Acute Brain Response to Alcohol: an fMRI Study

描述(申请人提供)：酒精是美国最常见的精神活性物质之一。它被61%的人口使用，其中7.4%的人符合酒精滥用或依赖的标准(APA DSM IV，1994)(Grant，1994)。尽管它得到了广泛的应用和多年的研究，但急性剂量酒精的神经解剖学目标仍然不清楚。对这些目标的更好理解可能会解释为什么一些人过度饮酒并出现酒精滥用问题，而另一些人则不是。酒精使用障碍的易感性存在个体差异的一个原因可能与药物产生的主观影响有关：一些人体验到的主要是积极的兴奋剂样作用，而另一些人只报告了镇静作用。体验兴奋剂样效应的人报告说，他们更喜欢药物效应，他们更有可能在偏好测试中饮酒。在这里，我们建议使用脑成像技术来分析对酒精的主观反应不同的健康志愿者的大脑激活模式。该项目的具体目标是：1)使用功能磁共振成像确定急性剂量酒精(0、40、80 mg%)的神经解剖靶点；2)比较报告酒精刺激样效应的个体和没有报告酒精刺激样效应的个体之间的神经激活模式。我们将使用非线性回归技术来识别给药后药物引起的静息状态信号的变化。在42名轻中度饮酒者中，我们假设酒精会在伏隔核、腹侧被盖、尾状核、壳核、杏仁核、前扣带核、前额叶皮质和小脑产生与剂量相关的信号变化。进一步我们假设，经历刺激的个体将在伏隔核、腹侧被盖、扣带和前额叶皮质表现出更大的信号变化，而没有经历刺激的个体，即主要是镇静，将在杏仁核、纹状体和小脑表现出更大的信号变化。这一新项目的发现将为了解酒精在大脑中的作用以及对酒精的神经反应如何影响酒精中毒的发展奠定基础。这项研究将提高我们对酒精反应的个体差异的理解，并将有助于我们对酒精中毒的病因的理解。这一创新项目将汇集功能磁共振成像和酒精研究领域的方法，并结合药物滥用、酒精中毒和成像领域的领先研究人员的经验。 公共卫生相关性：急性剂量酒精的神经解剖学目标尚不清楚，但对这些目标的了解可能有助于解释为什么一些人过度饮酒并出现酒精滥用问题，而另一些人则不是。酒精使用障碍易感性的个体差异可能与药物在大脑中的不同作用和不同的主观体验相对应。在这个项目中，我们将使用功能磁共振成像来识别健康人体参与者急性剂量酒精的神经解剖靶点。我们将比较酒精后感觉刺激或感觉镇静的个体在酒精后的神经激活模式。这些发现将是了解酒精在大脑中的作用以及对酒精的神经反应如何影响酒精中毒发展的基础。

DESCRIPTION (provided by applicant): Alcohol is one of the most commonly consumed psychoactive substances in the USA. It is used by 61% of the population, 7.4% of who meet criteria (APA DSM IV, 1994) for alcohol abuse or dependence (Grant, 1994). Despite its widespread use and many years of research, the neuroanatomical targets of acute doses of alcohol remain unclear. A better understanding of these targets may explain why some people drink alcohol excessively and develop alcohol abuse problems, whereas others do not. One reason for individual differences in the susceptibility to develop alcohol use disorders may be related to the subjective effects the drug produces: some people experience predominantly positive stimulant-like effects while others report only sedative effects. Individuals who experience stimulant-like effects report more "liking" of drug effects and they are more likely to consume alcohol in a preference test. Here, we propose to use brain imaging techniques to analyze patterns of brain activation in healthy volunteers who differ in their subjective responses to alcohol. The specific goals of this project are: 1) To identify the neuroanatomical targets of acute doses of alcohol (0, 40, 80mg%) using functional magnetic resonance imaging, and 2) To compare patterns of neural activation between individuals who report stimulant-like effects of alcohol and those who do not. We will use non-linear regression techniques to identify drug-induced changes in resting state signal after drug administration. In a sample of 42 light-moderate drinkers, we hypothesize that alcohol will produce dose-related signal changes in the nucleus accumbens, ventral tegmentum, caudate, putamen, amygdala, anterior cingulate, prefrontal cortex and cerebellum. Further we hypothesize that individuals who experience stimulation will exhibit greater signal change in the nucleus accumbens, ventral tegmentum, cingulate and prefrontal cortex whereas individuals who do not experience stimulation i.e., predominantly sedation, will exhibit greater signal change in the amygdala, striatum and cerebellum. The findings of this novel project will be fundamental to understanding how alcohol acts in the brain and how neural responses to alcohol influence the development of alcoholism. The research will improve our understanding of how individuals vary in their responses to alcohol and will contribute to our understanding of the etiology of alcoholism. This innovative project will bring together methodologies in the fMRI and alcohol research fields, and combines the experience of leading researchers in the drug abuse, alcoholism and imaging fields. PUBLIC HEALTH RELEVANCE: The neuroanatomical targets of acute doses of alcohol are unclear, but knowledge of these targets may help to explain why some people drink alcohol excessively and develop alcohol abuse problems, whereas others do not. Individual differences in susceptibility for alcohol use disorder may correspond to different actions of the drug in the brain and different subjective experiences. In this project we will use functional magnetic resonance imaging to identify the neuroanatomical targets of acute doses of alcohol in healthy human participants. We will compare patterns of neural activation after alcohol between individuals who report either feeling stimulated or feeling sedated after alcohol. These findings will be fundamental to understanding how alcohol acts in the brain and how neural responses to alcohol influence the development of alcoholism.