DOPAMINE SYSTEM IN ALCOHOL DEPENDENCE

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。这项拟议的研究将检查PET测量多巴胺系统与HPA轴动力学的关系。 越来越多的证据表明，滥用药物是通过涉及大脑神经递质多巴胺（DA）的机制起作用的。虽然药物滥用的影响几个不同的神经递质系统在大脑中，许多这些“初级”的反应导致涉及DA的二次效应。许多研究强调了遗传和环境的决定因素在建立这个脆弱的基板的相互作用。啮齿动物的研究表明，压力和mesolimbic mesoDA的产生之间的联系。在应激过程中释放的糖皮质激素增加中脑边缘mesoDA的产生。在应激过程中释放的糖皮质激素增加中脑边缘mesoDA的产生。已经表明，压力增加mesoDA的能力导致滥用药物的奖励改变。在本申请中，我们提出了mesoDA以使酒精依赖受试者在JHU GCRC上从酒精中戒断。在监督下戒断后，酗酒者和对照组将接受通过正电子发射断层扫描（PET）测量的大脑多巴胺释放评估以及HPA轴评估。我们假设，与对照组相比，酗酒者会减弱多巴胺的释放。我们预测正常人的压力诱导的皮质醇产生和大脑多巴胺释放之间存在正相关关系，但这种关系会被酒精中毒改变。除了与3个R 01提案相互作用外，IRPG 3中的实验“独立”。在目标I中，我们假设与对照组相比，酗酒者的DA释放（DArel）会变钝。在目标II中，我们假设家族史阳性（FHP）酗酒者的DArel比家族史阴性（FHN）酗酒者的DArel更钝。在目的III中，我们建议比较HPA轴动力学响应酒精依赖个体和对照组的心理压力。在目的四，我们假设，压力诱导的激活HPA轴皮质醇释放和DArel观察控制将改变酒精依赖的主题。我们假设酗酒者DArel改变的程度将预测GCRC出院后复发的时间。

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. This proposed research would examine PET measures of the dopamine system in relationship to HPA axis dynamics. Converging evidence suggests that drugs of abuse act through mechanisms involving the brain neurotransmitter, dopamine (DA). Although drugs of abuse influence several different neurotransmitter systems in the brain, many of these 'primary' responses lead to secondary effects involving DA. Numerous studies have emphasized the interplay of genetic and environmental determinants in establishing this vulnerable substrate. Rodent studies have suggested a link between stress and mesolimbic mesoDA generation. Glucocorticoids released during stress increase mesolimbic mesoDA generation. Glucocorticoids released during stress increase mesolimbic mesoDA generation. It has been suggested that the ability of stress to increase mesoDA results in altered reward from drugs of abuse. In this application we propose mesoDA to withdraw alcohol dependent subjects from alcohol on the JHU GCRC. Following supervised withdrawal, alcoholics and controls will undergo assessment of brain dopamine release measured by Positron Emission Tomography (PET) as well as assessment of their HPA axis. We hypothesize that alcoholics will have blunted dopamine release compared to controls. We predict a positive correlation between stress-induced cortisol production and brain dopamine release in normals but that this relationship will be altered by alcoholism. As well as interacting with 3 R01 proposals, the experiments in IRPG3 "stands alone". In Aim I, we hypothesized that alcoholics will have blunted DA release (DArel) compared to controls. In Aim II, we hypothesized that DArel in family history positive (FHP) alcoholics will have a more blunted DArel compared to family history negative (FHN) alcoholics. In Aim III, we propose to compare HPA axis dynamics in response to psychological stress in alcohol dependent individuals and controls. In Aim IV, we hypothesize that stress-induced activation of the HPA axis cortisol release and DArel observed in controls will be altered in alcohol dependent subjects. We hypothesize that the magnitude to altered DArel in alcoholics will predict time to relapse following discharge from the GCRC.