The bed nucleus of the stria terminalis is required for the expression of contextual but not auditory freezing in rats with basolateral amygdala lesions

Previous data suggest that overtraining can overcome fear conditioning deficits in rats with lesions of the basolateral complex of the amygdala (BLA). We have previously shown that the central nucleus of the amygdala (CEA) is essential for the acquisition and expression of conditional fear to both contextual and auditory conditioned stimuli (CSs) after overtraining. This provides strong evidence that the CEA can compensate for the loss of the BLA. Another brain area that may compensate for the loss of the BLA is the bed nucleus of the stria terminalis (BNST). We explored this possibility by examining the consequences of lesions or reversible inactivation of the BNST on the expression of overtrained fear in rats with BLA lesions. We demonstrate that lesions or inactivation of the BNST block the expression of freezing to the conditioning context, but not to an auditory conditional stimulus. These results reveal that the BNST has a critical role in the expression of contextual fear, but not fear to an auditory CS, and is therefore not the essential locus of compensation for fear learning in the absence of the BLA.     

Exploration and avoidance in rats with lesions in amygdala and piriform cortex

Lesions localized to specific areas of the amygdala and overlying cortex in rats produced differential effects in several behavioral tasks. Three different types of lesions were tested: central, basolateral, and cortex lateral to the amygdala. Lesions restricted to the central nucleus produced increased activity on all parameters studied in an open-field test, but the other two groups were not changed. In one-way active avoidance all three groups with lesions showed deficits. The most pronounced change was observed in the central group. All groups showed the same degree of retention loss, but in forced extinction of one-way active avoidance after retraining, the cortical and basolateral groups were most defective. A fear-reduction hypothesis is proposed for the central lesion. The basolateral and cortical areas may be more specifically involved in passive avoidance behavior.     

Stress-induced relapse to drug seeking in the rat: role of the bed nucleus of the stria terminalis and amygdala

There is growing interest in the role that the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA), components of the extended amygdala, play in drug addiction. Within the BNST and CeA, there is an extensive system of intrinsic, primarily GABAergic, interconnections known to synthesize a variety of neuropeptides, including corticotrophin-releasing factor (CRF). The actions of CRF at extrahypothalamic sites,including the BNST and CeA, have been implicated in stress responses and in the aversive effects of withdrawal from drugs of abuse. Most recently, we have shown a critical role for extrahypothalamic CRF in stress-induced reinstatement of drug seeking in rats. In attempting to determine which brain circuitry mediates the effect of stress on relapse and, more specifically, where in the brain CRF acts to initiate the behaviours involved in relapse, we focused on the BNST and CeA. In the present paper, we summarize studies we have conducted that explore the role of these brain sites in stress-induced relapse to heroin and cocaine seeking, and then consider how our findings can be understood within the more general context of what is known about the role of the BNST and CeA in stress-related and general approach behaviours, such as drug seeking.     

Differential effects of inferior temporal cortex lesions upon visual and auditory-evoked potentials in the amygdala of the squirrel monkey (Saimiri sciureus)

Visual-evoked potentials (VEPs) and auditory-evoked potentials (AEPs) were elicited from amygdala nuclei and inferior temporal (IT) cortex in chaired, alert squirrel monkeys to diffuse flash and click stimuli. VEPs were recorded from electrodes placed in basalis lateralis amygdalae (BLA) and basalis medialis amygdalae (BMA) while AEPs could also be obtained from additional electrode sites in basalis accessorius medialis (BAM), centralis amygdalae (CeA), and lateralis amygdalae (LA). The amygdala-evoked potentials resulting from stimulation of the two modalities were similar in terms of component configuration. AEPs recorded from the IT cortex had shorter latencies than the amygdala VEPs that were recorded. Both modalities of stimulation elicited potentials with shorter onset latencies in the amygdala than those recorded from the surface of IT cortex. Bilateral ablation of the IT cortex eliminated VEPs recorded from the BMA but not the BLA amygdala region. AEPs recorded from BMA as well as other amygdala areas were not consistently affected by these IT cortical ablations.     

