PHARMACOLOGICAL SUBSTRATES OF AMPHETAMINE ADDICTION

这项研究的目的是加深我们对苯丙胺成瘾的药理学基础的了解，并探索潜在的新治疗方法的可行性。对实验室动物的研究表明，神经递质多巴胺(DA)在安非他明的奖赏效应中起到了中介作用，但对人类的研究提供了不一致的结果。我们通过比较安慰剂、DA激动剂和DA拮抗剂对苯丙胺的主观和行为影响来探讨DA的作用。我们还旨在确定与DA激动剂和拮抗剂联合使用比单独使用任何一种治疗方法都能在多大程度上减少苯丙胺的影响，以努力扩大先前在吸烟者中的发现。研究按2(激动剂：D-苯丙胺或安慰剂[PLAC])×2(拮抗剂：氟哌啶醇[HAL]或PLAC)×2(挑战药物：AMP或PLAC)在受试者内和受试者之间混合设计进行。预处理药物是受试者内部的操作，而挑战药物的情况因受试者而异。所有药物都是在双盲条件下给药，不同受试者的条件顺序是平衡的。我们假设氟哌啶醇和d-苯丙胺都会减弱对d-苯丙胺激发剂量的主观反应(例如，兴奋反应)，但联合使用氟哌啶醇和d-苯丙胺将在更大程度上减弱对激发剂量的反应。此外，我们预计联合的预处理条件将产生比单独使用任何一种预处理药物更好的副作用方案。

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.