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: 6711819
• 负责人: Chris Conway Streeter
• 金额: $ 18.81万
• 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/6711819
• 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 申请者的目标是成为一名独立的、跨学科的 研究人员将功能磁共振成像(FMRI)应用于这项研究 与酒精相关的障碍。本申请建议书包括两份 组成部分：MR技术、统计分析和医学方面的正式培训 伦理和一个具体的研究项目，定义如下。背景资料：酗酒 是一种与巨大的个体残疾相关的多因素障碍 给社会带来了巨大的代价。纳曲酮是最近开发的一种阿片类阻滞剂 被批准用于治疗酒精中毒。加深了对 需要纳曲酮的神经生物学效应才能最大限度地发挥 这一药物并计划进行新的药物治疗。心情舒畅 苯二氮卓类药物激发的影响可作为研究 纳曲酮对酒精性情绪改善及脑组织的影响 功能。该协议将使用动态磁化率对比磁 磁共振成像(DSC MRI)来解决这些问题。方法：此项目将 对20名有酒精依赖史的戒酒者进行研究 在五年的时间里，有20个比较对象。每一组都将 参与双盲、安慰剂对照、平衡、交叉 设计协议。受试者将接受纳曲酮或安慰剂的预治疗 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 安慰剂和纳曲酮-阿普唑仑。每名受试者将参加四个 扫描疗程，每种治疗条件一次。每个扫描会话 将包括一系列三次扫描。以下假设将是 检验：假设1：在前处理之间会有交互作用 条件和挑战条件使得1a)当阿普唑仑 挑战给无人反对的酗酒者，RCBV下降的速度将是 最大的和L b)预先给予纳曲酮将显著减缓 RCBV下降率；假设2：阿普唑仑将产生更大的 酗酒者的情绪改善与正常对照组相比，通过 已建立的情绪量表；假设3：纳曲酮将减弱阿普唑仑的症状 改善情绪的特性；假设4：rCBV的快速下降将 与改善情绪的报道相关。纳曲酮预处理会 与以下情况相关：rCBV下降较慢，情绪改善较少 阿普唑仑是在没有对手的情况下给予的。