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 I V, 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.
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