FMRI OF THE MESOLIMBIC DOPAMINE SYSTEM IN RISKY DRINKERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究人员的长期目标是使用功能成像来研究导致酒精中毒和治疗复发的中脑边缘多巴胺脆弱性。这些知识对于了解疾病机制和开发药物治疗方法是必不可少的。GCRC应用程序的目的是：1)获得初步数据以支持R01应用于NIAAA，以及2)最终支持由NIAAA资助的NIAAA使用功能磁共振成像和酒精嗅觉线索来研究酒精中毒不同风险个体的腹侧被盖区和伏隔核。这项更大规模的研究的总体目标将是：1)识别嗅觉线索在大脑系统中引发的差异，区分患酒精中毒的高风险和低风险受试者；2)寻找对酒精线索的主观反应，预测中脑边缘多巴胺区域信号。为此，我们将使用fMRI来成像中脑边缘多巴胺区域对酒精气味线索的反应，以复制和扩展我们的初步发现，并将其扩展到更大的高危受试者(有酗酒家族史的酗酒者)和低风险对照组。我们将在低剂量酒精基础上和安慰剂对照期间做到这一点。我们还将研究在接触酒精线索后饮酒欲望的变化，并将这些变化与观察到的fMRI信号变化联系起来。这项研究的意义在于，它直接将实验动物的发现扩展到感兴趣的关键人群--有问题饮酒的人类受试者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The investigator's long term goal is to use functional imaging to study mesolimbic dopamine vulnerabilities that lead to alcoholism and treatment relapse. This knowledge is essential for understanding disease mechanisms and developing drug treatments. The aims of this GCRC application are to 1) gain preliminary data to support an R01 application to NIAAA and 2) eventually support a funded NIAAA that uses fMRI and alcohol olfactory cues to study the ventral tegmental area and nucleus accumbens in individuals at differential risk for alcoholism. The overall aims of the larger study will be to 1) identify olfactory cue-elicited differences in cerebral systems that differentiate between subjects at high- and low- risk for developing alcoholism, and 2) find subjective responses to alcohol cues that predict mesolimbic dopamine area signals. To do this, we will use fMRI to image mesolimbic dopamine area responses to alcoholic odor cues to replicate and extend our preliminary findings into larger groups of high-risk subjects (heavy drinkers with a family history of alcoholism) and low risk controls. We will do so with a low dose alcohol primary and during placebo control. We will also study changes in desire to drink following exposure to alcohol cues, and relate those changes to observed signal changes in fMRI. The significance of this research is that it directly extends experimental animal findings into the key population of interest - human subjects with problem drinking.