ETHANOL ANTAGONISM BY ATIPAMEZOLE ON MOTOR-PERFORMANCE IN MICE

The interactions of an alpha(2)-adrenoceptor antagonist, atipamezole, and an alpha(2)-adrenoceptor agonist, dexmedetomidine, with ethanol we re studied in male NIH Swiss mice. The mice were given (i.p.) atipamez ole 0.1, 0.3; 1, 3 and 10 mg/kg and dexmedetomidine 0.01, 0.03, 0.1, 0 .3, 1, 3 and 10 mg/kg; the ethanol doses were 1, 2 or 3 g/kg. Motor pe rformance was measured by spontaneous locomotor activity and rotarod t est. Dexmedetomidine impaired performance in both tests. The effect of dexmedetomidine peaked at the dose of 1 mg/kg. Three mg/kg of atipame zole abolished totally the effects of 0.3 mg/kg of dexmedetomidine and partially those of 1 mg/kg of dexmedetomidine. Atipamezole counteract ed and dexmedetomidine enchanced ethanol effects in both tests. The in teractions were not of pharmacokinetic origin since blood and brain et hanol and dexmedetomidine levels were unaltered at the time of testing . The results suggest that ethanol effects on motor performance in mic e are mediated in part via central noradrenergic mechanisms, and block ade of alpha(2)-adrenoceptors by atipamezole leads to considerable ant agonism of these ethanol effects.