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      High Dose Pimozide Does Not Block Amphetamine-Induced Euphoria in Normal Volunteers

      Pharmacology Biochemistry and Behavior
      Elsevier BV

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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.

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          Author and article information

          Journal
          Pharmacology Biochemistry and Behavior
          Elsevier BV
          00913057
          February 1997
          : 56
          : 2
          : 265-272
          Article
          10.1016/S0091-3057(96)00240-7
          9050084
          32193eea-9553-46f2-9113-8c75fafe8828
          © 1997

          https://www.elsevier.com/tdm/userlicense/1.0/

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