = {779-785}, doi = {10.1016/0091-3057(81)90361-0}, pmid = {7196046}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Drinking/drug effects ; Female ; Humans ; Memory/*drug effects ; Morphine/*pharmacology ; Morphine Dependence/psychology ; Naloxone/pharmacology ; Rats ; Taste ; }, abstract = {In the following experiment, multiple injections of morphine sulfate following the acquisition of a morphine-induced taste aversion had no effect on the retention of the previously acquired aversion. Post-conditioning injections of morphine resulted in the development of physical dependence to morphine and led to a decrement in the ability of morphine to induce a subsequent aversion to a second novel taste. This failure of post-conditioning exposures to morphine to affect a previously acquired morphine-induced taste aversion even though tolerance to morphine had occurred was discussed in the context of Rescorla's event-memory model of conditioning.}, } @article {pmid7225877, year = {1981}, author = {Coil, JD and Norgren, R}, title = {Taste aversions conditioned with intravenous copper sulfate: attenuation by ablation of the area postrema.}, journal = {Brain research}, volume = {212}, number = {2}, pages = {425-433}, doi = {10.1016/0006-8993(81)90474-1}, pmid = {7225877}, issn = {0006-8993}, support = {NS06041/NS/NINDS NIH HHS/United States ; NS10150/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*drug effects ; Brain Stem/physiology ; Cerebral Ventricles/*physiology ; Chemoreceptor Cells/physiology ; Conditioning, Psychological/*drug effects ; Injections, Intravenous ; Male ; Rats ; Stomach/innervation ; Taste/*drug effects ; }, abstract = {Borison and Wang identified the area postrema as the locus of chemoreceptors that mediate emetic reflexes elicited by blood-borne toxins. In the present experiments we have extended a systematic investigation of the afferent pathways mediating taste aversions by examining the effects of area postrema lesions on the aversions that follow either intravenous or intragastric administration of copper sulfate. Intrajugular cannulas were implanted in rats after ablation of the area postrema (Group AP-L) and in operated controls (Group AP-C). Every third day rats were offered a saccharin solution and immediately afterward were injected intravenously with 0.05 ml isotonic CuSO4. A group of pseudo-conditioned rats (Group SAC-C) was injected with CuSO4 approximately 24 h after ingestion of saccharin. Compared to controls animals, rats with area postrema damage acquired significantly weaker aversions to saccharin when it was paired repeatedly with intravenous CuSO4. After three conditioning trials, the rats in Group AP-L that were most resistant to acquisition of a taste aversion (Group AP-L) were again offered saccharin, but ingestion in this case was followed immediately by intragastric injection of CuSO4. After a single conditioning trial rats in Group AP-L demonstrated a robust aversion. The results are discussed in terms of the parallels in afferent systems between emetic physiology and some instances of taste aversion conditioning.}, } @article {pmid6269323, year = {1981}, author = {Kassil', VG and Makukhina, GV}, title = {[Age and sex differences in the elaboration and maintenance of conditioned taste aversion in rats].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {31}, number = {3}, pages = {630-632}, pmid = {6269323}, issn = {0044-4677}, mesh = {Age Factors ; Animals ; Avoidance Learning/*physiology ; Chlorides ; Conditioning, Classical/*physiology ; Female ; Lithium ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin ; Sex Factors ; Taste/*physiology ; }, } @article {pmid6263113, year = {1981}, author = {Anika, SM and Houpt, TR and Houpt, KA}, title = {Cholecystokinin and satiety in pigs.}, journal = {The American journal of physiology}, volume = {240}, number = {5}, pages = {R310-8}, doi = {10.1152/ajpregu.1981.240.5.R310}, pmid = {6263113}, issn = {0002-9513}, support = {AM-17601/AM/NIADDK NIH HHS/United States ; }, mesh = {Anesthetics, Local/pharmacology ; Animals ; Avoidance Learning/drug effects ; Ceruletide/pharmacology ; Cholecystokinin/administration & dosage/analogs & derivatives/*pharmacology ; Duodenum ; Female ; Infusions, Parenteral ; Injections ; Injections, Intraperitoneal ; Injections, Intravenous ; Intestinal Mucosa/physiology ; Male ; Satiation/*drug effects ; Sincalide ; Swine ; Taste/drug effects ; }, abstract = {Twenty-three pigs, 1-3 mo of age, were fitted variously with intraperitoneal, intrajugular, intraportal, and intraduodenal catheters. After a 4-h fast, porcine cholecystokinin (CCK), 5-40 Ivy dog units/kg body wt (IDU/kg); caerulein, 0.25-2 micrograms/kg; or the octapeptide of cholecystokinin (CCK-OP), 5-40 IDU/kg, was given parenterally; or 2-5% sodium oleate or 5% protein hydrolysate (5 ml/kg) was injected intraduodenally. Pelleted feed intake was then measured for 10 min. Food intake was depressed in a dose-related fashion in all instances as compared to after 0.9% NaCl control injections. For example, feed consumption following 5 and 40 IDU/kg of CCK intrajugularly was 84 +/- 2 and 6 +/- 4 (SE) %, respectively, of control intake. Intraportal infusion produced a greater depression of feeding. A conditioned taste aversion could not be formed to CCK, caerulein, or CCK-OP. Sodium oleate or protein hydrolysate, releasers of endogenous CCK, depressed feeding, and this satiety effect was attenuated when given with 0.5% tetracaine. The results support the hypothesis that CCK participates in rapid, presumably preabsorptive, satiety.}, } @article {pmid7225824, year = {1981}, author = {Jakinovich, W}, title = {Stimulation of the gerbil's gustatory receptors by artificial sweeteners.}, journal = {Brain research}, volume = {210}, number = {1-2}, pages = {69-81}, doi = {10.1016/0006-8993(81)90885-4}, pmid = {7225824}, issn = {0006-8993}, support = {1R01NS16022-01CMS/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Dose-Response Relationship, Drug ; Gerbillinae ; Structure-Activity Relationship ; Sucrose/pharmacology ; *Sweetening Agents/pharmacology ; *Taste ; Taste Buds/drug effects/*physiology ; Taste Threshold ; }, abstract = {Some electrophysiological and behavioral taste experiments have been undertaken to determine how the Mongolian gerbil responds to artificial sweeteners. In the electrophysiological experiment only fourteen of twenty-one sweeteners produced neural responses. The most potent compound was L-4'-cyano-3-(2,2,2-trifluoroacetamido)succinanilic acid. Halogenated derivatives were more potent stimuli than non-halogenated ones. D-Tryptophan was stimulatory while L-tryptophan was not. The electrophysiological responses to sucrose were not inhibited by the presence of non-stimulating sweeteners nor were the responses to D-tryptophan inhibited by L-tryptophan. All the compounds that were stimulatory electrophysiologically were used in the behavior experiment. Using conditioned taste aversion, the gerbils responded to 5 of the compounds as sweet, one as sweet-salty, two as sweet-bitter, one as sour and one as bitter. In addition, 3 compounds were drunk equally by all groups suggesting that they were tasteless or possessed some unknown taste quality. A correlation was found between the efficacy (Kd) of the sweet-tasting compounds (pure sweet or mixed sweet) and the sweetness ranking by humans.}, } @article {pmid7232471, year = {1981}, author = {Weinberg, J and Brett, LP and Levine, S and Dallman, PR}, title = {Long-term effects of early iron deficiency on consummatory behavior in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {14}, number = {4}, pages = {447-453}, doi = {10.1016/0091-3057(81)90301-4}, pmid = {7232471}, issn = {0091-3057}, support = {HD-02881/HD/NICHD NIH HHS/United States ; HD-13897/HD/NICHD NIH HHS/United States ; MH-15147/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Corticosterone/*blood ; *Drinking Behavior ; Female ; *Iron Deficiencies ; Male ; Pregnancy ; Rats ; Sex Factors ; Taste ; }, abstract = {Two experiments were designed to investigate the effects of early iron deficiency on consummatory behavior in the adult rat. In experiment 1, animals were placed in a novel chamber, either with or without water available. Although there were no effects of iron deficiency per se, the data suggested that decreased caloric intake experienced early in life may have different long-term consequences for males and females. While ad lib control males, and females in all diet conditions, exhibited less elevation of plasma corticosterone when water was available in the novel chamber, calorically restricted males appeared unable to use the cues or reinforcement provided by consummatory behavior to reduce arousal. In Experiment 2, a conditioned taste aversion situation involving conflict, we were able to separate effects due to early iron deficiency from those due to early caloric restriction. When reexposed to milk, calorically restricted (weight control) males exhibited an attenuated plasma corticoid response, compared to that of ad lib control males, while weight control females resembled ad lib control females in their response. Thus, as in Experiment 1, early caloric restriction affected males more than females. Early iron deficiency, however, markedly altered pituitary-adrenal responsiveness in both males and females. Not only was the response to reexposure completely reversed in rehabilitated males and females, but also, the corticoid response to deprivation was increased in rehabilitated males and decreased in rehabilitated females. Taken together with previous data, these results suggest that early iron deficiency alters both behavioral and physiological arousal or responsiveness, and may do so differentially in males than females.}, } @article {pmid6262682, year = {1981}, author = {Reddy, MM and Bures, J}, title = {Unit activity changes elicited in amygdala and neocortex of anaesthetized rats by intraperitoneal injection of lithium chloride.}, journal = {Neuroscience letters}, volume = {22}, number = {2}, pages = {169-172}, doi = {10.1016/0304-3940(81)90082-3}, pmid = {6262682}, issn = {0304-3940}, mesh = {Amygdala/drug effects/*physiology ; Animals ; Cerebral Cortex/drug effects/*physiology ; Chlorides/pharmacology ; Electric Conductivity ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Neurons/drug effects/*physiology ; Rats ; }, abstract = {Intraperitoneal injection of 0.15 M LiCl (2% body weight) to anaesthetized rats elicited, after a 6 min latency, discharge of about 50% units i basolateral amygdala (n = 27). The activation lasted for 15 min on the average. Cortical neurones were not affected by the LiCl injection. It is suggested that the amygdalar reaction to LiCl administration may account for the association of the gustatory trace with the visceral signals of poisoning which mediates acquisition of conditioned taste aversion under anaesthesia.}, } @article {pmid7225026, year = {1981}, author = {Buresová, O and Bures, J}, title = {Threshold hypothermia disrupting acquisition of conditioned taste aversion and attenuation of neophobia in rats.}, journal = {Behavioral and neural biology}, volume = {31}, number = {3}, pages = {274-282}, doi = {10.1016/s0163-1047(81)91289-9}, pmid = {7225026}, issn = {0163-1047}, mesh = {Animals ; Association Learning/*physiology ; Cold Temperature ; Hypothermia/*physiopathology ; Learning/*physiology ; Male ; Poisoning/physiopathology ; Rats ; Saccharin ; Sensory Thresholds/physiology ; Taste/*physiology ; }, } @article {pmid7217406, year = {1981}, author = {Kiefer, SW and Rusiniak, KW and Garcia, J and Coil, JD}, title = {Vagotomy facilitates extinction of conditioned taste aversions in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {95}, number = {1}, pages = {114-122}, pmid = {7217406}, issn = {0021-9940}, support = {AA 03513/AA/NIAAA NIH HHS/United States ; HD 05958/HD/NICHD NIH HHS/United States ; NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Brain Stem/physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Male ; Rats ; Taste/*physiology ; Vagotomy, Proximal Gastric ; Vagus Nerve/*physiology ; }, abstract = {Results from three experiments indicate that severing the subdiaphragmatic vagus in rats increased the rate of extinction of learned taste aversions. In Experiment 1, although vagotomized rats acquired a saccharin aversion equivalent to that of controls when the illness-inducing agent was the blood-borne toxin apomorphine, vagotomized rats tended to consume more saccharin than controls during repeated extinction tests. In Experiment 2, vagotomy disrupted retention and increased extinction of a preoperatively acquired saccharin aversion. Disruptions were found when the taste aversion was induced by copper sulfate, a local gastric irritant (Experiment 2A), or apomorphine, a systemic toxin (Experiment 2B); in each experiment vagotomized rats consumed more saccharin than controls on the first retention test and extinguished the prior to surgery. Experiment 3 demonstrated that vagotomy did not affect retention or extinction of a shock-induced conditioned emotional response (lick to suppression) to noise. It is concluded that integrity of the vagus is not necessary for acquisition of a learned taste aversion when a blood-borne toxin is used as the ill-inducing agent. However, the vagus apparently mediates an integral portion of the conditioned response following taste-illness acquisition regardless of whether the illness agent is a local gastric irritant or a systemic toxin.}, } @article {pmid7465611, year = {1981}, author = {Wagner, GC and Foltin, RW and Seiden, LS and Schuster, CR}, title = {Dopamine depletion by 6-hydroxydopamine prevents conditioned taste aversion induced by methylamphetamine but not lithium chloride.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {14}, number = {1}, pages = {85-88}, doi = {10.1016/0091-3057(81)90107-6}, pmid = {7465611}, issn = {0091-3057}, support = {DA00085/DA/NIDA NIH HHS/United States ; DA00250/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Dopamine/metabolism/*physiology ; Drinking Behavior/drug effects ; Hydroxydopamines/*pharmacology ; Lithium/*pharmacology ; Male ; Methamphetamine/antagonists & inhibitors/*pharmacology ; Norepinephrine/metabolism ; Rats ; Taste ; }, abstract = {Specific lesions of the central dopaminergic system produced by intraventricular injections of 6-hydroxydopamine with pargyline and desmethylimipramine pretreatment significantly attenuated conditioned taste aversions to a sweetened-condensed milk solution induced by methylamphetamine. Identically treated rats formed an aversion to the milk solution when lithium chloride was utilized. These results suggest that the methylamphetamine-induced aversion is dependent upon intact dopaminergic neurons.}, } @article {pmid7346161, year = {1981}, author = {Smith, JC and Blumsack, JT}, title = {Learned taste aversion as a factor in cancer therapy.}, journal = {Cancer treatment reports}, volume = {65 Suppl 5}, number = {}, pages = {37-42}, pmid = {7346161}, issn = {0361-5960}, support = {CA-22768-02/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Conditioning, Psychological ; Female ; Humans ; Male ; Neoplasms/*radiotherapy ; Radiotherapy/adverse effects ; Rats ; Rats, Inbred Strains ; Taste/physiology/radiation effects ; Taste Disorders/*etiology/psychology ; }, } @article {pmid7309332, year = {1981}, author = {Sclafani, A and Koopmans, HS}, title = {Intestinal bypass surgery produces conditioned taste aversion in rats.}, journal = {International journal of obesity}, volume = {5}, number = {5}, pages = {497-500}, pmid = {7309332}, support = {AM 00198/AM/NIADDK NIH HHS/United States ; AM 23064/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Body Weight ; Conditioning, Operant/physiology ; Female ; Ileum/physiology/*surgery ; Jejunum/physiology/*surgery ; Rats ; Taste/*physiology ; }, abstract = {Intestinal bypass surgery reduced the body weight of obese humans and rats primarily by decreasing food consumption. The present study reports that jejunoileal bypass surgery in rats produces a strong and persistent conditioned taste aversion to a novel-flavored solution with which it is paired. This finding indicates that the jejunioleal bypass produces a long-lasting malaise, which may be an important factor in the anorexia and weight loss produced by the operation.}, } @article {pmid7305805, year = {1981}, author = {Deutsch, JA and Parsons, SL}, title = {Bombesin produces taste aversion in rats.}, journal = {Behavioral and neural biology}, volume = {31}, number = {1}, pages = {110-113}, doi = {10.1016/s0163-1047(81)91194-8}, pmid = {7305805}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*drug effects ; Bombesin/*pharmacology ; Conditioning, Psychological ; Eating/drug effects ; Male ; Peptides/*pharmacology ; Rats ; Rats, Inbred Strains ; Satiation/*drug effects ; Taste/drug effects ; }, } @article {pmid7285791, year = {1981}, author = {Vartanian, GA and Makarova, TM}, title = {[Direct transfer of a conditioned taste aversion reflex].}, journal = {Doklady Akademii nauk SSSR}, volume = {259}, number = {5}, pages = {1265-1267}, pmid = {7285791}, issn = {0002-3264}, mesh = {Animals ; Cerebrospinal Fluid/physiology/transplantation ; Conditioning, Classical/*physiology ; Rats ; Taste/*physiology ; Time Factors ; }, } @article {pmid7268796, year = {1981}, author = {Yokel, RA and Ogzewalla, CD}, title = {Effects of plant ingestion in rats determined by the conditioned taste aversion procedure.}, journal = {Toxicon : official journal of the International Society on Toxinology}, volume = {19}, number = {2}, pages = {223-232}, doi = {10.1016/0041-0101(81)90025-8}, pmid = {7268796}, issn = {0041-0101}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Ethanol/pharmacology ; Lithium/pharmacology ; Male ; *Plants ; Plants, Toxic ; Rats ; Saccharin/pharmacology ; *Taste ; }, } @article {pmid7225218, year = {1981}, author = {Smotherman, WP and Kolp, LA and Coyle, S and Levine, S}, title = {Hippocampal lesion effects on conditioned taste aversion and pituitary-adrenal activity in rats.}, journal = {Behavioural brain research}, volume = {2}, number = {1}, pages = {33-48}, doi = {10.1016/0166-4328(81)90037-1}, pmid = {7225218}, issn = {0166-4328}, support = {HD 02881/HD/NICHD NIH HHS/United States ; K5-MH19936/MH/NIMH NIH HHS/United States ; RR 07079/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/physiology ; Conditioning, Classical/*physiology ; Corticosterone/blood ; Drinking/drug effects ; Extinction, Psychological/physiology ; Hippocampus/*physiology ; Lithium/poisoning ; Male ; Pituitary-Adrenal System/*physiology ; Rats ; Taste/*physiology ; }, abstract = {A series of experiments examined the effects of hippocampal lesions on conditioned taste aversion (CTA) and pituitary-adrenal activity. Experiment 1 examined recovery from a conditioned taste aversion under conditions of free extinction. Hippocampal and unoperated rats recovered from the aversion at the same rate. Further, this experiment showed that the suppression in drinking in both groups produced by lithium chloride (LiCl) injection was a conditioned taste aversion (was dependent upon the pairing of the taste stimulus with LiCl) and not enhanced neophobia. In Experiment 2 there were no behavioral effects of the lesion in a forced extinction CTA paradigm. In addition, hippocampal lesions failed to alter pituitary-adrenal responsiveness to LiCl. In the same experiment, pituitary-adrenal responsiveness of hippocampectomized rats, when re-exposed to the taste paired earlier with LiCl, was altered. Hippocampal lesions eliminated the elevation in corticosterone shown by unoperated control and neocortical-lesioned rats. The third experiment replicated this finding showing again that hippocampal-lesioned rats failed to show the forced extinction elevation in corticosterone when exposed to the aversive taste (Experiment 3). These data were integrated with other reports of behavioral and pituitary-adrenal alterations in hippocampal-lesioned rats.}, } @article {pmid6267645, year = {1981}, author = {Switzman, L and Fishman, B and Amit, Z}, title = {Pre-exposure effects of morphine, diazepam and delta 9-THC on the formation of conditioned taste aversions.}, journal = {Psychopharmacology}, volume = {74}, number = {2}, pages = {149-157}, pmid = {6267645}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Diazepam/*pharmacology ; Dronabinol/*pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {Prior to taste aversion conditioning with morphine, diazepam or delta 9-tetrahydrocannabinol (delta 9-THC), rats received pre-exposures to the vehicle or one of the three drugs. Morphine pre-exposures blocked the aversion normally induced by morphine, but not by delta 9-THC or diazepam. Diazepam pre-exposures attenuated both the morphine- and diazepam-induced taste aversions to a significantly greater degree than the taste aversion induced by delta 9-THC. As a result of delta 9-THC pre-exposures, the aversions induced by diazepam and delta 9-THC were attenuated as well as the morphine-induced aversion, which was the most greatly attenuated. These results demonstrate that pre-exposure effects are not necessarily bi-directional and, moreover, they are inconsistent with current hypotheses which attempt to account for the attenuating effect of drug pre-exposures on taste-aversion conditioning.}, } @article {pmid6267527, year = {1981}, author = {Rondeau, DB and Jolicoeur, FB and Merkel, AD and Wayner, MJ}, title = {Drugs and taste aversion.}, journal = {Neuroscience and biobehavioral reviews}, volume = {5}, number = {2}, pages = {279-294}, doi = {10.1016/0149-7634(81)90010-5}, pmid = {6267527}, issn = {0149-7634}, support = {MH-14258/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects/radiation effects ; Barbital/pharmacology ; Barbiturates/pharmacology ; Chlordiazepoxide/pharmacology ; Chlorides ; Chlorpromazine/pharmacology ; Hexobarbital/pharmacology ; Lithium ; Lithium Chloride ; Phenobarbital/pharmacology ; Psychotropic Drugs/*pharmacology ; Rats ; Taste/*drug effects/radiation effects ; X-Rays ; }, abstract = {The literature on the effects of drugs on the acquisition and the magnitude of taste aversion is reviewed and discussed. Then, the results of a series of experiments on the effects of phenobarbital and related drugs on taste aversion are reported. A standard taste aversion model was used in all experiments; test drugs were injected prior to drinking in a one bottle situation on the first test day following the taste aversion treatment. Phenobarbital in doses ranging from 20 to 80 mg/kg significantly attenuated taste aversion induced by lithium chloride (LiCl) and x-radiation, the maximal effect occurred with the 60 mg/kg dose. The attenuating effect was found to be dependent upon the magnitude of the aversion to the sapid solution. Phenobarbital completely abolished aversion produced by 0.375 mEq LiCl while the attenuation effect decreased linearly with higher doses of LiCl. Results also indicate that phenobarbital's attenuating effect cannot be solely attributed to its dipsogenic characteristic or to its state dependent learning effect. Attenuation of LiCl aversion to a saccharin solution was also observed following single doses of amobarbital, 30 mg/kg, pentobarbital, 15 mg/kg, and chloropromazine, 0.75 mg/kg. Taste aversion was not affected by other doses of those drugs or by hexobarbital, barbital, and chlordiazepoxide. Phenobarbital's attenuating effect on taste aversion is discussed in relation to other known behavioral and neurophysiological effects of the drug.}, } @article {pmid6264712, year = {1981}, author = {Vavilova, NM and Kassil', VG}, title = {[Formation and preservation of conditioned taste aversion in dogs].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {31}, number = {1}, pages = {171-172}, pmid = {6264712}, issn = {0044-4677}, mesh = {Animals ; *Avoidance Learning ; Chlorides ; Dogs ; Extinction, Psychological ; Lithium ; Lithium Chloride ; *Memory ; Sucrose ; *Taste ; }, } @article {pmid7212131, year = {1980}, author = {Mikulka, P and Klein, S}, title = {Resistance to extinction of a taste aversion: effects of level of training and procedures used in acquisition and extinction.}, journal = {The American journal of psychology}, volume = {93}, number = {4}, pages = {631-641}, pmid = {7212131}, issn = {0002-9556}, mesh = {Animals ; *Avoidance Learning/drug effects ; Drinking/drug effects ; *Extinction, Psychological/drug effects ; Female ; Lithium/poisoning ; Rats ; *Taste/drug effects ; }, abstract = {Two studies investigated the relationship between acquisition and extinction procedures on the development and elimination of a taste aversion. In the first experiment, subjects were given either forced or free choice acquisition to a common acquisition criterion. Then, their aversion was extinguished under either the free or forced choice procedure. The results of the first study showed that the greatest resistance to extinction was produced with a forced acquisition and free extinction procedure and the least resistance was produced by a free acquisition and forced procedure. Experiment 2 employed an equal number of acquisition trials (one or three) under either free or forced acquisition followed by either free or forced extinction. The results of Experiment 2 found that resistance to extinction was greater with three compared with one acquisition trial, but the acquisition technique did not influence resistance to extinction. As in the first experiment, extinction was more rapid with forced extinction. It appears that the strength of a taste-illness association is primarily dependent on the number of CS-US associations. Thus, when a common criterion is used, forced subjects take longer to extinguish their aversion due to their stronger taste-illness association. When an equivalent number of pairings is used, extinction rats are equal in free and forced animals (even though acquisition intake was higher in forced animals).}, } @article {pmid6261274, year = {1980}, author = {Buskist, WF and Miller, HL and Duncan, P and Fleming, DE}, title = {Associative history determines strength of taste-aversion conditioning in thiamine-deficient rats.}, journal = {Physiology & behavior}, volume = {25}, number = {6}, pages = {989-992}, doi = {10.1016/0031-9384(80)90323-6}, pmid = {6261274}, issn = {0031-9384}, mesh = {Animals ; Association ; *Association Learning ; *Avoidance Learning ; Chlorides/poisoning ; *Conditioning, Psychological ; Female ; *Food Preferences ; Food, Formulated ; *Learning ; Lithium/poisoning ; Lithium Chloride ; Rats ; Thiamine Deficiency/*physiopathology ; }, } @article {pmid6261272, year = {1980}, author = {Vawter, MP and Green, KF}, title = {Effects of desglycinamide-lysine vasopressin on a conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {25}, number = {6}, pages = {851-854}, doi = {10.1016/0031-9384(80)90303-0}, pmid = {6261272}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/administration & dosage ; Drinking Behavior ; Lithium/administration & dosage ; Lithium Chloride ; Lypressin/*analogs & derivatives/pharmacology ; Male ; Memory/drug effects ; Rats ; Saccharin ; Taste/*drug effects ; }, } @article {pmid6259666, year = {1980}, author = {Concannon, JT and Freda, J}, title = {Modulation of conditioned taste aversion by sodium pentobarbital.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {13}, number = {6}, pages = {761-764}, doi = {10.1016/0091-3057(80)90203-8}, pmid = {6259666}, issn = {0091-3057}, support = {AA-05046/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Conditioning, Psychological/*drug effects ; Lithium/pharmacology ; Lithium Chloride ; Male ; Pentobarbital/*pharmacology ; Rats ; Sucrose ; Taste/*drug effects ; }, abstract = {The effects of pentobarbital on the formation and expression of LiCl induced taste aversion were examined using a two-bottle preference test. Rats adapted to restricted fluid intake were offered a 15% sucrose solution 15 min after a pentobarbital or saline injection but prior to post-CS LiCl or control injections. All animals were tested 3 days later in either the same or opposite drug state, and were returned to the conditioning day drug state for a second test. The results showed that pentobarbital in testing disrupted evidence for taste aversion in a manner not simply accounted for by its dipsogenic effects. It was suggested that the present paradigm may prove to be a simple behavioral assay for screening putative anxiolytic drugs.}, } @article {pmid7417860, year = {1980}, author = {Ritter, S and McGlone, JJ and Kelley, KW}, title = {Absence of lithium-induced taste aversion after area postrema lesion.}, journal = {Brain research}, volume = {201}, number = {2}, pages = {501-506}, doi = {10.1016/0006-8993(80)91061-6}, pmid = {7417860}, issn = {0006-8993}, support = {MH 32812-01/MH/NIMH NIH HHS/United States ; NS 14450-02/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Ventricles/drug effects/*physiology ; Chemoreceptor Cells/drug effects/*physiology ; Dextroamphetamine/pharmacology ; Female ; Lithium/*poisoning ; Male ; Rats ; Scopolamine/pharmacology ; Taste/drug effects/*physiology ; }, } @article {pmid7417801, year = {1980}, author = {Denenberg, VH and Hofmann, M and Garbanati, JA and Sherman, GF and Rosen, GD and Yutzey, DA}, title = {Handling in infancy, taste aversion, and brain laterality in rats.}, journal = {Brain research}, volume = {200}, number = {1}, pages = {123-133}, doi = {10.1016/0006-8993(80)91099-9}, pmid = {7417801}, issn = {0006-8993}, support = {HD 12948/HD/NICHD NIH HHS/United States ; MH 14278/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Brain/*physiology ; Cerebral Cortex/physiology ; Female ; *Handling, Psychological ; Male ; Milk ; Rats ; Sucrose ; *Taste ; }, abstract = {Rats were handled for the first 20 days of life or were not disturbed. When adults, they were trained to approach and drink from a bottle containing sweetened milk and were then given an injection of lithium chloride to induce a taste aversion conditioned emotional response. Others were injected with physiological saline. Rats within each of the treatment groups were then randomly assigned to 4 surgical procedures: removal of the right or left neocortex; sham surgery; or no surgery. Postoperatively, they were tested for retention of taste aversion by presenting the sweetened milk and recording the amount consumed. The initial consummatory behavior was very low (showing retention of the aversion) and increased over time. There were no differences in the reacquisition curves of the non-handled groups which had received lithium chloride. The curves of the handled groups did differ: thos with an intact right hemisphere (left neocortical lesion) had the lowest asymptote, followed by the group with an intact left brain, while those with intact whole brains consumed the greatest amount of milk. In the groups given an injection of physiological saline, those with a left hemisphere lesion consumed less milk than the other groups, regardless of their early handling experience. The data show: (1) that the rat's brain is lateralized, with the right hemisphere being preferentially involved in conditioned emotional behavior; and (2) that handling in infancy makes the left hemisphere less suceptible to conditioned fear.}, } @article {pmid6934546, year = {1980}, author = {Chang, JJ and Gelperin, A}, title = {Rapid taste-aversion learning by an isolated molluscan central nervous system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {77}, number = {10}, pages = {6204-6206}, pmid = {6934546}, issn = {0027-8424}, mesh = {Action Potentials ; Animals ; Avoidance Learning/drug effects/*physiology ; Central Nervous System/physiology ; Colchicine/pharmacology ; Ganglia/physiology ; Hydrolyzable Tannins/pharmacology ; In Vitro Techniques ; Mollusca/*physiology ; Nicotine/pharmacology ; Taste/physiology ; Time Factors ; }, abstract = {The isolated lips and nervous system of the terrestrial slug Limax maximus will produce some of the feeding behavior of the intact animal; i.e., they generate the rhythmic neural activity characteristic of ingestion in response to food extracts applied to the lips. This preparation will respond to a variety of food extracts that elicit feeding in the whole animal. This provides the opportunity for aversive conditioning experiments involving taste discrimination. Pairing lip chemostimulation by attractive food extracts with lip chemostimulation by using bitte plant secondary substances can cause the isolatd brain to selectively suppress its neural response to one food extract while remaining responsive to another. Such isolated brains can learn after one or two trials and retain the learning for more than 8 hr.}, } @article {pmid6255931, year = {1980}, author = {Fischer, GJ and Vail, BJ}, title = {Preexposure to delta-9-THC blocks THC-induced conditioned taste aversion in rats.}, journal = {Behavioral and neural biology}, volume = {30}, number = {2}, pages = {191-196}, doi = {10.1016/s0163-1047(80)91065-1}, pmid = {6255931}, issn = {0163-1047}, support = {NIDA 01245/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Dronabinol/*pharmacology ; Female ; Male ; Premedication ; Rats ; Sex Factors ; Taste/*drug effects ; }, } @article {pmid6252499, year = {1980}, author = {Sinyor, D and Switzman, L and Amit, Z}, title = {ACTH potentiates morphine-induced conditioned taste aversion.}, journal = {Neuropharmacology}, volume = {19}, number = {10}, pages = {971-973}, doi = {10.1016/0028-3908(80)90007-6}, pmid = {6252499}, issn = {0028-3908}, mesh = {Adrenocorticotropic Hormone/administration & dosage/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Injections, Intraperitoneal ; Male ; Morphine/*pharmacology ; Rats ; Taste/*drug effects ; }, } @article {pmid7443808, year = {1980}, author = {Caza, P and Steinert, PA and Spear, NE}, title = {Comparison of circadian susceptibility to LiCl-induced taste aversion learning between preweanling and adult rats.}, journal = {Physiology & behavior}, volume = {25}, number = {3}, pages = {389-396}, doi = {10.1016/0031-9384(80)90278-4}, pmid = {7443808}, issn = {0031-9384}, mesh = {Age Factors ; Animals ; Avoidance Learning/*drug effects ; Circadian Rhythm/*drug effects ; Drinking/drug effects ; Female ; Lithium/*poisoning ; Male ; Rats ; Taste/*drug effects ; Weaning ; }, } @article {pmid7203539, year = {1980}, author = {Sridhara, S and Srihari, K}, title = {Bait shyness towards zinc phosphide & vacor in the larger bandicoot rat Bandicota indica (Bechstein).}, journal = {Indian journal of experimental biology}, volume = {18}, number = {9}, pages = {1029-1031}, pmid = {7203539}, issn = {0019-5189}, mesh = {Animals ; *Feeding Behavior ; Mice ; *Phenylurea Compounds ; *Phosphines ; Rats ; Rodentia ; *Rodenticides ; Species Specificity ; Zinc ; *Zinc Compounds ; }, } @article {pmid6107371, year = {1980}, author = {Goudie, AJ and Demellweek, C}, title = {Naloxone fails to block amphetamine-induced anorexia and conditioned taste aversion.}, journal = {The Journal of pharmacy and pharmacology}, volume = {32}, number = {9}, pages = {653-656}, doi = {10.1111/j.2042-7158.1980.tb13026.x}, pmid = {6107371}, issn = {0022-3573}, mesh = {Amphetamine/*antagonists & inhibitors ; Animals ; Appetite Depressants/*antagonists & inhibitors ; Avoidance Learning/*drug effects ; Female ; Naloxone/*pharmacology ; Rats ; Taste/drug effects ; }, } @article {pmid7403850, year = {1980}, author = {Chen, JS and Amsel, A}, title = {Recall (versus recognition) of taste and immunization against aversive taste anticipations based on illness.}, journal = {Science (New York, N.Y.)}, volume = {209}, number = {4458}, pages = {831-833}, doi = {10.1126/science.7403850}, pmid = {7403850}, issn = {0036-8075}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological ; Extinction, Psychological ; Female ; Lithium ; Male ; Memory/*physiology ; Mental Recall/*physiology ; Rats ; Reinforcement, Psychology ; Sodium Chloride ; Taste/*physiology ; Time Factors ; }, abstract = {Two experiments show that, after taste-aversion conditioning, rats can use external retrieval cues to recall or anticipate the aversive taste solution and avoid its location without making contact with the flavor. They also show that the rat's avoidance of a conditioned aversive taste and its consumption of the aversive flavored solution can be attenuated by giving it prior runway training in which taste reward is given inconsistently on a partial reinforcement schedule.}, } @article {pmid7447856, year = {1980}, author = {Ellins, SR and Catalano, SM}, title = {Field application of the conditioned taste aversion paradigm to the control of coyote predation on sheep and turkeys.}, journal = {Behavioral and neural biology}, volume = {29}, number = {4}, pages = {532-536}, doi = {10.1016/s0163-1047(80)92882-4}, pmid = {7447856}, issn = {0163-1047}, mesh = {Animals ; *Appetitive Behavior/drug effects ; *Avoidance Learning/drug effects ; *Conditioning, Classical/drug effects ; Dogs ; Lithium/poisoning ; *Predatory Behavior/drug effects ; Sheep ; *Taste/drug effects ; Turkeys ; }, } @article {pmid7410632, year = {1980}, author = {Gemberling, GA and Domjan, M and Amsel, A}, title = {Aversion learning in 5-day-old rats: taste-toxicosis and texture-shock associations.}, journal = {Journal of comparative and physiological psychology}, volume = {94}, number = {4}, pages = {734-745}, doi = {10.1037/h0077706}, pmid = {7410632}, issn = {0021-9940}, support = {MH-2078801/MH/NIMH NIH HHS/United States ; MH-30778/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; *Association Learning/drug effects ; *Avoidance Learning/drug effects ; Dose-Response Relationship, Drug ; Electroshock ; *Learning/drug effects ; Lithium/poisoning ; Rats ; *Taste/drug effects ; }, abstract = {Five-day-old rats that received a single pairing of a novel saccharin flavor with lithium treatment learned to suppress ingestion of saccharin on subsequent occasions (Experiment 1). This flavor aversion learning was inversely related to the interval between the novel flavor experience and drug administraton, wit h significant aversions being learned with intervals of 0 and 30 min but not with intervals of 60 and 90 min (experiment 2). The conditioning was observed when hypertonic lithium served as the unconditioned stimulus but did not occur with isotonic lithium or hypertonic saline injections (Experiment 3). These results indicate that flavor aversion learning in infant rats is a result of the joint action of two factors--pure drug effects and the somatic pain and irritation produced by the tonicity of the injected agent. The taste aversion learning was specific to the drug-paired flavor, and evidence was presented suggesting that 5-day-old rats display a natural hesitancy to consume novel edibles (neophobia) (Experiment 4). Experiment 5 demonstrated that 5-day-old rats selectively associate tactile stimuli with shock but not with the gastrointestinal consequences of lithium. Implications of the mechanisms involved in flavor aversion learning in infant rats are discussed as they relate to adaptation and food selection in adult animals.}, } @article {pmid7410628, year = {1980}, author = {Phillips, AG and LePiane, G}, title = {Disruption of conditioned taste aversion in the rat by stimulation of amygdale: a conditioning effect, not amnesia.}, journal = {Journal of comparative and physiological psychology}, volume = {94}, number = {4}, pages = {664-674}, doi = {10.1037/h0077701}, pmid = {7410628}, issn = {0021-9940}, mesh = {Amygdala/*physiology ; Animals ; Conditioning, Classical/*physiology ; Cues ; Electric Stimulation ; Lithium/poisoning ; Male ; Memory/*physiology ; Mental Recall/*physiology ; Rats ; Retention, Psychology/*physiology ; Taste/*physiology ; }, abstract = {Two experiments were conducted to determine whether the disruption of conditioned taste aversion by delivery of amygdaloid brain stimulation during conditioning could be attributed to the stimulus properties of the brain stimulation. In Experiment 1, animals receiving brain stimulation (a) while drinking saccharin, (b) during the onset of LiCl toxicosis, or (c) in the interval between taste exposure and toxicosis drank significantly more saccharin solution during a 48 hr retest than implanted or unoperated controls receiving similar taste-toxicosis pairings. In contrast, a group receiving brain stimulation during both conditioning and retention trials developed a strong conditioned aversion. Experiment 2 confirmed that amygdaloid stimulation can form a compound with the taste of the saccharin solution. A small but significant aversion was displayed by groups exposed to brain stimulation plus taste during conditioning and to either taste alone or brain stimulation alone during the retest. Again, the group presented with brain stimulation and taste prior to and following LiCl toxicosis displayed a strong conditioned aversion. These data suggest that disruption of conditioned taste aversion with amygdaloid stimulation represents a conditioning effect, not amnesia.}, } @article {pmid7295379, year = {1980}, author = {Buresová, O and Bures, J}, title = {Post-ingestion interference with brain function prevents attenuation of neophobia in rats.}, journal = {Behavioural brain research}, volume = {1}, number = {4}, pages = {299-312}, pmid = {7295379}, issn = {0166-4328}, mesh = {Anesthesia ; Animals ; Body Temperature ; Brain/*physiology ; Cortical Spreading Depression ; Electroshock ; Environment ; Ether ; Feeding Behavior/*physiology ; Male ; Rats ; Taste/physiology ; Time Factors ; }, abstract = {Attenuation of the neophobic rejection of novel flavours is mediated by a memorial process the properties of which were examined by testing its resistance to functional disruption. Rats maintained on a 24-h water deprivation schedule consumed only 3 ml of the novel apple juice but doubled its intake during the second presentation 2 days later. This attenuation of neophobia (AN) was prevented by pentobarbital anaesthesia (40 mg/kg) induced 0 and 1 h, but not 4 and 7 h, after the first apple juice presentation. AN was also disrupted by ether anaesthesia (5 min), hypothermia (20 degrees C body temperature), bilateral cortical spreading depression and electroconvulsive shock (50 mA, 1.5 sec) applied 0-1 h, but not 2 or more hours, after the first apple juice presentation. The results are consonant with the 'learned safety' hypothesis and indicate that a 2-4 h long continuous absence of noxious consequences of food ingestion is required to classify a gustatory stimulus as safe or neutral. Since interventions interfering with AN do not disrupt formation of conditioned taste aversion, the two forms of adaptive control of food selection are obviously mediated by fundamentally different neural mechanisms.}, } @article {pmid7413807, year = {1980}, author = {Domjan, M}, title = {Effects of the intertrial interval on taste-aversion learning in rats.}, journal = {Physiology & behavior}, volume = {25}, number = {1}, pages = {117-125}, doi = {10.1016/0031-9384(80)90191-2}, pmid = {7413807}, issn = {0031-9384}, support = {MH-30788-01/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Avoidance Learning/drug effects ; *Conditioning, Classical/drug effects ; Drinking/drug effects ; Female ; Lithium/toxicity ; Male ; Motor Activity/drug effects ; Rats ; *Taste/drug effects ; Time Factors ; }, } @article {pmid7403218, year = {1980}, author = {Sanger, DJ and Greenshaw, AJ and Thompson, IP and Mercer, JD}, title = {Learned taste aversion to saccharin produced by orally consumed d-amphetamine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {13}, number = {1}, pages = {31-36}, doi = {10.1016/0091-3057(80)90116-1}, pmid = {7403218}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Operant/*drug effects ; Dextroamphetamine/*pharmacology ; Drinking/drug effects ; Female ; Generalization, Psychological/drug effects ; Rats ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Rats were presented with solutions containing both saccharin and d-amphetamine and the development of taste aversions to solutions of either or both of these substances was studied. In Experiment 1 it was found that taste aversions developed to solutions of saccharin (1 mg/ml) which contained amphetamine at concentrations of 0.01, 0.03 and 0.1 mg/ml. Experiment 2 showed that a taste aversion conditioned to a solution of saccharin (2 mg/ml) and amphetamine (0.2 mg/ml) generalised to solutions containing saccharin at concentrations between 0.625 and 20 mg/ml but not to a solution containing only amphetamine. In the third experiment it was found that the degree of generalisation of a taste aversion to lower saccharin concentrations depended upon the concentration used during conditioning trials. When the conditioning concentration was 0.625 mg/ml the aversion generalised to concentrations as low as 0.075 mg/ml but when a 10 mg/ml solution was used for conditioning the aversion did not generalise to concentrations below 2 mg/ml. The characteristics of taste aversions conditioned with orally consumed amphetamine are similar to those of conditioning involving injections of the drug.}, } @article {pmid7403215, year = {1980}, author = {Dantzer, R}, title = {Conditioned taste aversion as an index of lead toxicity.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {13}, number = {1}, pages = {133-135}, doi = {10.1016/0091-3057(80)90133-1}, pmid = {7403215}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Drug Tolerance ; Lead Poisoning/*psychology ; Male ; Rats ; Taste ; }, abstract = {Rats treated with lead acetate following the consumption of a solution with a distinct taste exhibited an aversion to the initially consumed solution. Conditioned taste aversion was reliably induced with 10--20 mg/kg lead acetate. Repeated treatment with lead did not enhance this effect when measured either in forced or in free choice conditions. The utility of the taste aversion procedure for evaluation of toxic agents is discussed.}, } @article {pmid7413784, year = {1980}, author = {Chambers, KC}, title = {Progesterone, estradiol, testosterone and dihydrotestosterone: effects on rate of extinction of a conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {24}, number = {6}, pages = {1061-1065}, doi = {10.1016/0031-9384(80)90048-7}, pmid = {7413784}, issn = {0031-9384}, support = {RR-00163/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Castration ; Conditioning, Psychological/*drug effects ; Dihydrotestosterone/*pharmacology ; Estradiol/*pharmacology ; Female ; Progesterone/*pharmacology ; Rats ; Taste/*physiology ; Testosterone/antagonists & inhibitors/*pharmacology ; Time Factors ; }, abstract = {An investigation was made to determine why the prolonged rate of extinction of a conditioned taste aversion induced by testosterone is diminished when the ovarian system is intact. In the first experiment, 36 gonadectomized female rats received injections of progesterone, testosterone propionate (TP), progesterone plus TP, or sesame oil. Progesterone did not reduce the slow extinction rate induced by TP. In a second experiment, 36 gonadectomized female rats received injections of estradiol dipropionate (EP), TP, EP plus TP, or sesame oil. Estradiol dipropionate reduced the effectiveness of TP in prolonging the extinction rate. These same results (the ineffectiveness of progesterone and the effectiveness of EP in blocking TP-induced slow extinction) were also observed in male rats in a third experiment. Dihydrotestosterone, as well as testosterone, has been shown to prolong extinction: hence, in a fourth experiment 30 gonadectomized female rats received injections of EP, TP, dihydrotestosterone propionate (DHTP), EP plus DHTP, or sesame oil. Estradiol dipropionate reduced the DHTP-induced slow extinction. All the above data are consistent with the hypothesis that it is estradiol from the ovaries that diminishes the effect of testosterone on the rate of extinction of a conditioned taste aversion in intact females.}, } @article {pmid7413777, year = {1980}, author = {Kratz, CM and Levitsky, DA}, title = {The role of a noxious taste in determining food intake in the rat.}, journal = {Physiology & behavior}, volume = {24}, number = {6}, pages = {1027-1030}, doi = {10.1016/0031-9384(80)90041-4}, pmid = {7413777}, issn = {0031-9384}, mesh = {Acetates/pharmacology ; Animals ; Diet/*drug effects ; Dose-Response Relationship, Drug ; Eating ; Energy Intake/*drug effects ; Feeding Behavior/*physiology ; Female ; Food Additives/*pharmacology ; Food Preferences/*drug effects ; Rats ; Sucrose/pharmacology ; Taste/*physiology ; }, abstract = {Adult female rats were given access to cornstarch, fat, and 2 cups of casein ad lib. Sucrose octaacetate was added to one or both casein cups in concentrations of 0, 0.1, or 2.5%. The lower concentrations of SOA had no effect on total caloric intake or food choices, although a taste aversion experiment indicated that the rats could detect SOA at this level. The 2.5% concentration had no effect on total caloric intake. If only one casein cup was treated with SOA, the animals consumed 70% of their protein from the unadulterated casein supply, but total protein intake was unchanged. If both cups were treated with 2.5% SOA, protein intake decreased, but carbohydrate consumption showed a compensatory increase. Fat intake was unchanged.}, } @article {pmid7433616, year = {1980}, author = {Archer, T and Sjödén, PO and Nilsson, LG and Carter, N}, title = {Exteroceptive context in taste-aversion conditioning and extinction: odour, cage, and bottle stimuli.}, journal = {The Quarterly journal of experimental psychology}, volume = {32}, number = {2}, pages = {197-214}, doi = {10.1080/14640748008401157}, pmid = {7433616}, issn = {0033-555X}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; Cues ; *Extinction, Psychological ; Male ; Rats ; *Taste ; }, } @article {pmid7393976, year = {1980}, author = {Wayner, EA and Singer, G and Wayner, MJ and Barone, FC}, title = {The taste aversion induction properties of two long duration barbiturates.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {12}, number = {5}, pages = {807-810}, doi = {10.1016/0091-3057(80)90170-7}, pmid = {7393976}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Barbital/pharmacology ; Barbiturates/*pharmacology ; Drinking Behavior/drug effects ; Male ; Phenobarbital/pharmacology ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {The ability of sodium phenobarbital (60 mg/kg) and sodium barbital (80 mg/kg) to produce a taste aversion in 23 hr fluid deprived rats was examined using a discrimination or two bottle taste aversion task (0.125% sodium saccharin solution or water). The interaction of both barbiturates with the effects of 3.0 mEq/kg lithium chloride (LiCl) was also examined. Results indicate that phenobarbital treatment alone produces a stronger saccharin aversion than does barbital. Also, barbiturate treatment 24 hr after LICi administration does not attenuate saccharin avoidance, although phenobarbital treatment following LiCl administration was sufficient to induce a maximum aversion that did not extinguish after twenty days of continuous discrimination testing. These data suggest that the aversion inducing properties of the two barbiturates are dissimilar and that phenobarbital is the more effective agent in the production of saccharin aversion. In addition, barbiturate induced attenuation of conditioned taste aversion is apparently related to the periodic forced intake test model since it does not occur when a water and saccharin choice is available.}, } @article {pmid7393975, year = {1980}, author = {Wayner, EA and Singer, G and Wayner, MJ and Barone, FC}, title = {The effects of several barbiturates on lithium chloride induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {12}, number = {5}, pages = {803-806}, doi = {10.1016/0091-3057(80)90169-0}, pmid = {7393975}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Barbiturates/*pharmacology ; Drinking Behavior/drug effects ; Drug Interactions ; Lithium/*pharmacology ; Male ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {The effects of single doses of five barbiturates on LiCl induced saccharin aversion were examined. Twenty three hour fluid deprived rats were offered a novel 0.125% saccharin solution and then were injected with either 3.0 mEq/kg LiCl or 0.9% saline. On the first test day after conditioning the animals were injected with either 60 mg/kg sodium phenobarbital, 80 mg/kg sodium barbital, 30 mg/kg sodium amobarbital, 20 mg/kg sodium secobarbital, 9 mg/kg sodium pentobarbital or 0.9% saline, 15 min prior to the drinking session. Results indicate that only 9 mg/kg pentobarbital, 60 mg/kg phenobarbital, and 80 mg/kg barbital were effective in attenuating the LiCl induced saccharin aversion on the day of administration. In addition, dipsogenic effects for only 60 mg/kg phenobarbital and 30 mg/kg amobarbital were observed in the saline treated control groups. A synergistic interaction between the effects of LiCl and sodium phenobarbital, barbital, and secobarbital was also observed. Lithium chloride plus these barbiturates resulted in a longer term aversion to saccharin than LiCl alone and no barbiturate produced saccharin aversion when administered without LiCl.}, } @article {pmid7393957, year = {1980}, author = {Jolicoeur, FB and Wayner, MJ and Merkel, AD and Rondeau, DB and Mintz, RB}, title = {The effects of various barbiturates on LiCl induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {12}, number = {4}, pages = {613-617}, doi = {10.1016/0091-3057(80)90197-5}, pmid = {7393957}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Barbiturates/*pharmacology ; Drug Interactions ; Female ; Lithium/*pharmacology ; Rats ; Saccharin/pharmacology ; Taste ; Time Factors ; }, abstract = {The effects of various barbiturates on LiCl induced taste aversion were examined. Rats were adapted to a 23 hr and 50 min water deprivation schedule. On the Treatment Day, animals were offered a novel 0.125% saccharin solution and then administered 3.0 mEq/kg LiCl. The saccharin solution was presented again on three subsequent Test Days. Fifteen minutes prior to drinking on the first Test Day animals were injected subcutaneously with either 10, 30, and 50 mg/kg Amobarbital, 3, 9, and 15 mg/kg Pentobarbital, 40, 80, and 120 mg/kg Barbital, or 1, 3, and 9 mg/kg Hexobarbital. Results indicate that only 30 mg/kg of Amobarbital and 15 mg/kg of Pentobarbital significantly attenuated the magnitude of taste aversion.}, } @article {pmid7389781, year = {1980}, author = {Ingram, DK and Peacock, LJ}, title = {Conditioned taste aversion as a function of age in mature male rats.}, journal = {Experimental aging research}, volume = {6}, number = {2}, pages = {113-123}, doi = {10.1080/03610738008258349}, pmid = {7389781}, issn = {0361-073X}, mesh = {*Aging ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; Extinction, Psychological ; Lithium/toxicity ; Male ; Rats ; Rats, Inbred F344 ; *Taste ; }, abstract = {Experimental groups of young mature (90-120 days), mature (365-395 days), and aged (730-760 days) Fischer-344 rats were allowed to drink a saccharin solution followed by lithium chloride toxicosis initiated at one of three intervals, either 15, 60, or 240 minutes. Control groups were given saline placebos according to the same schedule. In a preference test conducted 48 hours after conditioning, there was little evidence of age differences in the acquisition of a saccharin aversion. Age differences were noted in the extinction of the aversion which was tested by monitoring preference over a period of 32 days of continuous access to saccharin and water. Older animals tended to show greater resistance to extinction.}, } @article {pmid6248911, year = {1980}, author = {Burt, GS and Smotherman, WP}, title = {Amygdalectomy induced deficits in conditioned taste aversion: possible pituitary-adrenal involvement.}, journal = {Physiology & behavior}, volume = {24}, number = {4}, pages = {651-655}, doi = {10.1016/0031-9384(80)90391-1}, pmid = {6248911}, issn = {0031-9384}, mesh = {Adrenocorticotropic Hormone/administration & dosage ; Amygdala/*physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Dominance, Cerebral/physiology ; Male ; Pituitary-Adrenal System/*physiology ; Rats ; Taste/drug effects/*physiology ; }, } @article {pmid6248910, year = {1980}, author = {Hennessy, JW and Smotherman, WP and Levine, S}, title = {Investigations into the nature of the dexamethasone and ACTH effects upon learned taste aversion.}, journal = {Physiology & behavior}, volume = {24}, number = {4}, pages = {645-649}, doi = {10.1016/0031-9384(80)90390-x}, pmid = {6248910}, issn = {0031-9384}, mesh = {Adrenocorticotropic Hormone/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Dexamethasone/*pharmacology ; Drinking/drug effects ; Extinction, Psychological/drug effects ; Lithium/toxicity ; Male ; Rats ; Taste/*drug effects ; }, } @article {pmid7393942, year = {1980}, author = {Ostrowski, NL and Foley, TL and Lind, MD and Reid, LD}, title = {Naloxone reduces fluid intake: effects of water and food deprivation.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {12}, number = {3}, pages = {431-435}, doi = {10.1016/0091-3057(80)90049-0}, pmid = {7393942}, issn = {0091-3057}, mesh = {Animals ; Body Weight/drug effects ; Drinking Behavior/*drug effects ; Food Deprivation/*physiology ; Male ; Naloxone/*pharmacology ; Rats ; Water Deprivation/*physiology ; }, abstract = {Food and fluid deprived and nondeprived male rats showed 36% and 46% decreases, respectively, in sucrose consumption 15-min after injection with 2 mg/kg of naloxone in one hr tests. The magnitude of this decrease was not correlated with an index of naloxone's ability to produce a sickness, as measured by the conditioned taste aversion test. Tests with animals scheduled to drink water in a 15-min daily session showed naloxone had similar effects in reducing water intake in 23-hr and 47-hr water deprived rats. Morphine, when self-administered, produced an increase in water intake during 6-hr sessions. The data support the idea that naloxone disrupts a component of normal regulation of ingestion.}, } @article {pmid7393933, year = {1980}, author = {Cunningham, CL and Linakis, JG}, title = {Paradoxical aversive conditioning with ethanol.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {12}, number = {3}, pages = {337-341}, doi = {10.1016/0091-3057(80)90033-7}, pmid = {7393933}, issn = {0091-3057}, mesh = {Animals ; *Aversive Therapy ; Conditioning, Operant/*drug effects ; Drug Tolerance ; Ethanol/administration & dosage/*pharmacology ; Female ; Handling, Psychological ; Injections ; Lithium/pharmacology ; Rats ; Reinforcement, Psychology ; Saccharin/pharmacology ; Taste/drug effects ; Water Deprivation ; }, abstract = {In three experiments with hooded rats, paired injections of ethanol and lithium chloride produced an aversion to the taste of ethanol, yet reduced ethanol's potency as an unconditioned stimulus during subsequent taste aversion conditioning with saccharin (i.e., saccharin leads to ethanol). Two of the experiments were designed to test an associative "blocking" account of the latter finding. In each of these experiments, an attempt was made to extinguish the aversion conditioned to a potential blocking stimulus after ethanol-lithium pairings, but before saccharin-ethanol conditioning. Nonreinforced exposure to intraperitoneally mediated ethanol taste cues did not eliminate the detrimental effect of ethanol-lithium pairings on subsequent saccharin-ethanol conditioning (Experiment 2), whereas nonreinforced exposure to handling-injection cues did (Experiment 3), thus providing support for the associative blocking interpretation. Implications of these findings for chemical aversion therapy are discussed.}, } @article {pmid7381933, year = {1980}, author = {Marholin, D and Luiselli, JK and Robinson, M and Lott, IT}, title = {Response-contingent taste-aversion in treating chronic ruminative vomiting of institutionalised profoundly retarded children.}, journal = {Journal of mental deficiency research}, volume = {24}, number = {1}, pages = {47-56}, doi = {10.1111/j.1365-2788.1980.tb00056.x}, pmid = {7381933}, issn = {0022-264X}, mesh = {Adolescent ; *Avoidance Learning ; Behavior Therapy/methods ; Child ; Child, Institutionalized/psychology ; Chronic Disease ; *Education of Intellectually Disabled ; Humans ; Male ; *Taste ; Vomiting/psychology/*therapy ; }, abstract = {Two case studies are presented describing the use of response-contingent taste-aversion procedures to treat chronic ruminative vomiting of profoundly retarded children. Each treatment programme was designed to be carried out by para-professional staff in an institutional setting. Each programme eliminated rumination, with effects maintained one to nine months following treatment. For one subject who exhibited major weight-loss prior to intervention, substantial weight-gain was also demonstrated.}, } @article {pmid7375485, year = {1980}, author = {Boland, FJ and Stern, MH}, title = {Suppression by lithium of voluntary alcohol intake in the rat: mechanism of action.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {12}, number = {2}, pages = {239-248}, doi = {10.1016/0091-3057(80)90363-9}, pmid = {7375485}, issn = {0091-3057}, mesh = {Alcohol Drinking/*drug effects ; Animals ; Avoidance Learning/drug effects ; Choice Behavior ; Depression, Chemical ; Electric Stimulation ; Lithium/blood/*pharmacology ; Male ; Rats ; Time Factors ; }, abstract = {Subjects were 70 Wistar rats showing either low preference for aversive alcohol solutions or a high preference induced by hypothalamic stimulation. Experiments 1 and 2 showed that a large lithium chloride injection.(3 meq/kg) suppressed alcohol intake only if alcohol was tasted. Pairing lithium contiguously with water or intubed alcohol failed to reduce subsequent alcohol intake despite the concurrent presence of high serum lithium levels. In Experiments 3 and 4 a series of seven lithium injections increased rather than decreased alcohol intake if lithium was allowed to accumulate in the blood and brain during alcohol exposure while the transitory sickness associated with each injection was prevented from association with the taste of alcohol. When sickness was allowed to occur during alcohol exposure a suppression of intake resulted after two injections. Contrary to current interpretations these results suggest that the suppression of voluntary alcohol intake by acute and chronic lithium administration is due to a learned taste aversion rather than to a pharmacological mechanism specific to alcohol;}, } @article {pmid7372855, year = {1980}, author = {Lorden, JF and Callahan, M and Dawson, R}, title = {Depletion of central catecholamines alters amphetamine- and fenfluramine-induced taste aversions in the rat.}, journal = {Journal of comparative and physiological psychology}, volume = {94}, number = {1}, pages = {99-114}, doi = {10.1037/h0077650}, pmid = {7372855}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Desipramine/pharmacology ; Dextroamphetamine/*pharmacology ; Dopamine/*metabolism ; Drinking/drug effects ; Fenfluramine/*pharmacology ; Hydroxydopamines/pharmacology ; Injections, Intraventricular ; Male ; Norepinephrine/*metabolism ; Rats ; Substantia Nigra/drug effects/metabolism ; Taste/*drug effects/physiology ; Telencephalon/drug effects/*metabolism ; }, abstract = {Conditioned taste aversions induced by pairing the consumption of saccharin with an amphetamine injection are attenuated in rats with depletion of central catecholamines caused by intraventricular administration of 6-hydroxydopamine (6-OHDA). The hypothesis that dopamine (DA) depletion is responsible for this effect was tested. The reduction in conditioning caused by intraventricular 6-OHDA could not be duplicated either with injections of 6-OHDA into the substantia nigra (Experiment 1) or with intraventricular 6-OHDA injections in animals pretreated with desmethylimipramine (Experiment 2). Both treatments, however, produced large depletions of telencephalic DA. 6-Hydroxydopa infusions caused a preferential loss of telencephalic norepinephrine (NE) but also failed to alter taste aversion learning. It is concluded that the effect of intraventricular 6-OHDA on amphetamine-induced aversions was the result of depletion of both NE and DA. In a third experiment the generality of the effect was examined by pairing saccharin consumption with injections of the amphetamine congener fenfluramine. Depletion of both NE and DA failed to alter fenfluramine-induced aversions. Infusion of 6-OHDA into the substantia nigra, however, retarded the extinction of such an aversion. Evidence is discussed for a peripheral site of action for fenfluramine in the conditioned aversion paradigm.}, } @article {pmid7362586, year = {1980}, author = {Terk, MP and Green, L}, title = {Taste aversion learning in the bat, Carollia perspicillata.}, journal = {Behavioral and neural biology}, volume = {28}, number = {2}, pages = {236-242}, doi = {10.1016/s0163-1047(80)91631-3}, pmid = {7362586}, issn = {0163-1047}, mesh = {Animals ; *Avoidance Learning/drug effects ; Chiroptera ; Choice Behavior/drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects ; *Taste/drug effects ; }, } @article {pmid7362585, year = {1980}, author = {Shaw, N and Webster, DM}, title = {ECS and CO2 anesthesia between tasting and illness: effects on taste aversion learning.}, journal = {Behavioral and neural biology}, volume = {28}, number = {2}, pages = {231-235}, doi = {10.1016/s0163-1047(80)91615-5}, pmid = {7362585}, issn = {0163-1047}, mesh = {Anesthesia, Inhalation ; Animals ; Avoidance Learning/*drug effects ; Carbon Dioxide/*pharmacology ; Conditioning, Classical/drug effects ; *Electroshock ; Lithium/toxicity ; Male ; Mental Recall/drug effects ; Rats ; Taste/*drug effects ; }, } @article {pmid7188741, year = {1980}, author = {Elkins, RL}, title = {A reconsideration of the relevance of recent animal studies for development of treatment procedures for alcoholics.}, journal = {Drug and alcohol dependence}, volume = {5}, number = {2}, pages = {101-113}, doi = {10.1016/0376-8716(80)90186-6}, pmid = {7188741}, issn = {0376-8716}, mesh = {Alcoholism/*therapy ; Animals ; *Aversive Therapy ; Behavior Therapy/methods ; Behavior, Animal ; Electroshock ; Humans ; Male ; Models, Biological ; Nausea/chemically induced ; Rats ; Taste/drug effects ; Vomiting/chemically induced ; }, abstract = {Amit and Sutherland's conclusions concerning the use of conditioned taste aversions for alcoholism treatment are critically evaluated. Their conclusion that painful electric shock is contraindicated as a basis for alcohol taste aversions is consistent with the animal and human literature which depicts nausea as a more biologically appropriate US for taste aversion formation. However, Amit and Sutherland also conclude that alcoholics will not develop illness-induced alcohol aversions because animal studies show that aversion acquisition is disrupted by preconditioning familiarity with the conditioned stimulus (CS) - flavor - or unconditioned stimulus (US) - illness. This conclusion is untenable because Amit and Sutherland only considered animal conditioning methods that differed markedly from aversion therapy practices. Other animal studies modeled after aversion therapy procedures clearly show CS and US preexposure effects to be transitory phenomena. Moreover, experimental and clinical data show humans to be quite susceptible to taste aversion formation, and that many alcoholics do form strong alcohol aversions under appropriate conditioning parameters. Additional implications of the animal literature for effective aversion therapy are explored, and the paper concludes with a discussion of covert sensitization, a promising verbal aversion therapy which has resulted in the development of strong alcohol aversions in many volunteer subjects at the Augusta Veterans Administration Medical Center.}, } @article {pmid6246148, year = {1980}, author = {Smotherman, WP and Margolis, A and Levine, S}, title = {Flavor preexposures in a conditioned taste aversion situation: a dissociation of behavioral and endocrine effects in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {94}, number = {1}, pages = {25-35}, doi = {10.1037/h0077643}, pmid = {6246148}, issn = {0021-9940}, mesh = {Adrenocorticotropic Hormone/blood ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Corticosterone/*blood ; Drinking/drug effects ; Lithium/toxicity ; Male ; Pituitary-Adrenal System/physiology ; Rats ; Taste/*physiology ; }, abstract = {A series of experiments examined the effects of flavor preexposures on pituitary-adrenal/behavior relations in a conditioned taste aversion paradigm. It was found that reexposure to a novel milk solution paired earlier with lithium chloride (LiCl) elicited conditioned activation of the pituitary-adrenal system (Experiment 1). The unconditioned response to LiCl (measured by changes in plasma levels of corticosterone) did not vary as a function of prior (2 and 5 vs. 10) exposures to the milk solution (Experiment 2). Increased familiarity with the substance (resulting from 10 prior exposures) rendered the conditioning of a taste aversion to this substance less effective. Further, reexposure to this familiar substance after its pairing with LiCl was not accompanied by the characteristic conditioned pituitary-adrenal activation (Experiment 3). By titrating the number of conditioned stimulus (CS) preexposures (Experiment 4) it was found that within the range of preexposures manipulated (5-10), subjects exhibited (a) a coupling of behavioral and pituitary-adrenocortical responses when the conditioned taste aversion to the milk solution was paralleled by elevated plasma corticosterone (5-6 preexposures), (b) a coupling of these two response systems when flavor consumption was accompanied by suppressed plasma titers of corticoids (9-10 preexposures), or (c) a dissociation of the two system when the conditioned taste aversion was not accompanied by conditioned adrenocortical activity (7-8 preexposures). These data are discussed in terms of a dissociation in the effects of CS preexposures on conditioned adrenocortical and behavioral response systems.}, } @article {pmid7390706, year = {1980}, author = {Islam, S}, title = {Snake neurotoxins and conditioned taste aversion in mice.}, journal = {The International journal of neuroscience}, volume = {11}, number = {1}, pages = {41-43}, doi = {10.3109/00207458009147577}, pmid = {7390706}, issn = {0020-7454}, mesh = {Animals ; *Avoidance Learning ; *Bungarotoxins ; *Cobra Neurotoxin Proteins ; Conditioning, Classical ; *Cues ; *Elapid Venoms ; Mice ; *Taste ; }, } @article {pmid7353719, year = {1980}, author = {Franchina, JJ and Domato, GC and Patsiokas, AT and Griesemer, HA}, title = {Effects of number of pre-exposures on sucrose taste aversion in weanling rats.}, journal = {Developmental psychobiology}, volume = {13}, number = {1}, pages = {25-31}, doi = {10.1002/dev.420130105}, pmid = {7353719}, issn = {0012-1630}, mesh = {Animals ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Female ; *Food Preferences ; Lithium/poisoning ; Male ; Rats ; Sucrose/administration & dosage ; Taste/*physiology ; Weaning ; }, abstract = {Weanling rats, 20 days old, received 0, 1, 2, 4, or 8 pre-exposures to 12% sucrose prior to a single pairing of sucrose with an intraperitoneal injection of lithium chloride (LiCl; 3.0 mEq of a .15Msolution) or distilled water (20 mg/kg). Testing for sucrose taste aversion with a 2-bottle-choice procedure on 9 test trials reliably showed that increasing numbers of pre-exposures to sucrose directly attenuated taste aversion effects in the LiCl-injected groups but did not appreciably affect intake performance in the distilled water-injected groups. Comparisons between the injection conditions yielded reliable evidence for sucrose taste aversion at each pre-exposure level. These results show that flavor stimulus pre-exposures reliably attenuate subsequent taste aversion in weanling rats as had previously been reported for adult rats.}, } @article {pmid6771809, year = {1980}, author = {Golus, P and McGee, R}, title = {Metrazol produces conditioned taste aversion in rats.}, journal = {Psychopharmacology}, volume = {68}, number = {3}, pages = {257-259}, pmid = {6771809}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Drinking Behavior/drug effects ; Male ; Pentylenetetrazole/*pharmacology ; Rats ; Saccharin/pharmacology ; Taste/drug effects ; }, abstract = {Employing a two bottle drinking procedure where an animal's preference is measured between plain water and a novel fluid, it was found that the convulsant drug Metrazol produced a conditioned taste aversion to saccharin. This finding is contrary to that of previous reports and highlights the sensitivity of the two bottle method in detecting a taste aversion.}, } @article {pmid6448423, year = {1980}, author = {Islam, S}, title = {Conditioned taste aversion elicited in anaesthetized rats by scorpion venom.}, journal = {Physiologia Bohemoslovaca}, volume = {29}, number = {4}, pages = {361-366}, pmid = {6448423}, issn = {0369-9463}, mesh = {*Anesthesia ; Animals ; Avoidance Learning/*drug effects ; Female ; Lithium/pharmacology ; Male ; Rats ; Scorpion Venoms/*pharmacology ; *Taste ; Thiopental ; }, abstract = {Conditioned saccharin aversion was elicited in rats by the use of scorpion venom. After 15 min of saccharin drinking, groups of rats were injected with venom, Nembutal, LiCl or isotonic saline. Two groups were anaesthetized 10 min after saccharin drinking and injected with venom or with LiCl. During retention test saccharin aversion was observed in the venom and LiCl groups. It is concluded that anaesthesia does not prevent conditioned taste aversion engram formation.}, } @article {pmid6262738, year = {1980}, author = {Smotherman, WP and Levine, S}, title = {ACTH4--10 affects behavior but not plasma corticosterone levels in a conditioned taste aversion situation.}, journal = {Peptides}, volume = {1}, number = {3}, pages = {207-210}, doi = {10.1016/0196-9781(80)90055-8}, pmid = {6262738}, issn = {0196-9781}, support = {HD 02881/HD/NICHD NIH HHS/United States ; K5-MH19936/MH/NIMH NIH HHS/United States ; RR 07079/RR/NCRR NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/*pharmacology ; Animals ; Conditioning, Psychological/*drug effects ; Corticosterone/*blood ; Drinking Behavior/*drug effects ; Male ; Milk ; Peptide Fragments/*pharmacology ; Rats ; Taste ; Water ; }, abstract = {Rats injected with LiCl after they consumed a sweetened milk solution subsequently avoided the milk. ACTH4--10 injection prior to a retention test for the aversion augmented the behavioral measure of the aversion. Rats consuming milk paired earlier with LiCl showed elevated plasma levels of corticosterone. The augmented avoidance response in ACTH4--10 injected rats was not paralleled by an augmented pituitary-adrenal response.}, } @article {pmid11803680, year = {1977}, author = {Sjödén, PO and Archer, T}, title = {Conditioned taste aversion to saccharin induced by 2, 4, 5-trichlorophenoxyacetic acid in albino rats.}, journal = {Physiology & behavior}, volume = {19}, number = {1}, pages = {159-161}, doi = {10.1016/0031-9384(77)90174-3}, pmid = {11803680}, issn = {0031-9384}, mesh = {2,4,5-Trichlorophenoxyacetic Acid/*toxicity ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Food Preferences/drug effects ; Male ; Rats ; Rats, Wistar ; Retention, Psychology/drug effects ; Saccharin ; Taste/*drug effects ; }, abstract = {Four groups of Wistar rats were exposed either to saccharin + 2,4,5-T (taste-aversion group, T-A), saccharin + oil vehicle (taste-aversion control, T-A C), water + 2,4,5-T (enhanced neophobia, E-N), or water + oil (neophobia, N). Rats in the T-A group evidenced a marked aversion to saccharin in 3 consecutive preference tests, performed every third day, starting 3 days after exposure. The aversion was less pronounced, although statistically significant in 2 additional preference tests, performed respectively after a 9-day rest period of ad lib water drinking, and a 24 hr period of forced exposure to saccharin. An enhanced neophobia effect was found in the E-N group in the first preference test. Suggestions are made concerning the possible long-term effects on food preferences among wild-living animals as a result of large-scale application of 2,4,5-T-containing herbicides.}, } @article {pmid4445286, year = {1974}, author = {Carroll, ME and Smith, JC}, title = {Tme course of radiation-induced taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {13}, number = {6}, pages = {809-812}, doi = {10.1016/0031-9384(74)90266-2}, pmid = {4445286}, issn = {0031-9384}, mesh = {Animals ; *Avoidance Learning ; Cobalt Radioisotopes ; Conditioning, Classical ; *Cues ; Male ; *Radiation ; Rats ; Rats, Inbred Strains ; Reaction Time ; Saccharin ; *Taste ; Time Factors ; }, } @article {pmid4437733, year = {1974}, author = {Carey, RJ and Goodall, EB}, title = {A conditioned taste aversion induced by alpha-methyl-p-tyrosine.}, journal = {Neuropharmacology}, volume = {13}, number = {7}, pages = {595-600}, doi = {10.1016/0028-3908(74)90048-3}, pmid = {4437733}, issn = {0028-3908}, mesh = {Animals ; Behavior, Animal/drug effects ; Brain Chemistry/drug effects ; Conditioning, Psychological/*drug effects ; Drinking Behavior/drug effects ; Male ; Methyltyrosines/*pharmacology ; Norepinephrine/analysis ; Rats ; Saccharin ; Taste/*drug effects ; Telencephalon/analysis ; Time Factors ; }, } @article {pmid4847525, year = {1974}, author = {Hobbs, SH and Elkins, RL and Peacock, LJ}, title = {Taste-aversion conditioning in rats with septal lesions.}, journal = {Behavioral biology}, volume = {11}, number = {2}, pages = {239-245}, doi = {10.1016/s0091-6773(74)90417-9}, pmid = {4847525}, issn = {0091-6773}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Operant ; Drinking Behavior ; Food Preferences ; Male ; Radiation Effects ; Rats ; Septum Pellucidum/*physiology ; Taste/*radiation effects ; }, } @article {pmid4837904, year = {1974}, author = {Carey, RJ and Goodall, EB}, title = {Amphetamine-induced taste aversion: a comparison of d- versus l-amphetamine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {2}, number = {3}, pages = {325-330}, doi = {10.1016/0091-3057(74)90076-8}, pmid = {4837904}, issn = {0091-3057}, mesh = {Amphetamine/pharmacology ; Animals ; Behavior, Animal/*drug effects ; Dextroamphetamine/*pharmacology ; Dose-Response Relationship, Drug ; Feeding Behavior/drug effects ; Isomerism ; Male ; Rats ; Saccharin ; Taste/*drug effects ; Time Factors ; }, } @article {pmid4837424, year = {1974}, author = {Baum, M and Foidart, DS and Lapointe, A}, title = {Rapid extinction of a conditioned taste aversion following unreinforced intraperitoneal injection of the fluid CS.}, journal = {Physiology & behavior}, volume = {12}, number = {5}, pages = {871-873}, doi = {10.1016/0031-9384(74)90024-9}, pmid = {4837424}, issn = {0031-9384}, mesh = {Animals ; Association ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cyclamates/*administration & dosage/pharmacology ; *Drinking ; Electroshock ; Extinction, Psychological/*drug effects ; Female ; Injections, Intraperitoneal ; Lithium/poisoning ; Rats ; Reinforcement, Psychology ; Saccharin/*administration & dosage/pharmacology ; *Taste ; }, } @article {pmid4820144, year = {1974}, author = {Holt, J and Antin, J and Gibbs, J and Young, RC and Smith, GP}, title = {Cholecystokinin does not produce bait shyness in rats.}, journal = {Physiology & behavior}, volume = {12}, number = {3}, pages = {497-498}, doi = {10.1016/0031-9384(74)90127-9}, pmid = {4820144}, issn = {0031-9384}, mesh = {Animals ; Apomorphine/pharmacology ; Avoidance Learning/*drug effects ; Cholecystokinin/*pharmacology ; Eating/drug effects ; Inhibition, Psychological/drug effects ; Male ; Rats ; Saccharin ; Satiation/drug effects ; Taste/*drug effects ; Water Deprivation ; }, } @article {pmid4809974, year = {1974}, author = {Kalat, JW}, title = {Taste salience depends on novelty, not concentration, in taste-aversion learning in the rat.}, journal = {Journal of comparative and physiological psychology}, volume = {86}, number = {1}, pages = {47-50}, doi = {10.1037/h0035958}, pmid = {4809974}, issn = {0021-9940}, mesh = {Acetates ; Animals ; Association ; *Avoidance Learning ; *Drinking ; Female ; Lithium/poisoning ; Male ; Osmolar Concentration ; Rats ; Saccharin ; *Taste ; Water ; }, } @article {pmid4760830, year = {1973}, author = {Hutchison, SL}, title = {Taste aversion in albino rats using centrifugal spin as an unconditioned stimulus.}, journal = {Psychological reports}, volume = {33}, number = {2}, pages = {467-470}, doi = {10.2466/pr0.1973.33.2.467}, pmid = {4760830}, issn = {0033-2941}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; *Conditioning, Psychological ; Drinking ; Male ; Rats ; *Rotation ; *Taste ; }, } @article {pmid4743422, year = {1973}, author = {Wise, RA and Albin, J}, title = {Stimulation-induced eating disrupted by a conditioned taste aversion.}, journal = {Behavioral biology}, volume = {9}, number = {3}, pages = {289-297}, doi = {10.1016/s0091-6773(73)80179-8}, pmid = {4743422}, issn = {0091-6773}, mesh = {Animals ; *Avoidance Learning ; Chlorides ; Conditioning, Psychological ; *Eating ; Electric Stimulation ; Food Deprivation ; Hunger ; Hypothalamus/*physiology ; Inhibition, Psychological ; Lithium/poisoning ; Male ; Rats ; Reaction Time ; Satiation ; *Taste ; }, } @article {pmid4721216, year = {1973}, author = {Elkins, RL}, title = {Attenuation of drug-induced bait shyness to a palatable solution as an increasing function of its availability prior to conditioning.}, journal = {Behavioral biology}, volume = {9}, number = {2}, pages = {221-226}, doi = {10.1016/s0091-6773(73)80156-7}, pmid = {4721216}, issn = {0091-6773}, mesh = {Analysis of Variance ; Animals ; *Avoidance Learning/drug effects ; *Conditioning, Psychological ; Cyclophosphamide/administration & dosage/pharmacology ; Dose-Response Relationship, Drug ; Drinking ; Extinction, Psychological ; Injections, Intraperitoneal ; Isotonic Solutions ; Male ; Probability ; Rats ; Saccharin ; Sodium Chloride ; *Taste ; }, } @article {pmid4706590, year = {1973}, author = {Kalat, JW and Rozin, P}, title = {"Learned safety" as a mechanism in long-delay taste-aversion learning in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {83}, number = {2}, pages = {198-207}, doi = {10.1037/h0034424}, pmid = {4706590}, issn = {0021-9940}, mesh = {Animals ; *Avoidance Learning ; Caseins ; Chlorides ; *Conditioning, Classical ; Drinking Behavior ; Exploratory Behavior ; Female ; Lithium ; Memory ; Models, Psychological ; Osmolar Concentration ; Probability ; Rats ; Sodium Chloride ; Solutions ; Sucrose ; *Taste ; }, } @article {pmid4706584, year = {1973}, author = {Berger, BD and Wise, CD and Stein, L}, title = {Area postrema damage and bait shyness.}, journal = {Journal of comparative and physiological psychology}, volume = {82}, number = {3}, pages = {475-479}, doi = {10.1037/h0034112}, pmid = {4706584}, issn = {0021-9940}, mesh = {Amphetamine/pharmacology ; Animals ; *Avoidance Learning/drug effects ; Cerebral Ventricles/*physiology ; Drinking Behavior/drug effects ; Eating/drug effects ; *Feeding Behavior/drug effects ; Male ; Rats ; Scopolamine/pharmacology ; Taste ; Thalamus/physiology ; }, } @article {pmid4698108, year = {1973}, author = {Brozek, G and Buresová, O and Burĕs, J}, title = {EEG correlates of conditioned taste aversion.}, journal = {Activitas nervosa superior}, volume = {15}, number = {1}, pages = {4-5}, pmid = {4698108}, issn = {0001-7604}, mesh = {Animals ; Cerebral Cortex/physiology ; Cortical Spreading Depression ; Electroencephalography ; Hippocampus/physiology ; Rats ; Saccharin ; *Taste ; Taste Buds/*physiology ; Taste Disorders/physiopathology ; }, } @article {pmid4575306, year = {1973}, author = {Best, PJ and Orr, J}, title = {Effects of hippocampal lesions on passive avoidance and taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {10}, number = {2}, pages = {193-196}, doi = {10.1016/0031-9384(73)90296-5}, pmid = {4575306}, issn = {0031-9384}, mesh = {Animals ; Apomorphine ; *Avoidance Learning ; Conditioning, Classical ; Drinking Behavior ; Electroshock ; Food Deprivation ; Hippocampus/*physiology ; Male ; Rats ; Reaction Time ; Saccharin ; Stereotaxic Techniques ; *Taste ; }, } @article {pmid4781918, year = {1973}, author = {Buresová, O and Bures, J}, title = {Cortical and subcortical components of conditioned saccharin aversion in rats.}, journal = {Acta neurobiologiae experimentalis}, volume = {33}, number = {4}, pages = {689-698}, pmid = {4781918}, issn = {0065-1400}, mesh = {Animals ; *Avoidance Learning ; Cerebral Cortex/*physiology/physiopathology ; *Conditioning, Psychological ; Cortical Spreading Depression ; Functional Laterality ; Hippocampus/physiology ; Lithium/poisoning ; *Memory, Short-Term ; Rats ; Saccharin ; *Taste ; }, abstract = {Taste aversion was elicited in rats offered 0.1 percent saccharin (conditioned stimulus) for 10 min and then poisoned 30 min later by lithium-chloride (unconditioned stimulus - 0.14 M, 2 ml/100 g i.p.). Similar reduction of saccharin intake on the next day was obtained in rats learning the task with intact brain or under unilateral cortical spreading depression (CSD) and tested with CSD in the same or opposite hemicortex. No taste aversion developed in rats with bilateral CSD when forced swallowing of saccharin was followed after 5-30 min by LiCl injection. Bilateral CSD elicited 15 min after saccharin ingestion and maintained during the rest of the variable (30 min to 5 h) CS-US interval, decreased the saccharin aversion only with taste-illness delays exceeding 1 h. It is concluded that during the CS-US interval the taste information is stored both at the cortical and the subcortical levels. Normal cortical function is a necessary prerequisite for the formation of the nonlateralized subcortical engram which can be changed by association with the gastrointestinal distress into a permanent memory trace even under bilateral CSD.}, } @article {pmid4735325, year = {1973}, author = {Kral, PA and Beggerly, HD}, title = {Electroconvulsive shock impedes association formation: conditioned taste aversion paradigm.}, journal = {Physiology & behavior}, volume = {10}, number = {1}, pages = {145-147}, doi = {10.1016/0031-9384(73)90099-1}, pmid = {4735325}, issn = {0031-9384}, mesh = {Amnesia ; Animals ; *Association ; *Avoidance Learning ; Chlorides ; *Conditioning, Classical ; Drinking Behavior ; *Electroshock ; Humans ; Lithium ; Male ; Memory ; Rats ; Saccharin ; Seizures ; *Taste ; }, } @article {pmid4697024, year = {1973}, author = {Lehr, PP and Nachman, M}, title = {Lateralization of learned taste aversion by cortical spreading depression.}, journal = {Physiology & behavior}, volume = {10}, number = {1}, pages = {79-83}, doi = {10.1016/0031-9384(73)90090-5}, pmid = {4697024}, issn = {0031-9384}, mesh = {Animals ; *Avoidance Learning ; Cerebral Cortex/physiology ; Chlorides ; *Cortical Spreading Depression ; Drinking ; *Functional Laterality ; Lithium ; Male ; Rats ; *Taste ; }, } @article {pmid5071895, year = {1972}, author = {Domjan, M and Wilson, NE}, title = {Contribution of ingestive behaviors to taste-aversion learning in the rat.}, journal = {Journal of comparative and physiological psychology}, volume = {80}, number = {3}, pages = {403-412}, doi = {10.1037/h0032972}, pmid = {5071895}, issn = {0021-9940}, mesh = {*Animal Nutritional Physiological Phenomena ; Animals ; *Avoidance Learning ; Chlorides ; Conditioning, Psychological ; Cues ; Drinking Behavior ; Eating ; *Feeding Behavior ; Food Preferences ; Lithium ; Male ; Orientation ; Rats ; Saccharin ; *Taste ; }, } @article {pmid4654730, year = {1972}, author = {Cappell, H and Leblanc, AE and Endrenyi, L}, title = {Effects of chlordiazepoxide and ethanol on the extinction of a conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {9}, number = {2}, pages = {167-169}, doi = {10.1016/0031-9384(72)90230-2}, pmid = {4654730}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlordiazepoxide/*pharmacology ; Chlorides ; Conditioning, Psychological/*drug effects ; Drinking Behavior/drug effects ; Ethanol/*pharmacology ; Extinction, Psychological/*drug effects ; Lithium/pharmacology ; Male ; Rats ; Saccharin ; *Taste ; }, } @article {pmid5046233, year = {1972}, author = {Garcia, J and Hankins, WG and Robinson, JH and Vogt, JL}, title = {Bait shyness: tests of CS-US mediation.}, journal = {Physiology & behavior}, volume = {8}, number = {5}, pages = {807-810}, doi = {10.1016/0031-9384(72)90288-0}, pmid = {5046233}, issn = {0031-9384}, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; *Avoidance Learning ; Conditioning, Classical ; *Conditioning, Psychological ; Cyclophosphamide ; Digestion ; Eating ; Electroshock ; Feeding Behavior ; Inhibition, Psychological ; Male ; Poisoning ; Rats ; *Taste ; Time Factors ; }, } @article {pmid5025991, year = {1972}, author = {Gold, RM and Proulx, DM}, title = {Bait-shyness acquisition is impaired by VMH lesions that produce obesity.}, journal = {Journal of comparative and physiological psychology}, volume = {79}, number = {2}, pages = {201-209}, doi = {10.1037/h0032529}, pmid = {5025991}, issn = {0021-9940}, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; Apomorphine ; *Avoidance Learning ; Behavior, Animal ; Conditioning, Psychological ; Cues ; Disease Models, Animal ; Drinking Behavior ; Eating ; Extinction, Psychological ; *Feeding Behavior ; Female ; Hypothalamus/*physiology/physiopathology ; Injections, Intraperitoneal ; Obesity ; Rats ; Saccharin ; *Taste ; }, } @article {pmid5164370, year = {1971}, author = {Kral, PA}, title = {ECS between tasting and illness: effects of current parameters on a taste aversion.}, journal = {Physiology & behavior}, volume = {7}, number = {5}, pages = {779-782}, doi = {10.1016/0031-9384(71)90148-x}, pmid = {5164370}, issn = {0031-9384}, mesh = {Animals ; *Association ; *Avoidance Learning ; *Conditioning, Classical ; *Drinking ; *Electroshock ; Lithium/poisoning ; Male ; Rats ; Seizures ; *Taste ; Water ; }, } @article {pmid5158145, year = {1971}, author = {Prakash, I and Jain, AP}, title = {Bait shyness of two gerbils, Tatera indica Hardwicke and Meriones hurrianae Jerdon.}, journal = {The Annals of applied biology}, volume = {69}, number = {2}, pages = {169-172}, doi = {10.1111/j.1744-7348.1971.tb04669.x}, pmid = {5158145}, issn = {0003-4746}, mesh = {Animals ; *Behavior, Animal ; *Feeding Behavior ; Gerbillinae ; Phosphorus ; *Rodenticides ; Zinc ; }, } @article {pmid5120685, year = {1971}, author = {Kalat, JW and Rozin, P}, title = {Role of interference in taste-aversion learning.}, journal = {Journal of comparative and physiological psychology}, volume = {77}, number = {1}, pages = {53-58}, doi = {10.1037/h0031585}, pmid = {5120685}, issn = {0021-9940}, mesh = {Animals ; *Avoidance Learning ; Behavior, Animal ; Caseins ; Conditioning, Classical ; *Conditioning, Psychological ; *Drinking Behavior ; Exploratory Behavior ; Female ; Food Deprivation ; Poisoning ; Rats ; Sucrose ; *Taste ; Time Factors ; Water Deprivation ; }, } @article {pmid5112296, year = {1971}, author = {Best, PJ and Zuckerman, K}, title = {Subcortical mediation of learned taste aversion.}, journal = {Physiology & behavior}, volume = {7}, number = {3}, pages = {317-320}, doi = {10.1016/0031-9384(71)90308-8}, pmid = {5112296}, issn = {0031-9384}, mesh = {Animals ; Apomorphine/physiology ; *Avoidance Learning ; Conditioning, Classical ; *Conditioning, Operant ; Cortical Spreading Depression ; Gastrointestinal Diseases ; Male ; Rats ; Saccharin/physiology ; *Taste ; Transfer, Psychology ; Water Deprivation ; }, } @article {pmid13673106, year = {1959}, author = {WARREN, RP and PFAFFMANN, C}, title = {Early experience and taste aversion.}, journal = {Journal of comparative and physiological psychology}, volume = {52}, number = {3}, pages = {263-271}, doi = {10.1037/h0047655}, pmid = {13673106}, issn = {0021-9940}, mesh = {Humans ; *Taste ; }, } @article {pmid14900369, year = {1952}, author = {GAINES, TB and HAYES, WJ}, title = {Bait shyness to ANTU in wild Norway rats.}, journal = {Public health reports (Washington, D.C. : 1896)}, volume = {67}, number = {3}, pages = {306-311}, pmid = {14900369}, issn = {0094-6214}, mesh = {Rats ; *Shyness ; *Thiourea ; }, } @article {pmid1484873, year = {1992}, author = {Hulsey, MG and Martin, RJ}, title = {An anorectic agent from adipose tissue of overfed rats: effects on feeding behavior.}, journal = {Physiology & behavior}, volume = {52}, number = {6}, pages = {1141-1149}, doi = {10.1016/0031-9384(92)90473-f}, pmid = {1484873}, issn = {0031-9384}, mesh = {Adipose Tissue/*physiology ; Animals ; Appetite/*physiology ; Appetite Depressants/administration & dosage/*metabolism ; Avoidance Learning/physiology ; Body Weight/*physiology ; Brain/drug effects/physiology ; Conditioning, Classical/physiology ; Feeding Behavior/*physiology ; Female ; Hunger/physiology ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; Satiety Response/*physiology ; Taste/physiology ; Tissue Extracts/administration & dosage/*metabolism ; }, abstract = {Parabiosis and blood-transfer studies with rodents suggest the existence of humoral factors capable of affecting energy balance. The nature and origin of these factors is undetermined. Aqueous extracts of adipose tissue from overfed rats significantly reduce food intake when administered intraperitoneally (IP) or intracerebroventricularly (ICV). We term the agent(s) responsible for this effect adipose satiety factor (ASF). A single IP dose of ASF, equivalent to 44 mg crude protein, suppresses cumulative food intake for over 12 h. ASF, prepared using a combination of adipose tissue from obese Zucker rats and overfed rats, is more potent per unit of protein than ASF prepared exclusively using adipose tissue from overfed rats. A single ICV dose of this hybrid preparation, equivalent to 14.6 micrograms of crude protein, suppresses cumulative food intake by 40% for up to 48 h. By ultrafiltration, the molecular weight associated with maximal ASF activity is between 30 and 100 kilodaltons (kDa). The behavioral specificity of ASF-induced anorexia is demonstrated using meal pattern, taste aversion, and differential starvation paradigms.}, } @article {pmid1484808, year = {1992}, author = {Compton, DM and Weed, J}, title = {Effects of septal lesions on a higher-order conditioned taste aversion: a preliminary analysis.}, journal = {Perceptual and motor skills}, volume = {75}, number = {3 Pt 2}, pages = {1351-1357}, doi = {10.2466/pms.1992.75.3f.1351}, pmid = {1484808}, issn = {0031-5125}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*pathology ; *Conditioning, Psychological ; Male ; Rats ; Rats, Sprague-Dawley ; *Taste ; }, abstract = {Septal-lesioned rats (n = 7) and nonsurgical controls (n = 7) were exposed to a higher-order conditioned taste aversion procedure and the effects of septal lesions on the development of a higher-order conditioned taste aversion examined. In Phase 1, septal and control rats were permitted to consume a sodium chloride solution and illness was produced by an injection of cyclophosphamide. Following a recovery period, in Phase 2, both groups were allowed access to a saccharin solution followed by 1 ml of sodium chloride placed directly inside the mouth of the rat. Subsequent preference tests for the septal-lesion group, the control group, and a second unconditioned control group (n = 5) showed the former two groups learned the higher-order conditioned taste aversion, as demonstrated by a marked aversion to the saccharin solution, and the septal lesions attenuated the severity of the conditioning process.