INHIBITION OF MU-OPIOID-INDUCED MOTOR-ACTIVITY IN THE VENTRAL PALLIDUM BY D1 RECEPTOR BLOCKADE

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