The relationship between the amygdala and bed nucleus of the stria terminalis in the cat: an evoked potential and single cell study

The effects of amygdala stimulation on excitability of cells in the bed nucleus of the stria terminalis (BNST) were investigated in the cat. The predominant effect of stimulation was to excite cells localized in the lateral BNST. Cells responded either with single spikes to a stimulus pulse or in short bursts. Spontaneous firing of cells after a pulse to the amygdala was observed to both increase and decrease over a 4-s interval. Increases in firing rate, however, were the predominant response. Cells in more anterior locations in the BNST responded with latencies shorter than those of cells in more posterior locations, reflecting either differences in conduction time of excitation from the amygdala or differences in transmitters mediating the excitatory effects. Associated with increases in cell firing was a compound field potential with an initial negative component and a later positive component. These components may be generated by different cell types within the BNST. The negative component likely represents a field EPSP. Effective sites of amygdala stimulation were restricted to the posterior basal amygdala, and effects observed in the BNST were restricted to the lateral BNST. These data correspond well with anatomical studies showing a monosynaptic projection of basal amygdala to lateral BNST in the cat. This study suggests that this projection is predominantly excitatory.     

The effects of lesions in the central nucleus of the amygdala on appetitive classical conditioning in rats

Abstract: Lesions in the central nucleus of the amygdala (cAMY) have been known to interfere with the acquisition of fear classical conditioning when footshock is used as an unconditioned stimulus (US). The present study examined whether or not a similar interference would occur with an appetitive US. Five rats with lesions in the cAMY (the cAMY group), and eight unoperated control rats were trained in an appetitive classical conditioning paradigm, which did not include elements of operant learning, using a visual conditioned stimulus (CS) (5 W of light for 10 s duration) paired with a food pellet US (45 mg, cheese flavor). The behavioral index of appetitive conditioning was an increase in rearing approach behavior to the CS after CS and US pairings. During CS and US pairings, the movement of the rat was limited so that this approach behavior could not occur. As a result, all control rats showed an increase in rearing, but the cAMY group did not. These results suggest that the cAMY is critical for appetitive as well as fear classical conditioning.     

Differential effects of beta-adrenergic receptor blockade in basolateral amygdala or insular cortex on incidental and associative taste learning

The importance of central β-adrenergic system has been essentially investigated in aversive/emotional learning tasks. However, recent data suggest that the β-adrenergic system is also required for incidental taste learning. In the present study we evaluated in rats whether β-adrenergic receptor activity is required for taste habituation, an incidental taste learning, and also for conditioned taste aversion (CTA) learning, an associative learning. To address this issue, a low dose of the β-adrenergic antagonist propranolol was infused before learning in either the basolateral amygdala (BLA) or the insular cortex (IC), two forebrain areas reported to play a key role in taste memory formation. Incidental taste learning was assessed using a single presentation of the sweet taste saccharin 0.1%, which is sufficient to increase saccharin consumption (relative to water baseline) during a second presentation. CTA was assessed by pairing the first saccharin 0.1% presentation with a delayed gastric malaise, thus causing a decrease in saccharin consumption (relative to water baseline) during a second presentation. Propranolol infusion in BLA (1 μg/0.2μl) or IC (2.5 μg/0.5 μl) before the first taste exposure impaired incidental taste learning but did not affect CTA. These results highlight the important role played by the β-adrenergic receptor activation in cortical and amygdaloid structures during taste learning. Moreover, they are the first to suggest that incidental learning is more sensitive to blockade of noradrenergic system than associative learning.     

Role of the bed nucleus of the stria terminalis in the cardiovascular responses to acute restraint stress in rats

The aim of this work was to test the hypothesis that the bed nucleus of the stria terminalis (BST) and noradrenergic neurotransmission therein mediate cardiovascular responses to acute restraint stress in rats. Bilateral microinjection of the non-specific synaptic blocker CoCl(2) (0.1 nmol/100 nl) into the BST enhanced the heart rate (HR) increase associated with acute restraint without affecting the blood pressure increase, indicating that synapses within the BST influence restraint-evoked HR changes. BST pretreatment with the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nl) caused similar effects to cobalt, indicating that local noradrenergic neurotransmission mediates the BST inhibitory influence on restraint-related HR responses. BST treatment with equimolar doses of the alpha(2)-adrenoceptor antagonist RX821002 or the beta-adrenoceptor antagonist propranolol did not affect restraint-related cardiovascular responses, reinforcing the inference that alpha(1)-adrenoceptors mediate the BST-related inhibitory influence on HR responses. Microinjection of WB4101 into the BST of rats pretreated intravenously with the anticholinergic drug homatropine methyl bromide (0.2 mg/kg) did not affect restraint-related cardiovascular responses, indicating that the inhibitory influence of the BST on the restraint-evoked HR increase could be related to an increase in parasympathetic activity. Thus, our results suggest an inhibitory influence of the BST on the HR increase evoked by restraint stress, and that this is mediated by local alpha(1)-adrenoceptors. The results also indicate that such an inhibitory influence is a result of parasympathetic activation.     

