This component describes plans for the support and management of a series of pilot projects, including procedures for scientific and technical review. Pilot studies in the UConn ARC have served as the basis for the development of programs of research that are integral to the Center, but which also extend beyond it through a variety of other funding mechanisms. During the current grant cycle, pilot studies have resulted in a total of 14 peer-review publications and have contributed to five successful grant applications, which have been funded through R01, R03, or R21 mechanisms. In these ways, the pilot studies program has played a crucial role in the vitality and growth of the UConn ARC. Seven separate projects are described, of which three will be initiated during the first two years of the grant period (Phase I). The remaining four projects are scheduled for implementation during the final three years of the grant (Phase II). Based upon the success of the pilot studies program during the current and previous grant periods, a tripartite approach is employed that focuses on three main investigational areas: neuropharmacology/neurobiology, electrophysiology/brain imaging, and treatment trials. This approach addresses the major research foci of the UConn ARC: vulnerability to alcohol-related problems; basic mechanisms of problem drinking, dependence, and relapse; and the treatment of alcohol dependence. During Phase I of the new grant period, proposed studies include the generation and phenotyping of transgenic mouse lines with altered expression of the GABAA receptor a6 subunit gene, a study of the electrophysiologic effects of hazardous drinking and depression in women, and a treatment trial that examines the safety and feasibility of using the opioid antagonist naltrexone to reduce problem drinking in adolescents. Studies to be conducted during Phase II of the grant cycle include a study of alcohol and neurosteroid modulation of GABA function and a study of the impact of purified antibodies directed against dopamine receptor subtypes on voluntary ethanol intake. This phase will also include a study of the effects of alcohol, cocaine, and antisocial personality disorder on cerebral blood flow, measured using functional MRI. Finally, Phase II will include a trial evaluating the effects of a low-cost, contingent reinforcement approach on ambulatory treatment attendance and retention, and on alcohol and drug use in alcohol-dependent patients.
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