Conditioned taste aversion and traditional learning

Summary The generality of the laws of learning has been questioned on the basis of the results of conditioned taste aversion (CTA) experiments. The results of CTA experiments and of traditional learning (TL) experiments are compared in order to evaluate whether CTA and TL indeed follow different rules. It is shown that (a) most of the observed differences between CTA and TL experiments may simply reflect peculiarities of the CSs and USs used in CTA, (b) that there are conflicting phenomena in both CTA and TL experiments which require further analysis, and (c) that the majority of learning phenomena seen in CTA experiments also occur in TL experiments. It is therefore suggested that the laws that hold for TL also apply to CTA.     

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.     

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 in humans using motion-induced sickness as the US

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.     

Context specificity of latent inhibition in taste aversion learning

In three experiments rats were given injections of LiCl after consuming distinctively flavoured water. The rats developed an aversion to the flavour and in all experiments the magnitude of the aversion was found to be reduced in subjects that had received pre-exposure to the flavour without aversive consequences. Experiment 1 demonstrated this pre-exposure effect to be a case of latent inhibition. The remaining experiments investigated the effects of pre-exposing the flavour in a context different from that used for conditioning. It was found (Experiment 2) diat latent inhibition transferred perfectly when the context change consisted of a move from one home cage to another. Context specificity of latent inhibition was found (Experiment 3) only when the subjects were given daily sessions in die experimental contexts, these being cages different from the home cage.     

Conditioned taste aversion modifies persistently the subsequent induction of neocortical long-term potentiation in vivo

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.     

Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

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.     

Conditioned taste aversion with sucrose and tactile stimuli in the pond snail Lymnaea stagnalis

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.     

Conditioned taste aversion and Ca/calmodulin-dependent kinase II in the parabrachial nucleus of rats

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.     

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.     

CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion in rats

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.     

Conditioned suppression, punishment, and aversion

Three experiments were conducted to assess the aversive properties of a visual stimulus in the presence of which one group of birds received response-contingent shock (discriminated punishment) while a yoked group of birds received non-contingent shocks (conditioned suppression). In Experiment 1, presentation of the visual stimulus contingent on key pecking reduced the response rate (conditioned punishment effect) for birds under the conditioned suppression procedure but did not reduce the response rate of birds under the discriminative punishment procedure. Non-contingent shocks also produced greater suppression of responding maintained by positive reinforcement in the presence of a visual stimulus than did response-contingent shocks. In Experiment 2, a greater shock intensity (2 mA) was used. All the differences between the two groups found in Experiment 1 were also found in Experiment 2. Experiment 3 demonstrated that response-contingent shock did not result in a conditioned punishment effect even when positive reinforcers were unavailable during the discriminative punishment schedule. The exteroceptive stimulus that was paired with shock in the conditioned suppression procedure acquired the ability to punish behavior. The exteroceptive stimulus in the discriminative punishment schedule did not acquire this ability.     

Cortical substrates of taste aversion learning: dorsal prepiriform (insular) lesions disrupt taste aversion learning

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.     

Reinstatement of latent inhibition following a reminder treatment in a conditioned taste aversion paradigm.

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.     

Loss of latent inhibition in conditioned taste aversion following exposure to a novel flavour before test

Killcross, Kiernan, Dwyer, andWestbrook (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 aretention interval between conditioning and test and retrieval-failure theories of LI are discussed.     

Stimulus generalization of conditioned taste aversion in rats

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.     

Further evidence for the summation of latent inhibition and overshadowing in rats’ conditioned taste aversion

Repeated exposures to a target taste (X) attenuated subsequent development of rats’ conditioned aversion to X (latent inhibition effect). Presentation of another taste (A) after X in conditioning (serial X-A compound conditioning) also attenuated conditioned X aversion compared with conditioning without A (overshadowing). Furthermore, the latent inhibition and overshadowing effects summed to show the least conditioned aversion in the rats given both the target preexposures and the serial X-A compound conditioning treatment. These results question the validity of the comparator hypothesis as an explanation for Pavlovian conditioning of rats’ conditioned taste aversion.