}, } @article {pmid1471766, year = {1992}, author = {Cunningham, CL and Niehus, JS and Bachtold, JF}, title = {Ambient temperature effects on taste aversion conditioned by ethanol: contribution of ethanol-induced hypothermia.}, journal = {Alcoholism, clinical and experimental research}, volume = {16}, number = {6}, pages = {1117-1124}, doi = {10.1111/j.1530-0277.1992.tb00707.x}, pmid = {1471766}, issn = {0145-6008}, support = {R01 AA007702/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Body Temperature Regulation/*drug effects ; Cold Temperature ; Conditioning, Classical/*drug effects ; Ethanol/pharmacokinetics/*pharmacology ; Hot Temperature ; Male ; Mental Recall/drug effects ; Rats ; Taste/*drug effects ; }, abstract = {Six experiments examined the effects of low (5-10 degrees C), normal (21 degrees C), or high (32 degrees) ambient temperature on conditioned taste aversion and body temperature changes produced by ethanol, lithium chloride, or morphine sulfate. Fluid-deprived rats received five to seven taste conditioning trials at 48-hr intervals. On each trial, access to saccharin at normal ambient temperature was followed by injection of drug or saline and placement for 6 hr into a temperature-controlled enclosure. Exposure to low ambient temperature facilitated, whereas exposure to high ambient temperature retarded acquisition of ethanol-induced conditioned taste aversion. The ability of an alteration in ambient temperature to influence conditioned taste aversion varied as a function of ethanol dose and was related to ambient temperature's effect on ethanol-induced hypothermia. More specifically, strength of conditioned taste aversion was negatively correlated with core body temperature after ethanol injection. Alterations in ambient temperature alone did not affect ingestion of a paired flavor solution in the absence of drug. Moreover, alterations in ambient temperature did not appear to influence conditioned taste aversion by changing ethanol pharmacokinetics. Finally, high and low ambient temperature did not affect development of taste aversion conditioned by lithium chloride or morphine sulfate. The overall pattern of data presented by these experiments supports the hypothesis that ambient-temperature influences strength of ethanol-induced conditioned taste aversion by altering the hypothermic response to ethanol. More generally, these data support the suggestion that body temperature change induced by ethanol is related to ethanol's aversive motivational effects and may be involved in modulating ethanol intake.}, } @article {pmid1337282, year = {1992}, author = {Yamamoto, T and Shimura, T and Sako, N and Azuma, S and Bai, WZ and Wakisaka, S}, title = {C-fos expression in the rat brain after intraperitoneal injection of lithium chloride.}, journal = {Neuroreport}, volume = {3}, number = {12}, pages = {1049-1052}, doi = {10.1097/00001756-199212000-00004}, pmid = {1337282}, issn = {0959-4965}, mesh = {Animals ; Biomarkers ; Brain/cytology ; Brain Chemistry/drug effects/*genetics ; Cerebral Ventricles/cytology/physiology ; Chlorides/*pharmacology ; Gene Expression/*drug effects ; Genes, fos/*drug effects ; Immunohistochemistry ; Injections, Intraperitoneal ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Medulla Oblongata/cytology/physiology ; Neurons/physiology ; Pons/cytology/physiology ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Wistar ; Vagotomy ; }, abstract = {The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl, which is commonly used to induce internal malaise in the conditioned taste aversion paradigm. C-fos-like immunoreactive neurones (c-fos neurones) were most densely observed in the central amygdaloid nucleus, external lateral subnucleus of the parabrachial nucleus (PBN), posteromedial and commissural parts of the nucleus of the tractus solitarius (NTS) and area postrema (AP). Experiments including vagotomy, intravenous injection of LiCl and lesions of the area postrema suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance. The activated NTS and AP neurones project mainly to the external lateral subnucleus of the PBN and lightly to the central lateral subnucleus of the PBN. These results are discussed in terms of the role of LiCl in the formation of conditioned taste aversion.}, } @article {pmid1335264, year = {1992}, author = {Gallo, M and Roldan, G and Bures, J}, title = {Differential involvement of gustatory insular cortex and amygdala in the acquisition and retrieval of conditioned taste aversion in rats.}, journal = {Behavioural brain research}, volume = {52}, number = {1}, pages = {91-97}, doi = {10.1016/s0166-4328(05)80328-6}, pmid = {1335264}, issn = {0166-4328}, mesh = {Amygdala/*physiology ; Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/*physiology ; Rats ; Rats, Wistar ; Retention, Psychology/physiology ; Taste/*physiology ; }, abstract = {Lesion studies of the role of the gustatory insular cortex (GC) and amygdala (Am) in conditioned taste aversion (CTA) are confounded by the irreversibility of the intervention. Functional ablation methods allow more specific influencing of different phases of CTA acquisition and retrieval. Bilateral tetrodotoxin (TTX) blockade of GC (10 ng) or Am (3 ng) before or after saccharin drinking in rats with chronically implanted intracerebral cannulae showed that GC is indispensable for the initial processing of the taste stimulus but not for the association of the gustatory trace with the symptoms of LiCl poisoning. Gustatory signals can by-pass the blocked Am, the inactivation of which, however, impairs the gustatory trace-poisoning association. TTX injection into both GC and Am impairs CTA retrieval more than isolated blockade of either of these structures. It is argued that GC and Am implement processing of gustatory and visceral signals, respectively, but that formation and consolidation of the CTA engram proceeds outside forebrain, probably at the level of the brainstem.}, } @article {pmid1456945, year = {1992}, author = {Skinner, DM and Martin, GM}, title = {Conditioned taste aversions support drug discrimination learning at low dosages of morphine.}, journal = {Behavioral and neural biology}, volume = {58}, number = {3}, pages = {236-241}, doi = {10.1016/0163-1047(92)90538-f}, pmid = {1456945}, issn = {0163-1047}, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cues ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Male ; Morphine/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology/drug effects ; Taste/*drug effects ; }, abstract = {The present experiment shows that a conditioned taste aversion procedure can support discrimination learning at dosages of morphine comparable to those required to produce motivational effects. Sprague-Dawley rats were injected with 4.0 mg/kg morphine sulfate prior to a saccharin-lithium chloride pairing, and physiological saline prior to a saccharin-saline pairing. The rats avoided the saccharin solution following the administration of morphine and consumed significantly more saccharin following saline administration after four discrimination cycles. After this initial discrimination the subjects were trained with progressively lower doses of morphine. Discrimination learning was apparent at doses of 2.0, 1.5, 1.0, 0.75 and 0.5 mg/kg. Animals initially trained with 1.0 mg/kg morphine also learned the discrimination but required 10 training cycles. After this initial discrimination the subjects were trained with progressively lower dosages of morphine and showed a discrimination at a dosage of 0.5 mg/kg.}, } @article {pmid1456944, year = {1992}, author = {Ackil, JK and Carman, HM and Bakner, L and Riccio, DC}, title = {Reinstatement of latent inhibition following a reminder treatment in a conditioned taste aversion paradigm.}, journal = {Behavioral and neural biology}, volume = {58}, number = {3}, pages = {232-235}, doi = {10.1016/0163-1047(92)90524-8}, pmid = {1456944}, issn = {0163-1047}, support = {NIMH 37535/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Cues ; Drinking ; *Inhibition, Psychological ; Male ; *Mental Recall ; Rats ; Rats, Sprague-Dawley ; Retention, Psychology ; *Taste ; }, abstract = {Reminder treatments have been shown to facilitate the retrieval of a variety of conditioned responses. Whether or not similar results would occur with an experimental paradigm which involves primarily memory for a stimulus, i.e., where no particular response is specified, is unclear. Accordingly, using Sprague-Dawley rats, we employed a latent inhibition paradigm with a long (10 days) retention interval between sucrose (CS) preexposure and sucrose-illness pairing (training). The results demonstrated a loss of latent inhibition following the 10-day retention interval suggesting "forgetting" of the CS preexposure. However, placing a single reminder exposure to the CS within the preexposure-to-training interval reinstated the preexposure effect. Controls indicated that in the absence of the initial preexposure the reminder per se did not produce latent inhibition. Thus, a reminder can reinstate a stimulus attribute (flavor representation) and explicit conditioned responses.}, } @article {pmid1333085, year = {1992}, author = {Smurthwaite, ST and Riley, AL}, title = {Diprenorphine as a stimulus in drug discrimination learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {43}, number = {3}, pages = {839-846}, doi = {10.1016/0091-3057(92)90416-d}, pmid = {1333085}, issn = {0091-3057}, mesh = {Animals ; Chlorides/pharmacology ; Conditioning, Psychological/drug effects ; Diprenorphine/*pharmacology ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Female ; Generalization, Psychological/drug effects ; Lithium/pharmacology ; Lithium Chloride ; Morphine/pharmacology ; Nalorphine/pharmacology ; Naloxone/pharmacology ; Naltrexone/pharmacology ; Pentobarbital/pharmacology ; Rats ; }, abstract = {Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate diprenorphine from distilled water. In subsequent generalization tests, the opiate antagonists naltrexone and naloxone and the mixed opiate agonist/antagonist nalorphine substituted for the diprenorphine stimulus in a dose-dependent manner, while the opiate agonist morphine and the nonopiate pentobarbital failed to substitute even at the highest doses tested. That a range of opiate antagonists substituted for the diprenorphine stimulus (and an opiate agonist and a nonopiate failed to substitute) suggest that diprenorphine's antagonist properties may mediate the discrimination, presumably by blocking endogenous opiate activity. The ability of these drugs to substitute for the diprenorphine stimulus may also be a function of this receptor activity. The differences in the specific generalization patterns reported in the present assessment and those of earlier reports were discussed.}, } @article {pmid1409932, year = {1992}, author = {de Beun, R and Jansen, E and Slangen, JL and Van de Poll, NE}, title = {Testosterone as appetitive and discriminative stimulus in rats: sex- and dose-dependent effects.}, journal = {Physiology & behavior}, volume = {52}, number = {4}, pages = {629-634}, doi = {10.1016/0031-9384(92)90389-j}, pmid = {1409932}, issn = {0031-9384}, mesh = {Animals ; Appetitive Behavior/*drug effects ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Choice Behavior/drug effects ; Conditioning, Classical/*drug effects ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Female ; Generalization, Psychological/drug effects ; Male ; Rats ; Rats, Wistar ; Sex Factors ; Social Environment ; Taste/*drug effects ; Testosterone/*pharmacology ; }, abstract = {Stimulus properties of subcutaneously injected testosterone were studied in male and female rats. In a conditioned place preference procedure, dose-dependent effects (doses: 0, 0.5, and 1 mg/kg) were observed in males. In females, no place preference could be established (doses: 0, 1, and 3 mg/kg). In addition, 1 mg/kg testosterone acquired discriminative stimulus control in male rats in a taste aversion procedure. Animals injected with this hormone prior to saccharin-LiCl pairings and with its vehicle prior to saccharin-NaCl pairings suppressed fluid intake following the administration of testosterone and not following the administration of the vehicle. Subsequent generalization tests revealed dose-dependent stimulus control of this hormone (range of substitution doses: 0.125-2 mg/kg). It is concluded from the results that at least pharmacological (supraphysiological) doses of testosterone may act as appetitive stimuli in male rats, but not in female rats. Furthermore, in male rats (pharmacological doses of) testosterone also possess discriminative stimulus properties.}, } @article {pmid1332525, year = {1992}, author = {Elkins, RL and Walters, PA and Orr, TE}, title = {Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats.}, journal = {Alcoholism, clinical and experimental research}, volume = {16}, number = {5}, pages = {928-934}, doi = {10.1111/j.1530-0277.1992.tb01895.x}, pmid = {1332525}, issn = {0145-6008}, support = {A06465//PHS HHS/United States ; }, mesh = {Alcohol Drinking/genetics ; Animals ; *Avoidance Learning/drug effects ; Body Temperature Regulation/drug effects/genetics ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Cyclophosphamide/toxicity ; Emetine/toxicity ; Ethanol/toxicity ; Lithium/toxicity ; Lithium Chloride ; *Phenotype ; Rats ; Rats, Sprague-Dawley ; *Selection, Genetic ; Taste/*genetics ; }, abstract = {This report updates the bidirectional selective breeding of taste aversion (TA) prone (TAP) and TA resistant (TAR) rat lines from the 8th through the 22nd generations. A palatable saccharin solution and the aversive consequences of a cyclophosphamide injection are the respective conditioned stimulus (CS) and unconditioned stimulus (US) of line development. Nonsibling matings within each of the two extremes of TA conditionability have produced TAP and TAR lines having markedly different TA propensities. As previously reported, the substitution of a rotational (i.e., motion sickness) US for cyclophosphamide during TA conditioning also produced characteristic line differences in conditioned taste aversion acquisition. The present report extends the effective line separating USs to include injections of lithium chloride, emetine hydrochloride, and EtOH. A range of EtOH dose levels produced dose-dependent TAs within TAP rats but failed to induce TAs in TAR rats. Following the conclusion of TA testing, the administration of a hypnotic EtOH dose produced equivalent loss of righting capability and equivalent hypothermia in both TAP and TAR rats. The line differences in EtOH induced TA conditionability therefore do not reflect general line differences in EtOH sensitivity. The lines may be useful within studies of biological bases of TA conditionability and animal analog studies of prevention and treatment of alcohol dependence.}, } @article {pmid1480520, year = {1992}, author = {Chance, WT and Balasubramaniam, A and Chen, X and Fischer, JE}, title = {Tests of adipsia and conditioned taste aversion following the intrahypothalamic injection of amylin.}, journal = {Peptides}, volume = {13}, number = {5}, pages = {961-964}, doi = {10.1016/0196-9781(92)90057-a}, pmid = {1480520}, issn = {0196-9781}, support = {CA 48057/CA/NCI NIH HHS/United States ; }, mesh = {Amyloid/administration & dosage/*pharmacology/physiology ; Animals ; Anorexia/chemically induced ; Calcitonin Gene-Related Peptide/administration & dosage/pharmacology ; Conditioning, Psychological/*drug effects/physiology ; Drinking/*drug effects/physiology ; Hypothalamus/drug effects/physiology ; Islet Amyloid Polypeptide ; Male ; Rats ; Rats, Sprague-Dawley ; Taste/*drug effects/physiology ; }, abstract = {Intrahypothalamic injection of amylin (AMY) was shown to reduce the intake of rat chow and water for 8 and 4 h, respectively, in schedule-fed rats. Amylin also reduced water intake to a much lesser degree in 24-h water-deprived rats. A test of the ability of AMY to form a conditioned taste aversion yielded no change in saccharin preference, as compared to controls treated with vehicle. These results suggest that although AMY has adipsic effects, the reduction in water is not of sufficient magnitude to cause the anorexia. In addition, the failure of AMY to support a conditioned taste aversion suggests that AMY does not cause anorexia by inducing malaise. Therefore, in addition to other metabolic effects, AMY may be involved in the control of food and water intake.}, } @article {pmid1393607, year = {1992}, author = {Kesner, RP and Berman, RF and Tardif, R}, title = {Place and taste aversion learning: role of basal forebrain, parietal cortex, and amygdala.}, journal = {Brain research bulletin}, volume = {29}, number = {3-4}, pages = {345-353}, doi = {10.1016/0361-9230(92)90066-7}, pmid = {1393607}, issn = {0361-9230}, support = {2RO1 NS20771-07AI/NS/NINDS NIH HHS/United States ; }, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Avoidance Learning/*drug effects ; Brain Chemistry ; Cerebral Cortex/anatomy & histology/*physiology ; Fear/physiology ; Learning/physiology ; Male ; Parietal Lobe/anatomy & histology/*physiology ; Prosencephalon/anatomy & histology/*physiology ; Rats ; Taste/*physiology ; }, abstract = {Animals with nucleus basalis magnocellularis (NBM), parietal cortex, dorsolateral frontal cortex, amygdala or control lesions were tested in a neophobia and taste aversion learning task. Only animals with basolateral amygdala lesions were impaired in taste aversion learning and in displaying neophobia to a novel flavor. This finding suggested a dissociation between the function of the NBM component of the basal forebrain cholinergic system and the amygdala. The same animals with NBM or control lesions were then tested for acquisition of a spatial navigation task using a dry-land version (cheese board) of the Morris water maze. Animals with NBM lesions were impaired in this task relative to control animals. Animals with parietal cortex lesions displayed a comparable deficit in the place navigation task. These findings suggest parallel functions for the NBM component of the basal forebrain system and the parietal cortex. The role of the NBM in mediating memory appears to be limited in that it does not play a role in all learning situations.}, } @article {pmid1333765, year = {1992}, author = {Rabin, BM and Hunt, WA}, title = {Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.}, journal = {Behavioral and neural biology}, volume = {58}, number = {2}, pages = {83-93}, doi = {10.1016/0163-1047(92)90291-b}, pmid = {1333765}, issn = {0163-1047}, mesh = {Amphetamine/pharmacology ; Analysis of Variance ; Animals ; Avoidance Learning/drug effects/*physiology/radiation effects ; Cats ; Chlorides/pharmacology ; Ferrets ; Lithium/pharmacology ; Lithium Chloride ; Male ; Radiation, Ionizing ; Rats ; Taste ; Vomiting/*psychology ; }, abstract = {The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.}, } @article {pmid1330594, year = {1992}, author = {Mele, PC and McDonough, JR and McLean, DB and O'Halloran, KP}, title = {Cisplatin-induced conditioned taste aversion: attenuation by dexamethasone but not zacopride or GR38032F.}, journal = {European journal of pharmacology}, volume = {218}, number = {2-3}, pages = {229-236}, doi = {10.1016/0014-2999(92)90173-2}, pmid = {1330594}, issn = {0014-2999}, mesh = {Analysis of Variance ; Animals ; Antiemetics/*therapeutic use ; Benzamides/*therapeutic use ; Bridged Bicyclo Compounds/*therapeutic use ; *Bridged Bicyclo Compounds, Heterocyclic ; Chlorides/antagonists & inhibitors ; Cisplatin/*antagonists & inhibitors ; Dexamethasone/therapeutic use ; Dose-Response Relationship, Drug ; Lithium/antagonists & inhibitors ; Lithium Chloride ; Male ; Ondansetron/*therapeutic use ; Rats ; Rats, Inbred Strains ; Serotonin Antagonists/*therapeutic use ; Taste Disorders/chemically induced/prevention & control ; }, abstract = {The 5-HT3 receptor antagonists zacopride and GR38032F are highly effective inhibitors of emesis induced by ionizing radiation and chemotherapeutic drugs such as cisplatin. The present study evaluated zacopride and GR38032F for efficacy in inhibiting the formation of the conditioned taste aversion (CTA) induced by cisplatin or lithium chloride in rats. The glucocorticoid dexamethasone, which has been reported to be effective against both the emetic and CTA-inducing effects of cisplatin, was included as a reference compound. When administered alone by i.p. injection, zacopride (0.1-10 mg/kg), GR38032F (10 mg/kg) and cisplatin (0.32-1.8 mg/kg) induced a CTA to an 0.1% saccharin solution; lower doses of each compound were ineffective. When administered as a pretreatment, neither zacopride (0.001-0.1 mg/kg) nor GR38032F (0.01-10 mg/kg) attenuated the CTA induced by cisplatin (0.32 and 0.56 mg/kg) or lithium chloride (10 mg/kg). In contrast, dexamethasone (0.32 and 1.0 mg/kg) attenuated the CTA induced by 0.32 but not 0.56 mg/kg of cisplatin. In an attempt to evaluate higher doses of zacopride against cisplatin without the potentially confounding factor that these doses by themselves induce a CTA, rats were injected with zacopride on three separate days prior to the aversion conditioning session. This pre-exposure treatment blocked the formation of the zacopride-induced CTA, but did not improve the efficacy of zacopride in attenuating the cisplatin-induced CTA. These results suggest that neither the cisplatin- nor the lithium-induced CTA in rats are due to effects that are sensitive to 5-HT3 receptor blockade.}, } @article {pmid1357674, year = {1992}, author = {Van Hest, A and Hijzen, TH and Slangen, JL and Olivier, B}, title = {Assessment of the stimulus properties of anxiolytic drugs by means of the conditioned taste aversion procedure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {42}, number = {3}, pages = {487-495}, doi = {10.1016/0091-3057(92)90144-5}, pmid = {1357674}, issn = {0091-3057}, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Anti-Anxiety Agents/*pharmacology ; Avoidance Learning/*drug effects ; Chlordiazepoxide/pharmacology ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Generalization, Psychological/drug effects ; Lithium/pharmacology ; Male ; Rats ; Rats, Wistar ; Serotonin/pharmacology ; Taste/*drug effects ; }, abstract = {The conditioned taste aversion (CTA) procedure has recently been described as a more rapid alternative to two-lever operant procedures in drug discrimination research. We trained different groups of rats to discriminate the benzodiazepine chlordiazepoxide (CDP, 20 mg/kg) or the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.4 mg/kg) from saline by means of the CTA procedure. The results were in agreement with findings from two-lever operant drug discrimination procedures. However, discrimination training took 40 sessions in the case of CDP and 72 sessions for 8-OH-DPAT, which is comparable to results obtained with two-lever operant procedures. Dose-response curves were determined and generalization tests were performed for different benzodiazepine and nonbenzodiazepine anxiolytics. Baseline behavior deteriorated in the course of generalization and substitution testing, thus preventing further generalization testing. Our experience is that the use of the CTA procedure in drug discrimination research does not have sufficient advantages over traditionally used procedures to replace the latter.}, } @article {pmid1326774, year = {1992}, author = {Kay, E and Nyby, J}, title = {LiCl aversive conditioning has transitory effects on pheromonal responsiveness in male house mice (Mus domesticus).}, journal = {Physiology & behavior}, volume = {52}, number = {1}, pages = {105-113}, doi = {10.1016/0031-9384(92)90439-9}, pmid = {1326774}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects ; Chlorides/*pharmacology ; Conditioning, Operant/*drug effects ; Copulation/drug effects ; Female ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Mice ; Mice, Inbred AKR ; Mice, Inbred C57BL ; Pentanols/pharmacology ; Pheromones/*pharmacology ; Saccharin/pharmacology ; Sexual Behavior, Animal/*drug effects ; Smell/drug effects ; Taste/drug effects ; Vocalization, Animal/drug effects ; }, abstract = {Appetitive and aversive experiences influence whether odors elicit precopulatory behavior from male rodents. A role for aversive experience in odor-elicited reproductive behaviors had been demonstrated for hamsters and rats, but similar work on house mice had not been performed. Four experiments examined whether lithium chloride (LiCl) aversive conditioning would alter two precopulatory behaviors (ultrasonic vocalizations and olfactory preference) that male house mice normally exhibit to female urine. Lithium chloride was used to aversively condition male house mice to either female urine odor, female urine in drinking water, the female herself, or a novel odor. Independent tests of taste aversion establishment were also conducted. In these experiments, LiCl aversive conditioning produced robust taste aversions to water adulterated with either female urine or a novel odorant/tastant (isoamylacetate), but only transitory decrements in odor-elicited, male-typical precopulatory behaviors. We conclude that aversive conditioning is unlikely to be a significant factor affecting male mouse precopulatory behavior.}, } @article {pmid1641431, year = {1992}, author = {Nicolaus, LK and Crowe, M and Lundquist, R}, title = {Oral estrogen retains potency as an aversion agent in eggs: implications to studies of community ecology and wildlife management.}, journal = {Physiology & behavior}, volume = {51}, number = {6}, pages = {1281-1284}, doi = {10.1016/0031-9384(92)90322-s}, pmid = {1641431}, issn = {0031-9384}, mesh = {Animals ; Animals, Wild ; Ecology ; Egg Yolk/chemistry ; Eggs/*analysis ; Ethinyl Estradiol/analysis/*pharmacology ; Feeding Behavior/*drug effects ; Female ; Ovalbumin/analysis ; Predatory Behavior/*drug effects ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; }, abstract = {The first of two experiments with laboratory rats demonstrated that oral estrogen (17 alpha-ethinylestradiol) can remain in the albumen of eggs at room temperature for up to 8 days with undiminished capacity to produce conditioned taste aversion. The second experiment showed that estrogen remains potent in the yolk of eggs for at least 4 days. There is now greater assurance that egg prey placed into the field will induce reliable CTA among mammalian predators. Community ecologists interested in such processes as competitive release and the responses of prey populations to reduced predation upon their eggs can selectively factor predation out of field experiments without the need for physically excluding predators. Wildlife biologists interested in reducing predation upon the eggs of endangered species now have greater assurance that estrogen-treated egg baits will suppress predation in a more cost-effective manner and with less likelihood of discrimination between treated eggs and those of endangered species.}, } @article {pmid1641424, year = {1992}, author = {McGregor, IS}, title = {Determinants of the slow acquisition of medical and sulcal prefrontal cortex self-stimulation: an individual differences approach.}, journal = {Physiology & behavior}, volume = {51}, number = {6}, pages = {1219-1225}, doi = {10.1016/0031-9384(92)90312-p}, pmid = {1641424}, issn = {0031-9384}, mesh = {Animals ; Conditioning, Operant/*physiology ; Defecation/physiology ; Electrodes ; Frontal Lobe/anatomy & histology/*physiology ; *Individuality ; Male ; Motor Activity/physiology ; Rats ; Rats, Inbred Strains ; Seizures/physiopathology ; Self Stimulation/*physiology ; Taste/physiology ; }, abstract = {Stimulation-naive rats were tested for motor activity during noncontingent electrical stimulation of the medial prefrontal cortex (MPC) or sulcal prefrontal cortex (SPC). Defecation during stimulation was also measured. The rats were then tested using a conditioned taste aversion paradigm for aversion to a novel flavor (0.1% saccharin) paired with stimulation. Finally, the rats were trained to acquire self-stimulation over 26 days of training. Large individual differences were seen in motor activity, defecation, and conditioned taste aversion to initial stimulation and in the subsequent speed of self-stimulation acquisition. In the MPC-stimulated group, acquisition speed was positively correlated with motor activity to initial stimulation and negatively correlated with defecation to this stimulation. In the SPC-stimulated group, the same correlations were evident, but only when rats suffering seizures prior to self-stimulation acquisition were excluded from the analysis. Such preacquisition seizures, which were only found in the SPC-stimulated group, retarded self-stimulation acquisition. In most rats, MPC or SPC stimulation failed to condition a taste aversion to saccharin. These results suggest that the slow acquisition of MPC and SPC self-stimulation may be partly related to the motor suppressive, aversive, and convulsive properties of initial stimulation.}, } @article {pmid1322542, year = {1992}, author = {Bourne, MJ and Calton, JL and Gustavson, KK and Schachtman, TR}, title = {Effects of acute swim stress on LiCl-induced conditioned taste aversions.}, journal = {Physiology & behavior}, volume = {51}, number = {6}, pages = {1227-1234}, doi = {10.1016/0031-9384(92)90313-q}, pmid = {1322542}, issn = {0031-9384}, mesh = {Animals ; Chlorides/*pharmacology ; Conditioning, Operant/*drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Stress, Psychological/*psychology ; Swimming ; Taste/*drug effects ; }, abstract = {The present study examined the effects of a 5-min period of swim stress experienced between a flavor (saccharin) and illness (LiCl) on conditioned taste aversion learning. Experiment 1 obtained a stress-induced attenuation of learning. Experiment 2 replicated the findings of Experiment 1, and also obtained a similar attenuation when stress was administered 30 min prior to the saccharin presentation. Experiment 3 examined the effects of swim stress either 15 min or 90 min after the LiCl had been administered. It was found that swim stress 15 min after LiCl significantly attenuated CTA, but swim stress 90 min after LiCl did not. These results are discussed with regard to current views of the relationship between external events and conditioned taste aversions.}, } @article {pmid1511848, year = {1992}, author = {Ebenezer, IS and Houston, AJ and Crook, TJ}, title = {Systemic administration of baclofen inhibits water intake in rats.}, journal = {General pharmacology}, volume = {23}, number = {3}, pages = {375-379}, doi = {10.1016/0306-3623(92)90097-4}, pmid = {1511848}, issn = {0306-3623}, mesh = {Animals ; Avoidance Learning/drug effects ; Baclofen/*pharmacology ; Depression, Chemical ; Drinking/*drug effects ; Male ; Rats ; Rats, Inbred Strains ; Saline Solution, Hypertonic/pharmacology ; Taste/drug effects ; Water Deprivation/physiology ; }, abstract = {1. The present experiments were carried out to investigate the effects of systemic administration of baclofen on water intake in rats. 2. Baclofen (1, 2 and 4 mg/kg, s.c.) inhibited water intake in 16 hr water-deprived rats in a dose-related manner, with maximal effects occurring during the first 30 min after administration. 3. Baclofen (0.25 and 2 mg/kg, s.c.) had no effects on water intake in non-deprived rats. 4. Baclofen (2 mg/kg) inhibited water intake elicited by i.p. injection of hypertonic NaCl in rats. 5. Baclofen (1 mg/kg) did not produce taste aversion in a taste aversion experiment. This indicates that the effects of baclofen on water intake is not due to an aversive effect of the drug.}, } @article {pmid1594683, year = {1992}, author = {Brot, MD and Bernstein, IL and Dorsa, DM}, title = {Vasopressin deficiency abolishes a sexually dimorphic behavior in Brattleboro rats.}, journal = {Physiology & behavior}, volume = {51}, number = {4}, pages = {839-843}, doi = {10.1016/0031-9384(92)90124-k}, pmid = {1594683}, issn = {0031-9384}, support = {NS 20311/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Arousal/*physiology ; Avoidance Learning/physiology ; Brain Mapping ; Conditioning, Classical/physiology ; Extinction, Psychological/physiology ; Female ; Hypothalamus/physiology ; Limbic System/physiology ; Male ; Rats ; Rats, Brattleboro ; *Sex Characteristics ; Taste/physiology ; Vasopressins/*physiology ; }, abstract = {The role of vasopressin (VP) in a sexually dimorphic behavior, the extinction of a conditioned taste aversion, was investigated in male and female rats of three different genotypes. This behavior was examined with a two bottle test in the wild-type Long-Evans (LE) rats, and then in partially VP deficient heterozygous (HET-BB) and completely VP deficient homozygous (HO-BB) Brattleboro rats. In Experiment 1, non-deprived male and female LE rats were given aversions to a sucrose solution by pairing it with a LiCl injection. The rate of extinction of the aversion upon reexposure to ad lib sucrose solution was examined and observed to be sexually dimorphic. Female LE rats extinguished at a significantly more rapid rate than males. Experiment 2 compared HET-BB and HO-BB male and female rats using the same paradigm. Neither of these VP-deficient groups showed sexual dimorphism of the extinction behavior. The data suggest that intact VP levels are necessary to observe the expression of this sexually dimorphic behavior.}, } @article {pmid1317183, year = {1992}, author = {Hatfield, T and Graham, PW and Gallagher, M}, title = {Taste-potentiated odor aversion learning: role of the amygdaloid basolateral complex and central nucleus.}, journal = {Behavioral neuroscience}, volume = {106}, number = {2}, pages = {286-293}, doi = {10.1037//0735-7044.106.2.286}, pmid = {1317183}, issn = {0735-7044}, support = {K02-MH00406/MH/NIMH NIH HHS/United States ; MH35554/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Drinking/physiology ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/physiology ; Neurons/physiology ; Rats ; Smell/*physiology ; Taste/*physiology ; }, abstract = {The present study examined the relative contributions of the amygdaloid basolateral complex (ABL) and central nucleus (CN) to taste-potentiated odor aversion (TPOA) learning--an associative learning task that is dependent on information processing in two sensory modalities. In Experiment 1, rats with neurotoxic lesions of these systems were trained on the TPOA task by presenting a compound taste-odor conditioned stimulus, which was followed by LiCl administration. Results showed that ABL damage caused an impairment in potentiated odor aversion learning but no deficit in the conditioned taste aversion. In contrast, rats with CN damage learned both tasks. Experiment 2 examined the effects of ABL damage on TPOA and odor discrimination learning. The odor discrimination procedure used a place preference task to demonstrate normal processing of olfactory information. Results indicated that although ABL-lesioned animals were impaired on TPOA, there was no deficit in odor discrimination learning.}, } @article {pmid1324085, year = {1992}, author = {Bernstein, IL and Chavez, M and Allen, D and Taylor, EM}, title = {Area postrema mediation of physiological and behavioral effects of lithium chloride in the rat.}, journal = {Brain research}, volume = {575}, number = {1}, pages = {132-137}, doi = {10.1016/0006-8993(92)90432-9}, pmid = {1324085}, issn = {0006-8993}, support = {CA26419/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/*drug effects ; Body Temperature/drug effects ; Brain Stem/drug effects/pathology/*physiology ; Chlorides/*pharmacology ; Conditioning, Classical/*drug effects ; Gastric Emptying/drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; }, abstract = {The area postrema (AP), a chemoreceptor trigger zone for nausea and vomiting, has been implicated in taste aversion conditioning with LiCl. In addition to taste aversion acquisition, the present studies indicate that a number of other responses to LiCl administration are eliminated by lesions of the AP. These include a behavioral response, 'lying-on-belly' as well as two physiological responses, delayed stomach emptying and hypothermia. These findings suggest that the area postrema is critically involved in the detection of LiCl and in a wide range of responses to this toxin. They also provide strong evidence that the failure to acquire conditioned taste aversions to LiCl-paired flavors after AP lesions can be attributed to the absence of a significant 'illness' response in lesioned animals.}, } @article {pmid1599629, year = {1992}, author = {Gauvin, DV and Holloway, FA}, title = {Ethanol tolerance developed during intoxicated operant performance in rats prevents subsequent ethanol-induced conditioned taste aversion.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {9}, number = {2}, pages = {167-170}, doi = {10.1016/0741-8329(92)90029-a}, pmid = {1599629}, issn = {0741-8329}, support = {R01 AA06351/AA/NIAAA NIH HHS/United States ; R01-AA8338-02/AA/NIAAA NIH HHS/United States ; T32-AA07222-13/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholic Intoxication/*physiopathology ; Animals ; Behavior, Animal/*drug effects/physiology ; *Conditioning, Psychological ; Drinking/drug effects ; Drug Tolerance ; Ethanol/administration & dosage/*pharmacology ; Learning ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; *Taste ; }, abstract = {Four groups of Sprague-Dawley rats (n = 10 per group) were trained in a two-phase conditioning experiment. All rats were initially trained in an FR30 operant task (phase 1), and subsequently trained in a conditioned taste aversion (CTA) task. The groups of rats differed in their ETOH exposure. All rats received 2-week chronic exposure in phase 1. Two groups received chronic presession ETOH and, therefore, the opportunity for intoxicated practice; another group, yoked to this latter group, received postsession ETOH; the final group received presession saline injections. The presession ETOH groups were conditioned in the CTA task with either ETOH or saline; both increased their intakes of the conditioned tastant. The presession saline and the postsession ETOH groups received ETOH CTA; both developed a robust CTA. Thus, prior history of intoxicated practice under the operant task prevented the development of ETOH-induced CTA. We argue that ETOH exposure may be a necessary but not sufficient condition for tolerance to develop to the aversive attributes of ETOH.}, } @article {pmid1586352, year = {1992}, author = {Taube, JS and Kesslak, JP and Cotman, CW}, title = {Lesions of the rat postsubiculum impair performance on spatial tasks.}, journal = {Behavioral and neural biology}, volume = {57}, number = {2}, pages = {131-143}, doi = {10.1016/0163-1047(92)90629-i}, pmid = {1586352}, issn = {0163-1047}, support = {AG00096/AG/NIA NIH HHS/United States ; AG07918/AG/NIA NIH HHS/United States ; MH19691/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Brain Mapping ; Cerebral Cortex/*physiology ; Conditioning, Classical/physiology ; Discrimination Learning/physiology ; Escape Reaction/physiology ; Fear/physiology ; Hippocampus/*physiology ; Male ; Mental Recall/*physiology ; Motor Activity/physiology ; Neural Pathways/physiology ; Neurons/physiology ; Orientation/*physiology ; Rats ; Retention, Psychology/*physiology ; *Social Environment ; Taste/physiology ; }, abstract = {Previous studies have identified a population of neurons in the postsubiculum that discharge as a function of the rat's head direction in the horizontal plane (Taube, Muller, & Ranck, 1990a). To assess the contribution of these cells in spatial learning, Long-Evans rats were tested in a variety of spatial and nonspatial tasks following bilateral electrolytic or neurotoxic lesions of the postsubiculum. Compared to unlesioned control animals, lesioned animals were impaired on two spatial tasks, a radial eight-arm maze task and a Morris water task, although the performance scores of both lesion groups improved over the course of behavioral testing. In contrast, lesioned animals were unimpaired on two nonspatial tasks, a cued version of the water maze task and a conditioned taste-aversion paradigm. In addition, lesioned animals showed transient hyperactivity in an open-field activity test. These results support the concept that neurons in the postsubiculum are part of a neural network involved in the processing of spatial information.}, } @article {pmid1586350, year = {1992}, author = {Tassoni, G and Bucherelli, C and Bures, J}, title = {Postacquisition injection of tetrodotoxin into the parabrachial nuclei elicits partial disruption of passive avoidance reaction in rats.}, journal = {Behavioral and neural biology}, volume = {57}, number = {2}, pages = {116-123}, doi = {10.1016/0163-1047(92)90605-4}, pmid = {1586350}, issn = {0163-1047}, mesh = {Amygdala/*drug effects ; Animals ; Avoidance Learning/*drug effects ; Brain Mapping ; Cerebral Cortex/*drug effects ; Conditioning, Classical/*drug effects ; Dominance, Cerebral/drug effects ; Electroshock ; Fear/*drug effects ; Male ; Mental Recall/*drug effects ; Neural Pathways/drug effects ; Rats ; Retention, Psychology/*drug effects ; Reticular Formation/drug effects ; Tetrodotoxin/*pharmacology ; }, abstract = {The recent discovery that post-trial functional blockade of the parabrachial nuclei by intracerebral injection of 10 ng tetrodotoxin (TTX) disrupts acquisition of conditioned taste aversion (CTA) (Ivanova & Bures, 1990a,b) has prompted attempts to ascertain the role of this structure in other types of inhibitory learning. In Experiment 1, rats with implanted parabrachial cannulae were trained in a step-through avoidance task and received bilateral TTX (2 x 10 ng) immediately after the acquisition trial; they displayed significantly weakened avoidance of the shock compartment 2 days later. In Experiment 2, rats were anesthetized with pentobarbital (50 mg/kg) immediately after passive avoidance acquisition and received parabrachial TTX 15 min later; whereas anesthesia alone left the passive avoidance reaction (PAR) unaffected, TTX elicited similar disruption as in unanesthetized animals. In Experiment 3, TTX was injected in anesthetized animals 0, 1, 2, or 4 days after PAR acquisition. The amnesic effect was significant when the acquisition-TTX delay had been prolonged to 24 but not to 48 or 96 h. Since CTA is disrupted by reversible blockade of parabrachial nuclei and of the adjacent reticular formation elicited up to 4 days after acquisition (Ivanova & Bures, 1990b), PAR seems to be impaired to a lesser degree and for a shorter time than CTA by similar TTX treatment.}, } @article {pmid1584835, year = {1992}, author = {Parker, LA and Rennie, M}, title = {Naltrexone-induced aversions: assessment by place conditioning, taste reactivity, and taste avoidance paradigms.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {41}, number = {3}, pages = {559-565}, doi = {10.1016/0091-3057(92)90373-n}, pmid = {1584835}, issn = {0091-3057}, support = {6559//PHS HHS/United States ; }, mesh = {Animals ; Aversive Therapy ; Avoidance Learning/*drug effects/physiology ; Conditioning, Psychological/*drug effects/physiology ; Dose-Response Relationship, Drug ; Male ; Naltrexone/administration & dosage/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {The reinforcing/aversive properties of various doses of naltrexone (0.01, 1, and 10 mg/kg) were assessed in three experiments that employed place conditioning, taste reactivity, and taste avoidance paradigms. Naltrexone produced a place aversion and a taste aversion, but did not produce aversive taste reactivity responses, even at the highest dose (10 mg/kg) tested. This suggests that drugs that produce a place aversion do not necessarily produce a conditional dislike for a flavored solution with which they are paired.}, } @article {pmid1733129, year = {1992}, author = {Pappas, TN}, title = {Physiological satiety implications of gastrointestinal antiobesity surgery.}, journal = {The American journal of clinical nutrition}, volume = {55}, number = {2 Suppl}, pages = {571S-572S}, doi = {10.1093/ajcn/55.2.571s}, pmid = {1733129}, issn = {0002-9165}, support = {R29 DK40790-03/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Obesity, Morbid/physiopathology/psychology/*surgery ; Satiety Response/*physiology ; }, abstract = {This manuscript reviews the known satiety signals and the impact of antiobesity surgery on these physiological satiety mechanisms. Satiety signals originate from the stomach and small bowel to stop eating behavior. Stomach signals (gastric distension) produce early satiety by releasing hypothalamic cholecystokinin (CCK). The intermeal interval is probably mediated by peripheral CCK released by a threshold level of intraluminal calories. Anti-obesity operations probably rely little on these physiological satiety signals. Gastric balloons and gastroplasty produce nonphysiological gastric distension whereas intestinal bypass causes malabsorption. Gastric bypass combines supramaximal gastric distension with taste aversion from dumping. Future physiological manipulation of the satiety cascade will lead to improve obesity intervention.}, } @article {pmid1596751, year = {1992}, author = {Peeters, BW and Smets, RJ and Broekkamp, CL}, title = {Sex steroids possess distinct stimulus properties in female and male mice.}, journal = {Brain research bulletin}, volume = {28}, number = {2}, pages = {319-321}, doi = {10.1016/0361-9230(92)90195-4}, pmid = {1596751}, issn = {0361-9230}, mesh = {Analysis of Variance ; Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Estradiol/*pharmacology ; Female ; Male ; Mice ; Mice, Inbred ICR ; Progesterone/*pharmacology ; Sex Characteristics ; Taste ; Testosterone/*pharmacology ; }, abstract = {Very few studies have investigated the aversive properties of sex steroids in animals. We studied these properties by testing oestradiol-3-benzoate, testosterone-propionate and progesterone in a conditioned taste aversion set-up, in intact female and male mice. Oestradiol-3-benzoate induced a taste aversion in both female and male mice; however, testosterone-propionate and progesterone had an effect only in females. These results show that sex steroids have intrinsic aversive properties. The different effects of the steroids in males and females cannot simply be explained by nausea induction or novelty.}, } @article {pmid1574537, year = {1992}, author = {June, HL and June, PL and Domangue, KR and Hicks, LH and Lummis, GH and Lewis, MJ}, title = {Failure of Ro15-4513 to alter an ethanol-induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {41}, number = {2}, pages = {455-460}, doi = {10.1016/0091-3057(92)90126-z}, pmid = {1574537}, issn = {0091-3057}, support = {AA06263/AA/NIAAA NIH HHS/United States ; RR08016/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Azides/*pharmacology ; Benzodiazepines/*pharmacology ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Taste/*drug effects ; }, abstract = {The ability of Ro15-4513, an imidazobenzodiazepine inverse benzodiazepine agonist, to attenuate/block the acquisition of an ethanol (ETOH)-induced conditioned taste aversion (CTA) was investigated in two experiments. Experiment 1 examined the effects of Ro15-4513 (3 mg/kg) on rats' consumption of a novel saccharin solution under a traditional CTA paradigm. Experiment 2 examined the effects of Ro15-4513 (3 mg/kg) on rats' consumption of a novel saccharin solution under a preexposure CTA paradigm. Under the preexposure paradigm, rats were given Ro15-4513 immediately before each of five daily consecutive preexposure treatments prior to the initial conditioning day. To obtain maximal preexposure and unconditioned stimulus effects, a 2-g/kg dose of ETOH (20% v/v) was used in the present study. As previously reported, animals given ETOH following 20-min access to a novel saccharin solution established moderate to strong aversions, with the degree of aversion being directly related to the number of conditioning days. Experiment 1 showed that Ro15-4513 failed to alter the CTA induced by ETOH. Experiment 2 further showed that Ro15-4513 failed to block the preexposure effect exerted on the ETOH-mediated CTA. The results confirm previous reports regarding the failure of Ro15-4513 to disrupt an ETOH-induced CTA. These data are in agreement with a number of behavioral studies demonstrating the failure of Ro15-4513 to antagonize certain actions of ETOH. Moreover, the present study along with a previous report suggests that ETOH-induced CTA's do not appear to be mediated via actions at the GABA-BDZ receptor complex.}, } @article {pmid1313242, year = {1992}, author = {Spector, AC and Norgren, R and Grill, HJ}, title = {Parabrachial gustatory lesions impair taste aversion learning in rats.}, journal = {Behavioral neuroscience}, volume = {106}, number = {1}, pages = {147-161}, doi = {10.1037//0735-7044.106.1.147}, pmid = {1313242}, issn = {0735-7044}, support = {DC-00161/DC/NIDCD NIH HHS/United States ; F32-NS07915/NS/NINDS NIH HHS/United States ; MH-43787/MH/NIMH NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Cortex/physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Dominance, Cerebral/physiology ; Lithium/toxicity ; Lithium Chloride ; Male ; Medulla Oblongata/*physiology ; Pons/*physiology ; Rats ; Rats, Inbred Strains ; Synapses/physiology ; Taste/*physiology ; Taste Buds/*physiology ; }, abstract = {Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit.}, } @article {pmid1552827, year = {1992}, author = {Risinger, FO and Cunningham, CL}, title = {Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion.}, journal = {Life sciences}, volume = {50}, number = {16}, pages = {PL113-8}, doi = {10.1016/0024-3205(92)90463-y}, pmid = {1552827}, issn = {0024-3205}, support = {R01 AA007702/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; AA08621/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Ethanol/*pharmacology ; Hyperglycemia/*chemically induced/genetics ; Male ; Mice ; Mice, Inbred Strains ; Taste/physiology ; }, abstract = {Genetic differences in the hyperglycemic response to acute ethanol exposure and ethanol-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J and DBA/2J mice were injected with ethanol (0-6 g/kg, I.P.) and blood glucose levels determined over 4 h. C57 mice demonstrated greater dose-dependent elevations in blood glucose compared to DBA mice. In a conditioned taste aversion procedure, water deprived mice received ethanol injections (1-4 g/kg, I.P.) immediately after access to a NaCl flavored solution. DBA mice developed aversion to the ethanol-paired flavor at a lower dose (2 g/kg) than C57 mice. These results provide further support for a possible inverse genetic relationship between sensitivity to ethanol-induced hyperglycemia and sensitivity to conditioned taste aversion.}, } @article {pmid1540109, year = {1992}, author = {Okifuji, A and Friedman, AG}, title = {Experimentally induced taste aversions in humans: effects of overshadowing on acquisition.}, journal = {Behaviour research and therapy}, volume = {30}, number = {1}, pages = {23-32}, doi = {10.1016/0005-7967(92)90092-u}, pmid = {1540109}, issn = {0005-7967}, mesh = {Adolescent ; Adult ; Association Learning ; Aversive Therapy/*methods ; *Avoidance Learning ; *Conditioning, Classical ; Female ; Humans ; Male ; Motion Sickness/psychology ; *Taste ; }, abstract = {This study used vection-induced symptoms of motion sickness as an unconditioned stimulus to condition food aversions in humans and to evaluate the efficacy of an overshadowing agent (novel flavored candy: CS2) to attenuate acquisition of the aversion. Subjects unfamiliar with a target food (CS1) were assigned to one of the following three groups which were identical except for order of exposure to stimuli: Taste Aversion Group (CS1-US-CS2-Test), Control Group (US-CS1-CS2-Test), and Overshadowing Group (CS1-CS2-US-Test). Subjects were tested on aversion ratings and consumption of the target flavor and ratings of the overshadowing agent. Subjects in the Taste Aversion group rated the target flavor as significantly more aversive and consumed less of it, although not significantly so, that did those in the Control group. The Overshadowing group consumed significantly more of the target food than did the Taste Aversion Group. Considering only subjects unfamiliar with the overshadowing agent, those in the Overshadowing group rated the agent (CS2) as significantly more aversive than the Taste Aversion and Control groups. Implications of these findings to taste aversions in humans are discussed.}, } @article {pmid1539079, year = {1992}, author = {Smurthwaite, ST and Kautz, MA and Geter, B and Riley, AL}, title = {Naloxone as a stimulus in drug discrimination learning: generalization to other opiate antagonists.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {41}, number = {1}, pages = {43-47}, doi = {10.1016/0091-3057(92)90056-l}, pmid = {1539079}, issn = {0091-3057}, mesh = {Animals ; Cues ; Diprenorphine/pharmacology ; Discrimination Learning/*drug effects ; Female ; Generalization, Psychological/*drug effects ; Nalorphine/pharmacology ; Naloxone/*pharmacology ; Naltrexone/pharmacology ; Narcotic Antagonists/*pharmacology ; Rats ; Saccharin/pharmacology ; }, abstract = {Nonopiate dependent animals were trained to discriminate the opiate antagonist naloxone (1 mg/kg) from distilled water within the conditioned taste aversion baseline of drug discrimination learning. Specifically, rats injected with naloxone prior to a saccharin-LiCl pairing, and with its vehicle prior to saccharin alone, rapidly acquired the drug discrimination, avoiding saccharin following the administration of naloxone and consuming saccharin following its vehicle after only three conditioning trials. Once the discrimination was acquired, generalization tests revealed that the opiate antagonists diprenorphine and naltrexone and the mixed opiate agonist/antagonist nalorphine completely generalized to the naloxone cue at doses of 1.8, 5.6 and 18 mg/kg, respectively. That discriminative control was established with a low dose of naloxone (i.e., 1 mg/kg) and other compounds with opiate antagonist activity generalized to the naloxone cue suggest that the stimulus effects of naloxone were likely mediated through the opiate receptor. Because each of these compounds are reported to bind to the mu receptor (with varying affinities and varying degrees of selectivity), the stimulus properties of naloxone are likely mediated at this specific receptor subtype.}, } @article {pmid1539076, year = {1992}, author = {Stevenson, GW and Pournaghash, S and Riley, AL}, title = {Antagonism of drug discrimination learning within the conditioned taste aversion procedure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {41}, number = {1}, pages = {245-249}, doi = {10.1016/0091-3057(92)90092-t}, pmid = {1539076}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Discrimination Learning/*drug effects ; Female ; Morphine/pharmacology ; Naloxone/pharmacology ; Rats ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Animals injected with morphine prior to the presentation of a saccharin-LiCl pairing and the morphine vehicle prior to saccharin alone rapidly acquired the drug discrimination, avoiding saccharin following the administration of morphine and consuming saccharin following its vehicle after only four conditioning trials. Once stimulus control was established, the opiate antagonist naloxone (1 mg/kg) was administered prior to morphine in a test of its ability to antagonize the morphine stimulus. Pretreatment times ranged from 10 to 180 min. Naloxone antagonized the stimulus properties of morphine for all subjects, although there were individual differences in the onset, duration (time course) and degree of antagonism. Together with the rapid acquisition typically reported in this design, the fact that antagonism was demonstrated in the present study suggests that the conditioned taste aversion procedure may be useful in the general assessment of drug discriminations.}, } @article {pmid1522757, year = {1992}, author = {Glowa, JR and Williams, AN}, title = {Effects of prior exposure to cocaine: interaction of reinforcing and suppressant effects.}, journal = {Life sciences}, volume = {51}, number = {13}, pages = {987-994}, doi = {10.1016/0024-3205(92)90496-c}, pmid = {1522757}, issn = {0024-3205}, mesh = {Animals ; Aversive Therapy ; Behavior, Animal ; Cocaine/*pharmacology ; *Conditioning, Psychological ; Drug Administration Schedule ; Male ; Reinforcement Schedule ; *Reinforcement, Psychology ; Saimiri ; Self Administration ; Substance-Related Disorders/*psychology ; Taste ; }, abstract = {Squirrel monkeys were trained to respond under second-order schedules of food presentation and then sequentially exposed to either a self-administration (SA) and then a conditioned taste aversion (CTA) procedure, or a CTA procedure and then a SA procedure. Initial exposure to stimuli associated with post-session delivery of cocaine (0.3 mg/kg) either maintained (SA) or suppressed (CTA) responding, respectively. In contrast, following exposure to CTA, SA procedures failed to maintain levels of responding comparable to those seen with initial exposure to SA. Following exposure to SA, the CTA procedure failed to suppress responding. Thus, prior exposure to either the reinforcing or suppressant effects of cocaine modified its subsequent behavioral effects, suggesting a unique role for behavioral history in the abuse potential of cocaine.}, } @article {pmid1418396, year = {1992}, author = {Larue-Achagiotis, C and Picard, M and Louis-Sylvestre, J}, title = {Feeding behavior in rats on a complete diet containing Concanavalin A.}, journal = {Reproduction, nutrition, development}, volume = {32}, number = {4}, pages = {343-350}, doi = {10.1051/rnd:19920404}, pmid = {1418396}, issn = {0926-5287}, mesh = {Animals ; Concanavalin A/administration & dosage/*pharmacology ; Diet ; Eating ; *Feeding Behavior ; Intubation, Gastrointestinal ; Male ; Rats ; Rats, Wistar ; Taste ; }, abstract = {Canavalia ensiformis is a tropical legume which could be used in animal feeding. However, it contains a lectin, Concanavalin A (Con A) which is harmful to animals. When rats are presented with a diet containing Con A, rejection of the food appears very soon after the beginning of ingestion. In order to examine this rejection phenomenon 3 studies were carried out. The rejection was found not to be due to a neophobic response, nor could it be attributed to a conditioned taste aversion. The gastric intubation study suggested the hypothesis that it could be the binding of the lectin to the glycosylated molecules from the gut membrane which impaired absorption and hence food intake.}, } @article {pmid1317039, year = {1992}, author = {Rowan, GA and Lucki, I}, title = {Discriminative stimulus properties of the benzodiazepine receptor antagonist flumazenil.}, journal = {Psychopharmacology}, volume = {107}, number = {1}, pages = {103-112}, pmid = {1317039}, issn = {0033-3158}, support = {DA 05186/DA/NIDA NIH HHS/United States ; DA 05367/DA/NIDA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Anticonvulsants/pharmacology ; Behavior, Animal/*drug effects ; Benzodiazepines/antagonists & inhibitors ; Carbolines/pharmacology ; Discrimination, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Flumazenil/*pharmacology ; *GABA-A Receptor Antagonists ; Male ; Pyrazoles/pharmacology ; Rats ; Rats, Inbred Strains ; }, abstract = {Rats were trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor antagonist flumazenil using a conditioned taste aversion procedure. On drug trials, fluid-restricted rats were injected with flumazenil (32 mg/kg), given access to a 0.25% saccharin solution for 30 min, and injected with LiCl (1.8 mEq/kg IP). On saline trials, injections of saline bracketed the period of saccharin consumption. Acquisition of the discriminated taste aversion, as measured by differential effects on drinking between saline and drug trials, developed after only five pairings of flumazenil with the LiCl injections. Flumazenil did not alter saccharin consumption in unconditioned controls (N = 9) that never received LiCl. The discrimination was also measured by flumazenil's ability to reduce the preference for saccharin over tap water using two-bottle choice tests. Flumazenil demonstrated dose-dependent generalization upon decreasing the training dose as low as 1 mg/kg. Two other BZ receptor antagonists of different chemical structure, CGS 8216 and ZK 93426, substituted completely for the flumazenil stimulus. Partial generalization was exhibited to the partial inverse agonists FG 7142 and beta-CCE, while the full inverse agonists DMCM and PTZ failed to substitute for the flumazenil stimulus. The BZ receptor agonists diazepam and alprazolam failed to substitute for the flumazenil stimulus, although partial generalization was shown with CDP. The results suggest that the BZ receptor antagonist flumazenil may produce intrinsic discriminative stimulus effects that are independent from those of BZ receptor agonists or inverse agonists.}, } @article {pmid1312728, year = {1992}, author = {Evenden, JL and Lavis, L and Iversen, SD}, title = {Blockade of conditioned taste aversion by scopolamine and N-methyl scopolamine: associative conditioning, not amnesia.}, journal = {Psychopharmacology}, volume = {106}, number = {2}, pages = {179-188}, pmid = {1312728}, issn = {0033-3158}, mesh = {Amnesia/*chemically induced/psychology ; Animals ; Ascorbic Acid/pharmacology ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Conditioning, Operant/*drug effects ; Lithium/pharmacology ; Lithium Chloride ; Male ; N-Methylscopolamine ; Neostigmine/pharmacology ; Parasympatholytics/*pharmacology ; Physostigmine/pharmacology ; Rats ; Rats, Inbred Strains ; Scopolamine/*pharmacology ; Scopolamine Derivatives/*pharmacology ; Sucrose/pharmacology ; Taste/*drug effects ; }, abstract = {The anticholinergic, scopolamine, consistently disrupts one-trial passive avoidance conditioning but the effects of such drugs on one-trial conditioned taste aversion (CTA) are variable and contradictory. In the present study, treatment of rats with scopolamine impaired the suppression of sucrose intake by post-ingestion administration of lithium chloride (LiCl) in a two-bottle choice test. A similar effect was obtained by using N-methyl scopolamine which penetrates the brain only to a limited degree on acute administration. The blockade of CTA could be prevented in three ways: (i) by exposing the rats to sucrose only on the training day, (ii) by pre-exposing the rats to both sucrose and scopolamine, and (iii) by using a less palatable sucrose/ascorbate mixture. The results demonstrate that the effect of scopolamine on taste aversion is not mediated by the central nervous system, and can be modified by altering the novelty and relative salience of the taste conditioned stimulus. These experiments suggest that conditioned associations between taste and LiCl, and scopolamine and LiCl may underlie the blockade of CTA by scopolamine.}, } @article {pmid1311109, year = {1992}, author = {Gauci, M and Bull, DF and Schedlowski, M and Husband, AJ and King, MG}, title = {Lithium chloride and immunomodulation in taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {51}, number = {1}, pages = {207-210}, doi = {10.1016/0031-9384(92)90225-q}, pmid = {1311109}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/*pharmacology ; Conditioning, Classical/*drug effects ; Cytotoxicity, Immunologic/*drug effects ; Immune Tolerance/drug effects ; Leukocyte Count/*drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Taste/*drug effects ; }, abstract = {Lithium chloride has been used in many studies of conditioning to induce taste aversion behaviour, and in some experiments investigating conditioning effects on immunity it has been used on the assumption that it is immunologically neutral. The studies reported here, however, indicate that LiCl is not immunologically neutral and when used to endow a UCS with noxious properties to enhance the behavioural response in taste aversion conditioned immunosuppression, it may antagonize the residual immunosuppression following initial UCS administration and also the conditioned immunosuppression occurring after CS reexposure. Therefore, conclusions drawn from studies of behaviourally conditioned immunomodulation where LiCl is used as part of either the CS or UCS may require reevaluation.}, } @article {pmid1667814, year = {1991}, author = {Gallo, M and Bures, J}, title = {Acquisition of conditioned taste aversion in rats is mediated by ipsilateral interaction of cortical and mesencephalic mechanisms.}, journal = {Neuroscience letters}, volume = {133}, number = {2}, pages = {187-190}, doi = {10.1016/0304-3940(91)90566-c}, pmid = {1667814}, issn = {0304-3940}, mesh = {Animals ; Brain/drug effects/physiology ; Cerebral Cortex/*physiology ; Chlorides/pharmacology ; *Conditioning, Operant ; Cortical Spreading Depression/drug effects ; Food Preferences ; Functional Laterality ; Lithium/pharmacology ; Lithium Chloride ; Male ; Mesencephalon/*physiology ; Rats ; Saccharin ; *Taste ; Tetrodotoxin/pharmacology ; Water Deprivation ; }, abstract = {The possibility to lateralize the neural circuits mediating conditioned taste aversion (CTA) has been examined by combination of functional hemidecortication and unilateral tetrodotoxin (TTX) injection into the parabrachial nucleus (PBN). Rats drinking saccharin (CS) during cortical spreading depression (CSD) in the right hemisphere and receiving unilateral PBN injection of TTX (3 ng) shortly before i.p. injection of lithium chloride (LiCl) (US) formed CTA when CSD and TTX were applied to the same hemisphere but not when applied to different hemispheres. Rats drinking saccharin with intact brain and receiving unilateral TTX overlapping with LiCl administration learned a weak CTA, the retrieval of which was disrupted by either ipsilateral or contralateral CSD during retention testing. It is concluded that CTA acquisition requires cooperation of ipsilateral cortical and subcortical centers but that formation of unilateral subcortical CTA engram does not warrant lateralization of the retrieval process.}, } @article {pmid1798787, year = {1991}, author = {Bakner, L and Strohen, K and Nordeen, M and Riccio, DC}, title = {Postconditioning recovery from the latent inhibition effect in conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {50}, number = {6}, pages = {1269-1272}, doi = {10.1016/0031-9384(91)90595-f}, pmid = {1798787}, issn = {0031-9384}, support = {MH37537/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Body Weight/drug effects ; Conditioning, Operant/*physiology ; Male ; Memory/drug effects ; Rats ; Sucrose/pharmacology ; Taste/*physiology ; }, abstract = {Two experiments were conducted examining the effects of flavor (CS) preexposure on the retention of conditioned taste aversion. In Experiment 1, rats received preexposure to sucrose solution followed by a sucrose-illness pairing. The expected "latent inhibition" effect was obtained when testing occurred after a two-day but not an eleven-day training-to-test interval. Experiment 2 extended these results by employing five- and twenty-one-day training-to-test interval parameters and provided evidence that the stronger taste aversion displayed by preexposed subjects following long retention intervals is not attributable to differences in training consumption of sucrose solution. This posttraining increase in conditioned taste aversion (CTA) suggests that preexposure blocks expression of memory.}, } @article {pmid1777729, year = {1991}, author = {Grochowicz, PM and Schedlowski, M and Husband, AJ and King, MG and Hibberd, AD and Bowen, KM}, title = {Behavioral conditioning prolongs heart allograft survival in rats.}, journal = {Brain, behavior, and immunity}, volume = {5}, number = {4}, pages = {349-356}, doi = {10.1016/0889-1591(91)90030-e}, pmid = {1777729}, issn = {0889-1591}, mesh = {Abdomen ; Animals ; *Avoidance Learning ; *Conditioning, Operant ; Cyclosporine/administration & dosage/*pharmacology ; Graft Survival/immunology ; Heart Transplantation/*immunology ; *Immune Tolerance ; Psychoneuroimmunology ; Rats ; Rats, Inbred Lew/immunology ; Rats, Inbred Strains/immunology ; Saccharin ; Taste ; Transplantation, Heterotopic ; Transplantation, Homologous ; }, abstract = {Conditioned immunosuppression using a taste aversion paradigm has been demonstrated in a number of laboratory models but few reports have demonstrated changes in immunity sufficient to be of clinical relevance. The experiments reported here demonstrate that the survival of heart allografts in rats can be prolonged by behaviorally conditioned immunosuppression using cyclosporin A (CsA) as an unconditioned stimulus in taste aversion conditioning. Conditioned animals received saccharin as the conditioned stimulus paired with an injection of CsA at 10 and 6 days prior to transplantation. They were reexposed to saccharin alone 1 day prior to and 3 days after transplantation. On these occasions the conditioned group displayed taste aversion behavior when offered saccharin and a significant prolongation of heart graft survival was observed compared to the conditioned and nonconditioned control groups. These experiments suggest that behaviorally conditioned immunosuppression may have important clinical implications as an adjunct to drug treatments in transplantation medicine.}, } @article {pmid1777109, year = {1991}, author = {Hunt, PS and Spear, LP and Spear, NE}, title = {An ontogenetic comparison of ethanol-mediated taste aversion learning and ethanol-induced hypothermia in preweanling rats.}, journal = {Behavioral neuroscience}, volume = {105}, number = {6}, pages = {971-983}, doi = {10.1037//0735-7044.105.6.971}, pmid = {1777109}, issn = {0735-7044}, support = {1 F31 AA05307/AA/NIAAA NIH HHS/United States ; 1 R01 MH35219/MH/NIMH NIH HHS/United States ; 5 R01 AA06634/AA/NIAAA NIH HHS/United States ; }, mesh = {Aging/*physiology ; Animals ; Animals, Suckling ; Avoidance Learning/*drug effects/*physiology ; Body Temperature Regulation/*drug effects/*physiology ; Conditioning, Classical/*drug effects/*physiology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Female ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects/*physiology ; }, abstract = {To examine the interactive effects of ethanol (EtOH) and ambient temperature, 10-, 16-, and 20-day-old rat pups ingested pairings of sucrose solution and various doses of ethanol (intubated intragastrically) and were then exposed to relatively low or relatively high ambient temperatures. Ten- and 20-day-old pups required a higher EtOH dose than did 16-day old pups for conditioning of a sucrose aversion and for hypothermia. These age-related differences might be due to ontogenetic changes in the production and accumulation of acetaldehyde, a metabolite of EtOH. For all ages, EtOH-induced hypothermia was necessary for conditioning of the taste aversion, which is in accord with results of previous tests with adult rats (Cunningham, Hawks, & Niehus, 1988).}, } @article {pmid1777107, year = {1991}, author = {Flynn, FW and Grill, HJ and Schulkin, J and Norgren, R}, title = {Central gustatory lesions: II. Effects on sodium appetite, taste aversion learning, and feeding behaviors.}, journal = {Behavioral neuroscience}, volume = {105}, number = {6}, pages = {944-954}, doi = {10.1037//0735-7044.105.6.944}, pmid = {1777107}, issn = {0735-7044}, support = {DC-00240/DC/NIDCD NIH HHS/United States ; DK-21397/DK/NIDDK NIH HHS/United States ; NS-24879/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Appetite/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain/*physiology ; Brain Mapping ; Conditioning, Classical/*physiology ; Drinking/physiology ; Facial Nerve/physiology ; Feeding Behavior/*physiology ; Glossopharyngeal Nerve/physiology ; Male ; Pons/physiology ; Rats ; Rats, Inbred Strains ; Sodium, Dietary/*administration & dosage ; Synapses/physiology ; Taste/*physiology ; Taste Threshold/physiology ; Thalamic Nuclei/physiology ; Vagus Nerve/physiology ; Water-Electrolyte Balance/*physiology ; }, abstract = {Intake and taste reactivity tests were used to determine the effects of bilateral lesions of the gustatory portions of the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN), and the ventral posteromedial nucleus of the thalamus (VPMpc) on several complex ingestive behaviors. In the 1st experiment, lesions of the PBN and the NST blocked, and VPMpc lesions impaired, the behavioral expression of salt appetite. In the 2nd experiment, alanine was paired with injections of LiCl. Control rats as well as rats with NST and VPMpc lesions acquired the taste aversion, but rats with PBN lesions did not. In the 3rd experiment, all animals increased their food intake after injections of 2 U/kg insulin and 250 mg/kg 2-deoxy-D-glucose, and their food intake was suppressed after nutritive stomach loads.}, } @article {pmid1752857, year = {1991}, author = {Hernandez, L and Parada, M and Baptista, T and Schwartz, D and West, HL and Mark, GP and Hoebel, BG}, title = {Hypothalamic serotonin in treatments for feeding disorders and depression as studied by brain microdialysis.}, journal = {The Journal of clinical psychiatry}, volume = {52 Suppl}, number = {}, pages = {32-40}, pmid = {1752857}, issn = {0160-6689}, support = {DA 03597/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Antidepressive Agents/*pharmacology/therapeutic use ; Depressive Disorder/drug therapy/physiopathology ; Extracellular Space/chemistry ; Feeding Behavior/drug effects/*physiology ; Humans ; Hypothalamus/*chemistry/physiology ; Rats ; Serotonin/*chemistry/physiology ; }, abstract = {Microdialysis was used to measure changes in extracellular serotonin in the hypothalamus of rats while they engaged in feeding behavior or received drug treatments used to treat feeding disorders and affective disorders in humans. Hypothalamic serotonin increased significantly relative to controls in response to (1) intraperitoneal tryptophan after food deprivation, (2) the smell of food and eating a meal, (3) a conditioned taste aversion, (4) d-fenfluramine and fluoxetine, and (5) an amphetamine challenge test after chronic low doses of lithium. In some cases, increases correlated with nonspecific behavioral arousal were seen in the hippocampus. The results suggest that diet, drug, and behavioral therapies, alone or combined, can be used to preferentially modify hypothalamic serotonin in the control of behavioral, emotional, and endocrine problems.}, } @article {pmid1663759, year = {1991}, author = {Davey, VA and Biederman, GB}, title = {Methodological issues in drug-drug conditioning in rats: nonassociative factors in heart rate and avfail.}, journal = {Behavioral neuroscience}, volume = {105}, number = {6}, pages = {850-859}, doi = {10.1037//0735-7044.105.6.850}, pmid = {1663759}, issn = {0735-7044}, mesh = {Animals ; Arousal/*drug effects ; Association Learning/*drug effects ; Avoidance Learning/drug effects ; Chlorides/pharmacology ; Conditioning, Classical/*drug effects ; Dextroamphetamine/*pharmacology ; Dose-Response Relationship, Drug ; Heart Rate/*drug effects ; Homeostasis/drug effects ; Injections, Intraperitoneal ; Lithium/pharmacology ; Lithium Chloride ; Male ; Pentobarbital/*pharmacology ; Rats ; Retention, Psychology/drug effects ; Taste/drug effects ; }, abstract = {Sodium pentobarbital injections followed 30 min later by d-amphetamine sulfate produce an effect over trials in the form of an increase in heart rate in response to pentobarbital in relation to rats that receive the 2 drugs 24 hr apart (long-delayed control: Revusky, Davey, & Zagorski, 1989). This study found equivalent increases in heart rate in forward and backward groups in relation to a long-delayed control regardless of whether training or testing was carried out in a heart rate recording apparatus or in the home cage, which suggests that a drug interaction due to drug administrations in forward and backward groups has yet to be eliminated in accounting for the heart rate effect. Comparison of backward and long-delayed controls in a drug-drug procedure that used a taste aversion test revealed that both forward and delayed pairings can produce attenuated aversions in relation to a backward group regardless of whether the unconditional stimulus is amphetamine (Experiment 1) or lithium chloride (Experiment 2).}, } @article {pmid1815219, year = {1991}, author = {Flood, JF and Morley, JE}, title = {Increased food intake by neuropeptide Y is due to an increased motivation to eat.}, journal = {Peptides}, volume = {12}, number = {6}, pages = {1329-1332}, doi = {10.1016/0196-9781(91)90215-b}, pmid = {1815219}, issn = {0196-9781}, mesh = {Animals ; Appetitive Behavior/drug effects ; Dose-Response Relationship, Drug ; Eating/*drug effects ; Electroshock ; Feeding Behavior/*drug effects ; Injections, Intraventricular ; Male ; Mice ; Motivation ; Neuropeptide Y/administration & dosage/*pharmacology ; Taste ; }, abstract = {Neuropeptide Y (NPY), administered intracerebroventricularly, is a potent orexigenic agent. To determine if NPY-induced eating represented an increase in motivation to eat (e.g., hunger) rather than pathological or stimulus-bound eating, we determined its effect on eating in three paradigms, including lever press, appetitive passive avoidance and quinine-adulterated milk. NPY-injected mice consumed more milk when required to work for it in a lever press apparatus and tolerated shock to the tongue for drinking milk. Increasing the dose of NPY also allowed mice to overcome a taste aversion for quinine-adulterated milk. Overall, these studies support the hypothesis that NPY causes a specific increase in the motivation to eat, rather than nonspecific or stimulus-bound behavior.}, } @article {pmid1805290, year = {1991}, author = {de Beun, R and Jansen, E and Smeets, MA and Niesing, J and Slangen, JL and van de Poll, NE}, title = {Estradiol-induced conditioned taste aversion and place aversion in rats: sex- and dose-dependent effects.}, journal = {Physiology & behavior}, volume = {50}, number = {5}, pages = {995-1000}, doi = {10.1016/0031-9384(91)90427-p}, pmid = {1805290}, issn = {0031-9384}, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Estradiol/*pharmacology ; Female ; Male ; Rats ; Rats, Inbred Strains ; Sex Factors ; *Social Environment ; Taste/*drug effects ; }, abstract = {Effects of various doses (0-250 micrograms/kg, SC) of estradiol-17 beta (E2) in a two-bottle choice conditioned taste aversion and a two-compartment conditioned place preference procedure were studied in male and female rats. Dose-dependent taste aversion and place aversion effects of E2 were established, and the conditioned taste aversion procedure was found to be more sensitive in detecting aversive properties of E2 than the conditioned place preference procedure. Although aversive properties of E2 were found in both sexes, the effects were clearly more prominent in males as compared to females. From this study, it was concluded that E2 acts as an unconditioned aversive stimulus in both male and female rats capable of gaining control over different types of behavior by associative learning.}, } @article {pmid1658847, year = {1991}, author = {Rabin, BM and Hunt, WA and Joseph, JA and Dalton, TK and Kandasamy, SB}, title = {Relationship between linear energy transfer and behavioral toxicity in rats following exposure to protons and heavy particles.}, journal = {Radiation research}, volume = {128}, number = {2}, pages = {216-221}, pmid = {1658847}, issn = {0033-7587}, mesh = {Animals ; Avoidance Learning/radiation effects ; Conditioning, Psychological/*radiation effects ; Dose-Response Relationship, Radiation ; *Energy Transfer ; Male ; Neutrons ; *Protons ; Rats ; }, abstract = {Rats were exposed to protons (155 MeV) or to helium (165 MeV/amu), neon (522 MeV/amu) or argon (670 MeV/amu) particles to evaluate the behavioral toxicity of these types of radiations. Behavioral toxicity was assessed using the conditioned taste aversion paradigm. Exposure to all types of radiation produced dose-dependent increases in the intensity of the acquired taste aversion. However, the intensity of the aversions, measured as the dose that produced a 50% decrease in the intake of the sucrose-conditioned stimulus, did not show significant variation as a function of the linear energy transfer (LET) of the radiation. The results are discussed in terms of the relationship between LET and behavioral toxicity.}, } @article {pmid1791889, year = {1991}, author = {Ader, R and Cohen, N}, title = {Conditioning of the immune response.}, journal = {The Netherlands journal of medicine}, volume = {39}, number = {3-4}, pages = {263-273}, pmid = {1791889}, issn = {0300-2977}, support = {K05-MH06318/MH/NIMH NIH HHS/United States ; MH 42051/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Conditioning, Psychological ; Humans ; Immune System/*physiology ; }, abstract = {Experimental studies in humans and experimental animals document the acquisition and extinction of classically conditioned alterations of different parameters of humoral- and cell-mediated immune responses. Although the aversive effects of cyclophosphamide in a taste aversion learning paradigm has been the most frequently used model, conditioned immunomodulatory effects are not confined to this conditioning procedure, and they are not limited to cyclophosphamide or, for that matter, the use of immunomodulating drugs as unconditioned stimuli. Conditioned changes in immunologic reactivity have also been found to modulate the progression of spontaneously-developing or experimentally-induced pathophysiological processes in experimental animals. The available data on the immunoregulatory effects of conditioning indicate that the immune system, like other systems operating in the interests of homeostasis, is integrated with other physiological processes and is therefore influenced by and capable of influencing the brain.}, } @article {pmid1775562, year = {1991}, author = {Ganesan, R and Simpkins, JW}, title = {Conditioned taste aversion induced by estradiol pellets.}, journal = {Physiology & behavior}, volume = {50}, number = {4}, pages = {849-852}, doi = {10.1016/0031-9384(91)90029-n}, pmid = {1775562}, issn = {0031-9384}, support = {HD 22540/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain/drug effects ; Conditioning, Classical/*drug effects ; Drug Implants ; Estradiol/*pharmacology ; Female ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {In two experiments, ovariectomized rats were given a novel diet prior to the implantation of a fused pellet of estradiol (E2 pellet). In short-term (3 weeks) ovariectomized rats, the suppression of food intake induced by estrogen was not affected by the introduction of the novel diet. However, a sensitive two-choice preference test revealed that subjects implanted with the E2 pellet had a lesser preference for the novel diet than controls implanted with the vehicle pellet. In long-term (18 weeks) ovariectomized rats, implantation of the E2 pellet had a large effect on the consumption of the novel diet. Intake was reduced to less than 1 g in all subjects on Days 3-7 after E2 pellet implantation. A subsequent two-choice preference test indicated the presence of a strong aversion to the novel diet in the estradiol-treated rats relative to the controls. These experiments show that estradiol can induce conditioned taste aversions that have either no effect on intake or totally suppress food intake, depending upon postovariectomy time.}, } @article {pmid1959034, year = {1991}, author = {Sclafani, A}, title = {Starch and sugar tastes in rodents: an update.}, journal = {Brain research bulletin}, volume = {27}, number = {3-4}, pages = {383-386}, doi = {10.1016/0361-9230(91)90129-8}, pmid = {1959034}, issn = {0361-9230}, support = {DK-31135/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Carbohydrates/*physiology ; Mouth/physiology ; Polysaccharides/physiology ; Rodentia/*physiology ; Sensation ; Starch/*physiology ; Taste/*physiology ; }, abstract = {Rats are strongly attracted to the sweet taste of sugar. Recent behavioral studies demonstrate that rats also have a well-developed taste for starch-derived polysaccharides (e.g., Polycose). In fact, rats prefer Polycose to sucrose and other sugars at low concentrations. Polycose appetite develops at a very young age (9 days) and, thus, appears to be innate. The results of conditioned taste aversion tests suggest that rats taste Polycose as qualitatively different from sucrose. Recent electrophysiological findings support the idea that rodents have separate taste channels for polysaccharides and sugars. In particular, copper chloride suppresses the chorda tympani nerve response to sucrose and other sugars but has minimal effect on the neural response to Polycose. Also, Polycose evokes a profile of neural activity in the nucleus tractus solitarius that differs substantially from that produced by sucrose. Preliminary results indicate that polysaccharide and sugar tastes also differ in their metabolic consequences, i.e., unlike sugars, Polycose does not elicit a cephalic phase insulin response. The presumed function of polysaccharide taste is to facilitate the identification of starch-rich foods. Recent findings demonstrate that rats can readily detect starch even at low concentrations, but whether polysaccharide taste receptors or other orosensory receptors mediate this response remains to be clarified.}, } @article {pmid1954405, year = {1991}, author = {Roudebush, RE and Bryant, HU}, title = {Conditioned immunosuppression of a murine delayed type hypersensitivity response: dissociation from corticosterone elevation.}, journal = {Brain, behavior, and immunity}, volume = {5}, number = {3}, pages = {308-317}, doi = {10.1016/0889-1591(91)90025-6}, pmid = {1954405}, issn = {0889-1591}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical ; Corticosterone/blood ; Cyclophosphamide/toxicity ; Dexamethasone/pharmacology ; Drinking Behavior ; Drug Hypersensitivity/complications/immunology/physiopathology ; Edema/etiology/immunology ; Foot ; Hypersensitivity, Delayed/*immunology/physiopathology ; *Immune Tolerance/physiology ; Immunity, Cellular ; Male ; Mice ; Mice, Inbred BALB C/immunology ; Nausea/chemically induced/complications ; Picryl Chloride/immunology/toxicity ; Saccharin/pharmacology ; Stress, Physiological/blood/etiology/*immunology/physiopathology ; T-Lymphocytes/immunology ; Taste ; }, abstract = {The mechanisms involved in behavioral modulation of immunity by Pavlovian conditioning have not been delineated, although an elevation in adrenocortical steroids has been invoked as an explanation. Therefore, we investigated whether or not a 4-day, murine delayed type hypersensitivity (DTH) response could be modified by a taste aversion conditioning paradigm. Mice were conditioned by the pairing of their saccharin (0.1%) drinking water (SAC) with a cyclophosphamide (CY) injection (50 mg/kg) on Day 0. Conditioned mice that were exposed on Day 3 to SAC + CY, SAC + normal saline, or water + CY exhibited significant suppression of DTH induced paw swelling when compared to nonconditioned controls. Conditioned immunosuppression was demonstrated, since the DTH response was suppressed by SAC without a concomitant reexposure to the immunosuppressant, CY. However, when dexamethasone (3 mg/kg) was used as the conditioning agent, the SAC + vehicle group showed no reduction in paw swelling. A serum corticosterone time course study was performed to examine possible involvement of glucocorticoids in conditioned immunosuppression. On Day 3, mice were sacrificed 30, 60, 90, 120 min and 24 h after reexposure to SAC or water. No significant differences in serum corticosterone levels were detected between nonconditioned controls and any conditioned group at any time point. These results demonstrate conditioned immunosuppression of a cell-mediated immune response that is not linked to a rise in glucocorticoid levels.}, } @article {pmid1720686, year = {1991}, author = {Bures, J and Buresova, O and Ivanova, SF}, title = {Brain stem mechanisms of conditioned taste aversion learning in rats.}, journal = {Archives internationales de physiologie, de biochimie et de biophysique}, volume = {99}, number = {5}, pages = {A131-4}, pmid = {1720686}, issn = {0778-3124}, mesh = {Amnesia/chemically induced ; Animals ; Avoidance Learning/*physiology ; Brain Stem/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Rats ; Tetrodotoxin/pharmacology ; }, abstract = {Acquisition of conditioned taste aversion (CTA) in rats is not prevented by functional decortication, anesthesia or hypothermia applied after intake of the flavored fluid and maintained throughout the action of the poison but is disrupted by bilateral application of 10 ng tetrodotoxin (TTX) into the parabrachial nuclei. The blockade is directly proportional to TTX dosage, indirectly proportional to distance of the injection site from parabrachial nuclei and equally affects CTAs using different CS (saccharin, NaCl) and different US (LiCl, carbachol, amphetamine, cycloheximide). CTA is disrupted by TTX applied up to 4 but not 8 days after a single CS-US pairing. TTX fails to disrupt overtrained CTA and elicits only a weak anterograde amnesia when applied 1 but 2 or more days before CTA acquisition. It is concluded that the parabrachial nuclei and the adjacent reticular formation probably represent the neural substrate of the permanent CTA engram the protracted consolidation of which is disrupted by prolonged cessation of impulse which is disrupted by prolonged cessation of impulse activity in the information storing network.}, } @article {pmid1683599, year = {1991}, author = {Yamamoto, T and Fujimoto, Y}, title = {Brain mechanisms of taste aversion learning in the rat.}, journal = {Brain research bulletin}, volume = {27}, number = {3-4}, pages = {403-406}, doi = {10.1016/0361-9230(91)90133-5}, pmid = {1683599}, issn = {0361-9230}, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Conditioning, Psychological/physiology ; Electrophysiology ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {This study aims to reveal brain mechanisms underlying the conditioned taste aversion (CTA) learning. To establish CTA in Wistar male adult rats, 0.01 M Na-saccharin and IP injection of 0.15 M LiCl were used for conditioned stimulus and unconditioned stimulus, respectively. Rats with ibotenic acid lesions of the pontine taste area, thalamic taste area, or basolateral nucleus of the amygdala, failed to establish CTA learning, but lesions of the amygdaloid nuclei other than the basolateral nucleus, cortical gustatory area, hippocampus, entorhinal cortex, bed nucleus of the stria terminalis, or substantia innominata, showed slight or little effects. Rats that received amino-phosphovaleric acid chronically in the amygdala failed to establish CTA. These results, together with our preliminary results, suggest that long-term potentiation of gustatory responses involving N-methyl-D-aspartate receptors in the basolateral nucleus of the amygdala is a basic mechanism for CTA learning.}, } @article {pmid1659608, year = {1991}, author = {Glowa, JR and Jeffreys, RD and Riley, AL}, title = {Drug discrimination using a conditioned taste-aversion paradigm in rhesus monkeys.}, journal = {Journal of the experimental analysis of behavior}, volume = {56}, number = {2}, pages = {303-312}, pmid = {1659608}, issn = {0022-5002}, mesh = {Alprazolam/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Chlorides/toxicity ; Conditioning, Classical/*drug effects ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Lithium/toxicity ; Lithium Chloride ; Macaca mulatta ; Male ; *Reinforcement Schedule ; Taste/*drug effects ; }, abstract = {The development of drug discrimination was assessed in rhesus monkeys using the conditioned taste-aversion paradigm. Monkeys were initially trained to respond under a fixed-ratio 30-response schedule of food-pellet delivery to assess the rate-decreasing effects of alprazolam (0.03 to 3 mg/kg, i.m., 60 min presession). Alprazolam decreased responding at doses greater than 0.1 mg/kg. Discriminative stimulus effects of alprazolam were then assessed by giving 0.03 mg/kg before sessions in which 1.8 mEq/kg lithium chloride was given immediately after the session (alprazolam/lithium session). On intervening days, saline was given before and after the session (saline/saline session). Rates of responding decreased over successive alprazolam/lithium sessions and also during the saline/saline session that immediately followed an alprazolam/lithium session. During subsequent saline/saline sessions, rates of responding returned to levels near baseline rates within two to four sessions. The discriminative stimulus effects of alprazolam were then assessed by giving 0.1 mg/kg before sessions in which 1 mg/kg d-amphetamine was given immediately after the session (alprazolam/d-amphetamine session). Rates of responding decreased during subsequent alprazolam/d-amphetamine sessions in drug-experienced monkeys, but did not decrease during intervening saline/saline sessions. These findings demonstrate that drug stimuli associated with postsession drug injections can rapidly develop control over behavior and suggest that similar methods be explored in the assessment of drug discrimination.}, } @article {pmid1718560, year = {1991}, author = {West, HL and Mark, GP and Hoebel, BG}, title = {Effects of conditioned taste aversion on extracellular serotonin in the lateral hypothalamus and hippocampus of freely moving rats.}, journal = {Brain research}, volume = {556}, number = {1}, pages = {95-100}, doi = {10.1016/0006-8993(91)90551-6}, pmid = {1718560}, issn = {0006-8993}, mesh = {Animals ; Chlorides/*pharmacology ; *Conditioning, Psychological ; Hippocampus/drug effects/*physiology ; Hydroxyindoleacetic Acid/metabolism ; Hypothalamic Area, Lateral/drug effects/*physiology ; Kinetics ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin ; Serotonin/*metabolism ; *Taste ; }, abstract = {This study used microdialysis to monitor extracellular levels of 5-HT and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the lateral hypothalamus (LH) and hippocampus of freely moving rats that had developed a CTA to a 2.5 mM saccharin solution (CS) following its pairing with illness induced by lithium chloride (US). Results showed that oral infusion of the saccharin CS significantly enhanced extracellular LH 5-HT in animals that had developed a taste aversion compared with control groups, including unconditioned (CS-no US) and pseudoconditioned (no CS-US) subjects. As an anatomical control, the hippocampus was identified based on previous research suggesting that it is not integrally involved in CTA learning or retrieval and that 5-HT in this brain site does not directly mediate feeding behavior but is closely correlated with arousal. In contrast with the results obtained in the LH, hippocampal 5-HT was not preferentially elevated in subjects in the CTA group but rather was increased to the same extend in both CTA and control groups after saccharin infusion. Moreover, the increase in LH 5-HT for the CTA group was nearly twice that observed in the hippocampus for any group. Acute administration of LiCl elevated extracellular 5-HT to similar levels in both sites, well above the changes observed following conditioning. 5-HIAA was unaffected in either brain site by oral infusion of saccharin solution or injection of LiCl.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid1763104, year = {1991}, author = {Woudenberg, F and Hijzen, TH}, title = {Discriminated taste aversion with chlordiazepoxide.