Acute Brain Response to Alcohol: an fMRI Study

大脑对酒精的急性反应：功能磁共振成像研究

基本信息

批准号：
7996061
负责人：
EMMA CHILDS
金额：
$ 18.74万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-05 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7996061
关键词：
Acute Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Amygdaloid structure Anterior Brain Brain imaging Cardiovascular system Cerebellum Corpus striatum structure Development Diagnostic and Statistical Manual Dose Drug Kinetics Drug abuse Drug effect disorder Etiology Exhibits Feeling Functional Magnetic Resonance Imaging Goals Grant Human Human Volunteers Image Image Analysis Imaging Techniques Individual Individual Differences Infusion procedures Intravenous Knowledge Light Linear Regressions Magnetic Resonance Imaging Maps Measures Methodology Methods Modeling Nucleus Accumbens Oral Participant Patient Self-Report Pattern Pharmaceutical Preparations Placebo Control Placebos Population Predisposition Prefrontal Cortex Process Randomized Regression Analysis Reporting Research Research Personnel Research Project Grants Rest Risk Route Sampling Sedation procedure Signal Transduction Techniques Testing Time Ventral Tegmental Area Work alcohol effect alcohol research alcohol response alcohol use disorder cingulate cortex design experience healthy volunteer high risk improved innovation meetings neural patterning novel pharmacokinetic model preference public health relevance putamen relating to nervous system response sedative social

项目摘要

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.

描述（由申请人提供）：酒精是美国最常消费的精神活性物质之一。 61% 的人口使用它，其中 7.4% 的人符合酒精滥用或依赖标准（APA DSM IV，1994 年）（Grant，1994 年）。尽管其广泛使用和多年的研究，但急性剂量酒精的神经解剖学目标仍不清楚。更好地了解这些目标可能可以解释为什么有些人过度饮酒并出现酗酒问题，而另一些人则不然。酒精使用障碍易感性存在个体差异的原因之一可能与药物产生的主观作用有关：有些人主要经历积极的兴奋剂样作用，而另一些人则报告只有镇静作用。经历过类似兴奋剂作用的个体报告称更“喜欢”药物作用，并且在偏好测试中他们更有可能饮酒。在这里，我们建议使用大脑成像技术来分析健康志愿者的大脑激活模式，这些志愿者对酒精的主观反应不同。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、80mg%）的神经解剖学目标，以及 2）比较报告类似兴奋剂的个体之间的神经激活模式酒精和非酒精的影响。我们将使用非线性回归技术来识别药物给药后药物引起的静息态信号的变化。在 42 名轻度适度饮酒者的样本中，我们假设酒精会在伏核、腹侧被盖、尾状核、壳核、杏仁核、前扣带回、前额皮质和小脑中产生剂量相关的信号变化。此外，我们假设经历刺激的个体将在伏核、腹侧被盖、扣带皮层和前额皮质中表现出更大的信号变化，而没有经历刺激（即主要镇静）的个体将在杏仁核、纹状体和小脑中表现出更大的信号变化。这个新项目的发现对于理解酒精在大脑中的作用以及对酒精的神经反应如何影响酗酒的发展至关重要。这项研究将增进我们对个体对酒精反应的差异的理解，并将有助于我们对酗酒病因的理解。这个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、酗酒和成像领域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，但了解这些目标可能有助于解释为什么有些人过量饮酒并出现酗酒问题，而另一些人却没有。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类参与者的急性剂量酒精的神经解剖学目标。我们将比较那些报告饮酒后感觉受到刺激或感觉镇静的个体在饮酒后的神经激活模式。这些发现对于理解酒精在大脑中的作用以及对酒精的神经反应如何影响酗酒的发展至关重要。