Drug exposure and the acquisition and retention of a conditioned taste aversion

Two experiments examined the effects of preexposure and postexposure to a drug on the acquisition and retention of a conditioned taste aversion induced by that drug. Experiment 1 demonstrated that although drug preexposure attenuated a subsequent conditioned aversion, repeated taste-drug pairings reversed the initial attenuation effect and resulted in nearly complete avoidance of consumption. Experiment 2, however, demonstrated that drug postexposure did not alter a previously established conditioned aversion, although the postexposure experiences were effective in attenuating a conditioned aversion to a second novel solution. It was suggested that conditioned aversions are mediated by ACTH and that preexposure to a drug results in tolerance to that drug, yielding a smaller ACTH response and thereby a weaker aversion.     

Uterine position and conditioned taste aversion.

Three experiments investigated the influence of uterine position on the performance of female offspring of female Sprague-Dawley and male Long-Evans rats in a conditioned taste aversion paradigm. 49 females that had males caudal to them in the same uterine horn (MF), 48 females with no caudal males (FF), and 24 males that had occupied a variety of different positions in the uterine horn were examined. Exps I and II confirmed a differential behavioral response by males and females during acquisition and extinction of the conditioned taste aversion. However, no differences were found between MF and FF Ss. In Exp III, in which testosterone was administered to females throughout testing, MF females showed an increased sensitivity to testosterone and a more prolonged rate of extinction than FF females. Exposure to testosterone during prenatal development heightened postnatal responsiveness to testosterone in female Ss. Results are discussed in terms of the organizational and activational effects of testosterone on behavior in a conditioned taste aversion situation. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ingestional aversion learning in preweanling rats.

In 4 experiments, ingestional aversions were conditioned in 12- and 15-day-old Sprague-Dawley rats by infusing a .5% solution of saccharin into the oral cavity and following this oral infusion by the injection of lithium chloride. At both ages, Ss for which the saccharin exposure was followed by lithium injection within 2–3 min drank less when the saccharin solution was again presented by oral infusion 12 hrs later; such suppressions of intake were not observed in Ss that previously received the saccharin and lithium in an unpaired fashion (Exps I and III). Ingestional aversions were also learned by 12-day-olds when a 30-min interval was introduced between saccharin exposure and lithium toxicosis but not when toxicosis was delayed by 120 min (Exp II). In contrast, 15-day-olds learned aversions with both the 30- and 120-min-delay intervals (Exp III). Despite the absence of long-delay learning in 12-day-olds, ingestional aversions conditioned at 12 days of age were retained for 2 wks (Exp IV). Results provide further evidence of the associative abilities of neonatal rats and illustrate a developmental aspect of long-delay learning. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats.

In 2 experiments, the development of adjuvant arthritis (an experimental autoimmune disease) was inhibited by exposing rats to a flavored solution that had previously been paired with injections of cyclosporine (an immunodepressive drug) compared with rats with the same history but exposed to a flavored solution that had previously not been paired with drug injections. In contrast to earlier experiments on conditioned cyclophosphamide effects, rats did not avoid the taste that had previously been paired with drug administration. Thus, conditioned immunopharmacologic effects were not confounded with taste aversion. These observations are interpreted as reflecting an associative learning process that affected the development of an autoimmmune disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hypothermia on the acquisition of conditioned taste aversion in rats.

Analyzed the mechanism of conditioned taste aversion (CTA) by subjecting 131 male and hooded rats in 5 experiments to reduced body temperature during various phases of CTA acquisition. A 15-min access to .1% saccharin served as the CS, and an ip injection of LiCl (.15 M, 4% of body weight) given 30 min later served as the UCS. Hypothermia (cooling to 20-22°C colonic temperature) alone or combined with anesthesia (Nembutal 20 or 40 mg/kg) did not prevent CTA acquisition when applied during the CS-UCS interval. Hypothermia induced immediately after LiCl administration to anesthetized or unanesthetized Ss failed to disrupt CTA or to increase neophobic rejection of saccharin. On the other hand, hypothermic Ss were not able to form the short-term gustatory trace when the CS (2% saccharin, 1% of body weight) was injected ip, although this procedure yielded significant CTA in euthermic Ss. It is concluded that the most vulnerable link of CTA acquisition is the formation of the short-term gustatory trace. Persistence of the short-term trace, its association with poisoning, and consolidation of the permanent CTA engram are accomplished by mechanisms that are resistant to hypothermia and/or anesthesia. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decreased testosterone levels and accelerated extinction of a conditioned taste aversion in fluid-deprived male rats.