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {39}, number = {4}, pages = {859-863}, doi = {10.1016/0091-3057(91)90044-3}, pmid = {1763104}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlordiazepoxide/*pharmacology ; Cues ; Discrimination, Psychological/*drug effects ; Drinking Behavior/drug effects ; Food ; Psychotropic Drugs/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Discriminative stimulus effects have been studied extensively with the two-response, food-reinforced operant procedure and more recently also with discriminated taste aversion (DTA) procedures. DTA procedures have the advantage of a more rapid discrimination training. However, the test phase, i.e., drug substitution, of the DTA procedure is more time consuming (1 test per 4 days) than the test phase of the two-response procedure (2 tests per 5 days). The present study investigated whether a DTA procedure with 2 tests per 5 days could be implemented. In addition, the specificity of the DTA procedure was investigated. Rats were trained to discriminate chlordiazepoxide (CDP, 20 mg/kg, IP) from vehicle using a discriminated taste aversion procedure. Selective suppression of saccharin consumption after CDP injections was maximal after seven CDP-LiCl pairings. In subsequent substitution tests, with 2 tests per 5 days, CDP-mimicking effects were found only for another benzodiazepine, diazepam, and for a barbiturate, pentobarbital. The results indicate that rats can be rapidly trained to discriminate CDP from vehicle in the discriminated taste aversion procedure and that the CDP-cue so produced has the same specificity as in a two-response, food-reinforced operant procedure. However, the DTA procedure has a number of drawbacks that make its advantage over the two-response procedure questionable.}, } @article {pmid1946720, year = {1991}, author = {Zalaquett, C and Thiessen, D}, title = {The effects of odors from stressed mice on conspecific behavior.}, journal = {Physiology & behavior}, volume = {50}, number = {1}, pages = {221-227}, doi = {10.1016/0031-9384(91)90524-r}, pmid = {1946720}, issn = {0031-9384}, support = {MH 14076-22/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Arousal/*physiology ; Avoidance Learning/physiology ; Chemoreceptor Cells/physiology ; Conditioning, Classical/physiology ; Fear/*physiology ; Female ; Mice ; Mice, Inbred BALB C ; Pheromones/*physiology ; Smell/*physiology ; *Social Environment ; Taste/physiology ; }, abstract = {Four experiments correlate conspecific reactions to odors from stressed (foot shocked) BALB/cJ mice with the frequency of specific motor activities and taste avoidance. Where behavior was restricted to forward and backward movement in a tube, animals tended to avoid the side where the odors from stressed animals entered. In a more socially complex home cage (3 recipients) a wide variety of behaviors were affected by odors from stressed conspecifics. Animals were alerted by the odor, searched out the source of the odor and showed increases in general activity, rearing, and air sampling. Many of these behaviors habituated with continuous exposure. The major response to odors from stressed animals was to increase "vigilance." A restriction of behavioral opportunities will lead to odor avoidance; however, when the environment permits, the behavioral reaction to odors becomes more complex. These odors failed to produce conditioned taste aversion, suggesting a sensory specificity in the use of these odors.}, } @article {pmid1913157, year = {1991}, author = {Mark, GP and Blander, DS and Hoebel, BG}, title = {A conditioned stimulus decreases extracellular dopamine in the nucleus accumbens after the development of a learned taste aversion.}, journal = {Brain research}, volume = {551}, number = {1-2}, pages = {308-310}, doi = {10.1016/0006-8993(91)90946-s}, pmid = {1913157}, issn = {0006-8993}, mesh = {Administration, Oral ; Animals ; *Conditioning, Psychological ; Dopamine/*metabolism ; Extracellular Space/*metabolism ; Male ; Nucleus Accumbens/*metabolism ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Stimulation, Chemical ; Taste/*physiology ; }, abstract = {The conditioned taste aversion (CTA) paradigm and microdialysis were used to determine if extracellular dopamine in the nucleus accumbens is related to the reward value of a stimulus. Intraorally applied saccharin caused a 37% increase in DA in naive rats and a 40% decrease in subjects with a CTA to this taste. These results suggest that accumbens DA is not just a function of arousal but is related to stimulus reward.}, } @article {pmid1654573, year = {1991}, author = {Bull, DF and Brown, R and King, MG and Husband, AJ}, title = {Modulation of body temperature through taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {49}, number = {6}, pages = {1229-1233}, doi = {10.1016/0031-9384(91)90356-s}, pmid = {1654573}, issn = {0031-9384}, mesh = {Animals ; Arousal/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Body Temperature Regulation/*physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Interleukin-1/biosynthesis ; Lipopolysaccharides/immunology ; Lithium/toxicity ; Lithium Chloride ; Psychoneuroimmunology ; Rats ; Taste/*physiology ; }, abstract = {Injection of rats with bacterial lipopolysaccharide (LPS) results in an initial fall in body temperature followed by a fever. Lithium chloride (LiCl) injection induces a fall in body temperature without subsequent fever production. When these substances were incorporated as unconditioned stimuli in a taste aversion conditioning paradigm, using saccharin flavour as the conditioning stimulus, these differential effects on body temperature were reenlisted on reexposure to saccharin alone 7 days after conditioning. The changes in body temperature on reexposure were similar in direction and kinetics as on the conditioning day although reduced in magnitude. The finding of a true conditioned effect in these studies is in contrast to the paradoxical or compensatory conditioned body temperature responses described elsewhere using different conditioning models. This apparent conflict may be explained on the basis of different unconditioned stimuli acting on efferent versus afferent arms of a negative feedback system. Since body temperature changes often occur in association with immune responses, these findings may have implications to behavioural conditioning of immunity, the outcome of which may reflect the indirect effects on immunity of inadvertent conditioning of thermoregulatory changes.}, } @article {pmid1654172, year = {1991}, author = {Bermudez-Rattoni, F and McGaugh, JL}, title = {Insular cortex and amygdala lesions differentially affect acquisition on inhibitory avoidance and conditioned taste aversion.}, journal = {Brain research}, volume = {549}, number = {1}, pages = {165-170}, doi = {10.1016/0006-8993(91)90616-4}, pmid = {1654172}, issn = {0006-8993}, support = {MH12526/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/drug effects/*physiology ; Animals ; *Avoidance Learning/drug effects ; Cerebral Cortex/drug effects/*physiology ; Chlorides/pharmacology ; *Conditioning, Operant/drug effects ; Drinking Behavior ; Lithium/pharmacology ; Lithium Chloride ; Male ; N-Methylaspartate/*pharmacology ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {These experiments examined the effects of NMDA-induced lesions of the amygdala and insular (gustatory) cortex (IC) on inhibitory avoidance learning and conditioned taste aversion (CTA) in rats. IC lesions, but not amygdala lesions, disrupted CTA. In contrast, lesions of either brain region disrupted inhibitory avoidance learning. These findings support the view that the IC is strongly involved in the acquisition of external as well as visceral aversively motivated behavior. Despite extensive functional interconnections, these 2 brain regions appear to have different roles in mediating different forms of aversively based learning.}, } @article {pmid1924498, year = {1991}, author = {Bellinger, LL and Mendel, VE}, title = {HPLC-purified human satietin does not produce conditioned taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {39}, number = {1}, pages = {161-165}, doi = {10.1016/0091-3057(91)90415-x}, pmid = {1924498}, issn = {0091-3057}, support = {DK42635/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Appetite Depressants/*pharmacology ; Avoidance Learning/*drug effects ; Chromatography, High Pressure Liquid ; Drinking/drug effects ; Eating/drug effects ; Glycopeptides/isolation & purification/*pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Human satietin is thought to be an endogenous glycoprotein that can suppress food intake and body weight. However, it was also found to be aversive when rats infused intracerebroventricularly (ICV) with human satietin were subjected to a two-bottle taste aversion test. More recently, the human satietin previously thought homogenous was separated by HPLC into two Peaks, denoted as A and B. In the present study, male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and presented with fluid for 1 h/day, while food was given ad lib. After training, the rats were ICV infused with either artificial cerebrospinal fluid, Peak A or Peak B of human satietin. Peak B significantly reduced short-term and 24-h food intake, whereas their fluid intake was nonsignificantly attenuated. Peak A had no affect on either food or fluid intake on the day it was administered. When the rats were given the two-bottle taste aversion test neither compound was found to be aversive. These data suggest that Peak B may contain satietin(s) which could be a candidate for an endogenous satiety agent.}, } @article {pmid1653437, year = {1991}, author = {Gietzen, DW and Duke, CM and Hammer, VA}, title = {Amino acid imbalance, a nutritional model: serotonin3 mediation of aversive responses.}, journal = {Physiology & behavior}, volume = {49}, number = {5}, pages = {981-985}, doi = {10.1016/0031-9384(91)90211-6}, pmid = {1653437}, issn = {0031-9384}, mesh = {Amino Acids/*physiology ; Animals ; Appetitive Behavior/physiology ; Avoidance Learning/*physiology ; Brain/physiology ; Conditioning, Classical/*physiology ; Food Preferences/*physiology ; Male ; Nutritional Status/*physiology ; Nutritive Value ; Rats ; Rats, Inbred Strains ; Receptors, Amino Acid ; Receptors, Cell Surface/physiology ; Receptors, Serotonin/*physiology ; Serotonin/*physiology ; Taste/*physiology ; }, abstract = {The feeding responses to essential dietary amino acid (AA) disproportion have been useful in nutritional studies. These responses involve first: recognition of the imbalance and second: rejection of the diet, likely via development of a learned aversion. In the rat, we have studied the role of the limiting AA and protein synthesis in the recognition phase by replacement of the limiting AA into a brain area essential for the initial depressed feeding response. We have also reported a reciprocal relationship between serotonin (5HT) activity and intake of imbalanced diets. High doses of the 5HT3 receptor antagonist, ICS 205-930 (ICS; 9 mg/kg IP), restored food intake to 85% or more of control intake. In the present experiments, similar treatment with ICS blocked the classical conditioned taste aversion to a saccharin solution paired with lithium chloride. These results suggest that the increased intake of AA imbalanced diets after ICS may be due to 5HT-mediated blockade of a learned aversion.}, } @article {pmid1653433, year = {1991}, author = {Yamamoto, T and Matsuo, R and Fujimoto, Y and Fukunaga, I and Miyasaka, A and Imoto, T}, title = {Electrophysiological and behavioral studies on the taste of umami substances in the rat.}, journal = {Physiology & behavior}, volume = {49}, number = {5}, pages = {919-925}, doi = {10.1016/0031-9384(91)90204-2}, pmid = {1653433}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Chorda Tympani Nerve/*physiology ; Conditioning, Classical/*physiology ; Discrimination Learning/physiology ; Evoked Potentials, Somatosensory/physiology ; *Glutamates/physiology ; Inosine Monophosphate ; Male ; Neural Inhibition/physiology ; Rats ; Rats, Inbred Strains ; Sodium Channels/physiology ; Sodium Glutamate ; Structure-Activity Relationship ; Taste/*physiology ; Taste Buds/*physiology ; }, abstract = {Electrophysiological and behavioral experiments were performed to reveal taste properties of "umami" substances such as monosodium glutamate (MSG) and disodium inosine monophosphate (IMP) in rats. To eliminate the taste effects of Na ions contained in these umami substances, we dissolved them in 0.01 mM amiloride, which is known to block sodium responses. In the electrophysiological study, taste responses of the whole chorda tympani nerve were recorded. The magnitude of responses to MSG (or IMP) at concentrations below 0.1 M (or 0.01 M) was less than 10% of that to 0.1 M NaCl. On the other hand, the mixtures of MSG and IMP showed responses 2-7 times larger than the arithmetric sum of the responses to each component of the mixtures. A new sweet taste inhibitor (Gymnema sylvestre extract) strongly suppressed neural responses to mixtures of MSG and IMP as well as sucrose, but only weakly or negligibly to individual solutions of these umami substances. In the behavioral study, the brief exposure two-bottle preference test and conditioned taste aversion paradigm were used. MSG was most preferred at 0.3 M (preference ratio = 57%), IMP, at 0.01 M (61%), and both were less preferred or rejected at higher concentrations. In contrast, mixtures of MSG and IMP were more preferred at a broad concentration range (e.g., 82% for 0.1 M MSG + 0.01 M IMP). Aversive conditioning to umami substances was generalized to sucrose, and vice versa, but not to 0.1 M NaCl, 0.01 M HCl, and 0.1 mM quinine hydrochloride.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2064389, year = {1991}, author = {Berridge, KC}, title = {Modulation of taste affect by hunger, caloric satiety, and sensory-specific satiety in the rat.}, journal = {Appetite}, volume = {16}, number = {2}, pages = {103-120}, doi = {10.1016/0195-6663(91)90036-r}, pmid = {2064389}, issn = {0195-6663}, support = {NS 23959/NS/NINDS NIH HHS/United States ; }, mesh = {Affect ; Analysis of Variance ; Animals ; *Energy Intake ; Female ; Hunger/*physiology ; Rats ; Rats, Inbred Strains ; Satiation/*physiology ; Taste/*physiology ; Videotape Recording ; }, abstract = {Human judgements of the pleasure of sweetness have been reported to be modulated by caloric hunger, satiety, and sensory-specific satiety. This study examined both hedonic and aversive facial/somatic reactions to taste in the rat, in order to confirm the relation of hunger and satiety to taste affect, and to assess whether affective modulation depends upon the cognitive factors that mediate human self-interpretation of affect. In the first experiment, the affective reactions of rats to sweet, bittersweet, and water tastes were assessed in five states of caloric hunger or satiety. Caloric satiety reduced positive hedonic reactions below normal levels. Conversely, 48-h food deprivation (but not 24-h deprivation) increased hedonic reactivity. Hedonic enhancement by hunger was not restricted to sweet tastes, but also extended to the palatability of water. Only the hedonic reactions to taste were changed by hunger or satiety: taste aversion was not altered. The second experiment compared the magnitude of affective change during sensory-specific satiety and caloric satiety. Taste-reactivity elicited by sucrose solution or milk was assessed after satiating meals of each of those foods. Sensory-specific satiety further reduced hedonic reactions below the level achieved by caloric satiety alone. Both for caloric satiety and for sensory-specific satiety changes in affect were restricted to positive hedonic reactions: no increase in aversion accompanied the hedonic decrements. These results confirm that taste affect is modulated during caloric hunger, caloric satiety, and sensory-specific satiety. In addition they indicate that the modulation of taste affect by hunger and satiety is confined to the positive limb of the two dimensions (hedonic vs. aversive) of palatability.}, } @article {pmid1652773, year = {1991}, author = {Janz, LJ and Brown, R and Zuo, L and Falk, J and Greenberg, AH and Dyck, DG}, title = {Conditioned taste aversion but not adrenal activity develops to ICV administration of interleukin-1 in rats.}, journal = {Physiology & behavior}, volume = {49}, number = {4}, pages = {691-694}, doi = {10.1016/0031-9384(91)90303-6}, pmid = {1652773}, issn = {0031-9384}, mesh = {Adrenocorticotropic Hormone/blood ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Corticosterone/blood ; Injections, Intraventricular ; Interleukin-1/*pharmacology ; Male ; Pituitary-Adrenal System/*drug effects ; Rats ; Rats, Inbred Strains ; Recombinant Proteins/pharmacology ; Taste/*drug effects ; }, abstract = {In a previous investigation with mice, the paired presentation of either odor or taste cues with the peripheral (IP) administration of the immunoactive peptide interleukin-1 (IL-1) led to the conditioned enhancement of glucocorticoid production. The present study found that an initial central infusion of IL-1 in the presence of saccharin cues produced a robust taste aversion but not a conditioned elevation of either ACTH or corticosterone production. These results indicate that the glucocorticoid response induced by centrally administered IL-1 in rats is independent of the behaviorally aversive properties of this cytokine which are conditionable. The differential effects of IP versus ICV administration of IL-1 on glucocorticoid conditioning requires a clearer specification of the respective signaling mechanisms and pathways activated by these two routes of administration.}, } @article {pmid2068188, year = {1991}, author = {Brockwell, NT and Eikelboom, R and Beninger, RJ}, title = {Caffeine-induced place and taste conditioning: production of dose-dependent preference and aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {38}, number = {3}, pages = {513-517}, doi = {10.1016/0091-3057(91)90006-n}, pmid = {2068188}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Caffeine/*pharmacology ; Choice Behavior/*drug effects ; Conditioning, Classical/*drug effects ; Male ; Rats ; Rats, Inbred Strains ; Reward ; Taste ; }, abstract = {Although caffeine may be the most widely used behaviorally active drug, few studies have examined its rewarding properties. In the present study, the designs of place-conditioning and taste-conditioning paradigms were combined in a single experiment to provide two independent measures of drug reward. During 3 preconditioning sessions, undrugged rats received access to 2 distinctive chambers connected by a small tunnel. During the 8-session conditioning phase, groups were given home cage access to either a sweet or salty solution, administered caffeine (0.3, 1.0, 3.0, 10.0, 30.0 mg/kg IP; 30.0 mg/kg SC), and confined to one of the chambers. On alternate sessions, rats were given home cage access to the remaining solution, injected with the vehicle, and confined to the opposite chamber. On test sessions 1 and 2, undrugged animals were given home cage access to one of the flavored solutions and water, and then allowed access to both conditioning chambers. On test session 3, rats were given access to both flavored solutions, injected with the drug used during conditioning, and again allowed access to both chambers. Caffeine (3.0 mg/kg) produced a significant place preference. The highest dose (30.0 mg/kg IP and SC) produced significant place and taste aversions. A control group given (+)-amphetamine illustrated a significant place preference and taste aversion as expected. Thus caffeine appeared to produce a dose-dependent biphasic effect; a lower dose was rewarding, whereas higher doses produced aversions to environmental stimuli associated with the drug.}, } @article {pmid2064756, year = {1991}, author = {Amit, Z and Gill, K and Ng Cheong Ton, JM}, title = {Attenuation of voluntary ethanol consumption by dopamine-beta-hydroxylase inhibition (FLA-57): mediated by changes in aversion, reinforcement or both.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {8}, number = {2}, pages = {79-85}, doi = {10.1016/0741-8329(91)91313-q}, pmid = {2064756}, issn = {0741-8329}, mesh = {Alcohol Deterrents ; Alcohol Drinking/*drug therapy ; Analysis of Variance ; Animals ; Azepines/*pharmacology ; Conditioning, Psychological/drug effects ; Dopamine beta-Hydroxylase/*antagonists & inhibitors ; Ethanol ; Male ; Quinine ; Rats ; Saccharin ; Taste/drug effects ; }, abstract = {The dopamine-beta-hydroxylase inhibitor, FLA-57, was reported by several investigators to reduce voluntary ethanol consumption in rats. The nature of the effect of FLA-57 on this behavior had been attributed to its involvement in both the mediation of positive reinforcing and aversive processes. In the present study, the capacity of FLA-57 to induce a conditioned taste aversion (CTA) in both a forward and a "nominally backward conditioning" paradigms was investigated. This was done in an attempt to assess the possible contribution of a FLA-57-induced CTA to the previously observed reduction in ethanol intake in several drinking studies. Furthermore, the ability of FLA-57 to induce a CTA in a nonnovel situation, where the taste of the presented solution (ethanol or saccharin) was familiar to the animals, was also assessed. The inclusion of these specific conditions was necessitated by the attempt to create conditions similar to those prevalent in drinking studies. We found that FLA-57, in both conditioning paradigms, induced a significant CTA. Animals, naive and experienced with the taste of ethanol or saccharin, exhibited a CTA following the administration of FLA-57. However, the magnitude and rate of extinction of the observed CTAs did not resemble those observed in studies on the effects of FLA-57 on ethanol intake. The results of this study suggest that while it is possible that FLA-57 exerts its effect on ethanol intake, at least in part, through an aversive mechanism, such a mechanism is unlikely to be the exclusive process through which ethanol ingestion is attenuated.}, } @article {pmid2059185, year = {1991}, author = {Arnedo, M and Gallo, M and Agüero, A and Puerto, A}, title = {Differential effects of subdiaphragmatic vagotomy on NaCl-induced aversion learning.}, journal = {Behavioral and neural biology}, volume = {55}, number = {2}, pages = {141-153}, doi = {10.1016/0163-1047(91)80135-2}, pmid = {2059185}, issn = {0163-1047}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Chemoreceptor Cells/*physiology ; Conditioning, Classical/*physiology ; Digestive System/*innervation ; Discrimination Learning/physiology ; Male ; Mental Recall/physiology ; Rats ; Rats, Inbred Strains ; Retention, Psychology/physiology ; Saline Solution, Hypertonic ; Taste/*physiology ; Vagus Nerve/*physiology ; }, abstract = {The vagus nerve has been proposed in numerous studies as one of the peripheral mechanisms involved in drug-induced taste aversion learning, although available data have been controversial. The differential results obtained in the present series of experiments with vagotomy and NaCl-induced short-term and long-term aversion learning suggest that the vagal system plays a decisive role in tasks requiring the rapid detection of an aversive substance in the gastrointestinal tract (short-term tasks). In contrast, this mechanism appears to be unnecessary in long-term tasks, where learning may be mediated by alternative slower-acting peripheral mechanisms such as the humoral system.}, } @article {pmid1647761, year = {1991}, author = {Fernández-Ruiz, J and Escobar, ML and Piña, AL and Diaz-Cintra, S and Cintra-McGlone, FL and Bermúdez-Rattoni, F}, title = {Time-dependent recovery of taste aversion learning by fetal brain transplants in gustatory neocortex-lesioned rats.}, journal = {Behavioral and neural biology}, volume = {55}, number = {2}, pages = {179-193}, doi = {10.1016/0163-1047(91)80138-5}, pmid = {1647761}, issn = {0163-1047}, mesh = {Acetylcholinesterase/biosynthesis ; Animals ; Avoidance Learning/*physiology ; Brain Tissue Transplantation/physiology ; Cerebral Cortex/embryology/*physiology/transplantation ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Fetal Tissue Transplantation/physiology ; Lithium/toxicity ; Lithium Chloride ; Nerve Regeneration/*physiology ; Neuronal Plasticity/*physiology ; Neurons/physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {We recently showed that fetal brain transplants produced a significant recovery in the ability of gustatory neocortex-lesioned rats to learn a conditioned taste aversion. In this report we assessed the capability of gustatory neocortex fetal brain transplants to produce behavioral recovery at different times. Four groups of male Wistar rats showing disrupted taste aversions due to gustatory neocortex lesions were studied. The lesioned animals received fetal cortical grafts, obtained from 16-day-old fetuses, and were retrained in the behavioral procedure after 15, 30, 45, or 60 days postgraft. Behavioral results showed a very good functional recuperation at 60 days, slight recovery at 45 and 30 days, and a poor recovery at 15 days postgraft. Results with HRP histochemistry revealed that at 30, 45, and 60 days postgrafting there were increased connections with the ventromedial nucleus of the thalamus and with the amygdala. At 15 days postgrafting there was an absence of HRP-labeled cells. In addition, behavioral recovery was correlated with increased acetylcholinesterase activity, detected histochemically, and with morphological neuronal maturation, revealed by Golgi staining. These results suggest that morphological maturity and reconnectivity between grafts and host tissue are important for behavioral recovery in gustatory neocortex-lesioned rats.}, } @article {pmid2025385, year = {1991}, author = {Sengstake, CB and Chambers, KC}, title = {Sensitivity of male, female, and androgenized female rats to testosterone during extinction of a conditioned taste aversion.}, journal = {Behavioral neuroscience}, volume = {105}, number = {1}, pages = {120-125}, doi = {10.1037//0735-7044.105.1.120}, pmid = {2025385}, issn = {0735-7044}, support = {HD 20970/HD/NICHD NIH HHS/United States ; RR-00163/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Arousal/*physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Extinction, Psychological/*physiology ; Female ; Mental Recall/physiology ; Rats ; Rats, Inbred Strains ; Sex Differentiation/physiology ; Sexual Behavior, Animal/*physiology ; Taste/*physiology ; Testosterone/*physiology ; }, abstract = {Experiment 1 tested the hypothesis that male and female rats differ in the amount of testosterone (T) required to prolong extinction of a conditioned taste aversion. Gonadectomized male and female rats were implanted with empty or 30-, 60-, or 120-mm T-filled capsules. The males had slower extinction rates than females when both were implanted with 30-mm and 60-mm capsules but not when implanted with 120-mm capsules. The dimorphic sensitivity was not due to differences in plasma T levels: the levels for males and females were not different. Experiment 2 tested the hypothesis that the presence of T during the perinatal period results in a greater sensitivity to T in adulthood. Females exposed to T during the perinatal period showed prolonged extinction when given a 30-mm T-filled capsule as an adult, whereas unexposed females did not. These results support the hypothesis that the amount of T required to activate the prolonged extinction in an adult depends on perinatal exposure to T.}, } @article {pmid2029341, year = {1991}, author = {Gallo, M and Arnedo, M and Agüero, A and Puerto, A}, title = {Participation of the area postrema in learned aversions induced by body rotation.}, journal = {Behavioural brain research}, volume = {42}, number = {1}, pages = {13-23}, doi = {10.1016/s0166-4328(05)80035-x}, pmid = {2029341}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Cerebral Ventricles/anatomy & histology/*physiology ; Male ; Rats ; Rats, Inbred Strains ; Rotation ; Stereotaxic Techniques ; Taste/*physiology ; Vagotomy ; Vomiting/physiopathology ; }, abstract = {Existing data on the effects of area postrema (AP) lesions on body rotation-induced emesis as well as on the participation of this zone in the acquisition of taste aversion learning (TAL) with other emetic agents suggest a possible role for the AP in learned aversions induced by body rotation. Nevertheless, earlier studies have shown that AP lesions do not prevent learned aversions induced by body rotation. The present experiments were performed in male Wistar rats in order to explore the effects of AP lesions on body rotation-induced flavor aversions as a function of the paradigm employed. Flavor aversions were induced by 30 min of circular body rotation (90 r.p.m.) using two different paradigms: a standard one including one trial learning, delay and single stimulus test and a three trials paradigm (with and without interstimulus delay) including both single stimulus test and choice test. AP lesions disrupt acquisition provided that the paradigm used includes interstimulus delay, i.e. when body rotation is applied 15 min after flavor intake. However, the AP seems to play no essential role when body rotation is applied immediately after flavor intake in a three-trial paradigm, as no effects were observed following AP lesions. In addition, subdiaphragmatic vagotomy plus simultaneous AP lesions leads to no interference in the acquisition of learned aversions induced by body rotation applied immediately after intake. It is concluded that body rotation may trigger a variety of aversive effects capable of inducing learned aversions, each apparently involving independent neural systems.}, } @article {pmid2015509, year = {1991}, author = {Adachi, A and Kobashi, M and Miyoshi, N and Tsukamoto, G}, title = {Chemosensitive neurons in the area postrema of the rat and their possible functions.}, journal = {Brain research bulletin}, volume = {26}, number = {1}, pages = {137-140}, doi = {10.1016/0361-9230(91)90198-s}, pmid = {2015509}, issn = {0361-9230}, mesh = {Animals ; Cerebral Ventricles/cytology/*physiology ; Chemoreceptor Cells/*physiology ; Feeding Behavior/physiology ; Glucose/physiology ; Nausea/*physiopathology ; Neurons/*physiology ; Osmotic Pressure ; Rats ; Rats, Inbred Strains ; }, abstract = {The present study is an attempt to demonstrate chemosensitive neurons within the area postrema (AP) electrophysiologically. Three types of chemosensitive neurons were identified: 1) glucose-responsive neurons that may participate in control of blood glucose and satiation, 2) sodium (osmotic pressure)-responsive neurons that may contribute to control of sodium and water balance of the body fluid and may be involved in salt appetite, 3) nausea-related neurons which respond to excess distension of stomach and LiCl as well. They may play a role in formation of conditioned taste aversion.}, } @article {pmid1924647, year = {1991}, author = {Mucha, RF}, title = {What is learned during opiate withdrawal conditioning? Evidence for a cue avoidance model.}, journal = {Psychopharmacology}, volume = {104}, number = {3}, pages = {391-396}, pmid = {1924647}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Behavior, Animal/drug effects ; Choice Behavior/drug effects ; *Cues ; Drug Implants ; Male ; Morphine/pharmacology ; Motivation ; Naloxone/pharmacology ; Rats ; Rats, Inbred Strains ; Substance Withdrawal Syndrome/*psychology ; Taste/drug effects ; }, abstract = {How conditioned opiate withdrawal gives rise to avoidance behaviour was examined using a defensive burying procedure in rats made dependent with a morphine pellet. The subjects underwent withdrawal precipitated by naloxone (0.1 mg/kg, SC) on two or three occasions in a box containing only a small object. When exposed to the object in the presence of sawdust one or more days later, the subjects avoided contact and buried this object, i.e., pushed and piled the sawdust against it. The behaviour was seen only when withdrawal had been paired with the object, which was the case even with a choice of objects on the test. Approach but no burying was seen in nondependent animals when the object was paired with 1 mg/kg morphine. Burying, therefore, was concluded to be a defensive response elicited in rats by an object specifically paired with precipitated opiate withdrawal. Consideration of burying and other defensive responses reported to be elicited by cues of withdrawal (conditioned place and taste aversion, and suppression), with respect to the behavioural demands of these responses and the test conditions needed to see them, suggested that a goal of avoidance may be a primary event encoded in a withdrawal cue, as is known for predictors of nonpharmacological noxious events (e.g., shock).}, } @article {pmid1876064, year = {1990}, author = {Villaneuva, HF and James, JR and Arezo, S and Rosecrans, JA}, title = {Withdrawal from nicotine fails to produce a conditioned taste aversion to saccharine in rats and mice.}, journal = {NIDA research monograph}, volume = {105}, number = {}, pages = {433-434}, pmid = {1876064}, issn = {1046-9516}, support = {DA04002-04/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Male ; Mice ; Mice, Inbred ICR ; Morphine Dependence/psychology ; Nicotine/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Substance Withdrawal Syndrome/*psychology ; }, } @article {pmid1771221, year = {1991}, author = {Stewart, RB and McBride, WJ and Lumeng, L and Li, TK and Murphy, JM}, title = {Chronic alcohol consumption in alcohol-preferring P rats attenuates subsequent conditioned taste aversion produced by ethanol injections.}, journal = {Psychopharmacology}, volume = {105}, number = {4}, pages = {530-534}, pmid = {1771221}, issn = {0033-3158}, support = {AA-03243/AA/NIAAA NIH HHS/United States ; AA-07462/AA/NIAAA NIH HHS/United States ; AA-07611/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/physiopathology ; Alcoholism/*physiopathology ; Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/physiology ; Drug Tolerance ; Ethanol/blood/*pharmacology ; Female ; Rats ; Taste/physiology ; }, abstract = {Rats of the P line were tested for the development of tolerance to the aversive effects of ethanol during 33 days of continuous availability of food, water and a 10% (v/v) ethanol solution. Beginning on the day following the removal of ethanol, five daily conditioned taste aversion (CTA) trials were administered to the ethanol-drinking P rats and an ethanol-naive control group. The CTA trials consisted of a 20-min access to a Polycose solution, followed by IP injection of saline, 0.5, 1.0, or 1.5 g ethanol/kg. The ethanol-drinking rats developed a preference for the Polycose solution when it was paired with 0.5 g ethanol injections, but the control rats did not. Both control and ethanol groups had similar CTAs at the 1.5 g dose. However, at the 1.0 g dose, the ethanol group had an attenuated CTA compared with the water control group. The results suggest that P rats develop tolerance to aversive effects of ethanol during chronic drinking. This tolerance could contribute to the high ethanol intake in these selectively-bred rats.}, } @article {pmid1741730, year = {1991}, author = {Elkins, RL}, title = {An appraisal of chemical aversion (emetic therapy) approaches to alcoholism treatment.}, journal = {Behaviour research and therapy}, volume = {29}, number = {5}, pages = {387-413}, doi = {10.1016/0005-7967(91)90123-k}, pmid = {1741730}, issn = {0005-7967}, support = {1 R01 DA05121-01A1/DA/NIDA NIH HHS/United States ; AA06465-02/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholism/psychology/*rehabilitation ; Aversive Therapy/*methods ; Conditioning, Classical/drug effects ; Emetics/*therapeutic use ; Follow-Up Studies ; Humans ; }, abstract = {More than 35,000 alcoholics have received chemical aversion (emetic therapy) in at least 75 settings worldwide since the 1930s. This consummatory aversion (CA) treatment, which pairs ethanol ingestion with emetically induced nausea, incorporates the highly efficient variety of learning known as taste aversion (TA) conditioning. The CA literature indicates that emetic therapy should induce conditioned alcohol aversions in many alcoholics. Such aversions have been widely reported by clinicians and have been confirmed by recent psychophysiological evidence. Long standing evidence of treatment effectiveness is found in the results of private hospitals which have consistently produced 1-yr abstinence rates approximating 60%. Diminished alcohol craving is a frequently reported benefit. Few experimental evaluations have been completed, as is generally the case for all alcoholism treatments, but those which used methodologically sound temporal parameters during conditioning have supported the clinical efficacy of emetic therapy. The clear need for more definitive research notwithstanding, there are compelling indications that emetic therapy is a useful component of multimodal treatment within certain alcoholic populations. However, its availability is severely limited. Many alcoholics could probably benefit from expanded treatment availability. The time is ripe for a reevaluation of resistances to the clinical use of emetic therapy alcoholism treatment.}, } @article {pmid1676531, year = {1991}, author = {Goudie, AJ and Leathley, MJ}, title = {Evaluation of the dependence potential of the selective 5-H1A agonist ipsapirone in rats and of its effects on benzodiazepine withdrawal.}, journal = {Psychopharmacology}, volume = {103}, number = {4}, pages = {529-537}, pmid = {1676531}, issn = {0033-3158}, mesh = {Animals ; Anti-Anxiety Agents/*pharmacology ; Benzodiazepines ; Body Weight/drug effects ; Feeding Behavior/drug effects ; Male ; Pyrimidines/*pharmacology ; Rats ; Rats, Inbred Strains ; Substance Withdrawal Syndrome/*psychology ; }, abstract = {Two initial studies investigated: i) the effects of withdrawal from ipsapirone [a putative non-benzodiazepine (BZ) anxiolytic] and chlordiazepoxide (CDP); and ii) effects of ipsapirone in animals withdrawn from CDP. Rats were injected b.i.d. for 21 days with saline, ipsapirone or CDP at doses up to 40 mg/kg/injection. Subsequently, controls received the treatment administered previously, other subjects received saline during withdrawal from ipsapirone or CDP. Further subjects received ipsapirone (3, 10 or 30 mg/kg b.i.d.) during CDP withdrawal. Withdrawal indices recorded were body weight and food intake. Withdrawal signs were absent after ipsapirone treatment but present after CDP treatment, when food intake and bodyweight measures fell and then recovered. At the high dose of 30 mg/kg (b.i.d.) ipsapirone potentiated CDP withdrawal signs. Potentiation of withdrawal was not seen in animals treated with ipsapirone at lower doses (3 and 10 mg/kg, b.i.d.). In a subsequent study we found that ipsapirone conditioned a taste aversion, a possible index of drug-induced "malaise", at doses as low as 7.5 mg/kg. Therefore a possible explanation for the potentiation of BZ withdrawal in subjects treated with high doses of ipsapirone was that drug-induced "malaise" reduced food intake and body weight, rather than ipsapirone causing true potentiation of BZ withdrawal. However, in a further study we showed that the ipsapirone treatment regime which potentiated BZ withdrawal did not significantly reduce food intake or body weight, suggesting that high doses of ipsapirone potentiate BZ withdrawal by a mechanism that does not simply involve "malaise".(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid1672462, year = {1991}, author = {Aragon, CM and Abitbol, M and Amit, Z}, title = {Ethanol-induced CTA mediated by acetaldehyde through central catecholamine activity.}, journal = {Psychopharmacology}, volume = {103}, number = {1}, pages = {74-77}, pmid = {1672462}, issn = {0033-3158}, mesh = {Acetaldehyde/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Brain/drug effects/*physiology ; Catecholamines/*physiology ; Ethanol/*pharmacology ; Male ; Methyltyrosines/pharmacology ; Rats ; Saccharin/pharmacology ; Taste/*drug effects ; Tyrosine 3-Monooxygenase/antagonists & inhibitors ; alpha-Methyltyrosine ; }, abstract = {The possible involvement of catecholamines (CA) in the mediation of acetaldehyde's conditioned taste aversion (CTA) was examined by testing the effects of alpha-methyl-para-tyrosine (AMPT, a tyrosine hydroxylase inhibitor) on the CTAs produced by acetaldehyde. AMPT blocked the acquisition of the CTA normally produced by a low dose of acetaldehyde (0.2 g/kg), but had no significant effect on CTA produced by a high dose of acetaldehyde (0.3 g/kg). In a second study, acetaldehyde's role in the CTA produced by ethanol was investigated using the pre-exposure conditioned taste aversion paradigm. Pre-exposure to acetaldehyde (both doses) blocked the ethanol CTAs but when pre-exposure with acetaldehyde was coupled with AMPT, only the larger dose of acetaldehyde blocked the ethanol aversion. These results suggest that while the CTA to the low dose of acetaldehyde may be primarily central and catecholamine-mediated, the mechanism underlying the high dose CTA is probably peripheral and emetic in nature. These findings support the conclusion that acetaldehyde may be mediating many of the actions of ethanol.}, } @article {pmid2178348, year = {1990}, author = {Ivanova, SF and Bures, J}, title = {Conditioned taste aversion is disrupted by prolonged retrograde effects of intracerebral injection of tetrodotoxin in rats.}, journal = {Behavioral neuroscience}, volume = {104}, number = {6}, pages = {948-954}, doi = {10.1037//0735-7044.104.6.948}, pmid = {2178348}, issn = {0735-7044}, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain/*drug effects ; Chlorides/toxicity ; Conditioning, Classical/*drug effects ; Drinking/drug effects ; Injections, Intraventricular ; Lithium/toxicity ; Lithium Chloride ; Male ; Memory, Short-Term/drug effects ; Mental Recall/*drug effects ; Overlearning/drug effects ; Rats ; Taste/*drug effects ; Taste Threshold/drug effects ; Tetrodotoxin/*pharmacology ; }, abstract = {Acquisition of conditioned taste aversion (CTA) is disrupted when 10 ng tetrodotoxin (TTX) is injected into both parabrachial nuclei of rats immediately after saccharin drinking and before LiCl poisoning (Ivanova & Bures, in press). Further analysis of this finding showed that parabrachial TTX injection (a) elicited retrograde amnesia also when applied 1, 2, or 4 days but not 8 days after CTA acquisition; (b) did not abolish CTA produced by 2 or 3 saccharin-LiCl pairings; (c) did not cause persistent increase of quinine threshold; and (d) elicited anterograde CTA amnesia when applied 1 but not 2, 4, or 8 days before CTA acquisition. TTX-induced amnesia is not due to persistent gustatory agnosia but rather to disruption of the protracted consolidation of the permanent CTA engram by prolonged cessation of impulse activity in the information storing network.}, } @article {pmid2087383, year = {1990}, author = {June, HL and Hicks, LH and Lewis, MJ and Ross, S}, title = {Denatonium saccharide as an aversive stimulus in a conditioned taste aversion paradigm.}, journal = {Perceptual and motor skills}, volume = {71}, number = {3 Pt 2}, pages = {1299-1307}, doi = {10.2466/pms.1990.71.3f.1299}, pmid = {2087383}, issn = {0031-5125}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Classical ; Drinking ; Male ; *Quaternary Ammonium Compounds ; Rats ; Rats, Inbred Strains ; *Taste ; Taste Threshold ; }, abstract = {The ability of denatonium saccharide (DS) to function as an aversive stimulus for the rat was studied in a conditioned taste-aversion paradigm in two experiments. Exp. 1 assessed the effects of DS during a 30-min. access period when only a saccharin solution was available. Exp. 2 assessed the effects of DS during both a 10- and a 30-min. access period when a saccharin solution and free water were available. The results showed that DS did not attenuate saccharin consumption reliably over all test days. The effect was most apparent during the 10-min. interval when free water was available. These results, together with previous reports, suggest that DS appears to function as a weak aversive stimulus in the rat.}, } @article {pmid1981616, year = {1990}, author = {Woolfson, A and Rothschild, M}, title = {Speculating about pyrazines.}, journal = {Proceedings. Biological sciences}, volume = {242}, number = {1304}, pages = {113-119}, doi = {10.1098/rspb.1990.0113}, pmid = {1981616}, issn = {0962-8452}, mesh = {Animals ; Immune System/physiology ; Learning/physiology ; *Odorants ; Pheromones/physiology ; Pyrazines/*metabolism ; }, abstract = {Of the various types of alerting signals found in nature, odours are the least well understood. The worldwide distribution of pyrazines in plants, insects, terrestrial vertebrates, marine organisms, fungi and bacteria suggests that they are of special significance. We speculate that these molecules served as natural points of convergence in the evolution of widespread alerting signals, which are used for differing but related intraspecific purposes by various species. In aposematic, self-advertising toxic insects and their mimics, for example, pyrazines function as additional warning signals; preliminary data indicates that their odour can potentiate taste aversion learning in rats and the associative learning of immune suppression in mice. The latter suggests that in addition to their alerting properties, pyrazine odours may act as ectohormones which interact with predator physiology.}, } @article {pmid2082364, year = {1990}, author = {Ganesan, R and Simpkins, JW}, title = {The role of conditioned taste aversion in the suppression of food intake by estradiol.}, journal = {Physiology & behavior}, volume = {48}, number = {5}, pages = {647-652}, doi = {10.1016/0031-9384(90)90205-i}, pmid = {2082364}, issn = {0031-9384}, support = {HD 22540/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain/drug effects ; Conditioning, Classical/*drug effects ; Drug Carriers ; Estradiol/*pharmacology ; Feeding Behavior/*drug effects ; Female ; Injections, Intravenous ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {In three experiments, ovariectomized rats were given a familiar or novel diet prior to treatment with a brain-enhanced estradiol-chemical delivery system (E2-CDS, 1 mg/kg). Experiment 1 showed that food intake was suppressed in subjects receiving either diet, but animals given a novel diet initially showed a profound anorexia which eventually recovered to the moderate suppression of animals given the familiar diet. In Experiment 2, rats showed an aversion to a novel diet paired with the E2-CDS in a two-choice preference test given on Day 2 after the injection, indicating that the initial large reduction in intake was mediated by a conditioned taste aversion. However, no aversion was observed seven days after the E2-CDS, suggesting that the residual intake suppression was mediated by unconditioned aversion or appetite suppression. Experiment 3 showed that lengthening the postovariectomy time resulted in a taste aversion that persisted for a longer duration.}, } @article {pmid2078162, year = {1990}, author = {Hunt, PS and Molina, JC and Spear, LP and Spear, NE}, title = {Ethanol-mediated taste aversions and state-dependency in preweanling (16-day-old) rats.}, journal = {Behavioral and neural biology}, volume = {54}, number = {3}, pages = {300-322}, doi = {10.1016/0163-1047(90)90650-u}, pmid = {2078162}, issn = {0163-1047}, support = {1 R01 MH35219/MH/NIMH NIH HHS/United States ; 5 R01 AA06634/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Mental Recall/drug effects ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Weaning ; }, abstract = {Requirements for conditioning of an ethanol-mediated taste aversion in 16-day-old rat pups were examined. Experiment 1 demonstrated that preweanling rats are capable of acquiring, in two trials, an aversion to a 15% sucrose solution when followed by intragastric intubation of a 1.2 g/kg dose of 17% v/v ethanol, but not when followed by a 0.4 g/kg dose. Comparison was with control animals given sucrose followed by an equivalent volume isocaloric Half and Half. When the 0.4 g/kg dose of ethanol preceded sucrose presentation by 30 min (Experiment 2), the aversion was learned, suggesting that the effective delay between the sucrose and the critical consequences of the ethanol had been too long with the former procedure. Expression of the sucrose aversion required, however, the reinstatement of the context of intoxication--state-dependent retention. Finally, the results of Experiment 3B indicated that, in addition to the association between the sucrose and the aversive consequences of alcohol intoxication, the orosensory cues resulting from alcohol's direct elimination, via such processes as respiration and salivation, became associated with the appetitive properties of the sucrose. This was evidenced by a conditioned increase in preference for ethanol odor. Possible age-related differences in the ability to associate stimuli with alcohol's unconditioned consequences, and in state dependency are discussed.}, } @article {pmid1980150, year = {1990}, author = {Kimble, DP}, title = {Functional effects of neural grafting in the mammalian central nervous system.}, journal = {Psychological bulletin}, volume = {108}, number = {3}, pages = {462-479}, doi = {10.1037/0033-2909.108.3.462}, pmid = {1980150}, issn = {0033-2909}, mesh = {Animals ; Brain/*physiology ; Brain Tissue Transplantation/*physiology ; Fetal Tissue Transplantation/physiology ; Nerve Regeneration/*physiology ; Neurotransmitter Agents/physiology ; }, abstract = {Grafts of fetal and nonfetal brain tissues have been successfully implanted into the mammalian central nervous system (CNS). The functional effects of neural grafting in the CNS of rodents and nonhuman primates in a variety of situations are reviewed. Research areas discussed included the effects of dopamine-rich grafts in animal models of Parkinson's disease and acetylcholine-rich grafts in animals with lesions of the cholinergic pathways to the neocortex and hippocampus. Graft effects also are examined in aged animals and genetic mutants. In addition, the effects of neural grafts on circadian rhythmicity, reproductive functions, and conditioned taste aversion are discussed. The beneficial functional effects of neural grafts and the possible mechanisms and implications for these effects are discussed, including the possibility that the CNS exhibits a regional biochemical specificity that influences the outcome of neural graft procedures.}, } @article {pmid1965042, year = {1990}, author = {DeHaven-Hudkins, DL and Brostrom, PA and Allen, JT and Lesko, LJ and Ferkany, JW and Kaplita, PV and Mavunkel, BJ and Rzeszotarski, WJ and Steranka, LR}, title = {Pharmacologic profile of NPC 168 (naltrexone phenyl oxime), a novel compound with activity at opioid receptors.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {37}, number = {3}, pages = {497-504}, doi = {10.1016/0091-3057(90)90019-e}, pmid = {1965042}, issn = {0091-3057}, support = {1 R43DA04258-01/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Binding, Competitive/drug effects ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; Enkephalin, Leucine-2-Alanine/metabolism ; Enkephalins/metabolism ; Food Deprivation ; Guinea Pigs ; Injections, Intraventricular ; Male ; Mice ; Morphine/pharmacology ; Naltrexone/*analogs & derivatives/*pharmacology/toxicity ; *Narcotic Antagonists/pharmacology ; Rats ; Rats, Inbred Strains ; Reaction Time/drug effects ; Reinforcement Schedule ; }, abstract = {NPC 168 (naltrexone phenyl oxime) was synthesized as a novel opioid antagonist and evaluated in several in vitro and in vivo assays. NPC 168 inhibited binding to the mu, delta and kappa subtypes of the opioid receptor with nanomolar potencies. The potency of NPC 168 to antagonize morphine-induced analgesia was slightly less than that of naltrexone and nalmefene following either intraperitoneal (ED50 = 0.07 mg/kg) or oral (ED50 = 0.82 mg/kg) administration. The duration of action of NPC 168 was approximately 8 hr following subcutaneous administration, compared to 4 hr for nalmefene, to antagonize oxymorphonazine-induced analgesia. The long duration of action of NPC 168 was substantiated by pharmacokinetic data that demonstrated rapid uptake and slow clearance of NPC 168 from brain. NPC 168 (5, 10 and 20 mg/kg) also inhibited cumulative 6-hr food intake in rats that were deprived of food for 24 hr, but chronic administration of this compound to rats over a three-week period resulted in a marginal reduction in cumulative body weight gain. NPC 168 at doses of up to 10 mg/kg did not produce a conditioned taste aversion. However, NPC 168 was slightly more toxic than either naltrexone or nalmefene when administered parenterally, and as toxic as nalmefene when administered by the oral route. These data demonstrate that NPC 168 is a novel opioid antagonist with a longer duration of action than either naltrexone or nalmefene.}, } @article {pmid1964504, year = {1990}, author = {Kling, JW and Yarita, M and Yamamoto, T and Matsumiya, Y}, title = {Memory for conditioned taste aversions is diminished by transcranial magnetic stimulation.}, journal = {Physiology & behavior}, volume = {48}, number = {5}, pages = {713-717}, doi = {10.1016/0031-9384(90)90216-q}, pmid = {1964504}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Drinking/physiology ; *Electromagnetic Fields ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/*physiology ; Rats ; Taste/*physiology ; }, abstract = {Rats were allowed to drink distinctively flavored water and later received an IP injection of LiCl. In Phase I, between drinking and the onset of the mild malaise, Experimental Group rats received stimulations of the head and Controls received equivalent stimulations of the back. Later, when the flavor was again presented. Experimentals drank 10-15% more, indicating that they had forgotten to some extent that the flavor was associated with illness. In Phase II, the procedure was repeated with a different distinctive flavor. Again, the Experimentals drank more on the test day. In Phase III, all rats received stimulations of the back between tasting and illness. Experimentals and Controls were not different on the test day, indicating that 100 prior head stimulations did not interfere with the establishment of a new taste aversion. Histological examinations revealed no gross morphopathology. We conclude that 50 brief pulse transcranial magnetic stimulations may cause a retrograde memory disruption, but we find no evidence for an anterograde memory effect or for structural changes.}, } @article {pmid2244980, year = {1990}, author = {Klosterhalfen, S and Klosterhalfen, W}, title = {Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats.}, journal = {Behavioral neuroscience}, volume = {104}, number = {5}, pages = {716-724}, doi = {10.1037//0735-7044.104.5.716}, pmid = {2244980}, issn = {0735-7044}, mesh = {Animals ; Arousal/drug effects ; Arthritis, Experimental/*immunology ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cyclosporins/*pharmacology ; Drinking/drug effects ; Female ; Freund's Adjuvant/immunology ; Immune Tolerance/drug effects ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {In 2 experiments, the development of adjuvant arthritis (an experimental autoimmune disease) was inhibited by exposing rats to a flavored solution that had previously been paired with injections of cyclosporine (an immunodepressive drug) compared with rats with the same history but exposed to a flavored solution that had previously not been paired with drug injections. In contrast to earlier experiments on conditioned cyclophosphamide effects, rats did not avoid the taste that had previously been paired with drug administration. Thus, conditioned immunopharmacologic effects were not confounded with taste aversion. These observations are interpreted as reflecting an associative learning process that affected the development of an autoimmune disease.}, } @article {pmid2244978, year = {1990}, author = {Revusky, S and Reilly, S}, title = {When pentobarbital is the conditioned stimulus and amphetamine is the unconditioned stimulus, conditioning depends on the type of conditioned response.}, journal = {Behavioral neuroscience}, volume = {104}, number = {5}, pages = {693-703}, doi = {10.1037//0735-7044.104.5.693}, pmid = {2244978}, issn = {0735-7044}, mesh = {Animals ; Arousal/*drug effects ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dextroamphetamine/*pharmacology ; Dose-Response Relationship, Drug ; Heart Rate/drug effects ; Male ; Pentobarbital/*pharmacology ; Rats ; Rats, Inbred Strains ; Retention, Psychology/drug effects ; Social Environment ; Taste/*drug effects ; }, abstract = {Injections of drugs into rats were used as conditioned stimuli (CSs) and as unconditioned stimuli (USs). With heart rate (HR) conditioning, the pentobarbital CS produces a higher HR than under control conditions. With avfail (aversion failure) conditioning, the pentobarbital CS loses much of its capacity to induce a conditioned taste aversion. HR conditioning was obtained with forward delays of up to 30 min and backward delays of up to 270 min, where the delays are defined by the interinjection interval. Avfail was obtained with forward delays of up to 270 min but not with backward delays. Neither HR conditioning nor avfail were context specific but could be demonstrated in a test apparatus after pairings that occurred in the home cage. This indicated that the external environment was not an important part of the effective stimulus complex. When HR conditioning was obtained, its latency and duration was not related to the delay between the CS and US injections or whether they were forward or backward.}, } @article {pmid2173934, year = {1990}, author = {Hill, DL and Formaker, BK and White, KS}, title = {Perceptual characteristics of the amiloride-suppressed sodium chloride taste response in the rat.}, journal = {Behavioral neuroscience}, volume = {104}, number = {5}, pages = {734-741}, doi = {10.1037//0735-7044.104.5.734}, pmid = {2173934}, issn = {0735-7044}, support = {DC00025/DC/NIDCD NIH HHS/United States ; DC00407/DC/NIDCD NIH HHS/United States ; }, mesh = {Amiloride/*pharmacology ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Chorda Tympani Nerve/drug effects ; Conditioning, Classical/*drug effects ; Generalization, Stimulus/drug effects ; Lithium/pharmacology ; Lithium Chloride ; Rats ; Rats, Inbred Strains ; Signal Transduction/drug effects ; Sodium, Dietary/*administration & dosage ; Taste/*drug effects ; }, abstract = {The contribution of amiloride-sensitive membrane components to the perception of NaCl taste was assessed by using a conditioned taste aversion procedure. Eight independent groups of adult rats were conditioned to avoid either 0.1M NaCl, 0.5M NaCl; 0.1M NH4Cl, or 1.0M sucrose while their tongues were exposed either to water or to the sodium transport blocker amiloride hydrochloride. In contrast to rats exposed to water during conditioning, rats exposed to amiloride were unable to acquire a conditioned taste aversion to 0.1M NaCl. Differences in the acquisition of taste aversions between the amiloride- and nonamiloride-treated groups were not apparent when the conditioned stimulus (CS) was 0.5M NaCl, 0.1M NH4Cl, or 1.0M sucrose. Although the magnitude of the 0.5M NaCl aversion was similar between amiloride- and non-amiloride-treated rats, the perceptual characteristics of the CS differed between groups. Analyses of stimulus generalization gradients revealed that amiloride-treated rats generally avoided all monochloride salts after conditioning to 0.5M NaCl but not nonsodium salts or nonsalt stimuli. In contrast, rats not treated with amiloride only generalized the 0.5M NaCl aversion to sodium salts. No differences in generalization gradients occurred between groups when the CS was 0.1M NH4Cl or 1.0M sucrose. These findings suggest that the "salty" taste of NaCl is primarily related to the amiloride-sensitive portion of the functional taste response in rats. Conversely, the portion of the NaCl response insensitive to amiloride appears to have "sour-salty" perceptual characteristics and does not appear to be perceived as being salty.}, } @article {pmid2173933, year = {1990}, author = {Meachum, CL and Bernstein, IL}, title = {Conditioned responses to a taste conditioned stimulus paired with lithium chloride administration.}, journal = {Behavioral neuroscience}, volume = {104}, number = {5}, pages = {711-715}, doi = {10.1037//0735-7044.104.5.711}, pmid = {2173933}, issn = {0735-7044}, support = {CA26419/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/drug effects ; Arousal/drug effects ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Chlorides/*pharmacology ; Conditioning, Classical/*drug effects ; Grooming/drug effects ; Injections, Intraperitoneal ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Motor Activity/drug effects ; Posture ; Rats ; Taste/*drug effects ; }, abstract = {The present experiments examined whether behavioral conditioned responses (CRs) develop to lithium chloride (LiCl)-paired tastes and whether these CRs are similar to the behaviors that follow administration of the drug. Rats were exposed to a saccharin solution via intraoral infusions before being injected with either LiCl or saline. CRs were assessed after conditioning when the saccharin conditioned stimulus was delivered alone. The unconditioned response to LiCl delivery is a very distinctive posture that has been termed "lying-on-belly." The present study indicates that this behavior pattern also occurs after the delivery of a LiCl-paired taste solution. The similarity between these unconditioned and conditioned behaviors is consistent with the hypothesis that responses are conditioned during taste aversion acquisition and that CRs are similar to those that are generated by the drugs used in conditioning.}, } @article {pmid2080197, year = {1990}, author = {Cannon, DS and Leeka, JK}, title = {Effect of body weight on ethanol-induced taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {37}, number = {2}, pages = {379-381}, doi = {10.1016/0091-3057(90)90352-i}, pmid = {2080197}, issn = {0091-3057}, support = {AA07707/AA/NIAAA NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/*drug effects ; Body Weight/*physiology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Male ; Rats ; Rats, Inbred WKY ; Saccharin/administration & dosage ; Taste ; }, abstract = {Saccharin aversions were conditioned using ethanol (EtOH) in rats of different body weights. There was a nonuniform relation between EtOH dose (g/kg) and strength of conditioned taste aversion. Heavier rats learned stronger aversions at the same dose, and a weak dose (i.e., 1.0 g/kg) was effective only in heavier rats. It is suggested that rats be equated on body weight in studies of EtOH-induced taste aversion learning and in studies of EtOH preference.}, } @article {pmid1963689, year = {1990}, author = {Ivanova, SF and Bures, J}, title = {Acquisition of conditioned taste aversion in rats is prevented by tetrodotoxin blockade of a small midbrain region centered around the parabrachial nuclei.}, journal = {Physiology & behavior}, volume = {48}, number = {4}, pages = {543-549}, doi = {10.1016/0031-9384(90)90297-h}, pmid = {1963689}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain ; Chlorides/pharmacology ; Injections ; Lithium/pharmacology ; Lithium Chloride ; Male ; Mesencephalon/*drug effects/physiology ; Rats ; Sodium Channels/drug effects ; Taste/*drug effects ; Tetrodotoxin/administration & dosage/*pharmacology ; Water Deprivation/physiology ; }, abstract = {A remarkable feature of conditioned taste aversion (CTA) is the resistance of the association between the gustatory trace and symptoms of poisoning against disruptive procedures. In an attempt to identify the neural substrate of this phase of CTA acquisition, thirsty rats were offered 0.1% saccharin for 15 min, were immediately afterwards anesthetized with pentobarbital, received stereotaxic injections of tetrodotoxin (TTX, 10 ng/microliters) into various brainstem regions and were poisoned with IP injection of LiCl (0.15 M, 2% body weight). In Experiment 1, TTX prevented CTA acquisition when injected into the parabrachial nuclei but was ineffective in the lower medulla. TTX alone did not elicit CTA even at brain sites in which it caused death in 30% of the animals. In Experiment 2, the brainstem was systematically explored by a grid of bilateral TTX injections. A spatial gradient of the CTA disruption pointed to the parabrachial nuclei as the brain region responsible for the amnesic effect observed. Experiment 3 showed that a single TTX injection into the parabrachial nucleus on one side did not prevent CTA acquisition and that similarly ineffective were TTX injections in the sagittal plane both at the mesencephalic and bulbar levels. It is concluded that the pivotal role of the parabrachial nuclei in the formation of the permanent CTA engram can only be revealed by functional blockade which is more radical than that achieved during general anesthesia.}, } @article {pmid2263667, year = {1990}, author = {Villanueva, HF and Arezo, S and James, JR and Rosecrans, JA}, title = {Withdrawal from chronic nicotine fails to produce a conditioned taste aversion to saccharin in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {37}, number = {1}, pages = {59-61}, doi = {10.1016/0091-3057(90)90041-f}, pmid = {2263667}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Choice Behavior/*drug effects ; Conditioning, Psychological/*drug effects ; Male ; Nicotine/administration & dosage/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin ; Substance Withdrawal Syndrome/*psychology ; Taste/drug effects ; Time Factors ; }, abstract = {Sprague-Dawley rats were maintained on a daily regimen of nicotine, morphine or saline administration for 28 days. Following the discontinuation of the daily drug regimen, rats were given a choice of tap water or a saccharin-water solution. The rats previously receiving morphine drank significantly less saccharin-water solution than did the rats receiving nicotine or saline injections. The failure of the nicotine rats to display a conditioned aversion to the novel saccharin flavor suggests that nicotine did not produce a physiological withdrawal syndrome analogous to morphine withdrawal in this paradigm.}, } @article {pmid2178245, year = {1990}, author = {Bull, DF and King, MG and Pfister, HP and Singer, G}, title = {Alpha-melanocyte-stimulating hormone conditioned suppression of a lipopolysaccharide-induced fever.}, journal = {Peptides}, volume = {11}, number = {5}, pages = {1027-1031}, doi = {10.1016/0196-9781(90)90028-4}, pmid = {2178245}, issn = {0196-9781}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use ; Aspirin/therapeutic use ; *Avoidance Learning ; Body Temperature Regulation/*drug effects ; *Conditioning, Classical ; Fever/chemically induced/drug therapy/*physiopathology ; Lipopolysaccharides/pharmacology/*toxicity ; Male ; Rats ; Rats, Inbred Strains ; Saccharin ; Specific Pathogen-Free Organisms ; Taste ; alpha-MSH/*pharmacology/therapeutic use ; }, abstract = {Recent investigations have demonstrated the susceptibility of various components of the immune system to behavioral conditioning, using a conditioned taste aversion (CTA) paradigm. In Experiment 1 the effective antipyretic dose (40 micrograms/kg) and duration of antipyretic action (up to 4 hr) of alpha-melanocyte-stimulating hormone (alpha-MSH) was determined in rats tested with lipopolysaccharide (LPS). In the second experiment, alpha-MSH was used as the unconditioned stimulus (UCS) and paired with a novel-tasting saccharin solution (0.1%) to elicit a conditioned antipyretic response to a fever induced one hour previously by LPS. Both the antipyretic effect of alpha-MSH and the pyrogenic effect of LPS were found to be significantly conditionable. The conditioning of fever/antipyretic responses demonstrates for the first time that still another aspect of the host response can be influenced by conditioning procedures.}, } @article {pmid1964617, year = {1990}, author = {Segall, MA and Crnic, LS}, title = {A test of conditioned taste aversion with mouse interferon-alpha.}, journal = {Brain, behavior, and immunity}, volume = {4}, number = {3}, pages = {223-231}, doi = {10.1016/0889-1591(90)90024-k}, pmid = {1964617}, issn = {0889-1591}, support = {MH00621/MH/NIMH NIH HHS/United States ; MH09718/MH/NIMH NIH HHS/United States ; MH44453/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Anorexia/chemically induced ; Avoidance Learning/*drug effects ; Cacao ; Chlorides/administration & dosage/toxicity ; Conditioning, Classical/*drug effects/physiology ; Drinking Behavior/drug effects ; Interferon Type I/*pharmacology/toxicity ; Lithium/administration & dosage/toxicity ; Lithium Chloride ; Male ; Mice ; Mice, Inbred DBA ; *Taste ; }, abstract = {Interferon-alpha treatment induces anorexia in cancer patients and in mice. The ability of interferon-alpha to induce a conditioned taste aversion (CTA) in mice was explored. Mice were injected with doses of interferon-alpha that had been shown to induce anorexia (M. A. Segall & L. S. Crnic, Behav. Neurosci., 1990; 1600 or 800 U/g of mouse) after being given a novel solution (chocolate milk). Neither dose of interferon resulted in a decrease of milk intake on the test day. To determine whether the known cognitive effects of interferon interfere with the ability of a mouse to learn CTA, a combined injection of interferon-alpha and LiCl (an illness-inducing agent) was given. The combination of interferon-alpha with LiCl did not interfere with the LiCl-induced CTA. Thus, any possible cognitive effects of interferon did not interfere with conditioned taste aversion. To test the possibility that repeated trials might establish a conditioned taste aversion to interferon, mice were given three conditioning trials spaced 3 days apart. No aversion developed. Doses of interferon-alpha that produce anorexia do not produce a conditioned taste aversion, indicating that separate mechanisms are activated in these two behaviors.}, } @article {pmid2401656, year = {1990}, author = {Houpt, KA and Zahorik, DM and Swartzman-Andert, JA}, title = {Taste aversion learning in horses.}, journal = {Journal of animal science}, volume = {68}, number = {8}, pages = {2340-2344}, doi = {10.2527/1990.6882340x}, pmid = {2401656}, issn = {0021-8812}, mesh = {Animal Feed ; Animals ; *Avoidance Learning ; Feeding Behavior/*psychology ; *Food Preferences ; Horses/physiology/*psychology ; *Taste ; }, abstract = {The ability of ponies to learn to avoid a relatively novel food associated with illness was tested in three situations: when illness occurred immediately after consuming a feed; when illness occurred 30 min after consuming a feed; and when illness was contingent upon eating one of three feeds offered simultaneously. Apomorphine was used to produce illness. The feeds associated with illness were corn, alfalfa pellets, sweet feed and a complete pelleted feed. The ponies learned to avoid all the fees except the complete feed when apomorphine injection immediately followed consumption of the feed. However, the ponies did not learn to avoid a feed if apomorphine was delayed 30 min after feed consumption. They could learn to avoid alfalfa pellets, but not corn, when these feeds were presented with the familiar "safe foods," oats and soybean meal. Ponies apparently are able to learn a taste aversion, but there were constraints on this learning ability. Under the conditions of this study, they did not learn to avoid a food that made them sick long after consumption of the food, and they had more difficulty learning to avoid highly palatable feeds.}, } @article {pmid2175032, year = {1990}, author = {Chambers, KC and Yuan, DL}, title = {Blockage of the effects of testosterone on extinction of a conditioned taste aversion by estradiol: time of action.}, journal = {Physiology & behavior}, volume = {48}, number = {2}, pages = {277-281}, doi = {10.1016/0031-9384(90)90313-s}, pmid = {2175032}, issn = {0031-9384}, support = {HD 20970/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/toxicity ; Conditioning, Classical/*drug effects ; Estradiol/*analogs & derivatives/pharmacology ; Extinction, Psychological/*drug effects ; Female ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/drug effects ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Testosterone/*antagonists & inhibitors/pharmacology ; }, abstract = {Testosterone (T) prolongs the extinction of a conditioned taste aversion only if it is present during extinction. Experiments were conducted to determine whether estradiol (E) blocks the effects of T by acting during acquisition or extinction. In the first experiment, gonadectomized male and female rats injected with estradiol dipropionate (EP) and testosterone propionate (TP) during extinction had significantly faster extinction rates than those only injected with TP. Treating gonadectomized rats with TP prior to as well as during extinction did not prevent EP from blocking the effects of T. In Experiment 2, E was equally effective in preventing T from prolonging extinction when it was implanted in gonadectomized males during acquisition, extinction, or both acquisition and extinction. Thus, E does not have to be present concurrently with T during extinction to be effective. This suggests that E does not act on a T-related mechanism but rather acts independently of T.}, } @article {pmid1976417, year = {1990}, author = {López-García, JC and Fernández-Ruiz, J and Bermúdez-Rattoni, F and Tapia, R}, title = {Correlation between acetylcholine release and recovery of conditioned taste aversion induced by fetal neocortex grafts.}, journal = {Brain research}, volume = {523}, number = {1}, pages = {105-110}, doi = {10.1016/0006-8993(90)91641-s}, pmid = {1976417}, issn = {0006-8993}, mesh = {Acetylcholine/*metabolism ; Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; *Brain Tissue Transplantation ; Cerebral Cortex/embryology/physiology/*transplantation ; Conditioning, Operant/*physiology ; Female ; *Fetal Tissue Transplantation ; Male ; Neurotransmitter Agents/metabolism ; Potassium/pharmacology ; Pregnancy ; Rats ; Rats, Inbred Strains ; Taste/physiology ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {Rats with lesions of the gustatory neocortex (GN) show deficits in the acquisition of taste aversion. Fetal GN grafts to a lesioned animal restore taste aversion learning and establish connections with the host brain. In this work, we examined whether the grafts are biochemically functional and whether this fact can be related to behavioral recovery. Gustatory or occipital cortices from rat fetuses were transplanted to GN-lesioned rats. Two months later, taste aversion recovery was tested and the release of labeled gamma-aminobutyric acid (GABA), acetylcholine (ACh), dopamine and glutamate from the grafted tissue was assayed. Fetal GN grafts promoted recovery of learning and released GABA, ACh and glutamate in response to K+ depolarization. Occipital cortex grafts did not induce behavioral recovery, although they were capable of releasing GABA. In contrast, these grafts did not release ACh. Moreover, GN-grafted rats in which behavioral recovery was not seen also failed to release ACh. These results are in agreement with previous findings that cholinergic transmission is important in the GN and suggest that ACh may play a role in the graft-mediated behavioral recovery observed in this model.}, } @article {pmid2174620, year = {1990}, author = {Ismaĭlova, KhIu and Gasanov, GG and Rakhmanova, SSh}, title = {[The effect of 5-hydroxytryptophan on conditioned taste aversion].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {40}, number = {4}, pages = {771-772}, pmid = {2174620}, issn = {0044-4677}, mesh = {5-Hydroxytryptophan/*pharmacology ; Animals ; Avoidance Learning/*drug effects/physiology ; Cats ; Chlorides/pharmacology ; Conditioning, Classical/*drug effects/physiology ; Feeding Behavior/drug effects/physiology ; Lithium/pharmacology ; Lithium Chloride ; Male ; Taste/*drug effects/physiology ; }, } @article {pmid2395911, year = {1990}, author = {Arnedo, M and Gallo, M and Agüero, A and Puerto, A}, title = {Effects of medullary afferent vagal axotomy and area postrema lesions on short-term and long-term NaCl-induced taste aversion learning.}, journal = {Physiology & behavior}, volume = {47}, number = {6}, pages = {1067-1074}, doi = {10.1016/0031-9384(90)90354-7}, pmid = {2395911}, issn = {0031-9384}, mesh = {Afferent Pathways/physiology ; Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Axons/*physiology ; Brain Mapping ; Chemoreceptor Cells/physiology ; Conditioning, Classical/*physiology ; Male ; Medulla Oblongata/*physiology ; Memory/*physiology ; Memory, Short-Term/physiology ; Mental Recall/*physiology ; Rats ; Rats, Inbred Strains ; Retention, Psychology/*physiology ; Stomach/innervation ; Taste/*physiology ; Vagus Nerve/*physiology ; Water-Electrolyte Balance/physiology ; }, abstract = {This series of experiments demonstrates a functional dissociation between the area postrema (AP) and the vagus nerve in short-term taste aversion learning (TAL). Although medullary axotomy of the afferent component of the vagus disrupted the learning observed with NaCl-induced short-term (nondelayed) TAL, lesioning the AP failed to interfere with the discriminative process employed by the animals under the same conditions. However, involvement of neither the vagus nerve nor the AP seemed to be indispensable for learning in NaCl-induced long-term (delayed) TAL. The possibility that the vagus nerve and the AP are involved in temporally distinct visceral processing is discussed.}, } @article {pmid2360687, year = {1990}, author = {Giza, BK and Scott, TR and Antonucci, RF}, title = {Effect of cholecystokinin on taste responsiveness in rats.}, journal = {The American journal of physiology}, volume = {258}, number = {6 Pt 2}, pages = {R1371-9}, doi = {10.1152/ajpregu.1990.258.6.R1371}, pmid = {2360687}, issn = {0002-9513}, support = {DK-30964/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Cholecystokinin/*pharmacology ; Electrophysiology ; Female ; Glucose ; Injections, Intravenous ; Medulla Oblongata/physiology ; Osmolar Concentration ; Rats ; Rats, Inbred Strains ; Solutions ; Taste/*drug effects/physiology ; }, abstract = {Alterations in taste responsiveness have been suggested to mediate the suppression of feeding that accompanies exogenous administration of cholecystokinin (CCK). We tested this possibility in electrophysiological and behavioral experiments. First we monitored taste-evoked activity in the nucleus tractus solitarii of anesthetized rats during intravenous injection of 2 or 6 micrograms/kg of CCK or vehicle. We found no significant effects on taste activity during the 30-min period after CCK administration. Then we employed a conditioned taste-aversion paradigm to measure the rat's perceived intensity of a series of glucose concentrations under the same three experimental conditions. At 2 micrograms/kg, CCK had no effect; at 6 micrograms/kg there was a significant increase in the perceived intensity of 2 of the 15 test solutions, which we attribute to elevated vagal tone. The potential contribution of gastric distension was eliminated in the electrophysiological study and was minimized by brief exposures to stimuli in the behavioral experiment. Thus CCK administration, in the absence of significant gastric distension, does not appear to alter taste responsiveness.}, } @article {pmid2168227, year = {1990}, author = {Dyck, DG and Janz, L and Osachuk, TA and Falk, J and Labinsky, J and Greenberg, AH}, title = {The Pavlovian conditioning of IL-1-induced glucocorticoid secretion.}, journal = {Brain, behavior, and immunity}, volume = {4}, number = {2}, pages = {93-104}, doi = {10.1016/0889-1591(90)90012-f}, pmid = {2168227}, issn = {0889-1591}, support = {MH43778-02/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Chlorides ; Conditioning, Psychological/*physiology ; Corticosterone/blood/*metabolism ; Female ; Immunosuppression Therapy ; Interleukin-1/*pharmacology ; Lithium ; Lithium Chloride ; Mice ; Mice, Inbred DBA ; Odorants ; Psychoneuroimmunology ; Saccharin ; Taste ; }, abstract = {Recombinant IL-1-beta, which is capable of stimulating the pituitary-adrenal axis to secrete corticosterone, was paired with environmental cues in either a taste aversion or odor conditioning procedure. Among mice receiving paired delivery of cues and IL-1, subsequent re-exposure to cues elicited corticosterone production. This response was significantly greater than in animals that were conditioned but not re-exposed to the cues or were exposed to the cues alone. These results indicate that the IL-1 activation of adrenal cortical secretion can be conditioned to environmental stimuli.}, } @article {pmid1977374, year = {1990}, author = {Kuribara, H and Tadokoro, S}, title = {Unpleasant and anticonflict effects of nicotine observed by conditioned taste aversion and hypertonic NaCl solution tests in mice.}, journal = {Arukoru kenkyu to yakubutsu izon = Japanese journal of alcohol studies & drug dependence}, volume = {25}, number = {3}, pages = {193-201}, pmid = {1977374}, issn = {0389-4118}, mesh = {Animals ; *Anti-Anxiety Agents ; Caffeine/pharmacology ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Hypertonic Solutions ; Injections, Subcutaneous ; Male ; Methamphetamine/pharmacology ; Mice ; Morphine/pharmacology ; Nicotine/administration & dosage/*pharmacology ; Sodium Chloride ; Taste/*drug effects ; }, abstract = {Effects of subcutaneously (s.c.) administered nicotine on preference for 0.1% saccharin solution and rejection for hypertonic (2%) NaCl solution were investigated in water-deprived mice. The results were compared with those after s.c. administration of methamphetamine, caffeine and morphine. When nicotine 0.3 and 1 mg/kg, methamphetamine 0.5, 1 and 2 mg/kg, and caffeine 30 mg/kg were administered to mice immediately after intake of the saccharin solution, they exhibited a significant decrease in the preference for saccharin solution on the next day (namely conditioned aversion), even though no drug administration was carried out. However, 2.5-10 mg/kg of morphine produced no marked change in the preference. Daily administration for 5 days of nicotine 1 mg/kg, methamphetamine 2 mg/kg, caffeine 30 mg/kg, and morphine 10 mg/kg did not produce any marked change in the individual drug effects on the conditioned taste aversion. On the other hand, rejection for the hypertonic NaCl solution was significantly attenuated when nicotine 0.3 mg/kg was administered prior to the experiment, probably showing an anticonflict effect. Caffeine 10 mg/kg, and morphine 2.5 and 5 mg/kg also attenuated the rejection for hypertonic NaCl solution. In contrast, methamphetamine 0.25-2 mg/kg enhanced the rejection in a dose-dependent manner. The present results suggest that, in spite of the same dose, nicotine shows both unpleasant and anticonflict (antianxiety) effects dependent on the environmental situation such as stimulus, timing of the drug administration etc. Furthermore, it is notable that the effects of nicotine observed in our experiments were similar to those of caffeine.}, } @article {pmid1975699, year = {1990}, author = {Córdoba, NE and Molina, JC and Basso, AM and Orsingher, OA}, title = {Perinatal undernutrition reduced ethanol intake preference in adult recovered rats.}, journal = {Physiology & behavior}, volume = {47}, number = {6}, pages = {1111-1116}, doi = {10.1016/0031-9384(90)90360-g}, pmid = {1975699}, issn = {0031-9384}, mesh = {Alcohol Drinking/*physiology ; Animals ; Avoidance Learning/*physiology ; Body Weight/physiology ; Brain/physiology ; Conditioning, Classical/physiology ; Dietary Proteins/administration & dosage ; Female ; Food Deprivation/*physiology ; Neurotransmitter Agents/physiology ; Pregnancy ; Rats ; Rats, Inbred Strains ; Social Environment ; Taste/*physiology ; }, abstract = {Adult female rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) were tested for alcohol intake in a preference test. When compared with control animals, experimental rats exhibited higher overall fluid intake. Nevertheless, in terms of ethanol preference these subjects evidenced lower preference to this drug. A test for assessing ethanol olfactory preference did not show any differences between control and experimental rats in basal conditions. However, after repeated exposure to alcohol, deprived rats showed an aversion to ethanol odor, while controls evidenced the opposite effect, i.e., heightened preference. Possible differences to the aversive effects of ethanol between control and experimental animals were assayed by means of two taste aversion tests, by associating alcohol to sucrose or NaCl. No differences were detected between both groups of rats. These results demonstrate that early undernutrition reduces ethanol preference in a free choice situation. Such an effect could be due, at least partially, to odor aversion developed by repeated exposure.}, } @article {pmid2388934, year = {1990}, author = {Langhans, W and Harlacher, R and Balkowski, G and Scharrer, E}, title = {Comparison of the effects of bacterial lipopolysaccharide and muramyl dipeptide on food intake.}, journal = {Physiology & behavior}, volume = {47}, number = {5}, pages = {805-813}, doi = {10.1016/0031-9384(90)90001-k}, pmid = {2388934}, issn = {0031-9384}, mesh = {Acetylmuramyl-Alanyl-Isoglutamine/*pharmacology ; Animals ; Appetite/*drug effects ; Drinking/drug effects ; Eating/*drug effects ; Energy Metabolism/drug effects ; Gastric Emptying/drug effects ; Indomethacin/pharmacology ; Lipopolysaccharides/*pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Satiety Response/drug effects ; Taste/drug effects ; Verapamil/pharmacology ; }, abstract = {For further characterization of the mechanism involved in the anorexia during bacterial infection, we investigated whether muramyl dipeptide (MDP), the minimal immunologically active structure of gram-positive bacterial cell walls, affects rats' food intake in the same way as lipopolysaccharide (LPS) from E. coli. MDP (1.6 mg/kg body weight = b.wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. Indomethacin (2.5 mg/kg b.wt., IP) but not verapamil (5 mg/kg b.wt., IP) attenuated the hypophagic effect of MDP. In further experiments, MDP and LPS (100 micrograms/kg b.wt., IP) both inhibited gastric emptying and indomethacin failed to block this effect of LPS. Hepatic vagotomy did not attenuate the hypophagic effects of MDP or LPS. LPS reduced water intake only when food was available, but reduced food intake also during water deprivation. MDP did not affect water intake. MDP and LPS both had an aversive effect, but LiCl, which was also aversive, failed to reduce feeding under the conditions tested. This questions the role of a conditioned taste aversion in the hypophagia induced by MDP or LPS. The results suggest that a stimulation of eicosanoid synthesis contributes to MDP-induced hypophagia and may therefore also contribute to the anorexia during infection. In contrast, an inhibition of gastric emptying, an activation of hepatic satiety signals or a reduction of water intake, does not seem to be crucial for the hypophagic effects of MDP or LPS.}, } @article {pmid2167487, year = {1990}, author = {Sterner, RT}, title = {Plasma lithium as a marker of lithium chloride in wild Norway rats (R. norvegicus).}, journal = {Physiology & behavior}, volume = {47}, number = {5}, pages = {1013-1015}, doi = {10.1016/0031-9384(90)90027-2}, pmid = {2167487}, issn = {0031-9384}, mesh = {Animals ; Animals, Wild ; Chlorides/administration & dosage/*pharmacokinetics ; Dose-Response Relationship, Drug ; Lithium/administration & dosage/*pharmacokinetics ; Lithium Chloride ; Male ; Rats ; }, abstract = {A parametric study was conducted to determine the efficacy of plasma lithium as a marker of lithium chloride ingestion and dose in conditioned taste aversion research with rats. Separate groups of male wild Norway rats were given 60, 120 and 240 mg/kg doses of a lithium chloride solution by gavage. At 0.5, 1, 2, 24, 48 and 72 hr after dosing, 2-3 cc samples of blood were taken from each rat: these were centrifuged and 0.5-1.0 cc specimens of plasma were frozen for later analysis. Flameless atomic absorption spectroscopy was then used to determine quantities (ppm) of lithium in these specimens. Analyses of the data revealed that plasma lithium was both dose and time dependent; however, uptake and elimination of the lithium was rapid (less than or equal to 48 hr for 60 and 120 mg/kg-dosed rats). Results showed that measurements of plasma lithium has some utility as a marker of lithium chloride ingestion in laboratory studies, but limited potential in field studies, of conditioned taste aversion with rats.}, } @article {pmid2161651, year = {1990}, author = {Jensen, RA and Gilbert, DG and Meliska, CJ and Landrum, TA and Szary, AB}, title = {Characterization of a dose-response curve for nicotine-induced conditioned taste aversion in rats: relationship to elevation of plasma beta-endorphin concentration.}, journal = {Behavioral and neural biology}, volume = {53}, number = {3}, pages = {428-440}, doi = {10.1016/0163-1047(90)90310-3}, pmid = {2161651}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Lithium/pharmacology ; Lithium Chloride ; Male ; Nicotine/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; beta-Endorphin/*blood ; }, abstract = {In the first experiment a conditioned taste aversion paradigm was used to characterize a dose-response curve for the aversive properties of nicotine in male Sprague-Dawley rats. Doses of nicotine ranging from 0.01 to 0.46 mg/kg, 2.0 ml of 0.47 M lithium chloride, or saline were injected, ip, 10 min after exposure to a novel saccharin solution. Amount of saccharin consumed in a two-bottle test was assessed 72 h later. Nicotine doses of 0.046 mg/kg and above produced a significant degree of conditioned taste aversion. In a second experiment, four groups of 10 rats each were injected with saline, 0.022 mg/kg nicotine, 0.46 mg/kg nicotine, or 2.0 ml 0.47 of M LiCl. Doses of 0.46 mg/kg nicotine and 0.47 M LiCl elevated plasma beta-endorphin concentrations significantly above saline control values. The 0.022 mg/kg dose, the highest dose that did not produce conditioned taste aversion in Experiment 1, did not significantly increase plasma beta-endorphin concentrations. This finding suggests that doses of nicotine that produce conditioned taste aversion also promote the release of pituitary stress hormones. Taken together these data suggest that some of the pharmacological and behavioral effects attributed to nicotine, including the release of endogenous neuromodulators, may be dose-dependent concomitants of the aversive effects of nicotine in nicotine-naive animals.}, } @article {pmid2346629, year = {1990}, author = {Formaker, BK and Hill, DL}, title = {Alterations of salt taste perception in the developing rat.}, journal = {Behavioral neuroscience}, volume = {104}, number = {2}, pages = {356-364}, doi = {10.1037//0735-7044.104.2.356}, pmid = {2346629}, issn = {0735-7044}, support = {NS01215/NS/NINDS NIH HHS/United States ; NS24741/NS/NINDS NIH HHS/United States ; }, mesh = {Aging/*physiology ; Animals ; Animals, Newborn ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain/physiology ; Chorda Tympani Nerve/physiology ; Conditioning, Classical/physiology ; Generalization, Stimulus/physiology ; Rats ; Rats, Inbred Strains ; *Sodium Chloride ; Taste/*physiology ; Taste Buds/*physiology ; Taste Threshold/physiology ; }, abstract = {Behavioral correlates of changing neurophysiological taste sensitivities during development were assessed with a conditioned taste aversion procedure. Young rats (age 25-30 days) avoided 0.1M monochloride salts and 1.0M sucrose reliably less than adults (age 90-105 days), but the two groups did not differ when the conditioned stimulus (CS) was 0.1M citric acid. Analyses of generalization gradients revealed that young rats were unable to discriminate among the tastes of NaCl, NH4Cl, and KCl, whereas adults readily made such discriminations. Both age groups had similar generalization gradients when the CS was 1.0M sucrose or 0.1M citric acid. These data indicate that quantitative and qualitative aspects of salt taste perception alter with age. Furthermore, the behavioral changes noted in the present study correspond closely with previous findings from developmental studies of neurophysiological taste responses.}, } @article {pmid2345759, year = {1990}, author = {Jeffreys, RD and Pournaghash, S and Glowa, JR and Riley, AL}, title = {The effects of Ro 15-4513 on ethanol-induced taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {35}, number = {4}, pages = {803-806}, doi = {10.1016/0091-3057(90)90362-l}, pmid = {2345759}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Azides/*pharmacology ; Behavior, Animal/*drug effects ; Benzodiazepines/*pharmacology ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Drug Interactions ; Ethanol/*pharmacology ; Female ; Rats ; Saccharin ; Taste ; }, abstract = {Ro 15-4513 is an imidazobenzodiazepine that has been reported to block a range of behavioral effects of ethanol. In the present experiments, the effects of Ro 15-4513 were assessed on the acquisition of an ethanol-induced conditioned taste aversion. Specifically, rats were given a novel saccharin solution to drink followed by an injection of one of a range of doses of Ro 15-4513 (0.5 and 1.0 mg/kg, Experiment 1A, and 2.0 and 3.0 mg/kg, Experiment 1B) and an injection of ethanol (1.75 g/kg). Ro 15-4513 failed to block the acquisition of the ethanol-induced taste aversion. Possible reasons for this failure were discussed.}, } @article {pmid1691952, year = {1990}, author = {Yamamoto, T and Kitamura, R}, title = {A search for the cortical gustatory area in the hamster.}, journal = {Brain research}, volume = {510}, number = {2}, pages = {309-320}, doi = {10.1016/0006-8993(90)91382-q}, pmid = {1691952}, issn = {0006-8993}, mesh = {Afferent Pathways/anatomy & histology/physiology ; Animals ; Cerebral Cortex/*physiology ; Cricetinae/*physiology ; Horseradish Peroxidase ; Male ; Mesocricetus/*physiology ; Neurons, Afferent/*cytology ; Reaction Time/physiology ; Taste/*physiology ; Tongue/*innervation ; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate ; Wheat Germ Agglutinins ; }, abstract = {The gustatory area was searched in the cerebral cortex of the hamster by means of a combined approach using electrophysiological, behavioral, and histological experiments. The chorda tympani (CT), which innervates taste buds on the anterior part of the tongue, projected to a confined area anterior to the middle cerebral artery and just dorsal to the rhinal fissure. The trigeminal component of the lingual nerve (LN) area was located anterodorsal to the CT area, and the glossopharyngeal nerve (GN), which innervates taste buds on the posterior part of the tongue, was posterior to the CT area. The center of the CT and GN areas belonged to the dorsal part of the dysgranular insular cortex, and the LN area was within the primary somatosensory granular cortex. Bilateral symmetrical ablations of the CT and GN areas abolished the conditioned taste aversion (to sodium saccharin) that had been acquired before ablations, indicating a role of these areas in some cognitive processes of taste perception. Injections of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the CT and GN areas, centered in the dysgranular insular cortex, revealed that this cortical region had major fiber connections with the contralateral homotypical cortical area, ipsilateral amygdala (central, lateral and basolateral nuclei), ipsilateral parvicellular part of the posteromedial ventral nucleus of the thalamus, bilateral parabrachial nucleus, contralateral nucleus of the solitary tract, raphe nuclei, and the locus ceruleus. Conversely, injections of WGA-HRP in these target areas showed anterograde and/or retrograde transport in the similar dysgranular insular cortex and additionally in the ventral part of the granular insular cortex. The present results suggest that the cortical gustatory area of the hamster is about 1.5 X 1.5 mm in size with the topographic organization between anterior and posterior parts of the tongue, and is located mainly in the dysgranular insular cortex around the middle cerebral artery.