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Chunk #41 — Discussion

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A multi-omic analysis of the dorsal striatum in an animal model of divergent genetic risk for alcohol use disorder.
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Here we present a complementary and integrated analysis of differential gene expression, protein regulation, and peptide phosphorylation in the DS of alcohol-naive mice genetically selected for high or low alcohol preference. Although prior genome wide analyses and microarrays have been performed in replicates of HAP and LAP mice (Bice et al. 2006; Bice et al. 2009; Bice et al. 2011; Mulligan et al. 2006), this study represents the first investigation of combined differential gene, protein, and phosphorylated protein expression and functional analyses of these differentially expressed networks in this mouse model of AUD. While considerable work has focused on the nucleus accumbens (a part of the ventral striatum) in alcohol research, the DS represents an additional region of interest where aberrant function is associated with pathological alcohol seeking and consumption. The DS receives dense glutamatergic inputs from the cortex, thalamus, and limbic regions, and these circuits play a critical role in alcohol drinking and alcohol-related neuroadaptations (Wang et al. 2010; DePoy et al. 2013; Fanelli et al. 2013; Corbit et al. 2012). Therefore, understanding differences in basal functioning between the