The effect of drug habituation before and after taste aversion learning in rats

In Experiment I, rats received eight habituation injections of either lithium chloride (LiCl) or sodium chloride (NaCl), then two aversion training trials in which access to saccharin solution was followed by LiCl injections, and finally eight extinction trials with saccharin but no injections. The rats habituated to LiCl showed less aversion to saccharin during training and extinction. In Experiment II, rats received two aversion training trials, then eight habituation trials to either LiCl or NaCl, then eight extinction trials, four more aversion training trials, and eight more extinction trials. The rats habituated to LiCl did not differ during the first extinction period from those habituated to NaCl, but showed less aversion to saccharin during the second training and extinction periods. Consequently, habituation to LiCl reduces the learning of an aversion to saccharin but does not reduce the performance of a previously learned aversion.     

The role of habituation of the response to LiCl in the US-preexposure effect

In two experiments, rats received preexposure consisting of six intraperitoneal injections of lithium chloride (LiCl). This treatment reduced the magnitude of the unconditioned response (UR; suppressed consumption of a novel flavor) evoked by an additional injection (Experiment 1) or by oral consumption (Experiment 2) of LiCl. In both experiments, preexposure also attenuated the acquisition of a conditioned aversion with an LiCl injection as the unconditioned stimulus (US) but had no effect on the aversion produced when the US was oral consumption of LiCl (Experiment 2). These results are consistent with the view that the reduced ability of the preexposed US to serve as a reinforcer depends on blocking by injection-related cues and is independent of habituation of the UR recorded in the present study. Possible interpretations of this dissociation are discussed.     

The role of injection cues in the production of the morphine preexposure effect in taste aversion learning

The attenuation of an LiCl-induced conditioned taste aversion (CTA) by LiCl preexposure is mediated primarily by associative blocking via injection-related cues. Given that preexposure to morphine attenuates morphine-induced CTAs, it was of interest to determine whether injection cues also mediate this effect. Certain morphine-induced behaviors such as analgesic tolerance are controlled associatively, via injection-related cues. Accordingly, animals in the present experiments were preexposed to morphine (or vehicle) every other day for five total exposures, followed by an extinction phase, in which the subjects were given saline injections (or no treatment) for 8 (Experiment 1) or 16 (Experiment 2) consecutive days. All of the animals then received five CTA trials with morphine (or vehicle). The morphine-preexposed animals in Experiment 1 displayed an attenuation of the morphine CTA that was unaffected by extinction saline injections, suggesting that blocking by injection cues during morphine preexposure does not mediate this effect. All of the morphine-preexposed subjects in Experiment 2 displayed a weakened preexposure effect, an effect inconsistent with a selective extinction of drug-associated stimuli. The attenuating effects of morphine preexposure in aversion learning are most likely controlled by nonassociative mechanisms, like drug tolerance.     

Extinction of a saccharin—lithium association: Assessment by consumption and taste reactivity

Extinction of a conditioned palatability shift preceded extinction of conditioned taste avoidance whether rats were tested using a within-subjects design or a between-subjects design. In each of two experiments, consumption of 0.1% saccharin was paired with either 20 ml/kg of 0.15 M LiCl or equivolume physiological saline on a single trial. In Experiment 1, on each of 10 extinction trials, rats were given a taste reactivity test immediately prior to a consumption test. In Experiment 2, half of the rats were extinguished by taste reactivity testing and half of the rats were extinguished by a consumption test on each of 10 extinction trials. In both experiments, the aversive reactions of gaping and passive dripping were extinguished in a single trial and the suppression of ingestive reactions was extinguished in 2 trials; however, extinction of taste avoidance required 4–5 trials. These results suggest that rats continue to avoid a lithium-paired flavor even when they do not have an aversion to the taste.     

