PROJECT SUMMARY The Charleston Alcohol Research Center (ARC) continues to focus on treatment and treatment implications as an overarching theme. The ARC maintains its long-standing tradition of embracing multidisciplinary and translational research approaches, integrating both basic research and clinical investigations all centered on this common theme. The ARC also continues its tradition of teaming junior faculty with more experienced investigators, capitalizing on new talent and bringing sophisticated cutting-edge technologies and research approaches that enhance research efforts in addressing the Center’s overall scientific goals. The ARC is comprised of five research projects and three cores. The Administrative Core provides the leadership and infrastructure to facilitate the overall scientific and educational mission of the Center as a whole. The Shared Resource Core provides vital scientific services needed by Center researchers to facilitate integration, maximize resources, and increase productivity. The Pilot Core attracts new investigators and new ideas to the Center, thereby broadening and augmenting its research and training activities. In this renewal application, proposed preclinical and clinical research projects all center on a common research focus – neuroadaptations in cortical processes that underlie transition to excessive drinking. Three basic research projects will use sophisticated circuitry mapping, cellular/molecular biology techniques, and behavioral procedures to examine how chronic alcohol exposure alters functional activity of cortical sub-regions and their projections, and how such adaptations in cortical-subcortical neurocircuitry mediate excessive drinking, which may be characterized as inflexible, compulsive/habit-like drinking. Two clinical research projects will employ sophisticated neuroimaging techniques to focus on similar cortical areas and projections in evaluating the ability of different treatment modalities (pharmacological and non-pharmacological) to alter the circuitry and reduce alcohol cue-induced brain activation, craving, and drinking. The Charleston ARC is poised to continue its national leadership role and demonstrated success in: (a) fostering multidisciplinary and translational state-of-the-art research efforts that are thematically-focused on the topic of treatment and treatment implications; (b) attracting new (especially early-stage) investigators into the Center, thereby invigorating its research efforts; and (c) providing a stimulating environment that enriches training opportunities and professional development for the next generation of researchers in the alcohol field.