Chronic exposure to alcohol results in neuroadaptive phenomena, including tolerance, sensitization, dependence, withdrawal, loss of control of drinking, and relapse that contribute to the development of excessive alcohol consumption. This application for a Consortium for the """"""""Integrative Neuroscience Initiative on Alcoholism"""""""" (MA) (RFA: AA-01-002) 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. Our goals are: 1). To establish animal models to study specific neurobiological targets for vulnerability that lead to excessive consumption of alcohol at the molecular, cellular and neural circuit levels of analysis. 2). To identify specific clusters of genes whose expression is regulated by alcohol and which are responsible for any given model of excessive alcohol consumption using gene expression arrays, differential display, mutagenesis directed at specific brain areas, and the development of new informatics tools to analyze and interpret gene expression, cellular circuitry and brain circuitry data and with the use of transgenic and knockout approaches. 3). To attract new and innovative investigators to the field of alcohol research by recruiting individuals for developmental UOI grants and pilot projects and by developing online interactive capacity among INIA scientists and others, and by making the neuroinformatics integrated data sets accessible, searchable and interactive with other databases for all scientists interested in alcoholism research. The structure of EIUA is envisioned as three subgroups that integrate across three domains: Animal Models of Dependence and Neuroadaptation Subgroup, Neurocircuitry Subgroup, and Molecular Basis of Excessive Drinking Subgroup. Core facilities are established in each domain and include the Genetic Animal Models Core, the Gene Expression Core and the Imaging Core, respectively. Each Subgroup is comprised of 4-5 UOI proposals and 1-3 Developmental UOI research proposals. A Pilot Project program is proposed to identify exciting new areas for research and the continual recruitment of new investigators to the alcohol field. The INIA program will be directed by an Administrative Core in close cooperation with the Integrated Neuroinforinatics Core via a Steering Committee and with the continual advice of the Scientific Advisory Committee.
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