Expression of a taste aversion conditioned with an odor-taste compound: Overshadowing is relatively weak in weanlings and decreases over a retention interval in adults

Adult rats were injected with lithium chloride (LiCl) after consumption of a novel flavor (chocolate milk) that either was or was not presented together with a novel ambient odor (banana) as a compound conditioned stimulus (CS). In Experiment 1, the adults’ consumption of the flavor 24 h after conditioning was compared with that of weanling rats given the same conditioning treatment on Postnatal Day 21. The results confirmed previous indications that the reduction in aversion observed for adults conditioned with the compound CS (overshadowing) was weak or nonexistent in weanlings. After a longer retention interval (21 days), there was no evidence of overshadowing in adults despite maintained retention of the basic conditioned aversion. In Experiment 2 this decrease in overshadowing after a long retention interval was replicated with adult animals and extended to a different method of testing. The form of the effect was the same as in Experiment 1: The decrease in overshadowing occurred over the retention interval without loss in retention of the basic taste aversion; the decrease in overshadowing was a consequence of anincrease in the flavor aversion displayed by animals conditioned with the compound CS. The impaired flavor aversion (i.e., the overshadowing) observed shortly after conditioning apparently was due to factors associated with memory retrieval, rather than to reduced attentional or associative strength.     

Variations in the retention of taste aversions: Evidence for retrieval competition

In six experiments, we examined taste and compound taste/taste aversions at different retention intervals. In Experiment 1, saccharin aversions were significantly weaker 1 day after conditioning than 21 days after conditioning. This effect was determined not to be caused by the aftereffects of illness or differential hydration. With the use of a saccharin/denatonium compound, Experiment 2 demonstrated overshadowing of a denatonium aversion at 21- and 1-day retention intervals, Experiment 4 showed a potentiated saccharin aversion only at the 21-day retention interval, and both Experiments 2 and 4 revealed that the aversion of the taste-only controls was stronger at the later retention interval. Experiments 3 and 5 demonstrated that the differences at the two retention intervals were not caused by unconditioned changes in taste preference. Finally, Experiment 6 showed that extinction of the conditioning environment prior to testing results in stronger saccharin aversions than occur in nonextinguished controls. Collectively, these experiments suggest that testing within a 24-h period after conditioning will result in significantly weaker taste aversions. Also, these results support a retrieval-competition explanation that may account for the weakened aversions at the 1-day testing interval of both groups conditioned to single elements and those conditioned to compounds.     

Cross-modality contrast: Exteroceptive context habituation enhances taste neophobia and conditioned taste aversions

The relationship between absolute and relative stimulus novelty was examined within the context of the conditioned taste aversion paradigm in which the relative novelty of the conditioned interoceptive stimulus was manipulated by differential exteroceptive context habituation. Rats received similar isolation histories but either 5 or 30 days of habituation to the test environment prior to treatment. One group was administered lithium chloride following saccharin consumption, a second group was administered isotonic saline following saccharin consumption, and a third group was administered saline after water consumption. The animals habituated for 30 days exhibited greater conditioned avoidance and greater neophobic avoidance of saccharin than did animals habituated for only 5 days. The results are interpreted in terms of a cross-modality stimulus contrast effect which implicates context habituation as an important parameter of both taste neophobia and taste aversion learning.     

Injected flavor as a CS in the conditioned aversion preparation

Three experiments were conducted to determine the effectiveness of intravenous (IV) flavor injections in the formation of conditioned taste aversions and in the attenuation of neophobia. In Experiment 1, two groups of rats were permitted to drink either a .1% saccharin solution or tap water followed immediately by IV injections of lithium chloride (LiCl), and two more groups were given IV injections of a 2% saccharin solution followed immediately by IV injections of either LiCl or distilled water. Injected flavor did not serve as an effective CS for the conditioning of an aversion to .1% saccharin. The second experiment employed a two-bottle procedure to detect attenuation of neophobia using the injected-flavor technique. It was found that, whether saccharin had been injected intravenously (2%), injected intraperitoneally (2% IP), or orally consumed (.1%), neophobia for .5% saccharin was attenuated equally relative to controls. CS-US intervals were manipulated in the final experiment such that IP injections of 2% saccharin solution were followed 0–480 min later by IP injections of LiCl. In this case, it was shown that injected flavor (2% saccharin) could act as an effective CS if the US was delayed (optimally about 120 min) and when the test solution was .1% saccharin. The delay gradient found in Experiment 3 was interpreted as a generalization gradient where optimum conditioning was displayed at the point where the concentration of saccharin circulating in the animal at the time of illness onset most closely matched the concentration of the test solution.     

