DOPAMINERGIC ANGENTS ON ACUTE RESPONSES TO SMOKING

这项正在进行的研究将评估多巴胺(DA)在香烟中的作用 抽烟。我们将评估DA激动剂(d-苯丙胺)、 拮抗剂(氟哌啶醇)和激动剂/拮抗剂组合物(d- 苯丙胺+氟哌啶醇)对香烟急性主观反应的影响 吸烟(例如，吸烟满意度、减少渴求的评分)。我们 假设通过阻断突触后DA受体，氟哌啶醇会 减弱从吸烟中获得的满足感，从而可能增加 对香烟的渴望。我们还预计d-苯丙胺将减少 吸烟满意度和减少对香烟的渴望，通过代之以 尼古丁的多巴胺释放作用。因为氟哌啶醇和d- 安非他明在使用时有望降低吸烟满意度 单独使用，我们预测联合使用氟哌啶醇和d- 安非他命会在更大程度上降低满足感。我们会 同时探讨MAO-B抑制剂的有效性和耐受性。 司来吉兰，作为戒烟的药物疗法。我们假设 服用司来吉兰的受试者吸烟率会更高 禁欲与接受安慰剂的受试者相比。最后，我们会 确定实验室中对多巴胺能药物的急性反应 可以预测临床环境中的吸烟状况。初步 来自少数受试者的数据表明，联合预处理法 使用氟哌啶醇和苯丙胺可将吸烟满意度降低到 比任何一种药物单独使用的程度都要大，是一种安全和可耐受的 综合治疗。 意义：近5000万美国人吸烟，尽管 吸烟与相当大的发病率和死亡率之间的联系， 包括冠心病、中风、慢性阻塞性肺病 疾病、外周血管疾病、消化性溃疡、肺癌和 死亡。不幸的是，吸烟者减少吸烟的尝试是 经常不成功，即使在目前可用的帮助下 药物治疗。更成功的治疗方法的发展 戒烟在很大程度上依赖于更好地了解 尼古丁成瘾的神经化学机制，以及 增加对导致吸烟的非尼古丁因素的认识 行为。本研究将有助于阐明DA在急性脑梗塞中的作用。 对吸烟的主观、行为和生理反应， 并评估多巴胺能疗法对吸烟的疗效 停止。

This ongoing study will evaluate the role of dopamine (DA) in cigarette smoking. We will assess the effects of a DA agonist (d-amphetamine), an antagonist (haloperidol), and an agonist/antagonist combination (d- amphetamine + haloperidol) on acute subjective responses to cigarette smoking (e.g., ratings of smoking satisfaction, craving reduction). We hypothesize that by blocking post-synaptic DA receptors, haloperidol will attenuate the satisfaction gained from smoking and thereby may increase craving for cigarettes. We also expect that d-amphetamine will reduce smoking satisfaction and reduce craving for cigarettes, by substituting for the DA-releasing effects of nicotine. Since both haloperidol and d- amphetamine are expected to reduce smoking satisfaction when administered alone, we predict that the combined administration of haloperidol and d- amphetamine will reduce satisfaction to an even greater extent. We will also explore the efficacy and tolerability of the MAO-B inhibitor, selegiline, as a pharmacotherapy for smoking cessation. We hypothesize that subjects receiving selegiline will show higher rates of smoking abstinence as compared to subjects receiving placebo. Finally, we will determine whether acute responses to dopaminergic agents in the laboratory are predictive of smoking status in the clinical setting. Preliminary data from a small number of subjects suggests that combined pretreatment with haloperidol and amphetamine attenuates smoking satisfaction to a greater extent than either drug alone, and is a safe and tolerable treatment combination. Significance: Nearly fifty million Americans smoke cigarettes, despite the association of smoking with substantial morbidity and mortality, including coronary heart disease, stroke, chronic obstructive pulmonary disease, peripheral vascular disease, peptic ulcers, lung cancer, and death. Unfortunately, smokers attempts to reduce their smoking are frequently unsuccessful, even with the aid of currently available pharmacological treatments. The development of more successful treatments for smoking cessation relies heavily on gaining a better understanding of the neurochemical mechanisms underlying nicotine addiction, as well as increased knowledge of non-nicotine factors that contribute to smoking behavior. This study will help to elucidate the role of DA in acute subjective, behavioral and physiological responses to cigarette smoking, and to assess the efficacy of a dopaminergic treatment for smoking cessation.