Exteroceptive context in tasteaversion conditioning and extinction: odour, cage, and bottle stimuli

Five experiments investigated the extent to which the exteroceptive context, present on a saccharin aversion conditioning trial with rats, controlled the resulting aversion on one-bottle extinction tests and subsequent preference tests. The presence or absence of the specific odour which had been present on the conditioning trial was found not to influence saccharin intake on extinction tests, whereas the presence of the particular compartment in which, and the bottle from which, the saccharin had been consumed greatly suppressed saccharin intake as compared to the absence of these elements. Preference tests, performed in the respective conditioning contexts, showed extinction to be specific to the compartment + bottle context: groups that had extinguished their saccharin aversion in a context different from the conditioning context, retained their aversion in the conditioning context. No such specificity was found for the odour context. However, in the absence of the taste stimulus during the extinction phase, the odour that had been present on the conditioning trial did control the amount of water consumed, whereas the compartment+bottle context did not. Moreover, on preference tests, groups that had consumed water during extinction in the presence of the odour context, evidenced a lesser saccharin aversion than groups not exposed to the odour. The results are interpreted as demonstrating that rats learn about taste, odour, cage and bottle stimuli on a taste-aversion conditioning trial, and that taste and bottle stimuli seem to be the most salient.     

Conditioned taste aversion learning in leptin-receptor-deficient db/db mice

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.     

Forgetting, preconditioning CS familiarization and taste aversion learning: An animal experiment with implications for alcoholism treatment

The rapid taste aversion acquisition, which typically occurs in many species when ingestion of a novel flavor precedes gastrointestinal distress, is retarded by preconditioning familiarity with the CS flavor. This CS familiarity effect (CSFE) might contraindicate taste aversion approaches to alcoholism treatment since alcoholics are quite accustomed to the tastes of alcoholic beverages. However, many alcoholics do develop strong nausea—induced alcohol aversions under appropriate conditioning parameters. Additionally, the CSFE is attenuated in rats by repeated conditioning trials including discrimination training. The present animal experiment was conducted to determine if the CSFE could additionally be weakened by process of forgetting, i.e. by preconditioning withdrawal of a familiar flavor analogous to an alcoholic's ‘drying out’ before psychotherapeutic intervention. Using saccharin as the CS flavor and cyclophosphamide as the conditioning agent, Sprague-Dawley derived rats acquired no aversions when conditioning was attempted immediately after flavor familiarization. However, significant and equivalent saccharin aversions were observed when conditioning was delayed for either 20 or 100 days after familiarization. These findings imply that the efficiency and cost effectiveness of taste aversion approaches to alcoholism treatment might be enhanced by a pretreatment period of abstinence from alcohol ingestion.     

Context-dependent latent inhibition in taste aversion learning

The effects of taste stimulus preexposure, either in the presence or in the absence of a specific contextual cue consisting of a specific noise-producing bottle, upon the conditioning and testing of conditioned taste aversions to the taste (saccharin) plus context (noisy-bottle) compound stimulus were investigated. Four groups of rats were given preexposure trials (latent inhibition) to either: (1) novel saccharin in novel noisy bottles, (2) novel saccharin in familiar silent bottles, (3) familiar water in novel noisy bottles, (4) familiar water in familiar silent bottles, in six trials. During conditioning, saccharin was presented in the noisy bottles followed by lithium chloride for all the groups. At testing, saccharin was presented in the noisy bottles for both one-bottle and two-bottle tests of aversion. It was indicated that the conditioning decrement produced after both saccharin and noisy bottle preexposure was overwhelmingly greater than any produced after preexposure to the elements. These results, discussed in relation to current theories of latent inhibition and perceptual learning, further underline the overwhelming significance of exteroceptive contextual elements in conditioned taste aversions.     

Taste-mediated potentiation of noningestional stimuli in rats

Holtzman rats drank saccharin in a distinctive environmental chamber prior to lithium-induced toxicosis. This treatment was administered four times. These animals subsequently drank less water or familiar saline in the chamber than animals which received water in the environment during conditioning. In addition, these environmental stimuli blocked the formation of a lithium-mediated coffee aversion more if they were conditioned in the presence of saccharin than if they were conditioned in the presence of water. Such differential blocking provided further evidence that the presence of a taste during conditioning facilitated aversion learning to the environmental chamber.     

Open-Field Foraging: The Influence of Prior Taste-Aversion Conditioning

The Psychological Record - Two experiments evaluating open-field foraging behavior of rats that had received prior taste aversion conditioning to liquid saccharin are reported. In both studies each...     

