Does tolerance develop to the activating, as well as the depressant, effects of ethanol?

Genetically determined differences were demonstrated in the response of mice to low doses of ethanol. Ethanol (1.35 g/kg) produced an increase in locomotion in DBA/2 and BALB/c mice, but did not alter the locomotor activity of C57B1/6 mice. Chronic administration of ethanol produced tolerance to the sedative/hypnotic effects of high doses of ethanol in DBA/2 and BALB/c mice, but the equivalent chronic ethanol administration paradigm produced no tolerance to the activating effects of ethanol in these animals. C57B1/6 mice became tolerant to the hypnotic effects of ethanol, but no change in the behavior of these mice, given a low dose of ethanol, was noted after the mice were withdrawn from chronic feeding with ethanol-containing diets. The results indicate the presence of different mechanisms for tolerance development to the activating and depressant effects of ethanol, and indicate that strain-dependent differences in the activating effects of ethanol are not determined by an animal's greater sensitivity to the sedating effects of this drug.