Serotonin 1B Receptor Imaging in Pathological Gambling and Alcohol Dependence

描述（由申请人提供）：由于慢性药物暴露可以影响大脑结构和功能，其方式可能与成瘾过程有关，也可能与成瘾过程无关，因此同时比较和对比物质成瘾和行为成瘾的调查对识别成瘾的核心要素具有重要的希望，特别是那些与成瘾中心“奖励回路”的改变有关的要素。为了理清我们认为对更好地理解成瘾过程至关重要的过程，我们建议研究酒精依赖（AD）和病理性赌博（PG）患者，并比较5-羟色胺（5-HT）、1B型（5-HT1B）受体的表达（通过正电子发射断层扫描（PET）和行为，包括AD和PG患者的渴望或戒断症状的严重程度）与健康对照者。5-HT1B受体在调节5-羟色胺传递和调节中脑边缘多巴胺能活性方面起着至关重要的作用，是成瘾研究领域的兴趣所在。这表明5-HT1B受体可能在调节成瘾行为的易感性方面起着关键作用。因此，对成瘾人群中5-HT1B受体的密度和分布进行体内定量可能为了解这些疾病的机制提供重要的见解。利用选择性5-HT1B受体放射配体[11C]P943和高分辨率研究层析成像（HRRT）上的PET，我们拟首次应用该创新配体研究5-HT1B受体与AD和PG相关的调控，该研究首次研究了成瘾受试者的5-HT1B受体结合电位（BPND），并将进一步研究5-HT1B受体作为成瘾疾病生物标志物的作用及其与成瘾表型的关系。

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.