Behavioral effects of alpha2 adrenoceptor antagonists and their interactions with ethanol in tests of locomotion, exploration and anxiety in mice

The behavioral effects of two highly selective alpha₂-adrenoceptor antagonists, atipamezole and idazoxan, were investigated in mice using the plusmaze test of anxiety and the holeboard test of directed exploration and locomotor activity. No anxiogenic effect, as assessed by the tendency to enter the closed as opposed to open arms of the plusmaze, was noted for either drug at any dose tested. Neither were there any significant effects on locomotor activity or directed exploration (head-dipping) in the holeboard, or total plusmaze arm entries at any dose of either drug. The co-administration of either atipamezole or idazoxan had no effect on either the anxiolytic effect of ethanol (2 g/kg) or its locomotor stimulant effect in the holeboard. Atipamezole (1.0 and 3.0 mg/kg) significantly reversed the ethanol-induced reduction in exploratory head-dipping; a similar trend was seen for idazoxan. There was also a significant potentiation of the ethanol-induced increase in the number of total arm entries made on the plusmaze caused by 1.0 mg/kg (but not 3.0 mg/kg) atipamezole and both 0.3 and 1.0 mg/kg idazoxan. The results suggest that some of the behavioral effects of ethanol can be reversed by alpha₂-adrenoceptor antagonists whilst others are unchanged.