D1 dopamine receptor regulates alcohol-motivated behaviors in the bed nucleus of the stria terminalis in alcohol-preferring (P) rats

Recent studies have implicated the bed nucleus of the stria terminalis (BST) as a potential brain substrate for mediating drug-related behaviors. Neuroanatomical studies have demonstrated that reciprocal projections exist from the BST to the ventral tegmental area (VTA), a dopamine reward substrate proposed to play a role in alcohol abuse. In the present study, we evaluated the role of the D-1 and D-2 dopamine receptors of the BST in regulating alcohol and sucrose-motivated behaviors. Alcohol-preferring (P) rats were trained under an FR4 operant schedule to self-administer either EtOH (10% v/v) or sucrose (2% w/v). Following training, we evaluated the capacity of a competitive D-1 (SCH 23390; 0.5-20.0 mug) and a D-2 (eticlopri,de; 0.5-20.0 mug) dopamine antagonist to selectively reduce EtOH-maintained responding. Naltrexone, (5-30.0 mug), the nonselective opioid antagonist, was used as a reference agent. The results showed that SCH 23390 dose-dependently reduced alcohol-motivated responding. Responding was reduced with the 20.0 mug dose to about 97% of control levels. SCH 23390 also reduced sucrose responding; however, the magnitude of effects was substantially lower with the highest doses (2.5, 20.0 mug) (68-79% of control levels). In contrast, eticlopride failed to significantly alter alcohol responding and reduced sucrose responding only with the 10.0 mug dose. Unlike the dopamine-antagonists, all naltrexone doses failed to alter EtOH or sucrose-maintained responding. The results suggest a salient role for the D-1, but not the D-2 and opioid receptors in selectively modulating EtOH-motivated behaviors in the BST.