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（由申请人提供）：最近的报告表明，年轻的暴饮暴食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尚未得到广泛的研究。先前在酒精依赖性的放射性示意剂成像研究可靠地表明，除了腹侧纹状体的多巴胺传播减少之外，这种疾病与多巴胺2/3（D2/3）受体结合的降低有关。饮酒啮齿动物的研究显示出相似的结果。此外，功能性MRI研究表明，酒精依赖性与腹侧纹状体中与奖励相关的激活的损失有关。 这项研究的目的是与对照组受试者相比，测量年轻成人饮酒者中多巴胺传播的这些参数。使用PET放射性成像，除了对精神刺激挑战的响应，我们还将测量D2/3受体结合，除了细胞外多巴胺的变化外。我们还将在人类受试者中首次形象，即体内的Kappa受体。先前的临床前研究表明，酒精暴露与内源性驱指蛋白的增加和Kappa受体的下降有关。 所有受试者还将使用货币激励延迟任务进行fMRI，该任务与酒精依赖性中腹侧纹状体激活减少有关。我们还将研究用PET测量的多巴胺传递与在同一受试者中腹侧纹状体中用fMRI测量的激活之间的相关性。此外，该应用将探讨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与Kappa受体可用性与多巴胺传播之间的关联之间的相关性。 以前已经假设，酒精依赖中多巴胺传播的减少与“奖励缺乏综合征”有关。为此，可能的机制是kappa受体处的驱动信号传导。因此，在这项研究中，我们提出了一组特定目标，旨在测量多巴胺的传播和与奖励相关的激活，假设纹状体多巴胺传播的破坏是这种脆弱人群中过量饮酒的基础。 公共卫生相关性：先前的研究表明，酒精依赖性中脑神经递质多巴胺的缺陷。人们认为多巴胺传播的这种下降在正常奖励处理中的破坏中起着重要作用。本研究的目的是研究年轻成年饮酒者中是否存在这些改变，并研究多巴胺传播破坏背后的潜在机制。