Differential effects of catecholamine antagonists on ethanol-induced excitation in mice

Catecholamine antagonists were assessed for their effects on ethanol-induced motor excitation. Motor excitation was measured in male Swiss-Webster mice using an open-field apparatus. Mice were treated with several doses of ethanol and at each dose, mice were pretreated with pimozide, a dopamine D2 antagonist, Schering 23390, a dopamine D1 antagonist, phenoxybenzamine, a noradrenergic alpha-1 antagonist, or yohimbine, a noradrenergic alpha-2 antagonist. Each mouse was subjected to only one dose regimen, and all injections were given IP. Ethanol produced an increase in locomotor activity. The degree to which pimozide attenuated ethanol excitation decreased with increasing ethanol dosage. At the highest dose of ethanol, pimozide increased ethanol excitation. Schering 23390 attenuated ethanol-induced excitation only at doses which affected motor activity per se. Phenoxybenzamine produced a dose-dependent reduction in ethanol excitation. Yohimbine had its greatest effects at the medium dose (4.0 mg/kg). These observations seem to indicate a role for both the dopamine D2 receptor and the noradrenergic alpha-1 receptor in ethanol-induced motor excitation.