1. ¹Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
2. ²Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN, USA
3. ³Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, TN, USA

Correspondence: Dr DG Winder, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 23rd and Pierce Ave S, Room 724B, RRB, Nashville, TN 37232-0615, USA. Tel: +1 615 322 1144; Fax: +1 615 322 1462; E-mail: Danny.winder@vanderbilt.edu

⁴Current address: Dr TL Kash, Department of Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina Chapel Hill, NC, USA

Received 16 February 2009; Revised 14 April 2009; Accepted 21 May 2009; Published online 24 June 2009.

Abstract

Chronic alcohol exposure can cause dramatic behavioral alterations, including increased anxiety-like behavior and depression. These alterations are proposed to be due in part to adaptations in the brain regions that regulate emotional behavior, including the bed nucleus of the stria terminalis (BNST), a principal output nucleus of the amygdala. However, to date there have been no studies that have examined the impact of in vivo alcohol exposure on synaptic function in the BNST. To better understand how alcohol can alter neuronal function, we examined the ability of in vivo alcohol exposure to alter glutamatergic transmission in the BNST using whole-cell voltage clamp recordings and biochemistry in brain slices obtained from C57Bl6 mice. Chronic intermittent, but not continuous, ethanol vapor exposure increased temporal summation of NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs). Both electrophysiological and biochemical approaches suggest that this difference is not because of an alteration in glutamate release, but rather an increase in the levels of NR2B-containing NMDARs. Further, we found that ethanol modulation of NMDAR in the vBNST is altered after intermittent alcohol exposure. Our results support the hypothesis that NMDAR-mediated synaptic transmission is sensitized at key synapses in the extended amygdala and thus may be a suitable target for manipulation of the behavioral deficits associated with acute withdrawal from chronic alcohol exposure.