DOPAMINE D-1 AND D-2 RECEPTOR ANTAGONISTS SUPPRESS ACUTE STIMULANT ACTION OF COCAINE, BUT ENHANCE COCAINE SENSITIZATION

The ambulation increase caused by the repeated dosing of cocaine (10 mg/kg s.c.) was dose-dependently reduced by the simultaneous administration of the selective dopamine D-1 and D-2 receptor antagonists, SCH 23390 (0.01, 0.03 and 0.1 mg/kg s.c.) and YM-09151-2 (nemonapride) (0.01, 0.03 and 0.1 mg/kg s.c.), respectively. However, the mice given cocaine with SCH 23390 (0.03 mg/kg) and cocaine with YM-09151-2 (0.03 and 0.1 mg/kg) 5 times at 3 to 4-day intervals showed significantly higher sensitivity than the mice given cocaine alone to the challenge cocaine. The present results suggest that, although the blockade of either dopamine D-1 or D-2 receptor is effective for a reduction in the stimulant action of cocaine, such treatment enhances the induction of cocaine sensitization.