The hypothesis that fluid deprivation accelerates extinction of a conditioned taste aversion in male Sprague-Dawley-derived rats by reducing serum testosterone levels was tested. Serum testosterone levels were found to be lower in fluid-deprived males than in nondeprived males (Exps 1 and 2). Exogenous testosterone treatment that results in high physiological levels of serum testosterone slowed the extinction of fluid-deprived gonadectomized males to rates comparable with those of nondeprived sham males (Exp 3). It was noted, however, that testosterone treatment was less effective in slowing extinction in fluid-deprived gonadectomized males than in nondeprived gonadectomized males even though the serum testosterone levels were the same (Exps 3 and 4). These results provide strong support for the original hypothesis, but they suggest that fluid deprivation also reduces sensitivity to testosterone. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic differences in nicotine-induced conditioned taste aversion

Genetic differences in nicotine-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J, DBA/2J, BALB/cJ and C3H/heJ mice were adapted to a 2-h per day water access regimen. Subsequently, mice received nicotine injections (0.5, 1.0 or 2.0 mg/kg) immediately after 1-h access to a NaCl flavored solution. DBA and C3H mice developed dose-dependent aversions to the nicotine-paired flavor. BALB mice showed only minor reductions in intake with no difference between the nicotine dose groups. C57BL mice did not show development of nicotine-induced conditioned taste aversion. These results demonstrate that nicotine's aversion motivational effect is strongly influenced by genotype. Further, genetic sensitivity (DBA mice) or insensitivity (C57BL mice) to nicotine-induced conditioned taste aversion was similar to reports of genetic sensitivity to ethanol's aversive effect measured in this design.     

Forebrain structures specifically activated by conditioned taste aversion.

This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste-malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste-malaise convergence during CTA acquisition depending on the strength of the aversion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethanol-induced conditioned taste aversion in 15 inbred mouse strains.

This study used a genetic correlational strategy to characterize the neurobiological basis of ethanol's (0, 2, or 4 g/kg) aversive effects as indexed by conditioned taste aversion. Substantial strain differences in taste aversion and hypothermia were observed, but the genetic correlation between these phenotypes was not significant. However, significant genetic correlations were observed between taste aversion and ethanol-related behaviors measured in previous studies, including home-cage ethanol preference (r = .68) and ethanol withdrawal severity (r = -.69). Strains showing stronger taste aversion tended to show lower ethanol preference and higher withdrawal severity. This pattern of findings is consistent with previous studies suggesting a commonality in neurobiological mechanisms underlying these phenotypes. These results do not support the hypothesis that ethanol-induced taste aversion is mediated by the drug's rewarding properties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of atropine on conditioned taste aversion

Atropine sulfate, which has a deleterious effect on various learning tasks, was found to have a similar effect on the acquisition of conditioned taste aversion. Thus, intraperitoneal injection of atropine sulfate shortly before tasting was found to interfere with conditioning of the aversion, but injection of atropine after tasting did not. The interference effect was also obtained with intraventricular administration of atropine sulfate, but not with intraperitoneal injection of the peripherally-acting atropine methylnitrate. These results show that central rather than peripheral mechanisms are involved in this effect, and suggest that conditioned taste aversion, like other kinds of learning, involves cholinergic mediation.     

