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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012837-04
Application #
6881284
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Witt, Ellen
Project Start
2002-07-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
4
Fiscal Year
2005
Total Cost
$459,408
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Alvanzo, Anika A H; Wand, Gary S; Kuwabara, Hiroto et al. (2017) Family history of alcoholism is related to increased D2/D3receptor binding potential: a marker of resilience or risk? Addict Biol 22:218-228
Weerts, Elise M; Wand, Gary S; Maher, Brion et al. (2017) Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers. Alcohol Clin Exp Res 41:1093-1104
Kuwabara, Hiroto; McCaul, Mary E; Wand, Gary S et al. (2012) Dissociative changes in the Bmax and KD of dopamine D2/D3 receptors with aging observed in functional subdivisions of the striatum: a revisit with an improved data analysis method. J Nucl Med 53:805-12
Zhou, Yun; Ye, Weiguo; Brasi?, James R et al. (2010) Multi-graphical analysis of dynamic PET. Neuroimage 49:2947-57
Uhart, Magdalena; Wand, Gary S (2009) Stress, alcohol and drug interaction: an update of human research. Addict Biol 14:43-64
Zhou, Yun; Ye, Weiguo; Brasi?, James R et al. (2009) A consistent and efficient graphical analysis method to improve the quantification of reversible tracer binding in radioligand receptor dynamic PET studies. Neuroimage 44:661-70
Wand, Gary S; Oswald, Lynn M; McCaul, Mary E et al. (2007) Association of amphetamine-induced striatal dopamine release and cortisol responses to psychological stress. Neuropsychopharmacology 32:2310-20
Oswald, Lynn M; Wong, Dean F; Zhou, Yun et al. (2007) Impulsivity and chronic stress are associated with amphetamine-induced striatal dopamine release. Neuroimage 36:153-66
Munro, Cynthia A; McCaul, Mary E; Oswald, Lynn M et al. (2006) Striatal dopamine release and family history of alcoholism. Alcohol Clin Exp Res 30:1143-51
Munro, Cynthia A; McCaul, Mary E; Wong, Dean F et al. (2006) Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry 59:966-74

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