Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis

Cocaine has been shown to produce both initial rewarding and delayed anxiogenic effects. Although the neurobiology of cocaine's rewarding effects has been well studied, the mechanisms underlying its anxiogenic effects remain unclear. We used two behavioral assays to study these opposing actions of cocaine: a runway self-administration test and a modified place conditioning test. In the runway, the positive and negative effects of cocaine are reflected in the frequency of approach-avoidance conflict that animals develop about entering a goal box associated with cocaine delivery. In the place conditioning test, animals develop preferences for environments paired with the immediate/rewarding effects of cocaine, but avoid environments paired with the drug's delayed/anxiogenic actions. In the present study, these two behavioral assays were used to examine the role of norepinephrine (NE) transmission within the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), each of which has been implicated in drug-withdrawal-induced anxiety and stress-induced response reinstatement. Rats experienced 15 single daily cocaine-reinforced (1.0 mg/kg, i.v.) runway trials 10 min after intracranial injection of the β1 and β2 NE receptor antagonists betaxolol and ICI 118551 or vehicle into the CeA or BNST. NE antagonism of either region dose dependently reduced approach-avoidance conflict behavior compared with that observed in vehicle-treated controls. In addition, NE antagonism selectively interfered with the expression of conditioned place aversions while leaving intact cocaine-induced place preferences. These data suggest a role for NE signaling within the BNST and the CeA in the anxiogenic actions of cocaine.

Anxiogenic

Extended amygdala

Basolateral amygdala

10.1523/jneurosci.3861-13.2014

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Citations (38)

Role of corticotropin-releasing hormone in the amygdala and bed nucleus of the stria terminalis in the behavioral, pain modulatory, and endocrine consequences of opiate withdrawal

Neuroscience (2002)

Gavan P. McNally Huda Akil

Corticotropin-releasing hormone

Extended amygdala

Septal nuclei

Corticosterone

Opiate

10.1016/s0306-4522(02)00105-7

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Citations (137)

Inhibition of the central extended amygdala by loud noise and restraint stress

European Journal of Neuroscience (2005)

Heidi E.W. Day Scott Nebel Sarah K. Sasse Serge Campeau

It is well established that the central nucleus of the amygdala (CEA) is involved in responses to stress, fear and anxiety. Many studies have used c-fos expression to map the brain's response to processive stress, but curiously the CEA generally is not highly activated. We have previously shown that exposure to a novel vs. home environment reduces amphetamine-induced activation of the lateral CEA (CEAl) and the oval nucleus of the bed nucleus of the stria terminalis (BSTov). This is consistent with the idea that processive stress inhibits neurons in these nuclei. We have tested this hypothesis by exposing rats to noise, at a range of intensities from non-stressful to stressful, or to restraint conditions, immediately after a remote injection of amphetamine, 2 mg/kg i.p., or interleukin-1beta (IL-1beta) 0.5 microg/kg i.p. (used to obtain a level of c-fos mRNA against which to measure inhibition). In keeping with our hypothesis, amphetamine- or IL-1beta-induced c-fos and zif-268 mRNA were significantly decreased in the CEAl and BSTov under conditions of loud noise or restraint stress compared with control conditions. This inhibition does not require a stress-induced rise in corticosterone because data were similar in animals that had been adrenalectomized with a low-dose corticosterone replacement. As both the CEAl and BSTov are highly gamma-aminobutyric acid (GABA) -ergic and project to the medial CEA (CEAm), their inhibition potentially causes an increased input to the CEAm. As the CEAm is a major output nucleus of the amygdala, this could have important consequences within the neural circuitry controlling responses to processive stress.

Corticosterone

Extended amygdala

c-Fos

10.1111/j.1460-9568.2005.03865.x

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Citations (79)

Roles of the bed nucleus of stria terminalis and of the amygdala in N/OFQ-mediated anxiety and HPA axis activation

Neuropeptides (2007)

Megan K. Green Emily V. Barbieri Brandon D. Brown Kir-Wei Chen Darragh P. Devine

Anxiogenic

Nociceptin receptor

Corticosterone

Elevated plus maze

Hypothalamic–pituitary–adrenal axis

Extended amygdala

10.1016/j.npep.2007.09.002

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Citations (51)

Stress-induced Relapse to Drug Seeking in the Rat; Role of the Bed Nucleus of the Stria Terminalis and Amygdala

Stress (2001)

Suzanne Erb Yavin Shaham Jane Stewart

AbstractThere 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.Key words: Bed nucleus of the stria terminalisCocaineCentral nucleus of the amygdalaDrug abuseHeroinStress

Extended amygdala

Septal nuclei

10.3109/10253890109014753

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Citations (74)