Effects of dopamine antagonism on methamphetamine sensitization: evaluation by ambulatory activity in mice.

Abstract SCH 23390 (SCH: 0.001–0.03 mg/kg SC) and YM: 0.001–0.03 mg/kg SC), the selective dopamine D 1 and D 2 antagonists, rspectively, reduced dose-dependently the ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg SC) in mice. The sensitization to MAP was inhibited 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 than that of SCH. However, the repeated treatment with either SCH or YM could not ameliorate the established MAP sensitization Rather, the repeated treatment with the highest dose of YM (0.03 mg/kg) increased the MAP sensitivity in both the MAP-sensitized and drug-naive mice. SCH had no such action. The present results suggest that the dopamine D 2 receptors are more intimately involved than the dopamine D 1 receptors in the increased sensitivity to MAP induced by the repeated treatment with MAP itself, behavioral sensitization, or dopamine antagonists, denervation supersensitivity.