Conditioned Ethanol Aversion in Rats Induced by Voluntary Wheel Running, Forced Swimming, and Electric Shock: An Implication for Aversion Therapy of Alcoholism

This study was planned to demonstrate rats' acquisition of aversion to ethanol solution consumed before voluntary running, forced swimming, or electric shock delivery. Wistar rats under water deprivation were allotted to four groups of eight rats each, and all rats were allowed to drink 5% ethanol solution for 15 min. Immediately after the ethanol drinking, rats of Group Run were put into the individual running wheels for 15 min, those of Group Swim were put into the individual swimming pools for 15 min, those of Group Shock received electric shocks for 15 min (15 0.45-mA shocks of 0.7s with the intershock interval of 1 min) in the individual small chambers, and those of Group Control were directly returned back to the home cages. This procedure was repeated for six days, followed by a two-day choice test of ethanol aversion where a bottle containing 5% ethanol solution and a bottle of tap water were simultaneously presented for 15 min. In the test, Groups Run, Swim, and Shock drank ethanol solution significantly less than tapwater, while Group Control drank both fluids equally. The effects of running, swimming, and shock were equivalent. The successful demonstration of acquired ethanol aversion induced by exercise (running and swimming) or shock in rats suggests an avenue for clinical application of exercise and shock treatments for human alcoholics, though there are many issues to be resolved before the practical use.     

Swimming-induced taste aversion and its prevention by a prior history of swimming

In two experiments, the evidence showed that 20 min of forced swimming by rats caused aversion to a taste solution consumed before swimming. When one of two taste solutions (sodium saccharin or sodium chloride, counterbalanced across rats) was paired with swimming and the other was not, the rats’ intakes of these two solutions showed less consumption of the former than the latter solution. Furthermore, a post-training two-bottle choice test clearly demonstrated long-lasting avoidance of the swimming-paired solution. These results imply that forced swimming acts as an unconditioned stimulus for establishing taste aversion. Preexposure to swimming opportunities before conditioning disrupts such conditioned taste aversion induced by forced swimming.     

The effect of swimming experience on acquisition and retention of swimming-based taste aversion learning in rats

Swimming endows rats with an aversion to a taste solution consumed before swimming. The present study explored whether the experience of swimming before or after the taste-swimming trials interferes with swimming-based taste aversion learning. Experiment 1 demonstrated that a single preexposure to 20 min of swimming was as effective as four or eight preexposures in causing the interference effect. Experiment 2 found that a single 5-min preexposure was enough to cause the interference effect. Experiment 3 showed that preexposure to swimming interfered with but did not completely thwart the acquisition of swimming-based taste aversion learning. Experiment 4 failed to demonstrate a reliable retroactive interference effect by swimming postexposures. With a modified procedure, however, Experiment 5 successfully demonstrated a reliable effect by four postexposures. The associative and habituation accounts of these results are discussed.     

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.     

Taste aversion learning: simulation of interference with the gustatory cue during conditioning

Rats were taught an aversion to a sucrose taste cue of varying strengths. The concentration of the sucrose solution was either, 10, 7.5, 5, 2.5, 1, 0.5, or 0.25% which the animals drank for 5 min. Thirty minutes later they were poisoned with lithium chloride. On the test day all animals had access to a 10% sucrose solution regardless of the concentration they had drunk on the conditioning day. Animals conditioned with a 10, 7.5, or 5% sucrose cue subsequently displayed an identically strong aversion to the 10% cue. Only those animals conditioned with a sucrose cue which was 1% or less displayed a significantly weaker aversion to the 10% cue. The results are discussed in terms of the theory that interference with taste aversion learning by such agents as pentylenetetrazol and electroconvulsive shock may have their effect by disrupting the gustatory engram. If this assumption is correct then it suggests that the memory of the gustatory cue may be stored, at least prior to poisoning, in a quite labile state and an apparently limited disruption of taste aversion learning may in fact represent a substantial amnesic effect.     

