期刊
NEUROPSYCHOPHARMACOLOGY
卷 37, 期 6, 页码 1483-1499出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2011.334
关键词
anabolic steroids; GABA(A) receptor; corticotropin-releasing factor; anxiety; acoustic startle response; extended amygdala
资金
- NIH [DA022716, DA014137, DK07508]
- SCCPIR from the NIH [U54 HD28934]
Increased anxiety is commonly observed in individuals who illicitly administer anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical role in the expression of diffuse anxiety and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naive mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. Neuropsychopharmacology (2012) 37, 1483-1499; doi: 10.1038/npp.2011.334; published online 1 February 2012
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