PRINCIPAL INVESTIGATOR: BECKER, HOWARD C.
GRANT NUMBER: P50 AA010761-19S1
ABSTRACT: This proposal is submitted in response to the NIH announcement (NOFO PA-13-275) for Administrative Supplements to Promote Collaborative Research on Addiction at NIH (CRAN): Comorbidity-Related Research. The purpose of this Administrative Supplement application is to expand and enhance on-going research efforts in the Charleston Alcohol Research Center (ARC) to study the clinically important problem of polydrug use/abuse and comorbidity. The Charleston ARC (P50 AA010761), which serves as the parent award for this supplement, engages in integrative and multipdisciplinary research approaches in studying alcohol/drug addiction, with an emphasis on treatment and treatment implications for alcohol use disorders. The Charleston ARC provides an excellent platform for facilitating research aimed at elucidating genetic, neurobiological, and environmental mechanisms that bear on risky drinking behavior and relapse vulnerability, identification of novel targets with treatment implications, and comprehensive evaluation of potential therapeutics for alcohol-related problems in animal models, clinical laboratory studies, and clinical trials. Thus, the Charleston ARC is ideally suited for expansion of studies that focus on polydrug use/abuse and, in particular, treatment for nicotine and alcohol comorbidity. Epidemiological evidence indicates that comorbid alcohol and nicotine use disorders are highly prevalent. Given the large scope of the problem, there is a need for both preclinical and clinical studies to focus on investigations on mechanisms underlying the interaction of these substances, as well as efficacy and mechanisms of treatments for comorbid nicotine and alcohol addiction. This proposal includes both basic science and clinical studies focused on nicotine and alcohol use comorbidity as well as the capacity of varenicline treatment to reduce alcohol consumption. Specifically, studies will extend the use of a mouse model of alcohol dependence to examine nicotine-alcohol reactions and the ability of varenicline to reduce drinking in dependent compared to nondependent animals (Aims 1 and 2). Additionally, the effects of varenicline treatment will be evaluated on drinking, smoking, alcohol cue-elicited brain activation, and brain activation related to enhanced cognitive control among heavy-drinking smokers (Aim 3). As such, this translational research approach extends work in the Charleston ARC to provide new and valuable information relevant to the development of more effective treatment for a major public health concern, namely alcohol and nicotine comorbidity.