Locomotor activity response to chronic ethanol treatment in selectively bred FAST and SLOW mice.

FAST and SLOW mice were selectively bred for differential sensitivity to the acute locomotor stimulant effects of alcohol. On average, FAST mice are stimulated by low alcohol doses, while SLOW mice are depressed or unaffected. We report here that, with chronic treatment, SLOW mice develop tolerance to an acute depressant effect, and subsequently exhibit a stimulant response. No evidence was obtained for tolerance to alcohol's stimulant effects during chronic exposure of FAST mice. However, evidence for the development of a sensitized response was found. If locomotor stimulation reflects reinforcement, and models the alcohol-induced euphoria reported by man, perhaps the absence of tolerance development to reinforcing effects provide a strong impetus for the development of alcoholism.