Effect of taste preexposure on taste and odor aversions

Thirsty Sprague-Dawley rats drank flavored water in a wind tunnel prior to lithium-induced toxicosis. Flavors were presented for 5 min; 30 min later a toxin, lithium chloride, was injected. After the rats had recovered, subsequent aversions to the taste and the odor were assessed separately. In Experiment 1, extensive preexposure to the taste component of the flavor attenuated neophobia to the flavor and the subsequent taste aversion. However, the subsequent odor aversion was unaffected. Experiment 2 partially replicated the results of Experiment 1 and showed that, in a situation in which only taste-potentiated odor aversions are usually found, nonpotentiated aversions were evident. Experiment 3 found that, in addition to attenuating taste aversions, taste preexposure enhances the capacity of rats to learn nonpotentiated odor aversions. The results are interpreted with a neural-based model of conditioned flavor aversions.     

What the rat’s nose tells the rat’s mouth: Long delay aversion conditioning with aqueous odors and potentiation of taste by odors

In Experiment 1, olfactory bulbectomized and control rats were trained using operant conditioning to determine the taste threshold of aqueous amyl acetate. Concentrations below gustatory threshold were used in Experiments 2–5 to compare the effectiveness of odors with various concentrations of saccharin as cues for illness. The results showed the following: (1) The effectiveness of odor and taste was directly related to concentration; (2) the strength of an aversion to a concentration of taste could be matched by an appropriate concentration of an odor; (3) odor was as effective as taste with CS-US delays of 4 h; and (4) an effective odor potentiated an aversion to an otherwise ineffective taste. The results challenge the privileged role accorded tastes in food aversion learning and the manner in which tastes are held to interact with odors according to the sensory-and-gate channeling analysis of potentiation (Rusiniak, Hankins, Garcia, & Brett, 1979).     

Acquisition and retention of conditioned aversions to context and taste in laboratory mice

We compared the rate of acquisition and strength of retention of conditioned context aversion (CCA) with conditioned taste aversion (CTA) using pigmented, genetically heterogeneous mice (derived from Large and Small strains). Extending previous findings, in Experiment 1, mice accustomed to drinking from large glass bottles in the colony room learned to avoid graduated tubes after a single conditioning trial when drinking from these novel tubes was paired with injections of LiCl. The results also showed that CCA could be developed even when there was a 30-minute delay between conditioned stimulus and unconditioned stimulus. Retention of the aversion lasted for 4 weeks in both Immediate and Delay groups. Studies of conditioned saccharin aversion were conducted in Experiment 2. CTA acquisition was very similar to that observed in CCA and duration of aversion retention was similar in the CCA and CTA Delay groups, although at least 2 weeks longer in the Immediate group. Thus, CCA acquisition and retention characteristics are closer to those seen for CTA than has previously been reported. In Experiment 3, we examined whether albino mice (which are known to have weaker visual abilities compared to pigmented mice) would develop CCA comparable to those of pigmented mice. The development of conditioned aversion and its duration of retention was similar in albinos and pigmented mice. Nonspecific aversion emerged as an important contributor to strength of aversion during retention trials in both CCA and CTA paradigms with pigmented (but not albino) mice and deserves additional scrutiny in this field of inquiry.     

