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]雷氯普利来完成这项工作。行为范式将被用来研究酒精中毒受试者的酒精管理、酒精暗示和对即将到来的酒精中毒的预期与多巴胺功能之间的关系。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。这种神经化学系统的改变被认为对酒精中毒和其他成瘾非常重要。像这样的研究有可能准确地显示酒精中毒时多巴胺神经传递是如何改变的，这一发现可能会导致更好的治疗和诊断。

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 positron emission tomography (PET) and the dopamine D2 ligand [11C]raclopride. Behavioral paradigms will be employed to study how alcohol administration, alcohol's cues, and expectations of impending alcohol-intoxication relate to dopamine function 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. Alterations in this neurochemical system are thought to be highly important to alcoholism, as well as to other addictions. Research such as this has the potential to show exactly how dopamine neurotransmission is altered in alcoholism, findings that may lead to better treatments and diagnosis.