Effects of stimulus preexposure on the generalization of conditioned taste aversions in infant rats

Generalization of a conditioned taste aversion in infant rats and how this is affected by stimulus preexposure was investigated in a series of experiments. In Experiment 1 generalization of a conditioned aversion between two tastes (sweet and salty) was found, and the effect of tastes preexposure was a reduction in generalization (Experiment 2). However, when these tastes were combined with a common taste (acid) that was less (Experiment 3) or more intense (Experiment 3b), the effect of stimulus preexposure was a stronger generalization of the conditioned aversion. In this case, a reduction on generalization was again observed by increasing the number of preexposure trials to the taste compounds (Experiment 4). In all cases the generalization levels were directly related to the effect of stimulus preexposure on the acquisition rate of conditioning. It can be concluded that, with the appropriate parameters, a reduction of generalization of a conditioned taste aversion can be obtained after taste exposure in preweanling rats.     

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.     

Interactions of temperature and taste in conditioned aversions

The influence of temperature on taste cues and the ability to discriminate and learn about different temperatures of foods are important factors regulating ingestion. The goal of this research was to demonstrate that thermal orosensory input can serve as a salient stimulus to guide ingestive behavior in the rat, and also that it interacts with gustatory input during choice and conditioned aversion experiments. A novel apparatus with Peltier refrigerators was used to control the temperature of solutions in 10-min, 2-bottle tests. It was determined that naive rats preferred cold water (10 °C) to warm water (40°). When cold water was paired with a toxic LiCl injection, rats avoided cold water and drank warm water, thus demonstrating that cold water could serve as the conditioned stimulus in a conditioned temperature aversion. Rats conditioned against cold water could discriminate 10 °C water from 16 °C water, but not from 13 °C water, thus showing an ability to discriminate orosensory thermal cues to within 3-6 °C. Rats also generalized conditioned aversions from cold water to cold saccharin and cold sucrose solutions. However, if rats were conditioned against a compound taste and thermal stimulus (10 °C, 0.125% saccharin), the rats could distinguish and avoid each component individually, i.e., by avoiding cold water or warm saccharin. Finally, daily 2-bottle extinction tests were used to assess the strength of aversions conditioned against a taste cue (0.25 M sucrose), a thermal cue (10 °C water), or the combination. Aversions to taste or temperature alone persisted for 7-14 days of extinction testing, but the combined taste-temperature aversion was stronger and did not extinguish after 20 days of extinction testing. These results demonstrate that temperature can serve as a salient cue in conditioned aversions that affect ingestion independent of taste cues or by potentiating taste cues.     

Effects of cross-fostering on cocaine-induced conditioned taste aversions in Fischer and Lewis rats

The systematic comparison between Fischer and Lewis rats is a popular animal model of genetic factors in drug abuse. Although genetic and environmental factors interact to affect drug abuse in humans, analogous effects have not yet been reported within the Fischer-Lewis model. In order to assess the contributions and interaction of genotype and early maternal environment on responses to a drug of abuse, the present study employed a cross-fostering design, where male and female Fischer and Lewis pups were reared by unrelated dams of their own strain (in-fostered) or of the other strain (cross-fostered). As adults, rats from both strains were tested for their ability to acquire a conditioned taste aversion to a novel saccharin solution that had been repeatedly paired with an injection of cocaine (32 mg/kg, subcutaneous). In-fostered Fischer females acquired significantly weaker aversions than in-fostered Lewis females across the multiple saccharin-cocaine pairings. However, cross-fostered Fischer females exhibited aversions that were not only significantly stronger than their in-fostered Fischer counterparts, but identical to all groups of the Lewis genotype. No strain differences or cross-fostering effects were observed in the males. The data with the female subjects cannot be accounted for simply by the genetic strain of the subjects and demonstrate a clear gene-environment interaction effect on responses to the aversive effects of cocaine in Fischer and Lewis rats. Implications for studying maternal behavior as a source of epigenetic modulation of drug abuse vulnerability were discussed.     

A measure of taste intensity discrimination in the rat through conditioned taste aversions

The ability of rats to make intensity discriminations was determined by forming a conditioned taste aversion to a moderate concentration of each of four basic taste stimuli, and then measuring the level of acceptance (number of licks during a 15 sec exposure) shown to a range of concentrations of the same chemical. Rats (N = 66) could discriminate between glucose concentrations that were separated by as little as 0.074 M, between NaCl concentrations that differed by 0.029 M, between HCl concentrations that were 9 X 10(-4) M apart, and between quinine HCl concentrations that differed by as little as 2.4 X 10(-6) M.     

The effects of haloperidol on cocaine-induced conditioned taste aversions

Although the mechanism underlying the rewarding effects of cocaine has been well characterized, little is known about the mechanism underlying its aversive effects. Several reports have indicated a possible role of dopamine (DA) in the aversive effects; however, several procedural issues limit any conclusions regarding its specific role. In order to investigate a possible dopaminergic role in cocaine-induced CTAs using procedures that circumvented these possible issues, the present series of investigations assessed the aversive effects of the DA antagonist haloperidol alone (Experiment 1) and in combination with cocaine (Experiment 2). Haloperidol, at doses that were determined to be non-aversive, yet behaviorally active in a locomotor assessment, attenuated cocaine-induced taste aversions, suggesting that cocaine's aversive effects are mediated in part by dopaminergic activity. These findings were discussed in consideration with other evidence implicating DA and other neurotransmitter systems in cocaine-induced CTAs.     

