Chronic Alcohol Induced Dysregulation of Central Anti-Stress Systems

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): Alcoholism and alcohol abuse are major health problems and represent a tremendous financial burden on our society. A growing literature indicates that chronic alcohol exposure leads to an imbalance between central stress and anti-stress systems in key brain circuits that regulate emotional behavior. These imbalances can lead to pathological behavior, including increased anxiety, stress-responsivity and enhanced risk of relapse. Despite these advances identifying the role these systems play in alcohol related behaviors, there remains a gap in our knowledge of the fundamental biological, cellular and circuit mechanisms that contribute to this dysregulated behavior. In order to more effectively treat alcohol abuse, it is necessary to define the impact of chronic alcohol exposure on the in the circuitry that is critical for regulation of this behavior. Here, we propose to characterize the impact of chronic alcohol exposure on anti-stress systems, specifically neuropeptide Y (NPY) and GABAergic neuroactive steroids, in the amygdala and extended amygdala, brain regions critical for regulation of stress and anxiety-like behavior. Additionally, we will utilize inducible channel rhodopsin viruses in combination with neurochemically specific Cre-recombinase driver lines to determine the impact of chronic alcohol exposure on GABAergic circuits in these brain regions. In total, the proposed work will begin to define specific alcohol-induced cellular and circuit adaptations that are likely to play key roles in pathological behaviors associated with alcoholism.