Imaging the Neurochemistry of Binge-Drinking in College-Aged Young Adults

大学生酗酒的神经化学成像

• 批准号: 7881339
• 负责人: Diana M Martinez
• 金额: $ 34.18万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7881339
• 关键词: Addictive Behavior; Age; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Animals; Blood; Brain; Brain imaging; Corpus striatum structure; Dependence; Development; Disease; Dopamine; Drug usage; Dynorphins; Ethanol; Exhibits; Family history of; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Head; Health; Heavy Drinking; Human; Image; Incentives; Left; Measures; Neurobiology; Neurosciences; Neurotransmitters; Outcome Measure; Participant; Play; Positron-Emission Tomography; Public Health; Raclopride; Reporting; Rewards; Risk; Risk Factors; Rodent; Role; Self Administration; Self-Administered; Signal Transduction; Surveys; Syndrome; System; Testing; Time; Up-Regulation; Ventral Striatum; Vulnerable Populations; age group; alcohol exposure; alcohol misuse; binge drinker; binge drinking; caudate nucleus; college; design; experience; extracellular; human subject; improved; in vivo; kappa opioid receptors; neurochemistry; neuropathology; neurotransmission; preclinical study; prevent; psychostimulant; public health relevance; putamen; radioligand; radiotracer; receptor; receptor binding; response; reward processing; social; transmission process; university student; volunteer; young adult

DESCRIPTION (provided by applicant): Recent reports show that young-adult binge drinking has become a major public health problem. Nevertheless, the neurochemistry associated with this type of alcohol misuse has not been extensively studied. Previous radiotracer imaging studies in alcohol dependence have reliably shown that this disorder is associated with a reduction in dopamine type 2/3 (D2/3) receptor binding in addition to a decrease in dopamine transmission of the ventral striatum. Studies in alcohol-preferring rodents show similar results. In addition, functional MRI studies have shown that alcohol dependence is associated with a loss of reward-related activation in the ventral striatum. The goal of this study is to measure these parameters of dopamine transmission in young- adult binge drinkers compared to control subjects. Using PET radioligand imaging, we will measure both D2/3 receptor binding in addition to changes in extracellular dopamine in response to a psychostimulant challenge. We will also image, for the first time in human subjects, the kappa receptor in vivo. Previous pre-clinical studies suggest that alcohol exposure is associated with an increase in endogenous dynorphin and a downregualtion of the kappa receptor. All subjects will also undergo an fMRI using the monetary incentive delay task, a task that is associated with decreased ventral striatal activation in alcohol dependence. We will also investigate the correlation between dopamine transmission measured with PET and activation measured with fMRI in the ventral striatum in the same subjects. In addition, this application will explore the correlations between the brain measures obtained, including the correlation between pre-synaptic dopamine function measured with PET and fMRI and the association between kappa receptor availability and dopamine transmission. It has previously been hypothesized that the decrease in dopamine transmission see in alcohol dependence is associated with a "reward deficiency syndrome". A possible mechanism for this is dynorphin signaling at the kappa receptor. Thus, in this study, we have proposed a set of specific aims that are designed to measure dopamine transmission and reward-related activation with the hypothesis that disruptions in striatal dopamine transmission underlie excessive alcohol consumption in this vulnerable population. PUBLIC HEALTH RELEVANCE: Previous studies have shown deficiencies in the brain neurotransmitter dopamine in alcohol dependence. This decrease in dopamine transmission is thought to play an important role in disruptions in normal reward processing. The goal of the present study is to investigate whether these alterations are present in young-adult binge drinkers, and to investigate potential mechanisms behind the disruptions in dopamine transmission.

描述(申请人提供)：最近的报告显示，年轻人酗酒已成为一个主要的公共卫生问题。然而，与这种类型的酒精滥用相关的神经化学还没有得到广泛的研究。先前对酒精依赖的放射性示踪成像研究可靠地表明，除了腹侧纹状体的多巴胺传递减少外，这种疾病还与多巴胺2/3(D2/3)受体结合减少有关。对喜欢饮酒的啮齿动物的研究也显示了类似的结果。此外，功能磁共振研究表明，酒精依赖与腹侧纹状体奖赏相关激活的丧失有关。这项研究的目的是测量青少年酗酒者与对照受试者多巴胺传递的这些参数。使用PET放射配基成像，我们将测量D2/3受体结合以及细胞外多巴胺对精神刺激剂挑战的反应变化。我们还将首次在人类受试者体内成像kappa受体。以前的临床前研究表明，酒精暴露与内源性强啡肽增加和kappa受体下调有关。所有受试者还将接受使用金钱诱因延迟任务的功能磁共振成像，这项任务与酒精依赖中腹侧纹状体激活减少有关。我们还将研究在相同受试者中，用正电子发射计算机断层扫描测量的多巴胺传递和用功能磁共振成像测量的腹侧纹状体激活之间的相关性。此外，这项应用还将探索所获得的大脑测量之间的相关性，包括用PET和fMRI测量的突触前多巴胺功能之间的相关性，以及kappa受体可用性和多巴胺传输之间的相关性。此前有假说认为，酒精依赖引起的多巴胺传递减少与“奖赏缺乏综合症”有关。一种可能的机制是Kappa受体上的强啡肽信号。因此，在这项研究中，我们提出了一系列特定的目标，旨在衡量多巴胺传递和奖赏相关的激活，假设纹状体多巴胺传递的中断是这一脆弱人群过度饮酒的基础。 与公共健康相关：以前的研究表明，酒精依赖导致大脑神经递质多巴胺缺乏。这种多巴胺传递的减少被认为在正常奖赏处理过程的中断中发挥了重要作用。本研究的目的是调查年轻人酗酒者是否存在这些变化，并调查多巴胺传递中断背后的潜在机制。