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. ³Department of Anatomy, Meharry Medical College, USA
4. ⁴JF Kennedy 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, Room 724B, MRB 1, 23rd and Pierce Ave, Nashville, TN 37232-0615, USA. Tel: +615 322 1144; Fax: +615 322 1462; E-mail: danny.winder@vanderbilt.edu

Received 9 September 2004; Revised 3 November 2004; Accepted 8 November 2004; Published online 15 December 2004.

Abstract

The bed nucleus of the stria terminalis (BNST) and its adrenergic input are key components in stress-induced reinstatement and maintenance of drug use. Intra-BNST injections of either -adrenergic receptor (-AR) antagonists or ₂-adrenergic receptor (₂-AR) agonists can inhibit footshock-induced reinstatement and maintenance of cocaine- and morphine-seeking. Using electrophysiological recording methods in an in vitro slice preparation from C57/Bl6j adult male mouse BNST, we have examined the effects of adrenergic receptor activation on excitatory synaptic transmission in the lateral dorsal supracommissural BNST (dBNST) and subcommissural BNST (vBNST). ₂-AR activation via UK-14,304 (10 M) results in a decrease in excitatory transmission in both dBNST and vBNST, an effect predominantly dependent upon the _2A-AR subtype. -AR activation via isoproterenol (1 M) results in an increase in excitatory transmission in dBNST, but not in vBNST. Consistent with the work with receptor subtype specific agonists, application of the endogenous ligand norepinephrine (NE, 100 M) elicits two distinct effects on glutamatergic transmission. In dBNST, NE elicits an increase in transmission (62% of dBNST NE experiments) or a decrease in transmission (38% of dBNST NE experiments). In vBNST, NE elicits a decrease in transmission in 100% of the experiments. In dBNST, the NE-induced increase in synaptic transmission is blocked by ₁/₂- and ₂-, but not ₁-specific antagonists. In addition, this increase is also reduced by the ₂-AR antagonist yohimbine and is absent in the _2A-AR knockout mouse. In vBNST, the NE-induced decrease in synaptic transmission is markedly reduced in the _2A-AR knockout mouse. Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with -AR function.