Haloperidol reduces stimulant and reinforcing effects of ethanol in social drinkers

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 subjective stimulant-like effects of acute doses of ethanol and on ethanol reinforcement in healthy human volunteers. It was hypothesized that a low dose of the DA D-2/D-3 antagonist haloperidol (3 mg) would attenuate stimulant-like subjective effects of ethanol (0.75 g/kg) and reduce the number of drinks chosen 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 containing ethanol (0.75 g/kg) or placebo, at 30-min intervals. Subjective and behavioral responses were measured before and after the beverages. After the third beverage, subjects could choose up to five additional doses of the beverage 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 experienced stimulation after ethanol. Haloperidol reduced stimulant-like and euphorigenic effects of ethanol in subjects who experienced stimulant effects (n=8) but had no effect in subjects who did not experience stimulation from ethanol (n=9). Conclusions: These findings suggest that DA plays a role in the stimulant-like, euphorigenic, and reinforcing qualities of ethanol in humans. However, the findings also raised new questions about the link between the subjective and reinforcing effects of ethanol.