Gonadal steroids and the extinction of conditioned taste aversions in young domestic fowl

Three experiments using domestic chicks demonstrate that the extinction of a conditioned taste aversion to a green-coloured sucrose solution is slowed by the administration of testosterone or 5 alpha-dihydrotestosterone but is unaffected by estradiol. Testosterone slows extinction in male and female chicks to an equal extent. Previously described effects of testosterone on attentional and memory mechanisms have also been produced by low doses of estradiol so a separate mechanism must be postulated to explain the present results. It is probably similar to the mechanism responsible for a steroid-dependent slowing of extinction in rats since those effects are also androgenic and present in both sexes.     

Effects of acute swim stress on LiCl-induced conditioned taste aversions.

The present study examined the effects of a 5-min period of swim stress experienced between a flavor (saccharin) and illness (LiCl) on conditioned taste aversion learning. Experiment 1 obtained a stress-induced attenuation of learning. Experiment 2 replicated the findings of Experiment 1, and also obtained a similar attenuation when stress was administered 30 min prior to the saccharin presentation. Experiment 3 examined the effects of swim stress either 15 min or 90 min after the LiCl had been administered. It was found that swim stress 15 min after LiCl significantly attenuated CTA, but swim stress 90 min after LiCl did not. These results are discussed with regard to current views of the relationship between external events and conditioned taste aversions.     

Disparity between formation of conditioned flavor aversions and neophobia during grooming in rats and mice

Mice (Mus musculus) allowed to groom a paste containing saccharin from their fur before injection with lithium chloride displayed a saccharin aversion in subsequent drinking preference tests. No attenuation of neophobia was observed in mice grooming saccharin because the animals failed to display a neophobia towards saccharin in drinking tests. Rattus norvegicus displayed neophobia towards saccharin in two- and single-bottle drinking tests but this neophobia was not attenuated by grooming experience with the saccharin paste. Rats apparently learn that if a taste is hazardous in the grooming context it is also likely hazardous in an appetitive context. Learned safety in grooming, however, does not generalize into the appetitive context. The results support the view that neophobia and learned taste aversion depend upon different mechanisms.     

Domperidone interferes with conditioned disgust reactions but not taste avoidance evoked by a LiCl-paired taste in infant rats

Rats exhibit taste avoidance and conditioned disgust reactions when stimulated with a tastant paired with lithium chloride (LiCl). Lithium-mediated activation of chemoreceptor nuclei at the brainstem appears to determine the acquisition of conditioned taste aversion (CTA) in adult rodents. Domperidone (DOM), an anti-emetic drug that does not cross the blood-brain barrier, was employed to analyze mechanisms underlying LiCl-mediated CTA in infant rats. On postnatal day 13 animals were given DOM followed by a pairing between intraoral saccharin and LiCl. Saccharin consumption at testing was lower in lithium-treated pups than in controls. DOM did not interfere with this LiCl-mediated taste avoidance but significantly decreased LiCl-mediated disgust reactions (head-shaking and wall climbing). Activation of the emetic system of the brainstem does not seem necessary for the acquisition of LiCl-mediated conditioned taste avoidance. Yet, these centers seem to be involved in the palatability shift resulting from taste-LiCl pairings. These results indicate an early dissociation between conditioned disgust reactions and conditioned taste avoidance.     

Stimulus modality effects on transformations of conditioned enhancement and conditioned suppression in rats

Unconditioned and conditioned effects of house-light offset and acoustic white noise on barpressing behavior maintained by intermittent food reinforcement were tested in male hooded rats. Presentations of these stimuli prior to their acquiring signal value initially tended to depress and then to enhance barpressing rate, but generally the rate of the on-going barpressing was lower during the light offset then during noise presentations. Subsequently, one stimulus was used to signal continuous food reinforcement, evoking conditioned enhancement, and the other to signal inescapable footshock eliciting conditioned suppression of barpressing. The enhancement was acquired more rapidly than the suppression, independent of the stimulus modality used. The stimulus modality effect emerged when the continuous food reinforcement was withdrawn, since enhancement elicited by light offset extinguished more rapidly than elicited by noise. The stimulus modality effect was stronger when the other stimulus continued to signal pain and was attenuated when conditioned suppression was also extinguished. During the next stage of the experiment, the signal values of the conditioned stimuli were reversed, resulting in easy transformation of conditioned suppression into conditioned enhancement and vice versa. The stimuli used and changes in their signal values exerted clear effects on the rate of barpressing during intertrial intervals and this, in turn, somewhat modulated the behavioral effects of the conditioned stimuli. These results indicate that unconditioned effects of the stimuli on the behavior interact with their properties acquired in the course of conditioning.     