The effect of amygdala lesions on conditional and unconditional vocalizations in rats

Electrolytic lesions centered on the amygdaloid central nucleus (ACe) resulted in the inability of rats to acquire a Pavlovian conditional vocalization response. Conditioning consisted of pairing a light conditional stimulus with a tailshock unconditional stimulus (US). The thresholds of three unconditional responses (URs) to tailshock were assessed prior to conditioning. These URs are organized at spinal (spinal motor reflexes), medullary (vocalizations during shock), and forebrain (vocalization afterdischarges, VADs) levels of the neuraxis. Compared to sham-lesioned controls, rats with amygdala lesions exhibited a selective elevation in the threshold of VADs. During conditioning the amplitude and duration of VADs were selectively reduced in amygdala-lesioned rats. These findings support earlier observations of that elicitation of VADs by tailshock correlates with the capacity of this US to support fear conditioning. The ACe may be involved in both associative and non-associative aspects of fear conditioning, but for progress in our understanding it is essential to evaluate its role in the generation of conditioning relevant URs.     

Comparison of emotional responses in monkeys with rhinal cortex or amygdala lesions

Four emotionally arousing stimuli were used to probe the behavior of monkeys with bilateral ablations of the entorhinal and perirhinal cortex. The monkeys' behavioral changes were then contrasted with those observed earlier (M. Meunier, J. Bachevalier, E. A. Murray, L. Málková, & M. Mishkin, 1999) in monkeys with either neurotoxic or aspiration lesions of the neighboring amygdala. Rhinal cortex ablations yielded several subtle behavioral changes but none of them resembled any of the disorders typically seen after amygdalectomies. The changes produced by rhinal damage took mainly the form of heightened defensiveness and attenuated submission and approach responses; that is, just the opposite of some of the most distinctive symptoms following amygdala damage. These findings raise the possibility that the rhinal cortex and amygdala have distinct, interactive functions in normal behavioral adaptation to affective stimuli.     

Differential effects of dorsal raphe lesions and intraraphe GABA and benzodiazepines on conflict behavior in rats

Both reductions in brain serotonin activity and injections of benzodiazepine drugs increase punished responding in rats, but the evidence is conflicting on the role of serotonin pathways in the benzodiazepine effect. Therefore a series of studies were carried out using a Geller-Seifter procedure with three components, to examine drug effects on rewarded, nonrewarded, and punished responding. Using male hooded Lister rats and chronic indwelling cannulae, it was found that neither chlordiazepoxide (1.5 and 5.0 micrograms in 0.5 microliter), midazolam (1.0 and 10.0 micrograms in 0.5 microliter), nor GABA (100, 500, 1000, and 5000 ng in 0.5 microliter), exerted significant anticonflict activity when injected into the dorsal raphe. Lesions of the dorsal raphe produced by injections of 5,6-dihydroxytryptamine significantly increased punished responding, and there were significant correlations between lesion size, extent of forebrain serotonin depletion, and increases in punished responding. Peripheral injections of chlordiazepoxide (5.0 and 10.0 mg/kg) and midazolam (1.25, 2.5, and 5.0 mg/kg) significantly increased punished responding both before and after raphe lesions. The increase in lesioned animals was significantly greater than after drug or lesion alone and represented a powerful additive effect which was specific to punished responding. As intraraphe benzodiazepines did not exert significant anticonflict activity, and raphe lesions did not attenuate the anticonflict activity of peripheral benzodiazepines, it is concluded that increases in punished responding seen after serotonin depletion and after benzodiazepine drugs may be dissociable.     

