Dopaminergic Function in Alcoholism

描述（由申请人提供）：多巴胺能在大脑中皮质边缘系统中的传递被认为是酒精滥用和依赖的重要因素。然而，大多数关于多巴胺对酒精及其条件提示的反应的研究都是在啮齿动物身上进行的。这些啮齿动物模型在多大程度上转化为人类酒精使用障碍尚不清楚。因此，我们提出的工作的长期目标是开发体内纹状体多巴胺能反应的人类生物标志物，可用于研究酒精中毒及其先前的风险。我们将使用正电子发射断层扫描（PET）和多巴胺D2配体[11C]raclopride以及功能磁共振成像（fMRI）来完成这项工作。行为范式将被用于研究酒精线索如何与酗酒者多巴胺功能和皮质激活相关。

DESCRIPTION (provided by applicant): Dopaminergic transmission in the brain's mesocorticolimbic system is thought to be a significant factor in alcohol abuse and dependence. Most research on the dopaminergic response to alcohol and its conditioned cues is nevertheless done in rodents. The extent to which these rodent models translate to human alcohol use disorders is unknown. Therefore the long term goal of our proposed work is the development of an in vivo human biomarker of striatal dopaminergic responses that can be applied to the study alcoholism and its antecedent risks. We will do this using both positron emission tomography (PET) and the dopamine D2 ligand [11C]raclopride, as well as fMRI. Behavioral paradigms will be employed to study how alcohol's cues relate to dopamine function and cortical activation in subjects with alcoholism. PUBLIC HEALTH RELEVANCE: This research will use a technology called positron emission tomography to study the neurochemical dopamine in the human brain. It will also use a second neuroimaging technique called functional magnetic resonance imaging to examine brain areas that become active in response to certain stimuli. Alterations in the dopamine system, and in the brain's frontal areas, are thought to be highly important to alcoholism, as well as to other addictions. Research such as this has the potential to show how dopamine neurotransmission is altered in alcoholism, and how these alterations relate to brain function in frontal cortex. A better understanding of these phenomena may lead to better diagnosis and treatment.