Haloperidol antagonism of cue-elicited cocaine craving

Background Studies of cocaine-dependent subjects have shown that re-exposure to environmental cues previously associated with cocaine use produces a strong conditioned response characterised by autonomic hyperarousal and increases in subjective measures of cocaine craving. Methods To evaluate the role of dopamine release by such cues, 20 cocaine-dependent inpatients were randomised in a single-dose, crossover, placebo-controlled design, to haloperidol (4 mg by mouth) and placebo. Plasma homovanillic acid (HVA, a dopamine metabolite), adrenocorticotropic hormone (ACTH), and cortisol were assayed before and after cue exposure, Craving and anxiety were measured before and after cues with visual analogue scales for desire to use cocaine now and for mood changes. Findings Cocaine cues significantly increased anxiety, ACTH, cortisol, and HVA. Increases in anxiety and craving resulting from cue exposure were significantly antagonised by pretreatment with haloperidol. Interpretation It has long been hypothesised that increases in extracellular concentrations of dopamine mediate the acute reinforcing effects of cocaine. Our data suggest that dopamine release may also mediate some of the conditioned responses to cocaine cues.