Dissociable effects of basolateral amygdala lesions on decision making biases in rats when loss or gain is emphasized

Individuals switch from risk seeking to risk aversion when mathematically identical options are described in terms of loss versus gains, as exemplified in the reflection and framing effects. Determining the neurobiology underlying such cognitive biases could inform our understanding of decision making in health and disease. Although reports vary, data using human subjects have implicated the amygdala in such biases. Animal models enable more detailed investigation of neurobiological mechanisms. We therefore tested whether basolateral amygdala (BLA) lesions would affect risk preference for gains or losses in rats. Choices in both paradigms were always between options of equal expected value—a guaranteed outcome, or the 50:50 chance of double or nothing. In the loss-chasing task, most rats exhibited strong risk seeking preferences, gambling at the risk of incurring double the penalty, regardless of the size of the guaranteed loss. In the betting task, the majority of animals were equivocal in their choice, irrespective of bet size; however, a wager-sensitive subgroup progressively shifted away from the uncertain option as the bet size increased, which is reminiscent of risk aversion. BLA lesions increased preference for the smaller guaranteed loss in the loss-chasing task, without affecting choice on the betting task, which is indicative of reduced risk seeking for losses, but intact risk aversion for gains. These data support the hypothesis that the amygdala plays a more prominent role in choice biases related to losses. Given the importance of the amygdala in representing negative affect, the aversive emotional reaction to loss, rather than aberrant estimations of probability or loss magnitude, may underlie risk seeking for losses.     

Defensive behaviors in rats following septal and septal--amygdala lesions

Rats with anterior septal lesions showed a pattern of consistent enhancement of defensive behaviors normally elicited by threatening conspecifics, with no enhancement of attack or general reactivity. Further division of this group indicated that damage to sites anterior and ventral to the septal area, sites previously implicated in the "septal syndrome," produces maximal effect on these behaviors. When amygdala lesions are combined with septal damage this enhanced defensive responding is almost completely eliminated. These results were interpreted as indicating that the septal syndrome represents hyperdefensiveness to conspecific threat stimuli rather than aggression or increased general reactivity, and that amygdaloid mechanisms are also involved in the regulation of conspecific defensive behaviors.     

Retracted: Effects of cartoon violence on aggressive thoughts and aggressive behaviors

This article reports on an experiment designed to test whether the cartoon manipulation leads to significant increases in aggressive thoughts and aggressive behaviors among Chinese children (n = 3,000). Results indicated that brief exposure to a violent cartoon triggered higher aggressive thoughts and aggressive behaviors than a nonviolent cartoon. Females displayed higher aggressive thoughts and aggressive behaviors than males in a nonviolent cartoon condition, while males displayed higher aggressive behaviors than females in a violent cartoon condition. Mediation analysis suggested that the effect on aggressive behaviors was mediated by aggressive thoughts. The findings imply that cartoon developers, parents, and teachers should develop cartoons that inhibit children's aggressive thoughts to avoid aggressive behaviors. Females are the key group for the prevention and intervention of aggression in a nonviolent cartoon context, while males are the key group for the prevention and intervention of aggression in a violent cartoon context.     

Differential effects of predator stress and the antidepressant tianeptine on physiological plasticity in the hippocampus and basolateral amygdala

Stress can profoundly affect memory and alter the functioning of the hippocampus and amygdala. Studies have also shown that the antidepressant tianeptine can block the effects of stress on hippocampal and amygdala morphology and synaptic plasticity. We examined the effects of acute predator stress and tianeptine on long-term potentiation (LTP; induced by 100 pulses in 1 s) and primed burst potentiation (PB; a low threshold form of LTP induced by only five physiologically patterned pulses) in CA1 and in the basolateral nucleus (BLA) of the amygdala in anesthetized rats. Predator stress blocked the induction of PB potentiation in CA1 and enhanced LTP in BLA. Tianeptine blocked the stress-induced suppression of PB potentiation in CA1 without affecting the stress-induced enhancement of LTP in BLA. In addition, tianeptine administered under non-stress conditions enhanced PB potentiation in the hippocampus and LTP in the amygdala. These findings support the hypothesis that acute stress impairs hippocampal functioning and enhances amygdaloid functioning. The work also provides insight into the actions of tianeptine with the finding that it enhanced electrophysiological measures of plasticity in the hippocampus and amygdala under stress, as well as non-stress, conditions.