Tobacco Smoking & Nicotinic Acetylcholine Receptors

描述（由申请人提供）：吸烟是高度上瘾的，是众多社会，经济和医疗后果的来源。吸烟导致的美国人死亡人数超过事故、酗酒、火灾、非法药物、艾滋病、谋杀和自杀的总和，每年约有40万人过早死亡。尽管有压倒性的证据表明与吸烟相关的医疗风险，但仍有约20%的美国人口继续吸烟。这些毁灭性的社会成本强调了研究吸烟成瘾发展和维持的神经化学机制的必要性。通过了解促进香烟成瘾的神经化学底物，可以开发出更好的治疗这种破坏性和昂贵的大脑疾病的方法。烟碱乙酰胆碱受体（nAChR）是烟草烟雾中主要成瘾化学物质尼古丁的初始作用部位。在本提案中，我们试图使用单光子发射计算机断层扫描（SPECT）和放射性示踪剂[123115-1A-85830（5-1A）]对戒烟第一个月的吸烟者进行β 2-烟碱乙酰胆碱受体（nAChR）上的激动剂结合位点成像。具体而言，我们建议：1）确定与年龄、种族和性别匹配的非吸烟者相比，最近戒烟的吸烟者脑中5-IA与nAChR的结合是否升高; 2）确定使用应急管理维持戒烟四周后，吸烟者中5-1A与nAChR的结合是否正常化，3）确定脑中5-1A与nAChR的结合是否与[3 H]相关多形核淋巴细胞中的尼古丁结合。这些研究将描述戒烟第一个月内吸烟者烟碱受体激动剂结合位点的调节状态，这将有助于指导制定有针对性的治疗策略，以帮助这一严重成瘾人群。

DESCRIPTION (provided by applicant): Tobacco smoking is highly addictive and the source of a multitude of social, economic and medical consequences. Tobacco smoking kills more Americans than accidents, alcoholism, fires, illegal drugs, AIDS, murder and suicide combined and is responsible for approximately 400,000 premature deaths per year in the USA. Despite the overwhelming evidence of the medical risks associated with cigarette smoking, approximately 20% of the US population continues to smoke. These devastating costs to society underscore the need for research into the neurochemical mechanisms underlying the development and maintenance of the addiction to cigarette smoking. By understanding the neurochemical substrates promoting the addiction to cigarettes better treatments for this destructive and costly brain disorder may be developed. The nicotinic acetylcholine receptor (nAChR) is the initial site action of nicotine, the primary addictive chemical in tobacco smoke. In the present proposal, we seek to image the agonist binding site on beta2-nicotinic acetylcholine receptor (nAChR) using single photon emission computed tomography (SPECT) and the radiotracer [123115-1A-85830 (5-1A) in tobacco smokers over their first month of abstinence. Specifically, we propose 1) to determine if 5-IA binding to nAChR in brain is elevated in recently abstinent tobacco smokers as compared to age, race and sex-matched nonsmokers; 2) to determine if 5-1A binding to nAChR in smokers normalizes after four weeks of abstinence maintained using contingency management and 3) to determine if 5-1A binding to nAChR in brain correlates with [3H]nicotine binding in polymorphonuclear lymphocytes. These studies will characterize the regulatory state of the agonist binding site on the nicotinic receptor in smokers over the first month of smoking cessation, which will help guide the development of targeted treatment strategies to assist this severely addicted population.