Imaging Nicotinic & GABAergic Markers in Smokers

烟碱成像

• 批准号: 6864141
• 负责人: JULIE K STALEY
• 金额: $ 26.81万
• 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: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6864141
• 关键词: GABA receptor; behavioral /social science research tag; benzodiazepine receptor; benzodiazepines; clinical research; drug addiction; gamma aminobutyrate; gender difference; human subject; neurochemistry; nicotine; nicotinic receptors; nuclear magnetic resonance spectroscopy; receptor binding; single photon emission computed tomography; smoking cessation; substance abuse related behavior; therapy compliance; tobacco abuse

Imaging Nicotinic & GABAergic Markers in Tobacco Smokers The nature of tobacco smoking and nicotine addiction is different between women and men. In particular, women appear to be less sensitive and more tolerant to the pharmacological effects of nicotine. Women also exhibit a poorer response to nicotine replacement therapies; are more vulnerable to smoking-related diseases (e.g. cancer and cardiovascular disease) and to subsyndromal mood disorders (depression and anxiety). Studies in animals and humans have linked subsyndromal anxiety and depressive symptoms to chronic nicotine exposure. In brain, nicotine binds to nicotinic acetylcholine receptors (nAChR) and initiates the release of most major neurotransmitters such as the major inhibitory neurotransmitter, gamma aminobutyric acid (GABA). High-affinity nicotinic agonist binding is elevated in animals chronically treated with nicotine and also in postmortem brain from tobacco smokers. The consequences of the regulatory changes in the nAChR, on GABAergic function are currently not well understood. In the present application, we propose 1) To determine if there are sex differences in high affinity nicotinic agonist binding to beta2-containing nAChR (beta2-nAChR) in men and women never smokers and recently abstinent smokers 2) To determine if cortical GABA and GABAA-benzodiazepine (GABAA-BZR) receptors are decreased in a sex-specific manner in actively dependent tobacco smokers compared to never smokers, and 3) To determine if there is a sex-specific elevation in cortical GABA levels over the first week of abstinence from smoking. Nicotine-induced adaptations in cortical beta2-nAChR, GABA and GABAA-BZR may underlie the anxiety and/or depressive symptoms often observed in women smokers. An understanding of the regulatory effects of smoking and acute abstinence on these key neurochemical targets in brain, may lead to the identification of better pharmacotherapies for smoking cessation in men and women smokers.

吸烟者尼古丁和gaba能标记物的成像研究