Dopaminergic Function in Alcoholism

描述(申请人提供)：大脑中皮质边缘系统中的多巴胺能传递被认为是酒精滥用和依赖的一个重要因素。然而，大多数关于酒精及其条件性线索的多巴胺能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，我们建议的工作的长期目标是开发一种体内人类纹状体多巴胺能反应的生物标记物，可用于研究酒精中毒及其前驱风险。我们将使用正电子发射断层扫描(PET)和多巴胺D2配体[11C]雷氯普利以及功能磁共振成像来实现这一点。行为范式将被用来研究酒精暗示与酒精中毒受试者的多巴胺功能和皮质激活之间的关系。 与公共健康相关：这项研究将使用一种名为正电子发射断层扫描的技术来研究人类大脑中的神经化学物质多巴胺。它还将使用另一种名为功能磁共振成像的神经成像技术来检查大脑中对某些刺激做出反应的活跃区域。多巴胺系统和大脑额叶区域的变化被认为对酒精中毒和其他成瘾非常重要。这样的研究有可能显示酒精中毒时多巴胺神经传递是如何改变的，以及这些改变是如何与额叶皮质的大脑功能相关的。更好地了解这些现象可能会导致更好的诊断和治疗。

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.