Central opioid antinociception in rats: Gender differences and gonadal effects.
Item
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Title
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Central opioid antinociception in rats: Gender differences and gonadal effects.
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Identifier
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AAI9130334
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identifier
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9130334
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Creator
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Kepler, Karen Lynn.
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Contributor
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Adviser: Richard J. Bodnar
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Date
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1991
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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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Biology, Neuroscience | Psychology, Psychobiology
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Abstract
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Gender and gonadal function have been shown to influence the magnitude of analgesia following systemic morphine and opioid and non-opioid forms of stress-induced analgesia with male rats displaying greater analgesia than female rats and gonadectomy reducing analgesic magnitude in both genders. These effects have been presumed to be centrally mediated. The purpose of the present dissertation was to assess the influence of gender, gonadectomy and estrus phase variables in central antinociception. The first experiment evaluated the roles of gender, gonadectomy, and estrous phase upon dose-response and time response functions of antinociception following intracerebroventricular administration of morphine as measured by the spinally mediated tail-flick test and the supraspinally jump test. Sham-operated male rats displayed significantly greater magnitudes of peak and total analgesia following central morphine than sham-operated female rats on both nociceptive measures. This striking effect was reflected both in terms of magnitude and potency. Gonadectomy, specifically castration produced small, but significant reductions in the magnitude of central morphine analgesia. Although female rats in either proestrous or estrous displayed significantly greater magnitudes of analgesia than ovariectomized rats or rats in the met/diestrous phase at some doses, potency of morphine analgesia was not effected by ovariectomy or estrous phase. Since mu and delta opioid receptor subtypes have been implicated in supraspinal analgesia, the second experiment evaluated the role of gender and gonadectomy following central administration of the mu-selective agonist, DAMGO, and the delta selective agonist, DSLET. Sham-operated male rats displayed significantly greater magnitudes of analgesia than sham-operated females on the tail-flick test following DAMGO, but not DSLET. Gonadectomy failed to consistently affect either DAMGO or DSLET analgesia. The interaction of opiate receptors and gonadal steroid receptors and differential metabolic rates of drug clearance are suggested as possible determinants of gender differences observed in antinociception following central administration.
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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.
