CAN POSTTREATMENT WITH THE SELECTIVE DOPAMINE D-2 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 in-3-yl)-5-chloro-2-me thoxy-4-methylaminobenzamide (YM), a potent and selective dopamine D-2 antagonist, on sensitization to methamphetamine (MAP) were investigat ed by means of ambulatory activity in mice. YM (0.003-0.03 mg/kg SC) r educed not only the acute ambulation-increasing effect of MAP (2 mg/kg SC) but also the induction of MAP sensitization when it was simultane ously 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 ambulat ion-increasing effect of MAP almost disappeared, significantly and dos e dependently inhibited the induction of MAP sensitization. The post 2 4-h treatment with YM did not show such effect. The present results su ggest that blockade of the dopamine D-2 receptors during postearly per iod following MAP administration is responsible for protecting the ind uction of MAP sensitization by means of ambulatory activity in mice.