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.     

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

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.     

Excessive weight gains in female rats with transections of the stria terminalis

Recent studies have demonstrated hyperphagia and excessive weight gains in female rats with small lesions in the most posterodorsal aspects of the medial amygdala. In the present study, similar results were observed in female rats with bilateral transections of the stria terminalis just as it exits the amygdala to begin its dorsal ascent (mean weight gain of 35.9 g/20 days compared to 0.1 g/20 days for operated control animals). Cellular damage caused by the retractable wire knife was limited to the caudal globus pallidus. The results of previous studies that failed to observe weight gains after stria terminalis transections were attributed to the use of male animals. The present results, along with the pattern of anterograde degeneration that is observed after obesity-inducing amygdaloid lesions, suggest a medial amygdala-stria terminalis-medial hypothalamic pathway in the regulation of food intake and body weight, but other possibilities are considered.     

Effects of basolateral amygdaloid lesions on schedule induced and schedule dependent behavior.

Rats were reduced to 80% body weight and were exposed to an FI-1 min food reinforcement schedule for 30 min daily until lever presses, licks, and water consumption stabilized for at least 10 days. Bilateral lesions were then made in the basolateral amygdala of all animals. Animals were tested for 40 days following the lesions at 80% body weight, were permitted to recover body weight by increasing food rations, and were tested for an additional 15 days under ad lib feeding. Animals were then subjected to the following tests: food consumption following food deprivation, drinking following water deprivation, and salt arousal of drinking. In addition, consumption of 6.85% sucrose, 25% sucrose, 8% glucose, 21% glucose, and 0.125% Na saccharin on a FI-1 min food reinforcement schedule and under home cage conditions were measured. On the basis of these data and lesion locus the 8 animals were divided into 2 groups, bilaterally symmetrical experimentals and asymmetrical controls. Although no effects were observed in licking, water consumption, and lever pressing, animals with bilateral symmetrical lesions of the basolateral amygdala displayed relatively permanent deficits in their responses to various taste stimuli. The effects of these lesions are evaluated and discussed in terms of the lateral hypothalamic involvement in schedule induced and schedule dependent behavior.     

Effects of food restriction and adrenalectomy in rats with VMH or PVH lesions

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.     

Possible routes of visceral information in the rat brain in formation of conditioned taste aversion.

When ingestion of a taste stimulus is paired with internal malaise, the animal remembers the taste and rejects its ingestion thereafter. This learning is referred to as conditioned taste aversion (CTA). To establish CTA in adult male Wistar rats, 0.1% saccharin and an i.p. injection of 0.15 M LiCl were used as the conditioned and unconditioned stimuli, respectively. Neuroanatomical study using the tracer method was performed to examine the ascending routes from the lateral part of the parabrachial nucleus (PBlat) which receives general visceral information and suggested the three possible routes to the amygdala: (1) direct route to the central nucleus of the amygdala (CeA); (2) diencephalic route to the basolateral nucleus of the amygdala (BLA) involving the zona incerta (ZI) and the midline and intralaminar thalamic complex (MITC); and (3) cortical route to the BLA involving insular cortex (IC). Rats with excitotoxic lesions of each of the CeA, ZI, MITC or IC had only a small or negligible effect on the acquisition of CTA. However, single lesions of the BLA and combined lesions of the ZI and IC, but not CeA and IC, almost completely abolished the acquisition of CTA. These results together with previous findings suggest that visceral (or unconditioned stimulus) information in the PBlat is sent to the BLA which is essential for the acquisition of CTA via the functionally important two parallel routes, the diencephalic and cortical routes, with either being able to create the aversion.     

The effects of amygdala lesions on conditioned stimulus-potentiated eating in rats

Both control rats and rats with neurotoxic lesions of the amygdala central nucleus ate more food during presentations of a conditioned stimulus (CS) previously paired with food than during an unpaired CS. This potentiation occurred regardless of whether the food was presented in its usual place or in a different location. By contrast, rats with neurotoxic lesions of basolateral amygdala showed no evidence for conditioned potentiation of eating. These results are considered in the context of anatomical projections from these amygdalar areas to other brain regions involved in feeding, and the role of amygdala subregions in the acquisition of motivational value in conditioning.     

