Conditioned Odor Aversion Research Articles

Ethanol impairs memory of a simple discrimination in adolescent rats at doses that leave adult memory unaffected

Adolescent rats are less sensitive than adults to the hypothermic, anxiolytic, motor impairing, hypnotic, and lethal effects of ethanol. In vitro experiments nevertheless suggest that hippocampal neural activity is more affected by ethanol in preweanling or adolescent rats than in adults. These data are complemented by in vivo results showing that pretraining ethanol impairs learning in adolescent rats at doses that do not affect adult learning. In order to determine if posttraining ethanol affects memory differently in adolescents than in adults, Sprague–Dawley albino rats of both ages were trained in an appetitively motivated odor discrimination in which they were required to dig in scented sand for sweetened cereal reward. Immediately after training subjects received intraperitoneal injections of 0, 0.5, or 1 g/kg ethanol (12.6%). At test, 48 h later, subjects were presented with unbaited discriminanda and the time (s) spent digging in the S+ and S− was measured. Adolescents, but not adults, showed impaired discrimination performance if training was followed by ethanol. A subsequent experiment discounted the possibility that impaired adolescent performance was due to ethanol-induced conditioned taste or odor aversions. It thus appears that relative to adults, memory in adolescent rats is more strongly affected by ethanol in a test of appetitive conditioning that excludes ethanol’s effects on sensory and motivational influences during the learning experience.

Taste preconditioning augments odor-aversion learning.

On the basis of previous work that has shown a taste can potentiate odor-aversion conditioning in AX+ conditioning, 6 experiments used rats to examine the effects of pairing a preconditioned taste (A) with a novel odor cue (X) in an A+/AX+ aversion conditioning design. Experiments 1A and 1B demonstrated that a preconditioned taste produced a robust odor aversion that was significantly stronger than a potentiated odor aversion. The results of Experiment 2 showed that the robust odor aversion produced by A+/AX+ conditioning was not the result of the potentiated odor aversion summating with generalization from the taste aversion. The augmented odor aversion was produced only when the taste and odor stimuli were presented simultaneously (Experiment 3) and the preconditioned taste aversion was intact at compound conditioning (Experiment 4). Pairing a novel odor with a preconditioned taste was not sufficient to condition an aversion to odor (Experiment 5), although other results implicated a role for an association between odor and taste in the odor augmentation effect (Experiment 6). The present results have implications for current models of taste + odor interactions in flavor-aversion conditioning.

Functional interaction between entorhinal cortex and basolateral amygdala during trace conditioning of odor aversion in the rat.

In rats, conditioned odor aversion (COA) occurs only if the time interval separating the odor from the subsequent intoxication is very short suggesting that the memory trace of the odor is subject to rapid decay. Recent results from our laboratory have found that lesion of the entorhinal cortex (EC), and activation of the basolateral nucleus of the amygdala (BLA) rendered COA tolerant to long interstimulus interval. The present study examined whether the odor memory trace depends on the interaction between the EC and the BLA. Rats lesioned in the EC received infusions of muscimol (a GABA(A) receptor agonist) into the BLA immediately after the odor presentation during acquisition of COA. Injection of muscimol into BLA prevented tolerance of COA to long interstimulus interval induced by EC lesions. This suggests that EC modulates the short-term memory trace of the odor by controlling the GABAergic activity of the BLA during acquisition of COA.

1PA123 ナメクジ単離脳における嗅覚性忌避連合学習

1PA123 ナメクジ単離脳における嗅覚性忌避連合学習

Reactivation treatment prevents the memory-impairing effects of scopolamine in preweanling rats.

The authors report that the expression of a conditioned odor aversion is impaired in preweanling rats when they are conditioned on Postnatal Day 12 and tested under the influence of scopolamine hydrobromide (0.2 or 0.5 mg/kg, intraperitoneal) after a 48-hr, but not after a 2-hr, retention interval (Experiment 1). This effect of scopolamine is not dependent on maturation of the cholinergic system between Days 12 and 14 (Experiment 2), nor is it due to peripheral mechanisms (Experiment 3). When pups are reexposed to the unconditioned stimulus (footshock) before drug administration, performance on the 48-hr retention test is not impaired by scopolamine (Experiment 4). These findings demonstrate that the cholinergic system may be critical for the retrieval and expression of long-term or weak memories in young rats. However, the expression of active memories (recent or recently reactivated) may not be dependent on the cholinergic system to the same extent as is the expression of inactive memories.

The parabrachial nucleus is essential for acquisition of a conditioned odor aversion in rats.

