IMAGING THE SEROTONIN TRANSPORTER IN ALCOHOLISM WITH PET

用宠物对酗酒时的血清素转运蛋白进行成像

• 批准号: 7378776
• 负责人: ZSOLT SZABO
• 金额: $ 0.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378776
• 关键词: IMAGING; SEROTONIN; TRANSPORTER; ALCOHOLISM; PET

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Impaired serotonin (5-HT) function has been implicated as a possible factor in the biological vulnerability for alcoholism, but most studies of the 5-HT system have been performed in animals or, if performed in humans, they involved only indirect measurements to assess the 5-HT system in the brain. The status of the 5-HT neurons in the brain of living alcohol dependent individuals remains unknown. To investigate the 5-HT system of the brain, quantitative PET studies of the brain 5-HT transporter (5-HTT; an established marker of serotonin neuron integrity) are proposed using [11C]McN5652 as radioligand for four groups of human subjects: family negative (FHN) controls, family history positive (FHP) controls, FHN recovering alcoholics, and FHP recovering alcoholics. The hypothesis to be tested is that radioligand binding to the 5-HT transporter is significantly reduced as a function of both alcoholism and family history of alcoholism. Serotonin function will also be measured by quantification of plasma prolactin and cortisol increase in response to fluoxetine. The genetic aspect of 5-HT impairment will be investigated by measuring the frequency of specific polymorphisms of the 5-HTT gene. The hypothesis is that FHP alcoholics and FHP controls will have a higher frequency of the s-variant allele, the allele, which has been associated with reduced 5-HTT expression/function in in vitro studies. The frequency of the s-variant allele is predicted to be higher in subjects with reduced 5-HTT densities (as determined by PET) and with reduced hormonal responses to fluoxetine. The results of this project will lead to better understanding of the role of serotonin in the biological vulnerability for alcoholism and may lead to improved approaches to prevent and treat alcoho

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。5-羟色胺（5-HT）功能受损被认为是酒精中毒生物学易感性的一个可能因素，但大多数5-羟色胺系统的研究都是在动物身上进行的，如果在人类身上进行，他们只涉及间接测量来评估大脑中的5-羟色胺系统。活体酒精依赖个体大脑中5-HT神经元的状态尚不清楚。为了研究大脑的5-羟色胺系统，采用[11C]McN5652作为放射配体，对四组人类受试者进行了脑5-羟色胺转运体（5-羟色胺；一种已建立的血清素神经元完整性标记物）的定量PET研究：家族阴性（FHN）对照，家族史阳性（FHP）对照，FHN戒酒者康复，FHP戒酒者康复。需要验证的假设是，与5-HT转运体结合的放射性配体作为酒精中毒和酗酒家族史的功能显着减少。血清素功能也将通过定量血浆催乳素和皮质醇在氟西汀作用下的增加来测量。5-羟色胺损伤的遗传方面将通过测量5-羟色胺基因特定多态性的频率来研究。假设是FHP酗酒者和FHP对照者将具有更高频率的s变异等位基因，该等位基因在体外研究中与5-HTT表达/功能降低有关。在5-HTT密度降低（由PET测定）和对氟西汀激素反应降低的受试者中，s变异等位基因的频率预计会更高。该项目的结果将使我们更好地了解血清素在酒精中毒的生物学脆弱性中的作用，并可能导致改进预防和治疗酒精的方法