}, } @article {pmid2359754, year = {1990}, author = {Ossenkopp, KP and Ossenkopp, MD}, title = {Motion sickness in guinea pigs (Cavia porcellus) indexed by body rotation-induced conditioned taste aversions.}, journal = {Physiology & behavior}, volume = {47}, number = {3}, pages = {467-470}, doi = {10.1016/0031-9384(90)90110-p}, pmid = {2359754}, issn = {0031-9384}, mesh = {Animals ; Conditioning, Classical/*physiology ; Cues ; *Extinction, Psychological ; Guinea Pigs ; Male ; Motion Sickness/*physiopathology ; Rotation ; *Taste ; }, abstract = {The presence of motion sickness in albino guinea pigs (Cavia porcellus) was examined by using a conditioned taste aversion (CTA) as an index. Eighteen animals were divided into three groups. One group received four pairings of a novel 0.15% saccharin solution followed by 20 min of body rotation at 70 rpm (on a schedule of 15 sec on and 5 sec off). Another group received four pairings of the saccharin solution followed by exposure to sham rotation. The third group experienced the rotation procedure following access to water. The group receiving the rotation procedure contingent on presentation of the novel saccharin taste exhibited a conditioned aversion to this fluid (relative to the control groups) over days of acquisition (p less than 0.01), which subsequently dissipated when rotation was no longer contingent on the presentation of the saccharin solution (extinction). These data thus demonstrate the presence of motion sickness in guinea pigs when CTA is used as an index.}, } @article {pmid2354630, year = {1990}, author = {Heyes, CM and Durlach, PJ}, title = {Social blockade of taste-aversion learning in Norway rats (Rattus norvegicus): is it a social phenomenon?.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {104}, number = {1}, pages = {82-87}, doi = {10.1037/0735-7036.104.1.82}, pmid = {2354630}, issn = {0735-7036}, mesh = {Animals ; Arousal ; *Avoidance Learning ; *Conditioning, Classical ; Cues ; *Discrimination Learning ; Male ; Mental Recall ; Rats ; Rats, Inbred Strains ; *Social Environment ; *Taste ; }, abstract = {In Experiment 1, hooded rats (Rattus norvegicus) were exposed to a novel diet in a food dish or on a conspecific; they were allowed to consume the same diet and then were injected with a toxin LiCl. Later both groups ate more of the novel diet than animals that had not been exposed, and the conspecific-exposed group ate more than the dish-exposed group. Reducing aversion learning by exposure on a conspecific is known as social blockade. We examined if this effect is because a conspecific intensifies dietary cues and thereby increases latent inhibition. Experiment 2 failed to show that diet on a conspecific is a more effective conditioned stimulus for taste-aversion learning than diet in a dish, and Experiment 3 showed that diet in a dish is an effective overshadowing stimulus in aversion learning but diet on a conspecific is not. These results suggest that social blockade cannot readily be assimilated to a latent-inhibition model and may be a distinctly social form of learning.}, } @article {pmid2110491, year = {1990}, author = {Kusnecov, AW and Husband, AJ and King, MG}, title = {The influence of dexamethasone on behaviorally conditioned immunomodulation and plasma corticosterone.}, journal = {Brain, behavior, and immunity}, volume = {4}, number = {1}, pages = {50-66}, doi = {10.1016/0889-1591(90)90006-c}, pmid = {2110491}, issn = {0889-1591}, mesh = {Animals ; Cell Division/drug effects ; Conditioning, Classical/*drug effects ; Corticosterone/*blood ; Dexamethasone/*pharmacology ; Immunoglobulin mu-Chains/*metabolism ; Male ; Pokeweed Mitogens/pharmacology ; Rats ; Rats, Inbred Strains ; Spleen/cytology/drug effects/*immunology ; Taste/drug effects ; }, abstract = {Utilizing a conditioned taste aversion paradigm we have previously shown that rats re-exposed to a saccharin solution previously paired with cyclophosphamide (CY) demonstrate significantly reduced in vitro mitogen-induced spleen cell proliferation and IgM secretion assessed 24 h after saccharin re-exposure. In this report treatment of similarly conditioned rats with dexamethasone (DEX) either before conditioning or before re-exposure abrogated the conditioned modulation of pokeweed mitogen (PWM)-induced spleen cell proliferation. The finding that DEX pretreatment on the conditioning day was as effective in abrogating the conditioned response as DEX treatment prior to the test day does not support pituitary-adrenal mediation of the conditioned immusuppressive effect following re-exposure of conditioned animals to the CS. There was no significant conditioned immunosuppression observed with respect to PHA- and Con A-induced proliferation and the influence of DEX on these parameters could not be assessed. The effect on PWM-induced IgM production was inconclusive since the reduced IgM response among conditioned animals was of only borderline significance.}, } @article {pmid2311004, year = {1990}, author = {Fox, RA and Corcoran, M and Brizzee, KR}, title = {Conditioned taste aversion and motion sickness in cats and squirrel monkeys.}, journal = {Canadian journal of physiology and pharmacology}, volume = {68}, number = {2}, pages = {269-278}, doi = {10.1139/y90-041}, pmid = {2311004}, issn = {0008-4212}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/anatomy & histology/physiology ; Cats ; Cerebral Ventricles/anatomy & histology/physiology ; Female ; Lithium/pharmacology ; Male ; Medulla Oblongata/anatomy & histology/physiology ; Motion Sickness/*physiopathology ; Saimiri ; Species Specificity ; Taste/*physiology ; Vomiting/*physiopathology ; }, abstract = {The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.}, } @article {pmid2407907, year = {1990}, author = {Mathis, DA and Emmett-Oglesby, MW}, title = {Quantal vs. graded generalization in drug discrimination: measuring a graded response.}, journal = {Journal of neuroscience methods}, volume = {31}, number = {1}, pages = {23-33}, doi = {10.1016/0165-0270(90)90005-z}, pmid = {2407907}, issn = {0165-0270}, support = {DA-RO1-3521/DA/NIDA NIH HHS/United States ; DA-RO1-4137/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Conditioning, Operant/drug effects ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Generalization, Psychological/*physiology ; Pentylenetetrazole/pharmacology ; Psychopharmacology ; Psychotropic Drugs/*pharmacology ; Reinforcement, Psychology ; Research Design ; Taste/physiology ; }, abstract = {In drug discrimination research, detection of drug stimuli by animals is used for investigating various properties of psychoactive drugs. The major issue addressed by this paper is whether detection of drug stimuli by animals is a quantal or graded event. Some data suggest that detection of a drug stimulus by animals is quantal in nature. Thus, variations in drug stimulus substitution may only reflect variations in threshold for detecting the training stimulus rather than the current concept of these data reflecting graded responding to stimulus intensity. Therefore, drug discrimination procedures may have limited utility for detecting quantitative differences in the subjective effects of varying drug doses. In order to examine this problem, a method for measuring continuous response gradients in individual animals is needed. Tests for quantal responding generally use the distribution of responses on two manipulanda as the dependent measure. However, this variable may be inadequate for detecting a graded response, and may actually reflect loss of stimulus control or a deterioration in performance, rather than changes in response magnitude. Most alternative measures utilize response rate. Unfortunately, these measures are influenced by the direct rate-altering properties of some drugs. One possible alternative method is conditioned taste aversion as the discriminative task. This paradigm provides a means for not only ascertaining if graded discriminative responses occur in individual animals, but also more rapidly training a drug discrimination. Thus, using conditioned taste aversion techniques for measuring a drug discrimination may provide better indices for detecting response gradations.}, } @article {pmid2348201, year = {1990}, author = {Jakinovich, W and Moon, C and Choi, YH and Kinghorn, AD}, title = {Evaluation of plant extracts for sweetness using the Mongolian gerbil.}, journal = {Journal of natural products}, volume = {53}, number = {1}, pages = {190-195}, doi = {10.1021/np50067a030}, pmid = {2348201}, issn = {0163-3864}, support = {R01-NS25381-01/NS/NINDS NIH HHS/United States ; R03-DE-07560/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning ; Chorda Tympani Nerve/drug effects ; Conditioning, Psychological ; Electrophysiology ; Gerbillinae ; Male ; Plant Extracts/*pharmacology ; Sweetening Agents/*isolation & purification ; }, abstract = {Extracts of Thladiantha grosvenorii fruits, Stevia rebaudiana leaves, and Abrus precatorius leaves were investigated using Mongolian gerbil electrophysiological and conditioned taste aversion procedures, which were designed to respond to sucrose. A close correlation was observed between extracts of these sweet plants known to contain sweet principles and those extracts indicated as being sweet by a combination of these gerbil bioassays. The methods employed seem to be suitable for use in aiding the purification of highly sweet compounds of plant origin.}, } @article {pmid2320709, year = {1990}, author = {Neisewander, JL and McDougall, SA and Bowling, SL and Bardo, MT}, title = {Conditioned taste aversion and place preference with buspirone and gepirone.}, journal = {Psychopharmacology}, volume = {100}, number = {4}, pages = {485-490}, pmid = {2320709}, issn = {0033-3158}, support = {DA05312/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Aromatic Amino Acid Decarboxylase Inhibitors ; Avoidance Learning/*drug effects ; Brain Chemistry/drug effects ; Buspirone/*pharmacology ; Choice Behavior/*drug effects ; Diazepam/pharmacology ; Dopamine/biosynthesis ; Hydrazines/pharmacology ; Male ; Neurons/drug effects ; Nucleus Accumbens/drug effects ; Pyrimidines/*pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {The effects of the nonbenzodiazepine anxiolytics buspirone and gepirone were compared to diazepam at 1, 3, and 10 mg/kg using the conditioned taste aversion (CTA) paradigm. Buspirone and gepirone produced stronger CTA than diazepam (3 and 10 mg/kg) across repeated conditioning trials, indicating that these nonbenzodiazepine anxiolytics may have stronger aversive properties than diazepam. The effects of buspirone and gepirone (1 and 3 mg/kg) were also assessed using the conditioned place preference (CPP) paradigm. Both buspirone (1 and 3 mg/kg) and gepirone (3 mg/kg only) produced CPP, indicating that these drugs may have rewarding properties, and that buspirone is more potent than gepirone in producing CPP. These findings demonstrate that buspirone and gepirone have affective properties similar to abused drugs, and may therefore have abuse potential. It was also demonstrated that buspirone (3 mg/kg), but not gepirone (3 mg/kg), increased dopamine (DA) synthesis in the nucleus accumbens, a mesolimbic brain area thought to be involved in drug reward.}, } @article {pmid2314363, year = {1990}, author = {Liu, WF and Shih, JH}, title = {Neurobehavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6.}, journal = {Neurotoxicology and teratology}, volume = {12}, number = {1}, pages = {73-78}, doi = {10.1016/0892-0362(90)90115-s}, pmid = {2314363}, issn = {0892-0362}, mesh = {Analysis of Variance ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Cholinesterase Reactivators/*toxicity ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Exploratory Behavior/drug effects ; Male ; Motor Activity/drug effects ; Oximes ; Pyridinium Compounds/*toxicity ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; }, abstract = {A series of neurobehavioral testing procedures was used to evaluate the behavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6 in male Sprague-Dawley rats. These procedures were fixed-ratio (FR) responding, shuttle-box conditioned avoidance response (CAR), conditioned taste aversion (CTA), drinking behavior, open-field exploratory behavior, negative geotaxis, and wire suspension time. Dose-response studies of HI-6 at dose-levels of 25, 50 and 100 mg/kg, or saline (IP) were evaluated. HI-6 disrupted FR responding in a dose-dependent fashion, with significant effects occurring at doses of 50 and 100 mg/kg. The pattern of disruption was characterized by extended periods of nonresponding having an abrupt onset and offset. HI-6 produced CTA in a dose-related manner, with significant effects at doses equal to those that disrupted FR performance. HI-6 did not alter CAR, drinking motivation, exploratory behavior, negative geotaxis, or wire suspension time. These data suggest that there may be a commonality in the underlying mechanism(s) for the disruption in FR performance and the induction of the CTA. This mechanism may relate to the presumed drug-induced adverse internal state inducing the CTA.}, } @article {pmid2305004, year = {1990}, author = {Jaeger, TV and Mucha, RF}, title = {A taste aversion model of drug discrimination learning: training drug and condition influence rate of learning, sensitivity and drug specificity.}, journal = {Psychopharmacology}, volume = {100}, number = {2}, pages = {145-150}, pmid = {2305004}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Drug Interactions ; Fentanyl/pharmacology ; Lithium/pharmacology ; Male ; Models, Psychological ; Pentobarbital/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {A model of drug discrimination based on a lithium chloride (LiCl) flavour aversion was described and examined. Mildly thirsty rats were presented daily with 4 ml of a distinctly flavoured solution which was followed on 50% of the days by an IP injection of LiCl. Prior to the flavour presentation, the rats were injection SC with saline or a training drug (0.04 mg/kg fentanyl or 20 mg/kg pentobarbital) to signal whether LiCl would follow. Almost all rats eventually exhibited stable behaviour that involved drinking most or all of the fluid when it was not to be followed by LiCl and little or no drinking when it was. Such discrimination occurred regardless of whether drug predicted LiCl (learned-discomfort) or predicted no LiCl (learned-safety). However, with fentanyl there were clear differences between rats trained with drug under learned-safety and under learned-discomfort conditions for 1) the rate of acquisition of stable performance as a function of LiCl dose, 2) generalization of the training dose to a test dose that was lower, and 3) elicitation of fentanyl responses by pentobarbital. These findings, together with indications that such effects did not always occur with pentobarbital as the training drug, were discussed from theoretical and practical perspectives.}, } @article {pmid2302312, year = {1990}, author = {Brito, GN and Brito, LS}, title = {Septohippocampal system and the prelimbic sector of frontal cortex: a neuropsychological battery analysis in the rat.}, journal = {Behavioural brain research}, volume = {36}, number = {1-2}, pages = {127-146}, doi = {10.1016/0166-4328(90)90167-d}, pmid = {2302312}, issn = {0166-4328}, mesh = {Animals ; Appetitive Behavior/physiology ; Arousal/physiology ; Avoidance Learning/physiology ; Behavior, Animal/*physiology ; Brain Mapping ; Conditioning, Classical/physiology ; Discrimination Learning/physiology ; Frontal Lobe/*physiology ; Hippocampus/*physiology ; Limbic System/*physiology ; Male ; Mental Recall/physiology ; Motor Activity/physiology ; Neural Pathways/physiology ; *Neuropsychological Tests ; Orientation/physiology ; Rats ; Rats, Inbred Strains ; Receptors, Cholinergic/physiology ; Retention, Psychology/physiology ; Septum Pellucidum/*physiology ; Taste/physiology ; }, abstract = {Rats with lesions in the posterodorsal septal area (aimed at transecting the precommissural fornix) and rats with lesions in the prelimbic sector of the medial frontal cortex were tested postoperatively on a neuropsychological test battery comprised of the following tasks: time-spent-eating in two adaptation boxes, time-to-emerge and ambulation in an open field, general activity, contingently-reinforced (continuous) and schedule-specific (delayed non-matching-to-sample) T-maze alternation, visual and olfactory discrimination in a T-maze, temporal alternation (response patterning) and tactile Go/No-Go discrimination in a runway, approach-avoidance conflict in the runway, step-through inhibitory avoidance, one-way active avoidance, two-way active avoidance, and conditioned taste aversion. It was found that: (1) rats with septal (SEP) lesions spent more time eating than control (CON) rats and rats with lesions in prelimbic cortex (PRE). PRE rats did not differ from CON rats; (2) PRE rats emerged into an open field faster, and spent less time in home cage than CON and SEP rats. SEP rats stayed in home cage less than CON rats. PRE and SEP rats crossed more squares in the open field than CON rats; (3) SEP and PRE rats were more active than CON rats; (4) SEP rats performed the contigently-reinforced and schedule-specific T-maze alternation tasks worse than PRE rats, and PRE rats performed these tasks worse than CON rats. PRE, but not SEP, rats showed improvement with continued practice at brief intertrial and interrun intervals.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid2167492, year = {1990}, author = {Miller, JS and Kelly, KS and Neisewander, JL and McCoy, DF and Bardo, MT}, title = {Conditioning of morphine-induced taste aversion and analgesia.}, journal = {Psychopharmacology}, volume = {101}, number = {4}, pages = {472-480}, pmid = {2167492}, issn = {0033-3158}, support = {1 R01 AA06634/AA/NIAAA NIH HHS/United States ; DA03460/DA/NIDA NIH HHS/United States ; }, mesh = {*Analgesia ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Cues ; Drinking/drug effects ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, Opioid/drug effects ; Taste/*drug effects ; }, abstract = {The process of selective associations is evident in the aversive conditioning literature, where it has been shown that external cues are readily associated with peripheral pain, whereas taste cues are more easily associated with effects of drug administration. Within this framework, it is of interest that the failures to obtain a conditioned analgesic response to a morphine-associated CS have used external cues as conditioned stimuli. In Experiment 1, subjects re-exposed to a morphine-associated CS not only expressed the anticipated taste aversion, but also exhibited a decrease in pain sensitivity that was evident 15 or 30 min following CS re-exposure. Experiment 2 suggested that the conditioned analgesic response was opioid mediated, as pre-test administration of naloxone blocked expression of the analgesic CR. In Experiment 3, an increase in opiate receptor sensitivity produced by chronic naltrexone treatment did not affect the strength of the taste aversion, but resulted in an increase in the magnitude of the conditioned analgesic response. Collectively, these data suggest a neuropharmacological dissociation in systems mediating the two responses.}, } @article {pmid2575410, year = {1989}, author = {Gorczynski, RM and Holmes, W}, title = {Neuroleptic and anti-depressant drug treatment abolishes conditioned immunosuppression in mice.}, journal = {Brain, behavior, and immunity}, volume = {3}, number = {4}, pages = {312-319}, doi = {10.1016/0889-1591(89)90030-5}, pmid = {2575410}, issn = {0889-1591}, mesh = {Amitriptyline/*pharmacology ; Animals ; Antidepressive Agents/pharmacology ; Antipsychotic Agents/pharmacology ; Chlorpromazine/*pharmacology ; Cyclophosphamide/*pharmacology ; Immune Tolerance/*drug effects ; Mice ; Mice, Inbred BALB C ; Taste ; }, abstract = {Mice previously exposed to cyclophosphamide in the presence of saccharin-flavored water will show a decreased antibody response to challenge with sheep erythrocytes if simultaneously they are again given saccharin to drink. These mice also show conditioned taste aversion. Treatment of conditioned animals with chlorpromazine or amitriptyline after challenge with erythrocytes in the presence of saccharin reduced the degree of immunosuppression and, though to a lesser degree, the conditioned taste aversion.}, } @article {pmid2519304, year = {1989}, author = {Horio, T and Kawamura, Y}, title = {Taste effectiveness of glutamate compounds with different cations in rat.}, journal = {Shika Kiso Igakkai zasshi = Japanese journal of oral biology}, volume = {31}, number = {6}, pages = {712-717}, doi = {10.2330/joralbiosci1965.31.712}, pmid = {2519304}, issn = {0385-0137}, mesh = {Animals ; Cations ; Chorda Tympani Nerve/physiology ; Food Preferences ; *Glutamates/chemistry ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {A role of a cation of glutamate compounds for their taste has not been well elucidated yet. In this experiment, the difference of taste quality of glutamate compounds which have a different cation was compared to reveal the role of cations in the glutamate compounds on their characteristics of taste. Monosodium L-glutamate (MSG), monopotassium glutamate (MPG) and monocalcium glutamate (MCG) were used. The preference test in rats revealed that the rate of drinking volume per day was not statistically different among MSG, MPG and MCG. In the next experiment, the conditioned taste aversion test was performed in rats, and rats were conditioned to hate to drink MSG, MPG and MCG respectively by pairing the intraperitoneal injection of LiCl. In the MSG conditioned animals, the drinking rate of MSG decreased, and that of MPG significantly increased, but that of MCG did not change. In the MPG conditioned animals, drinking rate of MPG was strongly depressed, but that of MCG tended to increase, and that of MSG did not change at all. In the MCG conditioned animals, the drinking rate of MCG decreased, but MSG and MPG did not change. The chorda tympani responses to 0.1 M MSG applied to the tongue surface was larger than those to 0.1 M MCG, and the responses to 0.1 M MPG were the smallest out of these three glutamate compounds. The nerve responses of the glossopharyngeal nerve to MSG, MCG and MPG were very similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2511930, year = {1989}, author = {Dittrich, W and Bode, L and Ludwig, H and Kao, M and Schneider, K}, title = {Learning deficiencies in Borna disease virus-infected but clinically healthy rats.}, journal = {Biological psychiatry}, volume = {26}, number = {8}, pages = {818-828}, doi = {10.1016/0006-3223(89)90122-4}, pmid = {2511930}, issn = {0006-3223}, mesh = {Animals ; Arousal/physiology ; Attention/physiology ; Avoidance Learning/physiology ; Borna Disease/*physiopathology ; Borna disease virus/*pathogenicity ; Brain/microbiology ; Discrimination Learning/physiology ; Disease Models, Animal ; Learning Disabilities/*physiopathology ; Neurocognitive Disorders/*physiopathology ; Orientation/physiology ; Rats ; Rats, Inbred Strains ; Taste/physiology ; Viruses, Unclassified/*pathogenicity ; }, abstract = {Borna disease (BD) virus, a still unclassified neurotropic agent, causes either fatal encephalomyelitis or persistent asymptomatic infection in a variety of animal species. We monitored the neuronal functions of intracerebrally infected but healthy rats with three types of learning experiments. Spatial discrimination learning, using the y maze and the hole board, was significantly less successful in BD virus-infected (I) compared with mock-infected (M) rats. Similarly, I rats tended to show a certain emotional disturbance (reduced resting behavior and less anxiety) as evaluated by open-field and neophobia tests. Furthermore, in two aversive learning experiments (taste aversion and reaction suppression via Skinner box), it appeared that the I rats expressed a significantly diminished ability to learn pain avoidance compared with M rats. In conclusion, we found specific learning deficiencies together with subtle behavioral alterations suggesting that BD virus causes certain modulations of high integrative brain functions which are only detectable under experimental conditions.}, } @article {pmid2620939, year = {1989}, author = {Parshad, VR}, title = {Conditioned taste aversion in lesser bandicoot rat, Bandicota bengalensis.}, journal = {Indian journal of experimental biology}, volume = {27}, number = {11}, pages = {980-982}, pmid = {2620939}, issn = {0019-5189}, mesh = {Administration, Oral ; Animal Feed ; Animals ; *Conditioning, Psychological ; Female ; Food Preferences ; Male ; Muridae/*physiology ; Phosphines/*administration & dosage ; Rodenticides/*administration & dosage ; *Taste ; Zinc/*administration & dosage ; *Zinc Compounds ; }, abstract = {The lesser bandicoot rat after ingesting a sublethal dose of 0.025% zinc phosphide, in preferred food millet (Pennisetum typhoides) grains, for 4 days, showed aversion for 5-6 days towards plain millet offered in choice with the less preferred sorghum (Sorghum vulgare) grains. The aversion response to nontoxic bait was stronger (aversion index greater than 0.7) for first 3-4 days in individual and for 1-2 days in paired rats. 100% or more shift in aversion index from pre-treatment to post-treatment periods indicated that the aversive and naive partners of the heterosexual and unisexual female pairs mutually influence the feeding preferences of each other as a result of which they showed aversion for first 2-3 days to the plain food in which poison was given to one of the partner earlier.}, } @article {pmid2553056, year = {1989}, author = {Kosten, T and Contreras, RJ}, title = {Deficits in conditioned heart rate and taste aversion in area postrema-lesioned rats.}, journal = {Behavioural brain research}, volume = {35}, number = {1}, pages = {9-21}, doi = {10.1016/s0166-4328(89)80003-8}, pmid = {2553056}, issn = {0166-4328}, support = {HL-38630/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Arousal/*physiology ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Chemoreceptor Cells/physiology ; Chlorides/pharmacology ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Heart Rate/drug effects ; Lithium/pharmacology ; Lithium Chloride ; Medulla Oblongata/*physiology ; N-Methylscopolamine ; Parasympatholytics/pharmacology ; Rats ; Rats, Inbred Strains ; Scopolamine Derivatives/pharmacology ; Taste/*physiology ; }, abstract = {Previous studies have shown that area postrema (AP) lesions cause deficits in conditioned taste aversion in the rat. They also lead to chronically lowered heart rate which can be reversed by the animals' increased appetite for and ingestion of hypertonic saline. Although not previously examined in conditioned taste aversion, changes in autonomic nervous system activity as reflected in heart rate may be an important aspect of conditioning. The present study investigated the effects of AP lesions on heart rate conditioned responses (CRs) and unconditioned responses (UCRs). Two groups of AP lesioned and sham-operated rats, one that did and one that did not drink saline solution to raise heart rate, were studied. Both LiCl and scopolamine, which have opposite effects on heart rate, were the unconditioned stimulus (UCS) agents in two separate studies. In intact rats, LiCl-mediated conditioned taste aversion was associated with decreased conditioned stimulus (CS) intake and decreased heart rate Both effects were blunted by AP lesions, although all rats displayed heart rate UCRs to LiCl. The AP rats that drank saline behaved like intact rats exhibiting both a conditioned taste aversion and conditioned heart rate responses to the CS. Although CS intake decreased, no heart rate CRs developed with scopolamine. Scopolamine-mediated conditioned taste aversion was attenuated in both saline and non-saline drinking AP-lesioned groups. Thus, when conditioned taste aversion was associated with heart rate CRs, the AP lesion-induced deficit was counteracted by saline ingestion. Conversely, when there were no heart rate CRs, conditioned taste aversion was disrupted by the lesion regardless of saline ingestion.}, } @article {pmid2519295, year = {1989}, author = {Ninomiya, Y and Sako, N and Yamaguchi, R and Funakoshi, M}, title = {Disappearance of preabsorptive insulin responses to sweet tasting stimuli in the rat conditioned taste aversion.}, journal = {Shika Kiso Igakkai zasshi = Japanese journal of oral biology}, volume = {31}, number = {5}, pages = {613-617}, doi = {10.2330/joralbiosci1965.31.613}, pmid = {2519295}, issn = {0385-0137}, mesh = {Animals ; *Avoidance Learning ; Glucose/pharmacology ; *Insulin ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Taste/drug effects/*physiology ; }, } @article {pmid2818840, year = {1989}, author = {Cunningham, CL and Niehus, DR}, title = {Effect of ingestion-contingent hypothermia on ethanol self-administration.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {6}, number = {5}, pages = {377-380}, doi = {10.1016/0741-8329(89)90007-4}, pmid = {2818840}, issn = {0741-8329}, support = {R01 AA007702/AA/NIAAA NIH HHS/United States ; AA07468/AA/NIAAA NIH HHS/United States ; AA07702/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/*physiology ; Animals ; Body Temperature ; *Ethanol ; Flavoring Agents ; Hypothermia/chemically induced/*physiopathology/psychology ; Male ; Rats ; Rats, Inbred Strains ; Self Administration ; }, abstract = {This study tested the hypothesis that ethanol intake and preference for ethanol-paired flavors are inversely related to the magnitude of hypothermia induced by ethanol. Fluid-deprived rats were given 15-min daily access to 7% ethanol in one of two flavored saccharin solutions. Consumption of one flavored ethanol solution (counterbalanced) was consistently followed by 6-hr placement in a room maintained at 32 degrees C, whereas, consumption of the other flavored ethanol solution was followed by maintenance at room temperature (21 degrees C). Animals experienced less hypothermia when ethanol was followed by exposure to 32 degrees C and eventually drank more of the flavored ethanol that preceded this exposure. Moreover, intermittent two-bottle choice tests revealed development of a preference for the flavor that preceded exposure to 32 degrees C. An "extinction" phase indicated that this preference was not due to association with the thermal environments, but depended on differences in ethanol-induced hypothermia. These results support the conclusion that oral intake of ethanol is modulated by ethanol-induced hypothermia, most likely through a conditioned taste aversion mechanism.}, } @article {pmid2623080, year = {1989}, author = {Myers, CE and Neita, A and Jakinovich, W}, title = {Modification of the gerbil's taste behavior by the sucrose taste antagonist p-nitrophenyl alpha-D-glucopyranoside.}, journal = {Physiology & behavior}, volume = {46}, number = {3}, pages = {541-545}, doi = {10.1016/0031-9384(89)90033-4}, pmid = {2623080}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Dose-Response Relationship, Drug ; Feeding Behavior/*drug effects ; Food Preferences/*drug effects ; Gerbillinae ; Glucosides/*pharmacology ; Glycosides/*pharmacology ; Male ; Quinine/*pharmacology ; Sucrose ; Taste/*drug effects ; }, abstract = {Since the gerbil's chorda tympani nerve response to sucrose is antagonized by p-nitrophenyl alpha-D-glucopyransoide (PNP-Glu), the present taste aversion behavioral experiments sought to determine whether the gerbil's behavioral gustatory responses could be modified by adding PNP-Glu to taste solutions. Results demonstrated that the gerbil's aversion to sucrose was affected by the addition of PNP-Glu, but that the avoidance was overcome by the addition of high enough concentrations of the antagonist. When mixtures of sucrose and quinine were tested, the gerbil's sucrose aversion was unaffected, nor was any change noted in the taste behavior of gerbils trained to avoid 0.1 M sodium chloride after the addition of PNP-Glu.}, } @article {pmid2616604, year = {1989}, author = {Rabin, BM and Hunt, WA}, title = {Interaction of haloperidol and area postrema lesions in the disruption of amphetamine-induced conditioned taste aversion learning in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {33}, number = {4}, pages = {847-851}, doi = {10.1016/0091-3057(89)90481-4}, pmid = {2616604}, issn = {0091-3057}, mesh = {Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects/physiology ; Brain Stem/physiology ; Cerebral Ventricles/*physiology ; Conditioning, Classical/*drug effects/physiology ; Dose-Response Relationship, Drug ; Haloperidol/*pharmacology ; Male ; Rats ; Taste ; }, abstract = {Two experiments were run to determine the mechanisms underlying the acquisition of an amphetamine-induced conditioned taste aversion. In the first experiment, it was shown that pretreatment with haloperidol (0.1-0.5 mg/kg, IP) attenuated. but did not prevent, taste aversion learning produced by amphetamine (3 mg/kg, IP). In the second experiment, combining area postrema lesions with haloperidol (0.5 mg/kg) pretreatment completely blocked the acquisition of an amphetamine-induced taste aversion. The results are interpreted as indicating that amphetamine-induced taste aversion learning has both a central component, which is mediated by dopaminergic receptors, and a nondopaminergic peripheral component, which is mediated by the area postrema.}, } @article {pmid2756102, year = {1989}, author = {Rabin, BM and Hunt, WA and Joseph, JA}, title = {An assessment of the behavioral toxicity of high-energy iron particles compared to other qualities of radiation.}, journal = {Radiation research}, volume = {119}, number = {1}, pages = {113-122}, pmid = {2756102}, issn = {0033-7587}, mesh = {Animals ; *Avoidance Learning ; Cobalt Radioisotopes ; Electrons ; Gamma Rays ; Ions ; *Iron ; Male ; Medulla Oblongata/physiology ; Neutrons ; Rats ; *Taste ; }, abstract = {Conditioned taste aversion was used to evaluate the behavioral toxicity of exposure to high-energy iron particles (56Fe, 600 MeV/amu) in comparison to that of gamma photons (60Co), high-energy electrons, or fission neutrons. Exposure to high-energy iron particles (5-500 cGy) produced a dose-dependent taste aversion with a maximal effect achieved with a dose of 30 cGy. Gamma photons and electrons were the least effective stimuli for producing a conditioned taste aversion, with a maximal aversion obtained only after exposure to 500 cGy, while the effectiveness of fission neutrons was intermediate to that of photons and iron particles, and a maximal aversion was obtained with a dose of 100 cGy. In the second experiment, rats with lesions of the area postrema were exposed to iron particles (30 cGy), but failed to acquire a taste aversion. The results indicate that (1) high-energy iron particles are more toxic than other qualities of radiation and (2) similar mechanisms mediate the behavioral toxicity of gamma photons and high-energy iron particles.}, } @article {pmid2554355, year = {1989}, author = {Messiha, FS}, title = {Maternally-mediated neonatal lithium-cesium interaction in the mouse.}, journal = {Physiology & behavior}, volume = {46}, number = {1}, pages = {89-95}, doi = {10.1016/0031-9384(89)90328-4}, pmid = {2554355}, issn = {0031-9384}, mesh = {Alcohol Dehydrogenase/*blood ; Aldehyde Dehydrogenase/*blood ; Animals ; Animals, Newborn/*growth & development ; Brain/drug effects ; Cesium/*toxicity ; Chlorides/*toxicity ; Female ; Isoenzymes ; Kidney/drug effects ; L-Lactate Dehydrogenase/*blood ; Lithium/*toxicity ; Lithium Chloride ; Liver/drug effects ; Male ; Mice ; Mice, Inbred Strains ; Organ Size/*drug effects ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Sex Factors ; Spleen/drug effects ; Testis/drug effects ; }, abstract = {The effect of maternal exposure to LiCl, CsCl or both salts in the weaning and developing offspring mice was studied on selected organ weights, hepatic and cardiac dehydrogenase enzymes. The concentration of alkali metal used in maternal drinking fluid during pregnancy and breast-feeding did not produce taste aversion and therefore approximate equal consumption was assured. Maternal exposure to either alkali metal reduced brain and testis weights of the developing offspring mice compared to controls. This suggests a delayed toxic effect on the CNS and endocrine organs. Coadministration of both salts negated this effect. The maternal neonatal Li-mediated increases of weanling spleen weight and the reduction of testis weight of developing offspring mice by Li or Cs were not evident when both alkali metals were given in combination. The combined maternal exposure to both Li and Cs salts also negated the induction of offspring mouse liver alcohol dehydrogenase produced by either alkali metal alone. Likewise, the induction of developing mouse heart lactate dehydrogenase isoenzyme (LDH5) by maternal exposure to LiCl was no more apparent by the combined Li and Cs treatment. These data suggest a Li+-Cs+ interaction in the offspring mouse due to maternal exposure to these alkali metals during pregnancy and breast-feeding periods. The results also suggest that both alkali metals most probably have been delivered to the suckling pups and some of their toxic effect was retarded.}, } @article {pmid2637350, year = {1989}, author = {Kitamura, R}, title = {[Localization and gustatory responsiveness of cortical taste area in the hamster].}, journal = {[Osaka Daigaku shigaku zasshi] The journal of Osaka University Dental Society}, volume = {34}, number = {1}, pages = {213-231}, pmid = {2637350}, issn = {0473-4629}, mesh = {Animals ; Cricetinae ; Evoked Potentials ; *Taste ; Tongue/*innervation ; }, abstract = {Mapping of evoked potentials on the cortical surface following electrical stimulation of the chorda tympani and the glossopharyngeal nerve, and anodal D.C. stimulation of the tongue indicated that the cortical taste area (CTA) was located in the dysgranular insular cortex just dorsal to the rhinal fissure near the middle cerebral artery in the hamster. Bilateral lesion of the CTA attenuated or disrupted the conditioned taste aversion that had been acquired preoperatively. This fact suggests that the CTA plays a role in some cognitive processes of taste. Experiments using anterograde and retrograde axonal transport of wheat-germ agglutinin conjugated horseradish peroxidase showed that the CTA received inputs from the contralateral CTA, amygdala, thalamic taste area and the pontine taste area, and that neurons in the CTA (chiefly in layer V) sent axons to the contralateral CTA, amygdala, and the thalamic, pontine and bulbar taste areas. Responses of 87 CTA neurons to the four basic taste stimuli were recorded in urethane-anesthetized hamsters. Majority of the CTA neurons (85%) existed in the dysgranular insular cortex. Neurons responding best to sucrose tended to be located rostrally, those to NaCl caudally, and those to HCl were distributed evenly in the CTA. Judging from the breadth of responses to the four tastes and across-neuron correlation coefficients, responsiveness of neurons in layer V is more narrowly tuned than in layers II-IV and VI.}, } @article {pmid2544203, year = {1989}, author = {Holder, MD and Yirmiya, R and Garcia, J and Raizer, J}, title = {Conditioned taste aversions are not readily disrupted by external excitation.}, journal = {Behavioral neuroscience}, volume = {103}, number = {3}, pages = {605-611}, doi = {10.1037//0735-7044.103.3.605}, pmid = {2544203}, issn = {0735-7044}, support = {NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Arousal/drug effects ; Association Learning/drug effects ; *Attention/drug effects ; *Avoidance Learning/drug effects ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Electroshock ; Extinction, Psychological/drug effects ; Fear/drug effects ; Female ; Lithium/toxicity ; Lithium Chloride ; Male ; Mental Recall/drug effects ; Nociceptors/drug effects ; Rats ; Rats, Inbred Strains ; Sexual Behavior, Animal/drug effects ; *Taste/drug effects ; Thermosensing/drug effects ; }, abstract = {Thirsty male rats were given saccharin water followed by delayed illness. During the delay, some of the rats were exposed to events designed to stimulate their external systems (i.e., the system that processes external events such as auditory and tactile stimulation). Access to females, mild footshocks, and pain from hypertonic saline injections did not interfere with either the acquisition or extinction of a taste aversion. In fact, when administered intraperitoneally, the hypertonic saline slightly increased the strength of the aversion. Exposure to heat, which changed both skin temperature and core temperature, slightly attenuated the formation of the aversion. Overall, these results emphasize the independence of the internal system (i.e., the system that deals with internal events such as taste, illness, and core temperature) and the external system. Furthermore, the associating of events related to the internal system is not readily interfered with by events related to the external system.}, } @article {pmid2780784, year = {1989}, author = {Smith, BR and Segal, RB and Amit, Z}, title = {Administration of a GABA antagonist selectively attenuates an ethanol-induced conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {33}, number = {1}, pages = {269-271}, doi = {10.1016/0091-3057(89)90462-0}, pmid = {2780784}, issn = {0091-3057}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Azides/pharmacology ; Benzodiazepines/pharmacology ; Ethanol/*pharmacology ; *GABA Antagonists ; Male ; Mice ; Picrotoxin/pharmacology ; Saccharin/pharmacology ; Taste/drug effects ; }, abstract = {Pretreatment with the GABA antagonist picrotoxin attenuated the development of an ethanol-induced conditioned taste aversion (CTA), while no effect of this compound was observed on the development of an amphetamine-induced CTA. These findings suggested some specificity of the effects of picrotoxin to the psychopharmacological properties of ethanol related to CTA. On the other hand, the benzodiazepine inverse agonist, Ro15-4513, purported to a specific ethanol antagonist, was shown to attenuate both an ethanol- and amphetamine-induced CTA. The results support the notion that ethanol intoxication may be mediated in part by GABAergic mechanisms. These GABA-mediated properties of ethanol may in fact underlie the development of an ethanol-induced CTA.}, } @article {pmid2566946, year = {1989}, author = {Jackson, A and Sanger, DJ}, title = {Conditioned taste aversions induced by phencyclidine and other antagonists of N-methyl-D-aspartate.}, journal = {Neuropharmacology}, volume = {28}, number = {5}, pages = {459-464}, doi = {10.1016/0028-3908(89)90079-8}, pmid = {2566946}, issn = {0028-3908}, mesh = {Adrenergic alpha-Antagonists/pharmacology ; Animals ; Aspartic Acid/*analogs & derivatives/antagonists & inhibitors ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Male ; N-Methylaspartate ; Phenazocine/analogs & derivatives/pharmacology ; Phencyclidine/*pharmacology ; Piperidines/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Taste aversions can be conditioned in rats by a variety of psychoactive drugs, including those with reinforcing properties. Previous research, however, has not established clearly whether phencyclidine and related drugs are active in such procedures. The present study was carried out to investigate whether phencyclidine would induce a conditioned taste aversion and whether several other compounds (MK-801, the stereoisomers of NANM and ifenprodil) which, like phencyclidine, are known to antagonise the actions of N-methyl-D-aspartate (NMDA), would produce similar effects. When rats received injections of these compounds, after consuming a novel solution of saccharin, their subsequent consumption of the same solution decreased. The smallest doses of the different drugs which induced clear taste aversions were: phencyclidine 3 mg/kg, MK-801 0.3 mg/kg, (+)-NANM 10 mg/kg, (-)-NANM 3 mg/kg and ifenprodil 10 mg/kg. Thus, all the drugs were active. However, as neither the potencies nor the efficacies of the different compounds in inducing taste aversions correlated with their other behavioural effects or with their relative potencies in antagonising the effects of NMDA or in displacing phencyclidine from its binding sites, the mechanisms involved are unclear.}, } @article {pmid2542844, year = {1989}, author = {Bures, J and Buresova, O}, title = {Conditioned taste aversion to injected flavor: differential effect of anesthesia on the formation of the gustatory trace and on its association with poisoning in rats.}, journal = {Neuroscience letters}, volume = {98}, number = {3}, pages = {305-309}, doi = {10.1016/0304-3940(89)90419-9}, pmid = {2542844}, issn = {0304-3940}, mesh = {*Anesthesia ; Animals ; Avoidance Learning/drug effects ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Lithium/poisoning ; Lithium Chloride ; Male ; Pentobarbital/administration & dosage ; Poisoning/*physiopathology ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {Anesthesia disrupts formation of conditioned taste aversion (CTA) when induced before presentation of the gustatory stimulus but does not prevent association of the already formed gustatory trace with delayed poisoning. The transition between the disruption-prone and disruption-resistant phases of CTA acquisition was examined under conditions eliminating the confounding effect of anesthesia on ingestive behavior. Intraperitoneal injection of 2% saccharin (1% b.wt.) was used as an intravascular gustatory conditioned stimulus (CS) followed 2 h later by the visceral unconditioned stimulus (US) (LiCl 0.15 mol/l, 2% b.wt.). Pentobarbital anesthesia (50 mg/kg) prevented CTA formation when applied 4 h before to 30 min after saccharin injection, but was ineffective in the second half of the CS-US interval (1-2 h after saccharin administration). CTA acquisition was also impaired by subanesthetic dosages of pentobarbital (10 and 20 mg/kg) preceding i.p. injection of saccharin. It is concluded that the abrupt disappearance of the disruptive effect of pentobarbital in the middle of the CS-US interval marks the formation of the gustatory trace which mediates CTA learning even when both CS and US are applied by i.p. injection.}, } @article {pmid2706078, year = {1989}, author = {Isaac, WL and Nonneman, AJ and Neisewander, J and Landers, T and Bardo, MT}, title = {Prefrontal cortex lesions differentially disrupt cocaine-reinforced conditioned place preference but not conditioned taste aversion.}, journal = {Behavioral neuroscience}, volume = {103}, number = {2}, pages = {345-355}, doi = {10.1037//0735-7044.103.2.345}, pmid = {2706078}, issn = {0735-7044}, support = {MH 27345/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain Mapping ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Frontal Lobe/*drug effects ; Injections, Subcutaneous ; Male ; Motivation/drug effects ; Neural Pathways/drug effects ; Nucleus Accumbens/drug effects ; Orientation/*drug effects ; Rats ; Rats, Inbred Strains ; Receptors, Dopamine/drug effects ; Taste/*drug effects ; Tegmentum Mesencephali/drug effects ; }, abstract = {The reinforcing efficacy of cocaine is thought to involve, at least in part, mesocortical dopaminergic (DA) neurons. Rats will self-administer cocaine applied directly into the medial prefrontal cortex but not into nucleus accumbens or the ventral tegmental area (Goeders & Smith, 1983). The present experiments were conducted to assess whether lesions of prefrontal cortex (mesocortical DA target regions) attenuate the reinforcing properties of systemically administered cocaine. Male Sprague-Dawley rats were anesthetized, and one of three subfields (medial, orbital, or precentral) of the prefrontal cortex was removed by aspiration or no brain injury was done (sham operates). In four experiments the rats were tested on conditioned place preference (CPP), conditioned taste aversion (saccharin conditioned stimulus, cocaine unconditioned stimulus), general activity in the running wheel and open field, and food-reinforced spatial alternation in the T-maze. Sham operates demonstrated a cocaine-induced place preference, rats with medial frontal lesions showed a cocaine-induced place aversion, and other operates showed neither a conditioned place preference nor an aversion. The results of this experiment suggest that lesions of the DA projection fields of the prefrontal cortex in the rat reduce the positive reinforcing properties of systemically injected cocaine. In the second experiment, all subjects showed a conditioned taste aversion of equal magnitude. This suggests that whereas the positive reinforcing properties were affected differentially by prefrontal cortex lesions, the aversive properties were not affected. In Experiment 3 there were no lesion-induced differences in activity in either the running wheel or the open field. Therefore, changes in motor activity cannot account for the CPP data. In the final experiment, the medial frontal operates were impaired relative to the precentral and sham operates on learning to alternate choices in the T-maze, but the orbital frontal operates' performance was not different from that of any other group. This suggests that a general disruption of all reinforcement mechanisms did not occur following these lesions. Instead, these results indicate that mesocortical DA projection regions are involved with mediating the reinforcing properties of cocaine and that there is a separate system mediating the aversive properties of cocaine.}, } @article {pmid2572001, year = {1989}, author = {Asin, KE and Montana, WE}, title = {Studies on D1 and D2 dopamine receptor involvement in conditioned taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {32}, number = {4}, pages = {1033-1041}, doi = {10.1016/0091-3057(89)90077-4}, pmid = {2572001}, issn = {0091-3057}, mesh = {2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/*pharmacology ; Animals ; Benzazepines/*pharmacology ; Cerebral Ventricles/pathology ; Conditioning, Classical/*drug effects ; Dopamine Agents/*pharmacology ; *Dopamine Antagonists ; Dose-Response Relationship, Drug ; Ergolines/*pharmacology ; Haloperidol/*pharmacology ; Male ; Quinpirole ; Rats ; Rats, Inbred Strains ; Taste ; }, abstract = {This series of studies investigated the ability of compounds selective for either the D1 or D2 dopamine receptor to induce a conditioned taste aversion (CTA) in thirsty rats. Neither the D1 antagonist SCH23390 (0.12-0.60 mg/kg) nor the D2 antagonist haloperidol (0.125-0.375 mg/kg) were able to induce CTAs to a saccharin solution. In contrast, the D1 agonist SKF38393 produced a dose-dependent taste aversion which was stereoselective to the (R-) enantiomer. The aversion to (R,S)-SKF38393 was not blocked by pretreatment with either SCH23390 or haloperidol, suggesting that the aversion is not mediated through stimulation of either dopamine receptor subtype. The D2 dopamine receptor agonist quinpirole was also found to produce a dose-dependent CTA. This aversion was blocked by injections of haloperidol and was attenuated following injections of domperidone, suggesting involvement of peripheral dopamine receptors in the aversion. Pretreatment with SCH23390 failed to affect the quinpirole-induced CTA, providing additional evidence that the D1 and D2 dopamine receptor subtypes can function independently of one another in the control of behavior. Finally, it does not appear that the area postrema is importantly involved in these taste aversions since lesions of this brain region did not affect the CTAs induced by either SKF38393 or quinpirole.}, } @article {pmid2540504, year = {1989}, author = {Misanin, JR and Hinderliter, CF}, title = {Role of the CS-US interval in the US preexposure effect.}, journal = {Psychological reports}, volume = {64}, number = {2}, pages = {611-614}, doi = {10.2466/pr0.1989.64.2.611}, pmid = {2540504}, issn = {0033-2941}, support = {HD 21161/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Chlorides/*poisoning ; *Conditioning, Classical ; Lithium/*poisoning ; Lithium Chloride ; Rats ; Rats, Inbred Strains ; Saccharin ; *Taste ; Time Factors ; }, abstract = {Theory and research suggest that long delay taste-aversion conditioning should be less affected by proximal US preexposure than short-delay conditioning. The present research tested this hypothesis by administering illness-inducing LiCl shortly before a saccharin-LiCl pairing in which the postsaccharin LiCl was administered either immediately or 20 min. after access to saccharin. The results suggest that US preexposure has a more deleterious effect on conditioning when the illness-inducing US is delayed in conditioning than when it is immediate. These results are to be expected on the basis of classical conditioning principles and question theory and research that suggest more deleterious effects of US preexposure with shorter intervals between the preexposed and conditioning US.}, } @article {pmid2740432, year = {1989}, author = {Clark, DE and Wellman, PJ}, title = {Conditioned saccharin taste aversion induced by mycotoxins in rats: lack of effect of ochratoxin A.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {32}, number = {3}, pages = {819-821}, doi = {10.1016/0091-3057(89)90040-3}, pmid = {2740432}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Male ; Mycotoxins/*pharmacology ; Ochratoxins/*pharmacology ; Rats ; Rats, Inbred Strains ; *Saccharin ; Taste/*drug effects ; }, abstract = {The present study examined the putative aversive action of ochratoxin A (OA) using a conditioned saccharin aversion paradigm. Adult male rats consumed a 0.1% saccharin solution then were treated (IP) with either a 5% NaHCO3 vehicle (negative control), 32 mg/kg LiCl (positive control) or 0.75, 1.5 or 3.0 mg/kg OA. Twenty-four hours later, the rats were given a choice between tap water and the 0.1% saccharin solution. Rats treated with the vehicle or any of the doses of OA exhibited a marked preference for the saccharin solution, whereas the rats treated with LiCl exhibited a marked rejection of the saccharin solution. The implications of these data for an understanding of mycotoxicosis are discussed.}, } @article {pmid2923664, year = {1989}, author = {Elkins, RL and Gerardot, RJ and Hobbs, SH}, title = {Differences in cyclophosphamide-induced suppression of cricket predation in selectively bred strains of taste-aversion prone and resistant rats.}, journal = {Behavioral neuroscience}, volume = {103}, number = {1}, pages = {112-116}, doi = {10.1037//0735-7044.103.1.112}, pmid = {2923664}, issn = {0735-7044}, support = {1 R01 AA064565-03/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/*physiology ; Avoidance Learning/drug effects/*physiology ; Cyclophosphamide/*pharmacology ; Gryllidae ; Male ; Predatory Behavior/drug effects/*physiology ; Rats ; Taste/drug effects/*physiology ; }, abstract = {Cyclophosphamide-induced conditioned suppression of cricket predation was observed in taste-aversion-prone (TAP) but not in taste-aversion-resistant (TAR) rats. These TAP and TAR strains had been selectively bred for efficient or inefficient acquisition of cyclophosphamide-induced saccharin taste aversions (TAs). Equivalent preconditioning cricket predation was practiced by nonfasted subjects of both strains. TAR rats that ate crickets before a cyclophosphamide injection were thereafter voracious predators as were saline-injected and pseudoconditioning controls of both strains. However, conditioned TAP rats subsequently displayed a marked suppression of cricket predation. Predation can provide a deprivation-free and species-natural consummatory response for studies of strain differences in TA conditionability of TAP and TAR rats. In addition, the present results indicate that TAP and TAR strain differences in TA conditionability are not restricted to the saccharin solution that was the conditioned stimulus basis of prior strain development.}, } @article {pmid2675991, year = {1989}, author = {Kusnecov, A and King, MG and Husband, AJ}, title = {Immunomodulation by behavioural conditioning.}, journal = {Biological psychology}, volume = {28}, number = {1}, pages = {25-39}, doi = {10.1016/0301-0511(89)90109-9}, pmid = {2675991}, issn = {0301-0511}, mesh = {Animals ; Arousal/*physiology ; Behavior, Animal/*physiology ; Conditioning, Classical/*physiology ; *Immune Tolerance ; *Immunity, Cellular ; Psychoneuroimmunology ; }, abstract = {The contemporary surge in studies of behaviourally conditioned immunomodulation following Ader and Cohen (1975) was preceded by Pavlovian conditioning conducted in the Soviet Union during the 1920s and 1950s. Data from these studies provided a tenable hypothesis for immunomodification using classical conditioning processes. In particular a variant of Pavlovian conditioning, the conditioned taste aversion (CTA) paradigm, has proved very robust; here a novel gustatory experience (CS) is paired with an aversive physiological event (UCS) and subsequent gustatory avoidance of the CS alone is measured. Similar procedures have also been successfully applied to the conditioned alteration of cellular immune responses. Studies demonstrating behaviourally conditioned effects on the immune system are reviewed. More recently, conditioned immunoenhancement studies have demonstrated that taste aversion can induce a conditioned increase in the helper: suppressor T cell subset ratio in rats, and a depressed DTH response in mice. Mediating mechanisms for the conditioned effects are examined, in particular the roles of adrenocorticotropin (ACTH) and beta-endorphin (BEP), and the routes of communication between the CNS and immune system. Clinical applications of immunomodification may also be demonstrated by the potential therapeutic efficacy of both conditioned immunosuppression and immunoenhancement.}, } @article {pmid2924135, year = {1989}, author = {Escobar, M and Fernández, J and Guevara-Aguilar, R and Bermúdez-Rattoni, F}, title = {Fetal brain grafts induce recovery of learning deficits and connectivity in rats with gustatory neocortex lesion.}, journal = {Brain research}, volume = {478}, number = {2}, pages = {368-374}, doi = {10.1016/0006-8993(89)91519-9}, pmid = {2924135}, issn = {0006-8993}, mesh = {Amygdala/*cytology/physiology ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/cytology/physiology/*transplantation ; Horseradish Peroxidase ; Male ; Neural Pathways/physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Thalamic Nuclei/*cytology/physiology ; }, abstract = {Three groups of rats showing disrupted taste aversion due to gustatory neocortex lesions, were studied. One group received a transplant of homotopic cortical tissue, another of heterotopic tectal tissue, obtained from 17-day-old fetuses. The third group remained without transplant as a lesioned control group. Comparisons of the taste aversion scores before and after graft, revealed that cortical grafted animals significantly improved the taste aversion, whereas those which received tectal grafts, and the cortical-lesioned controls did not. Moreover, results with horseradish peroxidase (HRP) histochemistry revealed that the homotopic, but not the heterotopic, brain transplants were able to re-establish connections with amygdala and with the ventromedial nucleus of the thalamus areas who normally kept connectivity with the gustatory neocortex. These results support the hypothesis that fetal brain transplants can reestablish cognitive functions, as well as connectivity with its host tissue.}, } @article {pmid2779356, year = {1989}, author = {Mucha, RF}, title = {Taste aversion involving central opioid antagonism is potentiated in morphine-dependent rats.}, journal = {Life sciences}, volume = {45}, number = {8}, pages = {671-678}, doi = {10.1016/0024-3205(89)90084-2}, pmid = {2779356}, issn = {0024-3205}, mesh = {Animals ; Blood-Brain Barrier ; Dose-Response Relationship, Drug ; Drug Synergism ; Infusions, Parenteral ; Injections, Subcutaneous ; Male ; Morphine Dependence/*physiopathology ; Nalorphine/administration & dosage/analogs & derivatives/pharmacokinetics/pharmacology ; Naltrexone/administration & dosage/analogs & derivatives/pharmacokinetics/pharmacology ; Narcotic Antagonists/administration & dosage/pharmacokinetics/*pharmacology ; Quaternary Ammonium Compounds ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {A sensitive taste conditioning test was used to measure the aversive effect of a single intraventricular (i.c.v.) or subcutaneous (s.c) injection of an opioid antagonist that readily crosses the blood brain barrier (naltrexone), and one of two that do not (methylnaltrexone and diallylnormorphinium). This was done in drug-naive rats and in rats implanted 5 days earlier with a pellet containing 75 mg morphine. It was found that the morphine exposure had no significant effect on the dose-response curve of the taste aversion produced by s.c. methylnaltrexone and s.c. diallynormorphinium but reduced the lowest effective dose for the other antagonist treatments from three to more than 100 times. Consideration of the data, together with the pharmacokinetic properties of the drugs and the routes of administration used, supported a conclusion that only those aversions involving central antagonist activity show the potentiation effect of chronic morphine treatment. The findings were also discussed with regard to the location of receptors important for aversions produced by opioid antagonists in naive rats.}, } @article {pmid2734328, year = {1989}, author = {Holder, MD and Yirmiya, R}, title = {Behavioral assessment of the toxicity of aspartame.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {32}, number = {1}, pages = {17-26}, doi = {10.1016/0091-3057(89)90205-0}, pmid = {2734328}, issn = {0091-3057}, support = {HDO5958/HD/NICHD NIH HHS/United States ; NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acids/blood ; Animals ; Aspartame/administration & dosage/*toxicity ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Conditioning, Classical/drug effects ; Dipeptides/*toxicity ; Drinking ; Injections, Intraperitoneal ; Intubation ; Male ; Motor Activity/drug effects ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {Six experiments with rats assessed the toxicity of aspartame with behavioral measures. The first three experiments used a conditioned taste aversion procedure since taste aversions are typically observed after a taste is followed by a toxin. Thirty min after thirsty rats drank a sweet solution they were intraperitoneally injected (Experiment 1) or intragastrically intubated (Experiment 2) with saline or 176, 352, or 704 mg/kg of aspartame. Relative to rats given saline, rats injected with 704 and 352 mg/kg aspartame showed strong and mild aversions, respectively. Rats injected with 176 mg/kg of aspartame or intubated with any dose of aspartame did not show taste aversions. In Experiment 3, rats voluntarily consumed an aspartame solution sweetened with saccharin for 7 hr each day. Consumption of the taste paired with aspartame was not reduced. When 352 mg/kg aspartame was injected (Experiment 4), but not when intubated (Experiment 5), 5 min prior to access to a running wheel, running was reduced. Wheel running was not affected by the voluntary consumption of aspartame (Experiment 6). The route of administration effect (intraperitoneal vs. intragastric) on behavior corresponded with the amino acid levels in blood plasma (Experiment 7). Aspartate, phenylalanine, tyrosine and glutamate levels increased more after the injection, than the intubation, of aspartame (176 mg/kg). Overall, the results suggest that aspartame may have adverse effects when intraperitoneally injected but not when the route of administration is oral.}, } @article {pmid2734321, year = {1989}, author = {Mastropaolo, JP and Moskowitz, KH and Dacanay, RJ and Riley, AL}, title = {Conditioned taste aversions as a behavioral baseline for drug discrimination learning: an assessment with phencyclidine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {32}, number = {1}, pages = {1-8}, doi = {10.1016/0091-3057(89)90203-7}, pmid = {2734321}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dextroamphetamine/pharmacology ; Discrimination Learning/*drug effects ; Female ; Ketamine/pharmacology ; Phencyclidine/*pharmacology ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {When PCP was given prior to the pairing of saccharin with LiCl (and the PCP vehicle prior to a nonpoisoned exposure to the same saccharin solution), rats rapidly acquired the discrimination, avoiding saccharin consumption following PCP and consuming saccharin following the vehicle after only three conditioning trials. Conversely, when the PCP vehicle was given prior to the saccharin-LiCl pairing and PCP prior to a nonpoisoned exposure to saccharin, other subjects avoided saccharin consumption following the vehicle injection and readily consumed saccharin after an injection of PCP. During dose substitution sessions, animals displayed greater drug-appropriate responding as the dose of PCP increased. When a range of doses of ketamine was given in place of PCP prior to saccharin access, subjects displayed dose-dependent PCP-appropriate responding. When a range of doses of d-amphetamine was substituted for PCP, subjects displayed vehicle-appropriate responding at all doses. The relative efficacy of the taste aversion procedure as a baseline for drug discrimination learning is discussed.}, } @article {pmid2730511, year = {1989}, author = {Arwas, S and Rolnick, A and Lubow, RE}, title = {Conditioned taste aversion in humans using motion-induced sickness as the US.}, journal = {Behaviour research and therapy}, volume = {27}, number = {3}, pages = {295-301}, doi = {10.1016/0005-7967(89)90049-1}, pmid = {2730511}, issn = {0005-7967}, mesh = {Adolescent ; Adult ; *Conditioning, Classical ; Humans ; Male ; Motion Sickness/*psychology ; Rotation ; *Taste ; }, abstract = {The purpose of the experiment was to demonstrate conditioned taste aversion (CTA) and latent inhibition (LI) of CTA in humans using rotation-induced motion sickness as the unconditioned stimulus. To accomplish this, flavour familiarity (familiar vs unfamiliar) and rotation (rotation vs no rotation) were manipulated in a 2 X 2 factorial design. Subjects consumed either a familiarly flavoured carbonated beverage or a novel one after which half of each group was rotated or not rotated. Two hours later the subjects were re-presented with the flavoured drink that they had previously drunk. The groups receiving rotation consumed less of the drink that the non-rotated groups, thus demonstrating CTA. The rotated group pre-exposed to the novel flavoured drink consumed less than the rotated group pre-exposed to the familiar drink, thus demonstrating LI. The effectiveness of the rotation procedure in producing motion sickness was confirmed by self-reports of general feelings and by symptom rating scales. In addition, it was found that, at the time of consuming the test drink the rotation groups' motion-sickness symptom scores were reduced to the level of the nonrotated groups. Applications of these data to the prophylactic treatment of chemotherapy-induced food aversions were discussed.}, } @article {pmid2727145, year = {1989}, author = {Bardos, G}, title = {Behavioral consequences of intestinal distention: aversivity and discomfort.}, journal = {Physiology & behavior}, volume = {45}, number = {1}, pages = {79-85}, doi = {10.1016/0031-9384(89)90168-6}, pmid = {2727145}, issn = {0031-9384}, mesh = {Afferent Pathways/physiology ; Animals ; Arousal/physiology ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; *Gastrointestinal Motility ; Intestine, Small/*innervation ; Male ; Nociceptors/*physiology ; Rats ; Rats, Inbred Strains ; Satiation/*physiology ; Satiety Response/*physiology ; Taste/*physiology ; }, abstract = {This study examines the role of different types of small intestinal distention of affective behavior. "Isovolemic" and volumetric distention were hypothesized to have different effects in rats. Both stimuli decreased fluid consumption in a free drinking situation equally. Behavioral correlates, however, were clearly different. Changes of the gut volume were accompanied by behavioral elements characteristic to aversivity while such changes were not observed when the distention was isovolemic. These results indicate that the cessation of intake, i.e., satiety, is not the consequence of the interference of concurrent aversive behavior. In contrast with these findings, isovolemic distention proved to be mildly unpleasant when tested by the taste-aversion method, although the effect was clearly distinct from that of volume changes. The results suggest that not avrsivity but discomfort may be a steady, inherent concomitant factor of physiological mechanoceptive gut stimuli.}, } @article {pmid2727123, year = {1989}, author = {Le Houezec, J and Martin, C and Cohen, C and Molimard, R}, title = {Failure of behavioral dependence induction and oral nicotine bioavailability in rats.}, journal = {Physiology & behavior}, volume = {45}, number = {1}, pages = {103-108}, doi = {10.1016/0031-9384(89)90171-6}, pmid = {2727123}, issn = {0031-9384}, mesh = {Administration, Oral ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Biological Availability ; Liver/metabolism ; Male ; *Nicotine/administration & dosage/pharmacokinetics ; Portacaval Shunt, Surgical ; Rats ; Rats, Inbred Strains ; Substance-Related Disorders/*blood ; Taste/drug effects ; }, abstract = {As failure to induce behavioral dependence to oral nicotine (0.31 mM) might be caused by taste aversion. Sixteen rats were presented nicotine around the taste aversion threshold (0.025 mM then 0.05 mM) as only source of fluid for 10 weeks. Eight of them had undergone portacaval anastomosis (PCA) to increase bioavailability of nicotine by preventing liver first-pass. Weekly choice sessions between nicotine and water demonstrated neither aversion nor preference for nicotine. In 10 control and 11 PCA rats accustomed to drink 0.31 mM nicotine, plasma nicotine was determined after 3 ml/kg intragastric nicotine-solution. In both groups, 0.05 mM nicotine did not lead to detectable levels but 0.31 mM nicotine led to peak levels higher than seen in man after smoking. Similar levels were recorded after spontaneous nicotine drinking in 8 isolated and 18 grouped normal rats accustomed to 0.31 mM nicotine. Drinking nicotine for at least 10 weeks did not induce behavioral dependence in these rats. This cannot be explained by poor nicotine bioavailability by oral route.}, } @article {pmid2725440, year = {1989}, author = {Mitchell, JA and Long, SF and Wilson, MC and Kallman, MJ}, title = {The behavioral effects of pesticides in male mice.}, journal = {Neurotoxicology and teratology}, volume = {11}, number = {1}, pages = {45-50}, doi = {10.1016/0892-0362(89)90084-6}, pmid = {2725440}, issn = {0892-0362}, mesh = {*2,4-Dinitrophenol/*analogs & derivatives ; Acetamides/administration & dosage/*toxicity ; Administration, Cutaneous ; Administration, Oral ; Aniline Compounds/administration & dosage/*toxicity ; Animals ; Avoidance Learning/drug effects ; Behavior, Animal/*drug effects ; Dinitrophenols/administration & dosage/*toxicity ; Herbicides/administration & dosage/*toxicity ; Male ; Maneb/administration & dosage/*toxicity ; Mice ; Mice, Inbred Strains ; Thiocarbamates/*toxicity ; }, abstract = {Male Swiss mice, 25-30 g, were utilized to define some of the behavioral effects of the herbicides Lasso [alachlor 43%; (A)], Basalin [fluchloralin 45%; (F)], Premerge 3 [dinoseb 51%; (D)], and the fungicide Maneb-80 [maneb 80%; (M)]. These compounds were tested for their effects on locomotor activity and for their ability to establish a conditioned taste aversion following oral or dermal exposure. Individual and grouped (N = 5) activity measures were assessed immediately following the dermal administration of the commercially available pesticide formulations. Grouped activity measures were also assessed following the oral administration of the compounds. Total activity was significantly (p less than 0.05) increased over vehicle controls in both grouped and individual subjects by A, F, and D following dermal administration. Grouped activity measures were also increased by A, F, D, and M following the oral administration of the compounds. Similar subjects were tested in a conditioned taste aversion paradigm using a normally preferred 0.3% saccharin solution. Animals were given 30 min access to the saccharin solution followed immediately by the administration of the pesticide or control solution. Twenty-four hours later, animals were given the choice of 2 solutions, one containing water and the other the 0.3% saccharin solution. The percent saccharin consumed and the total fluid intake were calculated for each group (N = 8/group). A, F, and D produced a significant aversion to (N = 8/group) the saccharin following both oral and dermal administration. Oral administration of M, but not dermal exposure, also resulted in a flavor aversion. Total fluid intake, however, was not altered by any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2694762, year = {1989}, author = {Bures, J and Buresová, O}, title = {Conditioned taste aversion elicited by intracerebral administration of drugs.}, journal = {Acta physiologica Hungarica}, volume = {74}, number = {1}, pages = {77-93}, pmid = {2694762}, issn = {0231-424X}, mesh = {Animals ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Psychological/*physiology ; *Drug Tolerance ; Rats ; Rats, Inbred Strains ; Smell ; Taste/*physiology ; }, abstract = {Conditioned taste aversion (CTA) is a vital adaptive reaction governed by highly reliable but poorly understood central mechanisms. In an attempt to elucidate the site of action of various CTA eliciting drugs, equipotent dosages were applied by the systemic (i.p.) and intracerebral (i.c.) route. Rats were offered water on days 1 and 2. On day 3 they received 0.1% sodium saccharin (CS) followed by pentobarbital anaesthesia and i.p. or i.c. injection of the drug (US). After water on day 4, the rats were allowed to choose between water and saccharin on day 5. The putative central action of amphetamine was not confirmed by this experimental arrangement, since CTA was evoked by only moderately (about 10 times) lower i.c. than i.p. dosages. Similar ratio of the i.c. to i.p. effective dosages was obtained with carbachol. On the other hand, CTA of clearly central origin was caused by harmaline and by other monoamine oxidase inhibitors, pargyline and clorgyline, which elicited comparable aversion using 500, 400 and 250 times lower i.c. than i.p. dosages, respectively. The intracerebral gradient of the effect pointed to the lower medulla (inferior olive, raphe nuclei) as the critical brain region and to serotonin as the transmitter participating in the aversive labeling of the gustatory stimulus. The CTA-forming mechanism can also be studied by analysing the action of drugs, e.g. convulsants, which do not produce CTA even when applied at highly toxic dosages (LD 50) eliciting long lasting convulsions (picrotoxin, 5 mg/kg; bicuculline, 5 mg/kg). It is concluded that comparison of brain events elicited by drugs which can or cannot serve as unconditioned stimuli in the CTA paradigm may substantially contribute to the exploration of the underlying neural mechanisms.}, } @article {pmid2648494, year = {1989}, author = {Gorelick, DA}, title = {Serotonin uptake blockers and the treatment of alcoholism.}, journal = {Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism}, volume = {7}, number = {}, pages = {267-281}, doi = {10.1007/978-1-4899-1678-5_14}, pmid = {2648494}, issn = {0738-422X}, mesh = {Alcohol Drinking/drug effects ; Alcoholism/*rehabilitation ; Animals ; Brain/drug effects ; Humans ; Receptors, Serotonin/drug effects ; Serotonin Antagonists/*therapeutic use ; }, abstract = {There is growing research and clinical interest in the role of brain serotonin in regulating alcohol consumption, based on two lines of evidence: negative correlations between brain serotonin levels and spontaneous alcohol consumption in rodents, and decreased alcohol intake produced by drug-induced increases in brain serotonin activity in rodents and humans. Specific blockers of neuronal serotonin uptake, such as citalopram, fluoxetine, and zimelidine, are the major drugs used in such studies. More than a dozen studies have consistently found that such specific serotonin uptake blockers reduce alcohol preference and intake in rodents, whereas nonspecific monoamine uptake blockers (e.g., amitriptyline, doxepin) do not. The effect begins within 1 hr of administration, wears off within several days of stopping drug, and often shows tolerance after 4-10 days of daily administration (the opposite time course from antidepressant action in humans). In four human, double-blind, placebo-controlled studies, citalopram (40 mg but not 20 mg daily), fluoxetine (80 mg daily), and zimelidine (200 mg more than 300 mg daily) significantly reduced alcohol intake 10-26% in social drinkers, early problem drinkers, and chronic alcoholics. The effect occurred within a few days, wore off within several days of stopping drug, and lasted throughout the 2-4 weeks of drug administration, except that in the fluoxetine study with chronic alcoholics the effect was significant only during the first week. The reduced alcohol intake was not due to sedation, antidepression, or antianxiety effects, or an aversive drug-alcohol interaction, but could be explained in part by decreased appetitive behavior (two studies found that subjects lost weight) or a conditioned (taste) aversion to alcohol promoted by serotonin (as occurs in animals). Further research is also needed to clarify the neuropharmacological mechanism of action, since the alcohol intake-reducing effects in rodents are not blocked by serotonin receptor antagonists or brain serotonin depletion. Regardless of mechanism, serotonin uptake blockers offer a potentially promising new treatment for alcoholism.}, } @article {pmid2565787, year = {1989}, author = {Ninomiya, Y and Funakoshi, M}, title = {Behavioral discrimination between glutamate and the four basic taste substances in mice.}, journal = {Comparative biochemistry and physiology. A, Comparative physiology}, volume = {92}, number = {3}, pages = {365-370}, doi = {10.1016/0300-9629(89)90577-x}, pmid = {2565787}, issn = {0300-9629}, mesh = {Animals ; Behavior, Animal/*physiology ; Discrimination Learning/*physiology ; Female ; *Glutamates ; Male ; Mice ; Mice, Inbred ICR ; *Sodium Glutamate ; Taste/*physiology ; }, abstract = {1. Behavioural studies using the conditioned taste aversion (CTA) paradigm in mice showed that aversion conditioned to monosodium L-glutamate (MSG), which elicits a unique taste in humans, did not strongly generalize to any of the four basic taste stimuli, suggesting that mice could behaviourally discriminate between MSG and the four basic taste stimuli. 2. Denervation of bilateral glossopharyngeal nerve significantly increased behavioural similarities (the strength of generalization in the CTA paradigm) between MSG and sodium salts. This was not the case after destruction of the bilateral chorda tympani nerve. 3. These results suggest that taste information of glossopharyngeal nerve plays a more important role in the behavioural discrimination between MSG and the four basic tastes than does that of the chorda tympani nerve.}, } @article {pmid2561852, year = {1989}, author = {Rowan, GA and Lucki, I}, title = {Discrimination of the benzodiazepine receptor antagonist Ro 15-1788 using the conditioned taste aversion procedure.}, journal = {NIDA research monograph}, volume = {95}, number = {}, pages = {536}, pmid = {2561852}, issn = {1046-9516}, support = {DA05186/DA/NIDA NIH HHS/United States ; DA05367/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Brain/*drug effects ; Chlorides/toxicity ; Conditioning, Classical/*drug effects ; Discrimination Learning/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Flumazenil/*pharmacology ; Generalization, Stimulus/drug effects ; Lithium/toxicity ; Lithium Chloride ; Rats ; Receptors, GABA-A/*drug effects ; Taste/*drug effects ; }, } @article {pmid2526955, year = {1989}, author = {Lett, BT and Grant, VL}, title = {Conditioned taste preference produced by pairing a taste with a low dose of morphine or sufentanil.}, journal = {Psychopharmacology}, volume = {98}, number = {2}, pages = {236-239}, pmid = {2526955}, issn = {0033-3158}, mesh = {Analgesics/*pharmacology ; Animals ; Conditioning, Operant/*drug effects ; Fentanyl/*analogs & derivatives/pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Reinforcement Schedule ; Sufentanil ; Taste/*drug effects ; }, abstract = {Taste conditioning produced by pairing a taste with low doses of morphine or sufentanil was studied in rats in five experiments. Conditioned taste preferences were obtained with a trace conditioning procedure in which ingestion of a flavored solution was followed by an injection of sufentanil, either 0.25 mcg/kg in experiment 1 or 0.50 mcg/kg in experiment 2. Morphine produced less consistent results than sufentanil. When a similar trace conditioning procedure was used with morphine, a dose of 0.25 mg/kg produced no observable taste conditioning in experiment 3 while 0.42 mg/kg was marginally effective in producing a conditioned taste aversion in experiment 4. In experiment 5, however, conditioning of a taste preference was produced by 0.42 mg/kg morphine with a simultaneous conditioning procedure in which the morphine injection preceded ingestion of the flavored solution. The simultaneous procedure was presumed to facilitate the conditioning of taste preference by minimizing the conditioning of taste aversion.}, } @article {pmid2506600, year = {1989}, author = {Mucha, RF and van Ree, JM}, title = {Infusion of gamma 2-MSH produce a conditioned taste aversion in morphine-dependent rats.}, journal = {Psychopharmacology}, volume = {99}, number = {1}, pages = {140-142}, pmid = {2506600}, issn = {0033-3158}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Food Preferences/*drug effects ; Male ; Melanocyte-Stimulating Hormones/*pharmacology ; Morphine Dependence/*psychology ; Motivation/drug effects ; Naloxone/pharmacology ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {A two flavour, unbiased, taste preference conditioning procedure was used to test for possible motivating effects of gamma 2-MSH. Three training trials failed to produce any significant effect with doses ranging from 2.4 to 40 micrograms/ICV infusion in drug-naive, non-operated or placebo-implanted rats. However, in rats made dependent by SC implantation of a morphine pellet 4 days earlier 15 micrograms gamma 2-MSH/infusion produced a taste aversion that was comparable to that produced by infusion of a low dose of the competitive opioid receptor antagonist naloxone (0.32 micrograms). The findings confirm with a conditioning procedure and with opiate-dependent animals the naloxone-like effects of gamma 2-MSH. They also suggest that this endogenously-located peptide may acquire an aversive property as a result of chronic morphine treatment.}, } @article {pmid2487254, year = {1989}, author = {Chedester, AL and Bakarich, AC and Rabin, BM and Banks, RE and Hadick, CL}, title = {Preparation and care of the area postrema-lesioned cat.}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {2}, number = {3}, pages = {253-262}, doi = {10.3109/08941938909057431}, pmid = {2487254}, issn = {0894-1939}, mesh = {Animals ; Cats/*surgery ; Female ; Male ; Medulla Oblongata/physiopathology/*surgery ; *Postoperative Care ; *Preoperative Care ; Surgical Instruments ; Vomiting/physiopathology ; }, abstract = {The area postrema (AP) is being widely studied to delineate its role in such varied functions as blood pressure regulation, conditioned taste aversion, water and energy balance, and radiation-induced emesis. This paper describes the preoperative preparation, surgical procedure, and postoperative care of cats kept long-term in which the AP was lesioned by electrocautery. A dorsal midline approach under gas anesthesia allowed access to selectively lesion the AP. Cats fully regained consciousness the same day and many became homeostatic within 24-48 h. Results of experiments using this model demonstrate the usefulness and effectiveness of the technique for model preparation.}, } @article {pmid3214541, year = {1988}, author = {Jarbe, TU and Falk, U and Mohammed, AL and Archer, T}, title = {Acquisition and reversal of taste/tactile discrimination after forebrain noradrenaline depletion.}, journal = {Behavioral neuroscience}, volume = {102}, number = {6}, pages = {925-933}, doi = {10.1037//0735-7044.102.6.925}, pmid = {3214541}, issn = {0735-7044}, mesh = {Animals ; Avoidance Learning/physiology ; Brain/*physiology ; Discrimination Learning/*physiology ; Locus Coeruleus/physiology ; Male ; Neural Pathways/physiology ; Norepinephrine/*physiology ; Rats ; Rats, Inbred Strains ; Reversal Learning/physiology ; Taste/*physiology ; Touch/*physiology ; }, abstract = {Two experiments were performed to assess the role of noradrenaline (NA) on the acquisition of an aversively motivated discrimination task and its reversal. A conditioned taste aversion procedure was used. The NA depletions were achieved through two different pharmacological means: systemic N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4) and destruction of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine. Both procedures caused marked reductions of NA in the frontal cortex and hippocampus. In neither of the studies (Experiment 1, DSP4, and in Experiment 2, DNAB) were there any significant changes between controls and NA-depleted rats in either the rate of acquisition of the original discrimination (Phase 1) or the subsequent reversal (Phase 2). This occurred irrespective of which of the two stimuli (a taste cue, i.e., saccharin presented in bottles with nozzles that do not have ball bearings, "silent bottles," or a tongue-tactile cue, i.e., water in bottles with nozzles that had ball bearings "noisy bottles") initially was used as the conditioned stimulus (CS1, i.e., the stimulus first followed by contingent administration of lithium chloride, and later, in Phase 2, followed by saline injections). Thus NA does not appear to be critically involved in the acquisition and reversal of a taste/tactile discrimination task. The significance of forebrain NA for other discrimination tasks is discussed.}, } @article {pmid2974486, year = {1988}, author = {Lucki, I}, title = {Rapid discrimination of the stimulus properties of 5-hydroxytryptamine agonists using conditioned taste aversion.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {247}, number = {3}, pages = {1120-1127}, pmid = {2974486}, issn = {0022-3565}, support = {GM 34781/GM/NIGMS NIH HHS/United States ; MH 36262/MH/NIMH NIH HHS/United States ; }, mesh = {8-Hydroxy-2-(di-n-propylamino)tetralin ; Animals ; Buspirone/pharmacology ; Conditioning, Psychological/*drug effects ; Discrimination Learning/*drug effects ; Male ; Piperazines/pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, Serotonin/*drug effects ; Saccharin ; *Taste ; Tetrahydronaphthalenes/pharmacology ; }, abstract = {Separate groups of rats were trained to discriminate the stimulus properties of selective agonists at 5-HT receptors using a conditioned taste aversion procedure. Fluid-restricted rats were injected with drug or saline and then given access to a 0.25% saccharin solution for 30 min. When rats received a drug trial, saccharin consumption was followed by an injection of LiCl (1.8 mEq/kg i.p.), whereas on saline trials saccharin consumption was followed by a second injection of saline instead of LiCl. Rats were trained using injections of either 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.), an agonist selective for the 5-HT1A receptor, or 1-(m-trifluoromethylphenyl)piperazine (0.8 mg/kg i.p.), an agonist selective for 5-HT1B and 5-HT1C receptors, as the drug stimuli. Acquisition of the discriminated taste aversion, as measured by the differential effects on saccharin drinking between drug and saline trials, required only two to three pairings of either drug stimulus with LiCl injections. The 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus cue generalized to other drugs that are selective for the 5-HT1A receptor, such as ipsapirone (8-16 mg/kg i.p.) or buspirone (4 mg/kg i.p.), but not to agonists that are selective for the 5-HT1B/1C receptor, such as 1-(m-trifluoromethylphenyl)piperazine or 1-(m-chlorophenyl)piperazine. The discriminative stimulus properties of 1-(m-trifluoromethylphenyl)piperazine generalized to 1-(m-chlorophenyl)piperazine (0.2-0.8 mg/kg i.p.) but not to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2855272, year = {1988}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Attenuation and cross-attenuation in taste aversion learning in the rat: studies with ionizing radiation, lithium chloride and ethanol.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {31}, number = {4}, pages = {909-918}, doi = {10.1016/0091-3057(88)90404-2}, pmid = {2855272}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*physiology ; Blood-Brain Barrier ; Chlorides/*pharmacology ; Cobalt Radioisotopes ; Drug Synergism ; Ethanol/*pharmacology ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Radiation, Ionizing ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO) disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.}, } @article {pmid2850815, year = {1988}, author = {Spector, AC and Breslin, P and Grill, HJ}, title = {Taste reactivity as a dependent measure of the rapid formation of conditioned taste aversion: a tool for the neural analysis of taste-visceral associations.}, journal = {Behavioral neuroscience}, volume = {102}, number = {6}, pages = {942-952}, doi = {10.1037//0735-7044.102.6.942}, pmid = {2850815}, issn = {0735-7044}, support = {F32-NS07915A/NS/NINDS NIH HHS/United States ; R01-AM21397/AM/NIADDK NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Association Learning/*physiology ; Avoidance Learning/*physiology ; Brain/*physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Digestive System/*innervation ; Drinking/drug effects ; Habituation, Psychophysiologic/physiology ; Learning/*physiology ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {Several explanations may account for deficits in the ability of animals to form taste aversions following neural manipulations. These encompass impairments in conditioned stimulus (CS) and unconditioned stimulus (US) processing, conditioned response (CR) measurement, and expression, memory, and taste-visceral integration. A behavioral procedure that aids in the distinction between some of these possibilities is presented. In Experiment 1, 10 rats received seven intraoral (IO) infusions of sucrose (30 s, 0.55 ml) spaced every 5 min starting immediately after the injection of 3.0 mEq/kg of lithium chloride (LiCl). Control rats (n = 12) were treated identically except that they were injected with sodium chloride (NaCl). Oromotor and somatic taste reactivity behaviors were videotaped and analyzed. Lithium-injected rats systematically decreased their ingestive taste reactivity behavior over time, whereas aversive behavior increased. Control rats maintained high and stable levels of ingestive responding and demonstrated virtually no aversive behavior over the 30-min period following sodium injection. Rats were tested several days later for the presence of a conditioned taste aversion (CTA). Rats previously injected with lithium during sucrose infusions demonstrated significantly more aversive behavior than the control group, which demonstrated none. There were no differences in the level of ingestive behavior displayed by the two groups on the CTA test. Experiment 3 revealed that when similarly treated rats were tested for a CTA while in a lithium-induced state, a difference in the ingestive behavior between the two groups was observed. In Experiment 2, naive rats were injected with either NaCl or LiCl but did not receive their first sucrose infusion until 20 min later. These rats also received sucrose infusions at 25 and 30 min postinjection. There were no differences in the taste reactivity behavior displayed by lithium- or sodium-injected rats during any of the sucrose infusions. Collectively, these findings indicate that rats dramatically change their oromotor responses to sucrose during the period following LiCl administration, provided that the infusions start immediately after injection. Furthermore, this time-related behavioral change is predominantly attributable to associative processes. This paradigm can be useful in distinguishing between neural manipulations that affect the establishment of taste-visceral associations from others that affect the animal's ability to retain such associations over the commonly employed 24-hr conditioning-test interval.}, } @article {pmid3266091, year = {1988}, author = {Tazi, A and Dantzer, R and Crestani, F and Le Moal, M}, title = {Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity.}, journal = {Brain research}, volume = {473}, number = {2}, pages = {369-371}, doi = {10.1016/0006-8993(88)90868-2}, pmid = {3266091}, issn = {0006-8993}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Interleukin-1/*pharmacology ; Lipopolysaccharides/pharmacology ; Male ; Pituitary-Adrenal System/*drug effects ; Rats ; Rats, Inbred Strains ; Reference Values ; Saccharin ; *Taste ; }, abstract = {To investigate the possible aversive stimulus properties of peripherally administered interleukin 1 (IL-1), rats received two pairings of ingestion of a saccharin solution with various doses of recombinant rat interleukin 1 in a conditioned taste aversion paradigm, using 20 mg/kg lipopolysaccharide endotoxin as a positive control. Rats treated with 1 and 10 micrograms IL-1 showed a dose-dependent reduced preference for saccharin together with dose-dependent impairments in weight gain. Since these effects were obtained within the range of doses that has been previously reported to stimulate the release of ACTH, it is proposed that this last action of IL-1 is likely to be secondary to the aversive effects of IL-1.}, } @article {pmid3202812, year = {1988}, author = {Fox, RA and McKenna, S}, title = {Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat.}, journal = {Behavioral and neural biology}, volume = {50}, number = {3}, pages = {275-284}, doi = {10.1016/s0163-1047(88)90954-5}, pmid = {3202812}, issn = {0163-1047}, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking ; Kinesthesis/*physiology ; Paraventricular Hypothalamic Nucleus/physiology ; Rats ; Rats, Inbred Strains ; Stomach/innervation ; Taste/*physiology ; Vagus Nerve/*physiology ; }, abstract = {The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 degrees/s. Results are discussed with reference to the use of CTA as a measure of motion-induced "sickness" or gastrointestinal disturbance, and, because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vagal and vestibular functions.