Serotonin 1B Receptor Imaging in Pathological Gambling and Alcohol Dependence

病理性赌博和酒精依赖中的血清素 1B 受体成像

• 批准号: 7894869
• 负责人: ALEXANDER NEUMEISTER
• 金额: $ 18.42万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7894869
• 关键词: Addictive Behavior; Affinity; Alcohol dependence; Amygdaloid structure; Animals; Anterior; Autoreceptors; Behavior; Behavioral; Biological; Biological Markers; Brain; Chronic; Clinical; Corpus striatum structure; Data; Decision Making; Development; Disease; Drug Exposure; Elements; Future; Gambling; Human; ICD-9; Image; Individual; Investigation; Ligands; Light; Measures; Methods; Modeling; Nature; Pathological Gambling; Pathway interactions; Patients; Phenotype; Play; Population; Positron-Emission Tomography; Predisposition; Process; Regulation; Relapse; Research; Resolution; Role; Serotonin; Serotonin Receptor 5-HT1B; Severities; Societies; Stress; Structure; Substance Use Disorder; Testing; Time; Ventral Striatum; Withdrawal Symptom; addiction; cingulate cortex; cost; craving; density; drug development; in vivo; innovation; insight; interest; public health relevance; radioligand; radiotracer; receptor binding; receptor expression; reward circuitry; transmission process

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.

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和行为成瘾的研究对于识别成瘾的核心要素具有重要意义，特别是那些与成瘾中心的“奖励回路”改变有关的要素。解开的过程，我们认为是中央更好地理解成瘾过程，我们建议研究患者酒精依赖（AD）和病理性赌博（PG）和比较血清素（5-HT），1B型（5-HT 1B）受体表达确定与正电子发射断层扫描（PET）和行为，包括渴望或严重程度的戒断症状在AD和PG患者和健康对照组。5-HT 1B受体在调节5-HT传递和调节中脑边缘多巴胺能活性中起着重要作用，因此在成瘾研究领域引起了人们的兴趣。这表明5-HT 1B受体可能在调节成瘾行为的易感性方面发挥关键作用。因此，在体内定量的密度和分布的5-HT 1B受体在成瘾人群中可能提供重要的见解，有助于这些疾病的机制。使用选择性5-HT 1B受体放射性配体[11 C]P943和PET在高分辨率研究断层扫描仪（HRRT）上，我们建议首次应用这种创新的配体来研究5-HT 1B受体与AD和PG相关的调节。这项拟议的研究是首次研究5-HT 1B受体结合潜力（BPND）在成瘾受试者中，将刺激进一步研究5-HT 1B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。 成瘾与重大的个人和家庭痛苦有关，每年花费美国社会超过5000亿美元。通过使用正电子发射断层扫描（PET）和放射性示踪剂，我们能够测量大脑中5-羟色胺1b受体的数量。这种方法可以确定酒精成瘾和赌博成瘾的人与没有这些疾病的健康人相比，大脑中的5-羟色胺1b受体数量是否不同。