Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake

Corticotropin-releasing factor (CRF) is widely distributed throughout the brain and has been shown to mediate numerous endocrine and behavioral responses to stressors. During acute ethanol withdrawl, CRF release is increased in the central nucleus of the amygdala (CeA), and there is evidence to suggest that this activation of amygdala CRF systems may mediated the anxiogenic properties of the ethanol withdrawl syndrome. The present study was conducted to determine if another CRF-containing limbic structure, the bed nucleus of the stria terminalis (BNST), we would exhibit similar increases in CRF neurotransmission during ethanol withdrawl. Rats were administered an ethanol-containing (6.7% v/v) or control liquid diet for 2 weeks and subsequently implanted with microdialysis probes into the lateral BNST. A 50-75% increase in dialysate CRF levels was observed following removal of the ethanol-containing diet, while no changes were observed in control animals. When ethanol-withdrawn animals were given subsequent access to the ethanol-containing diet, dialysate CRF levels returned to basal levels. However, when ethanol-withdrawn animals were given subsequent access to the control diet, dialysate CRF levels increased further to 101% above basal levels. These data demonstrate that extracellular CRF levels are increased in the BNST during ethanol withdrawl, and that these increase are reduced by subsequent ethanol intake. (C) 2002 Elsevier Science Inc. All rights reserved.