Roles of gender, gonadectomy and estrous phase in the analgesic effects of intracerebroventricular morphine in rats.

Gender and gonadal function have previously been shown to influence the magnitude of analgesia following systemic morphine and opioid and nonopioid forms of swim 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 present study evaluated the roles of gender, gonadectomy and estrous phase upon dose-response and time-response functions of analgesia following intracerebroventricular administration of morphine as measured by the tail-flick and jump tests. 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 ED50; while male rats displayed near-maximal analgesia at a 5 micrograms dose of morphine, female rats displayed moderate analgesia at doses as high as 40 micrograms of morphine. Castration produced small, but significant reductions in the magnitude of central morphine analgesia; the ED50 of morphine analgesia, however, was not changed. Although female rats in either proestrous or estrous displayed significantly greater magnitude of analgesia than ovariectomized rats or rats in a combined met-/di-estrous phase at some doses, the ED50 of morphine analgesia was not significantly altered as functions of estrous phase or ovariectomy. The interaction of opiate receptors and gonadal steroid receptors is considered as one possible determinant of gender differences observed in the magnitude and potency of central morphine analgesia.