Tobacco Smoking & Nicotinic Acetylcholine Receptors

吸烟

• 批准号: 7072665
• 负责人: JULIE K STALEY
• 金额: $ 24.85万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072665
• 关键词: acetylcholine; behavior modification; binding sites; blood tests; brain imaging /visualization /scanning; clinical research; drug /alcohol abstinence; drug addiction; drug withdrawal; human subject; interview; iodine; magnetic resonance imaging; neurochemistry; neutrophil; nicotine; nicotinic receptors; radiotracer; receptor binding; single photon emission computed tomography; smoking cessation; stimulant /agonist; tobacco abuse; tritium

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.

说明(申请人提供)：吸烟具有很强的成瘾性，是一系列社会、经济和医学后果的来源。吸烟导致的美国人死亡人数超过了事故、酗酒、火灾、非法药物、艾滋病、谋杀和自杀的总和，美国每年约有40万人因吸烟而过早死亡。尽管有压倒性的证据表明吸烟带来的医疗风险，但大约20%的美国人口仍在继续吸烟。这些对社会具有破坏性的代价强调了对吸烟成瘾形成和维持的神经化学机制进行研究的必要性。通过了解促进香烟成瘾的神经化学底物，可能会开发出更好的治疗这种破坏性和代价高昂的大脑疾病的方法。烟碱型乙酰胆碱受体(NAChR)是尼古丁的初始作用部位，尼古丁是烟草烟雾中的主要成瘾化学物质。在目前的建议中，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的β2-烟碱型乙酰胆碱受体(NAChR)上的激动剂结合部位进行成像。具体地说，我们建议1)确定最近戒烟的人与年龄、种族和性别匹配的非吸烟者相比，大脑中5-IA与nAChR的结合是否增加；2)通过应急管理确定吸烟者的5-1A与nAChR的结合是否在戒烟四周后恢复正常；3)确定脑中5-1A与nAChR的结合是否与多形核淋巴细胞中的[~3H]尼古丁结合相关。这些研究将表征吸烟者戒烟后第一个月尼古丁受体上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的人群。