FMRI OF THE MESOLIMBIC DOPAMINE SYSTEM IN RISKY DRINKERS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 研究者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。 这些知识对于理解疾病机制和开发药物治疗至关重要。 这项GCRC申请的目的是：1）获得初步数据，以支持R 01应用于NIAAA; 2）最终支持资助的NIAAA，该NIAAA使用fMRI和酒精嗅觉线索来研究具有不同酗酒风险的个体的腹侧被盖区和延髓核。 这项更大规模研究的总体目标是：1）确定嗅觉线索引起的大脑系统差异，以区分高风险和低风险的酒精中毒受试者; 2）发现对酒精线索的主观反应，预测中脑边缘多巴胺区域信号。 为了做到这一点，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，以复制并将我们的初步研究结果扩展到更大的高风险受试者（有酗酒家族史的重度饮酒者）和低风险对照组。 我们将用低剂量酒精初级和安慰剂对照进行研究。 我们还将研究暴露于酒精线索后饮酒欲望的变化，并将这些变化与fMRI中观察到的信号变化联系起来。 这项研究的重要性在于，它直接将实验动物的发现扩展到了关键的感兴趣的人群--有饮酒问题的人类受试者。

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.