Comparatively little is known about the ways in which behavioral factors themselves may influence the time course and extent of tolerance to behavioral effects of drugs. This project will attempt to more fully characterize the importance of behavioral factors during chronic administration of modulators at GABA and NMDA receptor sites, locations associated with activity for anxiolytics and psychotomimetics that are widely used on a chronic basis. The project will focus on operant behavior that is maintained (reinforced) by delivery of food and solutions of water & sucrose. This project is intended specifically to study influences on tolerance of: 1. Response Cost - Experiments will study influences on tolerance by drug-produced changes in reinforcer frequency for varied response requirements, reinforcer magnitudes, and reinforcer types. 2. Operant Discriminations - Experiments will study influences on tolerance by discriminative properties of both the subjective effects of a drug as well as the environment in which the drug is chronically administered. Additionally, """"""""multi-chamber"""""""" procedures will study generalization of those discriminative effects to performance of the same subjects in different circumstances.
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