NICOTINIC INFLUENCES ON ALCOHOL USE AND DEPENDENCE

申请人摘要：拟议的研究将描绘出主观的， 酒精和尼古丁之间的心血管和行为相互作用。 此外，一种新的戒烟和戒烟的药物方法 酒精中毒的治疗，包括尼古丁和尼古丁 将探索拮抗剂甲乙胺。在研究1中，急性互动 将测量受控剂量的酒精和香烟烟雾的影响 在实验室里。主观和心血管影响以及指数 将在不同剂量之前和之后测量认知能力 酒精的消耗量和含有尼古丁的香烟与非尼古丁香烟 都是烟熏的。在研究2中，酒精和尼古丁之间的相互作用 将评估以皮肤贴片形式使用的药物。研究3将调查 烟碱能神经递质在酒精奖赏中的作用 给药后控制剂量酒精的影响 烟碱拮抗剂甲乙胺。研究4和研究5将评估 尼古丁/甲基苯丙胺戒烟效果观察 酗酒者，还将决定是否临时饮酒 被这种治疗方法抑制了。在一项随机、双盲试验中， 受试者将接受为期八周的联合治疗 尼古丁/甲乙胺给药，单独尼古丁，单独甲乙胺或 安慰剂。饮酒和重新吸烟将在年内进行评估 并进行为期六个月的随访。研究6将评估其疗效 尼古丁/甲胺类药物在接受治疗的患者中的应用 酒精依赖。吸烟行为和酗酒将是 监控时间超过八周。这些研究的结果将有助于 对兼性强化作用中介因素的认识 酒精/尼古丁的使用，并将扩大有效吸烟的普遍性 对酗酒或过度饮酒的个人进行戒烟治疗 依赖。此外，这项研究可能会导致 减少酗酒者饮酒的尼古丁疗法 并促进酗酒者戒酒。

APPLICANT'S ABSTRACT: The proposed research will delineate the subjective, cardiovascular and behavioral interaction between alcohol and nicotine. Moreover, a novel pharmacologic approach for smoking cessation and alcoholism treatment involving administration of nicotine and the nicotinic antagonist mecamylamine will be explored. In Study 1, the acute interactive effects of controlled doses of alcohol and cigarette smoke will be measured in the laboratory. Subjective and cardiovascular effects as well as indices of cognitive performance will be measured before and after different doses of alcohol are consumed and nicotine-containing vs de-nicotinized cigarettes are smoked. In Study 2, the interactions between alcohol and nicotine administered in skin patches will be assessed. Study 3 will investigate the role of nicotinic neurotransmission in alcohol reward by measuring the effects of controlled doses of alcohol following administration of the nicotinic antagonist mecamylamine. Studies 4 and 5 will evaluate the efficacy of nicotine/mecamylamine treatment for smoking cessation among heavy drinkers, and will also determine whether ad lib alcohol consumption is suppressed by this treatment. In a randomized, double-blind trial, subjects will receive eight weeks of treatment using either combined nicotine/mecamylamine administration, nicotine alone, mecamylamine alone or placebo. Alcohol consumption and relapse to smoking will be assessed during treatment and at a six-month follow-up. Study 6 will evaluate the efficacy of nicotine/mecamylamine treatment in patients undergoing treatment for alcohol dependence. Smoking behavior as well as relapse to alcohol will be monitored over eight weeks. The results of these studies will contribute to the understanding of factors mediating the reinforcing actions of concurrent alcohol/nicotine use and will extend the generality of effective smoking cessation treatments to individuals exhibiting excessive alcohol use or dependence. In addition, this research may lead to the development of nicotinic treatments that reduce alcohol consumption among heavy drinkers and promote abstinence from alcohol in alcoholics.