Vestibular lesions selectively abolish body rotation-induced,but not lithium-induced,conditioned taste aversions (oral rejection responses) in rats

Pairing a novel taste with provocative vestibular stimulation results in conditioned taste aversions in both rats and humans. Vestibular system involvement in gustatory conditioning was examined in sham-lesioned or labyrinthectomized rats. Three conditioning trials consisted of 30 min access to asaccharin (0.1%) solution followed by 30 min of rotation (70 rpm) or sham rotation. In a taste reactivity test with saccharin, rotated sham-lesioned rats, but not labyrinthectomized rats, exhibited increased oral rejection reactions compared with control rats. When conditioned with lithium chloride, both labyrinthectomized and sham-lesioned rats displayed robust conditioned rejection reactions. The finding that normal vestibular function is necessary in obtaining rotation-induced conditioned taste aversions supports the face and construct validity of a rat model of motion sickness.     

Acid taste thresholds assessed by conditioned taste aversion and two-bottle preference in rats

The conditioned taste aversion (CTA) threshold for either citric acid (CA) or HCl solutions and the two-bottle taste preference (TBP) threshold were determined in rats that are familiarized to the odor of conditioning solutions or that are naive. The CTA method appeared to be more sensitive than the TBP test, particularly when rats were not familiarized to the odor of the conditioning solution. The CTA threshold for HCl-conditioned rats and familiarized to the odor of conditioning solution lies between 1.00 and 2.00 mmol; in unconditioned rats, it lies between 4.00 and 5.00 mmol. In CA-conditioned and odor-familiarized rats, the threshold lies between 0.09 and 0.20 mmol; in unconditioned rats, it lies between 7.00 and 10.00 mmol. In rats not familiarized to the odor of the conditioning solution, the threshold for HCl-conditioned rats lies between 0.90 and 1.00 mmol; in unconditioned rats, it lies between 2.00 and 3.00 mmol. In CA-conditioned rats, the CTA threshold lies between 0.03 and 0.05 mmol; in unconditioned rats, it lies between 4.00 and 7.00 mmol. The two-bottle test is less sensitive than the CTA method. The TBP threshold lies between HCl 4.00 and 5.00 mmol, and between CA 4.00 and 7.00 mmol. The odor of a solution may potentiate the ability of rats to detect the concentration of CA and HCl solutions.     

Gamma radiation-induced conditioned taste aversions in rats: a comparison of the protective effects of area postrema lesions with differing doses of radiation

Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In the present experiment, 4 groups of male rats received lesions of AP and 4 groups were given sham lesions. One sham-lesioned and one AP-lesioned group were given a single pairing of 1-hr access to a novel 0.10% sodium saccharin solution followed immediately with exposure to 0, 100, 200, or 400 rad of gamma radiation, respectively. Four days later all groups were given daily two-bottle preference tests (saccharin vs. water) on 4 consecutive days. The sham-lesioned groups exposed to the radiation (100, 200, or 400 rad) developed profound aversions to the saccharin on all test days (p less than 0.001). In contrast, all of the AP-lesioned groups as well as the sham-irradiated (0 rad) sham-lesioned group exhibited strong, comparable (p greater than 0.30) preferences for saccharin. Thus, lesion of AP abolished the radiation-induced CTA at all dose levels of radiation. These results raise the possibility of pharmacological intervention at the level of AP to prevent radiation-induced CTA in cancer patients undergoing radiation therapy.     

Motion sickness in guinea pigs (Cavia porcellus) indexed by body rotation-induced conditioned taste aversions

The presence of motion sickness in albino guinea pigs (Cavia porcellus) was examined by using a conditioned taste aversion (CTA) as an index. Eighteen animals were divided into three groups. One group received four pairings of a novel 0.15% saccharin solution followed by 20 min of body rotation at 70 rpm (on a schedule of 15 sec on and 5 sec off). Another group received four pairings of the saccharin solution followed by exposure to sham rotation. The third group experienced the rotation procedure following access to water. The group receiving the rotation procedure contingent on presentation of the novel saccharin taste exhibited a conditioned aversion to this fluid (relative to the control groups) over days of acquisition (p less than 0.01), which subsequently dissipated when rotation was no longer contingent on the presentation of the saccharin solution (extinction). These data thus demonstrate the presence of motion sickness in guinea pigs when CTA is used as an index.     

Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats

Administration of lithium chloride, copper sulfate, and apomorphine to rats each stimulated the secretion of oxytocin (OT) and, to a much lesser degree, arginine vasopressin. These agents are assumed to cause visceral illness in rats because of their effectiveness in promoting the acquisition of learned taste aversions. CuSO4 had a greater effect on plasma OT levels when administered ip rather than iv, whereas LiCl did not, results suggesting that LiCl probably stimulates OT secretion by central chemoreceptor activation whereas CuSO4 acts predominantly by local peritoneal irritation. A causal role for circulating OT in the acquisition of learned taste aversions was not found. These and other findings suggest that peripheral levels of OT may represent a quantifiable marker of visceral illness in rats and therefore might be useful in the interpretation of behavioral studies in which learned taste aversions are produced, provided that other stimuli of neurohypophyseal secretion are absent.