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.
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