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)     

Ibotenic acid lesions of the basolateral, but not the central, amygdala interfere with conditioned taste aversion: Evidence from a combined behavioral and anatomical tract-tracing investigation.

Rats (Rattus norvegicus) with almost complete ibotenic acid lesions (at least 90%) of the basolateral amygdaloid complex (BLA) failed to learn a conditioned taste aversion (CTA; Experiment 1A). In these same BLA rats, the bidirectional parabrachial–insular pathway that courses through the central nucleus of the amygdala (Ce) was shown to be spared (Experiment 1B), indicating that the BLA per se is critical for CTA learning. In contrast to the deleterious effect of BLA lesions on CTA, ibotenic acid lesions of the Ce did not block CTA learning (Experiment 2). Nonreinforced preexposure to the gustatory stimulus attenuated CTA acquisition in normal rats, and, under these conditions, rats with BLA lesions were no longer impaired (Experiment 3). Thus, ibotenic acid lesions centered over the Ce, sparing a considerable extent of the BLA, together with the testing procedure used in previous experiments (e.g., L. T. Dunn & B. J. Everitt, 1988), led to the belief that the CTA deficits reported after electrolytic lesions of the amygdala were the result of incidental damage to fibers of passage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brainstem lesions and gustatory function: III. The role of the nucleus of the solitary tract and the parabrachial nucleus in retention of a conditioned taste aversion in rats.

Bilateral electrolytic lesions of the nucleus of the solitary tract (NST) or ibotenic acid lesions of the pontine parabrachial nuclei (PBN) failed to disrupt retention of a preoperatively acquired conditioned taste aversion (CTA) to 0.3 M alanine. For both sham- and NST-lesioned rats, the CTA persisted following 3 nonreinforced conditioned stimulus (CS) presentations. For PBN-lesioned rats, retention was more labile. The preoperatively acquired CTA was extinguished by the 3rd nonreinforced CS exposure. When assessed postoperatively using a novel CS, NST-lesioned rats acquired a new CTA, although they were rendered anosmic with zinc sulfate (P. S. Grigson et al, see record 199707487-016). Rats with PBN lesions, however, failed to acquire a 2nd CTA postoperatively. Thus, the PBN is essential for the acquisition of a CTA, but neither of the brainstem gustatory nuclei need be intact for the retention of a preoperatively acquired CTA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning

The present study examined whether the basolateral amygdaloid complex (BLA) participates in the expression of fear conditioned to both an olfactory conditioned stimulus (CS) and the training context. In Experiment 1, pretraining excitotoxic lesions of the BLA abolished immediate postshock freezing, conditioned freezing to an olfactory CS, and conditioned freezing to the training context. Control experiments indicated that lesioned and sham-lesioned subjects did not differ in locomotor activity or in acquisition of a successive-cue odor discrimination task, suggesting that deficits in freezing behavior exhibited by BLA subjects were not due to an impairment in primary aspects of olfaction or to a general enhancement of locomotor activity. In Experiment 2, excitotoxic lesions of the BLA produced either 1 day or 15 days after olfactory fear conditioning abolished both odor-elicited and contextual freezing. Collectively, these data support the notion that the BLA participates in an enduring manner in the expression of conditioned freezing behavior elicited by both olfactory and contextual stimuli.     

Effects of lesions of the bed nucleus of the stria terminalis, lateral hypothalamus, or insular cortex on conditioned taste aversion and conditioned odor aversion.

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of lesions to noradrenergic projections from the locus coeruleus and lateral tegmental cell groups on conditioned taste aversion in the rat.

Lesions of the coeruleo-cortical noradrenergic projections caused marked cortical noradrenaline depletions but were not associated with deficits in the acquisition or extinction of a conditioned taste aversion (CTA). Lesions of lateral tegmental noradrenergic projections resulted in marked hypothalamic noradrenaline depletions, enhanced neophobia to the novel taste of saccharine, unimpaired acquisition but prolonged extinction of the CTA. However, when animals with lateral tegmental noradrenergic lesions received extensive preconditioning exposure to saccharine, acquisition of the CTA was attenuated and extinction was more rapid than in controls. Alterations in CTA learning and extinction following lesions of the lateral tegmental noradrenergic system appear to reflect alterations in the way that animals with lesions react toward the hedonic aspects of taste-related stimuli rather than alterations in associational or attentional mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.

Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parabrachial gustatory lesions impair taste aversion learning in rats.

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, 15 intact rats and 10 rats with PBN lesions (PBNX) received 7 intraoral taste stimulus infusions (30 sec, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profiles from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Boosting cholinergic activity in gustatory cortex enhances the salience of a familiar conditioned stimulus in taste aversion learning.

The cholinergic system is important for learning, memory, and responses to novel stimuli. Exposure to novel, but not familiar, tastes increases extracellular acetylcholine (ACh) levels in insular cortex (IC). To further examine whether cholinergic activation is a critical signal of taste novelty, in these studies carbachol, a direct cholinergic agonist, was infused into IC before conditioned taste aversion (CTA) training with a familiar taste. By mimicking the cholinergic activation generated by novel taste exposure, it was hypothesized that a familiar taste would be treated as novel and therefore a salient target for aversion learning. As predicted, rats infused with the agonist were able to acquire CTAs to familiar saccharin. Effects of carbachol infusion on patterns of neuronal activation during conditioned stimulus–unconditioned stimulus pairing were assessed using Fos-like immunoreactivity (FLI). Familiar taste–illness pairing following carbachol, but not vehicle, induced significant elevations of FLI in amygdala, a region with reciprocal connections to IC that is also important for CTA learning. These results support the view that IC ACh activity provides a critical signal of taste novelty that facilitates CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cortical substrates of taste aversion learning: Dorsal prepiriform (insular) lesions disrupt taste aversion learning.

