EFFECTS OF DOPAMINE ANTAGONISM ON METHAMPHETAMINE SENSITIZATION - EVALUATION BY AMBULATORY ACTIVITY IN MICE

SCH 23390 (SCH: 0.001-0.03 mg/kg SC) and YM-09151-2 (YM: 0.001-0.03 mg /kg SC), the selective dopamine D-1 and D-2 antagonists, respectively, reduced dose-dependently the ambulation-increasing effect of methamph etamine (MAP: 2 mg/kg SC) in mice. The sensitization to MAP was inhibi ted when it was administered in combination with SCH (0.003-0.03 mg/kg ) or YM (0.003-0.03 mg/kg) in the repeated administration regimen. The inhibitory action of YM on the MAP sensitization was more prominent t han that of SCH. However, the repeated treatment with either SCH or YM could not ameliorate the established MAP sensitization. Rather, the r epeated treatment with the highest dose of YM (0.03 mg/kg) increased t he MAP sensitivity in both the MAP-sensitized and drug-naive mice. SCH had no such action. The present results suggest that the dopamine D-1 receptors are more intimately involved than the dopamine D-2 receptor s in the increased sensitivity to MAP induced by the repeated treatmen t with MAP itself, behavioral sensitization, or dopamine antagonists, denervation supersensitivity.