Low body temperature,time dilation,and long-trace conditioned flavor aversion in rats

Conditioned flavor aversion was examined in Wistar-derived albino rats that were immersed in cold water for 0, 2.5, 5, or 10 min immediately following 10-min exposure to a.1% saccharin solution and given an intraperitoneal (i.p.) injection of 0.15 M lithium chloride (LiCl) either 90, 135, 180, or 225 min later. Cold water immersion for 2.5, 5, and 10 min led to body temperature decreases of approximately 4.5, 7, and 10 degrees C, respectively. Rats whose body temperatures were not reduced (0 min immersion) showed no saccharin aversion when the LiCl was delayed 90 min. Rats whose body temperatures were reduced 4.5, 7, and 10 degrees C displayed conditioned aversions at LiCl delays up to 135, 180, and 225 min, respectively. These results were interpreted in terms of a cold-induced slowing of a biochemical clock that may uniquely govern specific timing processes involved in associative learning over long delays, such as long-trace conditioned flavor aversion, learned safety, and certain types of learning that involve an extensive time lapse (e.g., extinction of fear).     

Biting attack by rats in response to aversive shock

Paired rats are known to behave aggressively when given painful electric shocks. The present study developed a procedure whereby individual rats given shocks might bite an inanimate target object. Unavoidable shock was delivered to the rat while it was restrained in a position close to, and facing a target object. Biting of the target was recorded automatically. Shock caused the rat to bite metal, wood, or rubber targets. Biting was most frequent immediately after shock and decreased as a direct function of time since the shock. Almost every shock produced biting and the behavior continued as long as the shocks were delivered. Biting ceased within and between sessions when shocks were discontinued. These results show how the pain-aggression relation can be studied objectively with rats.     

Taste Aversion Learning Based on Swimming and Lithium Chloride Injection in Rats: Implications From Cross-familiarization Tests and Stimulus Selectivity1

In rats, swimming causes avoidance of the taste solution consumed immediately before the swimming. Several lines of research have shown that this taste avoidance reflects Pavlovian conditioned aversion based on correlations between the taste and swimming-induced nausea. The present research compared swimming-based taste aversion learning (TAL) with conventional TAL based on nausea-inducing lithium chloride (LiCl). By exploiting cross-familiarization techniques, Experiments 1A and 1B suggested that different physiological states are induced by swimming and LiCl. This claim was supported by Experiment 2, which reports stimulus selectivity in saccharin and sucrose aversions based on swimming and LiCl.     

Facilitation of Sodium Aversion Learning in Sodium-Deprived Rats

Two experiments with rats explored the effects of sodium deprivation induced by furosemide injections upon acquisition of taste aversion to sodium chloride (NaCl). In Experiment 1, rats under either sodium deprivation or a balanced nutrition condition were given access to a limited amount of NaCl solution prior to poisoning. When all rats were tested under sodium repletion, the previously sodium-deprived rats consumed less NaCl than did the nondeprived rats. This finding was replicated in Experiment 2A in which ingestion of a compound solution of NaCl and hydrochloric acid (HCl) was followed by poisoning. Consumption of HCl, however, showed the opposite pattern: the sodium-deprived rats drank more HCl than did the nondeprived rats, a result that was replicated in Experiment 2B. These results suggest that sodium deprivation strengthens the salience of NaCl, thereby facilitating acquisition of aversion to this taste and strongly overshadowing that to a simultaneously presented taste.     

Perirhinal cortex lesions impair context aversion learning

Rats with perirhinal cortex lesions were compared with sham controls on a conditional discrimination in which saccharin was paired with LiCl in context 1, but paired with saline in context 2. Perirhinal-lesioned rats were slightly slower to acquire the discrimination but reached control levels by the end of acquisition. Both groups showed transfer to familiar tap water, consuming less in context 1 than in context 2. Unlike sham rats, perirhinal rats failed to show an aversion to context 1 on a place choice test. These data provide neuroanatomical support for the postulated difference between Pavlovian conditioning and conditional learning.     

