Effect of haloperidol on measures of craving and impaired control in alcoholic subjects.

We recently proposed that alcoholics suffer from a functional defect within the basal ganglia/limbic striatum or its modulation by dopaminergic projections from the ventral tegmentum, and that inhibition of striatal output caused by the prodopaminergic effects of alcohol ingestion induces or exacerbates craving and impaired control over alcohol consumption in alcoholic individuals. To test this hypothesis, 16 subjects with a diagnosis of alcohol dependence or abuse were studied in a double-blind, placebo-controlled experiment in which the effects of the D-2 antagonist haloperidol on measures of craving and impaired control were assessed before and after administration of a priming dose of alcohol. Subjects were pretreated with 0.015-0.025 mg/kg haloperidol (experimental condition) or 2 ml normal saline (control condition), and subsequently consumed 0.4-0.6 g/kg ethanol as their preferred alcohol-containing beverage. Significant increases in subjectively rated craving for alcohol and perceived difficulty resisting additional alcohol consumption occurred following the priming dose of alcohol when subjects were pretreated with saline. In contrast, no significant changes in reported ability to resist additional alcohol occurred when subjects were pretreated with haloperidol, and reported levels of craving decreased relative to baseline following haloperidol pretreatment. Subjects also consumed about 25% less optionally available alcohol when pretreated with haloperidol than when pretreated with saline. These findings support the hypothesis that craving and impaired control are induced or exacerbated by the prodopaminergic effects of alcohol consumption.