Early amygdala damage disrupts performance on medial prefrontal cortex-related tasks but spares spatial learning and memory in the rat

Recent studies have demonstrated that the postnatal development of connections between the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) mature around postnatal days 13-15 (pd13-15), whereas these between the BLA and other structures such as the nucleus accumbens and the mediodorsal thalamus are completed by pd7. Accordingly, it is hypothesized that mPFC cytoarchitecture and hence its function may be specifically affected by neonatal (i.e. on pd7) but not later induced (i.e. on pd21) damage to the BLA. To test this hypothesis, rats received excitotoxic lesions to the BLA on either pd7 or pd21 and were subjected to two tests putatively sensitive to mPFC dysfunction, namely food hoarding and spontaneous alternation. In addition, rats were tested for spatial learning and memory, to determine any possible effects on hippocampal function. Consistent with the documented effects of mPFC lesions, pd7 damage to the BLA impaired spontaneous alternation and food hoarding performance, an effect that was not found in rats with BLA lesions induced on pd21. Spatial learning and memory, however, were not affected by the (neonatal) lesion procedure. Together, these results indicate that neonatal BLA damage affects species-specific sequential behavior and flexibility, which may be attributed to abnormal functioning of the mPFC.     

The brain mapping of the retrieval of conditioned taste aversion memory using manganese-enhanced magnetic resonance imaging in rats

Manganese-enhanced MRI (MEMRI) is a newly developed noninvasive imaging technique of brain activities. The signal intensity of MEMRI reflects cumulative activities of the neurons. To validate the use of MEMRI technique to investigate the neural mechanisms of learning and memory, we tried to map brain areas involved in the retrieval of conditioned taste aversion (CTA) memory. CTAs were established to saccharin (conditioned stimulus: CS) by pairing its ingestion with an i.p. injection of LiCl (unconditioned stimulus: US). LiCl solutions (as a robust aversion chemical) of 0.15 M were injected i.p. 15 min after drinking the saccharine solution (CS). After the two times conditionings, these rats showed a robust aversion to the saccharine solution (CS). Rats of the control group were injected saline i.p. instead of LiCl solutions. The MRI signal intensities at the gustatory cortex (GC), the core subregion of the nucleus accumbens (NAcC), the shell subregion of the nucleus accumbens (NAcSh), the ventral pallidum (VP), the central nucleus of amygdala (CeA), the lateral hypothalamus (LH), and the basolateral nucleus of amygdala (BLA) of the conditioned group were higher than those of the control group. There were no significant differences between the conditioned and the control groups in the intensities for other regions, such as the striatum area, motor cortex, cingulate cortex, interstitial nucleus of the posterior limb of the anterior commissure and hippocampus. These indicate that the GC, NAcC, NAcSh, VP, CeA, LH and BLA have important roles in the memory retrieval of CTA.     

Basolateral amygdala and morphine-induced taste avoidance in the rat

The present experiment examined the influence of excitotoxic lesions of the basolateral amygdala (BLA) on morphine-induced saccharin avoidance. Neurologically intact subjects rapidly learned to avoid drinking the taste conditioned stimulus (CS), an effect that was sustained throughout the experiment. Although the BLA-lesioned (BLAX) rats showed CS avoidance over the first few trials, the effect was not sustained. That is, by the end of the experiment, the BLAX rats were drinking the same amount of saccharin after seven saccharin-morphine trials as they did on the first trial (i.e., prior to the morphine injections). Potential interpretations of the results are discussed including a disruption of the mechanism that governs drug-induced taste avoidance in normal subjects and the more rapid development of tolerance in BLAX rats.     

Effects of VMH lesions on schedule induced and schedule dependent behaviors

Ten male hooded rats were exposed to an FI 1 min food reinforcement generator schedule at 80% body weight and schedule dependent lever pressing and schedule induced licking and drinking were recorded. When lever pressing, licking, and drinking stabilized the 10 rats were divided into two groups. One group was composed of 4 animals subjected to sham lesion procedures plus one animal with asymmetrical ventromedial hypothalamic (VMH) lesions. The other group was composed of 5 animals with bilateral symmetrical VMH destruction. Results demonstrate that VMH destruction produces a slight transient decrease only in water intake when on schedule at 80% body weight. When animals are returned to ad lib eating and body weight increased and they are returned to the test chamber, the VMH lesion animals display increased licking and drinking. Although VMH lesion animals ate and drank more than controls, they did not eat more in response to food deprivation and did not drink more in response to water deprivation and the intraperitoneal administration of hypertonic saline. The presence or absence of food or water was the determining factor in the overeating or excessive drinking of the VMH lesion animals. Results are discussed in terms of gastrointestinal influences on the hypothalamic mechanisms involved in the production of schedule induced behaviors.     

