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.     

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.     

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.     

Extinction of conditioned taste aversions: Effects of concentration and overshadowing

Extinction of conditioned taste aversions was examined as a function of taste concentration and of the presence of an additional taste. The results of Experiment 1 were consistent with previous evidence in that a conditioned aversion to high concentration saline was more persistent in extinction than an aversion to a low concentration. However, when floor effects were avoided the rate of extinction was faster for the higher (1%) concentration than for 0.2% saline (Experiment 2), a result consistent with accounts of extinction in other preparations. Three further experiments examined extinction of a conditioned sucrose aversion. The addition of 1% saline, but not of 0.2% saline, to sucrose during extinction produced overshadowing ("protection from extinction"; Experiment 3). Such overshadowing by saline was detected after two, but not after a single extinction trial (Experiment 4). This last finding suggests that under the conditions of the present experiments sweet and salty tastes function as elemental stimuli competing for loss of associative strength. No overshadowing was found when almond (an aqueous odour) was used in place of saline as the added stimulus, even when high concentrations of almond were used that produced observable neophobia (Experiments 5A and 5B).     

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.     

Effects of Cerebroventricle Administration of Acidic Fibroblast Growth Factor on Conditioned Taste Aversion Learning in Rats

Wistar strain rats were given acidic fibroblast growth factor (aFGF) or denatured aFGF into their cerebroventricle before taste aversion conditioning for saccharin solution. Animals administrated 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.     

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.     

Taste reactivity and consumption measures in the assessment of overshadowing: Modulation of aversive,but not ingestive,reactivity

Three dependent measures—a taste reactivity test, a two-bottle preference test, and a one-bottle extinction test—were used to investigate the conditioning effects of pairing a taste/taste compound with LiCl-induced illness in rats. Avoidance of saccharin consumption in the one-bottle test was attenuated if saccharin and denatonium were paired during illness training (overshadowing). Also, saccharin was found to be more palatable if paired with denatonium during training as reflected by aversive (but not ingestive) taste reactivity measures. It is argued that overshadowing was reflected mainly by a modulation of aversive taste reactivity behavior with little influence on ingestive taste reactivity. The results are discussed in terms of current palatability issues, and it is suggested that applying taste reactivity tests to phenomena associated with taste avoidance learning (e.g., overshadowing or potentiation) may further our understanding of the mechanisms that guide such learning.     

Conditioned Inhibition Produced by Extinction of a Conditioned Stimulus

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.     

Negative anticipatory contrast and preference conditioning: flavor cues support preference conditioning, and environmental cues support contrast.

In 2 experiments, access to a 0.15% saccharin solution was followed on alternating days by access to a 32% sucrose solution and the same saccharin solution. In Experiment 1, rats increased both intake of and preference for a flavored saccharin solution that predicted sucrose, but neither effect was found using a predictive odor cue alone. Experiment 2 replicated the predictive flavor results but showed suppression of saccharin intake when environmental cues predicted sucrose. When both flavor and environment predicted sucrose, saccharin intake did not change, but preference for the predictive flavor increased. Discriminative taste cues appear to facilitate the development of preference conditioning, but environmental cues favor negative anticipatory contrast effects. Also, preference conditioning and contrast may develop concurrently and compete for expression.     

Age-dependent facilitation of taste-footshock conditioning by prior exposure to the training context

Among adult rats, gustatory stimuli are easily associated with illness, but not with external unconditioned stimuli such as footshock. Recent evidence indicates, however, that this cue-to-consequence specificity may vary ontongenetically. The present studies examined the acquisition of an aversion to a taste paired with footshock in 5- and 15-day-old rats. Consistent with previous reports, 5-day-old rats avoided the taste that preceded footshock, while 15-day-old subjects did not express an aversion to the taste paired with footshock. Exposure to the training context for either 1 or 5 h prior to conditioning disrupted taste-footshock conditioning in the 5-day-old subjects. For the 15-day-old subjects, 1 h of pre-conditioning exposure to the training context had no effect on conditioning, whereas a longer duration of preexposure promoted conditioning to the taste cue. The results suggest ontogenetic differences in stimulus selection.     

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.     

Augmentation of taste conditioning by a preconditioned odor.

