Genetic influences on locomotor activating effects of ethanol and sodium pentobarbital

The paradoxical capability of sedative-hypnotics to produce behavioral disinhibition varies among genotypes. In DBA/2 mice ethanol (ETOH) produced strong locomotor stimulation with the peak of the biphasic curve at 1.5 g/kg IP. C57BL/6 mice showed no activation, and F1S were intermediate. These characterizations held for a variety of behavioral indices derived from 15 min tests, such as distance, speed, and rest time, at doses in the 0-2.0 g/kg range. Analogous studies with sodium pentobarbital (0-40 mg/kg) yielded a similar pattern of strain differences in locomotor stimulation. In contrast, loss of righting reflex durations (60 mg/kg PENTO, IP) were similar in the two strains, indicating dissociation of activating and sedative effects. In complementary studies, long- and short-sleep mice, which were bred for differences in soporific effects of ETOH, showed similar activation profiles at ETOH doses up to 1.5 g/kg and PENTO doses up to 30 mg/kg. These studies provide support for an hypothesis of common genetic control of the activation effect for ETOH and PENTO.