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Abstract
Studies with laboratory animals have shown that dopamine antagonists block the rewarding
and interoceptive effects of amphetamine. However, studies using dopamine antagonists
with humans have not consistently shown 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-amphetamine
(10 and 20 mg) in normal volunteers. Male and female volunteers (N = 12) attended
six sessions on which they received pimozide or placebo (7:30 am) followed by d-amphetamine
or placebo (9:30 am). Subjective, physiological and behavioral measures were obtained
at baseline (7:15 am) and hourly over a 5 h period. d-Amphetamine and pimozide, when
administered alone, produced significant and opposite effects on ratings of Elation
and Vigor, as well as on psychomotor performance and physiological measures. However,
there were few significant interactions between pimozide and d-amphetamine. Thus,
pimozide failed to consistently antagonize the effects of d-amphetamine, even at doses
of pimozide that had behavioral and physiological effects when administered alone.
Possible reasons for lack of robust dopamine antagonism of amphetamine-induced euphoria
in humans are discussed.