Multiple neurotransmitter systems are involved in alcohol reinforcement. These systems are altered by environmental and genetic determinants of risk for alcohol use disorders. Recently, there has been considerable attention to the role of mesolimbic dopamine in alcohol and drug reward. For example, it has been demonstrated that D2 dopamine receptor density is negatively related to stimulant liking, such that individuals with low D2R density report more pleasant effects following stimulant administration than individuals with high D2R density. The proposed research will examine relationships between two key PET-derived measures of the dopamine system (D2 receptor density and dopamine transporter density) and alcohol sensitivity and liking. Additionally, the research will characterize the impact of several well-established predictors of alcoholism risk on these associations. Specific alcoholism risk factors will include family history of alcoholism, high trait anxiety and high excitement seeking. Subjects (N=100) will be social drinkers who do not meet diagnostic criteria for alcohol abuse or dependence but who differ on risk factors known to influence alcoholism development. All subjects will undergo a 13-day inpatient protocol that includes PET imaging of D2R and DAT density, and laboratory measurements of alcohol sensitivity and liking. Alcohol-related measures will include subjective, physiological and psychomotor responses to alcohol ingestion. This project represents an important extension of our earlier and current research on alcoholism. Knowledge gained from both this independent R01 proposal and through interaction with the other IRPG proposals will provide critical new scientific and clinical knowledge on involvement of the dopamine neurotransmitter system in alcohol reward, particularly in persons at differential risk for alcoholism.
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