Neural and Neuroendocrine response to compulsive alcohol motivation

对强迫性酒精动机的神经和神经内分泌反应

• 批准号: 9316393
• 负责人: Rajita Sinha
• 金额: $ 24.08万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316393
• 关键词: Accidents; Acute; Address; Adult; Age; Alcohol consumption; Alcohol dependence; Alcohols; Amygdaloid structure; Beer; Behavioral; Blood flow; Brain; Cerebrovascular Circulation; Cessation of life; Corpus striatum structure; Crime; Cues; Development; Disease; Dorsal; Family; Future; Gender; Glucocorticoids; Glucose; Healthcare; Heavy Drinking; Hour; Human; Hydrocortisone; Hypothalamic structure; Image; Individual; Intake; Lead; Measurement; Methods; Motivation; National Institute on Alcohol Abuse and Alcoholism; Neurosecretory Systems; Obesity; Pathway interactions; Phase; Play; Prefrontal Cortex; Prevention; Protocols documentation; Recording of previous events; Recruitment Activity; Reporting; Rewards; Role; Scanning; Sex Characteristics; Signal Transduction; Spin Labels; Stress; Taste Perception; Technology; Testing; Woman; alcohol craving; alcohol cue; alcohol measurement; alcohol relapse; alcohol testing; alcoholism therapy; alpha-amylase; base; behavior test; chronic alcohol ingestion; cost; craving; drinking; emotional stimulus; experimental study; hypothalamic-pituitary-adrenal axis; innovation; men; neurobehavioral; neuroimaging; non-alcoholic; novel; novel strategies; novel therapeutics; problem drinker; productivity loss; relating to nervous system; response; social

ABSTRACT Compulsive alcohol motivation and loss of control alcohol intake are hallmark features of binge/heavy and chronic alcohol use but the mechanisms that drive this excessive alcohol consumption are not well studied. Excessive alcohol use leads to neuroendocrine adaptations in the hypothalamic-pituitary adrenal (HPA) axis and neural changes in the reward and motivation pathways which may lead to compulsive alcohol motivation and loss of control alcohol intake. In preliminary studies we find in binge/heavy (BH) relative to moderate non- binge (MD) social drinkers that altered stress and cue related cortisol responses and high subjective alcohol craving predicts compulsive alcohol motivation and intake in the alcohol taste test (ATT), used here as an implicit test of compulsive alcohol motivation and intake. Furthermore, high alcohol intake led to an increased and sensitized cortisol response and high alcohol craving only in the BH and not the MD group. Expanding on these results, we propose to develop a neuroimaging approach utilizing multiband, arterial spin labelling (ASL) measurement combined with simultaneous neuroendocrine and breath alcohol levels to test the hypothesis that high alcohol motivation and intake leads to increased cortisol responses and greater dorsal striatal blood flow which in turn predicts increased subjective craving and compulsive alcohol motivation and intake in binge/heavy (BH) relative to moderate (MD) social drinkers. Thirty-two MD and 32 BH socially drinking men and women (ages 21-45; equal gender) will be studied in a neuroimaging session to address the following specific aims: Specific Aim 1: To assess subjective and behavioral alcohol motivation and intake, CBF changes in the striatum and ventromedial prefrontal cortex (VmPFC), HPA axis and alpha-amylase response in the non-alcoholic and alcoholic beer taste test conditions in binge heavy and moderate SD groups. Specific Aim 2: To evaluate if alcohol amount and ascending breath alcohol levels predict increased cortisol and CBF response in the ventral and dorsal striatum in the BH compared to MD group. Specific Aim 3: To examine whether increased cortisol and striatal CBF and lower VmPFC CBF predict increased subjective craving and alcohol motivation and intake in post-scan alcohol taste test. Exploratory Aims: To explore sex differences in the above aims and also assess alcohol- and cortisol-related changes in brain connectivity in BH and MD groups. Using state-of-the-art neuroimaging technologies, this project promises to develop and validate a multimethod neural and neuroendocrine imaging protocol to assess whether alcohol-related glucocorticoid signaling plays a role in compulsive alcohol motivation. Successful completion of the aims could lead to new approaches for testing novel therapeutics in prevention and treatment of alcoholism.

抽象的 强迫性酒精动机和控制酒精摄入量是暴饮暴食的标志性特征 慢性酒精使用，但促进这种过度饮酒的机制尚未得到很好的研究。 过量的饮酒会导致下丘脑 - 垂体肾上腺（HPA）轴的神经内分泌适应 以及奖励和动机途径的神经变化，这可能导致强迫性酒精动机 和控制酒精摄入量的损失。在初步研究中，我们在暴饮暴食/重（BH）中发现 暴饮暴食（MD）社交饮酒者改变了压力和提示相关皮质醇的反应和高主观酒精 渴望预测酒精味觉测试（ATT）中的强迫性酒精动机和摄入量，此处用作 强迫性酒精动机和摄入量的隐式检验。此外，高酒精摄入导致增加 仅在BH而不是MD组中，敏感的皮质醇反应和高酒精渴望。扩展 这些结果，我们建议利用多播，动脉自旋标记（ASL）开发一种神经影像学方法 测量结合同时神经内分泌和呼吸酒精水平来检验假设 高酒精的动机和摄入导致皮质醇反应增加和背纹状体血液 流量反过来预测主观的渴望和强迫性酒精动机和摄入量增加 相对于中等（MD）社交饮酒者的暴饮暴食/重型（BH）。三十二个医学博士和32 bh的社交饮酒 和妇女（21-45岁；平等性别）将在神经影像学课程中进行研究以解决以下 具体目的：具体目的1：评估主观和行为酒精的动机和摄入量，CBF 纹状体和腹侧前额叶皮层（VMPFC），HPA轴和α-淀粉酶反应的变化 暴饮暴食和中度SD组的非酒精和酒精啤酒口味测试条件。具体的 目标2：评估酒精含量和呼吸呼吸是否预测皮质醇和CBF的增加 与MD组相比，BH腹侧和背纹状体的反应。特定目标3：检查 皮质醇和纹状体CBF以及VMPFC CBF的增加是否可以预测主观渴望和 酒后扫描后酒精味测试中的酒精动机和摄入量。探索目的：探索性别差异 上述目的，还评估BH和MD中大脑连通性的酒精和皮质醇相关的变化 组。使用最先进的神经影像技术，该项目有望开发和验证 多方法神经和神经内分泌成像方案，以评估与酒精相关的糖皮质激素是否 信号在强迫性酒精动机中起作用。成功完成目标可能会导致新的 测试预防和治疗酒精中毒的新型治疗方法的方法。