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 were studied in male NIH Swiss mice. The mice were given (i.p.) atipamezole 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 performance was measured by spontaneous locomotor activity and rotarod test. Dexmedetomidine impaired performance in both tests. The effect of dexmedetomidine peaked at the dose of 1 mg/kg. Three mg/kg of atipamezole abolished totally the effects of 0.3 mg/kg of dexmedetomidine and partially those of 1 mg/kg of dexmedetomidine. Atipamezole counteracted and dexmedetomidine enchanced ethanol effects in both tests. The interactions were not of pharmacokinetic origin since blood and brain ethanol and dexmedetomidine levels were unaltered at the time of testing. The results suggest that ethanol effects on motor performance in mice are mediated in part via central noradrenergic mechanisms, and blockade of alpha 2-adrenoceptors by atipamezole leads to considerable antagonism of these ethanol effects.