Role of Dopamine in d-Amphetamine-Induced Euphoria in Normal, Healthy Volunteers

The present study evaluated the role of dopamine in the euphorigenic effects of d-amphetamine in normal volunteers. d-Amphetamine (20 mg) was administered alone and after pretreatment with pimozide (4 mg), fluphenazine (3 or 6 mg), or prazosin (1 or 2 mg) in 3 separate groups of participants. Subjective effects were measured at regular intervals. It was hypothesized that pimozide and fluphenazine, but not prazosin, would attenuate the euphorigenic effects of d-amphetamine. In all studies, d-amphetamine produced robust stimulant-like effects (e.g., increased scores on measures of arousal and euphoria). Although none of the antagonists significantly attenuated subjective responses to d-amphetamine, there were trends for both dopamine antagonists to reduce some responses. Both dopamine antagonists also produced modest effects when administered alone. These findings are inconsistent with those of studies with laboratory animals, perhaps because of differing experimental conditions. Alternatively, these findings raise the possibility that separate processes mediate drug reinforcement and euphoria.