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.     

Reversal of long-delay conditioned taste aversion learning in rats by sex hormone manipulation

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 5α-DHT pellets (metabolite of testosterone) displayed a stronger CTA response compared to gonadectomized males implanted with 17β-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.     

Potentiation of a conditioned taste aversion in preweanling and adult rats

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.     

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.     

Acquisition and extended retention of a conditioned taste aversion in preweanling rats

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.     

Impaired conditioned taste aversion learning in spinophilin knockout mice

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.     

Intragastric copper sulfate produces a more reliable conditioned taste aversion in vagotomized rats than in intact rats

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.     

Deprivation level affects extinction of a conditioned taste aversion

Hooded rats were conditioned to avoid drinking saccharin by following exposure to saccharin with injection of cyclophosphamide, a drug that produces visceral upset. Extinction trials were then given by presenting saccharin without cyclophosamide injections with the rats under low (10 hr) or high (23 hr) fluid deprivation. The aversion extinguished in fewer trials in rats under high deprivation.     

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+.     

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.     

Flavor preexposures in a conditioned taste aversion situation: a dissociation of behavioral and endocrine effects in rats

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.