GABA Effects of Nicotine in Men and Women

尼古丁 GABA 对男性和女性的影响

• 批准号: 8013571
• 负责人: GRAEME F. MASON
• 金额: $ 35.76万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8013571
• 关键词: Abstinence; Acute; Affect; Alcohol dependence; Alcoholism; Aminobutyric Acids; Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Binding; Brain; Cerebral cortex; Chronic; Cigarette; Data; Depressed mood; Development; Disease; Exclusion Criteria; Exhibits; Feeling; Gender; Glucose; Glutamates; Glutamine; Health; Hour; Human; Individual; Inhalators; Label; Lead; Link; Magnetic Resonance Spectroscopy; Maintenance; Measurement; Measures; Menstrual cycle; Mental Depression; Methods; Mood Disorders; Neurons; Neurotransmitters; Nicotine; Nicotine Dependence; Nicotine Inhaler; Outcome; Patients; Pharmaceutical Preparations; Placebos; Presynaptic Terminals; Questionnaires; Rattus; Recording of previous events; Recycling; Reporting; Severities; Sex Characteristics; Smoker; Smoking; System; Testing; Time; Tobacco; Tobacco smoking; Woman; Work; addiction; base; craving; experience; falls; gamma-Aminobutyric Acid; insight; men; neurochemistry; neuropsychiatry; neurotransmitter release; nicotine replacement; novel strategies; oxidation; receptor; response; sex; smoking cessation; success

DESCRIPTION (provided by applicant): Nicotine has been shown to affect GABAergic function in the brain. In rats, nicotine increases GABA release acutely, and human and animal studies have implicated the GABAergic system in the acquisition and maintenance of nicotine addiction. Transient increases in levels of human cortical GABA levels have been observed by magnetic resonance spectroscopy (MRS) with nicotine administration in preliminary studies in humans. Furthermore, nicotine has been seen to elevate brain GABA synthesis 2-4 fold in human brain. Knowing the effects of acute nicotine administration on brain GABA may provide insight into the interaction of tobacco smoking with prevalent disorders that are known to involve the GABAergic system, such as depression and alcoholism. This project may also provide further information about why it is so hard for some people to stop smoking. It has been shown that menstrual cycle related changes in brain GABA levels are abolished by smoking, and that men and women have some different responses to nicotine, so this project will also explore gender-based differences in GABAergic responses in the human brain. Several questions will be answered: 1) Does acute nicotine administration increase brain GABA? 2) How long does it take brain GABA to return to pre-nicotine levels? 3) Does nicotine increase GABA synthesis? 4) Does gender affect nicotine-induced changes in brain GABA levels and rates of synthesis? The concentration and rates of synthesis of brain GABA will be measured in 40 healthy smokers (20 men, 20 women) after overnight abstinence from smoking. The measurements will be conducted twice, once with a nicotine inhaler, and once with a placebo inhaler. Exclusion criteria will include current neuropsychiatric disorders, or a recent history of such. PUBLIC HEALTH RELEVANCE: This work will establish what changes in GABAergic neurons in the cerebral cortex are associated with nicotine and some of the subjective feelings that people experience with nicotine. The outcomes may help to explain why some of the newer drug-based smoking cessation approaches are effective and guide the development of new approaches. The results may also contribute to our understanding of why depressed people and patients with alcohol dependence have a greater likelihood of addiction to tobacco.

描述（由申请人提供）：尼古丁已被证明会影响大脑中的 GABA 功能。在大鼠中，尼古丁会急剧增加 GABA 的释放，人类和动物研究表明 GABA 能系统与尼古丁成瘾的获得和维持有关。在人类初步研究中，通过磁共振波谱 (MRS) 观察到，尼古丁注射后，人类皮质 GABA 水平会出现短暂增加。此外，尼古丁被发现可以将人脑中 GABA 的合成提高 2-4 倍。了解急性尼古丁对大脑 GABA 的影响可能有助于深入了解吸烟与已知涉及 GABA 系统的常见疾病（例如抑郁症和酗酒）之间的相互作用。该项目还可能提供更多关于为什么有些人戒烟如此困难的信息。研究表明，吸烟可以消除与月经周期相关的大脑 GABA 水平变化，而且男性和女性对尼古丁有一些不同的反应，因此该项目还将探讨人脑 GABA 反应的性别差异。几个问题将得到解答：1）急性尼古丁注射会增加大脑中的 GABA 水平吗？ 2) 大脑中的 GABA 需要多长时间才能恢复到尼古丁前的水平？ 3）尼古丁会增加GABA合成吗？ 4) 性别是否会影响尼古丁引起的大脑 GABA 水平和合成率的变化？将测量 40 名健康吸烟者（20 名男性，20 名女性）戒烟过夜后大脑 GABA 的浓度和合成率。测量将进行两次，一次使用尼古丁吸入器，一次使用安慰剂吸入器。排除标准将包括当前的神经精神疾病或最近的此类疾病史。公共健康相关性：这项工作将确定大脑皮层 GABA 能神经元的哪些变化与尼古丁相关，以及人们对尼古丁的一些主观感受。这些结果可能有助于解释为什么一些新的基于药物的戒烟方法是有效的，并指导新方法的开发。研究结果还可能有助于我们理解为什么抑郁症患者和酒精依赖患者更有可能烟瘾。