Sexually dimorphic acquisition of a conditioned taste aversion in rats: Effects of gonadectomy,testosterone replacement and water deprivation

Sexual dimorphism was found to exist with respect to the acquisition of a conditioned taste aversion. When 0.30 meq of LiCl was used as a toxin, the proportion of male rats in whom aversion developed was greater than the proportion of females. Gonadectomy had an unclear effect on the behavior of females. However, gonadectomized males had less of a tendency to acquire the aversion than did intact males. Testosterone replacement counteracted this effect. Water deprivation, which has been shown to feminize testosterone-dependent slow extinction of a conditioned taste aversion, reduced the proportion of males in whom aversion developed. Thus, sexual dimorphism in the acquisition of this behavior depends at least in part on the presence of testosterone.     

Rapid extinction of a conditioned taste aversion following unreinforced intraperitoneal injection of the fluid CS

After drinking a novel, saccharin-cyclamate solution, two groups of rats were poisoned with LiCl injection in order to establish a conditioned taste aversion, while a control group was not poisoned. Eighteen hours later, one of the poisoned groups of rats received differential unreinforced exposure to the sweet solution via an intraperitoneal injection. The group injected with the concentrated form of the saccharin-cyclamate solution showed subsequent rapid extinction of the conditioned taste aversion. An analogy was made to the technique of flooding (response prevention) used to hasten extinction of active, shock-motivated avoidance behavior.     

Failure of ACTH to prolong extinction of a conditioned taste aversion in the absence of the testes

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.     

Temporal aspects of the dependency of a dimorphic rate of extinction on testosterone.

Previous work has shown that rate of extinction of a conditioned taste aversion is affected by concurrent levels of testosterone in adult rats. In the present study, castrated male and female adult rates were given either oil or testosterone during acquisition of the conditioned taste aversion and then either oil or testosterone during extinction. The males and females that received testosterone during the extinction of the aversion showed the slower, masculine rate of extinction regardless of the type of injections they received during acquisition. Conversely, the animals that received oil during extinction showed the faster, feminine rate of extinction regardless of the type of injection during acquisition. In light of these findings, a number of alternative behavioral changes that could account for the effect of testosterone on the rate of extinction were evaluated.     

Effects of desglycinamide-lysine vasopressin on a conditioned taste aversion in rats

Vasopressin and other pituitary peptides have been shown to increase resistance to extinction of active and passive shock-avoidance responses. Both paradigms use external cues as warning and punishing stimuli. The present work asked if a variant of vasopressin would have a similar effect on conditioned taste aversions (CTA), which use internal cues as warning and punishing stimuli. Eight groups of rats were defined by factorial combination of Pretreatment during Neophobia and Conditioning (vasopressin vs saline), UCS during Conditioning (pairing saccharin-flavored water with injections of lithium chloride or saline), and Pretreatment during Extinction (vasopressin vs saline). Rats given three saccharin-lithium pairings developed strong aversions. Of the rats with CTAs, those given vasopressin during conditioning, extinction, or both showed increased resistance to extinction on the last four of eight extinction days. Vasopressin had no other effect on drinking of saccharin. Vasopressin thus appears to enhance resistance to extinction of avoidance responses in both external and internal milieus.     

Peripheral vasopressin accelerates extinction of conditioned taste avoidance

Both peripheral and central administration of vasopressin improves retention and delays extinction when given before or after acquisition of shock avoidance learning. For conditioned taste avoidance, however, vasopressin prolongs extinction when injected peripherally before acquisition tests and accelerates extinction when infused intracerebroventricularly after acquisition. The following experiments were designed to determine whether this inconsistency is based on the route of administration or timing of vasopressin treatment. Because acquisition of conditioned taste avoidance is strengthened when an agent that is capable of inducing avoidance is administered after LiCl injection, it was determined in experiment 1 that a 6 microg/kg dose of vasopressin did not induce conditioned taste avoidance when administered 50 min after consumption of a sucrose solution. In experiment 2, it was determined that this dose of vasopressin accelerated extinction of a LiCl-induced conditioned taste avoidance when given 50 min after LiCl injection. These results suggest that the inconsistency is not based on route of administration. In experiment 3, it was determined that there was a tendency for animals to show prolonged extinction when vasopressin was administered 20 min before access to a sucrose solution. All of the results taken together suggest that the differential effects of vasopressin on extinction are due to the timing of administration. It was suggested that vasopressin accelerates extinction when given after acquisition by reducing the effectiveness of LiCl and it prolongs extinction when given before acquisition by altering neural responsiveness in areas mediating conditioned taste avoidance.     

