DOPAMINE ANTAGONIST EFFECTS AN LOCOMOTOR-ACTIVITY IN NAIVE AND ETHANOL-TREATED FAST AND SLOW SELECTED LINES OF MICE

The FAST and SLOW lines of mice are being selectively bred in replicat e for differential sensitivities to the locomotor activating effects o f ethanol. Whereas FAST-1 and FAST-2 mice are stimulated by 2.0 g/kg e thanol, SLOW-1 and SLOW-2 mice are not stimulated, and are often depre ssed, by this dose. The dopamine antagonists, SCH-23390 (D-1) and racl opride (D-2), produced dose-dependent decreases in the locomotor activ ity of EtOH-naive mice of both lines and replicates; however, FAST and SLOW mice were not differentially sensitive to these effects. The abs ence of a line difference in activity response to the dopamine antagon ists suggests that dopamine receptor function has not been altered by selective breeding for differences in sensitivity to the stimulant eff ects of ethanol. The ethanol-stimulated activity of FAST-1 and FAST-2 mice was decreased by administration of the dopamine antagonists, halo peridol and raclopride, at doses that had no effect on basal locomotor activity. SCH-23390 decreased ethanol-stimulated activity of FAST-1, but not FAST-2 mice. The ethanol-induced activity changes of SLOW mice were generally unaffected by antagonist administration. These results suggest a role for dopaminergic systems in mediating ethanol-stimulat ed activity in selectively bred FAST mice. Coadministration of SCH-233 90 and raclopride decreased ethanol-induced activation to a greater de gree than either drug alone, further suggesting that both D-1 and D-2 receptor systems contribute to the full expression of the ethanol stim ulant response.