This is a competing renewal application for a Consortium for the Integrative Neuroscience Initiative on Alcoholism (INIA)-West (Notice# RFA-AA-11-006) to identify the molecular, cellular, and behavioral neuroadaptations that occur in specific brain neurocircuitries that result in excessive alcohol consumption. This multidisciplinary initiative focuses on the molecular and cellular neuroadaptations in brain addiction circuits associated with the basal forebrain, including reward circuitry in the ventral striatum and dependence circuitry in the extended amygdala. The overall hypothesis for INIA-West is that genetic differences and neuroadaptations in reward circuitry are responsible for individual differences in the vulnerability to the excessive alcohol consumption. Sixteen research components and six scientific cores will use excessive drinking models in animals to mimic the binge- and dependence-induced excessive drinking of alcohol abuse disorders. The overall goals of INIA-West are (1) to confirm gene targets nominated by expression assays or other methods by use of transgenic, knockout, inducible knockout, site-specific knockout, RNAi, in situ hybridization, in vivo electrophysiology, in vivo imaging, and next-generation sequencing, (2) to identify druggable targets that are most promising for medication development for the treatment of alcoholism by use of novel molecules in concert with molecules with existing FDA approval in animal models with the most predictive ability, and (3) to attract new and innovative investigators to the field of alcohol research by recruiting individuals for U01 grants and Pilot projects and by making the informatics integrated datasets accessible, searchable, and interactive with other databases for all scientists interested in alcoholism research. Core facilities are proposed that provide molecular genetic support and target assessment translation for medications target development. A Pilot Project program is proposed to identify exciting new areas of research and the continual recruitment of new investigators to the alcohol field. The INIA program will be directed by the Administrative Core in close cooperation with the Executive Committee and Steering Committee and with the continual advice of a distinguished Scientific Advisory Board.
These studies will identify genes that cause vulnerability for developing alcoholism using well established animal models of excessive drinking and state of the art molecular genetics approaches. The data to be gained will provide not only key information about the etiology of alcoholism but also provide new insights into prevention and treatment of alcoholism.
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