Amygdalectomy induced deficits in conditioned taste aversion: possible pituitary-adrenal involvement

Bilateral lesions to the amygdala in rats impaired a conditioned taste aversion produced by pairing the taste of sweetened milk with lithium chloride (Experiment 1). A second experiment investigated the role of adrencorticotropin (ACTH) in the amygdala lesion-induced deficits in conditioned taste aversion. ACTH injection on the day of conditioning was without effect in either sham or amygdala lesioned animals. ACTH injection on the day of testing was without an effect in sham animals. However, ACTH injection augmented the avoidance behavior of amygdala lesioned subjects (Experiment 2). These data suggest a pituitary-adrenal involvement in the amygdalectomy-induced deficits in conditioned taste aversion.     

Effects of swim stress on latent inhibition using a conditioned taste aversion procedure

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.     

Early handling effects on neophobia and conditioned taste aversion

The purpose of this study was to determine whether early handling, a manipulation which affects both behavioral and pituitary-adrenal responsiveness to novel and aversive situations, will affect responses in adult rats confronted with novel substances (neophobia) or with substances associated with illness (conditioned taste aversion). We found that (1) early handling reduces the neophobia shown by adult animals and that handled animals appear better able to distinguish between a preferred and a nonpreferred substance. (2) Handling reduces the magnitude of the initial taste aversion and also increases the rate of recovery of drinking to pretoxicosis levels. (3) These behavioral differences between handled and nonhandled animals are not due to differential pituitary-adrenal responses to LiCl. (4) Early handling does affect the conditioned elevation of plasma corticoids upon reexposure to milk under a Forced Extinction procedure. In this situation nonhandled animals show greater corticoid elevations than handled animals. (5) Manipulation of the number of exposures to a substance prior to pairing that substance with LiCl affects the magnitude of both the aversion and the elevation of plasma corticoids which are produced upon reexposure. As number of preexposures increase, both the magnitude of the aversion and the elevation of corticoids decrease.     

Differential effect of paradoxical sleep deprivation on acquisition and retrieval of conditioned taste aversion in rats.

Paradoxical sleep deprivation (PSD) was used to interfere with acquisition or retrieval of conditioned taste aversion (CTA). PSD was achieved by confining rats to small pedestals placed on an electrified grid floor. Fifteen-min access to 0.1% sodium saccharin (conditioned stimulus-CS) by water deprived rats was followed 30–120 min later by intraperitoneal injection of lithium chloride (unconditioned stimulus-US, 0.15 M, 2% to 4% body weight). Retention was tested 1 to 5 days later by offering the animal saccharin again. A 24-hr PSD preceding saccharin drinking prevented CTA acquisition. CTA disruption was diminished by a 2-hr, and completely abolished by an 8-hr interval of home cage recovery inserted between the 24-hr PSD and saccharin presentation. CTA was slightly facilitated by 2-hr PSD in the CS-US interval. The 24-hr PSD preceding CS caused the same CTA disruption when followed by free sleep opportunity or by continued PSD in the 2-hr CS-US interval. Twenty-four-hr PSD preceding retention testing slightly improved retrieval of well established CTA. It is concluded that PSD interferes with the formation of the short-term gustatory trace of CTA but does not affect retrieval of CTA engrams. Gradual compensation for the PSD effect on CTA learning by pre-acquisition sleep suggests that the processes responsible for CTA disruption and recovery correspond to depletion and repletion of the same neurotransmitter stores.     

