Can posttreatment with the selective dopamine D 2 antagonist, YM-09151-2, inhibit induction of methamphetamine sensitization? Evaluation by ambulatory activity in mice

Abstract

Effects of YM-09151-2; cis-N-(1-benzyl-2-methyl pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM), a potent and selective dopamine D 2 antagonist, on sensitization to methamphetamine (MAP) were investigated by means of ambulatory activity in mice. YM (0.003–0.03 mg/kg SC) reduced not only the acute ambulation-increasing effect of MAP (2 mg/kg SC) but also the induction of MAP sensitization when it was simultaneously administered with MAP in the repeated administration at 3/2-4 day intervals. Moreover, the post 3-h treatment with YM (0.01 and 0.03 mg/kg) following each MAP administration, at which time the acute ambulation-increasing effect of MAPalmost disappeared, significantly and dose dependently inhibited the induction of MAP sensitization. The post 24-h treatment with YM did not show such effect. The present results suggest that blockade of the dopamine D 2 receptors during postearly period following MAP administration is responsible for protecting the induction of MAP sensitization by means of ambulatory activity in mice.