The Developmental Center for Neuroregulation in Alcohol Dependence (CeNiAD) grew from the clinical observation that the CNS active generic CM adrenoreceptor (AR) antagonist prazosin reduced or eliminated alcohol drinking in veterans with posttraumatic stress disorder (PTSD) and comorbid alcohol dependence. Recently we demonstrated in placebo-controlled studies that prazosin reduces alcohol consumption in two animal models of alcohol dependence and in a human study in persons with alcohol dependence but without PTSD. Our clinical observation, our compelling prazosin preclinical and clinical treatment data, emerging neuroscience data implicating the CM AR in mechanisms of addiction, and the presence at VA Puget Sound and the University of Washington of a critical mass of faculty investigating alcohol dependence have led to the proposed developmental center. The CeNiAD has the following goals: (1) To create an interdisciplinary translational research team investigating oil AR and other neuroregulatory mechanisms and interventions in alcohol use disorders (ADD);(2) To establish the collaborations, facilities, research capabilities, preliminary findings, career development opportunities, intellectual milieu and planning process to justify an application for a future new Specialized P50 Alcohol Research Center. An Administrative Core will support the scientific mission, develop and coordinate career development of basic and clinical AUD investigators, provide biostatistics and data management support, and provide the planning process for a future P50 Center. A distinguished External Advisory Board will help guide the CeNiAD in these activities. There will be two first wave exploratory projects and two first wave pilot projects. Exploratory Project 1 addresses effects of pharmacologic reduction of noradrenergic signaling in alcohol ingestion in alcohol preferring rats. Exploratory Project 2 is a placebo-controlled prazosin trial in persons with co-occurring alcohol dependence and PTSD. Pilot Project 1 addresses prazosin effects on cue-induced alcohol craving in humans. Pilot Project 2 addresses prazosin effects on alcohol craving and consumption in military returnees from Iraq and Afghanistan with PTSD. A process for solicitation and review of especially relevant additional exploratory and pilot projects has been established to support a second wave of such projects in the second 2.5 years of the CeNiAD.
