GABA Effects of Nicotine in Men and Women

尼古丁 GABA 对男性和女性的影响

• 批准号: 7758827
• 负责人: GRAEME F. MASON
• 金额: $ 36.87万
• 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/7758827
• 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; 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; Smoke; 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; public health relevance; 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）：已证明尼古丁会影响大脑中的GABA能功能。在大鼠中，尼古丁会急剧增加GABA的释放，人类和动物的研究暗示了GABA能体系在获取和维持尼古丁成瘾方面。通过磁共振光谱法（MRS）在人类初步研究中使用尼古丁给药，已经观察到了人类皮质GABA水平水平的短暂增加。此外，已经看到尼古丁可以升高人脑中2-4倍的脑GABA合成。了解急性尼古丁给药对脑GABA的影响可能会深入了解吸烟与普遍的疾病的相互作用，这些疾病已知涉及GABA能系统，例如抑郁症和酒精中毒。该项目还可能提供有关为什么某些人如此难以停止吸烟的进一步信息。已经表明，吸烟消除了月经周期与大脑GABA水平的变化，并且男人和女性对尼古丁的反应有所不同，因此该项目还将探索人脑中GABA能反应的基于性别的差异。将回答几个问题：1）急性尼古丁给药会增加大脑GABA吗？ 2）脑gaba返回到绿色核酸前水平需要多长时间？ 3）尼古丁会增加GABA合成吗？ 4）性别会影响尼古丁引起的脑GABA水平和合成率的变化吗？在戒烟过夜后，将在40名健康吸烟者（20名男性，20名女性）中测量脑GABA合成的浓度和速率。测量结果将两次进行，一次用尼古丁吸入器进行，并与安慰剂吸入器进行。排除标准将包括当前的神经精神疾病或最近的历史。公共卫生相关性：这项工作将确定大脑皮层中GABA能神经元的变化与尼古丁以及人们患有尼古丁所经历的一些主观感觉有关。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有效并指导新方法的发展。结果也可能有助于我们理解为什么沮丧的人和酒精依赖患者对烟草的成瘾可能性更大。