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 强迫性饮酒动机和酒精摄入失控是暴饮暴食/重度酗酒的标志性特征 长期饮酒，但导致过度饮酒的机制尚未得到充分研究。 过量饮酒会导致下丘脑-垂体肾上腺 (HPA) 轴的神经内分泌适应 奖励和动机途径的神经变化可能导致强迫性饮酒动机 以及失去对酒精摄入的控制。在初步研究中，我们发现暴食/重度（BH）相对于中度非 酗酒（MD）社交饮酒者改变了压力和提示相关的皮质醇反应和高主观酒精 渴望预测酒精味觉测试（ATT）中的强迫性饮酒动机和摄入量，此处用作 强迫性饮酒动机和摄入量的内隐测试。此外，大量饮酒会导致 敏感的皮质醇反应和高酒精渴望仅出现在 BH 组，而 MD 组则没有。扩展于 根据这些结果，我们建议开发一种利用多波段动脉自旋标记 (ASL) 的神经成像方法 测量结合同步神经内分泌和呼吸酒精水平来检验假设 高酒精动机和摄入量会导致皮质醇反应增加和背侧纹状体血液增加 反过来又预测主观渴望和强迫性酒精动机和摄入量的增加 相对于中度（MD）社交饮酒者而言，暴食/重度（BH）。 32 位 MD 和 32 位 BH 社交饮酒男士 女性（21-45 岁；性别平等）将在神经影像学会议中进行研究，以解决以下问题 具体目标：具体目标 1：评估主观和行为酒精动机和摄入量，CBF 纹状体和腹内侧前额皮质 (VmPFC)、HPA 轴和 α-淀粉酶反应的变化 重度和中度酗酒组中的非酒精和酒精啤酒口味测试条件。具体的 目标 2：评估酒精量和呼吸酒精水平上升是否预示皮质醇和 CBF 增加 与 MD 组相比，BH 组腹侧和背侧纹状体的反应。具体目标 3：检查 皮质醇和纹状体 CBF 增加以及 VmPFC CBF 降低是否预示主观渴望增加 扫描后酒精味觉测试中的酒精动机和摄入量。探索性目标：探索性别差异 上述目标，并评估 BH 和 MD 中与酒精和皮质醇相关的大脑连接变化 组。该项目承诺使用最先进的神经影像技术来开发和验证 多方法神经和神经内分泌成像方案评估酒精相关糖皮质激素是否 信号传导在强迫性饮酒动机中发挥着作用。成功完成目标可能会带来新的成果 测试预防和治疗酒精中毒的新疗法的方法。