Weanlings' transfer of conditioned ethanol aversion from olfaction to ingestion depends on the unconditioned stimulus

Weanling (21-day-old) rats were exposed to an alcohol odor paired with either an interoceptive (apomorphine-induced illness) or exteroceptive (footshock-induced distress) reinforcer. Twenty-four hours later, ethanol preferences were measured in a locational olfactory test (ethanol vs lemon odor) or an ingestion test (5.6% v/v ethanol vs 0.25% v/v citric acid solution). Weanling rats expressed substantial olfactory aversions, independent of the reinforcer employed in conditioning. During the drinking test, however, only rats that had experienced the ethanol odor paired with internal malaise showed a significant reduction in the intake of the ethanol solution when compared to unpaired controls. Furthermore, rats that had experienced the ethanol odor paired with external distress drank significantly more of the ethanol solution than their controls. These results provide further evidence that olfactory experiences with ethanol can lead to changes in ethanol ingestion, and indicate that the nature of the unconditioned stimulus is critical in establishing the ingestive effect.     

Selective associations in one-day-old rats: taste-toxicosis and texture-shock aversion learning

One-day-old rats learned aversions to a novel taste paired with lithium-induced distress and to a tactile stimulus paired with brief electric shocks. However, aversions did not develop when taste was paired with shock or when the tactile stimulus was paired with lithium treatment. The aversions occurred only when lithium treatment immediately followed taste exposure and when shock was concurrent with exposure to the tactile stimulus. These findings indicate that selective associations in aversion learning are mediated by innate mechanisms that govern conditioning in the absence of extensive ontogenetic experience. The present research also shows that selective associations are sufficient for the occurrence of long-delay learning.     

Inactivation of the basolateral amygdala impairs the retrieval of recent and remote taste-potentiated odor aversion memory

Memory reorganization as a time-dependent process can be investigated using various learning tasks such as the taste-potentiated odor aversion (TPOA). In this paradigm rats acquire a strong aversion to an olfactory cue presented simultaneously with a gustatory cue. Together these cues are paired with a delayed visceral illness. The basolateral amygdaloid nucleus (BLA) plays a key role in TPOA acquisition but its involvement in retrieval remains unclear. We investigated the involvement of the BLA in either recent or remote retrieval of TPOA. In each case, the number of licks observed in response to the presentation of either the odor or the taste was used to assess retrieval. Before the retrieval test, rats received a bilateral infusion of lidocaine to inactivate the BLA. We observed that both recent and remote TPOA retrieval tests induced by the odor presentation were disrupted in the lidocaine-injected rats. By contrast, the BLA inactivation had no effect upon the aversion towards the taste cue regardless of the time of retrieval. The present study provides evidence that BLA functioning is necessary for retrieval of aversive odor memory, even with a long post-acquisition delay.     

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.     

Flavour aversion produced by running and attenuated by prior exposure to wheels

In two experiments hungry rats were given access to running wheels. When given the novel flavour, almond, prior to novel access to the wheels, a conditioned aversion to almond was revealed by a subsequent two-bottle test. No such aversion was found in rats with previous experience of wheel running, whether this prior running occurred in the absence of any novel flavour, as in Experiment 1, or following access to saccharin, as in Experiment 2. These results suggest that the failure of rats with prior experience of the running wheels to develop a flavour aversion (unconditioned stimulus, US, preexposure effect) is unlikely to be due to associative blocking. Instead it seems that increasing exposure to a wheel produces habituation of its nausea-inducing properties.     

