Proteomic Dissection of Withdrawal-Induced Excessive Drinking

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DESCRIPTION (provided by applicant): The overarching goal of the Integrative Neuroscience Initiative on Alcoholism (INIA)-West Consortium is to identify the molecular, cellular, and behavioral neuroadaptations that occur in the brain reward circuits associated with the extended amygdala and its connections. It is hypothesized that genetic differences and/or neuroadaptations in this circuitry are responsible for the individual differences in vulnerability to the excessive consumption of alcohol. Therefore, one of our main focuses is the identification of genes whose expression is regulated by alcohol and which are responsible for any given model of excessive alcohol consumption. The Wu UOl is one 18 U01s of the INIA-West Consortium and is focused on the differential proteomic analysis of brain fractions enriched from well-characterized animal models of drinking for the purpose of identifying gene targets associated with the behavioral phenotype. Recently, the collective efforts of the Consortium have converged on 51 gene targets. We propose to expand the scope of the Wu U01 parent grant to include a proteomic service component (to be referred to as the INIA-West Quantitative Proteomics Core) to meet the analytical proteomic needs of INIA-West. Specifically, targeted proteomic assays ("mass spectrometry Westerns") will be developed for each of the recently selected 51 INIA-West gene targets and will be used to quantify these targets in brain samples generated from the INIA-West investigators. Currently, INIA-West has no designated Proteomics Core Resource and no mechanism for the proteomic analyses of INIA-West samples. This request for supplementary funds through the Wu UOl parent grant will provide a centralized service component to INIA-West to focus analytical efforts on the quantification of INIA-West gene target proteins and facilitate comparative analyses across the multiple animal models and paradigms of excessive drinking. PUBLIC HEALTH RELEVANCE: High-throughput multiplexed measurements of selected gene target proteins will expedite the understanding of molecular differences underlying the vulnerability to excessive alcohol consumption.