N-methyl-D-aspartate antagonist D-APV selectively disrupts taste-potentiated odor aversion learning.

Examined in 2 experiments the effects of the competitive N-methyl-{d}-aspartate (NMDA) antagonist {d}-APV ({d}-2-amino-5-phosphonovalerate) on rats' ability to acquire potentiated aversions to the odor element of a taste–odor compound. In Exp 1, pretreatment with {d}-APV (2.5 μg/side icv) caused stereospecific deficits in potentiated odor aversion learning but left simple taste and odor aversion learning intact. In Exp 2, pretreatment with {d}-APV had no effect on rats' acquisition of an illness-based odor discrimination task. These results parallel those previously obtained using a noncompetitive NMDA antagonist (G. S. Robinson et al, 1989) and show that interference with NMDA receptors can selectively impair potentiated odor aversion learning. These results suggest that NMDA receptors play a critical role in some, but not all, forms of learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste-potentiated odor aversion learning: Role of the amygdaloid basolateral complex and central nucleus.

Examined the relative contributions of the amygdaloid basolateral complex (ABL) and central nucleus (CN) to taste-potentiated odor aversion (TPOA) learning, an associative learning task that is dependent on information processing in 2 sensory modalities. In Exp 1, rats with neurotoxic lesions of these systems were trained on the TPOA task by presenting a compound taste–odor conditioned stimulus (CS), which was followed by LiCl administration. Results showed that ABL damage caused an impairment in potentiated odor aversion learning but no deficit in the conditioned taste aversion. In contrast, rats with CN damage learned both tasks. Exp 2 examined the effects of ABL damage on TPOA and odor discrimination learning. The odor discrimination procedure used a place preference task to demonstrate normal processing of olfactory information. Results indicated that although ABL-lesioned animals were impaired on TPOA, there was no deficit in odor discrimination learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 GABAA 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition.

[Correction Notice: An erratum for this article was reported in Vol 121(6) of Behavioral Neuroscience (see record 2007-18058-034). Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral section) was incorrect. The correct figure is provided in the erratum.] The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

"Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition": Correction to St. Andre and Reilly (2007).

Reports an error in "Effects of Central and Basolateral Amygdala Lesions on Conditioned Taste Aversion and Latent Inhibition" by Justin St. Andre and Steve Reilly (Behavioral Neuroscience, 2007[Feb], Vol 121[1], 90-99). Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral section) was incorrect. The correct figure is provided in the erratum. (The following abstract of the original article appeared in record 2007-02025-008.) The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-{d}-aspartate (NMDA) receptor antagonist {dl}-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 μg/side AP5 immediately before 5 noise–footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5, because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of brain lesions on taste-potentiated odor aversion in rats.

Rats failed to acquire aversions to odor stimulus, which was followed 30 min later by an unconditioned stimulus (US). However, when the odor stimulus was accompanied by a taste stimulus, they acquired odor aversions as well as taste aversions. In this phenomenon, referred to as a taste-potentiated odor aversion, lesions of the amygdala disrupted both taste and odor aversions, whereas lesions of the parvicellular part of ventroposteromedial thalamic nucleus (VPMpc) or insular cortex (IC) disrupted taste aversion but attenuated only odor aversion. These results suggest that both taste and odor stimuli are associated with US in the amygdala and that taste inputs delivered to the amygdala through the IC and/or VPMpc play an important role in potentiation of odor aversion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Noradrenaline and sensory preconditioning in the rat.

Two experiments investigated the effect of noradrenaline (NA) depletion following intraperitoneal administration of the neurotoxin N-2-chloroethyl-N-ethyl-2-bromobenzylamine ({dsp4}[50 mg/kg]) on sensory preconditioning in male Sprague-Dawley rats. For sensory preconditioning, a saccharin taste conditioned stimulus (CS?) and a special type of drinking bottle (noisy bottle) were paired during Phase 1. During Phase 2, the noisy bottle (CS?) was paired with lithium chloride, and during Phase 3 the aversion to saccharin (CS?) was tested in saccharin preference tests. {dsp4} treatment disrupted Ss' ability to form sensory preconditioning, and this effect could not be explained on the basis of enhanced neophobia, stimulus generalization, or a deficit in 1st-order conditioning in {dsp4}-treated Ss. Findings are discussed in relation to issues of associative learning such as contextual control of latent inhibition and extinction. Data suggest that NA-depleted rats fail to form associations between the CS? and CS? during sensory preconditioning and are consisitent with other data from compound conditioning experiments on the functional role of NA in learning and memory. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age- and dose-dependent facilitation of associative eyeblink conditioning by {d}-cycloserine in rabbits.

