DOPAMINE D-1 RECEPTOR ANTAGONIST SCH-23390 RETARDS METHAMPHETAMINE SENSITIZATION IN BOTH COMBINED ADMINISTRATION AND EARLY POSTTREATMENT SCHEDULES IN MICE

SCH 23390 [0.003-0.03 mg/kg, subcutaneously (SC)], a dopamine D-1 rece ptor antagonist, dose-dependently inhibited the ambulation-stimulant e ffect of methamphetamine (MAP) (2 mg/kg, SC) in mice when two drugs we re combined in repeated administrations at 3- to 4-day intervals, repe ated five times. SCH 23390 (0.03 mg/kg), which was sufficient to aboli sh the acute effect of MAP completely throughout the repeated administ rations, significantly inhibited the induction of MAP sensitization. M oreover, when the mice were posttreated with SCH 23390 (0.01 and 0.03 mg/kg) 3 h after each MAP administration, at which the ambulation-stim ulant effect of MAP had almost disappeared, they showed a significant and dose-dependent retardation of the induction of MAP sensitization. However, the 24-h posttreatment with SCH 23390 had no such effect. The administration of SCH 23390 (0.003-0.03 mg/kg) alone in either the ac tivity cage or the home cage, or saline in the activity cage with 3- o r 24-h posttreatment with SCH 23390 (0.01 or 0.03 mg/kg) five times at 3- to 4-day intervals did not elicit any significant changes in MAP s ensitivity. The present results indicate that an intense blockade of d opamine D-1 receptors in the acute or subacute period after MAP admini stration causes retardation of MAP sensitization by means of ambulatio n in mice.