Sex/Gender and Nicotine Addiction: Hormones, Behavior and Neuroimaging

性别与尼古丁成瘾：激素、行为和神经影像

• 批准号: 8414883
• 负责人: NANCY K. MELLO
• 金额: $ 66.34万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8414883
• 关键词: Acute; Adrenal hormone preparation; Affect; Age; Alcohol abuse; Amygdaloid structure; Anterior Hypothalamus; Anterior Pituitary Hormones; Area; Attention; Behavior; Behavioral; Biological; Brain; Brain imaging; Cardiovascular Diseases; Cerebellum; Cessation of life; Clinical Research; Cognitive; Crossover Design; Data; Dependence; Dextroamphetamine; Disease; Disease Progression; Dopamine; Dose; Double-Blind Method; Drug Interactions; Drug abuse; Endocrine; Functional Magnetic Resonance Imaging; Gender; Gonadal Hormones; Gonadal Steroid Hormones; Hormonal; Hormones; Hypothalamic structure; Interdisciplinary Study; Intervention; Lead; Lung diseases; Luteal Phase; Malignant neoplasm of lung; Measures; Menstrual cycle; Mental disorders; National Institute of Drug Abuse; Neurobiology; Neurons; Neurosecretory Systems; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Nicotinic Receptors; Nucleus Accumbens; Pathway interactions; Pattern; Pharmaceutical Preparations; Phase; Pituitary Gland; Placebos; Progesterone; Public Health; Reaction; Relapse; Reporting; Rewards; Sampling; Sex Characteristics; Smoking; System; Thalamic structure; Time; Tobacco; United States National Institutes of Health; Woman; addiction; base; caudate nucleus; cigarette smoke-induced; cigarette smoking; density; drug of abuse; drug reward; effective therapy; improved; men; neural patterning; neuroimaging; neurosteroids; novel; novel strategies; proliferative phase Menstrual cycle; public health relevance; putamen; relating to nervous system; response; sex; sex cycle; smoking cessation; steroid hormone; therapy development; translational study

DESCRIPTION (provided by applicant): This is a revised application (A2) for interdisciplinary behavioral, neuroendocrine and neuroimaging studies of sex differences in response to nicotine submitted in response to NIDA PA-07-329. Among the addictive disorders, nicotine addiction is one of the most pervasive, and is associated with a number of potentially lethal diseases (lung cancer, cardiovascular and respiratory disease) that result in an estimated 448,000 deaths each year. Improved treatments for nicotine addiction are urgently needed, and will be facilitated by advances in our understanding of the basic neurobiology of nicotine. We propose clinical studies to examine the covariance between the hormonal, behavioral and neuroimaging effects of nicotine in nicotine- dependent men and women to determine if there are significant sex differences. Women will be studied during the mid-follicular and the mid-luteal phase of the menstrual cycle to determine if the effects of nicotine are influenced by changes in the neuroactive gonadal steroid hormones that define phases of the menstrual cycle. Functional magnetic resonance imaging (fMRI) will be used to study regional changes in brain activity. The effects of IV nicotine and placebo nicotine on neuronal activity in brain areas with a high density of nicotinic receptors, and also in regions that may be important drug reward pathways will be measured over time, and correlated with subjective and hormonal responses. Nicotine (0, 1.0 or 2.0 mg/70 kg, IV) will be administered under double-blind conditions. Samples for analysis of hypothalamic-pituitary-adrenal and gonadal hormones will be collected every 2 min to examine the temporal covariance with neuroimaging activation patterns and reports of subjective effects. We hypothesize that neuronal and hormonal activation and positive subjective responses to IV nicotine administration will be greater in men than in women. We also hypothesize that women will have greater neuronal and hormonal activation and positive responses to nicotine during the follicular phase of the menstrual cycle (when neuroactive steroid hormone levels are low) than during the luteal phase of the menstrual cycle (when neuroactive steroid hormone levels are high). Because the neuroactive steroid hormones are being used to treat a number of psychiatric disorders including drug abuse, this could lead to novel treatments for nicotine addiction. The results of these translational studies will increase our understanding of the interaction between sex, hormones, and the abuse-related effects of nicotine. These interdisciplinary studies will integrate behavioral, hormonal and neuroimaging measures to provide a comprehensive analysis of how sex differences and phases of the menstrual cycle may affect the abuse- related effects of nicotine. Advances in understanding the basic neurobiology of nicotine will inform efforts to develop better pharmacologic interventions to treat nicotine addiction.

描述（由申请人提供）：这是对跨学科行为，神经内分泌和神经影像学研究的修订应用程序（A2），响应于NIDA PA-07-329提交的性别差异研究。在令人上瘾的疾病中，尼古丁成瘾是最普遍的一种，并且与许多潜在的致命疾病（肺癌，心血管和呼吸道疾病）有关，每年估计会导致448,000例死亡。迫切需要改善尼古丁成瘾的治疗方法，并通过对尼古丁的基本神经生物学的理解来促进。我们建议临床研究检查尼古丁对尼古丁依赖性男性和女性的激素，行为和神经影像作用之间的协方差，以确定是否存在显着性别差异。将在月经周期的中间和中间阶段对妇女进行研究，以确定尼古丁的作用是否受到定义月经周期相的神经性性腺类固醇激素的变化的影响。 功能磁共振成像（fMRI）将用于研究脑活动的区域变化。静脉尼古丁和安慰剂尼古丁对烟碱受体密度高的大脑区域以及可能是重要的药物奖励途径的区域的神经元活性的影响，并将随着时间的推移测量，并且与主观和荷尔蒙反应相关。尼古丁（0、1.0或2.0 mg/70 kg，iv）将在双盲条件下进行。将每2分钟收集下丘脑 - 垂体 - 肾上腺和性腺激素的样品，以检查具有神经成像激活模式的时间协方差和主观效应的报告。 我们假设神经元和激素激活以及对静脉注射尼古丁给药的积极主观反应比女性更大。我们还假设，在月经周期的卵泡期（当神经活性类固醇激素水平较低时），女性将具有更大的神经元和激素激活以及对尼古丁的阳性反应，而不是在男性周期的黄体期（当神经活性类固醇水平较高时）。由于神经活性类固醇激素被用来治疗包括药物滥用在内的许多精神疾病，因此这可能导致新的尼古丁成瘾治疗方法。这些翻译研究的结果将增加我们对性别，激素和尼古丁与滥用相关作用之间相互作用的理解。这些跨学科研究将整合行为，荷尔蒙和神经影像学措施，以全面分析月经周期的性别差异和阶段如何影响尼古丁的滥用相关作用。理解尼古丁的基本神经生物学的进步将为您努力开发更好的药理干预措施来治疗尼古丁成瘾。