Behavioral stress impairs long-term potentiation in rodent hippocampus

A number of hormones secreted from the pituitary-adrenal system during stress affect learning and memory processes. The phenomenon of hippocampal long-term potentiation (LTP) is viewed by many as a putative mechanism of memory storage and has proved a most valuable model for study of neuronal plasticity at the cellular level. The present study was conducted to investigate the possibility that stressful events which occur prior (in vivo) to the preparation of brain slices may influence the electrophysiology of the in vitro hippocampal explant when tested for LTP. Adult male rats (Long-Evans male X Sprague-Dawley female) were pair-housed 1 week prior to testing. One animal in each pair was either placed in a restraining tube for 30 min and received no tail shocks (Restraint) or placed in a restraining tube and received tail shocks (1 microA, 1 s) every minute for 30 min (Restraint + Shock). The other animal in each pair was taken directly from the home cage and received no restraint or tail shock (Control). In vitro hippocampal slices were then prepared immediately from these animals according to standard methods. Our results demonstrate a marked impairment of LTP in hippocampal explants taken from rats exposed to stress. The significance of this result with respect to cellular mechanisms underlying the relationship between stress, cognition, and learning is discussed.     

Group aversion by imaginal, vicarious and shared recipient-observer shocks

Sixty college students completed waiting control or alternative group aversion conditions, matched for severity and chronicity of nail-biting. Treatments spanned four sessions. Imaginai aversion (covert sensitization) clients visualized shocks to themselves. Vicarious aversion clients observed shocks to a trained model. A ‘hotseat’ format randomized a few actual shocks to each client with observing peers shocked on remaining trials. The predominant pattern of outcome and subjective impact results was as follows: Hotseat consistently best; vicarious typically second; imaginal usually third; controls worst. Clinical and conceptual issues are raised.     

Shock-induced aggression as a function of prior experience with avoidance, fighting, or unavoidable shock

Rats were trained in shock-induced aggression, free operant avoidance, or were presented with unavoidable shocks. Fighting in response to shock was subsequently measured by intermatching individual animals that had received the three training procedures. The fighting probabilities of animals with histories of avoidance and dominant animals with histories of fighting were higher than the fighting probabilities of non-dominant fighting rats or rats with a history of unavoidable shocks. Animals with higher fighting probabilities disrupted avoidance baselines more than animals with lower fighting probabilities. Control experiments suggested that fighting decrements produced by administration of prior grid-shock were due to the acquisition of behaviors incompatible with aggression.     

Further Evidence for Swimming-Based Pica in Rats

Aberrant pica behavior (i.e., kaolin clay ingestion) has been regarded as a behavioral marker of nausea in rats that cannot vomit because of anatomical and/or neural reasons. The previous study reported that a single swimming session of 40 min generated pica behavior, implying that swimming induces nausea in rats. However, the rats tested in that report were not experimentally naive. The present study successfully replicated swimming-based pica with experimentally naive rats (Experiment 1). It also showed that pica was observed with pool confinement of 20 min but not with that of 10 min (Experiments 2A and 2B) and that roaming in shallow water did not generate pica (Experiment 3). These results taken together suggest that swimming for at least 20 min induces nausea in rats, implying that rats’ taste aversion learning based on swimming is mediated by gastrointestinal discomfort.     

Electrical aversion therapy with alcoholics: An analogue study

Chronic alcoholic patients matched on age, education and length of problem drinking were assigned to one of three treatment conditions, with 10 subjects in each group: (1) Electrical Aversion Conditioning (high shock paired with alcohol sips); (2) Control Conditioning (very low shock paired with alcohol sips); and (3) Group Therapy (confrontation psychotherapy). Groups 2 and 3 were included to control for possible ‘attention-placebo’ and expectancy factors involved in the conditioning procedures. Subjects in each group were given instructions designed to produce high expectancy for therapeutic success. Pre-post measures of alcohol consumption and attitudes toward alcohol were obtained using an analogue ‘taste test’ assessment procedure. No statistically significant differences in reduced alcohol consumption or attitudes toward alcohol were found among the groups. Trends in the data support the contention that effects of electrical aversion may be more related to such factors as therapeutic instructions, expectancy, specificity of the procedure or experimental demand characteristics than to conditioning factors.