Rats with bilateral ibotenic acid lesions of the gustatory zone of the parabrachial nuclei (PBN) failed to acquire a conditioned taste aversion (CTA) in Experiment 1. They also failed to acquire a conditioned odor aversion (COA) when the olfactory cue was presented on an odor disk in Experiment 2 or when it was presented in water in Experiment 3. The failure to acquire the COA was not due to an inability to detect or use olfactory stimuli because the lesioned rats displayed neophobia to a novel odor in Experiment 3 and used an olfactory cue to predict the availability of an aversive capsaicin solution in Experiment 4. Together, the results demonstrate that, as with CTA learning, PBN cell bodies are essential for the establishment of a specific association between an olfactory conditioned stimulus and a lithium chloride unconditioned stimulus.

The parabrachial nucleus is essential for acquisition of a conditioned odor aversion in rats.

The parabrachial nucleus is essential for acquisition of a conditioned odor aversion in rats.

Bicuculline Administration into Basolateral Amygdala Facilitates Trace Conditioning of Odor Aversion in the Rat

This study investigated the effect of bicuculline methiodide (BMI) microinjection into basolateral amygdala (BLA) on conditioned odor aversion. Bilateral injections of BMI (39 or 59 pmol/0.2 μl) or artificial CSF were done in the BLA 5 min after the presentation of the conditioned stimulus (water intake at an almond-scented tube). This was followed 30 min later by lithium chloride-induced toxicosis. Whereas under these experimental conditions control rats (CSF injected) did not develop a conditioned odor aversion, BMI-treated rats (59 pmol) did so, suggesting that the blockade of GABAAreceptors facilitated this learning. This facilitation was unlikely due to an unconditioned action of BMI, as a group microinjected with 59 pmol of BMI but not intoxicated did not display conditioned aversion. This result suggest that blockade of the GABAAreceptors can prolong the olfactory trace duration, making it accessible to association with delayed toxicosis. Combined with previous results, these data support the hypothesis that the GABAergic system of the basolateral amygdala exerts control over the duration of a short-term odor trace in our conditioned odor aversion paradigms.

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na+ appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Rats with lesions of the nucleus of the solitary tract (NST) that demonstrated flat concentration-response functions for NaCl and sucrose (T. Shimura, P. S. Grigson, & R. Norgren, 1997) expressed a significant (albeit reduced) salt appetite following sodium depletion, and a normal conditioned taste aversion (CTA) for alanine when paired with lithium chloride-induced toxicosis. Rats with lesions of the NST also could acquire a conditioned odor aversion, but the CTA to alanine was not mediated by odor cues because other rats with NST lesions also demonstrated normal CTA learning even when made anosmic with zinc sulfate. Together, the data suggest that the rostral NST is essential for responding appropriately to increasing concentrations of a tastant, but not for the chemical identification necessary for sodium appetite and CTA learning.

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na-super(+ ) appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na-super(+ ) appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Facilitation of conditioned odor aversion by entorhinal cortex lesions in the rat.

Facilitation of conditioned odor aversion by entorhinal cortex lesions in the rat.

Facilitation of conditioned odor aversion by entorhinal cortex lesions in the rat.

This study examined the role of the entorhinal cortex (EC) in conditioned odor aversion learning (COA). Lateral EC lesions did not impair but rather facilitated COA. In the experiments the delay separating the odor cue presentation from the subsequent toxicosis was varied during acquisition. EC-lesioned rats demonstrated COA for delays up to 2 hr, whereas sham-operated rats displayed COA only if toxicosis immediately followed the odor cue. This facilitation was not dependent on the intensity of the odor and corresponded to a facilitated long-delay learning. EC lesion did not affect conditioned taste aversion, confirming that the facilitation effect does not correspond to a general facilitation of conditioned aversion learning. Taken together, these results indicate that the removal of the EC may allow odor-toxicosis associations across longer delays by extending the duration of the olfactory trace.

Taste-potentiated odor aversion learning based on amphetamine

This study sought to determine whether a taste can potentiate a conditioned odor aversion based on amphetamine as well as those based on lithium. A taste-potentiated odor aversion (TPOA) based on lithium was obtained in Experiment 1 only with a low concentration of an almond odor. This concentration was used in Experiment 2 where the taste, 0.1% saccharin, potentiated an odor aversion based on 1 mg/kg d-amphetamine. This was replicated in Experiment 3 where potentiation was found with doses of both 1 and 3 mg/kg amphetamine, and no effect of dose was detected. It was concluded that TPOA learning is not restricted to drugs such as lithium that produce conditioned unpalatability as well as conditioned aversions to a taste, because amphetamine does not produce conditioned unpalatability at the doses used here. Furthermore, because in Experiment 3 postconditioning extinction of the saccharin aversion removed the potentiation effect, it appears that this form of TPOA may depend on an association between the odor and taste, as proposed by within-compound theory.

