BENZODIAZEPINES USE/ABUSE--EFFECTS ON MEMORY MECHANISMS

有人对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/催眠药物表示关注。苯二氮类药物最隐蔽的副作用之一是记忆障碍。该项目涉及在人类记忆研究的最新概念和方法发展的指导下，对苯二氮卓类药物的急性和慢性记忆损伤效应进行直接实验研究。实验一将探讨苯二氮类药物引起的外显记忆损伤(即有意或有意识地回忆先前的经验)的认知机制；该实验将首次直接检验以下假设：苯二氮卓类药物对背景信息(即事件期间注意外围的信息)在记忆中产生特定的损伤，这一现象在外显记忆中起着关键作用。在一项安慰剂对照的双盲独立小组设计中，使用最近开发的测量背景信息对记忆的影响的程序，将在健康志愿者中比较苯二氮卓类药物劳拉西潘和抗胆碱能药物东莨菪碱的急性背景记忆效应。实验2-3将评估苯二氮卓类药物对内隐记忆(即无意或无意地表达对先前经验的记忆)的急性影响，这是一种普遍存在的现象，具有相当大的理论和实践意义。劳拉西潘的内隐记忆效应将在健康志愿者身上进行比较，使用最近开发的测量内隐记忆的程序，采用安慰剂对照的双盲独立小组设计，在健康志愿者中比较东莨菪碱和苯二氮卓类安定的内隐记忆效应。实验4将通过评估长期服用苯二氮卓类药物的焦虑症确诊患者与适当匹配的对照组受试者的外显背景记忆和内隐记忆，提供直接临床相关的信息。来自该项目的数据将允许更全面地描述苯二氮卓类药物对记忆的影响，并将有助于理解人类记忆过程的特殊性。最终，这些数据还可能有助于改进药物滥用治疗策略的开发，并有助于开发具有降低记忆损害潜力的抗焦虑/催眠化合物。

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.