PET STUDIES IN ALCOHOLISM: MEASUREMENT OF BRAIN METABOLISM BRAIN DOPAMINE

酗酒的宠物研究：大脑代谢的测量 大脑多巴胺

• 批准号: 7375326
• 负责人: MARK J SEDLER
• 金额: $ 1.04万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375326
• 关键词: PET; STUDIES; ALCOHOLISM; MEASUREMENT; BRAIN

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 Neuro-chemical mechanisms by which ethanol induces self-administration and dependence are poorly understood. Using PET we have documented decreased brain GABA activity in alcoholics. While decreased GABA function could explain the use of alcohol as a way of increasing inhibitory neurotransmission it does not explain the addictive behavior per se. We hypothesize that the loss of control and the compulsive administration of alcohol in the alcoholic is secondary to decreased GABA modulation of the dopamine system, which results in abnormal function of brain regions modulated by DA and in accentuated responses to stimuli that increase DA. This makes alcohol more reinforcing but it also enhances the aversive quality of stressful stimuli. We also hypothesize that abnormal DA activity leads to dysfunction of orbit frontal regions, which we postulate is one of the mechanisms leading to the loss of control and the drive to compulsively administer alcohol. In alcoholic subjects we have documented reductions in DA D2 receptors, which are mostly located in the GABA cells, however no studies have been done to measure the function of the DA cells in alcoholics. DA release in brain, which we measure with PET and [11C] raclopride, provides an indirect measure of the function of the DA cells.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。乙醇诱导自我给药和依赖性的神经化学机制知之甚少。使用PET，我们记录了酗酒者大脑GABA活性的降低。虽然GABA功能下降可以解释酒精作为增加抑制性神经传递的一种方式，但它不能解释成瘾行为本身。我们假设，酒精的控制和强制性管理的酒精是次要的减少GABA调制的多巴胺系统，这导致异常的功能，大脑区域调制的DA和加重反应的刺激，增加DA。这使得酒精更加强，但它也提高了令人厌恶的质量的压力刺激。我们还假设异常的DA活性导致眶额区功能障碍，我们假设这是导致失控和强迫性饮酒的机制之一。在酗酒者中，我们已经记录了DA D2受体的减少，其主要位于GABA细胞中，但是还没有研究来测量酗酒者中DA细胞的功能。我们用PET和[11 C]雷氯必利测量大脑中的DA释放，提供了DA细胞功能的间接测量。