Dopaminergic Function in Alcoholism

酒精中毒中的多巴胺能功能

• 批准号: 7832911
• 负责人: DAVID A. KAREKEN
• 金额: $ 30.89万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7832911
• 关键词: Alcohol abuse; Alcoholism; Alcohols; Animal Model; Animals; Area; Behavioral Paradigm; Biological Assay; Biological Markers; Brain; Brain imaging; Chemicals; Corpus striatum structure; Cues; Dependence; Development; Diagnosis; Dopamine; Dose; Environment; Functional Magnetic Resonance Imaging; Funding; Goals; Human; Image; Imaging Techniques; Incentives; Indiana; Knowledge; Laboratories; Lead; Learning; Ligands; Link; Measures; Medial; Methods; Modeling; Parents; Positron-Emission Tomography; Prefrontal Cortex; Property; Raclopride; Recording of previous events; Relapse; Research; Research Personnel; Rewards; Risk; Rodent; Rodent Model; Scientist; Stimulus; Study Subject; System; Taste Perception; Techniques; Technology; Testing; Translating; Universities; Ventral Striatum; Work; Workplace; addiction; alcohol cue; alcohol exposure; alcohol research; alcohol response; alcohol use disorder; blood oxygen level dependent; dopamine system; expectation; frontal lobe; in vivo; multidisciplinary; neural circuit; neurochemistry; neuroimaging; neurotransmission; parent grant; problem drinker; public health relevance; response; success; transmission process

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.

描述（由申请人提供）：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重要因素。然而，大多数关于多巴胺能对酒精的反应及其条件暗示的研究都是在啮齿动物中进行的。这些啮齿动物模型转化为人类酒精使用障碍的程度尚不清楚。因此，我们提出的工作的长期目标是开发纹状体多巴胺能反应的体内人类生物标志物，其可应用于研究酒精中毒及其先前风险。我们将使用正电子发射断层扫描（PET）和多巴胺D2配体[11 C]雷氯必利以及功能磁共振成像来进行这项研究。将采用行为范式来研究酒精的暗示如何与酗酒受试者的多巴胺功能和皮质激活相关。 公共卫生关系：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脑中的神经化学物质多巴胺。它还将使用第二种神经成像技术，称为功能性磁共振成像，以检查大脑区域对某些刺激的反应。多巴胺系统和大脑额叶区域的改变被认为对酒精中毒以及其他成瘾非常重要。像这样的研究有可能显示多巴胺神经传递在酒精中毒中是如何改变的，以及这些改变如何与额叶皮层的大脑功能相关。更好地了解这些现象可能会导致更好的诊断和治疗。