The objective of the proposed research is to characterize the effects of different benzodiazepines on complex behavioral processes. Despite their dependence-producing potential and reports of intrinsic differences among the benzodiazepines in man, there have been few direct comparisons of their effects on complex behavioral processes such as learning and memory. Such effects may constitute a serious adverse consequence of the use of this class of drug. Complex operant tasks involving both the acquisition, retention and performance of discriminations in monkeys and rats will be the major focus of investigation. In monkeys, a multiple schedule will be used in order to make a direct comparison of drug effects on the acquisition and performance of conditional discriminations. Finally, repeated acquisition and delayed performance will be used as a baseline to assess drug effects on memory in monkeys. Thus these different baselines will allow us to determine drug effects on learning, memory and performance. The first series of experiments represents a continuation of our research characterizing the acute effects of various benzodiazepines on each of these baselines. As a comparison the effects of other benzodiazepine agonists, antagonists and inverse agonists will be characterized and used in order to determine the extent to which the effects of these compounds on different behavioral processes might be mediated by specific mechanisms of action. Specifically, studies are designed to evaluate effects of these drugs on various aspects of learning and memory, including storage and retrieval processes. A second series of studies are designed to determine whether various drugs produce anterograde and/or retrograde amnesia. Together these procedures will provide a significant amount of new information pertaining to how a drug effects five different complex behavioral processes. Through the use of relative potency measures, based upon complete dose-effect studies, we will be able to profile a drug's effect on these different complex behavioral processes. Similarly, we will be able to make meaningful comparisons among drugs in terms of their liability of abuse relative to complex behavior. Such information is of obvious potential significance in terms of both the rational therapeutic use of the benzodiazepines in the outpatient and in the management of the benzodiazepine abuser.
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