The Portland Alcohol Research Center (PARC) focuses on the etiology and prediction of risk of alcohol abuse, alcoholism, and specific alcohol-related health problems (e.g., withdrawal seizures, excessive drinking). The genetic risk and protective markers and gene networks that we are studying will help us to develop strategies for the prevention of alcoholism. The first overarching theme of the PARC is to use behavioral genomics strategies, through studies of gene mapping and expression, and development of new genetic animal models, to identify genes underlying ethanol neuroadaptation. The other main PARC theme is exploring mechanisms underlying and traits related to ethanol neuroadaptation. Two specific hypotheses have emerged from the synthesis of PARC and related projects'findings. The first hypothesis is the intriguing idea that withdrawal and drinking are influenced by some of the same genes and gene networks. Many different studies and genotypes have found that high-withdrawal genotypes are genetically predisposed to drink less than low-withdrawal genotypes. We now also consider the effect of chronic ethanol exposure on alcohol consumption. The second hypothesis is that high trait impulsivity is a significant genetic risk factor for high alcohol drinking. Genetic dissociation of different aspects of impulsivity is supported by PARC findings, with high impulsivity on "delay discounting" tasks predicting greater and high impulsivity on "go/no-go" tasks predicting less non-dependent drinking. The latter also predicts greaten withdrawal severity following dependence. Five research components, three core components, and a pilot project component address these themes and hypotheses using mouse models and non-human primates. To the extent possible across species, we are making a concerted effort to integrate the components with a "core circuit" of brain structures that relate to drinking, withdrawal, and impulsivity. Our expanded bioinformatics effort has enabled expansion of a key strength of our group from the analysis of the contributions of individual genes on behavioral functions of the whole organism to include gene network identification. The PARC Is recognized as a leader in quantitative trait gene (QTG) Identification, successfully pursuing a genetic locus Influencing withdrawal to discover the first alcohol-related behavioral response QTG, Mpdz, and recent studies identifying high-quality QTG candidates including Kcnj9. An Education and Outreach component trains pre- and post-doctoral students in alcohol research, disseminates research findings to the public, and engages in a range of activities with elementary-to-high school students.
Overall Center Project Narrative. The Portland Alcohol Research Center seeks to identify specific genes that place Individuals at risk of, or protect them from, alcoholism. Knowledge of such genes will facilitate the discovery of new drugs to treat alcohol dependence disorders.
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