Modification of unit responses to gustatory stimuli by conditioned taste aversion in rats

Secretion of trypsin, chymotrypsin, lipase and amylase was measured in male rats under urethane anaesthesia using a method of continuous perfusion of the duodenum. Prolonged infusion of cholecystokinin-pancreozymin (CCK-PZ) over a period lasting 200-360 min was administered either alone or together with a submaximal dose of secretin (1 unit/100 g - 10 min). Infusion of CCK-PZ was carried out using maximal doses (1--1.5 unit/100 g - 10 min) with and without secretin. Supramaximal doses of CCK-PZ (2 and 4 units/100 g - 10 min) were used only in combination with secretin. In all experiments secretion of enzymes showed a triphasic pattern including an initial peak followed by a plateau secretion after 10--20 min (phase 1), a decreasing second phase and finally base-line secretion (phase 3), thus demonstrating exhaustion of enzyme output from the gland with time. With increasing and supramaximal dose of CCK-PZ the cumulative output of enzymes from start to baseline secretion decreased progressively. Under the same conditions the levels of peak and plateau secretion were lower, the duration of plateau secretion was longer and the decreasing phase of secretion was shortened. These features indicate inhibition of secretion with increasing supramaximal doses of CCK-PZ infusion. Whereas the proteolytic enzymes and lipase reacted in a parallel way always amylase secretion was sustained on a higher level, implicating an alternative pathway for secretion.     

Hormonal influences on sexual dimorphism in rate of extinction of a conditioned taste aversion in rats

The hormonal influences on the slow extinction rate of a conditioned taste aversion shown by male rats and the fast extinction rate shown by female rats were investigated. When males were castrated, they extinguished as quickly as females. When castrated males were given testosterone propionate replacement, they had a slow extinction rate. Castration had no effect on the extinction rate of females. But when testosterone propionate was administered to castrated or intact females, they had a slow, malelike extinction rate. Thus, sexual dimorphism in the extinction rate of a conditioned taste aversion seems to be due to the activational effects of testosterone.     

Cycloheximide impairs reconsolidation of a contextually reactivated memory in a conditioned taste aversion paradigm.

Rats were used to examine the impact of systemic protein synthesis inhibition (PSI) on the reconsolidation of a contextually reactivated memory of conditioned taste aversion (CTA). Rats were administered intraperitoneal injections of saline or lithium chloride (LiCl; .15 M) following exposure to a novel sucrose solution in a unique context. Seven days later, rats were injected subcutaneously with saline or cycloheximide (CXM; 1 mg/kg) and returned to their home cage or placed into the CTA training context in the absence of the target conditioned stimulus to reactivate the training memory. At testing, LiCl-trained rats that had been given CXM at reactivation had significantly greater difference scores (sucrose-water) in comparison with LiCl/CXM rats that had not been given a reactivation treatment and LiCl/saline memory-reactivated rats. These results suggest that context re-exposure effectively reactivates memory of CTA training that may be weakened through PSI. Extinction tests revealed rapid attenuation of taste aversions in all of the LiCl-injected groups. The involvement of taste-potentiated aversions and the role of the context in taste aversion conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brainstem lesions and gustatory function: III. The role of the nucleus of the solitary tract and the parabrachial nucleus in retention of a conditioned taste aversion in rats.

Bilateral electrolytic lesions of the nucleus of the solitary tract (NST) or ibotenic acid lesions of the pontine parabrachial nuclei (PBN) failed to disrupt retention of a preoperatively acquired conditioned taste aversion (CTA) to 0.3 M alanine. For both sham- and NST-lesioned rats, the CTA persisted following 3 nonreinforced conditioned stimulus (CS) presentations. For PBN-lesioned rats, retention was more labile. The preoperatively acquired CTA was extinguished by the 3rd nonreinforced CS exposure. When assessed postoperatively using a novel CS, NST-lesioned rats acquired a new CTA, although they were rendered anosmic with zinc sulfate (P. S. Grigson et al, see record 199707487-016). Rats with PBN lesions, however, failed to acquire a 2nd CTA postoperatively. Thus, the PBN is essential for the acquisition of a CTA, but neither of the brainstem gustatory nuclei need be intact for the retention of a preoperatively acquired CTA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ibotenate lesions of the hippocampus enhance latent inhibition in conditioned taste aversion and increase resistance to extinction in conditioned taste preference.