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 brain stem/hypothalamus. It is the destruction of these projections which appear to underly 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.     

Comparative effects of lesion of the basolateral nucleus and lateral nucleus of the amygdaloid body on neophobia and conditioned taste aversion in the rat

The effects of bilateral lesions of the basolateral and lateral nuclei of the amygdala on the neophobic response and LiCl-conditioned taste aversion to a saccharin solution were studied in rats. Compared to intact animals, rats with basolateral lesions did not exhibit neophobia to the novel stimulus, while rats with lateral lesions demonstrated an initial preference to the sweet solution over water. The LiCl-induced aversion was suppressed after basolateral lesions and was unchanged after lateral lesions. It is concluded that these two amygdaloid nuclei play an important but distinct role in neophobia and conditioned taste aversion.     

Memory deficits following nucleus basalis magnocellularis lesions may be mediated through limbic, but not neocortical, targets

In order to test the contribution of the target areas of the nucleus basalis magnocellularis to the mediation of item and order recognition memory for spatial locations, one set of rats received lesions of the dorsolateral frontal cortex, parietal cortex, or basolateral amygdala after training in an order recognition memory task, whereas another set of animals received lesions of the nucleus basalis magnocellularis or basolateral amygdala in an item recognition memory task. Animals with basolateral amygdala lesions displayed a deficit for order recognition memory, but no deficit for item recognition memory, a pattern equivalent to that found for animals with nucleus basalis magnocellularis lesions. In contrast, animals with dorsolateral frontal cortex displayed no deficit, and animals with parietal cortex lesions displayed only a partial deficit for order recognition memory, results that differ from those found for animals with nucleus basalis magnocellularis lesions. It appears that the nucleus basalis magnocellularis influences item and order recognition memory for lists of spatial locations primarily through projections to limbic but not neocortical targets.     

Quetiapine produces a prolonged reversal of the sensorimotor gating-disruptive effects of basolateral amygdala lesions in rats

Prepulse inhibition (PPI) of startle is impaired in schizophrenia and in rats after manipulations of limbic cortical and subcortical regions. The atypical antipsychotic quetiapine was used to reverse PPI deficits after basolateral amygdala (BLA) lesions in rats. BLA quinolinic acid lesions significantly disrupted PPI 1 week postsurgery. Tests with quetiapine (0 vs. 7.5 mg/kg) in a within-subject design 2-3 weeks postsurgery revealed a normalization of PPI. Carry-over effects lasted up to 3 weeks, with a return of lesion-induced deficits by Week 5 postsurgery. This dose of quetiapine also blocked the PPI-disruptive effects of phencyclidine. PPI deficits after BLA lesions are reversed by quetiapine, in a manner that is sustained beyond its acute pharmacological effects and which may be mediated downstream from the BLA.     

Relationship between wheel running, feeding, drinking, and body weight in male rats

The amount of wheel running varies widely between rats. Wheel introduction and running also have profound effects on the animal's energy balance. We explored the effects of ad lib wheel access and running levels on feeding, drinking, and body weight in 30 young adult male rats with wheel access and in 30 rats without wheel access. The initial running period (Days 1-8) and a time of stable running [Days 29-32 (DEnd)] were analyzed using both between- and within-group approaches. Initially, wheel access suppressed feeding (by about 25% over the 8 days) but not drinking. There were no significant correlations between the amount of wheel running and the other behaviors. The degree of feeding suppression was also not correlated to the amount of running. When running had stabilized (animal ran from 841 to 13,124 wheel turns per day), food intake was increased by about 0.75 g per 1000 wheel turns. Running at this time correlated positively with feeding and drinking and negatively with body weight and weight gain. In animals without wheel access, feeding and drinking were positively correlated with weight and weight gain, but in animals with wheel access, these correlations were close to zero. Only early running predicted later levels of running but accounted for only 23% of the variance in running. Wheel access has profound but very different immediate and long-term effects on the rats' energy balance.     

Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum

The involvement of the amygdala in the potentiation of responding for conditioned reinforcers following intra-accumbens amphetamine injections has been studied. Thirsty rats were trained to associate a light-noise compound stimulus with water and then implanted with guide cannulae in the nucleus accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by infusing N-methyl-D-aspartate, whereas the other half received infusions of the vehicle. In the test phase, water was no longer presented but responding on one of two novel levers produced the light-noise compound (the conditioned reinforcer) whereas responding on the other lever had no effect. The two groups received four counterbalanced intra-accumbens infusions of amphetamine (3, 10 and 30 micrograms /microliter) or vehicle over four test days. Intra-accumbens amphetamine infusions dose-dependently increased responding on the lever providing a conditioned reinforcer but had no significant effect on responding on the lever which did not produce the conditioned reinforcer. Compared with controls, the lesioned group exhibited a significant, selective reduction in responding on the lever providing a conditioned reinforcer, with no change on the lever on which responding had no consequence, irrespective of drug or control treatment. Control experiments showed that the amygdala lesioned animals were not hypodipsic and exhibited similar levels of hyperactivity following intra-accumbens infusions of D-amphetamine. Furthermore, the capacity to discriminate the conditioned stimulus as well as to acquire a new motor task was not altered by the lesion. These results indicate a role for the amygdala in mediating the effects of stimulus-reward associations on behaviour, via an action on dopamine-dependent mechanisms of the ventral striatum.     

Conditioned and unconditioned fear organized in the inferior colliculus are differentially sensitive to injections of muscimol into the basolateral nucleus of the amygdala

Chemical stimulation of the inferior colliculus (IC) with semicarbazide--an inhibitor of the gamma aminobutyric acid synthesizing enzyme--functions as an unconditioned stimulus in the conditioned place aversion test (CPA), and electrolytic lesions of the basolateral amygdala (BLA) enhance the aversiveness of the IC stimulation. This study examined the effects of inactivation of the BLA with muscimol on the conditioned and unconditioned fear using semicarbazide injections into the IC of rats subjected to conditioned (CPA) or unconditioned (open field) fear tests. In both tests, the rats were injected with semicarbazide or saline into the IC and muscimol or saline into the BLA. Muscimol decreased the CPA and increased the unconditioned fear elicited by IC injections of semicarbazide. These findings indicate that distinct modulatory mechanisms in the BLA are recruited during the conditioned and unconditioned fear triggered by IC activation. ((c) 2006 APA, all rights reserved).     

Aging impairs amygdala-hippocampus interactions involved in hippocampal LTP.

Aging impairs amygdala-hippocampus interactions involved in hippocampal LTP. NEUROBIOL. AGING. We have recently shown that the stimulation of the basolateral nucleus of the amygdala (BLA) is able to prolong early-LTP (<4h) into late-LTP (>4h) in the dentate gyrus. To study whether aging affects this interaction, aged (24-27 months) rats were used, classified as cognitively impaired (I), or non-impaired (N) by means of their results in the Morris water maze. Paired pulses (30-90 ms interval) showed no differences among age groups. Among young controls, the early-LTP induced in the dentate gyrus by stimulation of the perforant path (PP) was prolonged in a late-LTP when the BLA was stimulated 15 min later. In aged-impaired rats the stimulation of the PP induced a reduced LTP, decaying to baseline in less than 2 h. BLA stimulation was without effect. Aged non-impaired rats showed an early-LTP identical to that of young animals; however, stimulation of the BLA showed no effect. These results suggest that deficient synaptic plasticity and memory functions in aged animals might be caused, in part by impaired mechanisms of heterosynaptic reinforcement.     

Pretraining NMDA receptor blockade in the basolateral complex,but not the central nucleus,of the amygdala prevents savings of conditional fear

The acquisition of conditional freezing is abolished by N-methyl-D-aspartate (NMDA) receptor antagonism in the basolateral complex of the amygdala (BLA) during fear conditioning, suggesting that memory formation is prevented. The present study examined whether there is residual memory, or "savings," for fear conditioning in rats trained under amygdaloid NMDA receptor blockade. Rats infused with D,L-2-amino-5-phosphonovalerate (APV) into the BLA or central nucleus of the amygdala (CEA) during fear conditioning did not acquire either auditory or contextual fear conditioning. However, savings of conditional fear was exhibited by rats infused with APV into the CEA but not the BLA. These results suggest that both the BLA and CEA play a critical role in the acquisition of conditional fear but that the BLA is able to process and retain some aspects of aversive memories in the absence of the CEA.