HIGH-DOSE PIMOZIDE DOES NOT BLOCK AMPHETAMINE-INDUCED EUPHORIA IN NORMAL VOLUNTEERS

Studies with laboratory animals have shown that dopamine antagonists b lock the rewarding and interoceptive effects of amphetamine. However, studies using dopamine antagonists with humans have not consistently s hown blockade of amphetamine-induced euphoria. The unexpected results in humans may relate to the low doses of dopamine antagonists tested. The purpose of this study was to evaluate the effects of a relatively high acute dose (8 mg) of the dopamine receptor antagonist, pimozide, on responses to d-amphetamiqe (10 and 20 mg) in normal volunteers. Mal e and female volunteers (N = 12) attended six sessions on which they r eceived pimozide or placebo (7:30 am) followed by d-amphetamine or pla cebo (9:30 am). Subjective, physiological and behavioral measures were obtained at baseline (7:15 am) and hourly over a 5 h period. d-Amphet amine and pimozide, when administered alone, produced significant and opposite effects on ratings of Elation and Vigor, as well as on psycho motor performance and physiological measures. However, there were few significant interactions between pimozide and d-amphetamine. Thus, pim ozide failed to consistently antagonize the effects of d-amphetamine, even at doses of pimozide that had behavioral and physiological effect s when administered alone. Possible reasons for lack of robust dopamin e antagonism of amphetamine-induced euphoria in humans are discussed. Copyright (C) 1997 Elsevier Science Inc.