BENZODIAZEPINES USE/ABUSE--EFFECTS ON MEMORY MECHANISMS

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/催眠药物的情况令人关注。 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的急性和慢性记忆损害效应的直接实验研究，以人类记忆研究的最新概念和方法发展为指导。 实验1将研究明确的苯二氮卓诱导的外显记忆障碍的认知机制（即，对先前经历的有意或有意识回忆）;该实验将提供对苯并二氮杂卓类对背景信息的记忆产生特定损害的假设的第一次直接检验（即，信息在注意力的外围在一个事件），这是一种现象，发挥了关键作用，在外显记忆。 在一项安慰剂对照、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，该设计涵盖一系列剂量，使用最近开发的程序测量对情境信息记忆的影响。 实验2-3将评估苯二氮卓类药物对内隐记忆的急性作用（即，对先前经验的记忆，是一种无意识或无意识地表达出来的经验），这是一种普遍存在的现象，具有相当的理论和实践意义。 将采用最近开发的测量内隐记忆的程序，在安慰剂对照、双盲、独立组设计中，在健康志愿者中比较劳拉西泮与东莨菪碱和苯二氮卓类地西泮的内隐记忆效应。 实验4将提供直接的临床相关性的信息，通过评估焦虑症诊断的个人与长期处方苯二氮卓类药物的使用，相对于适当匹配的控制对象的外显背景记忆和内隐记忆。 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异性。 最终，这些数据也可能有助于开发改进的药物滥用治疗策略和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.