Haloperidol reduces stimulant and reinforcing effects of ethanol in socialdrinkers

Background: Despite abundant preclinical support for a role of dopamine (DA ) in the stimulant-like and reinforcing effects of ethanol, there have been few studies directly investigating this mechanism in human subjects. This study examined the effect of a DA antagonist, haloperidol, on the subjectiv e stimulant-like effects of acute doses of ethanol and on ethanol reinforce ment in healthy human volunteers. It was hypothesized that a low dose of th e DA D-2/D-3 antagonist haloperidol (3 mg) would attenuate stimulant-like s ubjective effects of ethanol (0.75 g/kg) and reduce the number of drinks ch osen during a subsequent choice phase. Methods: Seventeen healthy men and women, 21 to 35 years old, participated in four laboratory sessions conducted at 1-week intervals. During the four sessions they received, in randomized order under double-blind conditions, capsules containing haloperidol or placebo followed by three drinks contain ing ethanol (0.75 g/kg) or placebo, at 30-min intervals. Subjective and beh avioral responses were measured before and after the beverages. After the t hird beverage, subjects could choose up to five additional doses of the bev erage they had ingested. Results: Haloperidol reduced the number of ethanol beverages subjects chose without altering placebo beverage choices. Haloperidol also dampened some of the subjective effects of ethanol, especially in subjects who experience d stimulation after ethanol. Haloperidol reduced stimulant-like and euphori genic effects of ethanol in subjects who experienced stimulant effects (n=8 ) but had no effect in subjects who did not experience stimulation from eth anol (n=9). Conclusions: These findings suggest that DA plays a role in the stimulant-l ike, euphorigenic, and reinforcing qualities of ethanol in humans. However, the findings also raised new questions about the link between the subjecti ve and reinforcing effects of ethanol.