Inhibition of mu opioid-induced motor activity in the ventral pallidum by D1 receptor blockade

Abstract

Microinjection of the mu opioid, [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) into the ventral pallidum (VP) elicits a motor stimulant response. The coadministration of dopamine (DA) antagonists with DAMGO into the VP was used to determine the role of DA transmission in the motor response. The mixed D1/D2 antagonist, fluphenazine, was found to produce a partial reduction in DAMGO-induced motor activity. To evaluate the role of DA receptor subtypes, the D1 and D2 selective antagonists, SCH-23390 and raclopride, respectively, were coadministered with DAMGO into the VP. SCH-23390 was found to produce a dose-dependent reduction in both horizontal and vertical motor activity with a minimum effective dose of 0.3nmol/side. However, only a partial reduction in horizontal activity occurred with a dose of SCH-23390 as high as 6.0nmol/side. Raclopride was without effect at any dose examined, and an equimolar mixture of SCH-23390 and raclopride did not alter the minimum effective dose nor the maximum reduction in motor activity produced by SCH-23390 alone. It is concluded that stimulation of D1 receptors is permissive to the motor stimulant effect elicited by DAMGO in the VP.