DOPAMINE AND RISKS FOR DRUG ABUSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的 这项研究的目的是评估多巴胺(DA)神经传递的改变是否提前并可能影响人类滥用药物的风险。在最近的神经成像研究中，在几个吸毒者群体中观察到了多巴胺功能的紊乱。然而，目前尚不清楚这些变化是慢性药物使用的原因还是结果。与物质使用障碍的发展和病程密切相关的两个心理社会因素是冒险行为和环境压力。在这项研究中，我们将使用正电子发射断层扫描(PET)技术来检查健康年轻人对苯丙胺的多巴胺能反应是否与这些变量的个体差异有关。我们认为，DA对药物的敏感性减弱是药物滥用的一个危险因素，冒险和压力通过这种机制增加了药物滥用的风险。 设计 受试者将是年龄在18岁到29岁之间的健康年轻人，他们是从巴尔的摩大都市地区通过广告和张贴传单招募的。根据最初的电话筛选，似乎符合研究条件的受访者将被邀请到我们的办公室提供知情同意。研究将分两个阶段进行。第一阶段：面对面的筛查将包括精神科诊断面谈和填写几份自我报告表。还将获得一份简短的病史。符合条件的人将完成一次实验室表现会议，其中包括对五项基于计算机的特征冲动测量的管理。第二阶段：完成实验室操作课程的受试者将被要求提供正电子发射断层扫描(PET)研究的知情同意。评估受试者是否有资格参加正电子发射计算机断层扫描所需的额外筛查将包括病史和体格检查、标准实验室检查(即血液化学、CBC、PT、PTT、TSH和尿检)和心电图(EKG)。合格的参与者将参加两次[11C]拉氯必利PET扫描，测量苯丙胺诱导的DA释放。磁共振成像(MRI)扫描将在PET扫描之前进行，以实现发射图像的联合配准。 时间表： 电话屏幕 阶段1面对面筛选和评估 实验室绩效会议 第二阶段筛查 核磁共振扫描 [11C]拉氯必利正电子发射计算机断层扫描 招募、筛选、心理评估和行为表现会议将在马里兰大学护理学院首席调查员的研究办公室进行。病史和体检、EKG筛查和标准实验室测试将在马里兰大学医学院综合临床研究中心(UM-GCRC)进行。核磁共振成像和正电子发射计算机断层扫描将在约翰霍普金斯医院放射科进行。

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. PURPOSE The purpose of this study is to evaluate whether alterations in dopamine (DA) neurotransmission predate and may influence risks for drug abuse in humans. Derangements in dopamine function have been observed in several populations of drug abusers in recent neuroimaging research. However, it remains unclear whether these alterations are a cause or a consequence of chronic drug use. Two psychosocial factors that have been strongly associated with the development and course of substance use disorders are risk-taking behavior and environmental stress. In this study, we will use positron emission tomography (PET) technology to examine whether dopaminergic responses to amphetamine are associated with individual differences in either of these variables in healthy young adults. We suggest that dampened DA sensitivity to drugs is a risk factor for substance abuse and that risk taking and stress increase risks for drug abuse through this mechanism. DESIGN Subjects will be healthy young adults, ages 18 through 29, recruited by advertisements and posted flyers from the Baltimore metropolitan area. Respondents who appear to qualify for the study based on an initial telephone screen will be invited to our offices to provide informed consent. The research will be conducted in two phases. Phase 1: In-person screening will include a psychiatric diagnostic interview and completion of several self-report forms. A brief medical history will also be obtained. Individuals who qualify will complete a laboratory performance session that includes administration of five computer-based measures of trait impulsivity. Phase 2: Subjects who complete the laboratory performance session will be asked to provide informed consent for a positron emission tomography (PET) study. Additional screening needed to assess subjects' eligibility to participate in the PET scans will include a history and physical exam, standard laboratory tests (i.e., blood chemistry panel, CBC, PT, PTT, TSH and urinalysis) and electrocardiogram (EKG). Qualified participants will participate in two [11C]raclopride PET scans measuring amphetamine-induced DA release. A magnetic resonance imaging (MRI) scan will be conducted prior to the PET scans for coregistration of emission images. TIMELINE: Telephone screen Phase 1 in-person screening and assessment Laboratory performance session Phase 2 screening MRI scan [11C]raclopride PET scans Recruitment, screening, psychological assessments, and behavioral performance sessions will be conducted in the research offices of the Principal Investigator at the University of Maryland School of Nursing. History and physical exams, screening EKGs and standard laboratory tests will be done at the University of Maryland School of Medicine General Clinical Research Center (UM-GCRC). MRIs and PET scans will be conducted at the Johns Hopkins Hospital Department of Radiology.