The objective of this Research Scientist Development Award (Level II) is to free Dr. Young of the majority of her teaching and administrative responsibilities so she can focus her efforts on a research program investigating behavioral and pharmacological variables that modify the development and expression of tolerance to opioid agonists and agonist-antagonists. The experimental methods of behavioral pharmacology will be used to identify ways in which the tolerance and dependence produced by acute or repeated opioid administration can be manipulated. The behavioral end-points assessed will include 1) ongoing rates and patterns of schedule-controlled behavior and 2) the discriminative stimulus properties of morphine. Specific experiments will assess the development and degree of tolerance to the rate-altering effects of morphine, etorphine, ad buprenorphine during repeated injection or osmotic infusion. Other experiments will evaluate the behavioral sequelae of long-term administration of the antagonist naltrexone. A third group of experiments will evaluate the contributions of the behavioral demands imposed by the reinforcement schedule to the development of tolerance to the rate-altering effects of morphine. A final group of experiments will assess changes in the discriminative stimulus profile of morphine and related compounds during repeated administration of opioid agonists, antagonists, and mixed agonist-antagonists. Pharmacotherapies are gaining increasing importance in the treatment of human drug abuse. Pre-clinical identification of the behavioral consequences of long-term opioid administration, and of the ways such consequences can be modified by both pharmacological and psychological factors, may have implications for our understanding both of tolerance processes in general and of the factors underlying opiate abuse.
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