Naltrexone and alprazolam-induced fMRI changes

纳曲酮和阿普唑仑引起的功能磁共振成像变化

• 批准号: 6621891
• 负责人: Chris Conway Streeter
• 金额: $ 18.27万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621891
• 关键词: alcoholism /alcohol abuse; alcoholism /alcohol abuse chemotherapy; behavioral /social science research tag; bioimaging /biomedical imaging; brain circulation; brain imaging /visualization /scanning; cognition; drug interactions; emotions; functional magnetic resonance imaging; human middle age (35-64); human subject; longitudinal human study; naltrexone; narcotic antagonists; neuropharmacology; patient oriented research; postdoctoral investigator; psychological tests; sedative /hypnotic; young adult human (21-34)

DESCRIPTION (provided by applicant): The long-term career goal of the applicant is to become an independent, interdisciplinary researcher applying functional magnetic resonance imaging (FMRI) to the study of alcohol related disorders. This application proposal includes two components: formal training in MR technology, statistical analysis and medical ethics and a specific research project defined below. Background: Alcoholism is a multifactorial disorder associated with tremendous individual disability and enormous cost to society. Naltrexone is an opioid blocker recently approved for the treatment of alcoholism. Increased understanding of the neurobiologic effects of naltrexone is needed to maximize the effectiveness of this drug and to plan for new pharmacologic treatments. The mood enhancing effects of a benzodiazepine challenge can serve as a probe to study the effects of naltrexone on alcohol-induced mood enhancement and cerebral function. This protocol will use Dynamic Susceptibility Contrast Magnetic Resonance Imaging (DSC MRI) to address these issues. Method: This project will study 20 abstinent individuals with a personal history of alcohol dependence and 20 comparison subjects over a five-year period. Each group will participate in a double blind, placebo-controlled, counterbalanced, crossover design protocol. Subjects will be pre-treated with naltrexone or placebo before receiving a challenge of alprazolam or placebo. This will result in 4 treatment conditions: placebo-placebo, placebo-alprazolam, naltrexone- placebo, and naltrexone-alprazolam. Each subject will participate in four scanning sessions, one for each treatment condition. Each scanning session will include a series of three scans. The following hypotheses will be tested: Hypothesis 1: There will be an interaction between the pretreatment conditions and the challenge conditions such that 1 a) When an alprazolam challenge is given to alcoholics unopposed, the rate of RCBV decrease will be greatest and l b) pretreatment with naltrexone will significantly slow the rate of rCBV decrease; Hypothesis 2: Alprazolam will produce greater mood-enhancement in alcoholics compared to normal controls, as measured by established mood scales; Hypothesis 3: Naltrexone will attenuate alprazolam's mood enhancing properties; Hypothesis 4: A rapid decrease in rCBV will correlate with reports of mood-enhancement. Pretreatment with naltrexone will correlate with a slower decrease in rCBV and less mood-enhancement than when alprazolam is given unopposed.

描述（由申请人提供）：长期职业 申请人的目标是成为独立的，跨学科的 研究人员将功能性磁共振成像（FMRI）应用于这项研究 酒精相关的疾病 该应用程序包括两个 组成部分：MR技术、统计分析和医疗方面的正式培训 道德和下面定义的具体研究项目。背景：酗酒 是一种与巨大的个体残疾有关的多因素疾病 给社会带来巨大的成本。 纳洛酮是一种阿片类药物， 被批准用于治疗酒精中毒 进一步了解如何 需要纳洛酮的神经生物学作用，以最大限度地发挥 这种药物，并计划新的药物治疗。 情绪增强 苯二氮卓类药物挑战的影响可以作为研究 纳洛酮对酒精诱导的情绪增强和脑功能的影响 功能本方案将使用动态磁化率对比磁 核磁共振成像（DSC MRI）来解决这些问题。方法：本项目将 研究了20名有酒精依赖史的戒酒者 和20个对比对象在五年内。 每组将 参加双盲、安慰剂对照、平衡、交叉 设计协议 受试者将接受纳洛酮或安慰剂预治疗 在接受阿普唑仑或安慰剂的挑战之前。 这将导致4 治疗条件：安慰剂-安慰剂、安慰剂-阿普唑仑、纳曲酮- 安慰剂和纳洛酮-阿普唑仑。 每名受试者将参加四个 扫描会话，每个治疗条件一个。 每次扫描会话 将包括一系列的三次扫描。 以下假设将 测试：假设1：预处理之间存在相互作用 条件和激发条件，使得1 a）当阿普唑仑 挑战是给酗酒者没有反对，RCBV下降率将是 最大和l B）用纳洛酮预处理将显著减缓 rCBV降低率;假设2：阿普唑仑将产生更大的 与正常对照组相比，酗酒者的情绪增强， 假设3：纳洛酮将减弱阿普唑仑的 情绪增强特性;假设4：rCBV的快速下降将 与情绪增强的报告相关。 纳洛酮预处理将 与rCBV下降较慢和情绪增强较少相关， 阿普唑仑是不加抵抗的。