Normal aging selectively impairs some forms of learning. For example, aging rabbits require more than twice as many trials to acquire 500-ms trace eyeblink conditioning than do young rabbits. N-methyl-{d}-aspartate (NMDA) receptor antagonists also impair trace conditioning. The effects of daily {d}-cycloserine (DCS; a partial agonist of the NMDA receptor-glycine site) treatment were tested on trace conditioning of young or aging rabbits using a conservative quantitative approach. DCS dose dependently improved acquisition, maximally reducing trials to criterion by ≈50%. Dose-response curves were right-shifted by aging (twice the dose was required to achieve the same enhancement compared with controls). DCS did not affect nonassociative performance but sharpened the conditioned stimulus tone intensity discrimination. DCS thus can functionally modulate NMDA receptors in normal aging, enhance associative learning at all ages, and reduce or reverse age-dependent learning deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of temporal order and odor intensity in taste-potentiated odor aversions.

The role of the temporal order of odor and taste was studied in two experiments, and a third experiment studied the role of odor intensity in flavor-toxicosis conditioning with thirsty rats licking water spouts in a "wind tunnel." In all experiments, odors and tastes were presented for 2 min to rats, and 30 min later, a toxin (lithium chloride) was intubated. In Experiment 1, an odor was presented 90 s before, during, or 90 s after a taste to independent groups. Experiment 2 was a within-subjects partial replication of the first. Each rat was presented with one odor, then a taste, then a second odor with each stimulus separated by 45 s. The results of Experiments 1 and 2 indicated that (a) odor alone is not associated with illness under our conditions, (b) presenting an odor and a taste at the same time potentiates the odor component so that it is associated with illness, (c) 45-s and 90-s intervals between odor and taste eliminate potentiation, and (d) taste and odor interact asymmetrically; that is, odor has little effect on the development of taste-illness associations. In Experiment 3, an odor and a taste were presented simultaneously, and odor intensity varied. As odor intensity increased, the strength of the taste-potentiated odor aversion increased, whereas the aversion to the taste remained constant. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flavor-illness aversions: Potentiation of odor by taste with toxin but not shock in rats.

Paired almond odor or saccharin taste as a single CS or as a compound CS for both a footshock UCS and a toxin UCS (LiCl) to test the generality of potentiation in male Sprague-Dawley rats. Extinction tests with the almond and saccharin components were then given. In single CS–toxin experiments, taste was more effective than odor, and after compound conditioning, the taste component potentiated the odor component. Conversely, in single CS–shock experiments, odor was more effective than taste, and after compound conditioning, no potentiation was observed. Instead, interference effects were observed. In Exps I and II, the addition of taste disrupted odor CS–shock conditioning, and in Exp III, odor interfered with taste CS–shock conditioning. Visceral feedback was apparently a necessary UCS for the potentiation of odor by taste. Data support the neural convergence and gating hypothesis of flavor aversion conditioning. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of dorsal hippocampus and basolateral amygdala NMDA receptors in the acquisition and retrieval of context and contextual fear memories.

The authors used 3-phase context preexposure facilitation methodology to study the contribution of N-methyl-D-aspartate (NMDA) receptors in dorsal hippocampus (DH) and the basal lateral region of the amygdala (BLA) to (a) acquisition of the context memory, (b) retrieval of the context memory, (c) acquisition of context-shock association, and (d) retrieval of the context-shock association. The NMDA receptor antagonist D-2-amino-5 phosphonopentanoic acid (D-AP5) was injected into either the DH or BLA prior to (a) the context preexposure phase, (b) the immediate shock phase, or (c) the test for contextual fear. Antagonizing NMDA receptors in the DH impaired the acquisition of the context memory but did not affect its retrieval or retrieval of the fear memory. Antagonizing NMDA receptors with D-AP5 in the BLA impaired acquisition of the context-shock association but had no effect on the expression of fear. However, both DL-AP5 and L-AP5 reduced the expression of fear when they were injected into the amygdala prior to testing for contextual fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste-potentiated odor conditioning: Impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala.

Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated odor conditioning: a form of learning that is dependent on information processing in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired in their acquisition of the potentiated learning to an odor cue. Expression of this learning and acquisition of a simple taste aversion remained intact following drug treatment. In Experiment 2, dose dependence and stereoselectivity were demonstrated for the antagonist compound. These results are consistent with previous studies demonstrating that either basolateral amygdala lesions, or treatment with NMDA antagonists, by other routes (systemic or intraventricular) produce selective deficits in taste-potentiated odor conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Detailed behavioral analysis of water maze acquisition under APV or CNQX: Contribution of sensorimotor disturbances to drug-induced acquisition deficits.

