Assistant Professor
Department of Internal Medicine
Charles R. Drew University of Medicine and Science

Project: Effects of varenicline on alcohol and nicotine consumption and changes in dopamine d2-like receptor availability in high-alcohol-preferring mice

Theodore Friedman, MD, PhD - Charles R. Drew University of Medicine and Science
Mark Mandelkern, MD, PhD - VA Greater Los Angeles Health System

Multidisciplinary Expertise:
Endocrinology, Medical Physics, Pharmacology, Psychology

Project Description:
Dopamine is a chemical in the brain with many important functions. This project aims to understand the role of the dopamine receptor system in concomitant alcohol and nicotine abuse and treatment.The project specifically focuses on the d2 dopamine receptor, which is involved in reward-seeking behavior. Lower d2 dopamine receptors have been shown in animal models of addiction and substance abusers. Positron emission tomography (PET) will be used to characterize the dopamine d2 receptor profile in the brains of high-alcohol-preferring (HAP) and low-alcohol-preferring (LAP) mice. We expect that HAP mice will have significantly lower dopamine d2 receptor availability in an area of the brain called the striatum when compared to LAP or normal, wild-type mice. This study also will examine the effects of varenicline, a smoking-cessation drug, on dopamine d2 receptor availability, nicotine and alcohol consumption in HAP and LAP mice. HAP mice will increase their voluntary alcohol consumption following chronic nicotine exposure; that increase will be related to decreases in striatal d2 receptor availability. However, following varenilcine treatment, HAP mice exposed to chronic nicotine are expected to decrease their voluntary intake of alcohol; that decrease in alcohol intake will be related to increases in dopamine d2 receptor availability. Results from this study will provide important scientific and clinical information regarding the role of the dopamine receptor system in the underlying mechanisms of comorbid alcohol and nicotine preference. Moreover, finding an effective pharmacotherapy for this addiction is crucial; as such, the project will determine whether changes in dopamine receptors are involved in the efficacy of varenicline treatment success.