Swimming-induced taste aversion and its prevention by a prior history of swimming

In two experiments, the evidence showed that 20 min of forced swimming by rats caused aversion to a taste solution consumed before swimming. When one of two taste solutions (sodium saccharin or sodium chloride, counterbalanced across rats) was paired with swimming and the other was not, the rats’ intakes of these two solutions showed less consumption of the former than the latter solution. Furthermore, a post-training two-bottle choice test clearly demonstrated long-lasting avoidance of the swimming-paired solution. These results imply that forced swimming acts as an unconditioned stimulus for establishing taste aversion. Preexposure to swimming opportunities before conditioning disrupts such conditioned taste aversion induced by forced swimming.     

Neuronal representation of conditioned taste in the basolateral amygdala of rats

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.     

杏仁核c-fos的表达与条件反射性免疫抑制

以糖精水为条件刺激（conditioned stimulus,,CS）,免疫抑制剂-环磷酰胺为非条件刺激 （(unconditioned stimulus,,UCS),在两次CS-UCS结合训练后,观测不同时程再次单独呈现条件刺激对条件反射性免疫抑制和味觉厌恶性行为反应的变化以及大鼠杏仁核各亚核团内c-fos蛋白表达的影响。结果表明,条件反射性免疫抑制作用在训练后第5天较强,第30天基本消失,而味觉厌恶性条件反射始终稳定保持到第30天。条件反射组大鼠杏仁中央核c-fos蛋白表达在第5天非常密集,而第30天明显减少,与细胞免疫功能改变在时程和趋势上具有一致性。通过c-fos蛋白表达时程差异比较,提示杏仁中央核可能既与条件性的味觉厌恶性行为建立有关,也是参与介导CS诱导的免疫抑制效应的重要核团。     

Developmental flavor experience affects utilization of odor, not taste in toxiphobic conditioning

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.     

Effects of CS concentration in taste-aversion learning: Problems in assessing aversion strength

The concentration of saccharin (CS) solutions was varied between groups of rats in four taste-aversion learning experiments, using lithium chloride as the aversive agent (US). Saccharin intake was measured on four one-bottle presentations yielding data on initial taste neophobia as well as postconditioning aversion strength. The results indicated that saccharin intake declined progressively with increasing concentrations on the first presentation, and that preconditioning intake to a large extent predicted postconditioning intake. In an attempt to correct postconditioning values for differences of saccharin intake on the preceding trial, a taste suppression ratio (TSR) was computed as the quotient of the amounts of saccharin consumed by individual rats on consecutive presentations. In general, the TSR was found to be too insensitive to detect differences of conditioning strength acquired by different saccharin concentrations. Alternative approaches to the CS-concen-tration problem in taste-aversion learning are discussed.     

Potentiation and overshadowing in odor-aversion learning: Role of method of odor presentation,the distal-proximal cue distinction,and the conditionability of odor

Four experiments with rat subjects examined interactions between odors and tastes in compound aversion conditioning. In Experiments 1 and 2, a saccharin taste potentiated the conditioning of an almond odorant presented on a cup near the location of the drinking spout, but overshadowed the same odorant when it was mixed in drinking water. This difference depended on the type of odor administered during conditioning rather than testing (Experiment 2). Experiments 3 and 4 examined implications of two other differences between the cup and drink odors: (1) while the cup odor was a distal cue that suppressed approach to the spout, the drink odor was primarily a proximal cue that suppressed consumption, and (2) the cup odor was less conditionable than the drink odor when the stimuli were conditioned alone. In Experiment 3, unlike the proximal saccharin taste, the proximal drink odor failed to potentiate the conditioning of a different distal odor. In Experiment 4, substantial dilution of the proximal drink's concentration resulted in both weaker conditioning of the stimulus alone, and potentiation of its conditioning by saccharin. The results suggest that the difference in the conditionability of the cup and drink odors, and not their status as distal and proximal cues, may be critical in the production of potentiation. Weakly conditionable target stimuli are uniquely potentiated by saccharin.     

Higher-order conditioning and sensory preconditioning of a taste aversion with an exteroceptive CS1

An exteroceptive stimulus compound (context) was employed as CS₁ in higherorder conditioning (H-OC, Experiments I and II), and sensory preconditioning (SPC, Experiment III) of a saccharin (CS₂) aversion in rats. The results indicated that aversions were established with the H-OC as well as with the SPC procedures. Stimulus generalization and first-order conditioning explanations were ruled out by appropriate controls. A CS₁-extinction period, performed prior to testing, did not affect the H-OC aversion, whereas it reduced the SPC aversion at least partially. These findings imply that interoceptive (taste, nausea) and exteroceptive stimuli (context) are readily associable in rats. Implications of the resemblance between the SPC procedure and long-delay taste-aversion learning are discussed.     

