Contributions of sex and genotype to morphine analgesic tolerance.
Item
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Title
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Contributions of sex and genotype to morphine analgesic tolerance.
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Identifier
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AAI3115257
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identifier
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3115257
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Creator
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Hopkins, Eileen.
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Contributor
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Adviser: Benjamin Kest
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Date
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2004
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Pharmacology | Psychology, Psychobiology | Biology, Neuroscience
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Abstract
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Individual differences in morphine's analgesic efficacy are important clinical concerns. While the contributions of sex and genotype to individual differences in acute morphine analgesia has received much recent attention in the research, little work has been done to explore the degree to which these factors contributed to morphine's ability to sustain its analgesic efficacy. The focus of the present dissertation was to examine the extent to which tolerance to morphine's effects varies as a function of sex and/or genotype.;It was determined, through experiments using CD-1 mice, that females show greater tolerance to the analgesic effects of morphine on the tail withdrawal test following chronically administered subcutaneous and intrathecal, but not intracerebroventricular, morphine. In contrast, male CD-1 mice showed greater tolerance to the hypothermic effects of morphine, demonstrating dissociation of tolerance development to the different behavioral/physiological effects of the drug. Sex did not have a significant main effect on tolerance development to morphine analgesia on the acetic acid writhing test, suggesting the possibility of dissociation in tolerance to analgesia for different types of pain. A comprehensive strain survey revealed significant genetic differences in tolerance to morphine's analgesic effects. Further, sex differences were observed within some strains under one method of calculating analgesia (ED50), but not another (AD50). Overall, it is clear from the experiments that sex and genotype play an important role in the development of morphine tolerance. Like findings of sex differences in morphine analgesia, however, the exact nature and direction of differences in tolerance found appears dependent on the specific experimental methods. Collectively, the findings of the present dissertation contribute to our understanding of individual differences in tolerance development, and suggest that such differences should be taken into account in the planning and interpretation of future research in this area.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