Pseudo-castration effects of social isolation on extinction of a taste aversion

The effects of social isolation on the slow rate of extinction of a conditioned taste aversion exhibited by male rats were investigated. When the males were isolated for six weeks prior to poisoning, they showed a nontypical, rapid rate of extinction from the conditioned taste aversion. The isolation had no effect on the already rapid rate of extinction exhibited by the females. Behaviorally, the change in the rate of extinction in the male following social isolation is identical to the change in rate that occurs following castration of the male. It was therefore proposed that isolation increased the rate of extinction in the male by decreasing the availability of testosterone. This proposal was supported by the finding that socially isolated males had lower plasma testosterone levels than did non-isolated males.     

Differential effects of amygdaloid lesions on conditioned taste aversion learning by rats

Rats with electrolytic lesions placed in either the basolateral or corticomedial divisions of the amygdala acquired a conditioned taste aversion to sucrose. Comparisons with a surgical control group indicated that damage to the corticomedial amygdala did not alter the animals' performance, while damage in the basolateral nuclei resulted in a small but significant attenuation of the aversion. Furthermore, these amygdaloid lesions did not alter the acceptability of two quinine hydrochloride solutions (0.01% and 0.001%). The daily drinking behavior of the rats with basolateral amygdaloid lesions appeared consistent with the hypothesis that this lesion affected the animals' appreciation of the novelty of the sucrose solution, and hence attenuated the subsequent aversion.     

Detection of free fatty acids following a conditioned taste aversion in rats

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.     

Recall of a previously acquired conditioned taste aversion in rats following lesions of the area postrema

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.     

High doses of vasopressin delay the onset of extinction and strengthen acquisition of LiCl-induced conditioned taste avoidance

When low doses of vasopressin are given 50 min after pairing sucrose consumption with a high dose of LiCl, extinction of the LiCl-induced conditioned taste avoidance is accelerated. These low doses of vasopressin do not themselves induce conditioned taste avoidance when paired with sucrose consumption. Predicated on previous studies administering two avoidance-inducing agents after sucrose consumption, studies were designed to determine whether high doses of vasopressin capable of inducing conditioned taste avoidance would (1) delay rather than accelerate extinction of a conditioned taste avoidance induced by a high dose of LiCl and (2) strengthen acquisition of a conditioned taste avoidance induced by a low dose of LiCl. The results of three studies showed that doses of 9 and 18 microg/kg of vasopressin induced a conditioned taste avoidance when injected 50 min after sucrose consumption, delayed the onset of extinction when injected 50 min after pairing sucrose consumption with a high dose of LiCl, and strengthened acquisition of a conditioned taste avoidance when injected 50 min after pairing sucrose consumption with a low dose of LiCl. Taken together, these data suggest that the delay in onset of extinction is due to a strengthening of acquisition. It has been suggested that vasopressin is a mnemonic neuropeptide that delays extinction of learned tasks. However, for conditioned taste avoidance, the evidence for the effects of low doses of vasopressin on extinction do not support this hypothesis and the evidence for high doses of vasopressin can be accounted for by the avoidance-inducing properties of vasopressin.     

Experience with activity based anorexia enhances conditioned taste aversion learning in rats

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, 0.3 M sucrose consumption was followed by low doses LiCl (0.009 M or 0.018 M at 1.33 ml/100 g 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.     

Aversive effects of vagotomy in the rat: a conditioned taste aversion analysis

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.     

Behavioral and corticosterone effects in conditioned taste aversion following hippocampal lesions

Hippocampal-lesioned rats engaged in more drinking bouts during the retention of a conditioned taste aversion, but failed to show the elevation of plasma cortocosterone levels seen in the neocortical-lesioned and unoperated control animals, thus showing a disassociation of behavioral and hormonal responses to the retention situation. The presence or absence of anomalous sympathetic innervation in the hippocampal-lesioned rats was demonstrated to be without any behavioral significance.     

Aversive consequences of jejunoileal bypass in the rat: a conditioned taste aversion analysis

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.