Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats: studies with low and high rate operant schedules

Although ethanol is typically classed as a sedative-hypnotic, low doses of ethanol have been shown to stimulate locomotor activity in mice. However, in rats the typical response to peripheral administration of ethanol is a dose-dependent suppression of motor activity and operant responding. The present study was undertaken to determine the effects of intraventricular (ICV) infusions of ethanol, acetaldehyde, and acetate on operant performance in rats. ICV injections of ethanol, acetaldehyde, or acetate were given to rats previously trained on either a differential-reinforcement-of-low-rates-of-responding (DRL) 30-s schedule, which generates low rates of responding, or a fixed ratio 5 (FR5) schedule, which generates relatively high rates. Ethanol, acetaldehyde, and acetate all produced a rate-increasing effect in rats on the DRL 30-s schedule at moderate doses (2.8 and 1.4 mumol, respectively). Acetate also produced a rate-decreasing effect on the DRL 30-s schedule at a larger dose (8.8 mumol). Performance on the FR5 schedule was unaltered by ethanol and acetaldehyde, even at doses as high as 17.6 mumol. However, acetate produced a rate-decreasing effect on the FR5 schedule at doses of 4.4, 5.6, and 8.8 mumol. Central administration of low doses of ethanol and its metabolites can increase operant responding on some schedules in rats. Acetate is the substance that is most potent for producing rate-suppressing effects. These results indicate that the major metabolites of ethanol are pharmacologically active when injected into the brain, and suggest that acetate may mediate some of the rate-suppressing effects of ethanol, such as sedation, ataxia or motor slowing. (C) 2003 Elsevier B.V. All rights reserved.