The functional relation between restricted damage to ventral primary somatosensory neocortex and the ability of rats to acquire conditioned taste aversions (CTA) was examined by a combination of behavioral and neurohistological techniques. Ss were 84 male Long-Evans hooded rats. Lesions confined exclusively to the established gustatory neocortex (GN) did not disrupt CTA acquisition, nor did lesions confined to suprarhinal cortical areas ventral to the GN. Lesions that encroached on dorsal prepiriform and insular cortices produced CTA acquisition deficits and damaged a large proportion of efferent projections to the prefrontal and precentral neocortex. Lesions of dorsal prepiriform and insular cortices did not modify taste preference–aversion thresholds to any of the 4 taste modalities. It is concluded that ventral somatosensory neocortical fields, including the established GN, do not mediate CTA acquisition and that rhinal cortices ventral and posterior to the GN are preferentially involved in associative learning for tastes and illness. (51 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Basolateral amygdala NMDA receptors are selectively involved in the acquisition of taste-potentiated odor aversion in the rat.

In the taste-potentiated odor aversion (TPOA) paradigm, animals acquire a strong aversion to an odor that is followed by delayed intoxication only if a gustatory stimulus is presented with the odor during conditioning. Although previous work has shown that N-methyl-D-aspartate (NMDA) receptors in the basolateral nucleus of the amygdala (BLA) play a role in the acquisition of TPOA, the present study aimed at.describing the process in which NMDA receptors in the BLA are involved during acquisition of TPOA. Male Long-Evans rats received intra-BLA infusions of the competitive NMDA receptor antagonist {d},{l}-2-2-amino-5-phosphonovalerate ({d}-APV; 0.05 and 0.50 μg) immediately before or after the odor–taste conditioned stimulus (CS) presentation, or immediately before the test. Results showed that {d}-APV impaired acquisition of TPOA when infused before, but not after, the CS presentation, but did not affect retrieval. These results suggest that NMDA receptors of the BLA are involved in the formation of potentiation—by taste—of the olfactory memory trace, but not in the maintenance of this process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mapping Conditioned Taste Aversion Associations Using c-Fos Reveals a Dynamic Role for Insular Cortex.

Novel tastes are more effective than familiar tastes as conditioned stimuli (CSs) in taste aversion learning. Parallel to this, a novel CS-unconditioned stimulus (US) pairing induced stronger Fos-like immunoreactivity (FLI) in insular cortex (IC), amygdala, and brainstem than familiar CS-US pairing, suggesting a large circuit is recruited for acquisition. To better define the role of IC, the authors combined immunostaining with lesion or reversible inactivation of IC. Lesions abolished FLI increases to novel taste pairing in amygdala, suggesting a role in novelty detection. Reversible inactivation during taste preexposure increased FLI to familiar taste pairing in amygdala and brainstem. The difference between temporary inactivation, which blocked establishment of "safe" taste memory, and lesions points to a dual role for IC in taste learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in vivo--effects of oxygen tension and glutathione

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning.     

"Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus": Correction to McNish et al (2000).

Reports an error in "Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus" by Kenneth A. McNish, Jonathan C. Gewirtz and Michael Davis (Behavioral Neuroscience, 2000[Feb], Vol 114[1], 64-76). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4. (The following abstract of the original article appeared in record 2000-13470-005.) The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion: Further evidence for an associative deficit in rats.

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Novel factors contributing to the expression of latent inhibition.

Behavioral and neural correlates of latent inhibition (LI) during eyeblink conditioning were studied in 2 experiments. In Experiment 1, rabbits (Oryctolagus cuniculus) were conditioned after 8 days of tone conditioned stimulus (CS) presentations or 8 days of context-alone experience. LI was seen in the CS-preexposed rabbits when a relatively intense (5 psi) airpuff unconditioned stimulus was paired with the CS. In Experiment 2, rabbits were given 0, 4, or 8 days of CS preexposures or context-alone experience. Hippocampal activity was monitored from the 8-day CS- or context-exposure rabbits. The LI effect was seen only in rabbits given 4 days of CS preexposure, thus suggesting that LI depended largely on the rate of acquisition in the context-preexposed control group. The neural recordings showed that the hippocampus was sensitive to the relative novelty of the stimuli and the overall context, regardless of whether exposure to stimuli and context promoted LI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mediodorsal thalamic lesions and Pavlovian conditioning of heart rate and eyeblink responses in the rabbit.

Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions. These animals were compared on 4 sessions of Pavlovian eyeblink and heart rate conditioning, in which a tone was the conditioned stimulus/stimuli (CS) and a paraorbital electrical shock was the unconditioned stimulus/stimuli (UCS). Lesions of MD retarded acquisition of the eyeblink conditioned response (CR) and abolished the late-occurring tachycardiac component of the heart rate CR. The data are compatible with previous experiments (H. Groenewegen, 1988), suggesting that MD participated in the sympathetic control associated with somatomotor learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned taste aversions and drugs of abuse: A reinterpretation.

A new hypothesis (and supporting data) provides a solution to the 25-yr-old paradox whereby positively reinforcing drugs of abuse also support a conditioned taste aversion (CTA). The results show that unlike LiCl-induced CTAs, morphine- and cocaine-induced suppression of conditioned stimulus (CS) intake depends on the rewarding properties of the gustatory CS. This finding argues against the long-standing CTA interpretation in favor of a new reward comparison account. That is, rats decrease intake of a gustatory CS following taste–drug pairings because the value of the CS is outweighed by that of a highly reinforcing psychoactive drug. Suppression of CS intake, then, is a consequence of the well-documented positive reinforcing, rather than the hypothetical aversive, properties of drugs of abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.