Neural and Neuroendocrine response to compulsive alcohol motivation

摘要 强迫性饮酒动机和酒精摄入失控是酗酒/重度和 长期饮酒，但驱动这种过度饮酒的机制尚未得到很好的研究。 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 以及可能导致强迫性酒精动机的奖励和动机途径的神经变化 以及酒精摄入失控在初步研究中，我们发现，在狂欢/重型（BH）相对于中度非 酗酒（MD）的社会饮酒者，改变了压力和线索相关的皮质醇反应和高主观酒精 在酒精品尝测试（ATT）中，渴望预测强迫性酒精动机和摄入量，在这里用作 强迫性饮酒动机和摄入的内隐测试。此外，高酒精摄入量导致 致敏皮质醇反应和高度酒精渴求仅在BH组而非MD组。扩大对 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 高酒精动机和摄入量导致皮质醇反应增加， 这反过来又预测增加主观渴望和强迫性酒精的动机和摄入量， 暴饮暴食/重度（BH）相对于中度（MD）社交饮酒者。32名MD和32名BH社交饮酒男性 和女性（年龄21-45岁;性别相同）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叶皮质（VmPFC），HPA轴和α-淀粉酶反应的变化， 重度和中度SD组的无酒精和酒精啤酒品尝试验条件。具体 目的2：评估酒精含量和呼气酒精水平的升高是否可预测皮质醇和CBF的增加 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的增加以及VmPFC CBF的降低是否预示着主观渴望的增加， 扫描后酒精味觉测试中的酒精动机和摄入量。探索性目的：探索 上述目标，并评估酒精和皮质醇相关的变化，大脑连接在BH和MD 组利用最先进的神经成像技术，该项目有望开发和验证一种 多方法神经和神经内分泌成像方案，以评估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。成功地完成这些目标可能会导致新的 测试预防和治疗酒精中毒的新疗法的方法。

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.