DOPAMINE ANTAGONISTS CAN INHIBIT METHAMPHETAMINE SENSITIZATION, BUT NOT COCAINE SENSITIZATION, WHEN ASSESSED BY AMBULATORY ACTIVITY IN MICE

The repeated subcutaneous administration of methamphetamine (2 mg kg(-1)) and cocaine (10 mg kg(-1)) at 3-4 day intervals induced sensitization to their ambulation-increasing effects in mice. Subcutaneous administration of SCH 23390 (R-(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.003-0-03 mg kg(-1)) and YM-09151-2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl) 2-methoxy-4-methylaminobenzamide; 0.003-0.03 mg kg(-1)), the selective dopamine D-1 and D-2 antagonists, respectively, reduced dose-dependently the acute ambulation-increasing effect of methamphetamine. The development of methamphetamine sensitization was inhibited when it was administered in combination with either SCH 23390 or YM-09151-2 in the repeated administration schedule. Although SCH 23390 (0.01-0.1 mg kg(-1)) and YM-09151-2 (0.01-0.1 mg kg(-1)) also reduced the ambulation-increasing effect of cocaine (10 mg kg(-1)), neither drug inhibited the cocaine sensitization. Mice given cocaine with SCH 23390 (0.03 mg kg(-1)) or YM-09151-2 (0.03 and 0.1 mg kg(-1)) showed higher sensitivity than those given cocaine alone. The present results suggest that, although both the dopamine D-1 and D-2 antagonists reduce the acute stimulant effects of both methamphetamine and cocaine, they are only effective for inhibition of the methamphetamine sensitization. Mechanisms other than the dopaminergic system appear to be involved in the cocaine sensitization.