Neuroimaging of Benzodiazepine-Induced Amnesia

苯二氮卓类药物引起的遗忘症的神经影像学

• 批准号: 6612864
• 负责人: MIRIAM Z. MINTZER
• 金额: $ 28.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612864
• 关键词: behavioral /social science research tag; benzodiazepines; bioimaging /biomedical imaging; blood flow measurement; blood tests; brain circulation; chemical structure function; clinical research; drug abuse; drug administration rate /duration; drug adverse effect; human subject; inhibitor /antagonist; memory disorders; neurochemistry; neuroimaging; neuropharmacology; neuropsychological tests; neuropsychology; pathologic process; positron emission tomography; scopolamine; substance abuse related behavior; triazolam; urinalysis

DESCRIPTION: (provided by applicant) There is concern about the abuse and long term use of benzodiazepine anxiolytic/hypnotic drugs by polydrug abusers and patients. One of the most insidious adverse effects of benzodiazepines is a profound impairment in the ability to form memories of personally experienced events (episodic memory encoding). This project will characterize the changes in brain activity reliably associated with benzodiazepine-induced impairment of episodic memory encoding by parametrically manipulating the level of impairment, and will examine the pharmacological and neurochemical mechanisms underlying these changes. Three double blind, placebo-controlled, within-subject outpatient studies in healthy volunteers are proposed, employing well-established methods in cognitive neuroscience. Following acute drug administration, brain activity associated with performance of a verbal episodic memory encoding task will be measured by regional cerebral blood flow (rCBF) using positron emission tomography (PET) with 15O-H20. Experiment 1 will manipulate the level of encoding impairment via administration of three dose levels of the benzodiazepine hypnotic triazolam. Experiment 2 will manipulate the level of encoding impairment via conjoint administration of triazolam and the benzodiazepine receptor specific antagonist flumazenil, which has been shown to reverse benzodiazepine-induced amnesia; this experiment will also provide information about the pharmacological mechanisms underlying benzodiazepine-induced changes in rCBF during encoding. Experiment 3 will provide information about the neurochemical specificity of benzodiazepine-induced changes in rCBF during encoding by comparing the pattern of rCBF changes produced by triazolam to that produced by scopolamine, a compound which induces comparable decrements in episodic memory encoding but which acts via different receptor site/neurochemical mechanisms. Results of this project will enhance the understanding of the brain mechanisms underlying a serious adverse effect of a widely prescribed and abused class of drugs. Ultimately, data from this research may contribute to the development of new classes of anxiolytic/hypnotic compounds with reduced memory impairing potential, as well as compounds which act to reverse the memory-impairing effects of benzodiazepines. Results of the proposed research also will enhance the understanding of the functional neuroanatomy of basic human memory processes.

描述：（申请人提供） 担心苯二氮卓的滥用和长期使用 聚药施用者和患者的抗焦虑药/催眠药物。最大的 在 能够形成个人经验的事件的记忆（情节记忆 编码）。该项目将表征大脑活动的变化 可靠地与苯二氮卓诱导的情节记忆损害相关 通过参数操纵损伤水平来编码，并将 检查这些基础的药理和神经化学机制 更改。三个双盲，安慰剂对照，受试者内门诊 提出了对健康志愿者的研究，采用公认的方法 在认知神经科学中。急性药物给药后，大脑活动 与语言情节记忆编码任务的性能有关 使用正电子发射通过区域脑血流（RCBF）测量 层析成像（PET），15O-H20。实验1将操纵 通过给药三个剂量水平来编码损害 苯二氮卓类催眠三唑。实验2将操纵 通过三唑兰和 苯二氮卓受体特异性拮抗剂flumazenil，已证明 反向苯二氮卓诱导的失忆症；该实验也将提供 有关药理机制的信息 苯二氮卓诱导的编码过程中RCBF的变化。实验3将 提供有关神经化学特异性的信息 苯二氮卓诱导的在编码过程中RCBF的变化通过比较模式 三唑仑对Scopolamine产生的RCBF变化的变化 诱导情节内存编码可比的化合物，但 通过不同的受体部位/神经化学机制起作用。结果 该项目将增强对大脑机制的理解 广泛规定和滥用类药物的严重不利影响。 最终，这项研究的数据可能有助于开发新的 抗焦虑/催眠化合物的类别，记忆力降低 潜力，以及可以逆转内存损害的化合物 苯二氮卓类药物的影响。拟议研究的结果也将增强 对基本人类记忆功能性神经解剖学的理解 过程。