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 sensitizat ion to their ambulation-increasing effects in mice. Subcutaneous admin istration of SCH 23390 roxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepi ne; 0.003-0-03 mg kg(-1)) and YM-09151-2 (cis-N-(1-benzyl-2-methylpyrr olidin-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 methampheta mine. The development of methamphetamine sensitization was inhibited w hen it was administered in combination with either SCH 23390 or YM-091 51-2 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 a mbulation-increasing effect of cocaine (10 mg kg(-1)), neither drug in hibited 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 s ensitivity than those given cocaine alone. The present results suggest that, although both the dopamine D-1 and D-2 antagonists reduce the a cute stimulant effects of both methamphetamine and cocaine, they are o nly effective for inhibition of the methamphetamine sensitization. Mec hanisms other than the dopaminergic system appear to be involved in th e cocaine sensitization.