}, } @article {pmid2849411, year = {1988}, author = {Franchina, JJ and Slank, KL}, title = {Salience and the effects of CS preexposure on aversion conditioning.}, journal = {Behavioral and neural biology}, volume = {50}, number = {3}, pages = {367-373}, doi = {10.1016/s0163-1047(88)91114-4}, pmid = {2849411}, issn = {0163-1047}, mesh = {Animals ; *Arousal/drug effects ; Association Learning/drug effects ; *Avoidance Learning/drug effects ; Caseins ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; Sucrose ; *Taste/drug effects ; }, abstract = {Rats (n = 84) received preexposure to distilled water or to one of two differently salient flavors, 5.0% casein or 10.0% sucrose, casein being the more salient. Each preexposure group then received aversion conditioning to a 5.0% casein or a 10.0% sucrose CS. Aversion effects were reliably more enduring to casein than to sucrose. Relative to water-preexposed groups, preexposure to casein attenuated aversion effects to the casein CS reliably less than preexposure to sucrose attenuated aversion effects to the sucrose CS. During preexposure, neophobia was reliably greater to casein than to sucrose, suggesting that the demonstration of salience in taste aversion learning may be based on the inherent aversive properties of novelty.}, } @article {pmid3179000, year = {1988}, author = {Gallo, M and Arnedo, M and Agüero, A and Puerto, A}, title = {Electrical intracerebral stimulation of the area postrema on taste aversion learning.}, journal = {Behavioural brain research}, volume = {30}, number = {3}, pages = {289-296}, doi = {10.1016/0166-4328(88)90172-6}, pmid = {3179000}, issn = {0166-4328}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Ventricles/*physiology ; Chemoreceptor Cells/*physiology ; Conditioning, Classical/*physiology ; Electric Stimulation ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {The structural characteristics of the area postrema, its anatomical connections, participation in the detection of emesis-provoking substances and the effects of area postrema lesions on taste aversion learning acquisition, are all factors which speak in favor of a role as a chemoreceptor zone involved in the detection of aversive agents which act as effective inducers of taste aversion learning. The feasibility of substituting electrical intracerebral stimulation of the area postrema for the aversive stimulus was investigated in a taste aversion learning paradigm. In Expt. 1, 0.1-ms rectangular pulses of 50 Hz, delivered intermittently or continuously for 4 h after a 15-min delay following ingestion of the gustatory stimulus, produced reliable learning. Expt. 2 showed the learning thus induced to reflect all the characteristics features attributed to taste aversion learning: one-trial learning, long interstimulus delay and cue-consequence specificity. These results suggest that the area postrema could participate in the detection of the aversive consequences of particular taste aversion learning-inducing agents.}, } @article {pmid3067619, year = {1988}, author = {Stewart, RB and Perlanski, E and Grupp, LA}, title = {Area postrema and alcohol: effects of area postrema lesions on ethanol self-administration, pharmacokinetics, and ethanol-induced conditioned taste aversion.}, journal = {Alcoholism, clinical and experimental research}, volume = {12}, number = {5}, pages = {698-704}, doi = {10.1111/j.1530-0277.1988.tb00268.x}, pmid = {3067619}, issn = {0145-6008}, mesh = {Alcohol Drinking/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Ventricles/*physiology ; Chemoreceptor Cells/*physiology ; Conditioning, Classical/*physiology ; Ethanol/pharmacokinetics ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {An investigation was carried out to test the hypothesis that the area postrema (AP) may detect ethanol as a blood-borne toxin and thereby mediate aversive postingestinal effects of the drug. These aversive effects in turn may impose an upper limit on the amount of drug that can be consumed. In Experiment 1 rats had continuous access to water and a 4% ethanol solution. Animals with AP lesions drank more ethanol than sham-operated controls. No differences in drug disposition or metabolism were found when these rats were injected with ethanol and blood ethanol levels were measured. If the AP lesions resulted in increased ethanol drinking because of a reduction in the aversive effects of the drug, then the lesions might also be expected to attenuate a conditioned taste aversion induced by ethanol. In Experiment 2, groups of lesioned and sham-operated rats drank a novel tasting fluid and then were given i.p. injections of ethanol (0.9, 1.2, or 1.6 g/kg) or vehicle. Similar degrees of aversion to the taste of the fluid developed in both the lesioned and the sham-control groups. Since the AP lesion did not result in the attenuation of the ethanol-induced conditioned taste aversion, it was suggested that the AP may not mediate the aversive consequences of ethanol and that the increased ethanol self-administration observed in Experiment 1 may be due to other effects of the lesion.}, } @article {pmid3252254, year = {1988}, author = {Froehlich, JC and Harts, J and Lumeng, L and Li, TK}, title = {Differences in response to the aversive properties of ethanol in rats selectively bred for oral ethanol preference.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {31}, number = {1}, pages = {215-222}, doi = {10.1016/0091-3057(88)90336-x}, pmid = {3252254}, issn = {0091-3057}, support = {AA-03243/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking/drug effects ; Alcoholism/*genetics ; Animals ; Conditioning, Psychological ; Drinking Behavior/*drug effects ; Ethanol/blood/*pharmacokinetics ; Female ; Rats ; Rats, Mutant Strains ; Reward ; Saccharin/administration & dosage ; Self Administration ; }, abstract = {A conditioned taste aversion (CTA) paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to genetic differences in voluntary ethanol consumption. Four doses of ethanol, administered IP, were paired with the consumption of a 0.1% saccharin solution in rats from the alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Repeated pairing of saccharin and ethanol in a dose of 1.0 g/kg produced stronger and more prolonged aversion to saccharin in NP rats, compared with P rats, at comparable blood ethanol levels. A low dose of ethanol (0.25 g/kg) produced transient conditioned facilitation of saccharin consumption in P rats, but not in NP rats, at comparable blood ethanol levels. The results suggest that rats of the NP line find the postingestional effects of high-dose ethanol more aversive, and low-dose ethanol less reinforcing, than do rats of the P line. Genetic differences in voluntary ethanol consumption may be due, in part, to differences in aversion to the postingestional effects of ethanol.}, } @article {pmid3242654, year = {1988}, author = {Kusnecov, AW and Husband, AJ and King, MG}, title = {Behaviorally conditioned suppression of mitogen-induced proliferation and immunoglobulin production: effect of time span between conditioning and reexposure to the conditioning stimulus.}, journal = {Brain, behavior, and immunity}, volume = {2}, number = {3}, pages = {198-211}, doi = {10.1016/0889-1591(88)90022-0}, pmid = {3242654}, issn = {0889-1591}, mesh = {Animals ; Conditioning, Classical/*physiology ; Cyclophosphamide/pharmacology ; Food Preferences/drug effects ; *Immune Tolerance ; Immunoglobulins/*biosynthesis ; *Lymphocyte Activation/drug effects ; Mitogens/immunology ; Rats ; Rats, Inbred Strains ; Spleen/immunology ; Time Factors ; }, abstract = {Rats were subjected to taste aversion conditioning using the immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus (UCS) paired with saccharin, the conditioned stimulus (CS), and were reexposed to the CS at 2, 5, or 10 days after a single conditioning trial. Twenty-four hours after reexposure the rats were sacrificed and spleen cells assayed for mitogen-induced proliferation and immunoglobulin production. A robust conditioned taste aversion (CTA) was observed irrespective of the day of CS reexposure. However, only conditioned rats reexposed to the CS 2 days after training displayed a conditioned reduction in proliferative responses to PHA and PWM. These rats also exhibited a reduction in the synthesis of IgM, but not IgG or IgA, by spleen cells cultured with PWM. These effects were not observed in conditioned rats reexposed 5 or 10 days after conditioning. In another experiment, rats were subjected to a backward conditioning (UCS prior to CS) training trial, tested 2 days later for the presence of CTA, and sacrificed 24 h later for assessment of immune function as described above. The results of this experiment demonstrated that rats do not develop an aversion to saccharin when it is first presented 4 h after CY, and no alterations in spleen cell proliferation and immunoglobulin production were noted. The data show that the CTA response established by explicit association between CY and saccharin depresses in vitro spleen cell proliferation and IgM production only when elicited shortly after the conditioning trial.}, } @article {pmid3198369, year = {1988}, author = {Sovak, M and Halkovich, CA and Foster, SJ}, title = {Current contrast media and ioxilan. Comparative evaluation of vascular pain by aversion conditioning.}, journal = {Investigative radiology}, volume = {23 Suppl 1}, number = {}, pages = {S84-7}, doi = {10.1097/00004424-198809001-00004}, pmid = {3198369}, issn = {0020-9996}, mesh = {Animals ; Conditioning, Psychological ; Contrast Media/*toxicity ; Female ; Iohexol/*analogs & derivatives/toxicity ; Iopamidol/toxicity ; Osmolar Concentration ; Pain/*chemically induced ; Rats ; Rats, Inbred Strains ; Sorbitol/toxicity ; Taste ; }, abstract = {Vascular pain caused by contrast media (CM) cannot be quantified by subjective patient reports or manifest pain reactions in experimental animals. Therefore, conditioned taste aversion (CTA), a psychopharmacological method, was used in double-blind femoral arteriography in rats to compare a new nonionic monomeric CM, ioxilan, with iohexol, iopamidol (all at 350 mgI/mL) and 22% sorbitol. A chronically implanted femoral artery catheter was used to inject 0.2 mL/kg body weight. By measuring the intake of water laced with the flavor that thirsty rats had learned to associate with the injection, the degree of aversion, assumed proportional to pain, was determined. Ioxilan (690 mOsm) produced the least pain, followed by iopamidol (810 mOsm), iohexol (844 mOsm) and sorbitol (1410 mOsm). Since all test substances are highly and similarly hydrophilic and nonionic, the intensity of vascular pain must depend on solution osmolality, rather than on chemotoxicity or ionicity. Compounds of the lowest osmolality, ig, ioxilan, elicit the least vascular pain.}, } @article {pmid2908061, year = {1988}, author = {Hoffman, DC and Beninger, RJ}, title = {Selective D1 and D2 dopamine agonists produce opposing effects in place conditioning but not in conditioned taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {31}, number = {1}, pages = {1-8}, doi = {10.1016/0091-3057(88)90302-4}, pmid = {2908061}, issn = {0091-3057}, mesh = {2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Amphetamines/pharmacology ; Animals ; Benzazepines/pharmacology ; Conditioning, Psychological/*drug effects ; Dopamine Agents/*pharmacology ; Ergolines/pharmacology ; Fenoldopam ; Homing Behavior/*drug effects ; Male ; Quinpirole ; Rats ; Rats, Inbred Strains ; Receptors, Dopamine/*drug effects/physiology ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Taste/*drug effects ; }, abstract = {The neurotransmitter, dopamine (DA), has been implicated in place conditioning but the role of D1 and D2 receptors has not been investigated. In Experiment 1, the effects of SKF 38393 (0, 0.01, 0.1, 1.0, 10.0 mg/kg) and quinpirole (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg), preferential D1 and D2 receptor agonists, respectively, were evaluated and compared to (+)-amphetamine (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg). The experiment consisted of three phases. During the preexposure phase, rats explored two distinctive end compartments adjoined by a small tunnel. The time spent in each compartment was recorded. During the 8-day conditioning phase, rats were treated with drug and confined to one compartment for 30 min. On alternate days, rats received saline and were placed in the opposite compartment. Test days occurred over the remaining three days during which drug-free animals explored both compartments. Rats conditioned with (+)-amphetamine demonstrated a dose-dependent increase in time spent in the drug-paired environment from preexposure to test indicating the establishment of a conditioned place preference. Treatment with quinpirole also resulted in a conditioned place preference, however, only an intermediate dose was effective. In contrast, SKF 38393 produced a dose-dependent decrease in time spent on the drug-paired side suggesting the establishment of a place aversion. The idea that D1 receptors may be exclusively involved in mediating the aversive properties of psychomotor stimulants was tested in Experiment 2 employing a conditioned taste aversion paradigm. The results did not support this notion; it was found that both quinpirole and SKF 38393 produced a conditioned taste aversion.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2852492, year = {1988}, author = {Sutton, RL and Fox, RA and Daunton, NG}, title = {Role of the area postrema in three putative measures of motion sickness in the rat.}, journal = {Behavioral and neural biology}, volume = {50}, number = {2}, pages = {133-152}, doi = {10.1016/s0163-1047(88)90841-2}, pmid = {2852492}, issn = {0163-1047}, mesh = {Animals ; Arousal/physiology ; Avoidance Learning/physiology ; Brain Mapping ; Chlorides/toxicity ; Conditioning, Classical/physiology ; Dose-Response Relationship, Drug ; Drinking Behavior/physiology ; Kinesthesis/physiology ; Lithium/toxicity ; Lithium Chloride ; Motion Sickness/*physiopathology ; Paraventricular Hypothalamic Nucleus/*physiopathology ; Rats ; Rats, Inbred Strains ; Taste/physiology ; }, abstract = {After thermal cauterization of the area postrema in rats the absence of conditioned taste aversion to sucrose paired with lithium chloride (0.15 M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 degrees/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.}, } @article {pmid3412639, year = {1988}, author = {Venugopal, M and Persinger, MA}, title = {Conditioned taste aversion is reduced in rats with a history of lithium/pilocarpine-induced limbic seizures.}, journal = {Neuroscience letters}, volume = {90}, number = {1-2}, pages = {177-180}, doi = {10.1016/0304-3940(88)90807-5}, pmid = {3412639}, issn = {0304-3940}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/drug effects ; Limbic System/drug effects/*physiopathology ; *Lithium ; Male ; *Pilocarpine ; Rats ; Rats, Inbred Strains ; Seizures/chemically induced/*physiopathology ; Taste/*drug effects ; }, abstract = {Limbic seizures were evoked in rats by single subcutaneous injections of lithium and pilocarpine that are known to elicit severe damage to gustatory-affective centers in the brain. About two months later 12 of these rats and 12 control rats that received either lithium or pilocarpine (no seizures) were given free access to 10% sucrose solutions and then injected with 0.15 M LiCl (10 ml/kg). Whereas the control rats demonstrated the expected conditioned taste aversion (CTA) to later presentations of sucrose during single bottle drinking tests, the rats that had been seizured demonstrated a significant attenuation in CTA.}, } @article {pmid3211979, year = {1988}, author = {Zito, KA and Bechara, A and Greenwood, C and van der Kooy, D}, title = {The dopamine innervation of the visceral cortex mediates the aversive effects of opiates.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {30}, number = {3}, pages = {693-699}, doi = {10.1016/0091-3057(88)90086-x}, pmid = {3211979}, issn = {0091-3057}, mesh = {Animals ; Cerebral Cortex/drug effects/*physiology ; Conditioning, Psychological/*drug effects ; Dopamine/*physiology ; Flupenthixol/*pharmacology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Reference Values ; Taste/*drug effects ; Thioxanthenes/*pharmacology ; }, abstract = {We have previously reported that opiates acting on peripheral receptors produce aversive effects whereas opiates acting on central brain receptors produce rewarding effects. The neurotransmitter dopamine (DA) has previously been implicated in both opiate reinforcing (positive) and aversive (negative) effects. We, therefore, chose to investigate the effects of disruption of DA systems on these two motivational properties of the opiate, morphine. Moreover, we sought to determine the brain site where dopamine might act as a mediator of these motivational effects. One group of rats received 6-hydroxydopamine (6-OHDA) lesions of the visceral (agranular insular) cortex to destroy dopaminergic innervation to this area. A separate group of animals were pretreated with intraperitoneal (IP) injections of the DA receptor blocker, alpha-flupenthixol (0.8 mg/kg), followed in both groups by 15 mg/kg (IP) morphine. Both 6-OHDA-lesioned and alpha-flupenthixol-pretreated subjects failed to develop the normal aversion to saccharin seen in control groups following conditioned taste aversion training with morphine. In a place conditioning paradigm, the aversive effects produced by low IP injections of morphine (acting on peripheral receptors) were blocked by 6-OHDA lesions of the visceral cortex. However, DA depletion of the visceral cortex did not disrupt the ability of animals to acquire a morphine place preference. Taken together, these results indicate that DA innervation of the visceral cortex mediates the aversive, but not the rewarding, properties of opiates.}, } @article {pmid2855211, year = {1988}, author = {Yamamoto, T and Matsuo, R and Kiyomitsu, Y and Kitamura, R}, title = {Taste effects of 'umami' substances in hamsters as studied by electrophysiological and conditioned taste aversion techniques.}, journal = {Brain research}, volume = {451}, number = {1-2}, pages = {147-162}, doi = {10.1016/0006-8993(88)90759-7}, pmid = {2855211}, issn = {0006-8993}, mesh = {Animals ; Conditioning, Psychological/*physiology ; Cricetinae ; Electrophysiology ; Glutamates/*physiology ; Guanosine Monophosphate/physiology ; Inosine Monophosphate/physiology ; Male ; Mesocricetus ; Sodium Chloride/physiology ; Sodium Glutamate/*physiology ; Taste/*physiology ; }, abstract = {Behavioral and electrophysiological experiments were performed to examine whether or not the taste of 'umami' substances such as monosodium glutamate (MSG), disodium 5'-inosinate (IMP), and disodium 5'-guanilate (GMP) is really unique in hamsters. When the animals were conditioned to avoid ingestion of MSG (or IMP) or their mixture by pairing its ingestion with an i.p. injection of LiCl, suppression of drinking generalized to IMP (or MSG), GMP, NaCl, and other sodium salts. Suppression of drinking after conditioning to NaCl generalized to MSG, IMP, GMP, and inorganic sodium salts. These learned aversions to umami substances and sodium salts were abolished by bilateral deafferentation of the chorda tympani, but were not affected by destruction of the bilateral glossopharyngeal nerves. The integrated whole-nerve responses of the chorda tympani to MSG, IMP, and NaCl were similar to each other, consisting of the initial dynamic phase and the following tonic phase. Synergism of chorda tympani responses to a mixture of MSG and IMP was not observed. Across-fiber response patterns of the chorda tympani for MSG, IMP, or their mixture were very similar to that for NaCl. Even the high concentrations of umami substances (0.3 M MSG, 0.3 M IMP, and the mixture) did not elicit any detectable responses in the glossopharyngeal nerve. These results suggest that the taste of umami substances is not unique in the hamster, but is similar to that of sodium salts, and is mediated exclusively via the chorda tympani.}, } @article {pmid3395438, year = {1988}, author = {Dogterom, GJ and van Hof, MW}, title = {Attenuation of neophobia and conditioned taste aversion in the rabbit.}, journal = {Behavioural brain research}, volume = {28}, number = {3}, pages = {253-257}, doi = {10.1016/0166-4328(88)90128-3}, pmid = {3395438}, issn = {0166-4328}, mesh = {Animals ; Apomorphine/toxicity ; *Association Learning/drug effects ; *Avoidance Learning/drug effects ; *Conditioning, Classical/drug effects ; Drinking/drug effects ; *Learning/drug effects ; Rabbits ; *Taste/drug effects ; }, abstract = {The phenomenon of taste neophobia to apple juice does exist in the rabbit. It was found that malic acid was the main stimulus source. Attenuation of taste neophobia was due to neuronal processes which took place between rather than during drinking sessions. Conditioned taste aversion learning took place if apomorphine was injected after apple juice intake.}, } @article {pmid3408442, year = {1988}, author = {Shaw, NA}, title = {Disruption of conditioned taste aversion: evidence that ECS weakens the gustatory engram.}, journal = {Behavioral and neural biology}, volume = {49}, number = {3}, pages = {302-309}, doi = {10.1016/s0163-1047(88)90290-7}, pmid = {3408442}, issn = {0163-1047}, mesh = {Amnesia/*physiopathology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Electroshock ; Male ; Memory/physiology ; Rats ; Taste/*physiology ; }, abstract = {Two experiments are reported concerning the neural substrate of conditioned taste aversion (CTA) and the amnesic mechanisms involved when such learning is disrupted by electroconvulsive shock (ECS). Subjects were adult male rats. In the first experiment it is demonstrated that an aversion established to a 2.5% sucrose solution can simulate the learning loss reported in earlier studies which was caused by interpolating ECS between tasting and illness when the aversion was established using a 10% sucrose cue. It is concluded that if ECS acts to disrupt the memory of the taste cue, it possibly reduces it to only about one-quarter of its original strength, a substantial deficit not readily apparent simply from the degree of aversion displayed. In the second experiment, CTAs were established using either a 2.5% sucrose cue or a 10% cue with ECS interpolated during the taste-illness interval. Animals in the two groups were subsequently confronted with a range of sucrose stimuli and their respective aversions were compared. Near identical responses were observed under all conditions tested. These findings are consistent with the theory that ECS disrupts CTA by weakening the gustatory engram.}, } @article {pmid3188640, year = {1988}, author = {Vavilova, NM and Kassil', VG}, title = {[Ontogenetic characteristics of the acquisition and extinction of a taste aversion in dogs following damage to the dorsal area of the hippocampus].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {38}, number = {3}, pages = {454-459}, pmid = {3188640}, issn = {0044-4677}, mesh = {Aging/*physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Dogs ; Extinction, Psychological/*physiology ; Female ; Hippocampus/*physiology ; Male ; Taste/*physiology ; }, abstract = {In 2-9 months dogs the influence was studied of ablation of the hippocampus dorsal area on formation and preservation of conditioned taste aversion (CTA), elaborated by combination of 30% sucrose solution with i.p. injection of 0.28 M LiCl solution. Lesion of the hippocampus dorsal area does not prevent acquisition after the first pairing of conditioned taste aversion in puppies and adult dogs. Heterogeneous influences are observed after hippocampus lesions on the process of CTA extinction in animals of different ages. Acquaintance with conditioned stimulus before CTA acquisition accelerates the process of its extinction in hippocampectomized indiviuals, but less than in animals with an intact hippocampus.}, } @article {pmid3174748, year = {1988}, author = {Stolerman, IP}, title = {Characterization of central nicotinic receptors by studies on the nicotine cue and conditioned taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {30}, number = {1}, pages = {235-242}, doi = {10.1016/0091-3057(88)90451-0}, pmid = {3174748}, issn = {0091-3057}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Psychological ; Cues ; Discrimination Learning ; Dose-Response Relationship, Drug ; Generalization, Psychological ; Male ; Nicotine/antagonists & inhibitors/*pharmacology ; Rats ; Receptors, Nicotinic/*analysis ; Stereoisomerism ; }, abstract = {Some recent studies on the discriminative stimulus (cue) and conditioned taste aversion (CTA) effects of nicotine are reviewed. The characteristics of the nicotine cue correlate well with those of high affinity nicotine binding in studies comparing different nicotinic agonists. The dose of nicotine used for training a discrimination is an important variable determining patterns of generalization. The effects of antagonists on the nicotine cue are also compatible with ligand-binding studies although the lack of competitive antagonists generates unsolved problems for investigators. The CTA produced by nicotine has pharmacological characteristics like the nicotine cue. Both effects are produced at CNS sites that resemble to a certain extent the cholinoceptive sites in autonomic ganglia. The small differences in the degree of stereoselectivity of the two effects or in their sensitivity to antagonists do not constitute substantive evidence for mediation by different receptors. The major differences between the procedures lies in their general psychopharmacological characteristics rather than in any special qualities of the response to nicotine. For example, the nicotine cue is not produced by agents from other pharmacological classes whereas a wide range of different drugs can produce CTA. The concept of multiple types of CNS nicotinic receptors, as supported by certain biochemical studies, requires further evaluation in behavioural systems.}, } @article {pmid2454710, year = {1988}, author = {Yirmiya, R and Zhou, FC and Holder, MD and Deems, DA and Garcia, J}, title = {Partial recovery of gustatory function after neural tissue transplantation to the lesioned gustatory neocortex.}, journal = {Brain research bulletin}, volume = {20}, number = {5}, pages = {619-625}, doi = {10.1016/0361-9230(88)90222-5}, pmid = {2454710}, issn = {0361-9230}, support = {HD 05958/HD/NICHD NIH HHS/United States ; NS 07628/NS/NINDS NIH HHS/United States ; NS 11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/physiology ; Cerebral Cortex/cytology/*transplantation ; Frontal Lobe/cytology/*physiology ; Male ; Rats ; Rats, Inbred Strains ; Silver ; Staining and Labeling ; Taste/*physiology ; Time Factors ; }, abstract = {The ability of homotypic cortical tissue grafts to induce recovery of function after a gustatory neocortex (GN) lesion was studied using the conditioned taste aversion (CTA) paradigm. On acquisition day, 26 GN-lesioned and 8 sham-lesioned rats were presented with a saccharin solution, followed by an injection of the illness-inducing agent lithium chloride (LiCl). On the test day, 2 days later, saccharin was presented again. The GN-lesioned rats showed significantly less aversion to saccharin on the test day, indicating that the lesion impaired their ability to form taste-illness association. Nine of the lesioned rats were then bilaterally transplanted with fetal GN tissue. Nine weeks after the transplantation, the rats were presented with a LiCl solution, which served as both a tastant and an illness-inducing agent. An NaCl solution, which tasted very similar to the LiCl solution, was used to test the CTA to salt 3 days later. The nontransplanted rats consumed significantly more LiCl than the transplanted and sham-operated rats on the acquisition day, but both transplanted and nontransplanted rats consumed more NaCl than sham-operated rats on the test day. Nissl and Golgi stainings showed numerous somata and extensive arborization of neurons within the grafts. The results indicate that fetal GN grafts can restore the ability to integrate gustatory and visceral inputs but not to form long-lasting taste-illness associations.}, } @article {pmid2896235, year = {1988}, author = {Ervin, GN and Cooper, BR}, title = {Use of conditioned taste aversion as a conflict model: effects of anxiolytic drugs.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {245}, number = {1}, pages = {137-146}, pmid = {2896235}, issn = {0022-3565}, mesh = {5-Hydroxytryptophan/pharmacology ; Animals ; Anti-Anxiety Agents/*pharmacology ; Avoidance Learning/*drug effects ; Chlordiazepoxide/pharmacology ; Conditioning, Operant/*drug effects ; Isoproterenol/pharmacology ; Male ; Phenobarbital/pharmacology ; Rats ; Saccharin/pharmacology ; Saline Solution, Hypertonic/pharmacology ; Taste/*drug effects ; }, abstract = {Moderate taste aversions were induced by pairing the initial consumption of 0.25% sodium saccharin (SACC) with either 25 mg/kg i.p. l-5-hydroxytryptophan or 30 mg/kg i.p. LiCl. The expression of these moderate conditioned SACC aversions was antagonized by pretreatments (i.p. or p.o.) with benzodiazepine and non-benzodiazepine anxiolytic drugs (lorazepam, diazepam, chlordiazepoxide, oxazepam, phenobarbital, meprobamate, and chlormezanone). Chlordiazepoxide produced less or no antagonism of the expression of stronger SACC aversions induced by 50 or 75 mg/kg l-5-hydroxytryptophan or by 60 or 90 mg/kg LiCl. Nonanxiolytic drugs, including dipsogenic compounds that increased the water intake of hydrated rats (2 M NaCl i.p.; isoproterenol HCl s.c.; and histamine diphosphate s.c.), and even additional 24 hr of fluid deprivation did not antagonize the expression of moderate conditioned taste aversions, indicating that anxiolytic drugs have a very selective effect and that they do not appear to act through homeostatic drinking mechanisms. An essential feature of the taste aversion conflict model is that thirsty rats encounter only SACC. When water was conspicuously available in addition to SACC in two-bottle tests, neither chlordiazepoxide nor phenobarbital antagonized the expression of conditioned taste aversion. Thus, anxiolytic drugs do not produce amnesia for the conditioned aversion, but attenuate the ability of conditioned SACC aversion to suppress SACC consumption in one-bottle tests. The antagonism of the expression of conditioned taste aversion measured with a one-bottle testing method offers a simple, sensitive, and selective screen for anxiolytic drugs. A possible mechanism by which anxiolytics increase both suppressed as well as unsuppressed fluid consumption is discussed.}, } @article {pmid2834018, year = {1988}, author = {Krahn, DD and Gosnell, BA and Levine, AS and Morley, JE}, title = {Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects.}, journal = {Brain research}, volume = {443}, number = {1-2}, pages = {63-69}, doi = {10.1016/0006-8993(88)91598-3}, pmid = {2834018}, issn = {0006-8993}, mesh = {Animals ; Brain/drug effects/*physiology ; Cerebral Ventricles/drug effects/*physiology ; Conditioning, Psychological/drug effects ; Corticotropin-Releasing Hormone/administration & dosage/metabolism/*pharmacology ; Feeding Behavior/*drug effects ; Food Deprivation ; Grooming/*drug effects ; Injections, Intraventricular ; Male ; Motor Activity/*drug effects ; Norepinephrine/pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, Corticotropin-Releasing Hormone ; Receptors, Neurotransmitter/metabolism ; Reference Values ; Taste ; }, abstract = {Corticotropin-releasing factor (CRF) has potent behavioral effects when administered intracerebroventricularly to rats. CRF and its receptors are found in an uneven distribution in the brain. In an effort to localize the site of the anorectic effect of CRF, exogenous CRF or saline was injected into cannulas directed toward the paraventricular hypothalamic nucleus (PVN), lateral hypothalamus, ventromedial hypothalamus, globus pallidus, or striatum of rats. CRF decreased food intake only when injected into the PVN. In subsequent experiments PVN injections of CRF were shown to (1) increase grooming and movement; (2) not induce a conditioned taste aversion to saccharin in a single bottle test; and (3) inhibit the increase in feeding induced by injections of norepinephrine into the PVN. These results suggest that CRF induces not only anorexia, but also increased movement and grooming by action in the PVN.}, } @article {pmid3398818, year = {1988}, author = {Mitchell, JA and Wilson, MC and Kallman, MJ}, title = {Behavioral effects of pydrin and ambush in male mice.}, journal = {Neurotoxicology and teratology}, volume = {10}, number = {2}, pages = {113-119}, doi = {10.1016/0892-0362(88)90074-8}, pmid = {3398818}, issn = {0892-0362}, mesh = {Administration, Cutaneous ; Administration, Oral ; Animals ; Behavior, Animal/*drug effects ; Insecticides/*toxicity ; Male ; Mice ; Mice, Inbred Strains ; Nitriles ; Permethrin ; Pyrethrins/*toxicity ; Taste/drug effects ; }, abstract = {Male Swiss mice, 20-25 g, were utilized to assess the effects of dermal and oral administration of the pyrethroid insecticide formulations Pydrin (30% fenvalerate) and Ambush (25.6% permethrin). Animals were subjected to a conditioned taste aversion procedure using a normally preferred 0.3% saccharin solution. Subjects were allowed 30 min access to a drinking syringe containing the saccharin solution, followed immediately by the administration of the pyrethroid or control solution. Pydrin (0.3, 3.0, or 30 mg/kg orally; 60, 600, or 1800 mg/kg dermally) and Ambush (0.5, 5.0, or 50 mg/kg orally; 30, or 300 mg/kg dermally) produced significant (p less than 0.05) reductions in the percent saccharin consumed. Total fluid intake, however, was not significantly altered by any of the treatments. The effect of the insecticides on both grouped and individual activity was also assessed in 20-25 g male Swiss mice. Activity measurements were taken over the 4-hr time period immediately following the administration of the pyrethroid or control solution. Pydrin (30 mg/kg orally; 600 and 1800 mg/kg dermally) and Ambush (50 mg/kg orally; 300 mg/kg dermally) significantly (p less than 0.05) increased activity in both grouped and individually tested mice. When subjects were individually tested, significant increases were seen in non-ambulatory, but not in ambulatory activity. The results of this work indicate that administration of the commercially available preparations of Pydrin and Ambush in mice at doses that do not induce the tremor and choreoathetosis-salivation syndromes usually associated with pyrethroid insecticides may result in behavioral changes.}, } @article {pmid3365944, year = {1988}, author = {Hill, RW and Eshuis, RK}, title = {Learning in mature mice (Peromyscus leucopus) subjected to deep hypothermia as neonates.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {102}, number = {1}, pages = {44-48}, doi = {10.1037/0735-7036.102.1.44}, pmid = {3365944}, issn = {0735-7036}, mesh = {Animals ; Animals, Newborn/*physiology ; Avoidance Learning/physiology ; *Body Temperature Regulation ; Brain/*physiology ; Cold Temperature/adverse effects ; Female ; Learning/*physiology ; Male ; Orientation/physiology ; Peromyscus/*physiology ; Taste/physiology ; }, abstract = {In certain species of nonhibernating rodents, although young nestlings cease breathing and heart action when their body temperature is lowered to near freezing, the nestlings need only be rewarmed to recover. This remarkable capacity for immediate recovery has been known many years, but long-range consequences of deep neonatal hypothermia have never before been investigated. Mice (Peromyscus leucopus) that had been exposed to four 2.5-hr episodes of deep (2-4 degrees C) hypothermia when 4-10 days old were later compared with littermate controls in their performance on two learning tasks. The two groups did not differ in their acquisition or extinction of a lithium-induced learned taste aversion to sucrose. Nor did they differ in learning to find a hidden platform in a swimming pool. Thus in a nonhibernating rodent species, deep hypothermia experienced neonatally--unlike similar hypothermia administered in adulthood--seems not to induce deficits in subsequent learning capabilities. The resistance of neonates to damage probably represents an adaptation, for their modest thermoregulatory abilities render them vulnerable to deep hypothermia in frigid environments.}, } @article {pmid3350472, year = {1988}, author = {Miele, J and Rosellini, RA and Svare, B}, title = {Estradiol benzoate can function as an unconditioned stimulus in a conditioned taste aversion paradigm.}, journal = {Hormones and behavior}, volume = {22}, number = {1}, pages = {116-130}, doi = {10.1016/0018-506x(88)90035-9}, pmid = {3350472}, issn = {0018-506X}, mesh = {Animals ; Castration ; Conditioning, Classical/*drug effects ; Estradiol/*pharmacology ; Extinction, Psychological/drug effects ; Female ; Male ; Mice ; Mice, Inbred Strains ; Progesterone/pharmacology ; Taste/drug effects ; Testosterone/pharmacology ; }, abstract = {The extent to which gonadal steroid hormones can serve as unconditioned stimuli in a conditioned taste aversion paradigm was examined in Rockland-Swiss albino mice. With saccharin serving as the conditioned stimulus, subcutaneously injected estradiol benzoate, but not progesterone or testosterone propionate, was found to be a potent unconditioned stimulus in both male and female mice. Dose-response effects were also observed; increasing dosages of estradiol benzoate led to increasingly stronger conditioned aversions in both males and females. The aversion detected in males was more resistant to extinction than that seen in females. Prepubertal gonadectomy reversed the sex-dependent effects of estradiol benzoate in learned aversions in adulthood; castration of males promoted the extinction process, whereas ovariectomy of females retarded extinction. The results may be useful for our understanding of the mechanisms involved in conditioned taste aversion learning as well as a wide array of hormone-dependent behavioral responses.}, } @article {pmid3179508, year = {1988}, author = {Djurić, VJ and Marković, BM and Lazarević, M and Janković, BD}, title = {Anaphylactic shock-induced conditioned taste aversion. II. Correlation between taste aversion and indicators of anaphylactic shock.}, journal = {Brain, behavior, and immunity}, volume = {2}, number = {1}, pages = {24-31}, doi = {10.1016/0889-1591(88)90003-7}, pmid = {3179508}, issn = {0889-1591}, mesh = {Anaphylaxis/immunology/*physiopathology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/drug effects/*physiology ; Dose-Response Relationship, Drug ; Female ; Male ; Ovalbumin ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; }, abstract = {Previous studies (V. J. Djurić, B. M. Marković, M. Lazarević, & B. D. Janković, 1987, in B. D. Janković, B. M. Marković, & N. H. Spector (Eds.), Neuroimmune interactions, pp. 561-568, New York: New York Acad. Sci.; B. M. Marković, V. J. Djurić, M. Lazarević, & B. D. Janković, 1988, Brain Behav. Immun. 2, 11-23) have shown that rats learn to associate the taste of saccharin with the induction of anaphylactic shock, thus exhibiting conditioned taste aversion (CTA) toward an otherwise preferred saccharin solution. The present experiment investigates the effect of unconditioned stimulus intensity (the amount of antigen used for the induction of shock) on CTA. Rats were sensitized to ovalbumin and subjected to a conditioning trial in which the conditioned stimulus (CS; saccharin solution given orally) signaled the presentation of the unconditioned stimulus (US; shocking doses of ovalbumin ranging from 0.5 to 3 mg given intraperitoneally). Behavioral signs, hematocrit, and rectal temperature were used for evaluation of anaphylactic shock. Twenty-four hours after the conditioning trial, rats were subjected to a two-bottle preference test between saccharin solution and water. Multiple regression statistical analysis revealed significant correlations among saccharin preference ratio, dose of antigen used for the induction of shock, behavioral signs of shock, rise in hematocrit, and fall in rectal temperature. A dose-dependent relation among saccharin preference ratio and physiological indicators of shock suggests that conditioned anaphylactic shock-induced avoidance behavior is functionally related to homeostatic factors involved in immune reactivity.}, } @article {pmid3179507, year = {1988}, author = {Marković, BM and Djurić, VJ and Lazarević, M and Janković, BD}, title = {Anaphylactic shock-induced conditioned taste aversion. I. Demonstration of the phenomenon by means of three modes of CS-US presentation.}, journal = {Brain, behavior, and immunity}, volume = {2}, number = {1}, pages = {11-23}, doi = {10.1016/0889-1591(88)90002-5}, pmid = {3179507}, issn = {0889-1591}, mesh = {Anaphylaxis/*physiopathology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/*physiology ; Female ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {A series of three experiments was conducted to investigate whether an anaphylactic response could induce a conditioned modification of behavior. Rats sensitized to ovalbumin were subjected to a conditioning trial in which the conditioned stimulus (CS; saccharin solution) signaled the presentation of the unconditioned stimulus (US; shocking dose of ovalbumin), eliciting the unconditioned response (UR; anaphylactic shock). In a subsequent two-bottle preference test, immunized rats given a CS-US pairing developed a conditioned taste aversion toward an otherwise preferred saccharin solution. The phenomenon of anaphylactic shock-induced conditioned taste aversion was found to be robust and resistant to extinction during the 6-day test period and was established employing three modes of CS-US presentation: (a) CS po, US ip; (b) CS po, US iv; and (c) CS iv, US iv. The most effective mode of CS-US presentation for producing anaphylactic shock-induced taste aversion was observed in Experiment 1 (CS po, US ip). Thus, aversive manifestations of anaphylactic shock can serve as afferent signals by which the immune system informs the central nervous system which in turn modulates behavior.}, } @article {pmid3362923, year = {1988}, author = {Kutscher, CL}, title = {Phenylethylamine-induced taste aversion in rats and mice.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {29}, number = {2}, pages = {287-293}, doi = {10.1016/0091-3057(88)90158-x}, pmid = {3362923}, issn = {0091-3057}, support = {207 RR077068-19/RR/NCRR NIH HHS/United States ; }, mesh = {Amphetamine/toxicity ; Animals ; Conditioning, Psychological/*drug effects ; Drug Interactions ; Female ; Male ; Mice ; Phenethylamines/*toxicity ; Rats ; Seizures/chemically induced/psychology ; Stereotyped Behavior/drug effects ; Taste/*drug effects ; }, abstract = {Phenylethylamine (PEA) has the same structure as amphetamine (AMP) except that PEA lacks a methyl group at the alpha carbon. Although these analogues produce many similar neurobehavioral actions, a previous study found that PEA did not support formation of conditioned taste aversion (CTA). Using somewhat different procedures, in the present study a transient taste aversion was seen in rats. Use of noradrenergic blocking agents to attempt to pharmacologically tailor PEA action to make it more like that of AMP did not improve efficacy to form CTA. A robust PEA-induced CTA was seen in mice even when PEA produced multiple seizures.}, } @article {pmid3358848, year = {1988}, author = {Wesierska, M and Buresová, O and Bures, J}, title = {Differential effect of prior paradoxical sleep deprivation on conditioned taste aversion, neophobia and attenuation of neophobia to solid food in rats.}, journal = {Behavioural brain research}, volume = {27}, number = {2}, pages = {115-121}, doi = {10.1016/0166-4328(88)90037-x}, pmid = {3358848}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Exploratory Behavior/*physiology ; Feeding Behavior/physiology ; Male ; Rats ; Sleep Deprivation/*physiology ; Sleep, REM/*physiology ; Taste/*physiology ; }, abstract = {The effect of paradoxical sleep deprivation (PSD) on subsequent acquisition of conditioned taste aversion (CTA) to liquid diets is confounded by the uncertain level of thirst when using the water tank procedure. This difficulty is eliminated when examining CTA and attenuation of neophobia (AN) to solid diets. Adult male rats (n = 100) were habituated to receive their daily ration of food during a 30-min stay in a box equipped with a row of 10 feeders baited with 2-3 g pieces of moist standard diet. 24-h PSD increased neophobic rejection of novel sweet food (with added 5% saccharose), but did not influence intensity of CTA elicited by LiCl poisoning. Addition of a bitter tasting red food dye to the sweet food caused marked neophobia which was enhanced by preceding PSD. Association of this unpalatable food with LiCl elicited strong CTA which extinguished faster in the PSD-pretreated animals. On the other hand, preacquisition PSD did not influence AN to the same stimulus. Sweet food with added blue dye elicited only mild neophobia which was enhanced by preceding 24-h PSD. Preacquisition PSD did not influence AN but significantly increased CTA to blue sweet food. It is concluded that PSD can either enhance or weaken CTA and that this complex effect on food selection learning cannot be explained by PSD-induced reduction of fear.}, } @article {pmid3281693, year = {1988}, author = {Dunn, LT and Everitt, BJ}, title = {Double dissociations of the effects of amygdala and insular cortex lesions on conditioned taste aversion, passive avoidance, and neophobia in the rat using the excitotoxin ibotenic acid.}, journal = {Behavioral neuroscience}, volume = {102}, number = {1}, pages = {3-23}, doi = {10.1037//0735-7044.102.1.3}, pmid = {3281693}, issn = {0735-7044}, mesh = {Amygdala/drug effects/pathology/*physiology ; Animals ; *Avoidance Learning ; Cerebral Cortex/drug effects/pathology/*physiology ; *Conditioning, Psychological ; Ibotenic Acid/*toxicity ; Male ; Oxazoles/*toxicity ; Phobic Disorders/physiopathology ; Rats ; Rats, Inbred Strains ; Saccharin ; Stereotaxic Techniques ; *Taste ; }, abstract = {The results in this article show that although electrolytic amygdala lesions disrupt learning of a conditioned taste aversion (CTA), ibotenic acid-induced, axon-sparing lesions of the amygdala do not. However, ibotenic acid lesions of the insular cortex do disrupt learning of a CTA. Electrolytic, but not ibotenic acid lesions of the amygdala, interrupt axons running between the insular (gustatory) cortex and the brain stem/hypothalamus. It is the destruction of these projections which appear to underly CTA deficits after amygdala lesions. Other results revealed that ibotenic acid lesions of the insular cortex attenuated the reaction to the novel taste of saccharin in a familiar environment but failed to affect the ingestion of a novel food in a novel environment or passive avoidance learning. Conversely, ibotenic acid lesions of the amygdala did not affect the reaction to novel saccharin in a familiar environment but did impair both the reaction to novel food in a novel environment and passive avoidance learning. We conclude that the insular cortex is involved in reactions to the novelty and associative salience exclusively of taste stimuli, whereas the amygdala is probably more concerned with the reaction to more general aspects of novelty in the environment and in fear-motivated behavior.}, } @article {pmid3413234, year = {1988}, author = {Tews, JK and Repa, JJ and Harper, AE}, title = {Induction of conditioned taste aversion in rats by GABA or other amino acids.}, journal = {Physiology & behavior}, volume = {42}, number = {6}, pages = {591-597}, doi = {10.1016/0031-9384(88)90162-x}, pmid = {3413234}, issn = {0031-9384}, support = {AM-10747/AM/NIADDK NIH HHS/United States ; DK-10747/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acids/administration & dosage/*pharmacology ; Aminobutyrates/administration & dosage/pharmacology ; Animals ; Behavior, Animal ; *Conditioning, Psychological ; Dietary Proteins/administration & dosage ; Feeding Behavior/*drug effects ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Taste/*drug effects ; gamma-Aminobutyric Acid/administration & dosage/*pharmacology ; }, abstract = {GABA included in the diet is known to reduce food intake and growth of rats fed a low protein diet. Experiments were designed to determine if GABA or other small neutral amino acids would affect food intake if they were administered separately from the diet, and if such amino acids could induce a conditioned taste aversion (CTA) to saccharin. Intubated or injected GABA or alpha-aminoisobutyric acid (AIB), a non-metabolizable isomer of GABA, reduced food intake. When rats were fed a low protein diet, IP injection of threonine (2 mmoles/200 g rat) induced CTA but did not depress food intake; serine (3 mmoles/200 g rat) induced CTA and caused only a small reduction in food intake. Another isomer, alpha-amino-n-butyric acid did not affect food intake or induce CTA at the tested concentrations. Adaptation to a high protein diet, which increases enzymatic degradation of many amino acids including GABA and serine, lessened severity of GABA-induced CTA and eliminated that caused by serine. CTA to saccharin can be induced by certain amino acids; the mechanism is unknown but may involve malaise or other adverse sensations.}, } @article {pmid3386415, year = {1988}, author = {Hunt, WA and Rabin, BM}, title = {Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance.}, journal = {Life sciences}, volume = {43}, number = {1}, pages = {59-66}, doi = {10.1016/0024-3205(88)90237-8}, pmid = {3386415}, issn = {0024-3205}, mesh = {Animals ; Conditioning, Classical/*drug effects/*radiation effects ; Drug Tolerance ; Ethanol/*pharmacology ; Gamma Rays ; Male ; Rats ; Rats, Inbred Strains ; Sleep/drug effects ; Taste ; }, abstract = {An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself.}, } @article {pmid3172982, year = {1988}, author = {Walker, MJ and Leavitt, B and Mucha, RF}, title = {Saccharin exposure increases the potency and aversive property of naloxone in drug-naive rats.}, journal = {Life sciences}, volume = {43}, number = {16}, pages = {1305-1311}, doi = {10.1016/0024-3205(88)90585-1}, pmid = {3172982}, issn = {0024-3205}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Temperature/drug effects ; Drug Synergism ; Male ; Naloxone/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin/*pharmacology ; }, abstract = {In naive rats previously given saccharin (0.1%) as the only drinking fluid for 14 days, naloxone produced a conditioned taste aversion at a dose (0.09 mg/kg, SC) that had little or no effect in normal controls. The magnitude of this effect of the saccharin increased between 2 and 7 days after cessation of the treatment. Under these experimental conditions, evidence of an interaction between the saccharin exposure and a naloxone response was also seen with rectal temperature measurements. Therefore, in rats having no history of morphine, previous consumption of saccharin may potentiate various actions of naloxone including its aversive property.}, } @article {pmid3137617, year = {1988}, author = {Cunningham, CL and Hawks, DM and Niehus, DR}, title = {Role of hypothermia in ethanol-induced conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {95}, number = {3}, pages = {318-322}, pmid = {3137617}, issn = {0033-3158}, support = {AA06161/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Operant/*drug effects ; Ethanol/*pharmacology ; Hypothermia/*physiopathology ; Male ; Rats ; Saccharin/pharmacology ; Taste/*drug effects ; Water Deprivation ; }, abstract = {Two experiments examined the effect of ambient temperature during ethanol exposure on development of conditioned taste aversion to saccharin. In both studies, male albino rats receiving saccharin-ethanol (1.5 g/kg, IP) pairings followed by 6-h exposure to a 32 degrees C environment developed a weaker saccharin aversion than did rats experiencing ethanol at room temperature. Exposure to the warm environment reduced ethanol-induced hypothermia, but enhanced ethanol's motor-impairing effect. The influence of ambient temperature on ethanol-induced taste aversion may be due to changes in body temperature, neural sensitivity, or elimination rate. Although alternative accounts cannot be entirely dismissed, this outcome suggests that ethanol-induced hypothermia plays a role in determining strength of conditioned taste aversion and thus may be involved in the regulation of oral ethanol intake in rats.}, } @article {pmid3131799, year = {1988}, author = {Durcan, MJ and Garcha, HS and Stolerman, IP}, title = {Conditioned taste aversions produced by nicotine in Roman High and Low Avoidance strains of rats.}, journal = {Psychopharmacology}, volume = {94}, number = {4}, pages = {532-535}, pmid = {3131799}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Discrimination, Psychological/drug effects ; Male ; Nicotine/*pharmacology ; Rats ; Rats, Inbred Strains ; Species Specificity ; *Taste ; }, abstract = {Rats of the RHA/iop and RLA/iop strains have been compared in a conditioned taste aversion procedure using nicotine (0.4 mg/kg SC) as the UCS. The procedure utilised a balanced, within-subject design for assessing discriminative aversions to drug- and saline-paired flavoured solutions. Nicotine produced clear aversions in both strains and there were no detectable differences in acquisition. During extinction, rats of the RHA/iop strain consumed more of the drug-paired flavoured solution than rats of the RLA/iop strain, and this difference became greater as the number of extinction trials proceeded. Differences in total fluid intake were too small to account for these effects that were also shown by changes in proportional intake when both flavoured solutions were presented simultaneously. Aversion was, therefore, rather weaker in RHA/iop rats than in RLA/iop rats. These results suggest that rats of the two strains do not differ in "learning ability" in a general way, and support interpretations based on differences in emotionality.}, } @article {pmid3059246, year = {1988}, author = {Dantzer, R and Bluthe, RM and LeMoal, M}, title = {Experimental assessment of drug-induced changes in cognitive function: vasopressin as a case study.}, journal = {Neurotoxicology}, volume = {9}, number = {3}, pages = {471-477}, pmid = {3059246}, issn = {0161-813X}, mesh = {Cognition/*drug effects ; Humans ; Vasopressins/*pharmacology ; }, abstract = {Two important forms of cognition are knowledge about internal states and social cognition. Knowledge about internal states is dependent on the ability to discriminate between different classes of visceral sensations and to associate them specifically to distinctive cues. The phenomenon of conditioned taste aversion (CTA) is the best example of this type of knowledge. Many chemicals induce interoceptive changes that can be perceived by animals and give rise not only to subjective sensations but also to causal attributions. However, the possibility that animals are able to discriminate different forms of interoceptive changes in a CTA paradigm has received little attention. Studies of the mechanisms of vasopressin-induced CTA provide evidence that it is the case and that animals are able to classify in different categories sensations related to the vasopressor activity of vasopressin and sensation induced by a prototypical aversive drug, apomorphine. Social cognition involves what individuals know about each other. One of the requirements for social cognition is social recognition, i.e., the ability to identify other individuals and classify them in different categories. Social recognition can be assessed by changes in duration of investigation of another animal when the stimulus animal is presented at different intervals. This form of memory is based on olfactory characteristics of the stimulus animal in rats and it can be enhanced or attenuated by memory-modulating drugs, as demonstrated by experiments with vasopressin.}, } @article {pmid2853383, year = {1988}, author = {Dess, NK and Raizer, J and Chapman, CD and Garcia, J}, title = {Stressors in the learned helplessness paradigm: effects on body weight and conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {44}, number = {4-5}, pages = {483-490}, doi = {10.1016/0031-9384(88)90309-5}, pmid = {2853383}, issn = {0031-9384}, support = {HD05958/HD/NICHD NIH HHS/United States ; NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Arousal/drug effects ; *Avoidance Learning/drug effects ; *Body Weight/drug effects ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Electroshock ; Helplessness, Learned/*psychology ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; *Taste/drug effects ; }, abstract = {Changes in body weight and taste aversion in the learned helplessness paradigm were examined. In Experiment 1, adult male Sprague-Dawley rats drank saccharin or a control solution, followed by either 100 inescapable shocks or simple restraint. Rats were weighted daily and were tested for saccharin aversion two days after the stress session. Shocked rats gained less weight in the days after stress than restrained controls. Saccharin aversion was apparent only among rats that had consumed saccharin before the stress session. Experiment 2 examined whether control over shock affected body weight or taste aversion. Home-cage controls were included to assess the effects of restraint alone. In addition, the combined effects of shock and a toxin on aversion were studied. Rats drank saccharin solution, followed by escapable or inescapable shock, restraint, or no treatment. Then half of each group was injected with saline; the other half was injected with lithium chloride. As in Experiment 1, shock reduced body weight relative to restraint or no treatment, and shock produced a taste aversion among saline-treated rats. However, shock attenuated the aversion produced by lithium chloride, as did simple restraint. There were no differences in body weight or taste aversion between escapably and inescapably shocked rats. These results suggest a role for stress in the anorexia and weight loss associated with clinical depression and may have implications for theories of learning and learned helplessness.}, } @article {pmid2853380, year = {1988}, author = {Dibattista, D}, title = {Conditioned taste aversion produced by 2-deoxy-D-glucose in rats and hamsters.}, journal = {Physiology & behavior}, volume = {44}, number = {2}, pages = {189-192}, doi = {10.1016/0031-9384(88)90136-9}, pmid = {2853380}, issn = {0031-9384}, mesh = {Animals ; Chlorides/pharmacology ; Conditioning, Psychological/*physiology ; Cricetinae ; Deoxy Sugars/*pharmacology ; Deoxyglucose/*pharmacology ; Hyperphagia/chemically induced ; Injections, Intraperitoneal ; Lithium/pharmacology ; Lithium Chloride ; Male ; Mesocricetus ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste/*drug effects ; }, abstract = {The glucose antimetabolite 2-deoxy-D-glucose (2DG) reliably causes hyperphagia in rats, but has consistently proven ineffective in producing overeating in golden hamsters. It was hypothesized that hamsters do not overeat following 2DG administration because of unusually strong aversive effects of the drug in this species. To test this hypothesis, rats and hamsters were tested in a conditioned taste aversion (CTA) paradigm, in which a novel 0.1% saccharin solution was paired on three occasions with intraperitoneal injections of either saline, lithium chloride (LiCl; 50 mg/kg), or 2DG (either 350 or 750 mg/kg). CTA was measured in 16 twenty-minute, two-bottle preference tests which were conducted at 2-3 day intervals following conditioning. LiCl and 2DG both produced strong and long-lasting aversions to saccharin solution in rats. However, 2DG was significantly less effective than LiCl in producing CTA in hamsters. It is unlikely, therefore, that the failure of 2DG to produce hyperphagia in hamsters is due primarily to an unusual sensitivity to the aversive effects of the drug.}, } @article {pmid2853374, year = {1988}, author = {Watson, PJ and Leitner, C}, title = {Patterns of increased and decreased ingestive behavior after injections of lithium chloride and 2-deoxy-D-glucose.}, journal = {Physiology & behavior}, volume = {43}, number = {6}, pages = {697-704}, doi = {10.1016/0031-9384(88)90366-6}, pmid = {2853374}, issn = {0031-9384}, mesh = {Animals ; Chlorides/*pharmacology ; Deoxy Sugars/*pharmacology ; Deoxyglucose/*pharmacology ; Eating/drug effects ; Feeding Behavior/*drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Pica/chemically induced ; Rats ; Taste/drug effects ; }, abstract = {In previous research, 750 mg/kg 2DG yielded a number of effects suggesting a postdrug nausea; and the present experiments revealed that the illness-inducing agent LiCl similarly produced taste aversion learning at 7.5 mg/kg, inhibited drinking in water-deprived animals at 30 mg/kg, depressed feeding in hungry rats at 60 mg/kg, and evoked food intake and pica at 120 mg/kg. The appearance of eating and pica at the same dosage suggested that rats may eat food as well as a nonnutritive substance as a species-specific reaction to illness and that postdrug feeding, including that observed after 2DG, is an insufficient condition for concluding that a treatment produces no internal distress. A liquid diet that reportedly ameliorates the glucoprivic feeding deficits produced by lateral hypothalamic and zona incerta lesions theoretically could produce its effects if lesions made rats more reactive to 2DG-induced malaise and if this diet were more palatable to animals experiencing internal distress. However, this liquid diet failed to facilitate food intake after LiCl, nor did it reduce the inhibited eating produced by LiCl in food-deprived subjects. Liquid diet effects in lesioned animals, therefore, may not be explained by factors related to a 2DG-induced malaise.}, } @article {pmid3432315, year = {1987}, author = {Etscorn, F and Moore, GA and Scott, EP and Hagen, LS and Caton, TM and Sanders, DL and Divine, KK}, title = {Conditioned saccharin aversions in rats as a result of cutaneous nicotine or intraperitoneal nicotine administered in divided doses.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {28}, number = {4}, pages = {495-502}, doi = {10.1016/0091-3057(87)90512-0}, pmid = {3432315}, issn = {0091-3057}, mesh = {Administration, Topical ; Animals ; Avoidance Learning/*drug effects ; Injections, Intraperitoneal ; Male ; Nicotine/administration & dosage/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin/pharmacology ; Taste/*drug effects ; }, abstract = {Nicotine base was used in a conditioned taste aversion (CTA) paradigm to avert male Sprague-Dawley rats to saccharin solution (0.1%, w/v). Experiments investigated different dose routes of nicotine administration and duration of action as determinants in nicotine-induced CTA. In Experiment 1 nicotine was injected intraperitoneally (IP) at doses of 0.5, 1.0, or 3.0 mg/kg 30 min after drinking saccharin solution. Using a two-bottle choice test, no CTA was observed, although all nicotine animals showed obvious symptoms of malaise including seizures in the highest dose group. Experiment 2 showed dose-related CTA when nicotine (10.0, 30.0, or 50.0 mg/kg) was cutaneously applied 30 min following saccharin drinking. Experiment 2B showed that the aversions were due to associative rather than nonassociative factors such as sensitization or enhanced neophobia. In Experiment 3, the following group treatments were begun 30 min after saccharin drinking to distribute identical total nicotine doses over an extended period of time: One IP injection of 2.0 mg/kg nicotine (in a saline vehicle) and four injections of saline solution, three injections of 0.67 mg/kg nicotine and two injections of saline, five injections of 0.40 mg/kg nicotine, or five injections of saline. All injections were spaced 30 min apart. Compared with saline-injected controls, CTA occurred in the rats receiving either three or five injections of nicotine but the group receiving one injection did not differ from the control group. There was no difference in CTA between the groups receiving three or five injections.}, } @article {pmid3324799, year = {1987}, author = {Spivak, K and Aragon, CM and Amit, Z}, title = {Alterations in brain aldehyde dehydrogenase activity modify ethanol-induced conditioned taste aversion.}, journal = {Alcoholism, clinical and experimental research}, volume = {11}, number = {6}, pages = {513-517}, doi = {10.1111/j.1530-0277.1987.tb00163.x}, pmid = {3324799}, issn = {0145-6008}, mesh = {Acetaldehyde/*blood ; Animals ; Conditioning, Psychological ; Cyanamide/antagonists & inhibitors/pharmacology ; Ethanol/blood/*pharmacology ; Fomepizole ; Male ; Pyrazoles/pharmacology ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {The role of peripherally and centrally acting acetaldehyde in ethanol-induced conditioned taste aversion (CTA) was investigated using various enzyme manipulations. Cyanamide, an aldehyde dehydrogenase inhibitor (ALDH) elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Under both treatment conditions brain and liver ALDH activity is inhibited. Water-deprived rats were pretreated 4 hr prior to fluid presentation with intraperitoneal injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C), or 4-methylpyrazole + cyanamide (4MP+C). Subsequently, animals were presented with a novel saccharin solution followed immediately by intraperitoneal injection of one of three doses of ethanol (0.4, 0.8, or 1.2 g/kg) or saline vehicle on four occasions. Results suggested that animals pretreated with cyanamide (groups S+C and 4MP+C) drank significantly less saccharin after conditioning with a subthreshold dose of ethanol (0.4 g/kg) in comparison to groups S+S and 4MP+S. Moreover, at the conditioning dose of 1.2 g/kg, cyanamide-treated animals demonstrated an attenuation of CTA compared to the other two groups. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral acetaldehyde accumulation. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of ethanol-induced CTAs. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.}, } @article {pmid2844375, year = {1987}, author = {Heth, CD and Stefan, LO}, title = {Within-compound learning with US presentation in taste aversion.}, journal = {Canadian journal of psychology}, volume = {41}, number = {4}, pages = {501-509}, doi = {10.1037/h0084169}, pmid = {2844375}, issn = {0008-4255}, mesh = {Animals ; Association Learning/*drug effects ; Avoidance Learning/*drug effects ; Chlorides/*toxicity ; Conditioning, Classical/*drug effects ; Learning/*drug effects ; Lithium/*toxicity ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, } @article {pmid3685067, year = {1987}, author = {Hunt, T and Segal, R and Amit, Z}, title = {Differential involvement of central cholinergic mechanisms in the aversive stimulus properties of morphine and amphetamine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {28}, number = {3}, pages = {335-339}, doi = {10.1016/0091-3057(87)90449-7}, pmid = {3685067}, issn = {0091-3057}, mesh = {Acetylcholine/*physiology ; Amphetamine/*pharmacology ; Animals ; Atropine/pharmacology ; Atropine Derivatives/pharmacology ; Conditioning, Psychological/*drug effects/physiology ; Male ; Morphine/*pharmacology ; Rats ; Rats, Inbred Strains ; Reinforcement, Psychology ; Taste/drug effects/physiology ; }, abstract = {Previously, it was reported that pretreatment with the centrally-acting cholinergic antagonist atropine, but not the peripherally-acting antagonist, methyl-atropine, may serve to attenuate the positive reinforcing properties of morphine and conversely, to enhance those of amphetamine as evidenced within a drug self-administration paradigm in rats. In parallel, evidence from several sources would suggest that there may be a functional relationship between the neurochemical mechanisms mediating these drugs' positive reinforcing properties and their seemingly paradoxical capacity to act as aversive stimuli, as evidenced within a conditioned taste aversion (CTA) paradigm. Accordingly, the present study undertook to examine whether a similar differential involvement of central cholinergic mechanisms established for these drugs' positive reinforcing effects may be obtained for morphine and amphetamine-induced CTA. Using a conventional CTA paradigm, animals were pretreated with either intraperitoneal (IP) atropine or methyl-atropine (0.6 mg/kg) 40 minutes prior to consuming a novel 0.1% saccharin solution. This taste stimulus was paired with IP injection of 15 mg/kg morphine or vehicle. Results showed that atropine (but not methyl-atropine) pretreatment served to attenuate the morphine CTA. In a second experiment, atropine-pretreatment failed to attenuate, and may have slightly potentiated, a CTA induced by 1 mg/kg amphetamine. Atropine pretreatment did not affect a CTA induced by the emetic agent, lithium chloride. Pretreatment with the peripherally-acting methyl-atropine had no effect on the amphetamine CTA and served, if anything, to slightly attenuate the lithium chloride CTA.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3431748, year = {1987}, author = {Ng Cheong Ton, JM and Amit, Z}, title = {Effects of naloxazone on morphine-ethanol interaction in the conditioned taste aversion paradigm.}, journal = {Neuroscience letters}, volume = {81}, number = {3}, pages = {335-338}, doi = {10.1016/0304-3940(87)90406-x}, pmid = {3431748}, issn = {0304-3940}, mesh = {Animals ; Conditioning, Classical/drug effects ; Drug Interactions ; Ethanol/metabolism/*pharmacology ; Male ; Morphine/metabolism/*pharmacology ; Naloxone/*analogs & derivatives/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {The effects of naloxazone on the interaction between alcohol and morphine were examined in the conditioned taste aversion paradigm (CTA). Naloxazone injected 4.5 h before the pre-exposure drug significantly attenuated the pre-exposure effect of morphine on ethanol CTA as well as the effect of ethanol on morphine CTA. The results are discussed in terms of possible mechanisms of opiate-alcohol interaction.}, } @article {pmid3659105, year = {1987}, author = {Cannon, DS and Carrell, LE}, title = {Rat strain differences in ethanol self-administration and taste aversion learning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {28}, number = {1}, pages = {57-63}, doi = {10.1016/0091-3057(87)90012-8}, pmid = {3659105}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Ethanol/*administration & dosage/pharmacology ; Female ; Male ; Phenotype ; Rats ; *Rats, Inbred Strains ; Rats, Inbred WKY ; Saccharin/administration & dosage ; *Self Administration ; Species Specificity ; *Taste ; }, abstract = {Taste aversion learning was investigated in two inbred strains of rats known to differ in amount of ethanol (EtOH) they will self-administer orally. The "low EtOH preference" strain, WKYs, acquired an aversion to an EtOH solution during self-administration; but a "high preference" strain, M520s, did not. It was shown that a lower dose of EtOH will condition saccharin aversion in WKYs than in M520s, suggesting EtOH is a more effective US in the low preference strain. Analysis of patterns of EtOH self-administration indicates the pattern of the low preference strain is more likely to result in taste aversion learning. The implications of these results for the presumed relation between EtOH preference and other EtOH-related phenotypes is discussed.}, } @article {pmid3659104, year = {1987}, author = {Cannon, DS and Carrell, LE}, title = {Effect of taste aversion learning on ethanol self-administration.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {28}, number = {1}, pages = {53-56}, doi = {10.1016/0091-3057(87)90011-6}, pmid = {3659104}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Ethanol/*administration & dosage/pharmacology ; Male ; Rats ; *Self Administration ; *Taste ; Water Deprivation ; }, abstract = {Ethanol (EtOH) oral self-administration studies using rats have had inconsistent outcomes: studies in which rats are fluid deprived report decreasing EtOH intake over trials, whereas studies not employing fluid deprivation report increasing intake over trials. The present study supports the hypothesis that differential taste aversion learning may account for some of this discrepancy. This study indicates that taste aversion learning is maximized under fluid deprivation conditions and that "latent inhibition," i.e., exposure to non-intoxicating amounts of the EtOH solution prior to conditioning, reduces taste aversion learning. It is suggested that the effect of fluid deprivation on taste aversion resulting from EtOH self-administration may be at least in part due to the development of latent inhibition in non-deprived animals during initial exposure to the EtOH solution.}, } @article {pmid3505758, year = {1987}, author = {Grota, LJ and Ader, R and Cohen, N}, title = {Taste aversion learning in autoimmune Mrl-lpr/lpr and Mrl +/+ mice.}, journal = {Brain, behavior, and immunity}, volume = {1}, number = {3}, pages = {238-250}, doi = {10.1016/0889-1591(87)90026-2}, pmid = {3505758}, issn = {0889-1591}, support = {K3-MH6318/MH/NIMH NIH HHS/United States ; NS22228/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/*psychology ; *Avoidance Learning ; Conditioning, Classical ; Disease Models, Animal ; Female ; *Food Preferences ; Male ; Mice ; Mice, Mutant Strains ; Reference Values ; Taste ; }, abstract = {Conditioned taste aversion to a neutral stimulus paired with an immunosuppressive drug (cyclophosphamide) was assessed in lupus-prone MRL-lpr/lpr and congenic control (MRL +/+) mice. The presence of lymphoproliferation in MRL-lpr/lpr mice was associated with poorer taste aversion learning and varied as a function of the dose of cyclophosphamide. There were no differences in learning performance between MRL-lpr/lpr and MRL +/+ mice when the animals were tested at an age prior to the development of lymphadenopathy, or when lithium chloride or electric shock were used as unconditioned stimuli. These results are consistent with the hypothesis that the immune status of an organism has an impact on behavior and the possibility that behavior can serve an in vivo immunoregulatory function.}, } @article {pmid3670594, year = {1987}, author = {Everitt, BJ and Robbins, TW and Evenden, JL and Marston, HM and Jones, GH and Sirkiä, TE}, title = {The effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on the acquisition and retention of a conditional visual discrimination: implications for cholinergic hypotheses of learning and memory.}, journal = {Neuroscience}, volume = {22}, number = {2}, pages = {441-469}, doi = {10.1016/0306-4522(87)90346-0}, pmid = {3670594}, issn = {0306-4522}, mesh = {Animals ; Basal Ganglia/*physiology ; Behavior, Animal/physiology ; *Conditioning, Psychological ; *Discrimination, Psychological ; Globus Pallidus/*physiology ; Ibotenic Acid ; Learning/*physiology ; Male ; Memory/*physiology ; Models, Neurological ; Parasympathetic Nervous System/physiology ; Rats ; Rats, Inbred Strains ; Retention, Psychology/*physiology ; Substantia Innominata/*physiology ; }, abstract = {The effects of ibotenic acid-induced lesions of the ventral pallidum/substantia innominata region, the dorsal pallidum or both on the acquisition and retention of a conditional visual discrimination have been studied in the rat. Lesions of the ventral pallidum and large lesions of the dorsal and ventral pallidum severely impaired both the acquisition and retention of the conditional discrimination. Dorsal pallidal lesions had similar, but less marked effects. The same lesions also impaired the retention of a passive avoidance task, but had no effect on a conditioned taste aversion. Neurobiological investigations revealed that the lesions destroyed cholinergic neurons in the magnocellular nucleus basalis and caused reductions in cortical choline acetyltransferase activity of about 30-40%. Tract-tracing experiments indicated that the lesions destroyed, in particular, cholinergic neurons projecting to the frontal dorsolateral cortex and also those projecting to more posterior cortex, but not the occipital lobes. Contingency analysis of the behavioural, neurochemical and neuroanatomical data indicated that those animals with the largest decreases in choline acetyltransferase activity, or the largest areas of neuronal loss in the ventral and dorsal globus pallidus, were most impaired in the retention of the conditional discrimination. The results do not, therefore, indicate a simple relationship between cholinergic neuronal loss and the retention of response rules essential for performance of the task ("reference memory"). The relevance of the results to cholinergic hypotheses of learning and memory is discussed.}, } @article {pmid2821558, year = {1987}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {27}, number = {4}, pages = {677-683}, doi = {10.1016/0091-3057(87)90194-8}, pmid = {2821558}, issn = {0091-3057}, mesh = {Amifostine/pharmacology ; Amphetamine/*pharmacology ; Animals ; *Avoidance Learning/drug effects/radiation effects ; *Conditioning, Classical/drug effects/radiation effects ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Male ; Rats ; Rats, Inbred Strains ; Sucrose ; *Taste/drug effects/radiation effects ; }, abstract = {Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intact rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion.}, } @article {pmid2821557, year = {1987}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Taste aversion learning produced by combined treatment with subthreshold radiation and lithium chloride.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {27}, number = {4}, pages = {671-675}, doi = {10.1016/0091-3057(87)90193-6}, pmid = {2821557}, issn = {0091-3057}, mesh = {Animals ; *Avoidance Learning/drug effects/radiation effects ; Chlorides/*pharmacology ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Sucrose ; *Taste/drug effects/radiation effects ; }, abstract = {These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.}, } @article {pmid3620950, year = {1987}, author = {Bermúdez-Rattoni, F and Fernández, J and Sánchez, MA and Aguilar-Roblero, R and Drucker-Colín, R}, title = {Fetal brain transplants induce recuperation of taste aversion learning.}, journal = {Brain research}, volume = {416}, number = {1}, pages = {147-152}, doi = {10.1016/0006-8993(87)91507-1}, pmid = {3620950}, issn = {0006-8993}, mesh = {Amygdala/embryology/physiology/*transplantation ; Animals ; Avoidance Learning/*physiology ; Cerebral Cortex/embryology/physiology/*transplantation ; Conditioning, Classical/physiology ; Fetus ; Horseradish Peroxidase ; Male ; Neural Pathways/physiology ; *Neuronal Plasticity ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {Rats showing disrupted taste aversion due to gustatory neocortex or amygdala lesions were transplanted into the lesioned area with homologous brain tissue obtained from 17-day-old fetuses. Comparisons of taste aversions scores before and after the graft, revealed that the grafted animals significantly recuperated taste aversions, whereas cortical lesioned animals without grafts did not. Surprisingly, however, amygdala-lesioned animals without graft presented spontaneous recovery. These results not only support the hypothesis that fetal brain transplants can restore cognitive functions, but also that there are some fundamental functional differences between the gustatory neocortex and the amygdala in the regulation of the processes involved in the acquisition and retention of taste aversion.}, } @article {pmid3038640, year = {1987}, author = {Hoffmann, H and Molina, JC and Kucharski, D and Spear, NE}, title = {Further examination of ontogenetic limitations on conditioned taste aversion.}, journal = {Developmental psychobiology}, volume = {20}, number = {4}, pages = {455-463}, doi = {10.1002/dev.420200409}, pmid = {3038640}, issn = {0012-1630}, support = {1 R01 MH35219/MH/NIMH NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Body Weight ; Catheterization ; Chlorides/administration & dosage ; Conditioning, Classical/*physiology ; Female ; *Food Preferences ; Lithium/administration & dosage ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Sucrose/administration & dosage ; Taste/*physiology ; Time Factors ; }, abstract = {This study was to resolve a discrepancy in the literature as to the capability of infant rats in acquiring conditioned taste aversion. Previous studies had indicated that during the 1st postnatal week, an aversion to saccharin could be conditioned when paired with lithium chloride (LiCl). Analogous conditioning with sucrose did not seem to occur until the end of the 2nd postnatal week, however, even though sucrose is discriminated from water and preferred before then. We observed that 5- and 9-day old pups express conditioned taste aversion to both saccharin and sucrose flavors that previously were paired with illness induced by LiCl. This learning occurred only when several hours separated cannulation and conditioning. A number of other factors that seemed likely to determine this early learning were found to have no effect. Thus it appears that rats can learn taste aversions very early in life, but only under certain circumstances. The results are discussed with reference to Vogt and Rudy's (1984) conclusions on the ontogeny of taste guided behaviors in the rat.}, } @article {pmid2821551, year = {1987}, author = {Blancquaert, JP and Lefebvre, RA and Willems, JL}, title = {Antiaversive properties of opioids in the conditioned taste aversion test in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {27}, number = {3}, pages = {437-441}, doi = {10.1016/0091-3057(87)90346-7}, pmid = {2821551}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Endorphins/*pharmacology ; Enkephalin, Leucine/pharmacology ; Enkephalin, Methionine/analogs & derivatives/pharmacology ; Female ; Fentanyl/pharmacology ; Male ; Methadone/pharmacology ; Morphine/pharmacology ; Narcotics/*pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, Opioid/drug effects ; Taste/*drug effects/physiology ; }, abstract = {The antiaversive effect of mu-, kappa- and delta-opioid receptor agonists against conditioned taste aversion (CTA) induced by apomorphine, lithium chloride and copper sulphate in the rat was studied, in order to evaluate whether prevention of CTA is a suitable model for the study of antiemetics. Anti-aversion was not a general characteristic of all opioid substances tested. Only one dose of the mu-agonist morphine and only one dose of the kappa-agonist ethylketocyclazocine had a consistent antiaversive effect against CTA induced by apomorphine; one dose of the delta-agonist [D-Ala2, Met5]enkephalinamide antagonized the aversion induced by lithium chloride. As the results do not correspond to our previous findings on the antiemetic effects of these opioids in the dog (all mu- and kappa-agonists tested having an antiemetic effect), we conclude that the CTA test cannot be used as a screening test for potentially antiemetic drugs.}, } @article {pmid3628439, year = {1987}, author = {Clark, DE and Wellman, PJ and Harvey, RB and Lerma, MS}, title = {Effects of vomitoxin (deoxynivalenol) on conditioned saccharin aversion and food consumption in adult rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {27}, number = {2}, pages = {247-252}, doi = {10.1016/0091-3057(87)90566-1}, pmid = {3628439}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Eating/drug effects ; Food Preferences/drug effects ; Lithium/poisoning ; Male ; Rats ; Saccharin ; Sesquiterpenes/*pharmacology ; Taste/*drug effects ; Trichothecenes/administration & dosage/*pharmacology ; }, abstract = {Vomitoxin is a trichothecene mycotoxin that induces feed refusal. Experiment I evaluated the potential aversive action of vomitoxin in a conditioned taste aversion paradigm. Adult male rats were fed either a control chow diet or a diet adulterated with 640 ppm lithium chloride (positive control) or with 2, 4 or 8 ppm vomitoxin and given access to a 0.1% saccharin solution and tap water during three training days. The rats were then shifted to a plain chow diet during 5 extinction days. Vomitoxin (8 ppm) and the positive control diet induced marked taste aversion commencing on the first day of exposure. Rats fed the 4 and 8 ppm vomitoxin diets ate less food only on the first day of contaminated diet exposure. Experiment II evaluated the potential action of vomitoxin on food palatability. Adult male rats were fed a powdered commercial chow for 5 days and then offered, in a preference test, a choice of chow and either: the same chow or chow adulterated with either 0.25, 0.50, 1.0, 2.0, 4.0 or 8.0 ppm vomitoxin. Relative to the total food intakes and the choice ratios (control chow consumed/total chow consumed) of the chow-chow groups, adulteration with 8 ppm vomitoxin resulted in a significant reduction in overall food intake, but not in food choice ratio and this effect of vomitoxin on feed consumption was observed only on day 1 of exposure. Vomitoxin, at 4 and 8 ppm, does not alter food palatability but does induce conditioned saccharin aversion.}, } @article {pmid3601602, year = {1987}, author = {Fischer, GJ and Gilman, SC and Blank, C}, title = {Corticosterone response underlying tolerance to stress induced by a gaseous (nitrous oxide) environment.}, journal = {Perceptual and motor skills}, volume = {64}, number = {3 Pt 1}, pages = {799-808}, doi = {10.2466/pms.1987.64.3.799}, pmid = {3601602}, issn = {0031-5125}, mesh = {Animals ; Arousal/*drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Corticosterone/*blood ; Drinking/drug effects ; Male ; Nitrous Oxide/*pharmacology ; Rats ; Rats, Inbred Strains ; Social Environment ; Taste/*drug effects ; }, abstract = {Conditioned taste aversion (CTA) was demonstrated in rats following a single pairing between ingestion of a novel saccharin solution (CS) and 60 min. inhalation of an 80% N2O2:20% N2O gas mixture (UCS). CTA from a single novel CS-N2O UCS pairing was achieved by methodological improvements including: an inhalation chamber for small animals that achieved complete gas diffusion, an increased UCS duration (60 min. of inhalation) and a decreased CS-UCS interval (1 min.). The increased N2O UCS inhalation probably contributed to CTA, since no duration less than 60 min. of N2O inhalation produced significantly greater plasma corticosterone elevation than 60 min. of N2:O2 inhalation. The hypothesis that CTA is stress-induced was supported, in that plasma corticosterone levels were elevated by N2O inhalation and adrenal catecholamines (CA) were depleted. Further, after 4 N2O pretreatments, which produced partial behavioral tolerance to N2O treatment, plasma corticosterone elevation abated somewhat. However, corticosterone level also was raised by N2:O2 treatment. As a result, abatement of corticosterone elevation cannot account for behavioral tolerance to N2O-induced CTA, though it may be a contributor. Since adrenal CA were depleted by N2O inhalation, this response also might abate and underlie or contribute to behavioral tolerance.}, } @article {pmid3591981, year = {1987}, author = {Maggio, CA and Koopmans, HS}, title = {Satiety effects of intragastric meals containing triglycerides with different chain lengths.}, journal = {The American journal of physiology}, volume = {252}, number = {6 Pt 2}, pages = {R1106-13}, doi = {10.1152/ajpregu.1987.252.6.R1106}, pmid = {3591981}, issn = {0002-9513}, support = {AM-17926/AM/NIADDK NIH HHS/United States ; AM-37918/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Appetite/*drug effects ; Dietary Fats/*pharmacology ; Gastric Emptying ; Male ; Rats ; Rats, Inbred Strains ; Structure-Activity Relationship ; Triglycerides/*pharmacology ; }, abstract = {Intragastric meals containing triglycerides with chain length of 2-18 significantly reduced intake in deprived Sprague-Dawley rats feeding 20 min after infusion. Satiety after long-chain triglyceride (LCT) infusions must have been mediated via a gastroenteric signal, since feeding was reduced prior to delivery of these fats into the bloodstream. Equicaloric infusions of triglycerides with chain length of 6 to 18 had similar inhibitory effects, indicating that the satiety effects of these triglycerides depended more on the number of calories infused than on chain length. Shorter-chain triglycerides were initially more effective in reducing feeding. Except for a poorly absorbed LCT the infusions did not result in conditioned taste aversion and thus did not appear to induce discomfort. Gastric recovery of a nonabsorbable marker at the time of the feeding test indicated that gastric emptying, like satiety, was related to the caloric properties of the infusions. These effects could be mediated through neural and/or hormonal mechanisms that are stimulated through energy-related properties of triglycerides.}, } @article {pmid3476972, year = {1987}, author = {Baum, M}, title = {Anorexia treatment based on extinction of a taste aversion: an addendum to Bernstein and Borson (1986).}, journal = {Psychological reports}, volume = {60}, number = {3 Pt 2}, pages = {1056-1058}, doi = {10.1177/0033294187060003-206.1}, pmid = {3476972}, issn = {0033-2941}, mesh = {Anorexia/psychology/*therapy ; *Avoidance Learning ; Behavior Therapy/*methods ; *Extinction, Psychological ; Feeding and Eating Disorders/*therapy ; Humans ; *Taste ; }, } @article {pmid3038137, year = {1987}, author = {Dunn, LT and Everitt, BJ}, title = {The effects of lesions to noradrenergic projections from the locus coeruleus and lateral tegmental cell groups on conditioned taste aversion in the rat.}, journal = {Behavioral neuroscience}, volume = {101}, number = {3}, pages = {409-422}, doi = {10.1037//0735-7044.101.3.409}, pmid = {3038137}, issn = {0735-7044}, mesh = {Animals ; Cerebral Cortex/physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Dopamine/physiology ; Drinking/drug effects ; Lithium/toxicity ; Lithium Chloride ; Locus Coeruleus/*physiology ; Male ; Mental Recall/physiology ; Neural Pathways/physiology ; Norepinephrine/physiology ; Rats ; Receptors, Adrenergic/*physiology ; Serotonin/physiology ; Taste/*physiology ; Tegmentum Mesencephali/*physiology ; }, abstract = {Lesions of the coeruleo-cortical noradrenergic projections caused marked cortical noradrenaline depletions but were not associated with deficits in the acquisition or extinction of a conditioned taste aversion (CTA). Lesions of lateral tegmental noradrenergic projections resulted in marked hypothalamic noradrenaline depletions, enhanced neophobia to the novel taste of saccharin, unimpaired acquisition but prolonged extinction of the CTA. However, when animals with lateral tegmental noradrenergic lesions received extensive preconditioning exposure to saccharin, acquisition of the CTA was attenuated and extinction was more rapid than in controls. Alterations in CTA learning and extinction following lesions of the lateral tegmental noradrenergic system appear to reflect alterations in the way that animals with lesions react toward the hedonic aspects of taste-related stimuli rather than alterations in associational or attentional mechanisms.}, } @article {pmid2820304, year = {1987}, author = {West, DB and Greenwood, MR and Marshall, KA and Woods, SC}, title = {Lithium chloride, cholecystokinin and meal patterns: evidence that cholecystokinin suppresses meal size in rats without causing malaise.}, journal = {Appetite}, volume = {8}, number = {3}, pages = {221-227}, doi = {10.1016/0195-6663(87)90021-3}, pmid = {2820304}, issn = {0195-6663}, support = {AM07332/AM/NIADDK NIH HHS/United States ; AM17844/AM/NIADDK NIH HHS/United States ; CD12637/CD/ODCDC CDC HHS/United States ; }, mesh = {Animals ; Chlorides/*pharmacology ; Cholecystokinin/*pharmacology ; Feeding Behavior/*drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Satiation/*drug effects ; }, abstract = {Gut hormones which are proposed as natural satiety factors may act through malaise to suppress short-term feeding instead of through a normal physiological process. Evaluation of the ability of candidate satiety hormones to serve as the unconditioned stimulus in the development of a conditioned taste aversion is not adequate evidence of malaise since agents which do not produce malaise in humans are also capable of conditioning aversions. Examination of the patterns of eating behavior when drugs are given during a meal in rats may serve as a better test of the potential of an agent to produce illness. To evaluate this approach, LiCl (a known aversive agent) was infused into five rats at the start of each free-feeding meal at a dose of 1.9 mg/meal/rat for four days and at 3.8 mg/meal/rat for an additional four days. Feeding patterns during drug infusion were compared with patterns for six days when no drugs were infused. LiCl infusion produced a significant dose-dependent reduction in feeding frequency while the size and duration of meals were not changed. At the higher dose of lithium, daily meal number was reduced from a normal 13.2 +/- 1.4 to 9.9 +/- 0.5 meals/day. This pattern of behavior is significantly different from the behavior exhibited when cholecystokinin octapeptide (CCK-8) was infused using the same paradigm. CCK-8 significantly reduced meal size while meal frequency increased to compensate for the smaller meals. These findings suggest that LiCl infusion during a meal will lead to an aversion to feeding while CCK-8 is not effective at producing an aversion.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3615551, year = {1987}, author = {Romano, JA and King, JM}, title = {Conditioned taste aversion and cholinergic drugs: pharmacological antagonism.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {27}, number = {1}, pages = {81-85}, doi = {10.1016/0091-3057(87)90480-1}, pmid = {3615551}, issn = {0091-3057}, mesh = {Animals ; Atropine/*pharmacology ; Avoidance Learning/*drug effects ; Benactyzine/pharmacology ; Conditioning, Classical/*drug effects ; Male ; Parasympathomimetics/*pharmacology ; Physostigmine/pharmacology ; Pyridostigmine Bromide/pharmacology ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {The effectiveness of drugs as unconditioned stimuli (UCSs) in the conditioned taste aversion (CTA) procedure may be influenced by specific pharmacological antagonism. The present studies examined the UCS effects of two carbamates, physostigmine salicylate (PS) and pyridostigmine bromide (PB), and three anticholinergic compounds, atropine methyl nitrate (AMN), atropine sulfate (AS), and benactyzine hydrochloride (BH). Individual drugs, as well as combinations of the carbamates and the anticholinergics, were studied in a two-bottle procedure in rats. The lowest effective doses for eliciting significant CTAs were PS, 0.32 mg/kg; PB, 1.00 mg/kg; AMN, 0.04 mg/kg; AS, 0.07 mg/kg and BH, 0.90 mg/kg, IP. Combinations of PS with either AMN or BH were mutually antagonistic as UCSs, whereas PS with AS was not. PB with AMN, but not with AS, also showed antagonism in the procedure. The present results suggest that the CTA procedure is well-suited for direct examination of cholinergic drug effects and may also be used to explore interactions of different classes of cholinergic drugs.}, } @article {pmid3593531, year = {1987}, author = {Hunt, WA and Rabin, BM and Lee, J}, title = {Ethanol-induced taste aversions: lack of involvement of acetaldehyde and the area postrema.