Slow reacquisition of a conditioned taste aversion

Rats were used to examine the extent to which extinction of an acquired conditioned taste aversion retards subsequent reacquisition. A saccharin-flavored solution (sac) was paired with LiCl and then followed by CS-alone extinction trials with this flavor. A control group received a different flavor, decaffeinated-coffee (coff), during initial conditioning and extinction. Sac was then paired with LiCl for all rats during a second conditioning phase. Reacquisition of the aversion to sac was retarded relative to the acquisition of an aversion to sac by the control group. A similar experiment with fewer extinction trials, but still with complete loss of the initial aversion, did not obtain slow reacquisition. The results are discussed with respect to an interference view of extinction and the slow-reacquisition effect.     

Taste aversion learning and schedule-induced polydipsia in rats

Experiment 1 sought to determine whether schedule-induced drinking could be abolished by means of a taste aversion. Polydipsic rats were given access to a .4% saccharin solution while they were exposed to an intermittent food schedule. Immediately after the session, they received an intraperitoneal injection of either lithium chloride or sodium chloride. Following a recovery day with water in the experimental chamber, the animals were again exposed to the saccharin solution. The poisoned animals (lithium chloride) drank very little saccharin compared to the control animals (sodium chloride), indicating that they had learned a taste aversion in only one conditioning trial. Experiment 2 established that polydipsic rats can learn a taste aversion despite a long delay between schedule-induced saccharin consumption and poisoning, and that the delay gradient displayed by polydipsic rats is similar to that observed in thirst-motivated rats.     

Reinstatement-induced recovery of a taste-LiCl association following extinction

Water-deprived rats were given a single exposure to saccharin and LiCl, either paired or unpaired. Half the subjects then received three saccharin-only exposures (extinction) in the training enclosure, followed by a single LiCl-only presentation (unconditioned stimulus reinstatement) 8 days after conditioning. The remaining subjects received six saccharin-only exposures, followed by LiCl reinstatement 13 days after conditioning. In both cases LiCl reinstatement occurred outside the training/test context. Appreciable recovery from extinction was observed after the partial loss of taste aversion obtained with three extinction sessions and the 8-day conditioning-reinstatement interval, but not after the asymptotic loss of taste aversion obtained with six extinction sessions and the 13-day conditioning-reinstatement interval. Conditioned taste aversions appear to be similar to more traditional associations with respect to both extinction and reinstatement-induced recovery from extinction. The results are discussed with reference to the event-memory, contextual-conditioning, and facilitated-retrieval hypotheses of postextinction reinstatement effects.     

Amount of solution drunk is a factor in the establishment of taste aversion

Experiment I demonstrated that the strength of a rat’s aversion to saccharin is a direct function of the amount of saccharin it consumed prior to poisoning. Using Kalat and Rozin’s (1973) procedure, Experiment II showed that results consistent with a “learned-safety” theory of taste aversion appear to depend on whether rats drink most saccharin on their first or second exposure to the solution prior to poisoning. Experiment III demonstrated that when animals drank equal amounts of saccharin solution on each of two exposures prior to poisoning, evidence strongly confirming the “learned-safety” theory was obtained. These experiments together demonstrate the importance of amount of solution drunk in the determination of taste aversion.     

The effect of morphine preexposure on the acquisition of morphine-induced taste aversions: A nonassociative effect

In Experiment 1, the amount of time rats spent engaged in a range of behaviors was recorded immediately prior to and following the intraperitoneal administration of morphine sulfate (6 mg/kg) or distilled water. No behavioral differences were observed between these groups. In Experiment 2, preexposure to this low dose of morphine attenuated the subsequent acquisition of a morphine-induced taste aversion independent of the similarity of the preexposure and conditioning environments. These results with a dose of morphine that does not produce any behavioral effects, which in turn could potentially mask associative conditioning during preexposure, confirm that the attenuating effects of morphine preexposure on taste aversion learning are nonassociative.     

The basic tastants in aversion conditioning: Evidence for sensory preconditioning and not potentiation

In Experiment 1, a potentiation paradigm was used to test the relative influence of odor and taste with two 2 basic tastants (i.e., salt and sweet) in conditioned aversion learning. Experiment 1 showed that aversions to tastants (salt or sweet presented in a manner by which it could be tasted) were established only in subjects trained with the tastant, not the odor (i.e., salt or sweet presented in a manner by which it could not be tasted). Experiment 2 demonstrated, with a sensory preconditioning procedure, that the expression of an aversion to tastants was dependent on previous tastant experience prior to odor aversion training. These results suggest that while subjects can smell salt and sweet solutions, these odors are neither sufficient nor necessary for the expression of a conditioned tastant aversion.     

