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of ethanol, but no change in the behavior of these mice, given a low dose of ethanol, was noted after the mice were withdrawn from chronic feeding with ethanol-containing diets.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 depresant 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.