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {4}, number = {3}, pages = {169-173}, doi = {10.1016/0741-8329(87)90039-5}, pmid = {3593531}, issn = {0741-8329}, mesh = {Acetaldehyde/*blood ; Animals ; Avoidance Learning/*drug effects ; Brain Stem/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Fomepizole ; Male ; Pyrazoles/pharmacology ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {Two experiments were run to evaluate the role of acetaldehyde and the area postrema in the acquisition of an ethanol-induced conditioned taste aversion. An ethanol-induced taste aversion was observed in male Sprague-Dawley rats with a dose of 4 g/kg. PO, but not after doses of 1 or 2 g/kg. Pretreatment with 4-methylpyrazole (8 mg/kg, IP), which itself did not induce an aversion as compared to pyrazole (68 mg/kg, IP) that did, and/or prior application of lesions of the area postrema had no influence on the development of an ethanol-induced taste aversion. The results indicate that ethanol-induced taste aversion learning does not result from the metabolism of ethanol to acetaldehyde and does not, like other toxins, involve the mediation of the area postrema.}, } @article {pmid3580131, year = {1987}, author = {Le Magnen, J and Tran, G and Durlach, J}, title = {Lack of effects of Ca-acetyl homotaurinate on chronic and acute toxicities of ethanol in rats.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {4}, number = {2}, pages = {103-108}, doi = {10.1016/0741-8329(87)90006-1}, pmid = {3580131}, issn = {0741-8329}, mesh = {Acamprosate ; Alcohol Drinking/*drug effects ; Animals ; Association Learning ; Body Temperature/drug effects ; Brain/drug effects ; Drinking ; Drug Interactions ; Ethanol/*physiology ; Male ; Motor Skills/drug effects ; Rats ; Rats, Inbred Strains ; Taurine/*analogs & derivatives/physiology ; }, abstract = {In a previous study, it was shown that in rats Ca-acetyl homotaurinate suppresses or eliminates the high oral intake of ethanol induced by earlier chronic ethanol administration, and to a lesser degree the spontaneous ethanol intake of ethanol-naive rats. The present study examines the effect of the drug on the chronic and acute toxicity of ethanol as a possible mechanism in its alteration of the reinforcing properties of ethanol intake. In the first experiment, it was demonstrated that chronic administration of the drug (45 mg/kg per day) for 15 days, alone or combined with chronic intragastric administration of high doses of ethanol, did not significantly alter subsequent ethanol intake. In two other experiments, it was shown that the drug did not interfere with acute ethanol toxicity as tested by ethanol-induced hypothermia, motor impairment and taste aversion in ethanol-naive rats. It is concluded that the acute activity of Ca-AOTA on CNS mechanisms presumably involved in the state of tolerance-dependence, other than those concerned in ethanol-induced hypothermia, motor impairment and taste aversion, may explain its action on the reinforcing property of ethanol intake.}, } @article {pmid3575370, year = {1987}, author = {Bermúdez-Rattoni, F and Coburn, KL and Fernández, J and Chávez, AF and Garcia, J}, title = {Potentiation of odor by taste and odor aversions in rats are regulated by cholinergic activity of dorsal hippocampus.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {26}, number = {3}, pages = {553-559}, doi = {10.1016/0091-3057(87)90165-1}, pmid = {3575370}, issn = {0091-3057}, support = {H05958//PHS HHS/United States ; NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*drug effects ; Cholinergic Fibers/drug effects/*physiology ; Drinking Behavior/physiology ; Hippocampus/drug effects/*physiology ; Male ; *Odorants ; Physostigmine/pharmacology ; Rats ; Rats, Inbred Strains ; Scopolamine/pharmacology ; Smell/*physiology ; Taste/*physiology ; }, abstract = {Limbic cholinergic activity is critically involved in the retention of learned aversions tasks. The purpose of these experiments was to assess the role of cholinergic mechanisms of the dorsal hippocampus in the acquisition of both odor and potentiated odor aversions through taste aversion. Cholinergic activity was increased by physostigmine (Phys). When Phys was applied before the presentation of an odor-taste compound during acquisition, the potentiation of odor-aversion was disrupted, while taste aversion was left intact. When hippocampal cholinergic activity was reduced with the muscarinic antagonist scopolamine (Scop), enhancement of potentiated odor aversion was observed, again with no effect on taste aversion. Moreover, when Phys was applied before an odor alone it also disrupted odor avoidance in two different odor tests conditioning situations, i.e., odor was followed immediately by lithium chloride or foot shock. Neither Scop nor Phys had any effect on taste or potential odor aversions when applied to fronto-parietal cortex. These results suggest that cholinergic activity of the hippocampus is involved in the acquisition of odor aversion conditioning.}, } @article {pmid3451783, year = {1987}, author = {Gorczynski, RM and Kennedy, M}, title = {Behavioral trait associated with conditioned immunity.}, journal = {Brain, behavior, and immunity}, volume = {1}, number = {1}, pages = {72-80}, doi = {10.1016/0889-1591(87)90008-0}, pmid = {3451783}, issn = {0889-1591}, mesh = {Animals ; Antibody Formation ; Avoidance Learning ; *Conditioning, Classical ; Cyclophosphamide/*pharmacology ; *Exploratory Behavior ; Fear ; Female ; *Immune Tolerance ; Inbreeding ; Male ; *Maternal Behavior ; Mice ; Mice, Inbred C57BL/genetics/immunology ; Saccharin ; }, abstract = {Inbred strains of mice were tested for their activity in an open field. Animals selected for high or low activity ("tails" of the normal distribution) were further inbred through nine generations (brother x sister) with further selection at each generation. Reciprocal skin grafts between the two groups were performed to ensure that little/no genetic drift occurred. Using a cyclophosphamide:saccharin conditioning paradigm (R. Ader & N. Cohen (1975) Psychosom. Med. 37, 333-342) we show that mice preselected for high activity in an open field were those in which it was most easy to demonstrate conditioned immunosuppression. There was no difference in the conditionability of the two groups as assessed by taste aversion. By use of a cross-fostering design we conclude that immunological conditioning (in adult mice) can be affected by a characteristic of the nursing mother which is associated with activity in an open-field trial.}, } @article {pmid3628535, year = {1987}, author = {Messmer, JM and Porter, JH and Fatouros, P and Prasad, U and Weisberg, M}, title = {Exposure to magnetic resonance imaging does not produce taste aversion in rats.}, journal = {Physiology & behavior}, volume = {40}, number = {2}, pages = {259-261}, doi = {10.1016/0031-9384(87)90217-4}, pmid = {3628535}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Magnetic Resonance Spectroscopy/*adverse effects ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {A taste aversion test was used to evaluate possible toxic effects of magnetic resonance imaging (MRI). Thirty male Sprague-Dawley rats were randomly assigned to four groups: Group One (n = 10) received 30 minutes exposure inside the MRI scanner; Group Two (n = 10) received a sham exposure to the MRI scanner; Group Three (n = 5) was injected with 0.15 M lithium chloride; and Group Four (n = 5) was injected with vehicle. All groups were given 10 minutes access to a 0.1% saccharin solution immediately prior to their respective treatment. The rats treated with lithium chloride displayed a taste aversion to the saccharin solution upon subsequent testing over an eight day period. The two control groups (Two and Four) and the rats exposed to MRI did not display any aversion to the saccharin solution. These results are compared to other studies that have shown that magnetic fields can influence biological systems.}, } @article {pmid3628529, year = {1987}, author = {Green, KF and Lee, DW}, title = {Effects of centrifugal rotation on analgesia and conditioned flavor aversions.}, journal = {Physiology & behavior}, volume = {40}, number = {2}, pages = {201-205}, doi = {10.1016/0031-9384(87)90208-3}, pmid = {3628529}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; *Centrifugation ; Female ; Naloxone/pharmacology ; Pain/*physiopathology ; Rats ; Rats, Inbred Strains ; Reaction Time/physiology ; Taste/*physiology ; Time Factors ; }, abstract = {In the first experiment, 48 female Wistar rats were water deprived and given three conditioning days with saccharin-flavored water (1.5 g/liter) followed by 0, 5, 10 or 15 min of centrifugal rotation (150 rpm). Analgesia was measured by the tail flick test immediately after rotation. Over conditioning days, taste aversions developed. In general, taste aversion strength increased with duration of rotation. Analgesia also was in proportion to duration of rotation; however, over days tolerance developed in all rotated groups. In the second experiment 12 female Wistar rats were water deprived and given naloxone (20 mg/kg) or saline prior to 15 min of rotation. Rotation-induced analgesia was not affected by naloxone. It was concluded that somatic and gastrointestinal reactions to rotation are not served by a single mechanism.}, } @article {pmid3628520, year = {1987}, author = {Spiegel, TA and Stunkard, AJ and Shrager, EE and O'Brien, CP and Morrison, MF and Stellar, E}, title = {Effect of naltrexone on food intake, hunger, and satiety in obese men.}, journal = {Physiology & behavior}, volume = {40}, number = {2}, pages = {135-141}, doi = {10.1016/0031-9384(87)90198-3}, pmid = {3628520}, issn = {0031-9384}, support = {5-KO5-MH-00245/MH/NIMH NIH HHS/United States ; 5-P01-MH-31050/MH/NIMH NIH HHS/United States ; AM32688/AM/NIADDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Appetite/drug effects ; Drinking Behavior/drug effects ; Feeding Behavior/*drug effects ; Humans ; Hunger/drug effects ; Male ; Middle Aged ; Naltrexone/administration & dosage/adverse effects/*pharmacology ; Obesity/*physiopathology ; Satiation/*drug effects ; Satiety Response/*drug effects ; Time Factors ; }, abstract = {Increasing doses of naltrexone (25 to 200 mg) given over 4 consecutive days reduced intake of laboratory luncheon meals by 30% in 17 obese men. Meal size remained suppressed in the laboratory during the week following naltrexone administration. Water intake in the laboratory and body weight were not affected. Rates of ingestion and subjective ratings suggested that naltrexone reduced appetite rather than promoted early satiation. Nausea and other side effects occurred on 1 or 2 days during the naltrexone week in seven subjects whose food intake was reduced. Food intake was also reduced in seven of the remaining 10 subjects who reported no adverse reactions. These results suggest that a conditioned taste aversion or a conditioned anorexia may have developed in some subjects.}, } @article {pmid3627080, year = {1987}, author = {Hunt, WA and Rabin, BM and Lee, J}, title = {Effects of subdiaphragmatic vagotomy on the acquisition of a radiation-induced conditioned taste aversion.}, journal = {Neurotoxicology and teratology}, volume = {9}, number = {1}, pages = {75-77}, doi = {10.1016/0892-0362(87)90073-0}, pmid = {3627080}, issn = {0892-0362}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Stem/physiology ; Digestive System/*radiation effects ; Male ; Neurosecretory Systems/physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Vagotomy ; Vagus Nerve/*physiology ; }, abstract = {The effect of subdiaphragmatic vagotomy on the acquisition of a radiation-induced taste aversion was examined to assess the importance of the vagus nerve in transmitting information on the peripheral toxicity of radiation to the brain. Vagotomy had no effect on taste aversion learning, consistent with reports using other toxins. The data support the involvement of a blood-borne factor in the acquisition of taste aversion induced by ionizing radiation.}, } @article {pmid3614785, year = {1987}, author = {Nissenbaum, JW and Sclafani, A}, title = {Qualitative differences in polysaccharide and sugar tastes in the rat: a two-carbohydrate taste model.}, journal = {Neuroscience and biobehavioral reviews}, volume = {11}, number = {2}, pages = {187-196}, doi = {10.1016/s0149-7634(87)80025-8}, pmid = {3614785}, issn = {0149-7634}, support = {DK-31135/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Carbohydrates ; Conditioning, Classical ; Female ; Fructose ; Glucans ; Glucose ; Maltose ; *Polysaccharides ; Rats ; Sucrose ; *Taste ; }, abstract = {A conditioned taste aversion paradigm was used to assess the qualitative similarities between the tastes of a polysaccharide (Polycose) solution and sugar solutions (sucrose, maltose, glucose, fructose). In Experiment I, three groups of female rats were water deprived and conditioned to avoid a 0.025 M Polycose, a 0.1 M sucrose, or a 0.1 M maltose solution by pairing solution consumption with a lithium chloride (LiCl) injection; in a control group water consumption was paired with the LiCl injection. The extent to which the experimental groups generalized their conditioned aversion to the other three solutions was then assessed. The Polycose-conditioned group avoided the maltose solution more than the sucrose solution, and the maltose-conditioned group avoided the Polycose solution more than the sucrose solution. The sucrose-conditioned group avoided the maltose and Polycose solutions to the same relatively low degree. In additional tests the three experimental groups showed similar aversions to a glucose solution, but only the sucrose-conditioned rats avoided a fructose solution. Rats in a second experiment also displayed relatively little cross-generalization between Polycose and sucrose aversions even though they were tested with different solution concentrations. Additional tests confirmed the results obtained in Experiment 1 with maltose, glucose, and fructose solutions, and also revealed that the sucrose-conditioned group, but not the Polycose-conditioned group avoided saccharin solutions. Neither Polycose- nor sucrose-conditioned groups avoided quinine, sodium chloride, or hydrochloric acid solutions. These results, along with other recent findings, suggest that rats have two types of "carbohydrate" taste receptors, one for polysaccharides and one for sucrose, which produce qualitatively distinct gustatory sensations.}, } @article {pmid3588708, year = {1987}, author = {Kasahara, T and Iwasaki, K and Sato, M}, title = {Taste effectiveness of some D- and L-amino acids in mice.}, journal = {Physiology & behavior}, volume = {39}, number = {5}, pages = {619-624}, doi = {10.1016/0031-9384(87)90162-4}, pmid = {3588708}, issn = {0031-9384}, mesh = {*Amino Acids ; Animals ; Avoidance Learning ; *Choice Behavior ; Conditioning, Classical ; Drinking ; Male ; Mice ; Mice, Inbred Strains ; Sucrose ; *Taste ; Taste Threshold ; }, abstract = {To measure the hedonic effectiveness of some D-amino acids two-bottle preference tests were carried out on ddy mice, and subsequently conditioned taste aversion (CTA) experiments were performed to determine to what degree hedonic responses to D- and L-amino acids are related to sweet taste in mice. Mice showed preferences for D-Trp, D-His, and D-Leu over certain concentration ranges, but were behaviorally neutral to D-Ser and D-Val up to 0.1 M. The preference magnitudes for D-amino acids increased with increasing molecular weight (MW) or the bulk of the side chain. CTA experiments using 0.2 M sucrose as a conditioning stimulus and 4 D- and 6 L-amino acids as test stimuli indicated that generalization of sucrose taste became stronger with increasing MW of D-amino acids and decreasing MW of L-amino acids. There was a highly significant positive correlation between the degree of generalization of sucrose taste and the preference magnitude for D- and L-amino acids. The results indicate that preferences for D- and L-amino acids in mice result from sweet taste produced by these chemicals. Comparison of the results with the human psychophysical data reveal similarity between humans and ddy mice in taste sensitivity to amino acids.}, } @article {pmid3588702, year = {1987}, author = {Supple, WF and Leaton, RN and Fanselow, MS}, title = {Effects of cerebellar vermal lesions on species-specific fear responses, neophobia, and taste-aversion learning in rats.}, journal = {Physiology & behavior}, volume = {39}, number = {5}, pages = {579-586}, doi = {10.1016/0031-9384(87)90156-9}, pmid = {3588702}, issn = {0031-9384}, support = {S507 RR07056-13H/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Arousal/*physiology ; Avoidance Learning/*physiology ; Brain Mapping ; Cats ; Cerebellum/*physiology ; Drinking Behavior/physiology ; Exploratory Behavior/physiology ; Fear/*physiology ; Female ; Male ; Motor Activity/physiology ; Rats ; Rats, Inbred Strains ; *Species Specificity ; Taste/*physiology ; }, abstract = {The cerebellar vermis has extensive anatomical connections with many brain stem and forebrain structures which have been implicated in emotional or affective behavior. Previous reports indicate that lesions of the vermis in a variety of experimental animals result in altered emotional behavior. The studies reported here attempted to clarify the nature of the change in emotional behavior following vermal lesions in rats by testing the animals in a variety of fear-eliciting situations. As compared with controls, vermal-lesioned rats froze less in the presence of a cat and showed fewer signs of fear in an open field. However, their responses to footshock did not differ fundamentally from controls. They recovered more quickly than controls from the neophobic response to a novel taste but showed robust taste-aversion learning. The results are discussed in terms of the role of the cerebellum in the modulation of fear-related behaviors and in terms of similarities and differences with the effects of amygdala lesions. The results expand the body of data implicating the cerebellum in the modulation of complex motivational behavior.}, } @article {pmid3575495, year = {1987}, author = {Yirmiya, R and Holder, MD and Garcia, J}, title = {Conditioned taste aversion in vasopressin-deficient rats (Brattleboro strain).}, journal = {Physiology & behavior}, volume = {39}, number = {4}, pages = {489-493}, doi = {10.1016/0031-9384(87)90378-7}, pmid = {3575495}, issn = {0031-9384}, support = {HD 05958/HD/NICHD NIH HHS/United States ; NS11618/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; Extinction, Psychological/physiology ; Lithium/pharmacology ; Rats ; Rats, Brattleboro ; Saccharin ; Taste/*physiology ; Vasopressins/*deficiency ; }, abstract = {Brattleboro rats are homozygous for diabetes insipidus (DI), lacking the ability to synthesize vasopressin. Previous studies reported learning deficits in DI rats on passive avoidance tasks using footshock. Other studies, however, could not replicate these results. In two experiments, we studied the learning of DI and control Long Evans (LE) rats in a different avoidance paradigm: conditioned taste aversion (CTA). In the first experiment a mild CTA to saccharin was established gradually using low levels of an illness-inducing agent (lithium chloride). In the second experiment a strong CTA was established in one acquisition trial and the extinction of the conditioned aversion was followed for 12 trials. The two experiments found no differences between the DI and LE rats in either the magnitude or the rate of acquisition and extinction of the CTA. These results suggest that vasopressin is not involved in the acquisition and retention of CTA, and support previous studies indicating that vasopressin may not be involved in avoidance learning.}, } @article {pmid3562650, year = {1987}, author = {Clifton, PG and Andrew, RJ}, title = {Gonadal steroids and the extinction of conditioned taste aversions in young domestic fowl.}, journal = {Physiology & behavior}, volume = {39}, number = {1}, pages = {27-31}, doi = {10.1016/0031-9384(87)90340-4}, pmid = {3562650}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chickens/*physiology ; Conditioning, Psychological/*drug effects ; Dihydrotestosterone/pharmacology ; Estradiol/pharmacology ; Female ; Gonadal Steroid Hormones/*pharmacology ; Male ; *Taste ; Testosterone/pharmacology ; }, abstract = {Three experiments using domestic chicks demonstrate that the extinction of a conditioned taste aversion to a green-coloured sucrose solution is slowed by the administration of testosterone or 5 alpha-dihydrotestosterone but is unaffected by estradiol. Testosterone slows extinction in male and female chicks to an equal extent. Previously described effects of testosterone on attentional and memory mechanisms have also been produced by low doses of estradiol so a separate mechanism must be postulated to explain the present results. It is probably similar to the mechanism responsible for a steroid-dependent slowing of extinction in rats since those effects are also androgenic and present in both sexes.}, } @article {pmid3554039, year = {1987}, author = {Hunt, T and Amit, Z}, title = {Conditioned taste aversion induced by self-administered drugs: paradox revisited.}, journal = {Neuroscience and biobehavioral reviews}, volume = {11}, number = {1}, pages = {107-130}, doi = {10.1016/s0149-7634(87)80005-2}, pmid = {3554039}, issn = {0149-7634}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Behavior, Animal/drug effects ; Biomechanical Phenomena ; Conditioning, Psychological/*drug effects/physiology ; Drug-Related Side Effects and Adverse Reactions ; Nervous System/metabolism ; *Self Administration ; Taste/*drug effects/physiology ; Vomiting/chemically induced ; }, abstract = {In this paper we have reviewed the literature on Conditioned Taste Aversion (CTA) with specific attention to the "apparent paradox" in this literature. This paradox refers to the fact that drugs which are self-administered (SA) by animals and are therefore presumed to possess positive reinforcing properties are also endowed with the capacity to induce a CTA. We have argued that the CTA literature contains evidence of the existence of two qualitatively distinct types of CTA, one which is mediated by emetic agents and the other induced by SA drugs. We first provided evidence to support the notion that the traditional explanation of CTA as a function of "drug toxicity" and its resultant gastrointestinal distress does not fit the data on the nature of CTA induced by SA drugs. We proposed instead that "drug shyness" or the novelty of the drug state of these psychoactive SA drugs constitutes a better explanation of the CTA of SA drugs. We provided further evidence suggesting a functional relationship between the positive reinforcing and aversive properties of SA drugs. We have based this contention on a review of the behavioral, physiological and neurochemical data concerning the nature of CTA of SA drugs. The examination of these data reveals that the neural mechanisms underlying both the positive and aversive properties of SA drugs are the same and at the same time different from the neural mechanisms underlying the induction of CTA by emetic agents. Finally, we discussed the relevance of this interaction between the positive and aversive properties of SA drugs in the context of their abuse liability and the control they exert on drug-oriented behavior.}, } @article {pmid3474989, year = {1987}, author = {Djurić, VJ and Marković, BM and Lazarević, M and Janković, BD}, title = {Conditioned taste aversion in rats subjected to anaphylactic shock.}, journal = {Annals of the New York Academy of Sciences}, volume = {496}, number = {}, pages = {561-568}, doi = {10.1111/j.1749-6632.1987.tb35814.x}, pmid = {3474989}, issn = {0077-8923}, mesh = {Aluminum Hydroxide ; *Anaphylaxis ; Animals ; *Avoidance Learning ; *Conditioning, Psychological ; Female ; Ovalbumin ; Rats ; Rats, Inbred Strains ; Taste ; }, } @article {pmid3432408, year = {1987}, author = {Bellinger, LL and Mendel, VE}, title = {Intracerebroventricular infusions of rat satietin into rats does not produce conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {41}, number = {5}, pages = {511-514}, doi = {10.1016/0031-9384(87)90089-8}, pmid = {3432408}, issn = {0031-9384}, mesh = {Animals ; Appetite Depressants/*pharmacology ; Body Weight/drug effects ; Cerebral Ventricles/drug effects/*physiology ; Conditioning, Psychological/*drug effects ; Drinking Behavior/drug effects ; Feeding Behavior/drug effects ; Glycopeptides/administration & dosage/*pharmacology ; Injections, Intraventricular ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; }, abstract = {In a previous study we found that while human satietin (h-SAT) suppressed the food intake of rats it was also aversive to them. In the present study rat satietin (r-SAT) was tested for aversiveness in rats fitted with chronic third ventricle (ICV) cannulas. The rats were then given access to water for 1-hr/day and food ad lib for ten days. Fluid intake, food intake during fluid access and 24-hr total food consumption were recorded. The rats were then ICV infused with saline and 30 min later half of the animals given access to banana flavored water (Group 1) while the remainder were presented with almond flavored water (Group 2). The next day Group 1 was infused with saline and Group 2 with 100 micrograms/rat of r-SAT. Thirty minutes later the flavors presented to the rats were the reverse of the previous day. Satietin significantly reduced food intake during fluid access and for 24 hours. Thereafter, fluid and food ingestion of the groups was normal and similar. Thus no rebound feeding occurred in the r-SAT treated group. Two days after r-SAT or saline the rats were given a two-bottle choice test. Both groups displaced equal preference for the flavors, therefore r-SAT produced no taste aversion. The r-SAT treated rats lost more body weight than saline treated animals the first day after treatment. This difference increased the next day and remained significant for seven days post infusion, whereas, food consumption did not differ between the groups after the first day. The data indicate the food intake suppression in rats produced by r-SAT is not due to the compound being aversive.}, } @article {pmid3432400, year = {1987}, author = {Giza, BK and Scott, TR}, title = {Blood glucose level affects perceived sweetness intensity in rats.}, journal = {Physiology & behavior}, volume = {41}, number = {5}, pages = {459-464}, doi = {10.1016/0031-9384(87)90081-3}, pmid = {3432400}, issn = {0031-9384}, support = {AM 30964/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Blood Glucose/*physiology ; Conditioning, Psychological ; Female ; Glucose ; Perception ; Quinine ; Rats ; *Taste ; }, abstract = {Electrophysiological data indicate that hyperglycemia is associated with decreased neural taste responsiveness to 1.0 M glucose, but not to 0.01 M quinine HCl, in the rat's hindbrain. The present behavioral experiment was conducted to determine whether this suppression of neural activity is manifested in a reduced intensity perception to glucose, but not quinine. Each rat learned to avoid 1.0 M glucose through development of a conditioned taste aversion. Perceived intensity was then measured in control and in hyperglycemic rats by the extent to which they generalized to each test concentration of glucose. Experimental subjects treated moderate glucose concentrations (0.6-2.0 M) as if their intensity perceptions were reduced by 47%. This is consistent with the mean reduction of 43% in taste-evoked neural activity associated with hyperglycemia. A corresponding experiment gave no indication of a change in intensity perception to quinine as a function of hyperglycemia, again in accord with earlier electrophysiological results. We conclude that nutritional state may selectively affect gustatory sensitivity in the rat.}, } @article {pmid3432384, year = {1987}, author = {Scott, TR and Giza, BK}, title = {A measure of taste intensity discrimination in the rat through conditioned taste aversions.}, journal = {Physiology & behavior}, volume = {41}, number = {4}, pages = {315-320}, doi = {10.1016/0031-9384(87)90394-5}, pmid = {3432384}, issn = {0031-9384}, support = {AM30964/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Conditioning, Classical/*physiology ; Discrimination Learning/*physiology ; Female ; Rats ; Taste/*physiology ; }, abstract = {The ability of rats to make intensity discriminations was determined by forming a conditioned taste aversion to a moderate concentration of each of four basic taste stimuli, and then measuring the level of acceptance (number of licks during a 15 sec exposure) shown to a range of concentrations of the same chemical. Rats (N = 66) could discriminate between glucose concentrations that were separated by as little as 0.074 M, between NaCl concentrations that differed by 0.029 M, between HCl concentrations that were 9 X 10(-4) M apart, and between quinine HCl concentrations that differed by as little as 2.4 X 10(-6) M.}, } @article {pmid3300474, year = {1987}, author = {Bovbjerg, D and Kim, YT and Siskind, GW and Weksler, ME}, title = {Conditioned suppression of plaque-forming cell responses with cyclophosphamide. The role of taste aversion.}, journal = {Annals of the New York Academy of Sciences}, volume = {496}, number = {}, pages = {588-594}, doi = {10.1111/j.1749-6632.1987.tb35818.x}, pmid = {3300474}, issn = {0077-8923}, mesh = {Animals ; *Avoidance Learning/drug effects ; *Conditioning, Psychological/drug effects ; Cyclophosphamide/*pharmacology ; Hemolytic Plaque Technique ; Immunization ; Immunosuppression Therapy ; Male ; Mice ; Mice, Inbred C57BL ; Taste ; }, } @article {pmid3124173, year = {1987}, author = {Grant, VL}, title = {Do conditioned taste aversions result from activation of emetic mechanisms?.}, journal = {Psychopharmacology}, volume = {93}, number = {4}, pages = {405-415}, pmid = {3124173}, issn = {0033-3158}, mesh = {Animals ; Conditioning, Operant/*physiology ; Humans ; Taste/*physiology ; Vomiting/*psychology ; }, abstract = {The conditioned taste aversion (CTA) literature is extensive, yet little is known about the mechanisms by which treatments induce CTA. This paper describes and evaluates Garcia's hypothesis (e.g., Garcia et al. 1985) that treatments produce taste aversions by activating the receptors and neural pathways proposed by Borison and Wang (1953) to underlie emesis. Research on the mechanisms by which various treatments induce emesis is reviewed and compared with similar research on CTA. Emetic mechanisms appear to be involved appear to be involved in the formation of CTAs produced by some treatments, but there is contrary evidence for other treatments. This suggests that some CTAs are mediated by emetic mechanisms and others are not, so that Garcia's hypothesis is not generally correct. However, methodological and theoretical ambiguities make it premature to draw this conclusion.}, } @article {pmid3110828, year = {1987}, author = {Schenk, S and Hunt, T and Klukowski, G and Amit, Z}, title = {Isolation housing decreases the effectiveness of morphine in the conditioned taste aversion paradigm.}, journal = {Psychopharmacology}, volume = {92}, number = {1}, pages = {48-51}, pmid = {3110828}, issn = {0033-3158}, mesh = {Animals ; Conditioning, Operant/*drug effects ; Habituation, Psychophysiologic/drug effects ; Male ; Morphine/*pharmacology ; Rats ; Sexual Behavior, Animal/drug effects ; *Social Isolation ; Taste/*drug effects ; }, abstract = {Male Long Evans rats were obtained at 21 days of age and were housed in either an aggregated (four per double cage) or isolated (one per single cage) condition for 6 weeks. They were then placed on a fluid deprivation schedule that allowed them access to fluids for 20 min daily. This schedule was maintained for the remainder of the experiment. Following habituation, sensitivity to morphine-induced conditioned taste aversion (CTA) was compared in the differentially housed rats. On the 1st day and every 5 days thereafter the rats were presented with a 0.1% solution of sodium saccharin for the 20-min drinking period, followed immediately by an injection of morphine (0, 2.5, 5.0, 10.0, or 20.0 mg/kg). On intervening days they received water as the fluid. No drugs were given on these days. There was no difference in baseline saccharin consumption as a function of housing condition. In comparison with the isolated rats, the grouped animals were more sensitive to the CTA-inducing properties of low doses of morphine. These data strengthen the already existing evidence for the influence of the early housing environment on drug sensitivity and provide additional support for the conclusion that variability in response to a number of drugs of abuse can be reduced by environmental means. Possible mechanisms for the differences between isolation and aggregation housed rats are discussed.}, } @article {pmid3107033, year = {1987}, author = {Buresová, O and Bures, J}, title = {Conditioned taste aversion induced in rats by intracerebral or systemic administration of monoamine oxidase inhibitors.}, journal = {Psychopharmacology}, volume = {91}, number = {2}, pages = {209-212}, pmid = {3107033}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Brain ; Clorgyline/pharmacology ; Injections ; Injections, Intraperitoneal ; Male ; Monoamine Oxidase Inhibitors/administration & dosage/*pharmacology ; Pargyline/pharmacology ; Rats ; Selegiline/pharmacology ; Taste/*drug effects ; }, abstract = {Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 microliter/min, 1-2 microliters) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n = 10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 micrograms per rat with intracerebral (n. raphé magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 micrograms C and 10 micrograms P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 micrograms P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D).}, } @article {pmid3033715, year = {1987}, author = {Kusnecov, AW and King, MG and Husband, AJ}, title = {Synergism of a compound unconditioned stimulus in taste aversion conditioning.}, journal = {Physiology & behavior}, volume = {39}, number = {4}, pages = {531-533}, doi = {10.1016/0031-9384(87)90385-4}, pmid = {3033715}, issn = {0031-9384}, mesh = {Animals ; Antilymphocyte Serum/*pharmacology ; Avoidance Learning/*physiology ; Chlorides/*pharmacology ; Conditioning, Psychological/*physiology ; Lithium/*pharmacology ; Lithium Chloride ; Rabbits ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste/*physiology ; Water Deprivation ; }, abstract = {Anti-lymphocyte serum (ALS) and lithium chloride have both previously been used successfully as unconditioned stimuli in taste aversion conditioning paradigms in rats. This report substantiates those findings but shows that when the two stimuli are given as a compound unconditioned stimulus in association with saccharin flavoured drinking solution, the conditioned taste aversion response following a second exposure to saccharin alone is more profound than that following conditioning with either ALS or LiCl alone. These results demonstrate synergism between the two stimuli when given together.}, } @article {pmid2953676, year = {1987}, author = {Husband, AJ and King, MG and Brown, R}, title = {Behaviourally conditioned modification of T cell subset ratios in rats.}, journal = {Immunology letters}, volume = {14}, number = {2}, pages = {91-94}, doi = {10.1016/0165-2478(87)90085-x}, pmid = {2953676}, issn = {0165-2478}, mesh = {Adjuvants, Immunologic/administration & dosage ; Animals ; Behavior, Animal/*physiology ; Injections, Subcutaneous ; Levamisole/administration & dosage/immunology ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; T-Lymphocytes/*classification/drug effects/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Helper-Inducer/cytology ; T-Lymphocytes, Regulatory/cytology ; Taste/physiology ; }, abstract = {Levamisole injection resulted in an elevation in the T helper:T suppressor (H:S) subset ratio in rats at 24 h after injection due to a selective depression in the cytotoxic/suppressor subset. This response was shown to be conditionable and could be reenlisted 14 days later by re-exposure to the conditioned stimulus. Rats were conditioned using a taste aversion paradigm by pairing levamisole injection with the novel taste of saccharin. Fourteen days later, after a second exposure to saccharin without levamisole injection, H:S ratios were elevated in the blood of these rats compared to control rats injected with levamisole but fed normal water or rats fed saccharin without levamisole injection.}, } @article {pmid3640654, year = {1986}, author = {Mohammed, AK and Jonsson, G and Sundström, E and Minor, BG and Söderberg, U and Archer, T}, title = {Selective attention and place navigation in rats treated prenatally with methylazoxymethanol.}, journal = {Brain research}, volume = {395}, number = {2}, pages = {145-155}, doi = {10.1016/s0006-8993(86)80194-9}, pmid = {3640654}, issn = {0006-8993}, mesh = {Abnormalities, Drug-Induced/*psychology ; Animals ; *Attention ; Azo Compounds/*toxicity ; Brain/*abnormalities ; Cognition Disorders/*chemically induced ; Female ; Inhibition, Psychological ; Learning Disabilities/chemically induced ; Methylazoxymethanol Acetate/analogs & derivatives/*toxicity ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Inbred Strains ; Reaction Time ; Space Perception ; }, abstract = {Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. The behavioral analyses included measures of spontaneous motor activity and tests for cognitive deficits, and were performed when the rats had reached adult age. Female MAM-treated rats failed to demonstrate contextual control of latent inhibition, which confirms earlier findings with male rats. Male MAM-treated rats demonstrated a notable impairment of place navigation in a swim-maze, but showed as strong sensory preconditioning as the control animals. Biochemical analyses indicated considerable increases in catecholamine levels in the cerebral cortex, hippocampus and striatum. The cognitive deficits, characterised by the various conditioning (taste-aversion) and instrumental learning (swim-maze) tasks, suggested that the MAM rats are deficient in their capacity to attend selectively to the relevant stimulus in complex arrangements of the stimulus situation.}, } @article {pmid3808178, year = {1986}, author = {Czech, DA and Faubert, P}, title = {Triethyl lead attenuates feeding and drinking, and induces a conditioned taste aversion, in adult rats.}, journal = {Neurobehavioral toxicology and teratology}, volume = {8}, number = {6}, pages = {627-630}, pmid = {3808178}, issn = {0275-1380}, mesh = {Animals ; Avoidance Learning/drug effects ; Body Weight ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior/*drug effects ; Feeding Behavior/*drug effects ; Lead/*pharmacology ; Male ; Organometallic Compounds/*pharmacology ; Rats ; Rats, Inbred Strains ; *Taste ; }, abstract = {The effect of triethyl lead (TEL) on ingestive behavior in adult male rats was studied in two experiments. In experiment 1, ad lib food and water intakes were monitored following SC injection of 1, 4, or 7 mg/kg body weight of TEL or vehicle; both were significantly attenuated at 4 and 7 mg/kg doses. In a second experiment, the same doses of TEL were given SC in a conditioned taste aversion (CTA) paradigm. Following a single pairing, a dose-related reduction in intake of a 0.1% saccharin solution was observed at all doses tested. Sensitivity of behavioral measures and potential role of discomfort in TEL-induced feeding/drinking shifts were considered.}, } @article {pmid3786372, year = {1986}, author = {Fletcher, PJ}, title = {Conditioned taste aversion induced by tryptamine: a temporal analysis.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {25}, number = {5}, pages = {995-999}, doi = {10.1016/0091-3057(86)90076-6}, pmid = {3786372}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/*drug effects ; Male ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste/*drug effects ; Tryptamines/*pharmacology ; }, abstract = {The effects of tryptamine on the induction of a conditioned taste aversion (CTA) to a novel saccharin solution were examined. In a single bottle-repeated injection paradigm, tryptamine (40, 60 and 80 mg/kg, IP) induced a significant CTA. This effect was relatively weak, with only the highest dose tested inducing a progressive decline in saccharin intake across trials. The weak action of tryptamine (40 and 60 mg/kg) was confirmed in a more sensitive CTA paradigm which measured the relative preference for saccharin and water. Results of this experiment also showed that prolonging the duration of action of tryptamine failed to enhance the formation of a CTA. This finding extends previous reports that prolonging the duration of action of a compound does not increase potency in the CTA paradigm, and thus casts doubt on the generality of the duration of action hypothesis.}, } @article {pmid3031896, year = {1986}, author = {Kassil', VG and Makukhina, GV}, title = {[Taste aversions in the ontogeny of the rat].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {36}, number = {6}, pages = {1054-1060}, pmid = {3031896}, issn = {0044-4677}, mesh = {Aging/*physiology ; Animals ; Avoidance Learning/*physiology ; Chlorides ; Conditioning, Classical/*physiology ; Extinction, Psychological/physiology ; Female ; Lithium ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saccharin ; Sex Characteristics ; Taste/*physiology ; }, abstract = {The characteristics of acquisition and extinction of conditioned taste aversion (CTA) were studied in rats of both sexes and various ages by pairing of saccharin solution consumption with discomfort (LiCl intoxication, rotation). Pairing of saccharin consumption with LiCl in adult rats led to acquisition of CTA, more profound in male rats than in female ones. In rats of both sexes 30 days old, a profound CTA, comparable in intensity with CTA of adult male rats was acquired. In 2 months after acquisition of CTA in adult rats its magnitude did not change, while in rats of the junior group which by that time had reached puberty, CTA was reduced in females and did not change in males. Pairing of saccharin intake and rotation led to acquisition of CTA only in rats 30 days old. The role of external factors in duration of retention of CTA acquired by pairing of saccharin solution consumption with LiCl injection was studied in male and female rats 1 and 3.5 months old. In all cases CTA was extinguished much sooner in home cages than in experimental chambers, and in the elder group sex dimorphism was found: in both situations CTA disappeared sooner in female rats. The obtained data allow to suggest modulating influences of hormonal background and of contextual stimuli on CTA acquisition and retention.}, } @article {pmid3028366, year = {1986}, author = {Vogt, MB and Rudy, JW}, title = {Neonatal hyperthyroidism in the rat: thyroxine accelerates the development of unconditioned but not learned responses to tastes.}, journal = {Behavioral and neural biology}, volume = {46}, number = {3}, pages = {358-371}, doi = {10.1016/s0163-1047(86)90338-9}, pmid = {3028366}, issn = {0163-1047}, support = {RR07013-1980/RR/NCRR NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Animals, Newborn ; Avoidance Learning/*physiology ; Chlorides/toxicity ; Feeding Behavior ; Female ; Hyperthyroidism/physiopathology/*psychology ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Thyroxine/*physiology ; Time Factors ; }, abstract = {The effects of neonatal hyperthyroidism induced by thyroxine injection on the development of unconditioned and learned behaviors mediated by the gustatory system of the rat were investigated. The development of unconditioned ingestive responses evoked by 10% sucrose and 0.1% HCl taste solutions was advanced several days by thyroxine treatment. However, the emergence of taste aversion learning involving 10% sucrose and LiCl injection was not advanced and may have been slightly delayed. Thus, the ontogenesis of unconditioned and learned behaviors mediated by the gustatory system was not influenced uniformly by neonatal thyroxine treatment.}, } @article {pmid3103148, year = {1986}, author = {Järbe, TU and Callenholm, NE and Mohammed, AK and Archer, T}, title = {Noradrenaline and the context-dependent extinction effect.}, journal = {Physiology & behavior}, volume = {38}, number = {4}, pages = {495-501}, doi = {10.1016/0031-9384(86)90416-6}, pmid = {3103148}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/physiology ; Benzylamines/pharmacology ; Brain/*physiology ; Brain Mapping ; Cues ; Extinction, Psychological/*physiology ; Hydroxydopamines/pharmacology ; Male ; Neural Pathways/physiology ; Norepinephrine/*physiology ; Oxidopamine ; Rats ; Saccharin ; Taste/physiology ; }, abstract = {Three experiments were performed to examine the effects of noradrenaline (NA) depletion upon the context-dependent extinction effects in conditioned taste-aversion learning. Three different methods were used to deplete NA: lesions of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine (6-OHDA), lesions induced by neonatal treatment with 6-OHDA and lesions induced by systemic administration with the NA neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). In each experiment, novel saccharin was presented in novel noisy bottle followed by lithium chloride. Later, during the extinction phase, half the control and half the NA depleted rats received saccharin in noisy bottles while the other half received saccharin in silent bottles. In the control condition, the rats that received saccharin in the noisy bottles (same context as conditioning) showed considerably more aversion than those that received saccharin in the silent bottles (different context to conditioning); NA depletion attenuated this effect. Reinstatement of the conditioning context (noisy bottle) resulted in a stronger aversion in the case where the different context (silent bottle) was present during extinction; this effect was attenuated in the NA depletion condition. These findings maintain a role for noradrenaline in compound conditioning tasks.}, } @article {pmid3022768, year = {1986}, author = {Revusky, S and Harding, RK}, title = {Pairing pentobarbital with one toxin causes it to attenuate taste aversions produced by a different toxin: implications for conditioned antisickness theory.}, journal = {Behavioral neuroscience}, volume = {100}, number = {5}, pages = {685-694}, doi = {10.1037//0735-7044.100.5.685}, pmid = {3022768}, issn = {0735-7044}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; *Conditioning, Classical ; Copper/pharmacology ; Copper Sulfate ; Dextroamphetamine/pharmacology ; Food Preferences/*drug effects ; Lithium/pharmacology ; Lithium Chloride ; Male ; Pentobarbital/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin ; Toxins, Biological/*pharmacology ; }, abstract = {Normally, if pentobarbital and then a toxin are injected after a rat drinks saccharin solution, a taste aversion produced by the pentobarbital summates with that produced by the toxin. An opposite effect is obtained after a preconditioning series in which pentobarbital is injected prior to a toxic dose of lithium or amphetamine in the absence of saccharin drinking: The pentobarbital attenuates the saccharin aversion normally produced by the toxin. Lett (1983) theorized that a conditioned antisickness response (CAR) to pentobarbital is responsible for this conditioned attenuation of saccharin aversion. It is reported here that this attenuation of taste aversion occurs even if the toxin paired with pentobarbital is different from the toxin used during saccharin aversion conditioning. Preconditioning pentobarbital with a high dose of amphetamine allows it to attenuate saccharin aversions produced by lithium and by gamma radiation (as well as by amphetamine itself). Preconditioning pentobarbital with a high dose of lithium allows it to attenuate aversions produced by amphetamine, gamma radiation, cisplatin, mechlorethamine, dactinomycin, and doxorubicin (as well as by lithium itself). This means that the CAR cannot be due to conditioned amelioration of specific effects of specific toxins (which would not be effective if the toxin were changed) and suggests a central alleviation of nausea, perhaps like the alleviation of pain by endogenous opiates. However, aversions produced by intraperitoneal copper sulfate were not attenuated by lithium-conditioned pentobarbital.}, } @article {pmid3800361, year = {1986}, author = {Carrell, LE and Cannon, DS and Best, MR and Stone, MJ}, title = {Nausea and radiation-induced taste aversions in cancer patients.}, journal = {Appetite}, volume = {7}, number = {3}, pages = {203-208}, doi = {10.1016/s0195-6663(86)80025-3}, pmid = {3800361}, issn = {0195-6663}, mesh = {Abdominal Neoplasms/radiotherapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Female ; Humans ; Male ; Middle Aged ; Nausea/*psychology ; Neoplasms/*radiotherapy ; Taste/*radiation effects ; }, abstract = {The development of taste aversions was studied in 34 oncology patients undergoing radiotherapy. A target flavor was paired with irradiation on four consecutive treatment days. Self-reported nausea on treatment days reliably predicted aversion learning. The implications of this finding for the anorexia of cancer patients and the role of nausea in human taste aversion learning are discussed.}, } @article {pmid3774129, year = {1986}, author = {Reavill, C and Stolerman, IP and Kumar, R and Garcha, HS}, title = {Chlorisondamine blocks acquisition of the conditioned taste aversion produced by (-)-nicotine.}, journal = {Neuropharmacology}, volume = {25}, number = {9}, pages = {1067-1069}, doi = {10.1016/0028-3908(86)90204-2}, pmid = {3774129}, issn = {0028-3908}, mesh = {Animals ; Apomorphine/administration & dosage/pharmacology ; Brain/drug effects ; Chlorisondamine/administration & dosage/*pharmacology ; Conditioning, Classical/*drug effects ; Drug Interactions ; Injections, Intraventricular ; Male ; Microinjections ; Nicotine/administration & dosage/*pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {Intraventricular microinjection (5 micrograms) of the bisquaternary ganglion-blocking drug chlorisondamine prevented acquisition of nicotine-induced conditioned taste aversion (CTA) in rats. This appeared to be a specific effect because chlorisondamine did not attenuate the conditioned taste aversion caused by apomorphine. These results support findings from other behavioural procedures indicating that centrally administered chlorisondamine causes a long-term blockade of central nicotinic mechanisms.}, } @article {pmid3755946, year = {1986}, author = {Mohammed, AK and Callenholm, NE and Järbe, TU and Swedberg, MD and Danysz, W and Robbins, TW and Archer, T}, title = {Role of central noradrenaline neurons in the contextual control of latent inhibition in taste aversion learning.}, journal = {Behavioural brain research}, volume = {21}, number = {2}, pages = {109-118}, doi = {10.1016/0166-4328(86)90089-6}, pmid = {3755946}, issn = {0166-4328}, mesh = {Animals ; Avoidance Learning/*physiology ; Behavior, Animal/physiology ; Brain/*physiology ; *Inhibition, Psychological ; Male ; Norepinephrine/*physiology ; Rats ; Taste/*physiology ; }, abstract = {Three experiments were performed to examine the effects of noradrenaline (NA) depletion, using 3 different methods: lesions of the dorsal noradrenergic bundle (DB) with 6-hydroxydopamine (6-OHDA), lesions induced by neonatal treatment with 6-OHDA and lesions induced by systemic DSP4 upon latent inhibition, using the taste-aversion learning procedure. NA depleted and control (sham, vehicle or saline) rats were given pre-exposure trials to either novel saccharin or to novel saccharin in a novel type of drinking bottle (the noisy bottle). Later, during conditioning trials saccharin was presented in the noisy bottles for all the rats, followed by lithium chloride injections. Saccharin aversions, tested for in the noisy bottles, indicated considerably weaker saccharin aversions (i.e. more latent inhibition) by the control groups pre-exposed to both saccharin and the noisy bottles. These context-dependent latent inhibition effects were clearly attenuated by all 3 treatments that depleted central NA. Biochemical assays confirmed the NA depletions in each case. The results, demonstrating the intimate role of central NA neurons in contextual control of latent inhibition in taste-aversion learning, appear to conform with current attentional theories of NA function in the forebrain.}, } @article {pmid3017373, year = {1986}, author = {Simbayi, LC and Boakes, RA and Burton, MJ}, title = {Effects of basolateral amygdala lesions on taste aversions produced by lactose and lithium chloride in the rat.}, journal = {Behavioral neuroscience}, volume = {100}, number = {4}, pages = {455-465}, doi = {10.1037//0735-7044.100.4.455}, pmid = {3017373}, issn = {0735-7044}, mesh = {Amygdala/*physiology ; Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Conditioning, Classical/physiology ; Drinking/drug effects ; Extinction, Psychological/physiology ; *Lactose/administration & dosage ; Lithium/poisoning ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; }, abstract = {In Experiment 1, intact rats were given either lactose or sucrose solutions. Although on first exposure they readily consumed lactose, its ingestion produced a conditioned taste avoidance which was partly extinguished by repeated sucrose exposure after lactose conditioning. In Experiment 2, rats with large bilateral electrolytic lesions of the basolateral amygdala and those with either sham or no operations were given two pairings of saline with LiCl injections (upper gastrointestinal tract discomfort) and in a separate condition access to high levels of lactose (lower gastrointestinal tract discomfort). Conditioned taste avoidances were measured both by two-bottle tests and by video recordings of the rats' orofacial and somatic responses. The lesions attenuated LiCl-induced taste aversion but not lactose-induced taste avoidance, results demonstrating that taste avoidance can occur without the basolateral amygdala. The results suggested that aversions based on distaste can be distinguished from avoidances based on danger, not only in terms of orofacial responses but also in terms of their neuroanatomical substrate.}, } @article {pmid3737621, year = {1986}, author = {Spivak, K and Amit, Z}, title = {The effects of pimozide on drinking behavior in the rat: an investigation using the conditioned taste aversion paradigm.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {24}, number = {6}, pages = {1527-1531}, doi = {10.1016/0091-3057(86)90479-x}, pmid = {3737621}, issn = {0091-3057}, mesh = {Analysis of Variance ; Animals ; Conditioning, Psychological/*drug effects ; Drinking/*drug effects ; Male ; Pimozide/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin/administration & dosage ; Tartrates/pharmacology ; Taste ; }, abstract = {In an attempt to examine the potential aversive properties of the neuroleptic pimozide, a conventional conditioned taste aversion (CTA) paradigm was employed. Rats were either pretreated with pimozide (1.0 mg/kg) before the presentation of a familiar or novel saccharin-flavored solution or tap water or received injections of pimozide after the presentation of a novel saccharin solution. Following this procedure, rats were given a two bottle choice test under drug-free conditions. All pretreated pimozide groups demonstrated a significant unconditioned reduction in fluid intake relative to the vehicle control group. These pimozide groups having different drinking histories did not differ from one another. Although pimozide did not induce a CTA in rats post-treated with this neuroleptic, overall this group drank significantly less saccharin than the control group. Furthermore, on the two bottle choice test, rats which received contingent exposure to pimozide and saccharin (pre and post conditions), did not demonstrate a preference for the saccharin solution. These results suggest that the reduction in fluid intake observed in the pretreated pimozide groups may be due to some unconditioned aversive state induced by the drug. These data indicate that the mechanisms involved in the reduction of fluid intake induced by pimozide may be unrelated to a manipulation of the reinforcing properties of the appetitive stimulus.}, } @article {pmid3724948, year = {1986}, author = {Brett, LP and Levine, R and Levine, S}, title = {Bidirectional responsiveness of the pituitary-adrenal system in old and young male and female rats.}, journal = {Neurobiology of aging}, volume = {7}, number = {3}, pages = {153-159}, doi = {10.1016/0197-4580(86)90036-9}, pmid = {3724948}, issn = {0197-4580}, support = {AG02210/AG/NIA NIH HHS/United States ; HD-02881/HD/NICHD NIH HHS/United States ; MH-19936/MH/NIMH NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Avoidance Learning/physiology ; Circadian Rhythm ; Corticosterone/*blood ; Female ; Male ; Pituitary-Adrenal System/*physiology ; Rats ; Rats, Inbred F344 ; Sex Factors ; Stress, Physiological/physiopathology ; Stress, Psychological/physiopathology ; Taste ; }, abstract = {Bidirectional responsiveness of the pituitary-adrenal system was examined in young adult (3-5 months) and old (24-26 months) male and female rats. In Experiment 1, an approach-avoidance conflict was created by exposing food- and water-deprived subjects to a flavored solution which had previously been paired with lithium chloride-induced illness in a conditioned taste aversion paradigm. Young and old males and young females elevated plasma corticosterone in response to deprivation; males showed a further elevation when reexposed to the solution, whereas young females did not. Old females did not exhibit a corticosterone elevation to deprivation or upon reexposure. In Experiment 2, water was restricted to a fixed period in the morning when corticosterone levels are typically low. Plasma corticosterone was measured before and after watering. Young and old males and young females reentrained their circadian corticosterone rhythm so that levels were elevated just prior to watering; consumption was followed by a drop in corticosterone. Old females failed to reentrain or to suppress corticosterone secretion upon drinking. These findings indicate that the lability of the pituitary-adrenal system is more markedly affected by senescence in females than in males.}, } @article {pmid3704116, year = {1986}, author = {Spector, AC and Smith, JC and Hollander, GR}, title = {Radiation-induced taste aversion: effects of radiation exposure level and the exposure-taste interval.}, journal = {Radiation research}, volume = {106}, number = {2}, pages = {271-277}, pmid = {3704116}, issn = {0033-7587}, mesh = {Animals ; Conditioning, Classical/*radiation effects ; Dose-Response Relationship, Radiation ; Gamma Rays ; Male ; Radiation Dosage ; Rats ; Rats, Inbred Strains ; Saccharin ; Taste/*radiation effects ; Time Factors ; Water ; }, abstract = {Radiation-induced taste aversion has been suggested to possibly play a role in the dietary difficulties observed in some radiotherapy patients. In rats, these aversions can still be formed even when the radiation exposure precedes the taste experience by several hours. This study was conducted to examine whether increasing the radiation exposure level could extend the range of the exposure-taste interval that would still support the formation of a taste aversion. Separate groups of rats received either a 100 or 300 R gamma-ray exposure followed 1, 3, 6, or 24 h later by a 10-min saccharin (0.1% w/v) presentation. A control group received a sham exposure followed 1 h later by a 10-min saccharin presentation. Twenty-four hours following the saccharin presentation all rats received a series of twelve 23-h two-bottle preference tests between saccharin and water. The results indicated that the duration of the exposure-taste interval plays an increasingly more important role in determining the initial extent of the aversion as the dose decreases. The course of recovery from taste aversion seems more affected by dose than by the temporal parameters of the conditioning trial.}, } @article {pmid3016801, year = {1986}, author = {Hall, G and Channell, S}, title = {Context specificity of latent inhibition in taste aversion learning.}, journal = {The Quarterly journal of experimental psychology. B, Comparative and physiological psychology}, volume = {38}, number = {2}, pages = {121-139}, pmid = {3016801}, issn = {0272-4995}, mesh = {Animals ; *Avoidance Learning ; Chlorides/*pharmacology ; *Inhibition, Psychological ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Taste/*drug effects ; }, } @article {pmid3016579, year = {1986}, author = {Mastropaolo, JP and Dacanay, RJ and Riley, AL}, title = {Effects of trimethyltin chloride on the LiCl dose-response function for conditioned taste aversions in rats.}, journal = {Neurobehavioral toxicology and teratology}, volume = {8}, number = {3}, pages = {297-300}, pmid = {3016579}, issn = {0275-1380}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Chlorides/*pharmacology ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Taste ; Trialkyltin Compounds/*pharmacology ; Trimethyltin Compounds/*pharmacology ; }, abstract = {Twenty-one days following intragastric administration of 6.0 mg/kg of TMT (TMT chloride base/kg) or equivolume distilled water, groups of rats were injected with various doses of LiCl (0, 0.15, 0.60 or 1.8 mEq/kg) following the consumption of a novel saccharin solution. Both groups subsequently avoided the consumption of saccharin, with the degree of the aversion directly related to the dose of LiCl. Further, there was no difference between the TMT- and non-TMT-treated rats in the degree of aversion at any dose. These data suggest that the previously-reported effect of TMT on long-delay taste aversion learning was not likely due to changes in sensory responsiveness.}, } @article {pmid3714788, year = {1986}, author = {Mohammed, AK and Jonsson, G and Söderberg, U and Archer, T}, title = {Impaired selective attention in methylazoxymethanol-induced microencephalic rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {24}, number = {4}, pages = {975-981}, doi = {10.1016/0091-3057(86)90445-4}, pmid = {3714788}, issn = {0091-3057}, mesh = {Animals ; Attention/*drug effects ; Avoidance Learning/drug effects ; Azo Compounds/*pharmacology ; Brain/metabolism ; Catecholamines/metabolism ; Discrimination Learning/drug effects ; Female ; Methylazoxymethanol Acetate/*pharmacology ; Microcephaly/*chemically induced ; Motor Activity/drug effects ; Pregnancy ; Rats ; Rats, Inbred Strains ; Taste/drug effects ; }, abstract = {Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. Several behavioral tests were performed when the rats had reached an adult age. MAM treated rats were hyperactive, and were severely impaired in the acquisition of successive position reversal in a T-maze. The microencephalic rats failed also to demonstrate contextual control of latent inhibition (the stimulus preexposure effect) in taste-aversion conditioning. These results indicate that MAM treatment disrupts attentional processes and that this may account for the learning impairment.}, } @article {pmid3703907, year = {1986}, author = {Roney, PL and Costa, LG and Murphy, SD}, title = {Conditioned taste aversion induced by organophosphate compounds in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {24}, number = {3}, pages = {737-742}, doi = {10.1016/0091-3057(86)90583-6}, pmid = {3703907}, issn = {0091-3057}, support = {ES 03424/ES/NIEHS NIH HHS/United States ; }, mesh = {Analgesics ; Animals ; Avoidance Learning/*drug effects ; Brain/enzymology ; Cholinesterases/blood/metabolism ; Dichlorvos/pharmacology ; Isoflurophate/pharmacology ; Male ; Organophosphorus Compounds/*pharmacology ; Parathion/pharmacology ; Rats ; Rats, Inbred Strains ; Reaction Time/drug effects ; Taste/*drug effects ; }, abstract = {Three organophosphate compounds, dichlorvos, parathion and diisopropylfluorophosphate were tested as an unconditioned stimulus in the conditioned taste aversion (CTA) test. All organophosphates caused a dose-dependent CTA in rats at doses which did not induce any other signs of toxicity. Experiments with dichlorvos showed that the minimum dose which caused CTA did not alter the rats' sensitivity to pain or their behavior in either an open field or an inclined plane. Cholinesterase activity was inhibited in a dose-dependent manner in brain and plasma after administration of the organophosphates and CTA was correlated with the degree of plasma cholinesterase inhibition. CTA appears to be a sensitive indicator of neurobehavioral effects of mild exposure to organophosphates which causes only 30-40% inhibition of plasma cholinesterase.}, } @article {pmid3010336, year = {1986}, author = {Etscorn, F and Moore, GA and Hagen, LS and Caton, TM and Sanders, DL}, title = {Saccharin aversions in hamsters as a result of nicotine injections.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {24}, number = {3}, pages = {567-570}, doi = {10.1016/0091-3057(86)90559-9}, pmid = {3010336}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Chlorides/pharmacology ; Cricetinae ; Injections, Intraperitoneal ; Lithium/pharmacology ; Lithium Chloride ; Male ; Mesocricetus ; Nicotine/*pharmacology ; Saccharin/*pharmacology ; Taste/*drug effects ; Time Factors ; }, abstract = {Golden Syrian hamsters (males, N = 70) showed dose-related conditioned taste aversion (CTA) when saccharin drinking was followed by delayed nicotine injections. Baseline consisted of measuring amounts consumed after 20 minutes of daily access to tap water. Measures were taken for five days. The hamsters were then conditioned by offering them saccharin solution (0.1%, w/v) for 20 minutes; afterwhich a 30 minute delay was imposed. Subsequent to the delay, groups of 10 animals were treated as follows: nicotine injection (1.0, 3.0, or 9.0 mg/kg, IP), saline injection, lithium chloride injection (2% body weight of a 0.15 M solution), sham injection, or left in their cages as handling/stress controls. Following two recovery days with plain water available for 20 minutes, all animals were tested for CTA by offering them saccharin solution. Dose-related CTA was demonstrated in the nicotine animals as measured by a decrease in saccharin consumption compared to drinking measures obtained from animals injected with saline. Lithium chloride produced the same degree of CTA as 9 mg/kg of nicotine, and the aversions had extinguished in all groups by the third test day.}, } @article {pmid3008705, year = {1986}, author = {Miller, JS and Nonneman, AJ and Kelly, KS and Neisewander, JL and Isaac, WL}, title = {Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions.}, journal = {Behavioral and neural biology}, volume = {45}, number = {2}, pages = {240-253}, doi = {10.1016/s0163-1047(86)90816-2}, pmid = {3008705}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Chlorides ; Conditioning, Classical/physiology ; *Food Preferences ; Hippocampus/*physiology ; Lithium ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Smell/*physiology ; Taste/*physiology ; }, abstract = {Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.}, } @article {pmid2939464, year = {1986}, author = {Gill, K and Shatz, K and Amit, Z and Ogren, SO}, title = {Conditioned taste aversion to ethanol induced by zimeldine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {24}, number = {3}, pages = {463-468}, doi = {10.1016/0091-3057(86)90542-3}, pmid = {2939464}, issn = {0091-3057}, mesh = {5-Hydroxytryptophan/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Ethanol/*pharmacology ; Male ; Rats ; Serotonin/metabolism ; Taste/drug effects ; Time Factors ; Zimeldine/*pharmacology ; }, abstract = {Conditioned taste aversions (CTA) were induced to both ethanol and saccharin solutions with the serotonin uptake inhibitor Zimeldine. When animals were pretreated with Zimeldine prior to the presentation of a novel flavour a CTA did not result. However, there is evidence that Zimeldine induces an unconditioned suppression of drinking. These results are discussed in terms of their relevance to Zimeldine's effects on voluntary ethanol consumption.}, } @article {pmid3774910, year = {1986}, author = {Rabin, BM and Hunt, WA and Chedester, AL and Lee, J}, title = {Role of the area postrema in radiation-induced taste aversion learning and emesis in cats.}, journal = {Physiology & behavior}, volume = {37}, number = {5}, pages = {815-818}, doi = {10.1016/0031-9384(86)90189-7}, pmid = {3774910}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cats ; Conditioning, Classical/*physiology ; Medulla Oblongata/*physiology/radiation effects ; Neurosecretory Systems/*physiology/radiation effects ; Taste/*physiology/radiation effects ; Vomiting/physiopathology ; }, abstract = {The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.}, } @article {pmid3739747, year = {1986}, author = {Schulz, H and Feuer, L}, title = {Gamma-L-glutamyl-taurine (Litoralon) affects conditioned taste aversion in rats.}, journal = {Acta physiologica Hungarica}, volume = {67}, number = {2}, pages = {233-242}, pmid = {3739747}, issn = {0231-424X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Diazepam/pharmacology ; Glutamine/*analogs & derivatives/pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Taste/*drug effects ; Taurine/*analogs & derivatives/pharmacology ; Time Factors ; gamma-Aminobutyric Acid/analogs & derivatives/pharmacology ; }, abstract = {The dipeptide gamma-L-glutamyl-taurine (Litoralon) reduced neophobia of rats at a dose of 5.0 mg/kg (i.p.) in a "one-bottle forced choice paradigm" for conditioned taste aversion (CTA), but did not significantly affect the rats' "memory" of intoxication following chronic treatment at doses of 0.05, 0.50 and 5.00 mg/kg (i.p.). Acute treatment with Litoralon (10-1000 micrograms/kg, i.p.) did not affect CTA checked in a "two-bottle test", when administered immediately following the unconditioned stimulus (LiCl injection). In contrast, when given 90 min prior to the retention test, the injection of Litoralon (50.0 micrograms/kg) and gamma-aminobutyryl ethanolamine phosphate (100 and 500 micrograms/kg) resulted in a significantly higher intake of saccharin solution by the rats. This effect is comparable to the action of diazepam tested in the same experimental procedure. The results support our hypothesis about the anti-conflict potencies of these dipeptides, exerted by reducing aversion of phobia and/or the anxiety level of the animals in the experimental situation.}, } @article {pmid3737743, year = {1986}, author = {Yamamoto, T and Asai, K}, title = {Effects of gustatory deafferentation on ingestion of taste solutions as seen by licking behavior in rats.}, journal = {Physiology & behavior}, volume = {37}, number = {2}, pages = {299-305}, doi = {10.1016/0031-9384(86)90237-4}, pmid = {3737743}, issn = {0031-9384}, mesh = {Afferent Pathways/physiology ; Animals ; Chorda Tympani Nerve/*physiology ; Drinking Behavior/*physiology ; Evoked Potentials ; Glossopharyngeal Nerve/*physiology ; Male ; Palate/*innervation ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Taste Buds/*physiology ; }, abstract = {The role of the taste nerves in licking behavior to various taste solutions was examined in rats. The study consisted of two experiments. In the electrophysiological experiment, the whole nerve recording of the anterior palatine nerve (PN) was performed to examine the response properties of this nerve to taste stimulation applied to the taste buds in the nasoincisal duct. When the moderate concentrations of solutions were used, the PN responded best to HCl, followed by sucrose and NaCl. Quinine hydrochloride elicited the smallest response. In the behavioral experiment, the number of licks/20 sec was measured for each of the test solutions such as 0.5 M sucrose, 0.01-1.0 M NaCl, 0.03 M HCl and 0.0005 M-0.01 M quinine in normal control and experimental rats. The experimental animals received bilateral deafferentation of the PN, chorda tympani (CT) and glossopharyngeal nerve (GN) alone or in various combinations. Rats without one of the 3 taste nerves still rejected the aversive HCl and quinine solutions. However, after lesions of both CT and GN, or all the 3 taste nerves, the rats showed a significant increase in the number of licks to these aversive solutions. These results suggest that taste aversion disappears after denervation of more than 80% of the total taste buds. The interlick interval, lick duration and the amount of intake per lick did not change significantly after sections of the taste nerves in any combinations.}, } @article {pmid3725923, year = {1986}, author = {Rabin, BM and Hunt, WA and Bakarich, AC and Chedester, AL and Lee, J}, title = {Angiotensin II-induced taste aversion learning in cats and rats and the role of the area postrema.}, journal = {Physiology & behavior}, volume = {36}, number = {6}, pages = {1173-1178}, doi = {10.1016/0031-9384(86)90496-8}, pmid = {3725923}, issn = {0031-9384}, mesh = {Angiotensin II/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Brain Mapping ; Cats ; Conditioning, Classical/physiology ; Male ; Medulla Oblongata/*drug effects/physiology ; Rats ; Rats, Inbred Strains ; Species Specificity ; Taste/*drug effects/physiology ; }, abstract = {The capacity of angiotensin II (AII, 1 mg/kg, IP) to produce a taste aversion was studied in cats and rats with and without lesions of the area postrema. Using a one-bottle test, injection of AII produced an aversion in cats but not in rats. Using a two-bottle test, injection of AII produced a slight, but significant, decrease in sucrose preference in intact rats, but had no effect on rats with area postrema lesions. Lesions of the area postrema prevented the acquisition of a taste aversion in cats. These results, which show a clear species difference in the capacity of AII to produce a taste aversion, are discussed as supporting the hypotheses that there is a relationship between the sensitivity of the area postrema to a compound and the capacity of that compound to produce a taste aversion; and that excitation of the area postrema constitutes a sufficient condition for taste aversion learning to occur.}, } @article {pmid3715422, year = {1986}, author = {Archer, T and Callenholm, NE and Järbe, TU and Minor, BG and Mohammed, AK}, title = {Taste/tactile cue discriminations in taste-aversion learning following depletion of noradrenaline.}, journal = {Scandinavian journal of psychology}, volume = {27}, number = {1}, pages = {39-51}, doi = {10.1111/j.1467-9450.1986.tb01185.x}, pmid = {3715422}, issn = {0036-5564}, mesh = {Animals ; Avoidance Learning/*physiology ; Benzylamines ; Cues ; Discrimination Learning/*physiology ; Male ; Norepinephrine/*physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; Touch/*physiology ; }, } @article {pmid3703982, year = {1986}, author = {De Luca, B and Monda, M}, title = {Neophobia, conditioned taste aversion and EEG arousal after globus pallidus lesion.}, journal = {Physiology & behavior}, volume = {36}, number = {3}, pages = {545-551}, doi = {10.1016/0031-9384(86)90329-x}, pmid = {3703982}, issn = {0031-9384}, mesh = {Animals ; *Arousal ; *Conditioning, Classical ; *Drinking Behavior ; Electroencephalography ; Exploratory Behavior ; *Feeding Behavior ; Functional Laterality ; Globus Pallidus/*physiology ; Male ; Phobic Disorders/*physiopathology ; Rats ; Rats, Inbred Strains ; Saccharin ; Smell ; *Taste ; Time Factors ; }, abstract = {Rats with unilateral or bilateral electrolytic lesions in the globus pallidus (GP) became aphagic and adipsic. Aphagia and adipsia lasted 2-3 days in rats with unilateral lesion, but were more persistent in animals with bilateral lesions. EEG arousal induced by nociceptive stimuli applied to the side of the body contralateral to the unilateral pallidal lesion was of shorter duration than that induced by ipsilateral stimulation; no difference was found between rats injured in left or right (GP). Total exploratory activity of rats with symmetrical or asymmetrical lesions, exposed to a novel environment for ten min, was not different from that of the control group, but the exploratory activity measured in a 60 sec block showed trends in the two injured groups being different than those in the controls. Rats with unilateral right or bilateral lesions showed a lower level of neophobia for saccharin than controls. Acquisition of conditioned taste aversion was similar in lesioned rats and controls, but extinction of the conditioned taste aversion was slower in the intact than in the injured animals.}, } @article {pmid3703975, year = {1986}, author = {Spivak, KJ and Amit, Z}, title = {Effects of pimozide on appetitive behavior and locomotor activity: dissimilarity of effects when compared to extinction.}, journal = {Physiology & behavior}, volume = {36}, number = {3}, pages = {457-463}, doi = {10.1016/0031-9384(86)90315-x}, pmid = {3703975}, issn = {0031-9384}, mesh = {Animals ; Appetitive Behavior/*drug effects ; Extinction, Psychological/*drug effects ; Male ; Motor Activity/*drug effects ; Pimozide/*pharmacology ; Rats ; Rats, Inbred Strains ; Saccharin ; Tartrates/pharmacology ; }, abstract = {The effects of pimozide were examined in a runway paradigm using food reward. Rats received one of three doses of pimozide, vehicle or Ringer's prior to testing. Two additional groups received pimozide or vehicle after the test trial in the home cage. An extinction group received no food in the goal box on test days. Several components of running behavior were assessed as was food consumed in the goal box. Effects of pimozide on general locomotor activity were assessed in the open-field following the runway phase. Results of the runway indicated that pimozide-treated rats differed from the extinction group in latencies to leave the start box and enter the goal box. Pimozide-treated rats consumed less saccharin-flavored food than controls. The post-treatment pimozide group showed a reduction in saccharin-food intake suggesting a conditioned taste aversion. Thus, the reduction observed in the pretreated pimozide group may be due to some unconditioned aversion induced by the drug. Open-field revealed that pimozide resulted in lower activity than controls. This study indicates that the effects of pimozide on food reinforcement are not similar to the effects seen in extinction. These data are consistent with the hypothesis that the effects of pimozide, in this paradigm, constitute an interference with motor responses as opposed to an attenuation of reward properties of the stimuli.}, } @article {pmid3520612, year = {1986}, author = {McCoy, DF and Roszman, TL and Miller, JS and Kelly, KS and Titus, MJ}, title = {Some parameters of conditioned immunosuppression: species difference and CS-US delay.}, journal = {Physiology & behavior}, volume = {36}, number = {4}, pages = {731-736}, doi = {10.1016/0031-9384(86)90361-6}, pmid = {3520612}, issn = {0031-9384}, support = {NS17423/NS/NINDS NIH HHS/United States ; NS21655/NS/NINDS NIH HHS/United States ; T32CA09509/CA/NCI NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Cyclophosphamide/*pharmacology ; Drinking Behavior ; Female ; Hemolytic Plaque Technique ; *Immunosuppression Therapy ; Mice ; Mice, Inbred BALB C ; Rats ; Rats, Inbred F344 ; Saccharin/*pharmacology ; Species Specificity ; }, abstract = {Three experiments were conducted in which an illness-inducing immunosuppressant, cyclophosphamide (an unconditioned stimulus, US) was associated with a previously presented saccharin solution conditioned stimulus (CS). In each experiment, reexposure to the CS produced a conditioned suppression of the plaque-forming-cell response in the experimental groups. Experiment I demonstrated this result with Fisher 344 rats. Experiment II replicated the effect with Balb/c mice. In Experiment III conditioned immunosuppression was demonstrated when mice received CS-US delays as long as 6 hours. No evidence of a delay gradient was present in either the behavioral or the immunologic data. These parallel findings offer no support for the idea of a dissociation between the taste aversion and conditioned immunosuppression processes.}, } @article {pmid3094066, year = {1986}, author = {Willner, P and Ellis, T and Williams, V and Chauvin, P and Muscat, R}, title = {Conditioned taste aversion and conditioned drinking: two independent and opposing effects of 5-hydroxytryptophan?.}, journal = {Psychopharmacology}, volume = {90}, number = {1}, pages = {79-84}, pmid = {3094066}, issn = {0033-3158}, mesh = {5-Hydroxytryptophan/*pharmacology ; Animals ; Benserazide/pharmacology ; Conditioning, Operant/*drug effects ; Drinking Behavior/*drug effects ; Male ; Rats ; Taste/*drug effects ; }, abstract = {Four experiments were carried out to examine the effects of 5-HTP in a conditioned taste aversion (CTA) paradigm. Using two-choice tests to measure the CTA, administration of 5-HTP following consumption of a novel flavour caused aversions to saline and saccharin solutions. In single-choice tests 5-HTP reduced consumption of saccharin, sugar cubes and beef-flavoured stock cubes, but only reduced saline consumption if animals had been pretreated with the 5-HTP decarboxylase inhibitor benserazide or the 5-HT receptor antagonist xylamidine, both of which act peripherally. Benserazide did not attenuate the CTA in any experiment. The results are interpreted in terms of two competing behavioural effects of 5-HTP: a centrally-mediated CTA and a peripherally-mediated conditioned drinking response.}, } @article {pmid3088661, year = {1986}, author = {Carr, GD and White, NM}, title = {Anatomical disassociation of amphetamine's rewarding and aversive effects: an intracranial microinjection study.}, journal = {Psychopharmacology}, volume = {89}, number = {3}, pages = {340-346}, pmid = {3088661}, issn = {0033-3158}, mesh = {Amygdala/drug effects ; Animals ; Avoidance Learning/drug effects ; Brain/*drug effects ; Caudate Nucleus/drug effects ; Dextroamphetamine/*pharmacology ; Frontal Lobe/drug effects ; Male ; Medulla Oblongata/drug effects ; Neurosecretory Systems/drug effects ; Nucleus Accumbens/drug effects ; Rats ; *Reward ; Taste/drug effects ; }, abstract = {Amphetamine has rewarding properties in some behavioral paradigms, such as self-administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The present study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 micrograms/0.5 microliter per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed.}, } @article {pmid3088658, year = {1986}, author = {Corrigall, WA and Linseman, MA and D'Onofrio, RM and Lei, H}, title = {An analysis of the paradoxical effect of morphine on runway speed and food consumption.}, journal = {Psychopharmacology}, volume = {89}, number = {3}, pages = {327-333}, pmid = {3088658}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning ; Feeding Behavior/*drug effects ; Food Deprivation ; Male ; Morphine/*pharmacology ; Motivation/*drug effects ; Naltrexone/analogs & derivatives/pharmacology ; Nervous System/*drug effects ; Quaternary Ammonium Compounds ; Rats ; Rats, Inbred Strains ; Reward ; Taste/drug effects ; Tegmentum Mesencephali/drug effects ; }, abstract = {A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference.}, } @article {pmid3024194, year = {1986}, author = {Shaw, N}, title = {Disruption of conditioned taste aversion: the effect of ECS after the taste-illness interval.}, journal = {Physiology & behavior}, volume = {38}, number = {3}, pages = {431-434}, doi = {10.1016/0031-9384(86)90117-4}, pmid = {3024194}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Chlorides/pharmacology ; *Conditioning, Classical/drug effects ; *Electroshock ; Lithium/pharmacology ; Lithium Chloride ; Male ; Memory/physiology ; Rats ; Taste/drug effects/*physiology ; }, abstract = {Rats were taught a conditioned taste aversion (CTA) by pairing a 10% sucrose solution (CS) with lithium chloride-induced poisoning (UCS) 30 min later. The extent to which electroconvulsive shock (ECS) (80 mA for 600 msec) impaired the acquisition of the CTA was studied by either interpolating the ECS within the CS-UCS interval or by administering it at various times following the UCS (0, 5, 10, 15, 30, 60 and 120 min). There was a pronounced although limited loss of learning among all groups when ECS was delivered no later than 10 min after the UCS. When ECS was administered between 15 and 120 min, the overall aversion acquired did not differ significantly from that of the poisoned controls. It is concluded that while the stability of CTA seems to increase at about the same time the behavioral concomitants of lithium toxicity become apparent (10 min), this phenomenon does not necessarily imply that the neural trace underlying CTA has consolidated into a less labile state.}, } @article {pmid3014579, year = {1986}, author = {Shaw, N}, title = {Disruption of conditioned taste aversion by ECS: the role of lithium chloride.}, journal = {Physiology & behavior}, volume = {36}, number = {6}, pages = {1193-1195}, doi = {10.1016/0031-9384(86)90500-7}, pmid = {3014579}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/*toxicity ; Electroshock/*adverse effects ; Learning Disabilities/*etiology ; Lithium/*toxicity ; Lithium Chloride ; Male ; Rats ; Sucrose ; Taste/*drug effects ; Temperature ; }, abstract = {Rats were taught a conditioned taste aversion (CTA) by pairing a 10% sucrose solution (CS) with lithium chloride (LiCl)-induced poisoning (UCS). The CS-UCS interval was 30 min. The LiCl dose (20 ml/kg) was either strong (0.15 M) or weaker (0.075 M). Electroconvulsive shock (ECS) (80 mA for 600 msec) was interpolated within the CS-UCS interval at either 15 or 30 min. ECS caused a significant disruption of CTA only when the aversion was established with the weaker dose of LiCl. There was also no indication that interference with CTA was dependent upon close temporal contiguity between the ECS and LiCl. In a second experiment a CTA was established with LiCl (0.15 M) which was heated to 45 degrees C. Under these conditions ECS produced a similar disruption of learning to that when the UCS was the weaker dose of LiCl (0.075 M). The results suggest that an apparent differential loss of learning within the CS-UCS interval described in a previous report was accidentally created when some groups of animals were poisoned with warm and others with cold LiCl.}, } @article {pmid3010348, year = {1986}, author = {Ervin, GN and Teeter, MN}, title = {Cholecystokinin octapeptide and lithium produce different effects on feeding and taste aversion learning.}, journal = {Physiology & behavior}, volume = {36}, number = {3}, pages = {507-512}, doi = {10.1016/0031-9384(86)90323-9}, pmid = {3010348}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Chlorides/*pharmacology ; Feeding Behavior/*drug effects ; Lithium/*pharmacology ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; Saline Solution, Hypertonic ; Sincalide/*pharmacology ; Sodium Chloride/pharmacology ; *Taste ; }, abstract = {The strengths of taste aversion induced by sulphated cholecystokinin 26-33 (CCK-8; 1,2,4 and 8 micrograms/kg IP) and lithium chloride (LiCl; 7.5, 15, 30 and 60 mg/kg IP) were determined in order to assess the relative aversiveness of the two compounds. All doses of LiCl induced strong aversion, but only the highest dose of CCK-8 induced aversion, which was mild. Effects of CCK-8 and LiCl on food intake were then compared in the hour (hr) following 8 hr of food deprivation; rats were on this food deprivation schedule for a relatively long time (78 days) throughout testing. All doses of CCK-8 reduced food intake significantly. Most doses of LiCl either did not affect or significantly increased food intake. Although 60 mg/kg LiCl did not affect food intake when administered 15 or 30 min before food presentation, it significantly increased food intake when administered 1, 2 or 3 hr before food presentation. Overeating of solid food may be an illness-induced behavior. Although a very high dose of LiCl (120 mg/kg) decreased food intake markedly, the rats were obviously distressed, not satiated. Failure of CCK-8 to affect feeding behavior like LiCl is indirect evidence that the reduction of food intake by CCK-8 is not merely the result of aversiveness, but is an extremely potent and specific behavioral effect.}, } @article {pmid3010144, year = {1986}, author = {Rabin, BM and Hunt, WA and Lee, J}, title = {Effects of area postrema lesions on taste aversions produced by treatment with WR-2721 in the rat.}, journal = {Neurobehavioral toxicology and teratology}, volume = {8}, number = {1}, pages = {83-87}, pmid = {3010144}, issn = {0275-1380}, mesh = {Amifostine/*pharmacology ; Animals ; Avoidance Learning/drug effects ; Drinking/drug effects ; Food Preferences/*drug effects ; Male ; Medulla Oblongata/*drug effects ; Neurosecretory Systems/*drug effects ; Organothiophosphorus Compounds/*pharmacology ; Rats ; Rats, Inbred Strains ; Sucrose ; Taste/*drug effects ; }, abstract = {The conditioned taste aversion procedure was used to further assess some behavioral effects of treatment with the putative radioprotectant WR-2721 and the role of the area postrema in mediating the behavioral effects of treatment. Treatment with 40, 150 or 300 mg/kg WR-2721 produced dose-dependent changes in sucrose intake in both control rats and rats with area postrema lesions. The effectiveness of the lesion in disrupting the acquisition of an aversion varied as a function of the dose administered, with the lesions producing the greatest disruption of aversion learning at the lowest dose and little disruption at the highest dose tested. At all dose levels, sucrose intake was greater for the rats with area postrema lesions than for the sham-operated control rats. Treatment with WR-2721 also produced significant decreases in total fluid intake, particularly at the higher dose levels. The results are discussed as indicating that treatment with WR-2721 produces highly toxic effects on behavior and that the use of the compound as a radioprotectant for radiotherapy requires additional assessment of its effects on brain function and behavior.}, } @article {pmid2871536, year = {1986}, author = {Rabin, BM and Hunt, WA}, title = {Mechanisms of radiation-induced conditioned taste aversion learning.}, journal = {Neuroscience and biobehavioral reviews}, volume = {10}, number = {1}, pages = {55-65}, doi = {10.1016/0149-7634(86)90033-3}, pmid = {2871536}, issn = {0149-7634}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/drug effects/*radiation effects ; Brain/metabolism/radiation effects ; Chlorides/pharmacology ; Conditioning, Classical ; Cues ; Digestive System/radiation effects ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Environment ; Lithium/pharmacology ; Lithium Chloride ; Macaca mulatta ; Male ; Mice ; Neurosecretory Systems/radiation effects ; Neurotransmitter Agents/radiation effects ; Rats ; Reinforcement Schedule ; Research Design ; Synaptic Transmission/radiation effects ; Taste/*radiation effects ; Vomiting ; }, abstract = {The literature on taste aversion learning is reviewed and discussed, with particular emphasis on those studies that have used exposure to ionizing radiation as an unconditioned stimulus to produce a conditioned taste aversion. The primary aim of the review is to attempt to define the mechanisms that lead to the initiation of the taste aversion response following exposure to ionizing radiation. Studies using drug treatments to produce a taste aversion have been included to the extent that they are relevant to understanding the mechanisms by which exposure to ionizing radiation can affect the behavior of the organism.}, } @article {pmid2999539, year = {1985}, author = {Aragon, CM and Spivak, K and Amit, Z}, title = {Blockade of ethanol induced conditioned taste aversion by 3-amino-1,2,4-triazole: evidence for catalase mediated synthesis of acetaldehyde in rat brain.}, journal = {Life sciences}, volume = {37}, number = {22}, pages = {2077-2084}, doi = {10.1016/0024-3205(85)90579-x}, pmid = {2999539}, issn = {0024-3205}, mesh = {Acetaldehyde/*biosynthesis ; Amitrole/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Brain/*enzymology ; Catalase/antagonists & inhibitors/*metabolism ; Chlorides/pharmacology ; Conditioning, Psychological/*drug effects ; Ethanol/antagonists & inhibitors/*metabolism ; Lithium/pharmacology ; Lithium Chloride ; Male ; Morphine/pharmacology ; Oxidation-Reduction ; Rats ; Taste ; Triazoles/*pharmacology ; }, abstract = {This investigation seeks to present evidence for the oxidation of ethanol in the brain via the peroxidatic activity of catalase and simultaneously provide evidence for the role of central acetaldehyde (ACH) in the mediation of an ethanol-induced conditioned taste aversion (CTA). Ethanol is capable of inducing a conditioned taste aversion. Pretreatment with the catalase inhibitor, 3-amino-1,2,4-triazole (AT), shows an attenuation of this ethanol-induced CTA. Animals receiving ethanol injections showed a CTA to a novel solution paired with a drug administration, while ethanol injected animals pretreated with AT did not show a CTA to ethanol administration. This effect of AT appears to be specific to the effects of ethanol as CTA's to morphine and lithium chloride were not affected by AT pretreatment. Peripheral levels of ethanol were the same in all animals regardless of pretreatment indicating that AT had no effect on peripheral levels of ethanol. These data increase support for the notion that acetaldehyde is produced directly in the brain and that it may be the agent mediating some of the psychopharmacological properties of ethanol.}, } @article {pmid3000297, year = {1985}, author = {Burns, RJ and Connolly, GE}, title = {A comment on "coyote control and taste aversion".}, journal = {Appetite}, volume = {6}, number = {3}, pages = {276-281}, doi = {10.1016/s0195-6663(85)80018-0}, pmid = {3000297}, issn = {0195-6663}, mesh = {Animals ; Appetitive Behavior/*drug effects ; Avoidance Learning/*drug effects ; Carnivora ; Chlorides/*toxicity ; Conditioning, Classical/*drug effects ; Lithium/*toxicity ; Lithium Chloride ; Predatory Behavior/*drug effects ; Taste/*drug effects ; }, } @article {pmid3000296, year = {1985}, author = {Ellins, SR}, title = {Coyote control and taste aversion: a predation problem or a people problem?.}, journal = {Appetite}, volume = {6}, number = {3}, pages = {272-275}, doi = {10.1016/s0195-6663(85)80017-9}, pmid = {3000296}, issn = {0195-6663}, mesh = {Animals ; Appetitive Behavior/*drug effects ; Avoidance Learning/*drug effects ; Carnivora ; Chlorides/*toxicity ; Conditioning, Classical/*drug effects ; Lithium/*toxicity ; Lithium Chloride ; Predatory Behavior/*drug effects ; Taste/*drug effects ; }, abstract = {Failures to suppress coyote predation on domestic livestock using the conditioned taste aversion paradigm may be due to such factors as poor livestock management procedures and overestimated coyote predation data, in addition to theoretical and methodological problems as indicated by Forthman Quick, Gustavson and Rusiniak.}, } @article {pmid3000295, year = {1985}, author = {Wade, DA}, title = {Brief comments on "coyote control and taste aversion".}, journal = {Appetite}, volume = {6}, number = {3}, pages = {268-271}, doi = {10.1016/s0195-6663(85)80016-7}, pmid = {3000295}, issn = {0195-6663}, mesh = {Animals ; Appetitive Behavior/*drug effects ; Avoidance Learning/*drug effects ; Carnivora ; Chlorides/*toxicity ; Conditioning, Classical/*drug effects ; Lithium/*toxicity ; Lithium Chloride ; Predatory Behavior/*drug effects ; Taste/*drug effects ; }, } @article {pmid3000293, year = {1985}, author = {Quick, DL and Gustavson, CR and Rusiniak, KW}, title = {Coyote control and taste aversion.