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.     

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.     

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.     

Flavour-odour compound conditioning: Odour-potentiation and flavour-attenuation

Five experiments employed a toxiphobia conditioning paradigm to examine the strengths of odour and flavour aversions when conditioned separately and in compound. When conditioned in compound, odour aversions were stronger than when conditioned separately, i.e., the flavour potentiated the odour (Experiment Ia), but flavour aversions were weaker than when conditioned separately, i.e., the odour attenuated the flavour (Experiment Ib). The duration of exposure to the reinforced compound governed the nature of the interaction between the components: at a brief exposure, the flavour overshadowed the odour; at a long exposure, the flavour potentiated the odour (Experiment II). The remaining experiments examined the mechanism subserving the potentiation effect. Experiment III demonstrated that extinction of the flavour associate of the odour attenuated the odour aversion but further conditioning of the flavour did not strengthen the odour aversion. Experiment IV confirmed this effect of extinction but also found a comparable attenuation of the odour aversion from extinction of a separately conditioned flavour. Experiment V examined the previous failure to influence the strength of the odour aversion by strengthening the flavour aversion. In this experiment, conditioning the flavour associate or a separately conditioned flavour with a more potent US augmented the strength of the odour aversion. The results did not provide support for the idea that the potentiation phenomenon reflects the formation of within-compound associations but did indicate that a potentiated odour aversion could be modulated by manipulations designed to alter the US representation.     

The addition of saccharin to taste cues affects taste preference conditioning in thirsty rats

Previous failures to condition preferences for the unacceptable taste cues sucrose octaacetate (SOA) and citric acid (CA) using a reverse-order, differential conditioning procedure (Forestell & LoLordo, 2000) may have been the result of low consumption of the taste cues in training or of their relatively low acceptability to rats that are thirsty and hungry. In the present study, rats that were thirsty but not hungry readily consumed the SOA and CA conditioned stimulus solutions in training. In test, stronger preferences were displayed for CS+ if the taste cues had been mixed in water (i.e., for the previously unacceptable taste cues) than if they had been made more acceptable by the addition of saccharin in training and test. In Experiment 2, again with rats that were thirsty but not hungry, stronger preferences for CS+ were observed when taste cues were presented in water in the test than when they were presented in saccharin. Addition of saccharin to the taste cues in test eliminated the preference for CS+.     

Noradrenaline loss and the disruption of between-CS stimulus generalisation effects in aversion learning

In stimulus blocking the previous conditioning to one stimulus, A, followed by conditioning to the compound stimulus, AB, results in less conditioning to the other stimulus, B. Three experiments were performed to study the effect of the prior pairing of a stimulus A (noisy bottle) with lithium chloride followed by stimulus AB (saccharin plus noisy bottle) and lithium chloride pairings upon the strength of the aversion to the target stimuls B (saccharin) in NA-depleted and control rats. The results obtained were not in keeping with a "blocking" explanation since enhancement, rather than blocking, of the saccharin aversion was obtained, and confirm several recent demonstrations of the "anti-blocking" effect from investigations using the conditioned suppression procedure. DSP4 treatment attenuated the aversion-enhancement ("anti-blocking") effects in all three experiments. The possibility that DSP4-induced noradrenaline depletions may cause some disruption of between-CS associations leading to a lesser higher order conditioning or stimulus generalisation is discussed and the present findings do add further evidence to the conclusion that noradrenaline is intimately involved in attentional processes.     

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.     

味觉厌恶性条件反射与条件反射性免疫抑制的研究

以环磷酰胺的注射为非条件刺激（ＵＣＳ）,糖精水的摄入为条件刺激（ＣＳ）,并以血白细胞和淋巴细胞数量及脾淋巴细胞的转化反应为免疫指标,糖精水的饮用量为行为指标,通过改变条件刺激与非条件刺激结合的次数来观察条件反射性厌恶行为与条件反射性免疫抑制的反应。结果表明不管是一次性的还是两次性的ＣＳ－ＵＣＳ结合训练都能使动物明显地建立起味觉厌恶性条件反射,然而条件反射性免疫抑制只在两次性ＣＳ－ＵＣＳ结合训练后才