PHARMACOLOGICAL SUBSTRATES OF AMPHETAMINE ADDICTION

Duke University, Durham NC

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Abstract

The goals of this study were to further our understanding of the pharmacological basis of amphetamine addiction, and to explore the feasibility of a potential new treatment approach. Studies with laboratory animals have demonstrated a role for the neurotransmitter, dopamine (DA) in mediating the rewarding effects of amphetamine but studies with humans have provided inconsistent results. We explored the role of DA by comparing the subjective and behavioral effects of amphetamine after pretreatment with placebo, a DA agonist and a DA antagonist. We also aimed to determine the extent to which combined pretreatment with a DA agonist and antagonist produces greater reduction of amphetamine's effects than either treatment alone, in an effort to extend previous findings in cigarette smokers. The study was conducted according to a 2 (Agonist: d-amphetamine [AMP] or placebo [PLAC]) x 2 (Antagonist: haloperidol [HAL] or PLAC) x 2 (Challenge drug: AMP or PLAC) mixed within- and between subjects design. The pretreatment drugs were within- subjects manipulations, whereas the challenge drug condition varies between subjects. All drugs were administered under double-blind conditions, with the order of conditions counterbalanced across subjects. We hypothesized that both haloperidol and d-amphetamine wouuld attenuate subjective (e.g., euphorigenic) responses to the challenge dose of d-amphetamine, but that combined pretreatment with haloperidol and d-amphetamine would attenuate responses to the challenge dose to a significantly greater extent. Furthermore, we expected the combined pretreatment condition to produce a better side effects protocol than either pretreatment drug alone.