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 receptor antagonist, dose-dependently inhibited the ambulation-stimulant effect of methamphetamine (MAP) (2 mg/kg, SC) in mice when two drugs were combined in repeated administrations at 3- to 4-day intervals, repeated five times. SCH 23390 (0.03 mg/kg), which was sufficient to abolish the acute effect of MAP completely throughout the repeated administrations, significantly inhibited the induction of MAP sensitization. Moreover, 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-stimulant 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 activity cage or the home cage, or saline in the activity cage with 3- or 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 sensitivity. The present results indicate that an intense blockade of dopamine D-1 receptors in the acute or subacute period after MAP administration causes retardation of MAP sensitization by means of ambulation in mice.