Comparatively little is known about the ways in which development and loss of tolerance may differ for different classes of abused drugs, or about ways in which behavioral factors themselves may influence the time course and extent of tolerance development. This project will attempt to more fully characterize the importance of behavioral factors in the development of tolerance to cocaine, delta-9-THC, and phencyclidine. The project will focus on schedule-controlled behavior that is maintained (reinforced) or suppressed (punished) by delivery or postponement of events such as food or electric stimulation. This project is intended specifically to study the influences on tolerance of: 1.Response Consequences - Experiments will study the importance and generality of the influence on tolerance development by drug-produced changes in frequency or distribution of reinforcers and punishers. 2.Situational Specificity of Tolerance Development - Experiments will study the influence on tolerance development of features of the environment which are regularly present during the chronic administration of a drug. Multi- environment procedures will permit evaluation of the effects of chronic drugs in complex and varied circumstances. 3.Pharmacologic Specificity - In experiments where changes in behavioral procedures have marked influences on tolerance to a particular drug, the intermittent substitution of different doses of related agonists and an- tagonists will be studied to provide systematic information about participating pharmacological processes.
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