Serotonin 1B Receptor Imaging in Pathological Gambling and Alcohol Dependence

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DESCRIPTION (provided by applicant): As chronic drug exposure can influence brain structure and function in manners that may or may not be related to the addictive process, investigations simultaneously comparing and contrasting substance and behavioral addictions hold significant promise for identifying core elements of addiction, particularly those related to alterations in the "reward circuitry" central to addictions. To untangle processes which we believe are central to better understand the addiction process, we propose to study patients with alcohol dependence (AD) and pathological gambling (PG) and compare serotonin (5-HT), type 1B (5-HT1B) receptor expression as determined with positron emission tomography (PET) and behavior, including craving or severity of withdrawal symptoms in AD and PG patients and healthy control subjects. 5-HT1B receptors are of interest to the field of addiction research in light of the crucial role that they play in regulating 5-HT transmission and modulating mesolimbic dopaminergic activity. This suggests that 5-HT1B receptors might play a critical role in moderating susceptibility for addictive behavior. Thus, in vivo quantitation of the density and distribution of 5-HT1B receptors in addicted populations might provide important insights into mechanisms contributing to these disorders. Using the selective 5-HT1B receptor radioligand, [11C]P943, and PET on a High Resolution Research Tomograph (HRRT), we propose to apply this innovative ligand to study for the first time the regulation of 5-HT1B receptors in association with AD and PG. The proposed study is the first to study 5-HT1B receptor binding potential (BPND) in addicted subjects and will stimulate further research about the role of the 5-HT1B receptor as a disease biomarker for addictions and its relation to the phenotype of addiction. PUBLIC HEALTH RELEVANCE: Addictions are associated with significant individual and familial suffering and cost US society over $500 billion annually. With the use of positron emission tomography (PET) and administration of a radiotracer, we are able to measure the number of serotonin 1b receptors in the brain. This method allows to determining whether people with alcohol addiction and people with gambling addiction show a different number of serotonin 1b receptors in the brain as compared to healthy people without these illnesses.