Can posttreatment with the selective dopamine D2 antagonist, YM-09151-2, inhibit induction of methamphetamine sensitization? Evaluation by ambulatory activity in mice.

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 D2 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 3-4 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 MAP almost 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 D2 receptors during postearly period following MAP administration is responsible for protecting the induction of MAP sensitization by means of ambulatory activity in mice.