Impact of brief or extended extinction of a taste aversion on inhibitory associations: Evidence from summation,retardation, and preference tests

In five conditioned taste aversion experiments with rats, summation, retardation, and preference tests were used to assess the effects of extinguishing a conditioned saccharin aversion for three or nine trials. In Experiment 1, a summation test showed that saccharin aversion extinguished over nine trials reduced the aversion to a merely conditioned flavor (vinegar), whereas three saccharin extinction trials did not subsequently influence the vinegar aversion. Experiment 2 clarified that result, with unpaired controls equated on flavor exposure prior to testing; the results with those controls suggested that the flavor extinguished for nine trials produced generalization decrement during testing. In Experiment 3, the saccharin aversion reconditioned slowly after nine extinction trials, but not after three. Those results suggested the development of latent inhibition after more than three extinction trials. Preference tests comparing saccharin consumption with a concurrently available fluid (water in Experiment 4, saline in Experiment 5) showed that the preference for saccharin was greater after nine extinction trials than after three. However, saccharin preference after nine extinction trials was not greater, as compared with that for either latent inhibition controls (Experiments 4 and 5) or a control given equated exposures to saccharin and trained to drink saline at a high rate prior to testing (Experiment 5). Concerns about whether conditioned inhibition has been demonstrated in any flavor aversion procedure are discussed. Our findings help explain both successes and failures in demonstrating postextinction conditioned response recovery effects reported in the conditioned taste aversion literature, and they can be explained using a memory interference account.     

Taste quality and extinction of a conditioned taste aversion in rats

Rats (Rattus norvegicus) that received a taste cue (saccharin, saline, quinine, or sucrose) paired with a lithium chloride (LiCl) injection displayed a robust decrease in consumption of that taste, relative to controls that had the taste unpaired with LiCl. Consumption of the paired taste increased with each nonreinforced presentation (i.e., extinction). After asymptotic extinction, rats that had had a 0.1% saccharin cue paired with LiCl consumed less of the saccharin solution than did controls. A similar data pattern was observed with a 10% sucrose solution. These results are consistent with the view that some aspect of the excitatory CS-US association remains after extinction. On the other hand, rats that had a bitter (0.005% or 0.001% quinine) or salty (1% or 0.5% saline) solution paired with LiCl drank similar amounts of the fluid as controls after asymptotic extinction treatment. Together, these experiments suggest that a taste that is either sweet or preferred is required in order to demonstrate the chronic decrease in fluid consumption after extinction treatment. The data suggest that the conditioning experience prevents the later development of a preference for the sweet taste, rather than there being a retained aversion that suppresses fluid consumption.     

A within-event analysis of taste-potentiated odor and contextual aversions

A series of experiments was conducted to examine the phenomenon of potentiation. Experiment 1 demonstrated potentiation of odor aversions by taste when morphine served as the unconditioned stimulus (US). Experiment 2 provided evidence that the observed potentiation was due to a within-event association between odor and taste stimuli, rather than reflecting an enhanced odor-morphine association. In Experiment 3, morphine supported place conditioning to contextual cues and aversive conditioning to a taste cue, but potentiation of place conditioning by a taste cue was not obtained. Apparently the absence of potentiation was due to the dual nature of the morphine US, as potentiation of a contextual aversion by taste was obtained in Experiment 4 when a strictly aversive US (lithium) was used. These data suggest that potentiation depends on (1) an initially weak association between the to-be-potentiated conditioned stimulus (CS) element and the US, and (2) the elicitation of qualitatively similar responses by the individual elements of the CS compound. Collectively, these results support an explanation of potentiation based on within-event learning.