Interactions of alpha 2-adrenoceptor antagonists with medetomidine and with ethanol in a holeboard test

The effects of two selective alpha 2-adrenoceptor agonists (clonidine and medetomidine) and antagonists (atipamezole and idazoxan) were examined in the holeboard test. The interactions of the two antagonists with ethanol were also investigated. Atipamezole (0.1-3.0 mg/kg) and idazoxan (0.01-0.3 mg/kg) were without effect on either directed exploration or locomotor activity in the holeboard test, whereas clonidine (0.003-0.1 mg/kg) and medetomedine (0.003-0.1 mg/kg) were sedative. Atipamezole (1-3 mg/kg) and idazoxan (0.3-1.0 mg/kg) reversed the behavioral effects of 0.1 mg/kg of medetomidine. When administered with ethanol (2 g/kg), atipamezole (1-3 mg/kg) showed a significant antagonism of the ethanol-induced reduction in exploratory head-dipping: no change in the locomotor stimulant properties of ethanol was seen. A similar trend was seen for exploration after a combination of idazoxan (1-3 mg/kg) with 2 g/kg ethanol; however, the 3 mg/kg dose attenuated the locomotor stimulant effect. Both antagonists caused a dose-related reduction in the increase in head-dipping seen after administration of 1 g/kg of ethanol, without any effect on the locomotor stimulant effect of this dose. These results suggest mediation of alpha 2-adrenoceptors in some of the behavioral effects of ethanol.