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)     

The parabrachial nucleus: A brain stem substrate critical for mediating the aversive motivational effects of morphine.

Bilateral ibotenic acid lesions of the lateral, but not the medial, parabrachial nucleus (PBN) blocked conditioned taste aversion (CTA) induced by morphine but not conditioned place preference induced by morphine. The same lateral PBN lesions also blocked conditioned place aversion produced by low intraperitoneal doses of morphine (shown to produce aversion, instead of preference, due to a restricted action on gut opiate receptors). Lateral PBN lesions did not block CTA produced by LiCl. Cerebral peduncle lesions that destroyed the direct descending projections from the visceral cortex to the PBN did not block CTA induced by morphine, nor did ibotenic acid lesions of the tegmental pedunculopontine nuclei (shown to block place preference produced by even high morphine doses). It is suggested that the lateral PBN is a critical link in the neural pathway carrying the aversive motivational effects of opiates from the gut into the CNS, independent of the neural pathway carrying the rewarding motivational effects of morphine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapeutic effects of HS-3, HS-6, benactyzine, and atropine in soman poisoning of dogs

Rats with intracranial self-stimulation (ICSS) electrodes in the locus coeruleus and adjacent pontine tegmental structures received stereotaxically placed bilateral injections of 6-hydroxydopamine (4 mug/2 mul) into the mesencephalic trajectory of the dorsal tegmental noradrenergic bundle. The consequent depletions of norepinephrine in the cerebral cortices and hippocampi (96.7%) did not result in significant changes in ICSS. Thus, diencephalic and telencephalic noradrenergic projections of the locus coeruleus do not appear to be critical for the occurrence of ICSS from that nucleus or its surrounding region. Nor do these projections appear to be crucially involved in the enhancement of this ICSS by D-amphetamine. Rats in this study showed two-fold increases in responding following injections of D-amphetamine sulfate (0.5 mg/kg) both before and after the lesions of the dorsal tegmental bundle. These results suggest that the ascending projections of the locus coeruleus are not critically involved in ICSS of the dorsal pontine tegmentum.     

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)     

Acquisition and reversal of taste/tactile discrimination after forebrain noradrenaline depletion.

Assessed the role of noradrenaline (NA) on the acquisition of an aversively motivated discrimination task and its reversal. A conditioned taste aversion procedure was used. NA depletions were achieved through 2 pharmacological means: systemic N-2 chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4) and destruction of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine (6-OHDA). Both procedures caused marked reductions of NA in the frontal cortex and hippocampus. In neither of the studies (Exp 1, DSP4 and Exp 2, DNAB) were there any significant changes between controls and NA-depleted rats in either the rate of acquisition of the original discrimination (Phase 1) or the subsequent reversal (Phase 2). This occurred irrespective of which of the 2 stimuli (a taste cue or a tongue-tactile cue) initially was used as the conditioned stimulus/stimuli (CS) (the stimulus first followed by contingent administration of lithium chloride and later, by saline injections). Thus NA does not appear to be critically involved in the acquisition and reversal of a taste/tactile discrimination task. The significance of forebrain NA for other discrimination tasks is discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Involvement of the supramammillary nucleus in aversive conditioning.

Mechanisms for the retention and retrieval of conditioned taste aversions (CTAs) have yet to be fully defined. The authors explored relevant subcortical forebrain regions by tracking the expression of immediate early genes, c-fos and zif268. The supramammillary nucleus (SuM) was activated following both viscerally based CTA and somatically based inhibitory avoidance (IA). Excitotoxic lesions of the SuM before conditioning caused no disruption of acquisition but accelerated the extinction of both the CTA and IA. In contrast, lesions after CTA conditioning did not impair retention or retrieval. The present study indicates that the SuM is activated by memory-elicited discomfort during retrieval, suggesting that it plays a role in resisting the extinction of a long-term aversive memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dorsal tegmental noradrenergic projection: An analysis of its role in maze learning.

Evaluated the hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning. Four experiments were conducted with 61 male Wistar rats. Maze performance was studied in Ss receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a 'T'-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Ss with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"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)     

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)     

Dissociable effects of lesions to the dorsal or ventral noradrenergic bundle on the acquisition, performance, and extinction of aversive conditioning.

