BENZODIAZEPINES USE/ABUSE--EFFECTS ON MEMORY MECHANISMS

苯二氮卓类药物的使用/滥用——对记忆机制的影响

• 批准号: 6378789
• 负责人: Roland R Griffiths
• 金额: $ 26.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378789
• 关键词: anxiety disorders; benzodiazepines; clinical research; cognition; diazepam; dosage; drug abuse; drug adverse effect; human subject; longitudinal human study; lorazepam; memory; memory disorders; neuropsychological tests; placebos; psychomotor function; questionnaires; scopolamine; sound perception; space perception; time perception; visual perception

There is concern about the long-term use and abuse of benzodiazepine anxiolytic/hypnotic drugs by prescribed users and polydrug abusers. One of the most insidious adverse effects of benzodiazepines is memory impairment. This project involves a direct experimental investigation of the acute and chronic memory-impairing effects of benzodiazepines, guided by recent conceptual and methodological developments in human memory research. Experiment 1 will investigate the cognitive mechanisms underlying the well-established benzodiazepine-induced impairment in explicit memory (i.e., intentional or conscious recollection of a previous experience); this experiment will provide the first direct test of the hypothesis that benzodiazepines produce a specific impairment in memory for contextual information (i.e., information in the periphery of attention during an event), a phenomenon which plays a critical role in explicit memory. The acute contextual-memory effects of the benzodiazepine lorazepam will be compared to those of the anticholinergic drug scopolamine in healthy volunteers in a placebo-controlled double-blind independent groups design across a range of doses, using recently developed procedures for measuring effects on memory for contextual information. Experiments 2-3 will evaluate the acute effects of benzodiazepines on implicit memory (i.e., memory for a previous experience expressed unintentionally or without conscious recollection of the experience), a ubiquitous phenomenon with considerable theoretical and practical significance. The implicit-memory effects of lorazepam will be compared to those of scopolamine and the benzodiazepine diazepam in healthy volunteers in a placebo-controlled double-blind independent groups design across a range of doses, using recently developed procedures for measuring implicit memory. Experiment 4 will provide information of direct clinical relevance by evaluating explicit contextual memory and implicit memory in anxiety disorder-diagnosed individuals with long-term prescribed benzodiazepine use, relative to appropriately-matched control subjects. Data from this project will permit a more complete characterization of the effects of benzodiazepines on memory and will contribute to the understanding of the specificity of human memory processes. Ultimately, these data may also contribute to the development of improved drug abuse treatment strategies and to the development of anxiolytic/hypnotic compounds with reduced memory-impairing potential.

处方使用者和多种药物滥用者长期使用和滥用苯二氮卓类抗焦虑/催眠药物令人担忧。苯二氮卓类药物最潜在的副作用之一是记忆障碍。该项目涉及对苯二氮卓类药物急性和慢性记忆损害效应的直接实验研究，以人类记忆研究中最近的概念和方法发展为指导。实验1将探讨苯二氮卓类药物引起的外显记忆损伤（即有意或有意识地回忆以前的经历）背后的认知机制；本实验将首次直接验证苯二氮卓类药物对情境信息（即事件中注意力外围的信息）的记忆产生特定损害的假设，这一现象在外显记忆中起着关键作用。在不同剂量的安慰剂对照双盲独立组设计中，将苯二氮卓类药物劳拉西泮与抗胆碱能药物东莨菪碱在健康志愿者中的急性情境记忆效应进行比较，使用最近开发的程序来测量情境信息对记忆的影响。实验2-3将评估苯二氮卓类药物对内隐记忆（即无意识地或没有有意识地回忆以前的经历）的急性影响，这是一种普遍存在的现象，具有相当的理论和实践意义。使用最近开发的测量内隐记忆的方法，在一个安慰剂控制的双盲独立组中，将劳拉西泮的内隐记忆效应与东莨菪碱和苯二氮卓类地西泮在健康志愿者中的内隐记忆效应进行比较。实验4将通过评估长期服用苯二氮卓类药物的焦虑障碍诊断个体的外显情境记忆和内隐记忆，相对于适当匹配的对照组，提供直接临床相关的信息。该项目的数据将允许更完整地描述苯二氮卓类药物对记忆的影响，并将有助于了解人类记忆过程的特殊性。最终，这些数据也可能有助于改进药物滥用治疗策略的发展，并有助于开发具有减少记忆损害潜力的抗焦虑/催眠化合物。