Locomotor stimulant effects of intraventricular injections of low doses of ethanol in rats: acute and repeated administration

Rationale. Low doses of ethanol stimulate locomotion in mice, but in rats the typical response to peripheral ethanol administration is a dose-dependent suppression of locomotion. Moreover, chronic ethanol administration fails to produce signs of locomotor sensitization in rats. Objective. The present study was undertaken to determine whether intraventricular (i.c.v.) infusions of low doses of ethanol (as determined by comparisons with systemic doses, and by analyses of brain extract ethanol levels) could increase locomotor activity in rats after acute or repeated administration. Methods. Male rats received acute doses of ethanol i.p. (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) or i.c.v. (0.0, 0.7, 1.4, or 2.8 mumol) and were tested for motor activity. In a third experiment, repeated i.c.v. vehicle or ethanol (2.8 mumol) was administered for 15 sessions over a 30-day period, and motor activity was recorded. This phase was followed by a single challenge session, in which a low dose of ethanol (0.7 mumol) was injected i.c.v. to both groups of rats. Results. Rats injected with i.p. ethanol showed no increase in activity at low doses, with higher doses suppressing activity. In contrast, i.c.v. injections of low doses of ethanol increased motor activity. After repeated administration, ethanol-treated rats were more sensitive than control-treated rats to the locomotor stimulant effect of ethanol. Conclusions. These results demonstrate that central administration of low doses of ethanol can increase locomotor activity in rats and suggest that i.c.v. ethanol can produce some signs of motor sensitization, a characteristic that has been related to the potential addictive properties of many drugs.