In six experiments, we studied the effects of lesions to either the dorsal or ventral noradrenergic bundle on the acquisition and extinction of the conditioned emotional response (CER) as measured in a conditioned suppression paradigm. Infusions of the neurotoxin 6-hydroxy-dopamine (6-OHDA) into the trajectory of the dorsal noradrenergic ascending bundle (DNAB) impaired the acquisition of on-the-baseline and off-the-baseline conditioned suppression. The acquisition impairment for on-the-baseline conditioning was also shown to still be present when training did not commence until 8 weeks following central noradrenergic depletion. However, in rats previously trained on the CER, DNAB lesions did not affect performance. There was also a small resistance to extinction following on-, but not off-the-baseline conditioning. The acquisition impairment was shown not to be because of an altered sensitivity to the footshock. In contrast, infusions of 6-OHDA into the ventral noradrenergic ascending bundle (VNAB) had no effect upon the acquisition of the CER in an on-the-baseline procedure, but retarded its extinction to a much greater extent. The results here are discussed in terms of other acquisition deficits shown by rats with DNAB lesions and with reference to Gray's "anxiety" and Mason's "selective attention" theories of locus coeruleus function. (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)     

Long-lasting increase in anxiety after electrolytic lesions of the pedunculopontine tegmental nucleus.

This study examined the effect of electrolytic lesions of the pedunculopontine tegmental nucleus (PPTg) on emotionality in rats. Rats with PPTg or sham lesions were tested in the elevated plus-maze, the social interaction test, the open-field test, and the conditioned fear paradigm. Histology showed that lesions were concentrated on the caudal half of the PPTg. In the plus-maze, behavioral scores were biased toward increased "anxiety" on the 1st testing day. Five consecutive exposures to the apparatus led to marked habituation in sham-lesioned but not in PPTg-lesioned rats. On the 5th day, most indexes of emotionality indicated elevated anxiety in PPTg-lesioned rats. Increased anxiety was also found in PPTg-lesioned rats in the social interaction test. In the conditioned fear paradigm, movement suppression during the postconditioned stimulus period was found in both groups on the 1st day of extinction but only in PPTg-lesioned rats on the 2nd extinction day, indicating extinction was slower in PPTg-lesioned rats. Lesions of the caudal PPTg appear to produce long-lasting anxiety in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disturbances of neophobia and taste-aversion learning after bilateral kainate microlesions in the rat pallidum.

These experiments aimed to elucidate feeding-associated behavioral roles of globus pallidus (GP) neurons in gustatory functions: The effects of bilateral microiontophoretic kainate (KA) lesions of the ventromedial pallidal (vmGP) region on neophobia and conditioned taste aversion (CTA) were studied. Lesioned rats displayed strong and persistent neophobia to a mild citric acid solution. Neuron-specific damage to the vmGP also prevented rats from proper acquisition of CTA. Rats that previously showed normal neophobia and successfully learned CTA demonstrated difficulties in CTA retention after GP lesions. KA-lesioned rats, in addition, exhibited deficits in orientation reactions but did not have aphagia, adipsia, or motor disturbances seen after larger pallidal lesions. These findings suggest that neurons of the GP are significant in acquisition, memory storage, and retrieval mechanisms of feeding-associated taste information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociations of the effects of amygdala and insular cortex lesions on conditioned taste aversion, passive avoidance, and neophobia in the rat using the excitotoxin ibotenic acid.

The results in this article show that although electrolytic amygdala lesions disrupt learning of a conditioned taste aversion (CTA), ibotenic acid-induced, axon-sparing lesions of the amygdala do not. However, ibotenic acid lesions of the insular cortex do disrupt learning of a CTA. Electrolytic, but not ibotenic acid lesions of the amygdala, interrupt axons running between the insular (gustatory) cortex and the brainstem/hypothalamus. It is the destruction of these projections which appears to underlie CTA deficits after amygdala lesions. Other results revealed that ibotenic acid lesions of the insular cortex attenuated the reaction to the novel taste of saccharin in a familiar environment but failed to affect the ingestion of a novel food in a novel environment or passive avoidance learning. Conversely, ibotenic acid lesions of the amygdala did not affect the reaction to novel saccharin in a familiar environment but did impair both the reaction to novel food in a novel environment and passive avoidance learning. We conclude that the insular cortex is involved in reactions to the novelty and associative salience exclusively of taste stimuli, whereas the amygdala is probably more concerned with the reaction to more general aspects of novelty in the environment and in fear-motivated behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of behavioral changes in rats resulting from lesions of the habenula versus fasciculus retroflexus and their possible anatomical substrates

Lesions in either the habenula or its primary efferent pathway, the fasciculus retroflexus (FR), impaired avoidance responding. However, lesions of only the FR provided a persistent elevation of locomotor activity. Immunocytochemical study of the interpeduncular nucleus (IPN) through injection of retrograde tracers into the IPN and the overlying ventral tegmental area indicated that habenular lesions spared both rostral habenula and forebrain projections to the caudal midbrain, but these projections were axotomized by FR lesions. Rostral sparing of the habenula resulted in normal peptidergic staining in the IPN, and normal cholinergic innervation was absent. Performance of individual rats in behavioral tests was consistent with variations in anatomical sparing. Such considerations may account for previous discrepancies in functional effects of habenular lesions.     

