EFFECTS OF SCH-23390 ON DOPAMINE D1 RECEPTOR OCCUPANCY AND LOCOMOTIONPRODUCED BY INTRAACCUMBENS COCAINE INFUSION

This study examined the effects of both systemic and intraaccumbens ad ministration of SCH-23390 in rats on dopamine D1 receptor occupancy an d on locomotor activity produced by intraaccumbens infusion of cocaine . In experiment 1, rats received SCH-23390 (0-1 mg/kg, IP) 15 minutes prior to intraaccumbens infusion of cocaine (0 or 100 mu g/side). In e xperiment 2, rats received coinfusion of SCH-23390 (0-1 mu g/side) and cocaine (0 or 100 mu g/side) into the nucleus accumbens (NAc). After behavioral testing, receptors occupied by SCH-23390 were quantified by injecting animals with their respective dose of SCH-23390, followed b y a systemic injection of the irreversible antagonist N-ethoxycarbonyl -2-ethoxy-1,2-dihydroquinoline (EEDQ). Receptors occupied by SCH-23390 , and therefore protected from EEDQ-induced inactivation: were quantif ied from autoradiograms of sections labeled with H-3-SCH-23390. System ic administration of SCH-23390 dose-dependently (0.1-1.0 mg/kg) revers ed cocaine-induced locomotion and occupied 72-100% of D1-like receptor s in the anterior NAc. D1 receptor occupancy following systemic admini stration of SCH-23390 was evident as an inverted U-shaped, dose-depend ent change, with the greatest occupancy observed at the intermediate d ose of 0.3 mg/kg. Intraaccumbens infusion of SCH-23390 did not alter c ocaine-induced locomotor activity despite occupying 40-60% of D1-like receptors in the anterior NAc core and shell. The findings that system ic, but not intraaccumbens, administration of SCH-23390 potently rever sed locomotion produced by intraaccumbens cocaine infusion suggest tha t stimulation of D1 receptors in regions other than the NAc is involve d in locomotion produced by intraaccumbens infusion of cocaine, and th at stimulation of D1 receptors in the NAc is not necessary for this be havior Synapse 30:194-204, 1998. (C) 1998 Wiley-Liss, Inc.