N-methyl-{d}-aspartate (NMDA) receptor antagonists disrupt acquisition of the water maze and cause sensorimotor disturbances. In a detailed behavioral analysis in male rats, it was found that the NMDA antagonist {dl}-2-aminophosphonovaleric acid (APV) caused sensorimotor disturbances in behaviors required for maze performance and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under APV. The results are consistent with the known role of NMDA receptors in sensorimotor mechanisms and suggest that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA may contribute to but does not appear to be essential for spatial learning in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Function of the "onset of illness" in the preference changes of alloxan-diabetic rats.

144 male Sprague-Dawley rats were given access to saccharin or NaCl solutions as a conditioned stimulus (CS) at 1 of several times before and after injection with alloxan as an unconditioned stimulus (UCS) and were compared with controls (given UCS but no CS exposure) on their preference for the CS 7 days after the diabetes was well established. Results indicate that Ss exposed to the UCS at 1 or 2 hrs prior to the CS or at 1, 2, or 6 hrs following the CS all formed a conditioned aversion, whereas those with 6, 24, or 48 hrs between UCS and CS showed no greater aversion to the CS than controls. It is suggested that while the onset of alloxan diabetes can serve as the UCS for a conditioned taste aversion, the behavior of alloxan-diabetic rats towards saccharin does not depend upon this process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats.

Three experiments examined the effects of intra-amygdaloid infusions of an N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), on contextual fear conditioning in rats. In Experiment 1, APV infusion into the basolateral amygdala (BLA), before training, disrupted the acquisition of contextual fear. In Experiment 2, APV produced a disruption of both the acquisition and expression of contextual fear. This blockade of contextual fear was not state dependent, not due to a shift in footshock sensitivity, and not the result of increased motor activity in APV-treated rats. In Experiment 3, fear conditioning was not affected by a posttraining APV infusion into the BLA. These results indicate that NMDA receptors in the BLA are necessary for both the acquisition and expression of Pavlovian fear conditioning to contextual cues in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats

NMDA receptors in the amygdala seem to be critical for fear conditioning in naive rats. Recent spatial-learning studies suggest that previous learning protected animals from the amnesic effect of NMDA antagonists on new learning (of a similar behavioral task). Therefore, the present study examined whether blocking of NMDA receptors in the basolateral nucleus of the amygdala (BLA) prevents new fear learning in previously fear-conditioned rats, as measured by freezing behavior. Intra-BLA infusions of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) completely blocked fear conditioning to a tone stimulus in animals that had previously been fear-conditioned to a light stimulus. Similar results were obtained with intra-BLA infusions of APV before contextual fear conditioning in rats that had been fear-conditioned to a different context. Additional experiments showed that intra-BLA APV infusions substantially interfere with the expression and extinction of conditioned fear to tone, light, and context stimuli. Together, these results indicate that NMDA receptors in the BLA are crucial for the encoding of new fear memories (i.e., the formation of specific conditioned stimulus-unconditioned stimulus association), the expression of conditioned fear responses, and the extinction of acquired fear.     

Perceptual characteristics of the amiloride-suppressed sodium chloride taste response in the rat.

Assessed the contribution of amiloride-sensitive membrane components to the perception of NaCl taste using a conditioned taste aversion procedure with 8 groups of adult rats conditioned to avoid either 0.1M NaCl, 0.5M NaCl, 0.1M NH?Cl, or 1.0M sucrose while their tongues were exposed either to water or to amiloride hydrochloride. Differences in the acquisition of taste aversions between the amiloride- and nonamiloride-treated groups were not apparent when the conditioned stimulus (CS) was 0.5M NaCl, 0.1M NH?Cl, or 1.0M sucrose. Although the magnitude of the 0.5M NaCl aversion was similar between amiloride- and nonamiloride-treated Ss, the perceptual characteristics of the CS differed between groups. Amiloride-treated Ss avoided monochloride salts after conditioning to 0.5M NaCl but not nonsodium salts or nonsalt stimuli. Ss not treated with amiloride only generalized the 0.5M NaCl aversion to sodium salts. The "salty" taste of NaCl is related to the amiloride-sensitive portion of the functional taste response in rats. The portion of the NaCl response insensitive to amiloride has "sour-salty" perceptual characteristics and is not perceived as being salty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)