In 2 experiments, the effects of axon-sparing lesions of the hippocampus on performance in aversive and appetitive taste conditioning tasks were investigated. In Exp 1, hippocampally lesioned rats showed no impairment of conditioned taste aversion learning relative to controls, but they did display an increased sensitivity to latent inhibition (LI). In Exp 2, the same hippocampectomized rats acquired a conditioned taste preference but failed to show any evidence of extinction. The influence of the neurotoxic lesion on LI is in the opposite direction to the effect typically found following hippocampal damage induced by traditional methods. Accordingly, the data present challenges for most current theories of hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal cortex lesions differentially disrupt cocaine-reinforced conditioned place preference but not conditioned taste aversion.

Male rats were anesthetized, and 1 of 3 subfields (medial, orbital, or precentral) of the prefrontal cortex (mesocortical dopaminergic [DA] target regions) was removed by aspiration, or no brain injury was done (sham Ss). In 4 experiments, Ss were tested on conditioned place preference, conditioned taste aversion (saccharin conditioned stimulus [CS], cocaine [CE] unconditioned stimulus [UCS]), general activity in the running wheel and open field, and food-reinforced spatial alternation in the T-maze. Results show that sham Ss showed a CE-induced place preference, medial frontal lesion Ss showed a CE-induced place aversion, and other Ss showed neither. All Ss showed a conditioned taste aversion of equal magnitude, and there were no lesion-induced differences in activity in either the running wheel or the open field. Medial frontal Ss were impaired relative to the precentral and sham Ss on learning to alternate choices in the T-maze, but orbital frontal Ss' performance was not different from that of any other group. Results indicate that mesocortical DA projection regions are involved with mediating the reinforcing properties of CE, and there is a separate system mediating the aversive properties of CE. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the perirhinal cortex in rats' conditioned taste aversion response memorization.

The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long-Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor and taste aversions conditioned in anesthetized rats.

Conditioned flavor aversions (CFA) are acquired by anesthetized rats but effects of various anesthetics on acquisition of aversions for separate odor and taste components are unknown. In Experiment 1, rats drank tomato juice and then were tranquilized with "Innovar-Vet" or "Rompun" before receiving injections of lithium chloride. Neither drug interfered with acquisition of aversions. Innovar-Vet alone produced no aversions; Rompun alone produced mild aversions but did not enhance aversions when combined with lithium. In Experiments 2 and 3, rats received a compound odor/taste cue as they drank and then were anesthetized with pentobarbital before lithium injections. Anesthesia alone produced negligible aversions but facilitated taste-lithium aversions. During odor tests, odor aversions were weaker than taste aversions. These data extend previous work and suggest that CFA does not result from ordinary classical conditioning. A tripartite notation that unites CFA and classical conditioning is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Caffeine promotes an ethanol-induced conditioned taste aversion: A dose-dependent interaction.

The present study examined whether caffeine administered within a dose range previously shown to promote ethanol drinking would also alter an ethanol-induced conditioned taste aversion (CTA). The results revealed a dose-dependent interaction between caffeine and ethanol where caffeine (2.5 and 10 mg/kg) promoted an ethanol-induced CTA at a low ethanol dose (1.0 g/kg) but had no effect in blocking CTA at the higher ethanol dose (1.5 g1kg). These results were found to be unrelated to an alteration in ethanol metabolism, as caffeine had no effect in altering blood ethanol levels at the doses tested. In agreement with the reward comparison hypothesis, the present results suggest that rather than attenuate ethanol's "aversive" effects, caffeine may have promoted an ethanol-induced CTA by increasing the reinforcing efficacy of ethanol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)