The influence of the information value provided by prior-cuing treatment on the reactivation of memory in preweanling rats

In two experiments, the influence of exposure to a CS− on the acquisition and retention of a conditioned odor aversion was examined. Preweanling rats were given exposure to the CS− either prior to (CS−/CS+) or following (CS + /CS−) the pairing of a second odor (the CS+) with footshock. The results of Experiment 1 indicated that subjects in both of the treatment conditions acquired aversions of comparable strength to the odor paired with footshock and that retention of the odor aversion was not affected by order of stimulus presentation during conditioning. Experiment 2 indicated, however, that the effectiveness of pretest exposure to various elements of the conditioning episode in reactivation of the memory for conditioningwas dependent on the order of stimulus presentation during conditioning. This differential effectiveness of the various reactivation treatments is discussed in terms of their relationship to the associative “status” of the stimuli present during conditioning and in terms of the information provided to the animal by the reactivation treatment.

Conditioned aversion to an intraperitoneally injected odor CS in rats

Two experiments were conducted to specify an CS property of intraperitoneally injected odor substance in conditioned odor aversion formation. In experiment 1, three groups of water-restricted rats received one trial of conditioning with intraperitoneal injections of orange-extract (CS) and LiCl(UCS). The CS-UCS intervals of experimental groups were 30 minutes (Group IE-30) and 120 minutes (Group IE-120). In the test trial, Group IE-30 rats showed aversion to the test solution (0.5% orange extract), whereas no significant difference was observed between the control group and Group IE-120. In experiment 2, three groups of rats received one or two or three conditioning trials (Groups E1, E2 and E3, respectively). The CS-UCS interval of all groups was 30 minutes. In the test trial, rats in Groups E2 and E3 consumed less amount of test solution (0.5% orange extract) than the control rats, whereas no significant difference was observed between Group E1 and the control group. These results suggest that the intraperitoneally injected odor substance have CS property on conditioned odor aversion.

Conditioned Odor Aversion can Enhance the Neophobia to a Novel Odor but not to a Novel Taste

Conditioned Odor Aversion can Enhance the Neophobia to a Novel Odor but not to a Novel Taste

Comparison of the sensitivity of C57BL/6J and AKR/J mice to airborne molecules of isovaleric acid and amyl acetate

Wysocki et al. (1977) have previously compared the abilities of several inbred strains of mice to avoid odorized drinks after odor-aversion conditioning and have proposed C57BL/6 mice as an animal model to study the specific anosmia to isovaleric acid. We have compared the olfactory performances of C57BL/6J mice and AKR/J mice using one-bottle and two-bottle tests to study the latencies of contacts with odorized or control drinks after odor-aversion conditioning. In both inbred strains, sensitivities to airborne molecules of amyl acetate (control odor) or isovaleric acid are demonstrated. Differences in behavioral strategies are suggested but the results are consistent with the hypothesis of a selective hyposmia to isovaleric acid in C57BL/6J mice.

Developmental change in reversal learning of an olfactory discrimination

We examined developmental changes in the reversal of a learned discrimination in an olfactory conditioning paradigm in three experiments. Preweanling rats were exposed to an odor (CS+) paired with footshock and a different odor (CS−) that was explicitly unpaired with footshock. The rats were then immediately tested for their preference between the CS+ and CS− odors. In Experiment 1, animals trained at 12 or 18 days of age showed equivalent conditioned aversions to the CS+. When the significance of the cues was reversed, the younger animals showed rapid reversal learning; that is, their aversion to the original CS-I- was displaced by an aversion to the original CS−. However, the 18-day-old animals were slower to acquire discrimination reversal. In Experiment 2, a similar pattern of results emerged when animals were given separate preference tests involving the CS+ versus a novel odor, or the CS− versus a novel odor. In Experiment 3, intact 18-day-old rats and 18-day-olds with damage to the septum and fornix showed equivalent conditioned aversions to the CS+. In contrast to the intact animals, however, the lesioned rats showed rapid reversal of the discrimination, which resembled that of intact 12-day-olds. Thus, there appears to be a dramatic change in reversal learning of conditioned odor aversions in rats after the second week of postnatal life. These data are discussed with reference to the role of septo-hippocampal maturation in the ontogeny of olfactory learning.

Potentiation of odor by taste and odor aversions in rats are regulated by cholinergic activity of dorsal hippocampus

Limbic cholinergic activity is critically involved in the retention of learned aversions tasks. The purpose of these experiments was to assess the role of cholinergic mechanisms of the dorsal hippocampus in the acquisition of both odor and potentiated odor aversions through taste aversion. Cholinergic activity was increased by physostigmine (Phys). When Phys was applied before the presentation of an odor-taste compound during acquisition, the potentiation of odor-aversion was disrupted, while taste aversion was left intact. When hippocampal cholinergic activity was reduced with the muscarinic antagonist scopolamine (Scop), enhancement of potentiated odor aversion was observed, again with no effect on taste aversion. Moreover, when Phys was applied before an odor alone it also disrupted odor avoidance in two different odor tests conditioning situations, i.e., odor was followed immediately by lithium chloride or foot shock. Neither Scop nor Phys had any effect on taste or potential odor aversions when applied to fronto-parietal cortex. These results suggest that cholinergic activity of the hippocampus is involved in the acquisition of odor aversion conditioning.

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.