Subjective responses to d-amphetamine alone and after pimozide pretreatment in normal, healthy volunteers.
The role of dopamine in d-amphetamine-induced euphoria has not been systematically examined in normal volunteers. Therefore, we examined the effects of the dopamine antagonist, pimozide, on responses to d-amphetamine in healthy volunteers, using a within-subjects, double-blind design. Ten subjects received single oral doses of d-amphetamine (0, 10, 20 mg) 2 hours following pretreatment with pimozide (0, 1, 2 mg). Subjective, behavioral, and physiological effects were assessed predrug and for 3 hours after d-amphetamine administration. d-Amphetamine alone produced prototypic effects on a variety of measures, including euphoria and drug liking. Pimozide did not produce any effects when administered alone and produced inconsistent effects on responses to d-amphetamine. Although higher doses of pimozide may be needed to antagonize the euphorigenic effects of d-amphetamine, these results raise the possibility that the role of dopamine in the subjective effects of stimulants may be more complex than initially appreciated.
Brauer
L H
LH
Department of Psychiatry, University of Chicago, IL 60639, USA.
de Wit
H
H
D000328:Adult; D000339:Affect / Q000187:drug effects; D001143:Arousal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005059:Euphoria / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010868:Pimozide / Q000494:pharmacology*; D011292:Premedication; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012016:Reference Values
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D010868:Pimozide; D003913:Dextroamphetamine