The development of a conditioned place preference to morphine: effects of microinjections into various CNS sites

This study examined the neural substrates underlying the development of a conditioned place preference (CPP) to morphine (2 mg/kg x 3 pairings) by testing whether lesions of 7 different neural sites block a morphine-induced CPP. Lesions of the pedunculopontine tegmental nucleus (PPTg), the periaqueductal gray (PAG), or the fornix reduced the preference for a morphine-paired compartment. When they were retested following morphine administration, fornix- or PAG-lesioned animals exhibited a CPP indicating that lesions did not block morphine-induced reward or the ability to associate this effect with salient environmental cues. PPTg-lesioned animals did not express a CPP during state-dependent testing, suggesting that the lesions may attenuate the rewarding effect of the drug. Lesions of the mesolimbic dopamine system, the ventral pallidum, the lateral nucleus of the amygdala, or the caudate putamen had no effect on a morphine-induced CPP.     

Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts.

Assessed the development of a conditioned taste aversion (CTA) in 60 female Sprague-Dawley rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Ss were water deprived and presented with a .1% saccharin solution paired with injections of either LiCl or NaCl. In Exp I, VMH Ss tested at a nonobese weight level did not differ from sham-operated controls in acquisition and extinction of the CTA. In Exp II, moderately obese VMH Ss displayed a stronger CTA than did sham-operated controls as evidenced by slower extinction. A 2nd group of obese VMH Ss given an amount of LiCl equivalent to that given to the controls also displayed retarded extinction of the CTA. Results reflect an obesity-induced suppression in appetitive motivation. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance

The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal noradrenergic bundle (DNB) were assessed in animals trained in a task designed to measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal cortical noradrenaline contents but did not significantly affect striatal and hypothalamic noradrenaline contents. The performance of lesioned animals did not differ significantly from sham-lesioned controls. The performance of both the lesioned and sham-lesioned animals was impaired by the presentation of a visual distractor and by a decrease in the probability for a signal. The results from this study largely coincide with the results from previous studies on the effects of noradrenergic lesions on various aspects of attention. In contrast to the attentional functions assessed in this experiment, the ability to detect and select stimuli that are associated with activation of sympathetic functions is hypothesized to be sensitive to the effects of DNB lesions.     

The development of a conditioned place preference to morphine: Effects of lesions of various CNS sites.

This study examined the neural substrates underlying the development of a conditioned place preference (CPP) to morphine (2 mg/kg?×?3 pairings) by testing whether lesions of 7 different neural sites block a morphine-induced CPP. Lesions of the pedunculopontine tegmental nucleus (PPTg), the periaqueductal gray (PAG), or the fornix reduced the preference for a morphine-paired compartment. When they were retested following morphine administration, fornix- or PAG-lesioned animals exhibited a CPP indicating that lesions did not block morphine-induced reward or the ability to associate this effect with salient environmental cues. PPTg-lesioned animals did not express a CPP during state-dependent testing, suggesting that the lesions may attenuate the rewarding effect of the drug. Lesions of the mesolimbic dopamine system, the ventral pallidum, the lateral nucleus of the amygdala, or the caudate putamen had no effect on a morphine-induced CPP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Noradrenergic and serotonergic involvement in brief shock-induced analgesia in rats.

Performed 4 experiments to investigate the effects of different techniques causing noradrenergic and serotonergic depletions in the brain and spinal cord on brief shock-induced analgesia (BSIA). Newborn pups were administered N-2-choloroethyl-N-ethyl-2-bromobenzylamine systemically and 6-hydroxydopamine (6-OHDA) administered either systemically or directly into the locus ceruleus region, or intrathecally into the lumbar subarachnoidal space, caused notable and consistent attenuations of analgesia. Treatments reduced noradrenaline concentrations in the spinal cord drastically. A potentiation of BSIA was caused by the administration of p-chlorophenyl-alanine, whereas administration of 5,7-dihydroxytryptamine, into the nucleus raphe magnus or intrathecally into the subarachnoidal space, produced attenuation of the analgesic effect. Biochemical analyses revealed marked 5-hydroxytryptamine (5-HT) depletions in the spinal cord. Findings are discussed with regard to the role of spinal noradrenaline and 5-HT involvement in BSIA and in reactions to stressful events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)