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

描述（由申请人提供）：最近的报告显示，年轻人酗酒已经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研究。先前对酒精依赖的放射性示踪成像研究已经可靠地表明，这种疾病与多巴胺2/3型（D2/3）受体结合减少以及腹侧纹状体多巴胺传递减少有关。对嗜酒的啮齿动物的研究也得出了类似的结果。此外，功能性MRI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这些参数的多巴胺传递在年轻的成年酗酒者与对照对象。使用PET放射配体成像，我们将测量D2/3受体结合以及细胞外多巴胺在精神兴奋剂刺激下的变化。我们还将首次在人类实验对象身上，对kappa受体进行成像。先前的临床前研究表明，酒精暴露与内源性dynorphin增加和kappa受体下调有关。所有受试者还将使用货币激励延迟任务进行功能磁共振成像，该任务与酒精依赖的腹侧纹状体激活减少有关。我们还将研究在同一受试者中，PET测量的多巴胺传递和fMRI测量的腹侧纹状体激活之间的相关性。此外，本应用程序将探索所获得的大脑测量之间的相关性，包括PET和fMRI测量的突触前多巴胺功能之间的相关性以及kappa受体可用性与多巴胺传递之间的关联。此前有假设认为，酒精依赖中多巴胺传递的减少与“奖励缺乏综合征”有关。一个可能的机制是kappa受体上的运动啡信号。因此，在本研究中，我们提出了一系列旨在测量多巴胺传递和奖励相关激活的具体目标，并假设纹状体多巴胺传递的中断是这一弱势群体过度饮酒的基础。

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.