}, journal = {Appetite}, volume = {6}, number = {3}, pages = {253-264}, doi = {10.1016/s0195-6663(85)80014-3}, pmid = {3000293}, issn = {0195-6663}, mesh = {Animals ; Appetitive Behavior/*drug effects ; Avoidance Learning/*drug effects ; Carnivora ; Chlorides/*toxicity ; Conditioning, Classical/*drug effects ; Lithium/*toxicity ; Lithium Chloride ; Predatory Behavior/*drug effects ; Research ; Taste/*drug effects ; }, abstract = {Studies in which conditioned taste aversion was used as a non-lethal method to suppress coyote predation are reviewed in light of the controversy that surrounds such research. It is concluded that the negative results obtained to date may have been due to theoretical and methodological problems in the studies. Uncritical acceptance of those results has slowed progress on an effective and inexpensive method of coyote management.}, } @article {pmid2997807, year = {1985}, author = {Landauer, MR and Balster, RL and Harris, LS}, title = {Attenuation of cyclophosphamide-induced taste aversions in mice by prochlorperazine, delta 9-tetrahydrocannabinol, nabilone and levonantradol.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {23}, number = {2}, pages = {259-266}, doi = {10.1016/0091-3057(85)90567-2}, pmid = {2997807}, issn = {0091-3057}, support = {DA-00490/DA/NIDA NIH HHS/United States ; ES-07087/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Apomorphine/pharmacology ; Avoidance Learning/drug effects ; Cyclophosphamide/*antagonists & inhibitors ; Dose-Response Relationship, Drug ; Dronabinol/*analogs & derivatives/*pharmacology ; Male ; Mice ; Phenanthridines/*pharmacology ; Prochlorperazine/*pharmacology ; Taste/*drug effects ; }, abstract = {A series of experiments were performed with adult CD-1 male mice to evaluate the antiemetic effects of several compounds using the conditioned taste aversion procedure. The antiemetics were administered IP immediately prior to a 30-min conditioning trial in which a novel tasting solution (0.3% saccharin) was presented to the subjects. The emetics, apomorphine and the cancer chemotherapeutic drug cyclophosphamide, were given IP immediately after the conditioning trial at doses that induced taste aversions. Three days later the mice received a two bottle preference test (saccharin vs. water) and the percent saccharin consumed of the total fluid intake was calculated. Doses of the phenothiazine antiemetic prochlorperazine (1 and 3 mg/kg) attenuated the aversions produced by 0.3 and 1.0 mg/kg apomorphine. Doses of drugs currently approved or under clinical investigation as antiemetics in conjunction with cancer chemotherapy, i.e., prochlorperazine (1.0 mg/kg), delta 9-tetrahydrocannabinol (0.3 and 1.0 mg/kg) and nabilone (0.01 and 0.03 mg/kg), significantly attenuated the taste aversions induced by cyclophosphamide. Levonantradol at doses of 0.03 and 0.06 mg/kg, however, did not attenuate cyclophosphamide-induced taste aversions. Conditioned taste aversions produced by emetic drugs warrants investigation as a model for evaluating potential antiemetics.}, } @article {pmid3040033, year = {1985}, author = {Lasiter, PS}, title = {Thalamocortical relations in taste aversion learning: II. Involvement of the medial ventrobasal thalamic complex in taste aversion learning.}, journal = {Behavioral neuroscience}, volume = {99}, number = {3}, pages = {477-495}, doi = {10.1037//0735-7044.99.3.477}, pmid = {3040033}, issn = {0735-7044}, support = {NS-11618/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cerebral Cortex/*physiology ; Chlorides/pharmacology ; Digestive System/drug effects ; Lithium/pharmacology ; Lithium Chloride ; Male ; Rats ; Reaction Time/physiology ; Retention, Psychology/physiology ; Taste/*physiology ; Thalamic Nuclei/*physiology ; }, abstract = {Previous neurobehavioral studies have implicated the gustatory thalamocortical relay as a functional substrate of conditioned taste aversion (CTA) learning. These experiments were conducted to examine the involvement of the gustatory thalamic nuclei in fundamental taste reactivity, gastrointestinal reactivity, and CTA learning. In Experiment 1, bilateral electrolytic lesions were produced in the medial ventrobasal thalamic complex (VBm), including the thalamic gustatory nuclei, in one group of rats. A separate group of rats received control lesion placements in the mediodorsal-periventricular (MD-PV) thalamic nuclei. Animals then received preference-aversion taste tests followed by CTA conditioning. At the conclusion of conditioning, lesions were produced in the anterior insular gustatory neocortex (AIGN) to evaluate whether or not the AIGN contributed to CTA learning in animals lacking VBm thalamus. Results of Experiment 1 indicated that control lesions did not disrupt taste reactivity, gastrointestinal reactivity, or CTA learning. Destruction of VBm thalamus attenuated taste reactivity to sucrose, citric acid, and quinine hydrochloride; however, such lesions did not impair normal taste reactivity to sodium chloride. Lesion placements in VBm thalamus also did not reliably impair gastrointestinal reactivity to ingested LiCl. Elimination of VBm thalamus markedly attenuated CTA learning. Results of neocortical lesion manipulations showed that the AIGN contributed to initial CTA learning in animals lacking MD-PV thalamus but that the AIGN did not mediate initial CTA learning in animals lacking VBm thalamus. Whether animals lacking VBm thalamus used olfactory cues associated with drinking solutions to acquire CTAs was evaluated in Experiment 2. Results of Experiment 2 demonstrated that animals lacking VBm thalamus and the olfactory bulbs could not acquire aversions to ingested LiCl following eight conditioning trials. These experiments demonstrate that destruction of VBm thalamus, including the gustatory thalamic nuclei, is sufficient to prevent CTA learning.}, } @article {pmid2991950, year = {1985}, author = {Hunt, T and Switzman, L and Amit, Z}, title = {Involvement of dopamine in the aversive stimulus properties of cocaine in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {22}, number = {6}, pages = {945-948}, doi = {10.1016/0091-3057(85)90300-4}, pmid = {2991950}, issn = {0091-3057}, mesh = {Animals ; Chlorides/pharmacology ; Cocaine/*pharmacology ; Conditioning, Operant/*drug effects ; Dopamine/*physiology ; Drinking/drug effects ; Drug Interactions ; Lithium/pharmacology ; Lithium Chloride ; Male ; Pimozide/pharmacology ; Rats ; Rats, Inbred Strains ; Reinforcement, Psychology ; }, abstract = {Previous studies of cocaine self-administration have demonstrated central dopaminergic involvement in cocaine's positive reinforcing properties. The present study reports the ability of pimozide, a dopamine receptor antagonist, to attenuate a conditioned taste aversion induced by repeated injections of cocaine. Rats placed on a daily water deprivation schedule were subsequently presented with a novel saccharin taste in their drinking fluid immediately followed by administration of four 9 mg/kg injections of cocaine spaced at 20 min intervals. These animals exhibited a reduction in saccharin intake on subsequent presentations. Animals pretreated with pimozide 90 min prior to the saccharin-cocaine pairings failed to show this reduction. In a second experiment using an identical procedure, repeated injections of lithium chloride were shown to induce a CTA both in pimozide-pretreated and control animals. The results of these two experiments are consistent with the notion that a functional relationship may exist between neurochemical mechanisms underlying both the aversive (CTA-inducing) and positive reinforcing properties of self-administered drugs such as cocaine.}, } @article {pmid2986548, year = {1985}, author = {Cannon, DS and Best, MR and Batson, JD and Brown, ER and Rubenstein, JA and Carrell, LE}, title = {Interfering with taste aversion learning in rats: the role of associative interference.}, journal = {Appetite}, volume = {6}, number = {1}, pages = {1-19}, doi = {10.1016/s0195-6663(85)80046-5}, pmid = {2986548}, issn = {0195-6663}, mesh = {Animals ; *Association Learning/drug effects ; *Avoidance Learning/drug effects ; Chlorides/toxicity ; *Conditioning, Classical/drug effects ; Discrimination Learning/drug effects ; Drinking/drug effects ; *Learning/drug effects ; Lithium/toxicity ; Lithium Chloride ; Male ; Rats ; Rats, Inbred Strains ; *Taste/drug effects ; }, abstract = {Six experiments with rats investigated the conditions under which one flavor interferes with aversion conditioning to a second, familiar flavor. Conditioning to the familiar flavor was weakest when the interference flavor was contiguous to lithium-induced toxicosis, novel, more intense, and strongly associated with toxicosis. In addition, conditioning to the familiar flavor was weakened even if multiple conditioning trials were used. The repeated finding of an inverse relationship between strength of aversion to the target and interference flavors is interpreted as support for an associative competition hypothesis of the interference effect. The possible relevance of the interference effect to the attenuation of taste aversions in cancer patients is discussed.}, } @article {pmid2987987, year = {1985}, author = {Kelley, KW and Dantzer, R and Mormede, P and Salmon, H and Aynaud, JM}, title = {Conditioned taste aversion suppresses induction of delayed-type hypersensitivity immune reactions.}, journal = {Physiology & behavior}, volume = {34}, number = {2}, pages = {189-193}, doi = {10.1016/0031-9384(85)90104-0}, pmid = {2987987}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Chlorides/poisoning ; Conditioning, Classical/*physiology ; Drinking/drug effects ; Female ; Hypersensitivity, Delayed/*immunology ; Immunity, Cellular/drug effects ; Lithium/poisoning ; Lithium Chloride ; Mice ; Mice, Inbred BALB C ; Taste/*physiology ; }, abstract = {Conditioned taste aversion was induced in mice by pairing saccharin drinking with an intraperitoneal injection of lithium chloride, a toxic but nonimmunosuppressive drug. Conditioned mice showed not only suppressed saccharin drinking but also a 75% reduction in the induction of delayed-type hypersensitivity immune responses to low doses of sheep erythrocytes. This effect was observed with doses of lithium chloride which had no effect of their own on immune functions. In addition, a reduction in water consumption was not responsible for the reduced immune response of conditioned mice since the immune responses of water deprived mice did not differ from those of nondeprived mice. Conditioned mice exposed to saccharin had higher plasma levels of glucocorticoids than nonconditioned mice, suggesting that the experience of being reexposed to a taste paired with lithium chloride was perceived as aversive. These data demonstrate that alterations in immune functions can be induced by a conditioned taste aversion procedure independently of any immunosuppressive drug.}, } @article {pmid2984704, year = {1985}, author = {Ng Cheong Ton, JM and Amit, Z}, title = {Receptor stereospecificity in opiate-ethanol interaction using the preexposure-conditioned taste aversion (CTA) paradigm.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {22}, number = {2}, pages = {255-259}, doi = {10.1016/0091-3057(85)90387-9}, pmid = {2984704}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dextrorphan/pharmacology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Extinction, Psychological ; Levorphanol/pharmacology ; Male ; Rats ; Rats, Inbred Strains ; Receptors, Opioid/*drug effects ; Stereoisomerism ; Taste/*drug effects ; }, abstract = {In the first experiment, rats were conditioned with different doses of levorphanol or dextrorphan to a novel tasting saccharin solution. In the second experiment, rats were either preexposed to levorphanol or dextrorphan and conditioned with either morphine or ethanol to the saccharin solution. The results showed that levorphanol, but not dextrorphan, at 1, 5 and 10 mg/kg doses effectively induced a CTA. Preexposure to the 5 mg/kg dose of levorphanol blocked both morphine- and ethanol-induced CTAs. Dextrorphan at the same dose did not affect the CTAs. These findings are discussed in terms of the involvement of the opiate receptors in opiate-ethanol interaction.}, } @article {pmid3014580, year = {1985}, author = {Brozek, G and Buresová, O and Brácha, V and Bures, J}, title = {Substitution of natural conditioned and unconditioned stimuli by artificial stimuli does not prevent acquisition of conditioned taste aversion in rats.}, journal = {Physiologia Bohemoslovaca}, volume = {34 Suppl}, number = {}, pages = {13-16}, pmid = {3014580}, issn = {0369-9463}, mesh = {Animals ; Chlorides/poisoning ; Conditioning, Psychological/drug effects/*physiology ; Electric Stimulation ; Electrophysiology ; Evoked Potentials ; Harmaline/administration & dosage ; Injections, Intraventricular ; Lithium/poisoning ; Lithium Chloride ; Rats ; Self Stimulation/drug effects/physiology ; Taste/drug effects/*physiology ; }, abstract = {Attempts to replace a natural conditioned stimulus (taste) by electrical stimulation and a natural unconditioned stimulus (gastrointestinal disorder) by intracranial application of harmaline in the conditioned taste aversion (CTA) paradigm are described. The taste is replaced either by electrical stimulation of taste receptors of the tongue or by intracranial self-stimulation of the lateral hypothalamus, both triggered by licking. Both stimuli lose their rewarding properties when paired with gastrointestinal distress whereas self-stimulation triggered by nose poking is not affected by the same procedure. The unconditioned stimulus was replaced successfully by intracerebral injection of harmaline hydrochloride. The effect of the injection of 3-6 micrograms harmaline into the region of the inferior olive is comparable to that of systemic injection of 10 mg/kg harmaline. Electrophysiological analysis of the effect of locally and systemically applied harmaline indicates that the drug probably elicits CTA by activation of bulbar structures including the lateral reticular nucleus and lateral vestibular nucleus.}, } @article {pmid3001808, year = {1985}, author = {Hoffman, DC and Beninger, RJ}, title = {The effects of pimozide on the establishment of conditioned reinforcement as a function of the amount of conditioning.}, journal = {Psychopharmacology}, volume = {87}, number = {4}, pages = {454-460}, pmid = {3001808}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning ; Brain/*physiology ; Conditioning, Classical/*drug effects/physiology ; Dopamine/*physiology ; Male ; Pimozide/*pharmacology ; Rats ; Rats, Inbred Strains ; Reinforcement, Psychology ; Synaptic Transmission ; Taste ; }, abstract = {In an attempt to understand some inconsistent findings, the present experiment investigated the effects of pimozide, a dopamine (DA) receptor blocker, on the establishment of conditioned reinforcement as a function of the amount of conditioning. In Experiment 1, rats received three phases of training in a two-lever box. The pre-exposure phase measured the operant rates of pressing the levers; one produced a 3-s tone and the other turned the lights off for 3 s. In the conditioning phase, with the levers absent, the light-off stimulus was paired with food for two or four sessions. The test phase again measured the rate of pressing the levers. Conditioned reinforcement was shown by a relative increase in responding on the light lever during the test. Of the groups receiving four conditioning sessions, pimozide (0.5, 1.0, 2.0 and 4.0 mg/kg) produced a dose-dependent attenuation of conditioned reinforcement, those rats treated with 4.0 mg/kg failing to demonstrate a significant effect. When 2 conditioning days were employed, pimozide treatment also produced a dose-dependent attenuation; however, in these less conditioned animals 2.0 mg/kg blocked the effect. The possibility that pimozide produced a conditioned taste aversion to the food was ruled out in Experiment 2. These data suggest that DA transmission may be necessary for the establishment of conditioned reinforcement and that the effects of receptor blockade may be related to the amount of conditioning.}, } @article {pmid2990286, year = {1985}, author = {Bernstein, IL}, title = {Learned food aversions in the progression of cancer and its treatment.}, journal = {Annals of the New York Academy of Sciences}, volume = {443}, number = {}, pages = {365-380}, doi = {10.1111/j.1749-6632.1985.tb27086.x}, pmid = {2990286}, issn = {0077-8923}, support = {R01-CA26419/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*adverse effects ; Appetite/drug effects ; Avoidance Learning/*drug effects ; Chlorides/pharmacology ; Conditioning, Classical/*drug effects ; Food Preferences/drug effects ; Humans ; Lithium/pharmacology ; Lithium Chloride ; Neoplasms/*drug therapy/psychology ; Taste/*drug effects ; }, abstract = {The studies included in this chapter examine the learned food aversions that develop as a result of cancer and cancer treatment. Clinical studies have shown that cancer patients can develop learned aversions to a novel ice cream flavor when it is consumed before drug treatments that produce nausea and vomiting. They also provided evidence that patients can acquire aversions to food in their usual diets when these foods are eaten before similar drug treatments. Observations in the clinic, supported by complementary studies with animal models, suggest that learned aversions are more likely to arise to protein foods than to other nutrient sources and that the presentation of a novel food in association with drug treatments may act as a "scapegoat" in blocking the development of aversions to foods in the normal diet. Laboratory studies using transplantable tumors in rats have shown that tumor growth can be associated with the development of strong aversions to the available diet. These aversions are specific to the diet eaten during tumor growth and they appear to play a causal role in the development of tumor-induced anorexia. The food aversions apparent in animals with certain experimental tumors point to physiological consequences of tumor growth that act as unconditioned stimuli in taste aversion conditioning. The identification of these changes and development of methods for correcting them are the current goals of our research in this area.}, } @article {pmid2990283, year = {1985}, author = {Revusky, S}, title = {Drug interactions measured through taste aversion procedures with an emphasis on medical implications.}, journal = {Annals of the New York Academy of Sciences}, volume = {443}, number = {}, pages = {250-271}, doi = {10.1111/j.1749-6632.1985.tb27078.x}, pmid = {2990283}, issn = {0077-8923}, mesh = {Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Chlordiazepoxide/pharmacology ; Chlorides/pharmacology ; Chlorpromazine/pharmacology ; Cisplatin/pharmacology ; Conditioning, Classical/*drug effects ; Cyclophosphamide/pharmacology ; Dexamethasone/pharmacology ; Dextroamphetamine/pharmacology ; Drinking/drug effects ; *Drug Interactions ; Ethanol/pharmacology ; Generalization, Stimulus/drug effects ; Humans ; Lithium/pharmacology ; Lithium Chloride ; Morphine/pharmacology ; Pentobarbital/pharmacology ; Rats ; Taste/*drug effects ; Transfer, Psychology ; }, } @article {pmid2990281, year = {1985}, author = {Smotherman, WP}, title = {Glucocorticoid and other hormonal substrates of conditioned taste aversion.}, journal = {Annals of the New York Academy of Sciences}, volume = {443}, number = {}, pages = {126-144}, doi = {10.1111/j.1749-6632.1985.tb27068.x}, pmid = {2990281}, issn = {0077-8923}, support = {16102//PHS HHS/United States ; 1F32 MH 05555-01/MH/NIMH NIH HHS/United States ; RR 07079/RR/NCRR NIH HHS/United States ; }, mesh = {Adrenal Cortex/physiology ; Adrenocorticotropic Hormone/physiology ; Animals ; Avoidance Learning/*physiology ; Chlorides/toxicity ; Conditioning, Classical/*physiology ; Corticosterone/physiology ; Corticotropin-Releasing Hormone/physiology ; Drinking ; Endorphins/physiology ; Extinction, Psychological/physiology ; Glucocorticoids/*physiology ; Hormones/*physiology ; Hypothalamo-Hypophyseal System/physiology ; Lithium/toxicity ; Lithium Chloride ; Male ; Norepinephrine/physiology ; Rats ; Rats, Inbred Strains ; Taste/*physiology ; beta-Endorphin ; }, abstract = {Results of research reported in this paper show that lithium chloride (LiCl) injection causes a marked and prolonged elevation of adrenocorticotropic hormone (ACTH) and corticosterone. Peak elevations occur within 30 min after injection and continue for 60 to 120 min depending upon the molarity of the LiCl solution. CS preexposures do not alter the pituitary-adrenal response to LiCl. Although this response occurs, evidence argues that pituitary-adrenal activity is neither a sufficient nor essential condition for CTA to occur. It is possible that this prolonged ACTH secretion, which would be essential to maintain corticosterone levels elevated for one to two hours, is acting as a component of the unconditioned response associated with LiCl injections. Under certain types of extinction (forced extinction) the P-A system is activated. Thus, when an animal drinks an aversive solution following deprivation, intake of the solution causes a conditioned elevation of plasma corticosterone. Two measures of CTA, behavioral and hormonal, do not always coincide with one another. Preexposure to the CS alters both behavioral and corticosterone indices of CTA. These two systems will show either a coupling (e.g., parallel change) or a dissociation depending on the number of preexposures prior to conditioning. Manipulating the hormones associated with the pituitary-adrenal system also affects the acquisition of CTA and influences extinction. Thus, if one pretests with dexamethasone phosphate (DEX) prior to the administration of LiCl, CTA is attenuated. It would appear that ACTH is involved in the acquisition of CTA since a central block of ACTH also affects the magnitude of the aversion. If ACTH is injected during recovery, animals show a prolonged suppression of drinking. These data appear to be best explained using a memory-retrieval model. The manipulation of hormones and their effects on CTA appear to follow the effects observed endogenously. Thus, ACTH administered to rats during the conditioning phase does not appear to have any effect upon the learning of the aversion. Since LiCl markedly elevates ACTH, as indicated by prolonged elevations of corticosterone, the additional ACTH given exogenously at the time of conditioning does not appear to add to the effects already attributable to endogenous ACTH. Conversely, DEX given during recovery appears to have no effect upon the recovery function. Because endogenous levels of ACTH are already low during the free extinction procedure, DEX treatment does not appear to further reduce ACTH and has no effect upon recovery.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid538060, year = {1979}, author = {Jolicoeur, FB and Wayner, MJ and Rondeau, DB and Merkel, AD and Bassano, DA}, title = {Effects of phenobarbital on taste aversion induced by X-radiation.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {11}, number = {6}, pages = {709-712}, doi = {10.1016/0091-3057(79)90267-3}, pmid = {538060}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*radiation effects ; Female ; Phenobarbital/*pharmacology ; Rats ; Taste ; Time Factors ; }, abstract = {The effects of phenobarbital on taste aversion induced by X-radiation were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were given a novel 0.125% Na saccharin solution during the 10 min drinking session and were then exposed to 100 rads of X-radiation. The saccharin solution was presented again on six subsequent Test Days. Phenobarbital in doses of 20, 40, 60 and 80 mg/kg was administered 15 min prior to drinking on the first Test Day. Results demonstrate that phenobarbital in all doses tested has a significant attenuating effect on radiation induced taste aversion.}, } @article {pmid530372, year = {1979}, author = {D'Mello, GD and Goldberg, DM and Goldberg, SR and Stolerman, IP}, title = {Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428).}, journal = {Neuropharmacology}, volume = {18}, number = {12}, pages = {1009-1010}, doi = {10.1016/0028-3908(79)90167-9}, pmid = {530372}, issn = {0028-3908}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cocaine/*analogs & derivatives/*pharmacology ; Conditioning, Operant/*drug effects ; Rats ; }, } @article {pmid530370, year = {1979}, author = {Berger, BD and Cwengel, P and Peshkin, N and Schuster, R}, title = {Social factors in taste aversion.}, journal = {Neuropharmacology}, volume = {18}, number = {12}, pages = {1003-1006}, doi = {10.1016/0028-3908(79)90165-5}, pmid = {530370}, issn = {0028-3908}, mesh = {Animals ; Avoidance Learning/*drug effects ; Lithium/pharmacology ; Male ; Milk ; Rats ; *Social Environment ; Taste/*drug effects ; }, } @article {pmid526228, year = {1979}, author = {Steinert, PA and Infurna, RN and Jardula, MF and Spear, NE}, title = {Effects of CS concentration on long-delay taste aversion learning in preweaning and adult rats.}, journal = {Behavioral and neural biology}, volume = {27}, number = {4}, pages = {487-502}, doi = {10.1016/s0163-1047(79)92082-x}, pmid = {526228}, issn = {0163-1047}, mesh = {Age Factors ; Animals ; Association Learning/drug effects ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Female ; Lithium/toxicity ; Male ; Mental Recall/drug effects ; Rats ; Sucrose/*pharmacology ; Taste/*drug effects ; }, } @article {pmid521521, year = {1979}, author = {Infurna, RN and Steinert, PA and Spear, NE}, title = {Ontogenetic changes in the modulation of taste aversion learning by home environmental cues in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {93}, number = {6}, pages = {1097-1108}, doi = {10.1037/h0077625}, pmid = {521521}, issn = {0021-9940}, mesh = {Animals ; Animals, Newborn ; Association Learning ; *Avoidance Learning ; Choice Behavior ; Conditioning, Classical ; *Cues ; Drinking ; Female ; Male ; Rats ; Retention, Psychology ; *Social Environment ; *Taste ; }, abstract = {Eight experiments using 611 rats as subjects were conducted to define and analyze an age-related phenomenon of conditioned taste aversion. When consumption of sucrose solution was followed by LiCl-induced illness in the animals' home, acquisition of the aversion to sucrose solution was retarded in preweanling (18-day-old) rats. This effect was not found in adults or in slightly older (21-day-old) rats. Place of testing had no effect in the younger two age-groups, but in adults manifestation of the acquired aversion was retarded when they were tested in the home. There was no interaction between place of conditioning and testing for any age. The locus of the environmental influence on conditioning in preweanling rats was found to be the place of tasting rather than place of illness, retention interval, or testing. Also, the effect was found to be invariant under minor variations in familiarization of the animal with the non-home environment. The principle emerging from these data and others is that the home environment can have a significant influence on learning and conditioning in the immature rat.}, } @article {pmid493987, year = {1979}, author = {Freed, WJ and Perlow, MJ and Wyatt, RJ}, title = {Calcitonin: inhibitory effect on eating in rats.}, journal = {Science (New York, N.Y.)}, volume = {206}, number = {4420}, pages = {850-852}, doi = {10.1126/science.493987}, pmid = {493987}, issn = {0036-8075}, mesh = {Animals ; Brain/drug effects ; Calcitonin/administration & dosage/*pharmacology ; Depression, Chemical ; Diuresis/drug effects ; Dose-Response Relationship, Drug ; Feeding Behavior/*drug effects ; Injections, Intraventricular ; Rats ; }, abstract = {Subcutaneous and intracerebral injections of calcitonin inhibited feeding in rats. The anorectic activity of calcitonin was destroyed by exposing the hormone to heat, trypsin, or hydrogen peroxide. Calcitonin did not produce a conditioned taste aversion to saccharin, and maximum inhibition of feeding occurred 4.5 to 8.3 hours after subcutaneous administration. It is concluded that calcitonin inhibits feeding by acting directly on the central nervous system.}, } @article {pmid523550, year = {1979}, author = {Domjan, M and Foster, K and Gillan, DJ}, title = {Effects of distribution of the drug unconditioned stimulus on taste-aversion learning.}, journal = {Physiology & behavior}, volume = {23}, number = {5}, pages = {931-938}, doi = {10.1016/0031-9384(79)90203-8}, pmid = {523550}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cues ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Drug Administration Schedule ; Female ; Lithium/*administration & dosage ; Male ; Rats ; Smell/drug effects ; Taste/*drug effects ; }, abstract = {Rats injected with lithium chloride after exposure to a taste or olfactory stimulus learn stronger aversions to these cues if the drug is administered in two small injections 35 min apart than if all of the drug is given in a single injection. This facilitation of conditioning produced by distribution of the drug unconditioned stimulus occurs with both low and high lithium doses (Experiments 1 and 2), is more evident in male than in female rats (Experiment 1), and is directly related to the amount of the flavored solution consumed prior to drug treatment (Experiment 4). Increasing the interval between two small drug injections beyond an optimal value results in a progressive loss of the facilitation of conditioning (Experiments 2 and 3), and the optimal drug distribution interval may be shorter for olfactory cues (Experiment 3) than for taste stimuli (Experiments 1 and 2). Control observations (Experiments 5A and 5B) showed that the drug distribution effect is not due to handling or other non-drug factors involved in giving two rather than only one injection. The phenomenon is consistent with recently-proposed models of conditioning and suggests that the differential effectiveness of various drugs in taste aversion conditioning may be related to differences in the time course of the unconditioned drug effects.}, } @article {pmid119263, year = {1979}, author = {Shaw, N and Webster, DM}, title = {Disruption of taste aversion learning by pentylenetetrazol.}, journal = {Psychopharmacology}, volume = {66}, number = {2}, pages = {195-198}, pmid = {119263}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Female ; Lithium/pharmacology ; Pentylenetetrazole/*pharmacology ; Rats ; Taste ; Time Factors ; }, abstract = {Rats were taught an aversion to a sucrose taste cue (CS) by pairing it with lithium chloride-induced toxicosis (UCS). The CS-UCS interval was 30 min. Animals were injected with pentylenetetrazol (PTZ) (50 mg/kg at 0, 15, 25, 28 or 30 min after the CS in an attempt to disrupt taste aversion learning. Only animals given PTZ 30 min after the CS (simultaneously with the UCS) showed a significant learning deficit. However, learning deficits were also observed in individual animals in groups given PTZ at 15, 25 and 28 min. As lithium salts may produce seizures and abnormal electroencephalographic activity, it is suggested that the neurophysiological consequences of PTZ administration may interact with those of LiCl, causing a greater amnesic effect than PTZ by itself. The resulting interference with the memory trace is probably affecting either the neural engram underlying the CS or the associative bond between the CS and UCS. Evidence was also found that PTZ could act as a UCS with which to establish a mild taste aversion.}, } @article {pmid531142, year = {1979}, author = {Cohen, N and Ader, R and Green, N and Bovbjerg, D}, title = {Conditioned suppression of a thymus-independent antibody response.}, journal = {Psychosomatic medicine}, volume = {41}, number = {6}, pages = {487-491}, doi = {10.1097/00006842-197910000-00005}, pmid = {531142}, issn = {0033-3174}, mesh = {*Antibody Formation ; Avoidance Learning ; *Conditioning, Psychological ; Cyclophosphamide/administration & dosage ; Drinking Behavior ; Haptens ; Humans ; *Immune Tolerance ; Lipopolysaccharides ; Lithium/poisoning ; Saccharin ; Taste ; }, abstract = {An illness-induced taste aversion was conditioned in mice by pairing cyclophosphamide, an immunosuppressive drug, with the consumption of saccharin, a novel drinking solution. Two weeks after conditioning, animals were injected with the hapten trinitrophenyl (TNP) coupled to the thymus-independent carrier, lipopolysaccharide. Serum antibodies to TNP were titered 6 days later by passive hemagglutination. Relative to control groups, conditioned animals provided with saccharin at the time of antigenic stimulation and, again, 3 days later showed a significant attenuation of their anti-TNP antibody response. In a second experiment, the conditioned stimulus (CS) consisted of the novel saccharin drinking solution plus the noxious internal effects of an injection of LiCl. Conditioned animals reexposed to the CS again showed the lowest antibody titers, but differed significantly from only one of the control groups. Taken together, the results of these experiments confirm previous reports of conditioned immunosuppression and suggest that the effects of conditioning on a primary humoral antibody response can be observed in response to a T-cell independent antigen in the mouse.}, } @article {pmid523497, year = {1979}, author = {Miceli, D and Marfaing-Jallat, P and Le Magnen, J}, title = {Non-specific enhancement of ethanol-induced taste aversion by naloxone.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {11}, number = {4}, pages = {391-394}, doi = {10.1016/0091-3057(79)90113-8}, pmid = {523497}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Drug Synergism ; Ethanol/*pharmacology ; Extinction, Psychological/drug effects ; Lithium/pharmacology ; Male ; Naloxone/*pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {The conditioned taste aversion paradigm (CTA) was used to examine the effects of naloxone on ethanol-induced aversion towards a saccharine solution (3 conditioning and 11 extinction trials). Six groups of rats received conditioning trials consisting of two IP injections after saccharine presentation of different combinations of either ethanol (E: 1.75 g/kg), LiCl (L: 12 mEq/kg, 0.1 M), naloxone (N: 10 mg/kg) or saline (S); S-S, S-N, E-S, E-N, L-S and L-N. Naloxone by itself produced no aversion to the saccharin flavor. Based on the onset and extinction of aversion, naloxone significantly enhanced ethanol but also LiCl-induced CTA. The comparative data argues in favor of different mechanisms of action (1) between the aversive central effects of ethanol and morphine and (2) between ethanol's acute behavioral effects and negatively reinforcing properties. Enhancement of ethanol and LiCl-induced CTA by naloxone is compatible with hypernociceptive action of the opiate-antagonist and with the pain-modulating role of opiates in the CNS.}, } @article {pmid512099, year = {1979}, author = {Earley, CJ and Leonard, BE}, title = {Effects of prior exposure on conditioned taste aversion in the rat: androgen- and estrogen-dependent events.}, journal = {Journal of comparative and physiological psychology}, volume = {93}, number = {5}, pages = {793-805}, doi = {10.1037/h0077620}, pmid = {512099}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dihydrotestosterone/*pharmacology ; Estradiol/*pharmacology ; Extinction, Psychological/drug effects ; Female ; Male ; Rats ; Taste/*drug effects ; Testosterone/*pharmacology ; }, abstract = {The effects of preexposure and gonadal hormone manipulation on the extinction of a conditioned taste aversion were investigated. In Experiment 1, male rats were given one prior exposure to sucrose at some selected time (Days 4, 2, or 1) before a second exposure (Day 0) to sucrose and an LiCl injection. Controls received no prior exposure to sucrose but experienced only the sucrose + LiCl condition (Day 0). under the single exposure condition (Day 0) castrated animals extinguished the aversion faster than either testosterone-treated castrated rats or sham-operated rats. Sham-operated and castrated rats that had received preexposure treatment (Days 4, 2, or 1) were not distinguishable on a within-groups comparison of behavior but differed from their respective controls by exhibiting faster rates of extinction. However, in the testosterone-treated group only the Day 4 preexposure group exhibited a faster extinction rate. In Experiment 2, estradiol, dihydrotestosterone, and testosterone were studied by using only a Day 1 preexposure condition. The testosterone-treated group maintained the aversion for the longest period of time, followed by dihydrotestosterone-treated, sham, castrated, and estradiol-treated groups. It appears that estradiol augments the castration effect whereas dihydrotestosterone attenuates the effect. In Experiment 3, estradiol was administered alone or in combination with two different doses of dihydrotestosterone, and a Day 1 preexposure condition was used. The findings indicate that the outcome of behavior is dependent on the ratio of estradiol to dihydrotestosterone, with variations in this ratio resulting in fast (estrogen effect) to slow (androgen effect) rates of extinction.}, } @article {pmid504458, year = {1979}, author = {Brozek, G and Siegfried, B and Klimenko, VM and Bures, J}, title = {Lick triggered intracranial stimulation interferes with retrieval of conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {23}, number = {4}, pages = {625-631}, doi = {10.1016/0031-9384(79)90150-1}, pmid = {504458}, issn = {0031-9384}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Discrimination Learning/physiology ; Dominance, Cerebral/physiology ; *Drinking ; Electric Stimulation ; Hypothalamus/*physiology ; Male ; Memory/*physiology ; Mental Recall/*physiology ; Rats ; Taste/*physiology ; }, } @article {pmid488281, year = {1979}, author = {Islam, S}, title = {Severe conditioned taste aversion elicited by venom of Russell's viper.}, journal = {Experientia}, volume = {35}, number = {9}, pages = {1206-1207}, pmid = {488281}, issn = {0014-4754}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Female ; Male ; Rats ; Saccharin ; Taste/*drug effects ; Viper Venoms/*pharmacology ; }, abstract = {Conditioned taste aversion (CTA) established in rats by associating saccharin drinking with subsequent poisoning by Russell's viper venom. Retention test revealed 76 and 56% reduction of saccharin intake in venom and antivenom-venom groups. No CTA was observed in antivenom and control groups.}, } @article {pmid504406, year = {1979}, author = {Kimble, DP and Bremiller, R and Schroeder, L and Smotherman, WP}, title = {Hippocampal lesions slow extinction of a conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {23}, number = {2}, pages = {217-222}, doi = {10.1016/0031-9384(79)90357-3}, pmid = {504406}, issn = {0031-9384}, mesh = {Adrenergic Fibers/physiology ; Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Drinking ; Extinction, Psychological/*physiology ; Ganglia, Sympathetic/physiology ; Hippocampus/*physiology ; Male ; Nerve Regeneration ; Neural Pathways/physiology ; Norepinephrine/metabolism ; Rats ; Taste/*physiology ; }, } @article {pmid515207, year = {1979}, author = {Ettenberg, A}, title = {Conditioned taste preferences as a measure of brain-stimulation reward in rats.}, journal = {Physiology & behavior}, volume = {23}, number = {1}, pages = {167-172}, doi = {10.1016/0031-9384(79)90138-0}, pmid = {515207}, issn = {0031-9384}, mesh = {Animals ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Hypothalamus/*physiology ; Male ; Rats ; Reward ; *Self Stimulation ; Taste/*physiology ; }, abstract = {Conditioned taste preferences (CTPs) were demonstrated in rats after one, three or five pairings of a novel tasting solution with sessions of intracranial self-stimulation (ICSS). Control groups that experienced single or repeated unpaired presentations of the novel taste or the ICSS did not exhibit such preferences. Although there were no group differences in the absolute size of the CPTs, the resistance of those preferences to extinction reliably increased with the number of novel taste/ICSS pairings. A second experiment was devised to study the effects of changes in ICSS Current intensity on the CTPs produced by that ICSS. There were statistically reliable differences in the CTPs produced by Low-Current and High-Current groups. A No-Current control group did not demonstrate a CTP. Taken together these data suggest that the conditioned taste preference is a learned phenomenon analogous to the conditioned taste aversion that occurs following novel taste/illness pairings. The use of the CTP paradigm as a measure of the rewarding nature of intracranial self-stimulation is proposed.}, } @article {pmid493297, year = {1979}, author = {Infurna, RN and Spear, LP}, title = {Developmental changes in amphetamine-induced taste aversions.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {11}, number = {1}, pages = {31-35}, doi = {10.1016/0091-3057(79)90293-4}, pmid = {493297}, issn = {0091-3057}, mesh = {Aging ; Amphetamine/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Dose-Response Relationship, Drug ; Female ; Male ; Motor Activity/drug effects ; Rats ; Taste/*drug effects ; }, abstract = {In this study a conditioned taste aversion paradigm was employed to examine the ontogenetic trend in psychopharmacological responsiveness to amphetamine among infant (18 days of age), periadolescent (35 days of age), and young adult (52 days of age) rats. The ability of amphetamine to alter taste preference increased with dosage level and this effect interacted with age. Infant rats demonstrated greater sensitivity to the taste aversion inducing properties of amphetamine than either periadolescent or young adult animals. In contrast, periadolescent animals demonstrated a marked resistance to amphetamine's taste aversion inducing properties when compared with either infant or young adult animals. This developmental pattern in amphetamine drug responsiveness seen utilizing the taste aversion paradigm parallels the previously examined ontogenetic trend in amphetamine response using locomotor activity as a response measure.}, } @article {pmid88352, year = {1979}, author = {Steiner, JE and Reuveni, J}, title = {Differential arousal response to gustatory stimuli in the awake rabbit.}, journal = {Electroencephalography and clinical neurophysiology}, volume = {47}, number = {1}, pages = {1-11}, doi = {10.1016/0013-4694(79)90027-0}, pmid = {88352}, issn = {0013-4694}, mesh = {Acetates ; Animals ; Arousal/*physiology ; Electroencephalography ; Male ; Physical Stimulation ; Quinine ; Rabbits ; Taste/*physiology ; Wakefulness ; }, abstract = {ECoG arousal response as elicited by deionized water and by several concentrations of sweet, salty, sour and bitter tasting substances, all applied intraorally, were studied in the awake restrained rabbit. The study was carried out on 17 chronic preparations of adult male animals (2.6 kg average body weight). Water as a stimulant was presented in 60 trials and tastants across qualities and concentrations in 245 trials. Arousal was quantitatively characterized by its duration, frequency increment and amplitude decrement as compared to prestimulus conditions. Arousal induced by tastants was compared to that induced by water. Water and tastants induced arousals differentiable by the parameters measured. Further, most tastants produced a dose-dependent response. Comparison of ECoG and behavioral data clearly indicate that tastants inducing behavioral aversion also produce an arousal which significantly differs from response to water while behavioral preference was found not to show similar correspondence with ECoG data. The possibility of using arousal as an objective indicator for taste aversion is discussed.}, } @article {pmid113833, year = {1979}, author = {Linakis, JG and Cunningham, CL}, title = {Effects of concentration of ethanol injected intraperitoneally on taste aversion, body temperature, and activity.}, journal = {Psychopharmacology}, volume = {64}, number = {1}, pages = {61-65}, pmid = {113833}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Temperature/*drug effects ; Conditioning, Psychological/drug effects ; Dose-Response Relationship, Drug ; Ethanol/*administration & dosage/blood/pharmacology ; Female ; Injections, Intraperitoneal ; Motor Activity/*drug effects ; Osmolar Concentration ; Rats ; Taste ; }, abstract = {Levels of ethanol-induced conditioned taste aversion and hypothermia were found to be directly related to the concentration of fixed amounts of ethanol injected i.p. in a range of doses (1.0--1.8 g/kg) and concentrations (8--32% v/v) commonly used in behavioral studies. No effect of ethanol concentration on locomotor activity was obtained. The results of blood-ethanol determinations indicate that a given dose of ethanol is absorbed more rapidly, and thus reaches greater peak levels, when injected in a higher concentration. Thus ethanol dosage might be better manipulated by varying the volume of a single concentration rather than by altering concentration. In this way, dose-response data will not be obscured by concentration-induced differences in absorption.}, } @article {pmid479392, year = {1979}, author = {Martin, LT and Alberts, JR}, title = {Taste aversions to mother's milk: the age-related role of nursing in acquisition and expression of a learned association.}, journal = {Journal of comparative and physiological psychology}, volume = {93}, number = {3}, pages = {430-445}, doi = {10.1037/h0077568}, pmid = {479392}, issn = {0021-9940}, mesh = {Age Factors ; Animals ; Animals, Suckling ; Association Learning/physiology ; Avoidance Learning/*physiology ; Cues ; *Food Preferences ; *Milk ; Rats ; Taste/*physiology ; Weaning ; }, abstract = {The development of taste aversion learning to novel cues contained in mother's milk was examined in rat pups. Pups receiving distinctive mild by experimenter-delivered oral infusions followed by toxicosis formed an aversion to the dam's diet. Robust aversions were learned as early as Day 10 and were retained for at least 11 days. When the same distinctive milk was obtained directly from a foster mother through nursing, however, only weanling-age pups (over 20 days) formed an aversion. X-ray analysis of nipple location in the mouths of suckling pups suggested that pups between the ages of 10 and 21 days receive milk at a similar tongue locus. Flavored milk was then delivered at specific time intervals in controlled quantities through tongue cannulas implanted at loci corresponding to the nipple position shown by the X-rays. Cannulated preweanling pups that were attached to a nipple during milk delivery failed to associate the taste cue with illness, whereas both preweanlings off the nipple and weanlings on the nipple acquired aversions to the taste cue in the milk. The evidence obtained in these experiments suggests that pups of all ages are incapable of expressing a taste aversion in a nursing situation and that preweanling pups in particular are also dificient in acquiring aversions within a suckling context. The inability of preweanling pups to acquire taste aversions in a nursing situation appears to result from a failure to associate taste cues with illness rather than a failure to detect taste cues obtained from a nipple.}, } @article {pmid573113, year = {1979}, author = {Marfaing-Jallat, P and Le Magnen, J}, title = {Ethanol-induced taste aversion in ethanol-dependent and normal rats.}, journal = {Behavioral and neural biology}, volume = {26}, number = {1}, pages = {106-114}, doi = {10.1016/s0163-1047(79)92946-7}, pmid = {573113}, issn = {0163-1047}, mesh = {Alcohol Drinking ; Alcoholism/*psychology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/drug effects ; Ethanol/*pharmacology ; Humans ; Male ; Rats ; Saccharin ; Substance Withdrawal Syndrome/psychology ; Taste/*drug effects ; }, } @article {pmid487192, year = {1979}, author = {Smith, DV and Travers, JB and Van Buskirk, RL}, title = {Brainstem correlates of gustatory similarity in the hamster.}, journal = {Brain research bulletin}, volume = {4}, number = {3}, pages = {359-372}, doi = {10.1016/s0361-9230(79)80014-3}, pmid = {487192}, issn = {0361-9230}, mesh = {Animals ; Avoidance Learning/physiology ; Brain Stem/*physiology ; Conditioning, Psychological/physiology ; Cricetinae ; Evoked Potentials ; Generalization, Stimulus/physiology ; Male ; Mesocricetus ; Neural Pathways/physiology ; Neurons/physiology ; Pons/physiology ; Taste/*physiology ; }, abstract = {Responses of neurons in the nucleus tractus solitarius (NTS) and parabrachial pons (Pb pons) of the hamster to 10 gustatory stimuli were compared to behavioral similarities among these compounds. Animals were given a conditioned taste aversion to one of the 10 stimuli by pairing it with an induced gastrointestinal illness. Following this procedure, the degree of generalization of the learned taste aversion to each of the other compounds was measured. Behavioral similarity profiles were derived for each stimulus from the similarities in the generalization profiles of each pair of compounds. The across-neuron correlations in the firing rates evoked by these stimuli in the NTS cells corresponded quite well to these behavioral profiles, as did these neural correlations among Pb pontine cells, except for those correlations involving quinine. Sucrose-best cells in the Pb pons are too broadly responsive to account for the behavioral similarity functions for sweet-tasting stimuli, although other best-stimulus categories of cells (NaCl- and HCl-best) showed response profiles quite similar to the behavioral profiles, as did all best-stimulus classes of cells in the NTS.}, } @article {pmid482421, year = {1979}, author = {Kemble, ED and Studelska, DR and Schmidt, MK}, title = {Effects of central amygdaloid nucleus lesions on ingestion, taste reactivity, exploration and taste aversion.}, journal = {Physiology & behavior}, volume = {22}, number = {4}, pages = {789-793}, doi = {10.1016/0031-9384(79)90250-6}, pmid = {482421}, issn = {0031-9384}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Dominance, Cerebral/physiology ; *Drinking ; *Eating ; Exploratory Behavior/*physiology ; Food Deprivation ; Male ; Rats ; Taste/*physiology ; }, } @article {pmid482404, year = {1979}, author = {Buresová, O and Bures, J}, title = {The anterograde effect of ECS on the acquisition, retrieval and extinction of conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {22}, number = {4}, pages = {641-645}, doi = {10.1016/0031-9384(79)90223-3}, pmid = {482404}, issn = {0031-9384}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Classical ; Drinking ; Electroshock ; *Extinction, Psychological ; Male ; *Memory ; *Mental Recall ; Proactive Inhibition ; Rats ; Saccharin ; *Taste ; }, } @article {pmid108747, year = {1979}, author = {Riley, EP and Lochry, EA and Shapiro, NR}, title = {Lack of response inhibition in rats prenatally exposed to alcohol.}, journal = {Psychopharmacology}, volume = {62}, number = {1}, pages = {47-52}, pmid = {108747}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Body Weight/drug effects ; Diet ; Drinking Behavior/drug effects ; Ethanol/*pharmacology ; Female ; Fetus/*drug effects ; Gestational Age ; Lithium/pharmacology ; Male ; Pregnancy ; Rats ; Time Factors ; Water Deprivation ; }, abstract = {Offspring of mothers who consumed either 32, 19, 8, or 0% of their daily caloric intake in the form of ethanol during pregnancy were tested for passive avoidance. At 18 days of age, the number of trials to criterion and the within-group variability were direct functions of the amount of ethanol consumed by the mother during pregnancy. At 41--53 days of age, alcohol-treated pups still required more trials to criterion than controls and had faster speeds into the shock compartment on the first trial. When the progeny of mothers consuming either 35, 17, or 0% ethanol-derived calories during pregnancy were compared for conditioned taste aversion to a lithium chloride solution, a linear dose-response function was again evident. Animals in the alcohol-treated groups showed less suppression of drinking than controls. These investigations indicated that the effects of alcohol exposure in utero were manifested in behavioral outcomes involving response inhibition that were not correlated with the more familiar physical symptoms.}, } @article {pmid464974, year = {1979}, author = {Archer, T and Sjödén, PO and Carter, N}, title = {Control of taste-aversion extinction by exteroceptive cues.}, journal = {Behavioral and neural biology}, volume = {25}, number = {2}, pages = {217-226}, doi = {10.1016/s0163-1047(79)90571-5}, pmid = {464974}, issn = {0163-1047}, mesh = {Acoustic Stimulation ; Animals ; *Avoidance Learning ; Choice Behavior ; Conditioning, Operant ; *Cues ; Drinking ; *Extinction, Psychological ; Physical Stimulation ; Rats ; *Taste ; Tongue ; Touch ; }, } @article {pmid464973, year = {1979}, author = {Mason, ST and Fibiger, HC}, title = {Noradrenaline and extinction of conditioned taste aversion in the rat.}, journal = {Behavioral and neural biology}, volume = {25}, number = {2}, pages = {206-216}, doi = {10.1016/s0163-1047(79)90558-2}, pmid = {464973}, issn = {0163-1047}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Cerebral Cortex/drug effects ; Conditioning, Operant/drug effects/*physiology ; Drinking/drug effects ; Extinction, Psychological/drug effects/*physiology ; Hippocampus/drug effects ; Hydroxydopamines/toxicity ; Lithium/poisoning ; Male ; Norepinephrine/*physiology ; Rats ; Receptors, Adrenergic/drug effects ; Saccharin ; Sodium Chloride ; }, } @article {pmid437009, year = {1979}, author = {Gordon, D}, title = {Effects of forebrain ablation on taste aversion in goldfish (Carassius auratus).}, journal = {Experimental neurology}, volume = {63}, number = {2}, pages = {356-366}, doi = {10.1016/0014-4886(79)90131-6}, pmid = {437009}, issn = {0014-4886}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Cues ; Eating ; Goldfish ; Taste/*physiology ; Telencephalon/*physiology ; }, } @article {pmid431903, year = {1979}, author = {}, title = {A taste aversion can develop during cancer chemotherapy.}, journal = {Nutrition reviews}, volume = {37}, number = {2}, pages = {40-41}, doi = {10.1111/j.1753-4887.1979.tb02198.x}, pmid = {431903}, issn = {0029-6643}, mesh = {Adolescent ; Antineoplastic Agents/*pharmacology ; Child ; Child, Preschool ; Female ; Food Preferences/*drug effects ; Humans ; Ice Cream ; Male ; Neoplasms/*drug therapy ; Taste/*drug effects ; }, } @article {pmid286692, year = {1979}, author = {Zacharko, RM and Wishart, TB and Loew, FM}, title = {Thiamin deprivation in ventromedial hypothalamic hyperphagic rats: anorexia, specificity of food aversion, and a dietary consideration.}, journal = {Journal of comparative and physiological psychology}, volume = {93}, number = {1}, pages = {140-150}, doi = {10.1037/h0077585}, pmid = {286692}, issn = {0021-9940}, mesh = {Animals ; Anorexia/*etiology ; Avoidance Learning/physiology ; Brain Diseases/complications ; Dietary Fats/administration & dosage ; Feeding and Eating Disorders/*etiology ; *Food Preferences ; Humans ; *Hypothalamus ; *Hypothalamus, Middle/physiology ; Male ; Rats ; Thiamine Deficiency/*complications ; }, abstract = {The anorexic consequence of thiamin deprivation was investigated in ventromedial hypothalamic (VMH) hyperphagic rats under either high-fat or low-fat thiamin-free diet conditions. The low-fat diet maintained feeding significantly longer in thiamin-deprived VMH rats than in intact rats, whereas the hig-fat diet sustained feeding in thiamin-deficient intact rats and accelerated anorexia onset in vitamin B1 deprived VMH rats. This effect was noted under both ad lib and pair-feeding conditions. Thiamin-deprived VMH rats subjected to weight control developed anorexia sooner than intact subjects regardless of the diet employed. The VMH rats fed a high-fat diet failed to resume feeding after thiamin readministration, which was interpreted as a permanent aversion to this diet. The relation between dietary intake and conditioned taste aversion is discussed with reference to the VMH and intact rat.}, } @article {pmid575038, year = {1979}, author = {Elkins, R and Hobbs, SH}, title = {Forgetting, preconditioning CS familiarization and taste aversion learning: an animal experiment with implications for alcoholism treatment.}, journal = {Behaviour research and therapy}, volume = {17}, number = {6}, pages = {567-573}, doi = {10.1016/0005-7967(79)90100-1}, pmid = {575038}, issn = {0005-7967}, mesh = {Alcoholism/psychology/*rehabilitation ; Animals ; *Avoidance Learning/drug effects ; *Conditioning, Classical/drug effects ; Cyclophosphamide/pharmacology ; Humans ; Male ; *Memory/drug effects ; *Mental Recall/drug effects ; Rats ; *Taste/drug effects ; }, } @article {pmid553240, year = {1979}, author = {Kutscher, CL and Yamamoto, BK}, title = {Altered saccharin preference during chronic dietary administration of lead in adult rats.}, journal = {Neurobehavioral toxicology}, volume = {1}, number = {4}, pages = {259-262}, pmid = {553240}, issn = {0191-3581}, mesh = {Analysis of Variance ; Animals ; Behavior, Animal/drug effects ; Diet ; Food Preferences/*drug effects ; Lead/*toxicity ; Male ; Rats ; Saccharin ; Taste/drug effects ; Time Factors ; }, abstract = {Procedural variables are crucial in using taste aversion as a measure of lead toxicity. Rats were given saccharin and water to drink while ingesting a diet containing lead acetate (PbAc). Rats showed high preference for saccharin (over water) before lead was introduced. Saccharian preference fell during PbAc ingestion and rose when PbAc was removed from the diet suggesting that saccharin preference may correlate with the physiologic action of the toxicant. When saccharin was introduced simultaneously with PbAc aversion was almost total, but recovered with continuous PbAc exposure. When saccharin was introduced after the start of PbAc exposure saccharin aversion diminished with the duration of presaccharin PbAc exposure.}, } @article {pmid526240, year = {1979}, author = {Baker, TB and Cannon, DS}, title = {Taste aversion therapy with alcoholics: techniques and evidence of a conditioned response.}, journal = {Behaviour research and therapy}, volume = {17}, number = {3}, pages = {229-242}, doi = {10.1016/0005-7967(79)90038-x}, pmid = {526240}, issn = {0005-7967}, mesh = {Adult ; Alcoholism/psychology/*rehabilitation ; Aversive Therapy/*methods ; *Conditioning, Classical ; Humans ; Male ; Taste ; }, } @article {pmid454338, year = {1979}, author = {Schneider, K and Wothe, K}, title = {The contribution of naso-oral and postingestional factors in taste aversion learning in the rat.}, journal = {Behavioral and neural biology}, volume = {25}, number = {1}, pages = {30-38}, doi = {10.1016/s0163-1047(79)90722-2}, pmid = {454338}, issn = {0163-1047}, mesh = {Animals ; Association Learning ; *Avoidance Learning ; Caseins ; Cues ; Drinking ; Lithium ; Male ; Rats ; *Smell ; *Taste ; }, } @article {pmid441091, year = {1979}, author = {Brown, ZW and Amit, Z and Smith, B and Rockman, G}, title = {Disruption of taste aversion learning by pretreatment with diazepam and morphine.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {10}, number = {1}, pages = {17-20}, doi = {10.1016/0091-3057(79)90162-x}, pmid = {441091}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Diazepam/*pharmacology ; Male ; Morphine/*pharmacology ; Rats ; *Taste ; Time Factors ; }, abstract = {Laboratory rats were pretreated with either morphine (9 mg/kg IP), diazepam (4 mg/kg 1P) or Ringer's solution 2, 3 1/2, and 2 hr, respectively, prior to ingestion of a novel tasting saccharin solution followed immediately by a single injection of one of these agents. Animals pretreated with Ringer's solution followed by an injection of either morphine or diazepam showed a conditioned taste aversion (CTA) as determined by a significant reduction in the mean saccharin intake on a subsequent test trial. Although the drug pretreatments alone produced no conditioned avoidance behavior, the diazepam pretreatment completely blocked the development of both diazepam and morphine-evoked CTAs while the morphine pretreatment prevented a CTA induced by itself but not by diazepam. The results were discussed in terms of the attenuating effects of the pretreatments on the relative saliency of the subsequent conditioning drug injection.}, } @article {pmid222253, year = {1979}, author = {Venkatakrishna-Bhatt, H and Bures, J and Buresová, O}, title = {Paradoxical sleep deprivation retards extinction of conditioned taste aversion.}, journal = {Behavioral and neural biology}, volume = {25}, number = {1}, pages = {133-137}, doi = {10.1016/s0163-1047(79)90875-6}, pmid = {222253}, issn = {0163-1047}, mesh = {Animals ; *Avoidance Learning ; Conditioning, Psychological ; Drinking ; *Extinction, Psychological ; Lithium ; Male ; Rats ; Saccharin ; *Sleep Deprivation ; *Sleep, REM ; Taste ; }, } @article {pmid160575, year = {1979}, author = {Brozek, G and Buresová, O and Bures, J}, title = {Electrophysiological analysis of retrieval of conditioned taste aversion. Physiological techniques and data processing.}, journal = {Physiologia Bohemoslovaca}, volume = {28}, number = {6}, pages = {537-544}, pmid = {160575}, issn = {0369-9463}, mesh = {Action Potentials ; Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Chlorides ; *Computers ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Electrophysiology ; Lithium ; Rats ; Sodium Chloride ; Taste/*physiology ; }, abstract = {New techniques suitable for electrophysiological investigation of retrieval of conditioned taste aversion (CTA) were developed. The gustatory discrimination apparatus consisted of two parallel drinking spouts (20 mm apart) equipped with photoelectric lick sensors. The spouts contained water or the aversive fluid (0.15 M LiCl), respectively, and their position could be rapidly (50 ms) interchanged with a reversive electromotor. Licking at either spout and the position of the fluids were recorded on one channel of a tape recorder. Unit activity was picked up with tungsten microelectrodes (40 micrometers) inserted into the brain of a freely moving rat with a head-mounted microdrive system (weight 2 g), fixed to an implanted guiding cannula. The electrode was connected through a head-carried FET signal follower to a wide band integrated circuit amplifier and the unit activity was recorded in the other channel of the tape recorder. The records were evaluated using an off-line computer program (LINC 8) consisting of a spike detection subroutine followed by amplitude histogram analysis. The mean (M) and SD values were computed for uni- or bimodal amplitude distributions of the principal spike components. Spike falling within the M+/-2 SD range of the selected parameter were identified as single units and used for construction of post stimulus histograms triggered by licking or by spout switching.}, } @article {pmid160574, year = {1979}, author = {Buresová, O and Aleksanyan, ZA and Bures, J}, title = {Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions.}, journal = {Physiologia Bohemoslovaca}, volume = {28}, number = {6}, pages = {525-536}, pmid = {160574}, issn = {0369-9463}, mesh = {Action Potentials ; Amygdala/physiology ; Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Cerebral Cortex/physiology ; Chlorides ; Conditioning, Classical/*physiology ; Electrophysiology ; Hypothalamus/physiology ; Lithium ; Male ; Medulla Oblongata/physiology ; Rats ; Sodium Chloride ; Taste/*physiology ; Thalamus/physiology ; }, abstract = {Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible.}, } @article {pmid755061, year = {1978}, author = {Sengstake, CB and Chambers, KC and Thrower, JH}, title = {Interactive effects of fluid deprivation and testosterone on the expression of a sexually dimorphic conditioned taste aversion.}, journal = {Journal of comparative and physiological psychology}, volume = {92}, number = {6}, pages = {1150-1155}, doi = {10.1037/h0077508}, pmid = {755061}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/*drug effects/physiology ; Extinction, Psychological/*drug effects ; Female ; Male ; Rats ; Taste/*drug effects/physiology ; Testosterone/*pharmacology ; *Water Deprivation ; }, abstract = {The effects of fluid deprivation on the sexually dimorphic rate of extinction of a conditioned taste aversion in rats was investigated. Under ad lib water conditions, males extinguished a conditioned taste aversion more slowly than females. However, when rats were fluid deprived, there was no difference in the extinction rates of females and males even when the more sensitive two-bottle test was used. This absence of the sexual dimorphism was due to a differential effect of deprivation on females and males. Fluid deprivation increased the rate of extinction of the male but had no effect on the extinction rate of the female. It was proposed that the more rapid extinction rate of the deprived male could be accounted for by a deprivation-induced change in a testosterone-dependent mechanism. This proposal was supported by demonstrating that injection of testosterone propionate blocked the effects of fluid deprivation on rate of extinction in the male rat.}, } @article {pmid747593, year = {1978}, author = {Ellins, SR and Gustavson, CR and Garcia, J}, title = {Conditioned taste aversion in predators: response to Sterner and Shumake.}, journal = {Behavioral biology}, volume = {24}, number = {4}, pages = {554-556}, doi = {10.1016/s0091-6773(78)91043-x}, pmid = {747593}, issn = {0091-6773}, mesh = {Animals ; *Appetitive Behavior/drug effects ; *Avoidance Learning/drug effects ; *Conditioning, Classical/drug effects ; Lithium/poisoning ; *Predatory Behavior/drug effects ; Sheep ; *Taste/drug effects ; }, } @article {pmid746057, year = {1978}, author = {Jolicoeur, FB and Wayner, MJ and Rondeau, DB and Merkel, AD}, title = {The effects of phenobarbital on lithium chloride induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {9}, number = {6}, pages = {845-847}, doi = {10.1016/0091-3057(78)90366-0}, pmid = {746057}, issn = {0091-3057}, mesh = {Animals ; Female ; Lithium/*antagonists & inhibitors/pharmacology ; Phenobarbital/*pharmacology ; Rats ; Taste/*drug effects ; Time Factors ; }, abstract = {The dose related effects of phenobarbital on LiCl induced taste aversion were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were offered a novel 0.125% saccharin solution during the 10 min drinking session and were then administered 3.0 mEq/kg LiCl. The saccharin solution was presented again on six subsequent Test Days. Sodium phenobarbital 20, 40, 60 and 80 mg/kg was administered 15 min prior to drinking on the first Test Day. Results indicated that all doses significantly attenuated taste aversion with the maximal effect occurring with the 60 mg/kg dose.}, } @article {pmid746047, year = {1978}, author = {Corfield-Sumner, PK and Bond, NW}, title = {Taste aversion learning and schedule-induced alcohol consumption in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {9}, number = {6}, pages = {731-733}, doi = {10.1016/0091-3057(78)90348-9}, pmid = {746047}, issn = {0091-3057}, mesh = {*Alcohol Drinking ; Animals ; Avoidance Learning/*physiology ; Drinking Behavior/physiology ; Lithium/pharmacology ; Male ; Rats ; Reinforcement Schedule ; Taste/*physiology ; }, } @article {pmid746046, year = {1978}, author = {Persinger, MA and Fiss, TB}, title = {Mesenteric mast cell degranulation is not essential for conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {9}, number = {6}, pages = {725-730}, doi = {10.1016/0091-3057(78)90347-7}, pmid = {746046}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*physiology ; Chlorpheniramine/pharmacology ; Cytoplasmic Granules/*physiology ; Drinking Behavior/drug effects ; Lithium/pharmacology ; Male ; Mast Cells/*physiology/ultrastructure ; Mesentery/*cytology ; Rats ; Taste/*physiology ; p-Methoxy-N-methylphenethylamine/pharmacology ; }, abstract = {The possible role of mesenteric mast cell degranulation as the mediator of the initial UCS effects in the complex sequences leading to conditioned taste aversion (CTA) was studied. Both LiCl and Compound 48/80, a potent mast cell degranulator, produced CTA to 10% sucrose. Whereas the Compound 48/80 groups displayed massive mast cell degranulation, neither the LiCl treated nor saline control groups demonstrated any histologically determinable alterations. Administration of the antihistamine chlorpheniramine at dosages known to block radiation-induced CTA before the sucrose CS-UCS pairings did not block either LiCl- or Compound 48/80-induced CTA; the antihistamine actually facilitated the aversion. However, pretreatment with the antihistamine did not alter mesenteric mast cell morphology.}, } @article {pmid552089, year = {1978}, author = {LePiane, FG and Phillips, AG}, title = {Differential effects of electrical stimulation of amygdala, caudate-putamen or substantia nigra pars compacta on taste aversion and passive avoidance in rats.}, journal = {Physiology & behavior}, volume = {21}, number = {6}, pages = {979-985}, doi = {10.1016/0031-9384(78)90175-0}, pmid = {552089}, issn = {0031-9384}, mesh = {Amygdala/physiology ; Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Caudate Nucleus/physiology ; Electric Stimulation ; Lithium/pharmacology ; Male ; Putamen/physiology ; Rats ; Substantia Nigra/physiology ; Taste/*physiology ; }, } @article {pmid121817, year = {1978}, author = {Wayner, EA and Flannery, GR and Singer, G}, title = {Effects of taste aversion conditioning on the primary antibody response to sheep red blood cells and Brucella abortus in the albino rat.}, journal = {Physiology & behavior}, volume = {21}, number = {6}, pages = {995-1000}, doi = {10.1016/0031-9384(78)90177-4}, pmid = {121817}, issn = {0031-9384}, mesh = {Animals ; *Antibody Formation ; Avoidance Learning/*physiology ; Brucella abortus/immunology ; Cyclophosphamide/pharmacology ; Erythrocytes/immunology ; Male ; Rats ; Reinforcement Schedule ; Sheep/immunology ; Taste/*physiology ; }, } @article {pmid733852, year = {1978}, author = {Stewart, J and Eikelboom, R}, title = {Pre-exposure to morphine and the attenuation of conditioned taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {9}, number = {5}, pages = {639-645}, doi = {10.1016/0091-3057(78)90215-0}, pmid = {733852}, issn = {0091-3057}, mesh = {Analgesics ; Animals ; Avoidance Learning/*drug effects ; Drug Tolerance ; Male ; Morphine/*pharmacology ; Rats ; Saccharin/pharmacology ; Taste ; }, abstract = {Three experiments were done using male Wistar rats to determine whether the mechanisms underlying the attenuation of a conditioned taste aversion to morphine by pre-exposure to the drug were similar to those involved in the development of tolerance to the analgesic response to morphine. This was tested by determining whether the effect of pre-exposure on conditioned taste aversion was situation-specific. In Experiment 1 it was found that having different environments for the pre-exposure injections and for the conditioning injections of morphine had no effect on the attenuation of the taste aversion. This finding was replicated in Experiment 2 in which it was also found that the attenuation of the analgesic effect, tested for in the same animals, was specific to the environment in which repeated injections were given. It was concluded that the attenuation of conditioned taste aversion involved processes different from those responsible for the attenuation of the analgesic effect of morphine. Experiment 3 showed that pairing the pre-exposure injections of morphine with one distinctive taste stimulus prevented the attenuation of the conditioned taste aversion to a second taste stimulus. These results suggest that different associative processes are responsible for the two types of attenuation.}, } @article {pmid733846, year = {1978}, author = {Goudie, AJ and Dickins, DW}, title = {Nitrous oxide-induced conditioned taste aversions in rats: the role of duration of drug exposure and its relation to the taste aversion-self-administration "paradox".}, journal = {Pharmacology, biochemistry, and behavior}, volume = {9}, number = {5}, pages = {587-592}, doi = {10.1016/0091-3057(78)90207-1}, pmid = {733846}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Female ; Nitrous Oxide/*pharmacology ; Rats ; Self Administration ; Taste ; Time Factors ; }, abstract = {Inhalation by rats of nitrous oxide immediately after ingestion of a solution of 0.1% saccharin resulted in a conditioned avoidance of the solution following recovery from the drug (Conditioned Taste Aversion). With a constant duration of inhalation (30 min), aversive properties of nitrous oxide in this behavioural paradigm were related to concentration over the range 0-80%. At constant concentrations (70% and 80%), the aversive potency of nitrous oxide was directly related to duration of inhalation of the gas over the range 0-4 hr. These data provide the first direct support for the hypothesis [5,6] that a major determinant of aversive potency of a drug in the taste aversion paradigm is its duration of action. Different temporal components of drug action may mediate self-administration and conditioned aversion.}, } @article {pmid724100, year = {1978}, author = {Brown, ZW and Amit, Z and Smith, B and Rockman, GE}, title = {Differential effects on conditioned taste aversion learning with peripherally and centrally administered acetaldehyde.}, journal = {Neuropharmacology}, volume = {17}, number = {11}, pages = {931-935}, doi = {10.1016/0028-3908(78)90134-x}, pmid = {724100}, issn = {0028-3908}, mesh = {Acetaldehyde/administration & dosage/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Injections, Intraperitoneal ; Injections, Intraventricular ; Male ; Rats ; Taste ; }, } @article {pmid707670, year = {1978}, author = {Baker, TB and Cannon, DS and Stephenson, GM and Droubay, E}, title = {Procedures for taste aversion therapy for alcoholism.}, journal = {The American journal of psychiatry}, volume = {135}, number = {11}, pages = {1439}, doi = {10.1176/ajp.135.11.1439}, pmid = {707670}, issn = {0002-953X}, mesh = {Alcoholism/*therapy ; Aversive Therapy/*methods ; Emetics/administration & dosage ; Humans ; *Taste ; }, } @article {pmid751424, year = {1978}, author = {Buresová, O}, title = {Neocortico-amygdalar interaction in the conditioned taste aversion in rats.}, journal = {Activitas nervosa superior}, volume = {20}, number = {3}, pages = {224-230}, pmid = {751424}, issn = {0001-7604}, mesh = {Amygdala/*surgery ; Animals ; *Avoidance Learning ; Cerebral Cortex/*surgery ; Cortical Spreading Depression ; Drinking ; Male ; Rats ; Saccharin ; *Taste ; }, abstract = {Corticoamygdalar interaction in the acquisition and retrieval of the conditioned taste aversion (CTA) was studied in rats by combination of unilateral lesion of basolateral amygdala with unilateral functional decortication by cortical spreading depression (CSD). Sodium saccharin (0.1%, 15 min) served as the CS, intraperitoneal injection od LiCl (0.15 M, 4% body weight) as the US. The CS-US delay was 20 min. Aversion was tested by measuring sacharin consumption 5 days later. Marked CTA was found in the unoperated and in the unilaterally lesioned controls. Amygdalectomized rats subjected during CTA acquisition to unilateral CSD ipsilateral or contralateral to the lesion, drank less saccharin and developed weaker CTA than the controls. Retrieval of CTA acquired by undepressed operated animals was prevented by funcitonal hemidecortication of the intact but not of the lesioned hemisphere. It is concluded that ipsilateral connections between neocortex and basolateral amygdala are more important for retrieval than for acquisition of CTA.}, } @article {pmid750489, year = {1978}, author = {Islam, S}, title = {Eliciting conditioned taste aversion by cobra venom neurotoxin in rats.}, journal = {Indian journal of physiology and pharmacology}, volume = {22}, number = {4}, pages = {368-371}, pmid = {750489}, issn = {0019-5499}, mesh = {Animals ; Antivenins/pharmacology ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Elapid Venoms/*pharmacology ; Female ; Lithium/pharmacology ; Male ; Neurotoxins/*pharmacology ; Rats ; *Taste ; Time Factors ; }, abstract = {An attempt is made to study conditioned taste aversion (CTA) using cobra venom antivenom or lithium chloride as the Unconditioned Stimulus (US). Twenty-four hour water deprived rats were habituated for two consecutive days to drinking tap water in the drinking box for 15 minutes daily. On 3rd day they were allowed to drink 0.1% sodium saccharin. Thirty minutes later, they were injected with cobra venom (45 micrograms), antivenom (0.022 microliter), antivenom followed by venom, lithium chloride (0.15 M, 4% body weight) or physiological saline. After two days of recovery the animals were water deprived for twenty four hours and water intake was measured on the 7th and 8th day. Retention test on the 9th day shows reduced saccharin consumption in the lithium chloride and venom groups. CTA was significantly reduced in the antivenom-venom group and absent in the antivenom and control group. It is concluded cobra venom can induce clear-cut CTA in rats.}, } @article {pmid721454, year = {1978}, author = {Jessup, B}, title = {The role of diet in migraine: conditioned taste aversion.}, journal = {Headache}, volume = {18}, number = {4}, pages = {229}, doi = {10.1111/j.1526-4610.1978.hed1804229.x}, pmid = {721454}, issn = {0017-8748}, mesh = {Conditioning, Operant ; *Diet ; Humans ; Migraine Disorders/*prevention & control ; *Taste ; }, } @article {pmid714977, year = {1978}, author = {Clarke, JC and Westbrook, RF}, title = {Control of polydipsic drinking by a taste aversion procedure.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {9}, number = {3}, pages = {283-286}, doi = {10.1016/0091-3057(78)90286-1}, pmid = {714977}, issn = {0091-3057}, mesh = {Animals ; *Avoidance Learning/physiology ; Chlorides ; Conditioning, Psychological ; *Drinking Behavior/physiology ; Female ; Lithium/*poisoning ; Rats ; *Taste/drug effects/physiology ; }, abstract = {Rats were given daily sessions with free access to food and saccharin flavored water. After fluid consumption had stabilized food was delivered once every minute. Water was always available in the home cage. All rats showed the marked increase in fluid consumption known as schedule-induced polydipsia. The rats were then poisoned with lithium chloride after each of three sessions in an attempt to condition a taste aversion to the saccharin. On recovery from the toxicosis all rats showed first a reduction and then a recovery in saccharin intake. To establish the nature of this effect, the rats were poisoned after saccharin consumption in the home cage. Again there was a marked reduction in polydipsic drinking in the experimental chamber. These results indicate that common incentive mechanisms govern normal and polydipsic drinking and stand in contrast to published results pointing to different drive systems in the brain mediating normal and polydipsic drinking.}, } @article {pmid209871, year = {1978}, author = {Venkatakrishna-Bhatt, H and Bures, J}, title = {Electrophysiological changes induced by paradoxical sleep deprivation and lithium chloride poisoning in rats.}, journal = {Brain research}, volume = {152}, number = {1}, pages = {97-103}, doi = {10.1016/0006-8993(78)90136-1}, pmid = {209871}, issn = {0006-8993}, mesh = {Activity Cycles/drug effects ; Animals ; Arousal/drug effects ; Avoidance Learning/drug effects ; Cerebral Cortex/physiology ; *Electroencephalography ; *Electromyography ; Hippocampus/physiology ; Lithium/*poisoning ; Male ; Rats ; *Sleep Deprivation ; *Sleep, REM/drug effects ; Taste/drug effects ; }, abstract = {In an attempt to analyze the disruption of conditioned taste aversion (CTA) caused by pre-acquisition paradoxical sleep deprivation (PSD), the effect of poisoning (0.15 M LiCl, 4% body weight) on the sleep--wakefulness pattern was studied in 12 rats with chronically implanted electrodes. The polygraphic recording showed that poisoning reduced the total sleep time in the subsequent 3 h from 57 to 42% and REM sleep from 6 to 2%. The lithium chloride effect was still more pronounced after 24-h REM sleep deprivation: the total sleep time decreased from 67 to 46% and REM sleep from 13 to 2%. The change of sleep--wakefulness pattern, most pronounced during the first hour of poisoning, gradually returned to normal but REM sleep was significantly reduced even 3 h after poisoning. It is concluded that 24-h PSD does not alleviate the subsequent poisoning. On the other hand, the lithium chloride induced reduction of post-acquisition REM sleep many enhance the learning impairment caused by pre-acquisition PSD.}, } @article {pmid663673, year = {1978}, author = {Phillips, AG and LePiane, FG}, title = {Electrical stimulation of the amygdala as a conditioned stimulus in a bait-shyness paradigm.}, journal = {Science (New York, N.Y.)}, volume = {201}, number = {4355}, pages = {536-538}, doi = {10.1126/science.663673}, pmid = {663673}, issn = {0036-8075}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Caudate Nucleus/physiology ; Conditioning, Classical/*physiology ; Electric Stimulation ; Male ; Rats ; Retention, Psychology/physiology ; Taste/*physiology ; }, abstract = {Animals receiving low-intensity electrical stimulation of the basolateral nucleus of the amygdala while drinking plain tap water were injected with toxic doses of lithium chloride to examine whether brain stimulation can serve as a conditioned stimulus in a bait-shyness paradigm. Subjects receiving this pairing greatly reduced their water intake in a retention test, in a similar manner to a group in which saccharin was paired with poisoning. Pairing lithium chloride with stimulation of the amygdala had no effect on subsequent water intake in the absence of brain stimulation. This effect appears to be locus specific, as caudate stimulation could not serve as a conditioned stimulus.}, } @article {pmid748139, year = {1978}, author = {Earley, CJ and Leonard, BE}, title = {Androgenic involvement in conditioned taste aversion.}, journal = {Hormones and behavior}, volume = {11}, number = {1}, pages = {1-11}, doi = {10.1016/0018-506x(78)90053-3}, pmid = {748139}, issn = {0018-506X}, mesh = {Androgens/*physiology ; Animals ; Behavior, Animal/drug effects ; Castration ; Cyproterone/*pharmacology ; Dihydrotestosterone/metabolism/*pharmacology ; Estradiol/metabolism ; Hydroxytestosterones/*pharmacology ; Lithium/pharmacology ; Male ; Rats ; Sucrose/administration & dosage ; Taste/drug effects/*physiology ; Testosterone/*analogs & derivatives/metabolism/*pharmacology ; }, } @article {pmid690294, year = {1978}, author = {Dudek, BC and Fuller, JL}, title = {Task-dependent genetic influences on behavioral response of mice (Mus musculus) to acetaldehyde.}, journal = {Journal of comparative and physiological psychology}, volume = {92}, number = {4}, pages = {749-758}, doi = {10.1037/h0077506}, pmid = {690294}, issn = {0021-9940}, mesh = {Acetaldehyde/*pharmacology ; Animals ; Avoidance Learning/*physiology ; Cues ; Ethanol ; Food Preferences ; *Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Models, Psychological ; Posture ; Reflex/drug effects ; Saccharin ; Species Specificity ; }, abstract = {Acetaldehyde was employed as a pharmacological agent in behavioral tests designed to assess genetic influences upon response to the drug. When used as a poison in a conditioned taste aversion study, acetaldehyde was more effective at inducing aversions in DBA/2J mice than in C57BL/6J mice. In another experiment, however, C57 mice were more affected than were DBA mice by acetaldehyde effects on loss of righting reflex. Implications for postulated genetic control of ethanol preference and neurosensitivity are discussed.}, } @article {pmid690290, year = {1978}, author = {Kraly, FS and Carty, WJ and Resnick, S and Smith, GP}, title = {Effect of cholecystokinin on meal size and intermeal interval in the sham-feeding rat.}, journal = {Journal of comparative and physiological psychology}, volume = {92}, number = {4}, pages = {697-707}, doi = {10.1037/h0077501}, pmid = {690290}, issn = {0021-9940}, mesh = {Animals ; Cholecystokinin/*pharmacology ; Dose-Response Relationship, Drug ; Feeding Behavior/*drug effects ; Male ; Rats ; Reaction Time ; Satiation/*drug effects ; Satiety Response/*drug effects ; }, abstract = {After 3-hr food deprivation, rats with gastric fistulas ate liquid food with the fistula closed (normal feeding) or open (sham feeding). Meal size (MS) was larger, latency to rest (LR) after a meal was longer, and intermeal interval (IMI) was shorter during sham feeding than during normal feeding. The putative satiety signal cholecystokinin (CCK, 20% pure) decreased MS and LR and increased IMI during sham feeding. After CCK (30 U/kg) the MS, LR, and IMI were the same during sham feeding as during normal feeding. The synthetic octapeptide (OCT) of CCK, which has the known biological actions of the complete hormone, reproduced the effects of CCK (30 U/kg) on MS and LR but not on IMI. Ingestive behavior was not nonspecifically suppressed by CCK or OCT because water drinking was not inhibited by CCK or OCT. The CCK and OCT were also tested for their ability to serve as unconditioned stimuli (UCS) for the formation of a conditioned taste aversion (CTA) in the 3-hr food-deprived sham-feeding rat. The OCT (30 U/kg) did not serve as a UCS for a CTA in the same sham-feeding conditions in which OCT produced normal MS and LR. Impure CCK (30 U/kg), however, did serve as a UCS for a CTA under these conditions. The differential effectiveness of CCK and OCT for IMI and CTA may be due to non-CCK factors in the impure extract of CCK. These experiments demonstrate that the preabsorptive food-contingent stimuli of sham feeding plus exogenous CCK are sufficient for normal short-term satiety under certain conditions, and they provide further evidence consistent with the hypothesis that cholecystokinin produces satiety in rats.}, } @article {pmid690287, year = {1978}, author = {Robbins, RJ}, title = {Poison-based taste aversion learning in deer mice (Peromyscus maniculatus bairdi).}, journal = {Journal of comparative and physiological psychology}, volume = {92}, number = {4}, pages = {642-650}, doi = {10.1037/h0077493}, pmid = {690287}, issn = {0021-9940}, mesh = {Animals ; *Avoidance Learning ; Female ; Lithium ; Male ; Peromyscus ; *Taste ; }, abstract = {A series of experiments tested the ability of mice of the native genus Peromyscus to form learned taste aversions. It was found that (a) the mice acquired a strong aversion after a single flavor/toxicosis pairing, (b) naive mice drinking a LiCl solution apparently began to experience toxic effects within 90 sec after the beginning of consumption, (c) the mice acquired a total aversion after a single flavor/delayed illness pairing when high doses of toxin were employed, and (d) the aversion produced by a single flavor/delayed-illness pairing was specific to the flavor paired with illness and was dependent on the contingency between the flavor and illness. Although these responses are qualitatively similar to those reported for domestic rats, the mice formed considerably weaker aversions than those previously reported for laboratory rats tested with the same weight-specific doses of LiCl.}, } @article {pmid689850, year = {1978}, author = {Earley, CJ}, title = {Taste aversion as a method for assessing the effects of gonadal hormones on behaviour.}, journal = {Irish journal of medical science}, volume = {147 Suppl 1}, number = {}, pages = {24-27}, pmid = {689850}, issn = {0021-1265}, mesh = {Animals ; Behavior, Animal/*drug effects ; Cyproterone/*pharmacology ; Estradiol/*analogs & derivatives/pharmacology ; Male ; Rats ; Taste/*drug effects ; Taste Threshold/*drug effects ; Testosterone/analogs & derivatives/*pharmacology ; }, } @article {pmid663655, year = {1978}, author = {Grill, HJ and Norgren, R}, title = {Chronically decerebrate rats demonstrate satiation but not bait shyness.}, journal = {Science (New York, N.Y.)}, volume = {201}, number = {4352}, pages = {267-269}, doi = {10.1126/science.663655}, pmid = {663655}, issn = {0036-8075}, mesh = {Animals ; Arousal/physiology ; Association Learning/*physiology ; Brain Stem/*physiology ; *Decerebrate State ; Feeding Behavior/*physiology ; Food Deprivation ; Hypothalamus/physiology ; Learning/*physiology ; Lithium ; Rats ; Satiation/physiology ; Sucrose ; Taste/physiology ; }, abstract = {Taste substances applied to the oral cavity result in either ingestion or rejection, each with a characteristic muscular response pattern. These responses are the same in decerebrate and intact rats; the caudal brainstem appears to be the neural substrate of ingestion and rejection responses. The experiment determined whether decerebrates can alter these discriminative responses as a function of food deprivation or toxicosis. Food-deprived decerebrate rats, like intact ones, ingested a taste substance they had rejected when sated. However, these same decerebrates, in contrast to controls, neither rejected nor decreased ingestive reactions to a novel taste after that taste had been repeatedly paired with lithium chloride-induced illness. Although the forebrain may be important for integrating ingestion, some aspects of this control seem to be represented in caudal brain areas.}, } @article {pmid667617, year = {1978}, author = {Mason, ST and Iversen, SD}, title = {Reward, attention and the dorsal noradrenergic bundle.}, journal = {Brain research}, volume = {150}, number = {1}, pages = {135-148}, doi = {10.1016/0006-8993(78)90658-3}, pmid = {667617}, issn = {0006-8993}, mesh = {Adrenergic Fibers/*physiology ; Animals ; Attention/*physiology ; Avoidance Learning/physiology ; Discrimination Learning/physiology ; Dopamine/physiology ; Extinction, Psychological/physiology ; Hippocampus/physiology ; Hypothalamus/physiology ; Locus Coeruleus/*physiology ; Male ; Neural Inhibition ; Neural Pathways/physiology ; Norepinephrine/*physiology ; Rats ; *Reward ; Telencephalon/*physiology ; Visual Perception/physiology ; }, abstract = {The resistance to extinction seen after lesion to the dorsal noradrenergic bundle has been suggested to arise from a deficit in internal inhibition or a 'perseverative' type of deficit. This hypothesis is tested by examining the ability of 6-hydroxydopamine-treated animals to inhibit a previously developed preference for saccharine solution as a result of poisoning with lithium chloride. Unimpaired taste aversion is found, arguing against a deficit in the ability to inhibit a prepotent response. An alternative explanation of the dorsal bundle extinction effect (DBEE), that of alterations in attention, is tested by acquisition and reversal of a successive light-dark discrimination. Both acquisition and reversal are severely impaired, suggesting that the treated animals have difficulty in attending to a specific stimulus in the environment when this is required in order to structure behaviour appropriately, and thus being consistent with a role for the dorsal bundle in the control of attentional processes.}, } @article {pmid693631, year = {1978}, author = {Chambers, KC and Sengstake, CB}, title = {Pseudo-castration effects of social isolation on extinction of a taste aversion.}, journal = {Physiology & behavior}, volume = {21}, number = {1}, pages = {29-32}, doi = {10.1016/0031-9384(78)90272-x}, pmid = {693631}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Extinction, Psychological/*physiology ; Female ; Male ; Rats ; Sex Factors ; *Social Isolation ; Taste/*physiology ; Testosterone/physiology ; }, } @article {pmid693627, year = {1978}, author = {Martin, JR and Cheng, FY and Novin, D}, title = {Acquisition of learned taste aversion following bilateral subdiaphragmatic vagotomy in rats.}, journal = {Physiology & behavior}, volume = {21}, number = {1}, pages = {13-17}, doi = {10.1016/0031-9384(78)90269-x}, pmid = {693627}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/physiology ; Female ; *Food Preferences ; Lithium ; Male ; Poisons ; Rats ; Taste/*physiology ; Vagus Nerve/*physiology ; }, } @article {pmid677336, year = {1978}, author = {Houpt, TR and Anika, SM and Wolff, NC}, title = {Satiety effects of cholecystokinin and caerulein in rabbits.}, journal = {The American journal of physiology}, volume = {235}, number = {1}, pages = {R23-8}, doi = {10.1152/ajpregu.1978.235.1.R23}, pmid = {677336}, issn = {0002-9513}, mesh = {Animals ; Ceruletide/*pharmacology ; Cholecystokinin/*pharmacology ; Denervation ; Dose-Response Relationship, Drug ; Eating ; Fasting ; Female ; Male ; Rabbits ; Satiation/*drug effects/physiology ; Taste Disorders ; Vagus Nerve/*physiology ; }, abstract = {Six adult rabbits were maintained on an 18 h fast, 6 h feeding schedule. At the end of the fast either 0.5-40 Ivy dog units (IDU)/kg cholecystokinin (CCK) or 0.9% NaCl were injected intravenously. Feed intake was then measured for 15 min. Significant depression of intake was found at 1 IDU/kg, a 50% depression of intake after 5.5 IDU/kg, and no intake after 40 IDU/kg. Caerulein in similar experiments gave significant depression of intake at 0.125 microgram/kg, a 50% depression after 0.28 microgram/kg, and no intake after 5.0 microgram/kg. In three of these rabbits subdiaphragmatic vagotomy did not abolish the satiety effects of CCK and caerulein. The synthetic octapeptide of CCK was less potent in causing satiety. After CCK or caerulein the rabbits showed typical postprandial behavior. Taste aversion tests failed to demonstrate a strong aversion to flavors associated with the compounds used. These results indicate that exogenous CCK can act as a satiety agent at levels of the same order as the physiological range.}, } @article {pmid693561, year = {1978}, author = {Goudie, AJ and Dickins, DW and Thornton, EW}, title = {Cocaine-induced conditioned taste aversions in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {8}, number = {6}, pages = {757-761}, doi = {10.1016/0091-3057(78)90279-4}, pmid = {693561}, issn = {0091-3057}, mesh = {Animals ; Cocaine/*pharmacology ; Conditioning, Operant/*drug effects ; Drinking Behavior/drug effects ; Female ; Rats ; Saccharin/pharmacology ; Taste/*physiology ; }, abstract = {In two separate studies cocaine hydrochloride at doses between 10--36 mg/kg was found to induce a dose-related conditioned taste aversion (C.T.A.) to saccharin, and to be an effective conditioning agent even when injections of the drug were delayed 90 min after saccharin intake. These data contrast with conditioning agent when unjectuons of the drug were delayed 90 min after saccharin intake. These data contrast with an earlier report [3] which suggested that cocaine was totally devoid of aversive properties. However, they do indicate that cocaine is only a weak aversion-inducing agent. In contrast to other drugs, the doses of cocaine which are required to induce a C.T.A. are very large relative to those commonly employed in behavioural studies. The weak potency of cocaine in inducing C.T.A. may be related to the drug's marked potency in the self-administration paradigm. Some possible determinants of cocaine's weak effects are discussed.