Taste preconditioning augments odor-aversion learning

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.     

The role of cue additivity in salience in taste aversion conditioning

In toxiphobia conditioning certain cues are more easily associated with malaise (i.e., more salient) than others. The present experiments show that cue additivity can account for previously found differences in salience of certain fluids. The relative salience of saccharin, saline and casein hydrolysate was tested in normal rats and in animals rendered anosmic by treatment of their nasal passages with zinc sulphate. The normally more salient casein was reduced in salience to the same level as saccharin and saline in the anosmic animals, while anosmia did not affect the relative salience of saccharin and saline. A second study tested the cue properties of vanilla, a fluid of very low salience. Anosmic animals could not show a conditioned aversion to vanilla. Normal animals readily learned the aversion but could not show it following a later anosmia treatment. Anosmia did not disrupt a saccharin aversion previously conditioned in normal animals. The data show that some of the “tastes” used in toxiphobia conditioning have olfactory components, and some are purely olfactory. Further, olfactory cues can summate with taste cues to form a more salient stimulus.     

条件反射性免疫抑制激活过程中下丘脑核团c-fos的表达

利用经典条件反射性免疫抑制的动物模型,以糖精水为条件刺激（CS）,免疫抑制剂-环磷酰胺为非条件刺激 （UCS）,观测两次CS-UCS结合训练后,再次条件刺激诱发条件反射性免疫抑制作用的动态改变,获得条件反射性免疫抑制和味觉厌恶性条件反射各自保持的情况,并在此基础上,采用c-fos免疫组化技术, 进一步观察再次条件刺激诱发条件反射性免疫抑制反应时大鼠下丘脑各核团内FOS蛋白的表达情况。结果表明,条件反射性免疫抑制作用在训练后第5天较强,第30天基本消失,而味觉厌恶性条件反射始终稳定保持到第30天。进一步研究显示出,下丘脑室旁核FOS蛋白表达在第5天非常密集,而第30天几乎没有表达,与细胞免疫功能改变在时程和趋势上具有一致性。通过FOS蛋白表达时程差异比较,提示下丘脑室旁核可能是CNS内介导CS诱导的免疫抑制效应的重要核团。     

Characterization of a dose-response curve for nicotine-induced conditioned taste aversion in rats: relationship to elevation of plasma beta-endorphin concentration

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.     

Conditioned taste aversion is enhanced when the unconditioned stimulus is presented in a different context

Using a conditioned taste aversion procedure with rats as the subjects, two experiments examined the effect of presenting a conditioned stimulus (CS saccharin solution) in one context followed by an unconditioned stimulus (US LiCl) in a different context. Experiment 1 showed that animals which received the above-mentioned procedure (Group D) showed a more marked conditioned aversion to the CS than animals which were given both the CS and the US in the same context (Group S). Experiment 2 found that in both Group D and Group S, aversion to the CS increased when the subjects were exposed to the conditioned context after the conditioning. These findings supported the argument that the strength of the CS-US association acquired during conditioning is compared with that of the context-US to determine the magnitude of aversion revealed to the CS.     

Alcohol-induced conditioned aversion: genotypie specificity in mice (Mus musculus).

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.     

The effect of three procedures for eliminating a conditioned taste aversion in the rat

Although extinction procedures have been the most common techniques used to eliminate conditioned taste aversions, several studies have employed postconditioning exposure to the US instead. To date, a comparison of the effectiveness of these two techniques has not been possible, because there were differences in the conditioning phases of these studies. In the present study, after an aversion to saccharin had been established, rats were administered 1, 5, or 10 extinction trials, 1, 5, or 10 postconditioning exposures to the US, or a period of no treatment. Then, all rats received seven two-bottle extinction tests. Five or ten extinction trials reduced the aversion to saccharin most effectively. Five or ten postconditioning presentations of the US were also effective. However, this effect was not noticeable until the fourth of seven test trials, suggesting an elimination procedure-test trials interaction. Neither the extinction nor the US postexposure procedure completely eliminated the aversion. In addition: (i) a single postconditioning exposure to either the CS or the US was ineffective in attenuating the aversion; and (ii) when no postconditioning treatment was administered, the strength of the aversion was undiminished for 20 days.