}, } @article {pmid693553, year = {1978}, author = {Deutsch, R}, title = {Effects of atropine on conditioned taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {8}, number = {6}, pages = {685-694}, doi = {10.1016/0091-3057(78)90267-8}, pmid = {693553}, issn = {0091-3057}, mesh = {Animals ; Atropine/administration & dosage/*pharmacology ; Conditioning, Operant/*drug effects ; Injections, Intraperitoneal ; Injections, Intravenous ; Lithium/pharmacology ; Male ; Rats ; Saccharin/pharmacology ; *Taste ; }, abstract = {Atropine sulfate, which has a deleterious effect on various learning tasks, was found to have a similar effect on the acquisition of conditioned taste aversion. Thus, intraperitoneal injection of atropine sulfate shortly before tasting was found to interfere with conditioning of the aversion, but injection of atropine after tasting did not. The interference effect was also obtained with intraventricular administration of atropine sulfate, but not with intraperitoneal injection of the peripherally-acting atropine methylnitrate. These results show that central rather than peripheral mechanisms are involved in this effect, and suggest that conditioned taste aversion, like other kinds of learning, involves cholinergic mediation.}, } @article {pmid684100, year = {1978}, author = {Loullis, CC and Wayner, MJ and Jolicoeur, FB}, title = {Thalamic taste nuclei lesions and taste aversion.}, journal = {Physiology & behavior}, volume = {20}, number = {5}, pages = {653-655}, doi = {10.1016/0031-9384(78)90259-7}, pmid = {684100}, issn = {0031-9384}, mesh = {Afferent Pathways/physiology ; Animals ; Avoidance Learning/*physiology ; Drinking Behavior/physiology ; Lithium/poisoning ; Male ; Rats ; Saccharin ; Taste/*physiology ; Thalamus/*physiology ; }, } @article {pmid567356, year = {1978}, author = {Weinberg, J and Smotherman, WP and Levine, S}, title = {Early handling effects on neophobia and conditioned taste aversion.}, journal = {Physiology & behavior}, volume = {20}, number = {5}, pages = {589-596}, doi = {10.1016/0031-9384(78)90251-2}, pmid = {567356}, issn = {0031-9384}, mesh = {Animals ; *Animals, Newborn ; *Avoidance Learning/physiology ; *Conditioning, Operant ; Corticosterone/blood ; Discrimination, Psychological ; Exploratory Behavior ; Female ; Food Preferences ; *Handling, Psychological ; Humans ; Lithium/poisoning ; Rats ; Stress, Psychological ; *Taste ; }, } @article {pmid674245, year = {1978}, author = {Stolerman, IP and D'mello, GD}, title = {Amphetamine-induced hypodipsia and its implications for conditioned taste aversion in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {8}, number = {4}, pages = {333-338}, doi = {10.1016/0091-3057(78)90066-7}, pmid = {674245}, issn = {0091-3057}, mesh = {Amphetamine/pharmacology ; Amphetamines/*pharmacology ; Animals ; Avoidance Learning/*drug effects ; Chlorphentermine/pharmacology ; Cocaine/pharmacology ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking/*drug effects ; Fenfluramine/pharmacology ; Male ; Rats ; Taste/*drug effects ; }, abstract = {According to the conditioned anorexia hypothesis, conditioned taste aversions occur when flavour stimuli are classically conditioned to the anorexigenic or hypodipsic effects of drugs. The effects on water intake of a range of doses of amphetamine and of several related compounds have therefore been examined in an attempt to correlate their known potentices in tate aversion experiments with their hypodipsic potencies (+)-Amphetamine was more potent than (-)-amphetamine in suppressing water intake but under similar experimental conditions, the isomers were equipotent in the conditioning of taste aversions. Methamphetamine and p-chloromethamphetamine were equipotent in suppressing water intake, but the latter was a more potent agent for conditioning taste aversions. Furthermore, fenfluramine produced taste aversions at doses well below those which suppressed water intake. It was concluded that the ability of the drugs to induce taste aversion was not related to their unconditioned, hypodipsic effects. However, it was confirmed that when drugs with different durations of action are compared for anorexic or hypodipsic potency, the outcome can be greatly influenced by the time over which measurements are made.}, } @article {pmid670448, year = {1978}, author = {Bealer, SL}, title = {Intensity coding in the transient portion of the rat chorda tympani response.}, journal = {Journal of comparative and physiological psychology}, volume = {92}, number = {2}, pages = {185-195}, doi = {10.1037/h0077461}, pmid = {670448}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/physiology ; Chorda Tympani Nerve/*physiology ; Conditioning, Operant/physiology ; Cyclophosphamide/poisoning ; Discrimination Learning/*physiology ; Electrophysiology ; Generalization, Stimulus ; Male ; Osmolar Concentration ; Rats ; Sodium Chloride/administration & dosage ; Taste/*physiology ; }, abstract = {For assessment of the relative importance of the transient and steady state components of the chorda tympani response to intensity coding of gustatory stimuli, the rat's ability to discriminate aversive solutions following adaptation was compared with changes in the neural response also resulting from adaptation. A taste aversion was conditioned to .9% NaCl, and subsequent acceptance of several NaCl concentrations (range: .1%-1.5%) was tested following infusion of 1 ml of adapting solution (H2O or .1%, .9%, or 1.5% NaCl) through an intra-oral cannula. Adaptation significantly decreased gustatory intensity discrimination and decreased the magnitude of the transient portion of the chorda tympani response. The degree of reduction in transient magnitude correlated significantly with reduced discrimination in all adapting conditions. However, the magnitude of the steady state response negatively correlated with discrimination. These data suggest that gustatory intensity discrimination depends upon information contained in the transient portion of the neural response and that the transient is necessary as well as sufficient for taste intensity discrimination.}, } @article {pmid652820, year = {1978}, author = {Stolerman, IP and D'Mello, GD}, title = {Amphetamine-induced taste aversion demonstrated with operant behaviour.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {8}, number = {2}, pages = {107-111}, doi = {10.1016/0091-3057(78)90324-6}, pmid = {652820}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Operant/*drug effects ; Dextroamphetamine/*pharmacology ; Female ; Rats ; Reinforcement Schedule ; Taste/*drug effects ; Time Factors ; }, abstract = {Amphetamine can be used to condition strong taste aversions, but little is known about the possible effects of flavour-amphetamine pairings on operant behaviour. Rats were trained to press bars for water reinforcers delivered after every 40 responses (FR 40). Flavoured reinforcers were then substituted for the water and post-session injections of amphetamine (1 mg/kg) were given. Even a single flavour-amphetamine pairing produced some decrement in responding for that flavour, whereas three flavour-amphetamine pairings almost completely suppressed responding. In the same rats, a flavour which was paired with saline injections did not suppress responding. Flavour-amphetamine pairings can therefore have a powerful influence on operant behaviour and the different outcomes of flavour-conditioning and self-administration procedures cannot be attributed simply to the type of response required from the rat.}, } @article {pmid203610, year = {1978}, author = {Smotherman, WP and Levine, S}, title = {ACTH and ACTH4-10 modification of neophobia and taste aversion responses in the rat.}, journal = {Journal of comparative and physiological psychology}, volume = {92}, number = {1}, pages = {22-33}, doi = {10.1037/h0077453}, pmid = {203610}, issn = {0021-9940}, mesh = {Adrenocorticotropic Hormone/*analogs & derivatives/*pharmacology ; Animals ; Avoidance Learning/*drug effects/physiology ; Corticosterone/blood/pharmacology ; Drinking Behavior/drug effects ; Exploratory Behavior/*drug effects ; Extinction, Psychological/drug effects ; Lithium/poisoning ; Male ; Rats ; Taste ; }, abstract = {A series of experiments assessed the effects of ACTH and the ACTH analogue ACTH4-10 on drinking in conditioned taste aversion and neophobic situations. Both substances delayed the extinction of a conditioned taste aversion established by a single pairing of lithium chloride with milk (Experiment 1). However, in this situation, the ACTH parent peptide was more potent behaviorally. Administration of ACTH suppressed milk consumption in animals with no toxicosis experience (Experiment 2). This effect was apparently not due to the conditioning of a taste aversion (Experiment 3) with ACTH serving as a weak aversive unconditioned stimulus. Administration of exogenous ACTH (Experiment 4) or ACTH4-10 (Experiment 5) did not enhance neophobia; however, repeated injections of ACTH suppressed drinking. This ACTH suppression was related to the familiarity/novelty of the subtance being consumed. The neophobic response to milk eas no accompanied by pituitary-adrenal activation (Experiment 6). Both neophobic and conditioned taste aversion situation appear to be useful for assessing peptide effects on consummatory behavior.}, } @article {pmid26928, year = {1978}, author = {Venkatakrishna-Bhatt, H and Bures, J and Buresova, O}, title = {Differential effect of paradoxical sleep deprivation on acquisition and retrieval of conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {20}, number = {2}, pages = {101-107}, doi = {10.1016/0031-9384(78)90058-6}, pmid = {26928}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; *Conditioning, Operant ; Drinking Behavior ; Lithium/poisoning ; Male ; Memory/*physiology ; Neurotransmitter Agents/physiology ; Rats ; Retention, Psychology/*physiology ; Saccharin ; Sleep/physiology ; *Sleep Deprivation ; Sleep, REM/*physiology ; *Taste ; Time Factors ; }, } @article {pmid415322, year = {1978}, author = {Coil, JD and Hankins, WG and Jenden, DJ and Garcia, J}, title = {The attenuation of a specific cue-to-consequence association by antiemetic agents.}, journal = {Psychopharmacology}, volume = {56}, number = {1}, pages = {21-25}, pmid = {415322}, issn = {0033-3158}, mesh = {Animals ; Antiemetics/*pharmacology ; Conditioning, Classical/*drug effects ; *Cues ; Male ; Rats ; Reinforcement, Psychology ; Taste ; Time Factors ; }, abstract = {Previous research has been shown that rats develop a conditioned taste aversion after a single pairing of a distinct taste and subsequent toxicosis. The experiments reported here test the hypothesis that the expression of a taste aversion may reflect classically conditioned nausea mediated by activation of brainstem emetic centers by taste stimuli. Rats were allowed to drink a saccharin solution (1 g/l) and 10 min later were intubated with LiCl (180 mg/kg) to produce nausea. When control rats were posttested for saccharin preference they consumed less than 50% of their pretest intake. Experimental rats were injected with one of four pharmacologically distinct antiemetic drugs 30 min prior to their posttest with saccharin. Each drug significantly attenuated the aversion to saccharin at one dose level. The antiemetic drugs we used were scopolamine HBr, cyclizine, prochlorperazine dimaleate, and trimethobenzamide. These drugs had no effect on the conditioned fear of a noise that signaled foot shock or on a natural aversion to a bitter fluid (quinine monohydrochloride, 100 mg/l). Our data suggest that pharmacological suppression of the neural mechanisms of emesis selectively disrupts conditioned taste aversions, and that moderate dose levels are critical for obtaining this effect.}, } @article {pmid633907, year = {1978}, author = {Barker, LM and Johns, T}, title = {Effect of ethanol preexposure on ethanol-induced conditioned taste aversion.}, journal = {Journal of studies on alcohol}, volume = {39}, number = {1}, pages = {39-46}, doi = {10.15288/jsa.1978.39.39}, pmid = {633907}, issn = {0096-882X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Drinking/drug effects ; Drug Tolerance ; Ethanol/*pharmacology ; Male ; Rats ; Saccharin ; Taste/*drug effects ; }, abstract = {In a taste-aversion test pairing saccharin and ethanol, rats that had recently ingest ethanol showed attenuated aversion to saccharin.}, } @article {pmid305048, year = {1978}, author = {Lorden, JF}, title = {Alteration of the characteristics of learned taste aversion by manipulation of serotonin levels in the rat.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {8}, number = {1}, pages = {13-18}, doi = {10.1016/0091-3057(78)90116-8}, pmid = {305048}, issn = {0091-3057}, mesh = {5-Hydroxytryptophan/administration & dosage ; Animals ; Avoidance Learning/drug effects/*physiology ; Choice Behavior/physiology ; Drinking ; Male ; Premedication ; Raphe Nuclei/physiology ; Rats ; Serotonin/administration & dosage/*physiology ; *Taste ; }, abstract = {Electrolytic lesions placed in the dorsal and median raphe nuclei of the rat brain deplete hypothalamic and telencephalic serotonin. These lesions also enhance the learned suppression of saccharin consumption which results from pairing the ingestion of a saccharin solution with the injection of a toxic drug. Pretreatment of rats with raphe lesions with the serotonin precursor DL-5-hydroxy-tryptophan (5HTP) immediately prior to the conditioning trial blocks the learning of the aversion to saccharin. In normal rats, 5HTP pretreatment also attenuates the suppressive effects of conditioning on saccharin drinking. These results differ from the findings of previous research using the flinch-jump technique. When sensitivity to shock is measured, 5HTP pretreatment in rats with forebrain serotonin depletion has been reported to restore both serotonin levels and behavior to normal. No behavioral effects are observed in normal animals. Possible explanations for the differential effects obtained in the two paradigms are discussed.}, } @article {pmid414277, year = {1977}, author = {Roberts, DC and Fibiger, HC}, title = {Lesions of the dorsal noradrenergic projection attenuate morphine- but not amphetamine-induced conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {55}, number = {2}, pages = {183-186}, pmid = {414277}, issn = {0033-3158}, mesh = {Animals ; Brain Chemistry ; Conditioning, Psychological ; Dextroamphetamine/*pharmacology ; Hydroxydopamines/*pharmacology ; Male ; Morphine/*pharmacology ; Norepinephrine/analysis ; Rats ; Saccharin ; Stereotaxic Techniques ; Taste/*drug effects ; }, } @article {pmid597669, year = {1977}, author = {Booth, DA and Pilcher, CW and D'Mello, GD and Stolerman, IP}, title = {Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats.}, journal = {British journal of pharmacology}, volume = {61}, number = {4}, pages = {669-677}, pmid = {597669}, issn = {0007-1188}, mesh = {Amphetamines/*pharmacology ; Animals ; Avoidance Learning/drug effects ; Chlorphentermine/pharmacology ; Cocaine/pharmacology ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Fenfluramine/pharmacology ; Male ; Methamphetamine/analogs & derivatives/pharmacology ; Rats ; Taste/*drug effects ; }, abstract = {1 Rats failed to drink a flavoured solution when its consumption had been followed by injection of amphetamine (conditioned taste aversion).2 There was very little difference between the potencies of (+)- and (-)-amphetamine.3p-Chloromethamphetamine was a more potent aversive agent than methamphetamine.4 Strong taste aversions were also conditioned with other congeners of amphetamine. The rank order of potency was: fenfluramine > chlorphentermine >p-hydroxyamphetamine.5 Cocaine induced only moderate taste aversions, even at high doses.6 Aversive potency did not appear to be correlated with known neurochemical actions of the drugs or with behavioural stimulation, but appeared to be a central action which may have been linked to anorexigenic potency or time course of action.}, } @article {pmid598620, year = {1977}, author = {Domjan, M and Schorr, R and Best, M}, title = {Early environmental influences on conditioned and unconditioned ingestional and locomotor behaviors.}, journal = {Developmental psychobiology}, volume = {10}, number = {6}, pages = {499-506}, doi = {10.1002/dev.420100603}, pmid = {598620}, issn = {0012-1630}, mesh = {Animals ; Avoidance Learning ; *Conditioning, Classical ; Electroshock ; *Environment ; Extinction, Psychological ; *Feeding Behavior/drug effects ; Female ; Lithium/pharmacology ; Male ; *Motor Activity ; Rats ; Saccharin ; Social Isolation ; Taste ; Water Deprivation ; }, abstract = {For 34-44 days after weaning one group of rats was raised in a socially enriched environment, whereas another group was raised in isolated individual cages without handling. Following this differential rearing subjects were tested for ingestional neophobia and its attenuation, enhancement of ingestional neophobia by aversive drug administration, taste-aversion learning and extinction, open-field activity, and passive shock-avoidance learning. Although the differential rearing influenced open-field activity and shock-avoidance this manipulation did not have a significant effect on the various measures of conditioned and unconditioned ingestional behaviors. The results provide further evidence for the distinctiveness of gustatory-visceral and telereceptor-cutaneous sensory systems.}, } @article {pmid595875, year = {1977}, author = {Brozhek, G and Velits, G and Klimenko, VM and Bureshova, O and Buresh, La}, title = {[Role of licking and concomitant changes in the excitability of nerve centers in the elaboration of gustatory information in rats].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {27}, number = {6}, pages = {1216-1223}, pmid = {595875}, issn = {0044-4677}, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Classical/physiology ; Drinking Behavior/*physiology ; Electric Stimulation ; Electrophysiology ; Frontal Lobe/physiopathology ; Hypothalamus/*physiology ; Neural Analyzers/physiology ; Rats ; Seizures/physiopathology ; Taste/*physiology ; }, abstract = {The mechanism of nervous control of licking was studied in the frame work of the electrophysiological analysis of conditioned taste aversion. The licking rhythm is so stable that the rats are unable to slow it down by 20 percent. If the solution which was previously used for establishing the conditioned taste aversion, appears in the drinking spout, the rat stops drinking after one or two licks. Analysis of temporal relationships between afferent and efferent impulse activity of licking shows that the comparison of gustatory signals with memory traces and the corresponding decision occurs within 80 to 120 ms after lick onset. Electrical stimulation of the hypothalamic centres through implanted electrodes has shown that the amplitude of evoked responses and the impairment of licking increases, in proportion to the delay between lick onset and stimulus application. Isolated discharges of epileptic foci in the frontal cortex and the hypothalamus cause an omission of one or several licks, without interfering with the activity of the licking generator.}, } @article {pmid563606, year = {1977}, author = {Mitchell, D and Winter, W and Morisaki, CM}, title = {Conditioned taste aversions accompanied by geophagia: evidence for the occurrence of "psychological" factors in the etiology of pica.}, journal = {Psychosomatic medicine}, volume = {39}, number = {6}, pages = {401-412}, pmid = {563606}, issn = {0033-3174}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Operant ; Cyclophosphamide/poisoning ; Feeding Behavior ; Humans ; Kaolin ; Lithium/poisoning ; Male ; Pica/etiology/*psychology ; Rats ; Saccharin ; *Taste ; }, abstract = {A conditioned taste aversion procedure was used to produce an avoidance of saccharin by rats. In the first experiment, saccharin consumption was paired with cyclophosphamide in two conditioning trials during which the animals were permitted to engage in pica. In the second experiment, saccharin consumption was paired with lithium chloride in four conditioning trials during which the animals were not allowed to engage in pica. Conditioned animals in both experiments subsequently engaged in geophagia when presented with saccharin alone. The absence of geophagia in noncontingently poisoned and "sham" injected control groups indicates that the pica was due to the acquisition of a conditioned illness during the conditioning trials. In addition to providing a demonstration of "psychological" involvement in the etiology of pica, these results indicate that visceral conditioning may accompany the formation of conditioned taste aversions. It is suggested that if there is a relationship between infantile pica and adult drug addiction, a plausible mediational mechanism is that pica-prone and addiction-prone individuals are similar in possessing a high susceptibility to visceral conditioning.}, } @article {pmid915436, year = {1977}, author = {Domjan, M and Best, MR}, title = {Paradoxical effects of proximal unconditioned stimulus preexposure: interference with and conditioning of a taste aversion.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {3}, number = {4}, pages = {310-321}, doi = {10.1037//0097-7403.3.4.310}, pmid = {915436}, issn = {0097-7403}, mesh = {Animals ; Association ; *Avoidance Learning ; *Conditioning, Operant ; Drinking Behavior/drug effects ; Lithium/administration & dosage/poisoning ; Male ; Rats ; Saccharin/administration & dosage ; *Taste ; Time Factors ; }, abstract = {Taste aversions were conditioned in rats by giving the subjects an injection of lithium following exposure to saccharin. Treatment with lithium shortly (30 to 60 min.) before such a conditioning trial disrupted the taste-aversion learning produced by the postsaccharin drug injection. In Experiment 1, this interference effect was found to be a monotonically decreasing function of the preexposure-to-conditioning interval. The greatest disruption of conditioning was observed with a 30-min. preexposure-to-conditioning interval, and no interference occurred if the preexposure was administered 1 or 2 days before conditioning. These results suggest that in addition to the more durable effects of unconditioned stimulus (US) preexposure emphasized by previous investigators, US preexposure also activates temporary mechanisms that likewise attenuate subsequent conditioning. Experiment 2 demonstrated that lithium given before saccharin exposure disrupts the conditioning produced by a postsaccharin drug injection even if the presaccharin injection would itself otherwise be effective in producing a "backward" conditioned saccharin aversion. This outcome indicates that proximal US preexposure can have two opposite and paradoxical effects: It can interfere with as well as condition a taste aversion.}, } @article {pmid915435, year = {1977}, author = {Gillan, DJ and Domjan, M}, title = {Taste-aversion conditioning with expected versus unexpected drug treatment.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {3}, number = {4}, pages = {297-309}, doi = {10.1037//0097-7403.3.4.297}, pmid = {915435}, issn = {0097-7403}, mesh = {Administration, Oral ; Animals ; Association Learning ; *Avoidance Learning ; *Conditioning, Operant ; Extinction, Psychological ; Female ; Lithium/poisoning ; Male ; Rats ; Saccharin/administration & dosage ; Sensation ; *Taste ; Water/administration & dosage ; }, abstract = {Following differential conditioning in which a drug-predictive taste solution (D) infused into the oral cavity of rats was followed by a lithium injection and a no-drug-predictive solution (ND) was not reinforced, animals received a backward pairing between lithium and a novel saccharin flavor. Subjects infused with either the D solution or tap water immediately before backward conditioning learned weaker saccharin aversions than animals infused with the ND solution and animals given no infusion at this time (Experiments 1 and 3). These latter groups did not differ from each other (Experiment 3). The interference with aversion learning produced by water infusion appeared to be due to conditioned excitation that accrued to sensations of the infusion process. Extinction of the infusion sensations eliminated blocking produced by the infusion of water (Experiments 4 and 5). The blocking of saccharin-aversion learning produced by infusion of the D solution was due, to a large extent, to the conditioned aversiveness of the D taste. Extinction of the aversion to the D taste eliminated the interference with saccharin conditioning (Experiment 2), whereas extinction of the excitatory properties of the infusion process did not prevent the blocking of conditioning by infusion of the D solution (Experiment 5). These results are inconsistent with suggestions that taste-aversion learning is a primitive form of conditioning; rather, they demonstrate the influence of informational variables on conditioned taste aversions.}, } @article {pmid593528, year = {1977}, author = {Sklar, LS and Amit, Z}, title = {Manipulations of catecholamine systems block the conditioned taste aversion induced by self-administered drugs.}, journal = {Neuropharmacology}, volume = {16}, number = {10}, pages = {649-655}, doi = {10.1016/0028-3908(77)90115-0}, pmid = {593528}, issn = {0028-3908}, mesh = {Animals ; Avoidance Learning/*drug effects ; Cannabinoids/pharmacology ; Catecholamines/*antagonists & inhibitors ; Chlorides/pharmacology ; Conditioning, Operant/*drug effects ; Ethanol/pharmacology ; Lithium/pharmacology ; Male ; Methyltyrosines/pharmacology ; Morphine/pharmacology ; Pimozide/pharmacology ; Rats ; Reinforcement, Psychology ; Taste/*drug effects ; }, } @article {pmid408851, year = {1977}, author = {Grupp, LA}, title = {Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion.}, journal = {Psychopharmacology}, volume = {53}, number = {3}, pages = {235-242}, pmid = {408851}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dextroamphetamine/*pharmacology ; Drinking/drug effects ; Extinction, Psychological/*drug effects ; Male ; Memory/*drug effects ; Pimozide/administration & dosage/*pharmacology ; Rats ; Retention, Psychology/*drug effects ; Saccharin ; Taste ; Time Factors ; }, abstract = {Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine dulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in the functional strength of amphetamine as an unconditioned stimulus.}, } @article {pmid607235, year = {1977}, author = {Silva, MT}, title = {Saccharin aversion in the rat following adrenalectomy.}, journal = {Physiology & behavior}, volume = {19}, number = {2}, pages = {239-244}, doi = {10.1016/0031-9384(77)90332-8}, pmid = {607235}, issn = {0031-9384}, mesh = {*Adrenalectomy ; Animals ; Dexamethasone/pharmacology ; Dose-Response Relationship, Drug ; Drinking ; Male ; Rats ; *Saccharin ; Taste/drug effects/*physiology ; Time Factors ; }, abstract = {Changes in saccharin preference as a function of concentration were studied in rats after either adrenalectomy of sham surgery. A 48 hr two-bottle preference test was used. Under two different sets of testing conditions, adrenalectomized animals rejected saccharin solutions at concentrations that were highly acceptible to controls and did not show an appetitive behavior towards andy of the concentrations tested. This aversion pattern persisted even when preference tests were conducted for as long as 10 days. However, it was abolished when the adrenalectomized rats wre exposed to saccharin for 6 days prior to surgery, or when they were administered the glucocorticoid dexamethasone. Results are discussed with respect to the effects of adrenal hormones on sensory systems and to taste-aversion learning.}, } @article {pmid263668, year = {1977}, author = {Van der Kooy, D and Phillips, AG}, title = {Temporal analysis of naloxone attenuation of morphine-induced taste aversion.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {6}, number = {6}, pages = {637-641}, doi = {10.1016/0091-3057(77)90088-0}, pmid = {263668}, issn = {0091-3057}, mesh = {Animals ; Conditioning, Psychological/*drug effects ; Dose-Response Relationship, Drug ; Humans ; Male ; Morphine/*antagonists & inhibitors ; Morphine Dependence ; Naloxone/administration & dosage/*pharmacology ; Rats ; Rats, Inbred Strains ; Self Stimulation ; Taste/*drug effects ; Time Factors ; }, abstract = {In a dose-response study, 7.5 mg/kg of naloxone produced maximal attenuation of conditioned taste aversion to saccharin induced by 10 mg/kg of morphine. Naloxone was administered immediately after the morphine in this study. In a second experiment, naloxone still caused a significant attenuation of taste aversions when administered with a 1 hr delay after morphine, but not after delays of 4 or 8 hr. These results suggest that behavioral consequences of morphine which peak during the first hr after injection (analgesia, catalepsy, and depression of intracranial self-stimulation) are not correlated with the aversive effect of morphine. Nor can the aversiveness of morphine be attributed to withdrawal effects. Only the facilitative actions of morphine occurring 1 to 4 hr after injection, including the facilitation of intracranial self-stimulation, are temporally correlated with the naloxone-sensitive aversive effect. Thus, a temporal analysis cannot be used to dissociate the paradoxical positive reinforcement and aversive effects of morphine. Rather, the temporal correlation between the two opposite motivational effects of morphine serves to emphasize the nature of this paradox.}, } @article {pmid905387, year = {1977}, author = {Kesner, RP and Berman, RF}, title = {Effects of midbrain reticular formation, hippocampal, and lateral hypothalamic stimulation upon recovery from neophobia and taste aversion learning.}, journal = {Physiology & behavior}, volume = {18}, number = {5}, pages = {763-768}, doi = {10.1016/0031-9384(77)90180-9}, pmid = {905387}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Drinking Behavior/*physiology ; Electric Stimulation ; Hippocampus/*physiology ; Hypothalamus/*physiology ; Male ; Mesencephalon/*physiology ; Rats ; Reticular Formation/*physiology ; Taste/*physiology ; Time Factors ; }, } @article {pmid863118, year = {1977}, author = {Ader, R and Peck, JH}, title = {Early learning and retention of a conditioned taste aversion.}, journal = {Developmental psychobiology}, volume = {10}, number = {3}, pages = {213-218}, doi = {10.1002/dev.420100305}, pmid = {863118}, issn = {0012-1630}, mesh = {Age Factors ; Animals ; Avoidance Learning/*physiology ; Competitive Behavior/physiology ; Conditioning, Psychological ; Dominance-Subordination ; Male ; Memory/*physiology ; Rats ; Retention, Psychology/*physiology ; Taste/*physiology ; }, abstract = {Weanling rats were trained on a taste aversion task and tested 60 days later using the single bottle and preference methods for assessing the retention of a taste aversion, and a competitive situation in which the CS was eventually substituted for plain water. Only the competitive situation showed the effects of the early taste aversion training. The results are discussed in terms of the conditioning and reactivation of adrenocortical steroid elevations and how these might affect subsequent retrieval.}, } @article {pmid17382, year = {1977}, author = {Buresová, O and Bures, J}, title = {The effect of anesthesia on acquisition and extinction of conditioned taste aversion.}, journal = {Behavioral biology}, volume = {20}, number = {1}, pages = {41-50}, doi = {10.1016/s0091-6773(77)90473-4}, pmid = {17382}, issn = {0091-6773}, mesh = {*Anesthesia, General ; Animals ; Avoidance Learning/*drug effects ; *Barbiturates ; Cerebral Cortex/physiology ; Conditioning, Operant/*drug effects ; Cortical Spreading Depression ; Electroencephalography ; Extinction, Psychological/*drug effects ; Lithium/poisoning ; Male ; Memory, Short-Term/drug effects ; Pentobarbital ; Rats ; Taste/*drug effects ; }, } @article {pmid860985, year = {1977}, author = {Mikulka, PJ and Freeman, FG and Lidstrom, P}, title = {The effect of training technique and amygdala lesions on the acquisition and retention of a taste aversion.}, journal = {Behavioral biology}, volume = {19}, number = {4}, pages = {509-517}, doi = {10.1016/s0091-6773(77)91978-2}, pmid = {860985}, issn = {0091-6773}, mesh = {Amygdala/*physiology ; Animals ; Avoidance Learning/*physiology ; Extinction, Psychological/physiology ; Male ; Memory/*physiology ; Methods ; Rats ; Retention, Psychology/*physiology ; Taste/*physiology ; }, } @article {pmid856931, year = {1977}, author = {Mikulka, PJ and Leard, B and Klein, SB}, title = {Illness-alone exposure as a source of interference with the acquisition and retention of a taste aversion.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {3}, number = {2}, pages = {189-201}, doi = {10.1037//0097-7403.3.2.189}, pmid = {856931}, issn = {0097-7403}, mesh = {Animals ; *Association ; *Avoidance Learning ; Conditioning, Operant ; Drinking Behavior/drug effects ; Female ; Flavoring Agents ; Lithium/*poisoning ; Rats ; Sucrose ; *Taste ; }, abstract = {Four studies were conducted to explore the effects of unpaired lithium chloride (LiCl) injections, the unconditioned stimulus (US), on the acquisition and retention of a taste aversion. In Experiment 1, subjects were preexposed to a US; for one group the US was paired with a distinctive taste, whereas for a second group it was not. Following this preparation, both groups received the US paired with a novel taste. Only the US-alone group showed a retardation of subsequent taste-aversion conditioning. Experiment 2 indicated that an exposure to LiCl without a specific gustatory cue will interfere with the avoidance of a specific taste, regardless of whether the US experience occurs before or after a single taste-LiCl pairing. Following sucrose-LiCl pairings in Experiment 3A, LiCl-alone exposures retroactively interfered with the retention of the prior aversion to sucrose, with the level of post-US interference becoming an increasing function of the number of US-alone experiences. In Experiment 3B, the association of sucrose with LiCl did not interfere with the development of an almond aversion, whereas LiCl-alone exposures following the acquisition of a sucrose aversion proactively interfered with the development of a second taste aversion (almond). It is suggested that a physiological explanation will not adequately account for the present results of these experiments. The results are discussed within the framework of alternative associative models.}, } @article {pmid403544, year = {1977}, author = {Manning, FJ and Jackson, MC}, title = {Enduring effects of morphine pellets revealed by conditioned taste aversion.}, journal = {Psychopharmacology}, volume = {51}, number = {3}, pages = {279-283}, pmid = {403544}, issn = {0033-3158}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Psychological/drug effects/*physiology ; Drug Implants ; Humans ; Male ; Morphine/administration & dosage/blood/*pharmacology ; Morphine Dependence/*physiopathology ; Naloxone/pharmacology ; Rats ; Substance Withdrawal Syndrome/chemically induced ; Taste ; Time Factors ; }, abstract = {Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including "wet dog shakes"and weight loss, were noted in these subjects, but not in controls given placebo pellets and /or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.}, } @article {pmid859599, year = {1977}, author = {Deutsch, JA and Hardy, WT}, title = {Cholecystokinin produces bait shyness in rats.}, journal = {Nature}, volume = {266}, number = {5598}, pages = {196}, doi = {10.1038/266196a0}, pmid = {859599}, issn = {0028-0836}, mesh = {Animals ; Cholecystokinin/*pharmacology ; Drinking Behavior/*drug effects ; Male ; Rats ; Satiation/drug effects ; Taste/drug effects ; }, } @article {pmid899649, year = {1977}, author = {Aleksanyan, ZA and Buresová, O and Bures, J and Vassilevski, NN}, title = {Modification of hypothalamic unit activity by conditioned taste aversion and instrumental control of blood pressure [proceedings].}, journal = {Activitas nervosa superior}, volume = {19}, number = {1}, pages = {59-60}, pmid = {899649}, issn = {0001-7604}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain Mapping ; Cats ; Electrophysiology ; Hypothalamus/*physiology ; Rabbits ; Reticular Formation/physiology ; Taste/*physiology ; Thalamus/physiology ; }, } @article {pmid854518, year = {1977}, author = {Ionescu, E and Buresová, O}, title = {Failure to elicit conditioned taste aversion by severe poisoning.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {6}, number = {3}, pages = {251-254}, doi = {10.1016/0091-3057(77)90021-1}, pmid = {854518}, issn = {0091-3057}, mesh = {Animals ; Chlorides/poisoning ; Conditioning, Classical/*drug effects ; Cyanides/poisoning ; Fluoride Poisoning ; Gallamine Triethiodide/poisoning ; Iodoacetates/poisoning ; Lithium/poisoning ; Male ; Malonates/poisoning ; Pyrroles/poisoning ; Rats ; Taste/*drug effects ; }, abstract = {In an attempt to assess the universal validity of the conditioned taste aversion (CTA) paradigm, various types of poisoning (UC) were associated with the gustatory CS. Water deprived rats were habituated for two days to the drinking box, where water was available for 15 min. On Day 3, access to the CS (0.1% saccharin 15 min) was followed after 30 min by a sublethal dose of the poison (0.15 M LiCl, 4% body weight; 0.1 M sodium malonate, 1% body weight; pyrrolopyrimidine drug BW 58-271, 15 mg/kg; sodium cyanide 4 mg/kg; sodium iodoacetate 40 mg/kg; sodium fluoride 30 mg/kg; gallamine triethiodide 40 mg/kg). Rats injected with the last drug were maintained under artificial respiration until muscular paralysis disappeared. After 4 days of recovery, water deprivation schedule was resumed on Days 8 and 9. During the retention test on Day 10 saccharin consumption dropped by 60% in the LiCl poisoned rats, but not CTA developed in animals poisoned by pyrrolopyrimidine, gallamine, malonate and cyanide. CTA of intermediate intensity was evoked by iodoacetate and fluoride. The absence of CTA was not due to the amnesic effect of poisoning, since LiCl administration to NaCN poisoned rats produced CTA of usual intensity. It is concluded that CTA is not related to the overall severity of poisoning but rather to the effect of the poison on specific interoceptors.}, } @article {pmid840369, year = {1977}, author = {Amit, Z and Levitan, DE and Brown, ZW and Rogan, F}, title = {Possible involvement of central factors in the mediation of conditioned taste aversion.}, journal = {Neuropharmacology}, volume = {16}, number = {2}, pages = {121-124}, doi = {10.1016/0028-3908(77)90058-2}, pmid = {840369}, issn = {0028-3908}, mesh = {Animals ; Avoidance Learning/*drug effects ; Caudate Nucleus/drug effects ; Dronabinol/*pharmacology ; Ethanol/pharmacology ; Hippocampus/*drug effects ; Male ; Morphine/pharmacology ; Rats ; Taste/*drug effects ; }, } @article {pmid905385, year = {1977}, author = {Kutscher, CL and Wright, WA}, title = {Unconditioned taste aversion to quinine induced by injections of NaCl and LiCl: dissociation of aversion from cellular dehydration.}, journal = {Physiology & behavior}, volume = {18}, number = {1}, pages = {87-94}, doi = {10.1016/0031-9384(77)90098-1}, pmid = {905385}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*drug effects ; Blood Proteins/metabolism ; Blood Volume/drug effects ; Dehydration/blood/chemically induced ; Drinking Behavior/drug effects ; Female ; Hematocrit ; Intracellular Fluid/metabolism ; Lithium/*pharmacology ; Polyethylene Glycols/administration & dosage ; *Quinine/administration & dosage ; Rats ; Saline Solution, Hypertonic ; Sodium Chloride/*pharmacology ; Taste/*drug effects ; Water Deprivation ; }, } @article {pmid905381, year = {1977}, author = {Domjan, M and Gregg, B}, title = {Long-delay backward taste-aversion conditioning with lithium.}, journal = {Physiology & behavior}, volume = {18}, number = {1}, pages = {59-62}, doi = {10.1016/0031-9384(77)90094-4}, pmid = {905381}, issn = {0031-9384}, mesh = {Animals ; *Avoidance Learning/drug effects ; *Conditioning, Operant ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Female ; Lithium/*administration & dosage ; Male ; Rats ; *Reaction Time ; Saccharin/administration & dosage ; *Taste/drug effects ; }, } @article {pmid862075, year = {1977}, author = {Bures, J and Bursová, S}, title = {[Conditioned taste aversion].}, journal = {Ceskoslovenska fysiologie}, volume = {26}, number = {1}, pages = {11-39}, pmid = {862075}, issn = {1210-6313}, mesh = {Animals ; *Conditioning, Psychological/drug effects ; Electrophysiology ; Electroshock ; Female ; Food ; Male ; Rats ; Rejection, Psychology ; *Taste/*physiology ; }, } @article {pmid850692, year = {1977}, author = {Cannon, DS and Baker, TB and Berman, RF}, title = {Taste aversion disruption by drug pretreatment: dissociative and drug-specific effects.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {6}, number = {1}, pages = {93-100}, doi = {10.1016/0091-3057(77)90164-2}, pmid = {850692}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/drug effects ; Conditioning, Psychological/*drug effects ; Drinking/drug effects ; Drug Tolerance ; Ethanol/pharmacology ; Lithium/pharmacology ; Male ; Postural Balance/drug effects ; Rats ; Saccharin ; *Taste ; Time Factors ; }, abstract = {Disruption of taste aversion learning following the administration of the same drug prior to and during conditioning (intra-agent disruption) was shown to be greater than disruption following the administration of one drug prior to conditioning and another during conditioning (inter-agent disruption). Comparable dosages of ethanol and lithium chloride served as unconditioned stimuli. Inter-agent disruptions are attributed to a dissociation of conditioned and unconditioned stimuli, while intra-agent disruptions are attributed to both a dissociative effect and drug-specific effects. Intra-agent disruption was correlated with an independent measure of tolerance, suggesting tolerance constitutes at least a portion of the drug-specific effects.}, } @article {pmid845543, year = {1977}, author = {Rudy, JW and Rosenberg, L and Sandell, JH}, title = {Disruption of a taste familiarity effect by novel exteroceptive stimulation.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {3}, number = {1}, pages = {26-36}, doi = {10.1037//0097-7403.3.1.26}, pmid = {845543}, issn = {0097-7403}, mesh = {Animals ; *Association ; *Avoidance Learning ; Conditioning, Operant ; Drinking Behavior ; *Environment ; Lithium/poisoning ; Male ; Rats ; Saccharin/pharmacology ; *Taste ; Time Factors ; }, abstract = {Preexposed or familiar tastes are normally retarded relative to novel tastes in acquiring aversive properties as a consequence of being paired with an illness-inducing event. Four experiments are reported which demonstrate that such a taste familiarity effect can be significantly disrupted by exposing the animal to novel exteroceptive stimulation just prior to conditioning with the familiar taste. Implications of this finding for theories of taste aversion learning are discussed, and two potential theoretical accounts of the data are suggested.}, } @article {pmid562610, year = {1977}, author = {Worsham, ED and Riley, EP and Anandam, N and Lister, P and Freed, EX and Lester, D}, title = {Selective breeding of rats for differences in reactivity to alcohol: an approach to an animal model of alcoholism. III. Some physical and behavioral measures.}, journal = {Advances in experimental medicine and biology}, volume = {85A}, number = {}, pages = {71-81}, doi = {10.1007/978-1-4899-5181-6_5}, pmid = {562610}, issn = {0065-2598}, mesh = {Alcoholism/*genetics/physiopathology ; Animals ; Body Weight ; *Breeding ; Disease Models, Animal ; Ethanol/pharmacology ; Female ; Humans ; Lithium/pharmacology ; Male ; Motor Activity/*drug effects ; Organ Size ; Rats/*genetics ; Self Administration ; }, abstract = {The results of selective breeding for differential impairment of motor activity after alcohol injection is shown for the first 13 generations of the LA and MA rat strains. In F13 rats, the mean decrement of activity after 1.5 g ethanol per kg i/p. is 90% for MA rats and 42% for LA rats, the strain difference significant at a "p" of 1.8 x 10(-11). Blood alcohol levels, body weight, litter size, organ weights and induction of taste aversion to alcohol and lithium chloride are described for these strains in various of the generations. Although strain differences are apparent on some of these measures, none are of a degree or kind which offers more than a speculative explanation of the large difference between the strains in their central nervous system sensitivity to alcohol.}, } @article {pmid200076, year = {1977}, author = {Levine, S and Smotherman, WP and Hennessy, JW}, title = {Pituitary-adrenal hormones and learned taste aversion.}, journal = {Advances in biochemical psychopharmacology}, volume = {17}, number = {}, pages = {163-177}, pmid = {200076}, issn = {0065-2229}, mesh = {Adrenal Cortex Hormones/*physiology ; Adrenocorticotropic Hormone/pharmacology ; Animals ; Avoidance Learning/drug effects/*physiology ; Corticosterone/blood ; Dexamethasone/pharmacology ; Lithium/pharmacology ; Male ; Pituitary Hormones/*physiology ; Rats ; *Taste ; }, } @article {pmid1016184, year = {1976}, author = {Deutsch, JA and Davis, JK and Cap, M}, title = {Conditioned taste aversion: oral and postingestional factors.}, journal = {Behavioral biology}, volume = {18}, number = {4}, pages = {545-550}, doi = {10.1016/s0091-6773(76)92560-8}, pmid = {1016184}, issn = {0091-6773}, mesh = {*Administration, Oral ; Animals ; Association/physiology ; *Avoidance Learning ; Caseins/administration & dosage ; Central Nervous System/physiology ; *Conditioning, Operant ; Drinking Behavior ; Lithium/poisoning ; Male ; Rats ; *Taste ; Time Factors ; }, } @article {pmid993394, year = {1976}, author = {Ader, R}, title = {Conditioned adrenocortical steroid elevations in the rat.}, journal = {Journal of comparative and physiological psychology}, volume = {90}, number = {12}, pages = {1156-1163}, doi = {10.1037/h0077290}, pmid = {993394}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/physiology ; Chlorides/administration & dosage ; Conditioning, Classical/*physiology ; Corticosterone/*blood ; Cyclophosphamide/administration & dosage ; Drinking Behavior/physiology ; Extinction, Psychological/physiology ; Lithium/administration & dosage ; Male ; Rats ; Saccharin/administration & dosage ; Taste/physiology ; }, abstract = {An illness-induced taste aversion paradigm was used to condition an elevation in plasma corticosterone level. Rats were injected with cyclophosphamide 30 min after consuming a novel saccharin drinking solution. Plasma corticosterone levels were measured before conditioning to determine unconditioned steroid levels and 3 and 6 days after training when conditioned and nonconditioned animals were provided with the saccharin solution or plain water, or were left deprived. The pairing of saccharin and cyclophosphamide was effective in inducing a passive avoidance response. There were no differences between the steroid levels of conditioned and nonconditioned animals supplied with plain water or those that remained deprived, although deprivation increased corticosterone levels. Nonconditioned rats presented with saccharin had steroid levels that did not differ from control values. Conditioned animals presented with saccharin showed an elevation in steroid level which was significantly greater than that observed in any other group. Comparable results were obtained when LiCl was used as the unconditioned stimulus.}, } @article {pmid1026982, year = {1976}, author = {Siegel, JL}, title = {Effect of medial septal lesions on conditioned taste aversion in the rat.}, journal = {Physiology & behavior}, volume = {17}, number = {5}, pages = {761-765}, doi = {10.1016/0031-9384(76)90036-6}, pmid = {1026982}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/drug effects/*physiology ; Dose-Response Relationship, Drug ; Lithium/pharmacology ; Male ; Rats ; Septum Pellucidum/*physiology ; Taste/drug effects/*physiology ; Time Factors ; }, } @article {pmid965532, year = {1976}, author = {Chambers, KC}, title = {Hormonal influences on sexual dimorphism in rate of extinction of a conditioned taste aversion in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {90}, number = {9}, pages = {851-856}, doi = {10.1037/h0077270}, pmid = {965532}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/*physiology ; Castration ; Conditioning, Operant/drug effects/physiology ; Drinking Behavior/drug effects/physiology ; Extinction, Psychological/*physiology ; Female ; Lithium/poisoning ; Male ; Rats ; Sex Factors ; Sodium Chloride/poisoning ; Taste/*physiology ; Testosterone/pharmacology/*physiology ; }, abstract = {The hormonal influences on the slow extinction rate of a conditioned taste aversion shown by male rats and the fast extinction rate shown by female rats were investigated. When males were castrated, they extinguished as quickly as females. When castrated males were given testosterone propionate replacement, they had a slow extinction rate. Castration had no effect on the extinction rate of females. But when testosterone propionate was administered to castrated or intact females, they had a slow, malelike extinction rate. Thus, sexual dimorphism in the extinction rate of a conditioned taste aversion seems to be due to the activational effects of testosterone.}, } @article {pmid996153, year = {1976}, author = {Aleksanyan, ZA and Buresová, O and Bures, J}, title = {Modification of unit responses to gustatory stimuli by conditioned taste aversion in rats.}, journal = {Physiology & behavior}, volume = {17}, number = {2}, pages = {173-179}, doi = {10.1016/0031-9384(76)90060-3}, pmid = {996153}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Classical/*physiology ; Evoked Potentials ; Hypothalamus/*physiology ; Lithium/poisoning ; Neural Inhibition ; Rats ; Saccharin ; Taste/*physiology ; Thalamus/physiology ; }, } @article {pmid965528, year = {1976}, author = {Riley, AL and Jacobs, WJ and LoLordo, VM}, title = {Drug exposure and the acquisition and retention of a conditioned taste aversion.}, journal = {Journal of comparative and physiological psychology}, volume = {90}, number = {8}, pages = {799-807}, doi = {10.1037/h0077251}, pmid = {965528}, issn = {0021-9940}, mesh = {Animals ; Avoidance Learning/*drug effects ; *Conditioning, Classical/*drug effects ; Conditioning, Operant/drug effects ; Drinking Behavior/drug effects ; Drug Tolerance ; Female ; Injections, Intraperitoneal ; Lithium/*pharmacology/poisoning ; Rats ; Retention, Psychology/drug effects ; Saccharin ; Taste/*drug effects ; Time Factors ; Water ; }, abstract = {Two experiments examined the effects of preexposure and postexposure to a drug on the acquisition and retention of a conditioned taste aversion induced by that drug. Experiment 1 demonstrated that although drug preexposure attenuated a subsequent conditioned aversion, repeated taste-drug pairings reversed the initial attenuation effect and resulted in nearly complete avoidance of consumption. Experiment 2, however, demonstrated that drug postexposure did not alter a previously established conditioned aversion, although the postexposure experiences were effective in attenuating a conditioned aversion to a second novel solution. It was suggested that conditioned aversions are mediated by ACTH and that preexposure to a drug results in tolerance to that drug, yielding a smaller ACTH response and thereby a weaker aversion.}, } @article {pmid825264, year = {1976}, author = {Soubrié, P and Simon, P and Boissier, JR}, title = {[Amnesia induced in rats by benzodiazepines in a non-painful situation].}, journal = {Comptes rendus hebdomadaires des seances de l'Academie des sciences. Serie D: Sciences naturelles}, volume = {283}, number = {2}, pages = {203-205}, pmid = {825264}, mesh = {Amnesia/*chemically induced ; Animals ; Avoidance Learning/drug effects ; *Benzodiazepines/pharmacology ; Feeding Behavior/drug effects ; Humans ; Male ; Rats ; }, abstract = {During their first exposure to a non-familiar situation, food deprived rats eat only for a short time. During their second exposure, the rats eat for a longer time. Rats treated with benzodiazepines before their first exposure showed no enhanced food intake during the second exposure. This effect did not seem related to an acquired taste aversion but more likely could be explained by an impaired retention of the first experience.}, } @article {pmid950393, year = {1976}, author = {Krane, RV and Sinnamon, HM and Thomas, GJ}, title = {Conditioned taste aversions and neophobia in rats with hippocampal lesions.}, journal = {Journal of comparative and physiological psychology}, volume = {90}, number = {7}, pages = {680-693}, doi = {10.1037/h0077236}, pmid = {950393}, issn = {0021-9940}, mesh = {Animals ; Apomorphine/poisoning ; Association Learning/physiology ; Avoidance Learning/*physiology ; *Awareness ; *Cognition ; Conditioning, Classical/*physiology ; Drinking Behavior/physiology ; Extinction, Psychological ; Hippocampus/*physiology ; Male ; Memory/physiology ; Rats ; Reinforcement, Psychology ; Sodium Chloride ; Taste/*physiology ; Time Factors ; }, abstract = {In the first experiment extensive hippocampal lesions retarded, but did not prohibit, the conditioning of a strong taste aversion to physiological saline (the conditioned stimulus; CS) when illness (the unconditioned stimulus; UCS) was induced by injecting rats with apomorphine 15 min following ingestion of the saline. In the second experiment hippocampal lesions reduced the aversiveness of novelty in a drinking fluid for the thirsty rat. It was suggested that the mild impairment of taste aversion learning in the rats with hippocampal lesions was not the result of destruction of mnemonic mechanisms that serve to span the long CS-UCS interval but rather that the reduced intensity of the aversion resulted from a lesion-altered neophobic disposition that weakened the saliency of the novel flavor CS.}, } @article {pmid950392, year = {1976}, author = {Lorden, JF}, title = {Effects of lesions of the gustatory necortex on taste aversion learning in the rat.}, journal = {Journal of comparative and physiological psychology}, volume = {90}, number = {7}, pages = {665-679}, doi = {10.1037/h0077237}, pmid = {950392}, issn = {0021-9940}, mesh = {Animals ; Association Learning/physiology ; Avoidance Learning/*physiology ; Cerebral Cortex/*physiology ; Cyclophosphamide/poisoning ; Discrimination, Psychological ; Drinking Behavior/physiology ; Food Preferences ; Hydrochloric Acid ; Male ; Osmolar Concentration ; Quinine ; Rats ; Sodium Chloride ; Sucrose ; Taste/*physiology ; Taste Threshold/physiology ; Visual Cortex/physiology ; }, abstract = {Normal rats and rats with lesions of the gustatory neocortex (GN) were compared for their ability to learn aversions to taste cues paired with toxicosis. When the taste presentation was followed immediately by toxicosis, normal rats and rats with lesions of the posterior (visual) neocortex learned aversions to sucrose, sodium chloride, quinine hydrochloride, and hydrochloric acid solutions. Rats with GN lesions learned aversions to all solutions except sucrose. In preference tests, all solutions were shown to be discriminable from water by both normal rats and rats with GN lesions. Under conditions in which a 6-hr delay separated taste presentation and toxicosis, normal rats again learned specific aversions to all four solutions, but rats with GN lesions failed to learn specific aversions to sucrose, sodium chloride, and hydrochloric acid solutions. It was shown that the ability of rats with GN lesions to learn aversions to sucrose and quinine depended on stimulus concentration; and it was proposed that the data could be accounted for by postulating a change in the threshold for taste-illness associations following GN lesions.}, } @article {pmid941632, year = {1976}, author = {Buresová, O}, title = {Differential role of the cerebral cortex and subcortical centres in the acquisition and extinction of conditioned taste aversion.}, journal = {Activitas nervosa superior}, volume = {18}, number = {1-2}, pages = {118-119}, pmid = {941632}, issn = {0001-7604}, mesh = {Animals ; Avoidance Learning/*physiology ; Brain/*physiology ; Cerebral Cortex/physiology ; Conditioning, Classical ; Cortical Spreading Depression ; Rats ; Taste ; }, } @article {pmid183654, year = {1976}, author = {Kendler, K and Hennessy, JW and Smotherman, WP and Levine, S}, title = {An ACTH effect on recovery from conditioned taste aversion.}, journal = {Behavioral biology}, volume = {17}, number = {2}, pages = {225-229}, doi = {10.1016/s0091-6773(76)90512-5}, pmid = {183654}, issn = {0091-6773}, mesh = {Adrenocorticotropic Hormone/*pharmacology/physiology ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Psychological/*drug effects ; Extinction, Psychological/*drug effects ; Food Preferences/drug effects ; Lithium/poisoning ; Male ; Milk ; Rats ; Taste/*drug effects ; Time Factors ; }, } @article {pmid977820, year = {1976}, author = {Rusiniak, KW and Gracia, J and Hankins, WG}, title = {Bait shyness: avoidance of the taste without escape from the illness in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {90}, number = {5}, pages = {460-467}, doi = {10.1037/h0077217}, pmid = {977820}, issn = {0021-9940}, mesh = {Administration, Oral ; Animals ; *Avoidance Learning ; Conditioning, Operant ; Cues ; Discrimination, Psychological ; *Drinking Behavior ; Habituation, Psychophysiologic ; Intubation, Gastrointestinal ; Lithium/administration & dosage/poisoning ; Male ; Rats ; Reaction Time ; Saccharin/pharmacology ; Sodium Chloride/administration & dosage ; *Taste ; }, abstract = {Thirsty rats habituated to drinking .12 M sodium chloride accepted .12 M lithium chloride for 5 min on the first trial but stopped short of their sodium baseline. With repeated trials they reduced consumption of the toxin by either (a) detecting subtle oral (conditioned stimulus, CS) differences, thus avoiding toxicosis (unconditioned stimulus, US) or (b) detecting earlier signs of malaise (US), thus escaping further distress. When both solutions were masked with saccharin, the discrimination was more difficult but still possible. When both solutions were mixed in a solution masking all four taste qualities, the discrimination was severely disrupted. When oral sensors were bypassed with nasopharyngeal tubes, intragastric pumping rats were unable to use postingestional cues to escape, even though such cues were proximal to the ultimate malaise. Oral cues at the distal end of the consummatory chain were extremely effective.}, } @article {pmid966770, year = {1976}, author = {Davison, C and Corwin, G and McGowan, T}, title = {Alcohol-induced taste aversion in golden hamsters.}, journal = {Journal of studies on alcohol}, volume = {37}, number = {5}, pages = {606-610}, doi = {10.15288/jsa.1976.37.606}, pmid = {966770}, issn = {0096-882X}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant ; Cricetinae ; Dose-Response Relationship, Drug ; Drinking Behavior/*drug effects ; Ethanol/administration & dosage/*pharmacology ; Extinction, Psychological ; Injections, Intraperitoneal ; Male ; Saccharin ; Taste/*drug effects ; Time Factors ; }, abstract = {Multiple injections of alcohol were effective in producing substantial aversions to saccharin-flavored water in golden hamsters. A dose of 1.76 g of alcohol per kg produced a long-lasting aversion, whereas aversion produced by injections of 1.17 g per kg extinguished rapidly.}, } @article {pmid964449, year = {1976}, author = {Brown, RT and Stewart, RI and Hall, TL}, title = {Extinction of a taste aversion in the absence of the consummatory response.}, journal = {Animal learning & behavior}, volume = {4}, number = {2}, pages = {213-216}, pmid = {964449}, issn = {0090-4996}, mesh = {Administration, Oral ; Animals ; *Avoidance Learning ; *Extinction, Psychological ; Injections, Intravenous ; Lithium/poisoning ; Male ; Rats ; Saccharin/*administration & dosage ; *Taste ; }, } @article {pmid964443, year = {1976}, author = {Chambers, KC and Sengstake, CB}, title = {Sexually dimorphic extinction of a conditioned taste aversion in rats.}, journal = {Animal learning & behavior}, volume = {4}, number = {2}, pages = {181-185}, pmid = {964443}, issn = {0090-4996}, mesh = {Animals ; *Avoidance Learning ; Cannabis/poisoning ; *Conditioning, Operant ; *Extinction, Psychological ; Female ; Lithium/poisoning ; Male ; Rats ; Sex Factors ; *Taste ; *Water Deprivation ; }, } @article {pmid951441, year = {1976}, author = {Goudie, AJ and Thornton, EW and Wheller, TJ}, title = {Drug pretreatment effects in drug induced taste aversions: effects of dose and duration of pretreatment.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {4}, number = {5}, pages = {629-633}, doi = {10.1016/0091-3057(76)90210-0}, pmid = {951441}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Dose-Response Relationship, Drug ; Drinking Behavior/*drug effects ; Female ; Fenfluramine/pharmacology ; Methamphetamine/*pharmacology ; Morphine/pharmacology ; Rats ; Saccharin ; Taste/*drug effects ; Time Factors ; Water Deprivation ; p-Chloroamphetamine/pharmacology ; }, abstract = {The effectiveness of a dose of 3.0 mg/kg methamphetamine in inducing a conditioned taste aversion to saccharin was found to be reduced by chronic pretreatment with the same dose of the drug. The degree of attenuation of the aversive properties of the drug was found to be directly proportional to the duration of pretreatment, a pretreatment regime of 9 or more daily injections completely abolishing the aversive properties of the drug. However, such a regime was only slightly effective in attenuating the aversive properties of a higher dose of methamphetamine (10 mg/kg) and failed to attenuate the aversive properties of a number of other drugs (p-chloramphetamine at 5.0 mg/kg, fenfluramine at 5.0 mg/kg and morphine at 20 mg/kg). Interpretations of these data are considered and it is suggested that the most parsimonious explanation of the effectiveness of chronic drug pretreatment in attenuating the aversive properties of a drug is that the effect is due to the development of tolerance to the drug administered.}, } @article {pmid781692, year = {1976}, author = {Grupp, LA and Linseman, MA and Cappell, H}, title = {Effects of amygdala lesions on taste aversions produced by amphetamine and LiCl.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {4}, number = {5}, pages = {541-544}, doi = {10.1016/0091-3057(76)90195-7}, pmid = {781692}, issn = {0091-3057}, mesh = {Amygdala/anatomy & histology/*physiology ; Animals ; Conditioning, Operant/drug effects ; Dextroamphetamine/*pharmacology ; Drinking Behavior/drug effects ; Lithium/*pharmacology ; Male ; Rats ; Saccharin/pharmacology ; Stereotaxic Techniques ; Taste/*drug effects ; }, abstract = {Rats which sustained bilateral damage to the amygdala were treated with one of two diversely acting agents (either d-amphetamine sulphate 4 mg/kg, or lithium chloride 0.24 M) in a taste aversion paradigm. Both groups of animals showed an attenuation of the aversion on the first test day after the initial pairing with the drug thus demonstrating that this effect of the lesion was not UCS specific. The implication of these findings for the hypothesis concerning the role of the amygdala in taste aversion conditioning is discussed.}, } @article {pmid7799, year = {1976}, author = {Rigter, H and Popping, A}, title = {Hormonal influences of the extinction of conditioned taste aversion.}, journal = {Psychopharmacologia}, volume = {46}, number = {3}, pages = {255-261}, pmid = {7799}, mesh = {Adrenocorticotropic Hormone/*analogs & derivatives/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Drinking Behavior/drug effects ; Extinction, Psychological/*drug effects ; MSH Release-Inhibiting Hormone/*pharmacology ; Male ; Melanocyte-Stimulating Hormones/*pharmacology ; Peptides/pharmacology ; Rats ; Taste ; }, abstract = {Conditioned taste aversion for a 5% glucose solution (sugar water) was induced in rats by an i.p. injection of LiCl 30 min after the first presentation of sugar water. Extinction of conditioned taste aversion was measured either in the forced-drinking test or in the preference-drinking test. In the forced-drinking test sugar water was the only fluid presented to the animals during extinction sessions. In the preference-drinking test the animals had the choice of tap water or sugar water. The rate of extinction was much slower in the preference test. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 7d Phe, and alpha-MSH delayed extinction in the preference test but not extinction in the forced-drinking test. ACTH 11-24 was without any effect. MSH-release inhibiting factor (MIF) facilitated extinction in the forced-drinking test but did not alter extinction in the preference test. The peptides did not affect intake of tap water of preference of sugar water over tap water by control rats.}, } @article {pmid183642, year = {1976}, author = {Hennessy, JW and Smotherman, WP and Levine, S}, title = {Conditioned taste aversion and the pituitary-adrenal system.}, journal = {Behavioral biology}, volume = {16}, number = {4}, pages = {413-424}, doi = {10.1016/s0091-6773(76)91571-6}, pmid = {183642}, issn = {0091-6773}, mesh = {Adrenocorticotropic Hormone/antagonists & inhibitors/pharmacology/physiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Operant/*physiology ; Corticosterone/blood ; Dexamethasone/pharmacology ; Extinction, Psychological/drug effects/physiology ; Lithium/poisoning ; Male ; Pituitary-Adrenal System/drug effects/*physiology ; Rats ; Taste/*physiology ; Time Factors ; }, } @article {pmid1275854, year = {1976}, author = {Braun, JJ and Rosenthal, B}, title = {Relative salience of saccharin and quinine in long-delay taste aversion learning.}, journal = {Behavioral biology}, volume = {16}, number = {3}, pages = {341-352}, doi = {10.1016/s0091-6773(76)91473-5}, pmid = {1275854}, issn = {0091-6773}, mesh = {Animals ; Avoidance Learning/*drug effects ; Conditioning, Classical/*drug effects ; Cues ; Cyclophosphamide/poisoning ; Dose-Response Relationship, Drug ; Drinking Behavior/drug effects ; Extinction, Psychological ; Male ; Quinine/*pharmacology ; Rats ; Saccharin/*pharmacology ; Time Factors ; }, } @article {pmid4668, year = {1976}, author = {Eckardt, MJ}, title = {Alcohol-induced conditioned taste aversion in rats. Effect of concentration and prior exposure to alcohol.}, journal = {Journal of studies on alcohol}, volume = {37}, number = {3}, pages = {334-346}, doi = {10.15288/jsa.1976.37.334}, pmid = {4668}, issn = {0096-882X}, mesh = {*Alcohol Drinking ; Animals ; Avoidance Learning/*drug effects ; Awareness ; Conditioning, Classical ; Ethanol/blood/*pharmacology ; Female ; Food Preferences ; Osmolar Concentration ; Rats ; Taste/*drug effects ; }, abstract = {The effects of prior opportunities to drink alcohol solutions on the subsequent production of conditioned taste aversion by the oral ingestion of alcohol were evaluated. The consumption of 5 and 7% alcohol solutions produced conditioned aversion; the consumption of 3% alcohol solution did not result in aversion. Prior exposure to alcohol did not alter the extent of the aversion.}, } @article {pmid1259677, year = {1976}, author = {Deutsch, JA and Molina, F and Puerto, A}, title = {Conditioned taste aversion caused by palatable nontoxic nutrients.}, journal = {Behavioral biology}, volume = {16}, number = {2}, pages = {161-174}, doi = {10.1016/s0091-6773(76)91268-2}, pmid = {1259677}, issn = {0091-6773}, mesh = {Administration, Oral ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Discrimination Learning/drug effects ; Drinking Behavior/*drug effects ; Duodenum ; Environment ; Flavoring Agents/administration & dosage ; Generalization, Psychological ; Glucose/administration & dosage/pharmacology ; Intubation, Gastrointestinal ; Male ; Rats ; Saliva/physiology ; Sesame Oil/*administration & dosage/pharmacology ; Stomach ; *Taste ; Time Factors ; }, } @article {pmid944453, year = {1976}, author = {Tucker, A and Gibbs, M}, title = {Cycloheximide-induced amnesia for taste aversion memory in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {4}, number = {2}, pages = {181-184}, doi = {10.1016/0091-3057(76)90012-5}, pmid = {944453}, issn = {0091-3057}, mesh = {Amnesia/chemically induced/*physiopathology ; Animals ; Conditioning, Classical/drug effects ; Cycloheximide/*pharmacology ; Humans ; Male ; Memory/*drug effects ; Rats ; Saccharin ; *Taste ; }, abstract = {Male hooded rats were conditioned in one trial to avoid saccharin by pairing saccharin drinking with an intragastric injection of LiC1. A 24 hr water-saccharin preference test showed that conditioned rats exhibited a very low preference for saccharin whereas rats injected intraventricularly with cycloheximide (CXM, 400 mug) 5, 7, or 9 hr before training exhibited a greatly increased saccharin preference which differed significantly from NaC1 injected controls. This 24 hr amnesia was found to be dependent upon the time of administration of CXM, since injection at 1, 3 or 17 hr before training did not confer amnesia. The nature of the task, a control measure and a control experiment indicate that the CXM-induced change in saccharin preference at 24 hr is not due to a CXM-induced aversion, nor a loss in drinking ability nor an inability to retrieve information whilst under the influence of CXM.}, } @article {pmid1208761, year = {1975}, author = {Eckardt, MJ}, title = {The role of orosensory stimuli from ethanol and blood-alcohol levels in producing conditioned taste aversion in the rat.}, journal = {Psychopharmacologia}, volume = {44}, number = {3}, pages = {267-271}, pmid = {1208761}, mesh = {Alcohol Drinking ; Animals ; *Avoidance Learning ; *Conditioning, Psychological ; Ethanol/blood/*pharmacology ; Female ; Rats ; Reinforcement Schedule ; *Taste ; }, abstract = {A taste-aversion paradigm was used to demonstrate that aversive consequences accompany the rapid oral ingestion of 5% (v/v) ethanol solutions. The learned taste aversion resulted from five 10-min self-administrations of alcohol mixed with an originally preferred flavor at a dosage of 1.69 g alcohol/kg body weight/day. In contrast, when the consumption of the alcohol solution was distributed throughout the day, a conditioned aversion was not obtained. This outcome was observed even though the distributed drinking animals were exposed to more orosensory stimuli and ingested more g/kg than the 10-min animals. The observation that those animals that drank their daily fluid in 10 min demonstrated higher peak blood-alcohol levels than the distributed animals supports the conclusion that a centrally mediated aversive state of inebriation must be present to produce a conditioned aversion.}, } @article {pmid52194, year = {1975}, author = {Sessions, GR}, title = {Letter: Histamine and radiation-induced taste aversion conditioning.}, journal = {Science (New York, N.Y.)}, volume = {190}, number = {4212}, pages = {402-403}, doi = {10.1126/science.52194}, pmid = {52194}, issn = {0036-8075}, mesh = {Animals ; Avoidance Learning/*physiology ; Conditioning, Psychological/*physiology ; *Histamine Release ; Radiation ; Rats ; Research Design ; Taste/*physiology ; X-Rays ; }, } @article {pmid1184801, year = {1975}, author = {Liebling, DS and Eisner, JD and Gibbs, J and Smith, GP}, title = {Intestinal satiety in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {89}, number = {8}, pages = {955-965}, doi = {10.1037/h0077163}, pmid = {1184801}, issn = {0021-9940}, mesh = {Animals ; Cholecystokinin/metabolism/pharmacology ; Duodenum/metabolism/*physiology ; Feeding Behavior/drug effects ; Male ; Rats ; Satiation/*physiology ; Time Factors ; }, abstract = {Infusion of liquid food into the duodenum inhibited sham feeding. The inhibition of sham feeding reflected satiety because the duodenal infusion elicited the complete behavioral sequence characteristic of satiety. The chemical and/or colligative load that the infusion imposed on the intestine appeared to be the adequate stimulus for satiety. Duodenal infusions that inhibit sham feeding and elicit satiety are not aversive because they will not function as the unconditioned stimulus for the formation of a conditioned taste aversion for saccharin. We call the satiety elicited by the infusion of food into the duodenum "intestinal satiety." This emphasizes our belief that satiety is a reflex that can be elicited by the activation of receptors in the wall of the intestine. It is known that the activation of some intestinal receptors releases the hormone cholecystokinin (CCK). Since CCK mimics a duodenal infusion by inhibiting sham feeding and eliciting the complete behavioral sequence of satiety, we suggest, but do not prove, that CCK mediates intestinal satiety in the rat.}, } @article {pmid172176, year = {1975}, author = {Righter, H}, title = {Proceedings: Peptide hormones and the extinction of conditioned taste aversion.}, journal = {British journal of pharmacology}, volume = {55}, number = {2}, pages = {270P-271P}, pmid = {172176}, issn = {0007-1188}, mesh = {Adrenocorticotropic Hormone/*analogs & derivatives/pharmacology ; Amino Acid Sequence ; Animals ; Conditioning, Psychological/*drug effects ; Extinction, Psychological/*drug effects ; Rats ; Structure-Activity Relationship ; Taste/*drug effects ; }, } @article {pmid1241535, year = {1975}, author = {Kalat, JW}, title = {Taste-aversion learning in infant guinea pigs.}, journal = {Developmental psychobiology}, volume = {8}, number = {5}, pages = {383-387}, doi = {10.1002/dev.420080502}, pmid = {1241535}, issn = {0012-1630}, mesh = {Adaptation, Biological ; Animals ; Animals, Newborn/*growth & development ; *Avoidance Learning ; Extinction, Psychological ; Female ; Guinea Pigs ; Humans ; Lithium/poisoning ; Male ; Phobic Disorders ; Sucrose ; *Taste ; }, abstract = {Infant guinea pigs were hand-fed a 10% sucrose solution and poisoned after delays of 0 min, 30 min, or 24+ hr. Subjects in the first 2 groups showed significant sucrose aversions when tested more than a month later. No significant difference existed between the 0- and 30-min groups; no deficiency in this type of learning was evident even in neonates. All 3 groups showed a lower sucrose preference if first exposed at ages 0-6 days than at 7-11 days. Evidently exposure to sucrose at the earlier ages was less effective in reducing later neophobia to sucrose; although the youngest animals had no evident deficiency in learning aversions, they may have been deficient in learning "safety".}, } @article {pmid1208640, year = {1975}, author = {Goudie, AJ and Taylor, M and Atherton, H}, title = {Effects of prior drug experience on the establishment of taste aversions in rats.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {3}, number = {5}, pages = {947-952}, doi = {10.1016/0091-3057(75)90135-5}, pmid = {1208640}, issn = {0091-3057}, mesh = {Animals ; Avoidance Learning/*drug effects ; Dextroamphetamine/pharmacology ; Drinking Behavior/drug effects ; Fenfluramine/pharmacology ; In Vitro Techniques ; Male ; *Set, Psychology ; Taste/*drug effects ; Time Factors ; }, abstract = {Groups of food and water deprived rats were injected with either 2 mg/kg d-amphetamine, 9mg/kg dl-fenfluramine or isotonic saline immediately after the first presentation of a 25 percent solution of condensed milk for a 30 min period. When animals were tested for aversion to condensed milk 8 days later both drugs were found to cause a highly significant decrease in total amounts drunk; in contrast saline injected animals showed significant increases in the amount drunk. However, it was found that the development of a conditioned taste aversion could be markedly attenuated or abolished altogether by providing groups of animals with experience of both drugs prior to aversion establishment, and that the degree of attenuation of aversion was proportional to the amount of prior experience. Novelty of drug administered would seem to be a critical variable in the establishment of taste aversions. The results are discussed with reference to some of the paradoxical aspects of drug induced taste aversions.}, } @article {pmid1239022, year = {1975}, author = {Winn, FJ and Kent, MA and Libkuman, TM}, title = {Learned taste aversion induced by cortical spreading depression.}, journal = {Physiology & behavior}, volume = {15}, number = {1}, pages = {21-24}, doi = {10.1016/0031-9384(75)90273-5}, pmid = {1239022}, issn = {0031-9384}, mesh = {Amnesia, Retrograde/etiology ; Animals ; Avoidance Learning/drug effects/*physiology ; Conditioning, Classical/physiology ; *Cortical Spreading Depression ; Dose-Response Relationship, Drug ; Drinking Behavior/physiology ; Functional Laterality ; Humans ; Male ; Potassium Chloride/pharmacology ; Rats ; Sucrose ; Taste/*physiology ; Water Deprivation ; }, abstract = {Male albino rats were cannulated and placed on a 24 hr water deprivation schedule. The animals were allowed 10 min access to water in a large animal cage for 5 days. On the sixth day of deprivation the animals were randomly divided into 6 groups and given either 12 percent KCl, 25 percent KCl, or Ringers solution applied unilaterally or bilaterally to the cortex immediately after access to 8 percent sucrose. On the seventh day of deprivation, each rat was placed in a two-choice situation with the sucrose solution and water. Only the unilateral and bilateral 12 percent KCl groups developed an aversion to the sucrose. These results indicate that CSD has aversive as well as amnesic properties, there exists a gradient of amnesia, dependent on concentration, and that the cortex is not necessary for learning a taste aversion.}, } @article {pmid1162023, year = {1975}, author = {Ader, R and Cohen, N}, title = {Behaviorally conditioned immunosuppression.}, journal = {Psychosomatic medicine}, volume = {37}, number = {4}, pages = {333-340}, doi = {10.1097/00006842-197507000-00007}, pmid = {1162023}, issn = {0033-3174}, mesh = {Animals ; Antibody Formation ; Association ; *Conditioning, Classical ; Cyclophosphamide/administration & dosage/pharmacology ; Erythrocytes ; Hemagglutination Tests ; *Immunosuppression Therapy ; Injections, Intraperitoneal ; Lithium/pharmacology ; Nausea/chemically induced ; Placebos ; Rats ; Saccharin/pharmacology ; Sheep/immunology ; *Taste ; Time Factors ; }, abstract = {An illness-induced taste aversion was conditioned in rats by pairing saccharin with cyclophosphamide, an immunosuppressive agent. Three days after conditioning, all animals were injected with sheep erythrocytes. Hemagglutinating antibody titers measured 6 days after antigen administration were high in placebo-treated rats. High titers were also observed in nonconditioned animals and in conditioned animals that were nor subsequently exposed to saccharin. No agglutinating antibody was detected in conditioned animals treated with cyclophosphamide at the time of antigen administration. Conditioned animals exposed to saccharin at the time of or following the injection of antigen were significantly immunosuppressed. An illness-induced taste aversion was also conditioned using LiCl, a nonimmunosuppressive agent. In this instance, however, there was no attenuation of hemagglutinating antibody titers in response to injection with antigen.}, } @article {pmid45810, year = {1975}, author = {Cannon, DS and Berman, RF and Baker, TB and Atkins, CA}, title = {Effect of preconditioning unconditioned stimulus experience on learned taste aversions.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {1}, number = {3}, pages = {270-284}, doi = {10.1037//0097-7403.1.3.270}, pmid = {45810}, issn = {0097-7403}, mesh = {Animals ; *Avoidance Learning ; *Conditioning, Operant ; Ethanol ; Lithium ; Male ; Rats ; *Taste ; Time Factors ; }, abstract = {One taste-aversion study using male Long-Evans rats in which ethanol was the unconditioned stimulus (UCS) and six studies in which lithium chloride (LiCl) was the UCS demonstrate that (a) exposure to the UCS prior to conditioning retards subsequent acquisition of learned taste aversions; (b) a single preconditioning UCS exposure is sufficient to attenuate conditioning; (c) the preconditioning UCS exposure must occur within a limited period prior to conditioning to attenuate learning; (d) repeated conditioning trials will override the effect of prior exposure to the UCS; (e) tolerance to the UCS is not a necessary condition for the attenuation effect to occur; (f) pairing the preconditioning UCS with a novel flavor other than the CS does not remove the preexposure effect, although it may reduce its magnitude; and (g) the degree of disruption is a positive function of preconditioning UCS dosage and an inverse function of conditioning UCS dosage.}, } @article {pmid1187836, year = {1975}, author = {Domjan, M}, title = {The nature of the thirst stimulus: a factor in conditioned taste-aversion behavior.}, journal = {Physiology & behavior}, volume = {14}, number = {6}, pages = {809-813}, doi = {10.1016/0031-9384(75)90074-8}, pmid = {1187836}, issn = {0031-9384}, mesh = {Animals ; Avoidance Learning/physiology ; Conditioning, Operant/*physiology ; Dehydration ; Drinking Behavior/*physiology ; Female ; Male ; Motivation ; Rats ; Taste/physiology ; Thirst/*physiology ; Water Deprivation ; }, abstract = {Independent groups of rats were compared drinking in response to either water deprivation or osmotic thirst induced by intraperitoneal injections of hypertonic saline. When water or a palatable saccharin solution served as the drinking fluid, deprivation and osmotic thirst produced comparable fluid intakes. In contrast, when a saccharin solution previously associated with the aversive effects of lithium served as the drinking fluid, animals injected with hypertonic saline drank substantially less than water deprived animals. Experiment 2 indicated that this hyperreactivity to a conditioned aversive flavor in animals suffering from osmotic thirst was due to the reduced palatability of the saccharin flavor rather than the previous experience with lithium. Experiment 3 showed that the effect also could not be attributed to differential taste-aversion learning, handling, food deprivation or weight loss before the test sessions. The phenomenon is discussed in terms of various differences between thirst induced by water deprivation and thirst induced by acute cellular dehydration.}, } @article {pmid1176658, year = {1975}, author = {Horowitz, GP and Whitney, G}, title = {Alcohol-induced conditioned aversion: genotypie specificity in mice (Mus musculus).}, journal = {Journal of comparative and physiological psychology}, volume = {89}, number = {4}, pages = {340-346}, doi = {10.1037/h0076803}, pmid = {1176658}, issn = {0021-9940}, mesh = {Acetaldehyde/metabolism/poisoning ; *Alcohol Drinking ; Aldehyde Oxidoreductases/metabolism ; Animals ; Avoidance Learning/*drug effects ; Conditioning, Operant/*drug effects ; Dose-Response Relationship, Drug ; Ethanol/metabolism/*pharmacology ; *Genotype ; Liver/enzymology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Saccharin ; Species Specificity ; }, abstract = {Acetaldehyde poisoning from ethanol ingestion may lead to aversion to ethanol among DBA mice but not among C57s, since the former are relatively deficient in aldehyde dehydrogenase activity. The present study paired ingestion of saccharin with a single intraperitoneal injection of one of four concentrations of ethanol for DBA/2J and C57BL/6J mice. Subjects were then given a two-bottle saccharin versus water preference test for 10 days. Substitution of saccharin for the taste of ethanol resulted in avoidance of saccharin with all concentrations of ethanol by DBAs but not by C57s, consistent with the conditioned taste aversion paradigm as a model for genetically mediated ethanol avoidance.}, } @article {pmid1139290, year = {1975}, author = {Smith, GP and Levin, BE and Ervin, GN}, title = {Loss of active avoidance of responding after lateral hypothalamic injections of 6-hydroxydopamine.}, journal = {Brain research}, volume = {88}, number = {3}, pages = {483-498}, doi = {10.1016/0006-8993(75)90659-9}, pmid = {1139290}, issn = {0006-8993}, mesh = {Amphetamine/pharmacology ; Animals ; Avoidance Learning/*drug effects ; Brain Mapping ; Conditioning, Classical/drug effects ; Dihydroxyphenylalanine/pharmacology ; Escape Reaction/drug effects ; Hydroxydopamines/administration & dosage/*pharmacology ; Hypothalamus/*drug effects/pathology/physiology ; Injections ; Male ; Rats ; Taste ; }, abstract = {After injections of 6-hydroxydopamine (6-OHDA) along the medial forebrain bundle in the lateral hypothalamus, rats failed to acquire a one-way active avoidance response or failed to perform a previously acquired active avoidance response. Such rats, however, acquired a passive avoidance response and a conditioned taste aversion normally. Thus the effect of lateral hypothalamic injections of 6-OHDA was not a total loss of the capacity to acquire or perform conditioned responses, but was a failure to initiate forward movement in the presence of a conditional stimulus. Most of these rats could initiate a similar forward movement to escape from the unconditioned stimulus (foot shock). Failure to acquire or perform the active avoidance response was correlated with the loss of hypothalamic, striatal and forebrain catecholamines produced by lateral hypothalamic 6-OHDA injections. Identical injections of 6-ohda placed along the medial hypothalamus produced a similar loss of regional catecholamines, but medial 6-OHDA injections did not affect active avoidance responding. We interpret this dissociation between loss of catecholamines and the capacity for active avoidance responding to mean that medial 6-OHDA injections did not damage the same catecholaminergic terminal fields as lateral 6-OHDA injections and that the integrity of the terminal fields damaged by lateral 6-OHDA injections is necessary for active avoidance responding.}, } @article {pmid1141823, year = {1975}, author = {Best, MR}, title = {Conditioned and latent inhibition in taste-aversion learning: clarifying the role of learned safety.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {1}, number = {2}, pages = {97-113}, doi = {10.1037//0097-7403.1.2.97}, pmid = {1141823}, issn = {0097-7403}, mesh = {Animals ; Apomorphine/poisoning ; *Avoidance Learning ; Caseins ; Choice Behavior ; *Conditioning, Classical ; Drinking Behavior ; *Inhibition, Psychological ; Male ; Rats ; Saccharin/poisoning ; Sodium Chloride ; *Taste ; }, abstract = {Experiments 1-3 investigated the applicability of the classical conditioning concept of conditioned inhibition to taste-aversion learning. Rats made ill after drinking saccharin and subsequently administered a "safe" exposure to saline (or casein hydrolysate) evidenced an enhanced preference for the safe fluid (relative to either a third, slightly aversive, solution or to water) when compared to controls in which saccharin was not previously poisoned. Such active condition inhibition was significantly reduced in Experiment 4 when two safe exposures to saline preceded saccharin-illness pairings. These results indicate that conditioned inhibition can be established in a taste-aversion procedure and that a latent inhibition manipulation reduces the ability of a taste to become a signal for safety. Implications of these findings for the learned safety theory of taste-aversion learning and the relevance to bait-shyness of principles established within the classical conditioning paradigm are considered.}, } @article {pmid1144480, year = {1975}, author = {Millner, JR and Palfai, T}, title = {Metrazol impairs conditioned aversion produced by LiCl: a time dependent effect.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {3}, number = {2}, pages = {201-204}, doi = {10.1016/0091-3057(75)90149-5}, pmid = {1144480}, issn = {0091-3057}, mesh = {Animals ; *Association ; Avoidance Learning/*drug effects ; Conditioning, Classical/drug effects ; Conditioning, Psychological/*drug effects ; Drug Interactions ; Feeding Behavior/drug effects ; Lithium/administration & dosage/*poisoning ; Male ; Memory ; Pentylenetetrazole/administration & dosage/*pharmacology ; Rats ; Saccharin ; Seizures/chemically induced ; Taste/*drug effects ; Time Factors ; }, abstract = {The effects of 40 mg/kg Metrazol on a conditioned saccharin aversion produced by LiCl were studied in two experiments. In Experiment 1, it was found that Metrazol administered 10 min before or after LiCl did not impair conditioned aversion to saccharin. In Experiment 2, Metrazol was given 2 min before, 9 or 3 min after the administration of LiCl. Under these conditions, impairment did occur. It was concluded that Metrazol may impair conditioned taste aversion in a time-dependent manner. The present findings are discussed in terms of their relationship to ECS as an interfering agent and retroactive and proactive effects on the CS and/or the UCS.}, } @article {pmid1144479, year = {1975}, author = {Vogel, JR and Nathan, BA}, title = {Learned taste aversions induced by hypnotic drugs.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {3}, number = {2}, pages = {189-194}, doi = {10.1016/0091-3057(75)90147-1}, pmid = {1144479}, issn = {0091-3057}, mesh = {Animals ; Ataxia/chemically induced ; Avoidance Learning/*drug effects ; Barbiturates/pharmacology ; Chloral Hydrate/pharmacology ; Depression, Chemical ; Ethyl Ethers/pharmacology ; Flurazepam/pharmacology ; Hypnotics and Sedatives/*pharmacology ; Injections ; Male ; Methaqualone/pharmacology ; Motor Activity/drug effects ; Rats ; Reflex/drug effects ; Taste/*drug effects ; }, abstract = {Taste aversions reflect the association of drug-produced noxious interoceptive stimuli with distinctive tastes. In the present experiments, taste aversions to sweetened condensed milk were induced in rats by a wide range of doses of the hypnotic drugs, hexobarbital, amobarbital, chloral hydrate, flurazepam and methaqualone and by anesthetization with ethyl ether. Observation of changes in motor behavior following drug administration could not be used to predict the development of taste aversions. Despite the fact that hypnotic drugs have punishing properties, which these paradox is discussed in terms of procedural differences between taste aversion and self-administration experiments.}, } @article {pmid1120048, year = {1975}, author = {Arthur, JB}, title = {Taste aversion learning is impaired by interpolated amygdaloid stimulation but not by posttraining amygdaloid stimulation.}, journal = {Behavioral biology}, volume = {13}, number = {3}, pages = {369-376}, doi = {10.1016/s0091-6773(75)91430-3}, pmid = {1120048}, issn = {0091-6773}, mesh = {Amygdala/*physiology ; Animals ; *Avoidance Learning ; *Conditioning, Classical ; Corpus Callosum/physiology ; *Drinking ; Electric Stimulation ; Electroshock ; Lithium/poisoning ; Male ; Rats ; Saccharin ; Seizures/etiology ; *Taste ; Time Factors ; }, } @article {pmid1120046, year = {1975}, author = {Kesner, RP and Berman, RF and Burton, B and Hankins, WG}, title = {Effects of electrical stimulation of amygdala upon neophobia and taste aversion.}, journal = {Behavioral biology}, volume = {13}, number = {3}, pages = {349-358}, doi = {10.1016/s0091-6773(75)91402-9}, pmid = {1120046}, issn = {0091-6773}, mesh = {Amygdala/*physiology ; Animals ; Apomorphine/administration & dosage/pharmacology ; Association ; *Avoidance Learning ; Conditioning, Classical ; *Drinking ; Drinking Behavior/drug effects ; *Eating ; Electric Stimulation ; Injections, Intraperitoneal ; Male ; Nausea/chemically induced ; Rats ; Reaction Time ; *Taste ; Time Factors ; }, } @article {pmid1226396, year = {1975}, author = {Kawamura, Y}, title = {Role of sensory factors in chewing and feeding behavior.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {3}, number = {1 Suppl}, pages = {163-173}, pmid = {1226396}, issn = {0091-3057}, mesh = {Animals ; Chorda Tympani Nerve/physiology ; Dogs ; Evoked Potentials ; *Feeding Behavior ; Glossopharyngeal Nerve/physiology ; Hypothalamus/*physiology ; *Mastication ; Models, Biological ; Quinine ; Rats ; Sodium Chloride ; Sucrose ; Tartrates ; *Taste ; }, abstract = {Since feeding behavior has a complex physiological background, in the physiology of feeding behavoir not only the mechanisms in the hypothalamus, but also input and output physiologic factors which stimulate and/or inhibit the central network for feeding and aversion behavior, must be considered. Normal feeding and aversion behavior are accomplished by a series of highly co-ordinated physiological functions involving various parts of the body, and humoral, hormonal, metabolic, and sensory and motor functions for feeding behavior must be well considered from a wider wiew point. For this purpose, morphological, biochemical, and neurophysiological extensive approaches to study the feeding behavior mechanisms are essentially important. In the present paper, neurophysiological network concerning feeding and aversion behavior was under discussion. Particularly, relations between input, central and output factors for these behaviors were considered. As an input factor, a role of the nerve impulses of the chorda tympani and lingual nerves was evaluated. As a central factor, involvement of the neurons in the cortical taste area was discussed, and response patterns of cortical taste neurons to negative and positive taste information was analyzed with regard to taste perception mechanisms. In addition, mechanisms in the posterior hypothalamus for the taste aversion behavior were explained through ablation and recording techniques in the rat; and the neuromuscular mechanisms of chewing, which complete the feeding behavior, were also discussed. Importance of such comprehensive systematic approach to proper understanding of feeding and aversion behaviors was emphasized.}, } @article {pmid1120817, year = {1975}, author = {Buresová, O and Bures, J}, title = {Functional decortication by cortical spreading depression does not prevent forced extinction of conditioned saccharin aversion in rats.}, journal = {Journal of comparative and physiological psychology}, volume = {88}, number = {1}, pages = {47-52}, doi = {10.1037/h0076188}, pmid = {1120817}, issn = {0021-9940}, mesh = {Animals ; *Avoidance Learning/drug effects ; Cerebral Cortex/*physiology ; Chlorides/pharmacology ; *Extinction, Psychological/drug effects ; Lithium/pharmacology ; Memory ; Memory, Short-Term ; Models, Psychological ; Rats ; Saccharin ; *Taste ; Time Factors ; }, abstract = {Conditioned taste aversion established in rats by association of saccharin drinking with subsequent lithium chloride intoxication decreased saccharin intake to 22% of normal consumption. Force-feeding saccharin to intact and functionally decorticate trained rats returned saccharin consumption on the next day to 62% (n equals 18) and 77% (n equals 19), respectively. Over-trained conditioned saccharin aversion was affected by forced extinction in a similar way (saccharin intake increased from 28% to 50% and 63%, respectively). Intact brain rats refused to swallow saccharin during forced feeding. while functionally decorticate animals showed no signs of aversion; but extinction was almost equal in both cases. Application of lithium chloride after forced feeding of saccharin in functionally decorticate rats neither prevented extinction of conditioned taste aversion nor reestablished the aversion habit extinguished earlier with intact brain. It is concluded that acquisition of the conditioned taste aversion requires cortical input to a short-term memory file, whereas decorticate extinction can be induced by subcortical gustatory processing analogous to the mechanism controlling feeding behavior during the preweaning period.}, }