Pharmacology Bwchemlstry & Behavior, Vol 34, pp 119-127 ©Pergamon Press plc, 1989 Printedin the U S A 0091-3057/89 $3 00 + 00 Roles of Gender, Gonadectomy and Estrous Phase in the Analgesic Effects of Intracerebroventricular Morphine in Rats KAREN L. KEPLER,1 BENJAMIN KEST, JACQUELINE M. KIEFEL, MADELINE L. COOPER AND RICHARD J. BODNAR 2 Department of Psychology and Neuropsychology Doctoral Sub-Program Queens College, CUNY, Flushing, NY 11367 Received 27 June 1989 KEPLER, K L, B KEST, J M KIEFEL, M L COOPER AND R J BODNAR Roles of gender, gonadectomyand estrousphase m the analgesw effects of mtracerebroventrwular morphine m rats PHARMACOL BIOCHEM BEHAV 34(1) 119-127, 1989 --Gender and gonadal function have previously been shown to influence the magnitude of analgesia following systenuc morphine and oplo~d and nonopiold forms of swim analgesia with male rats displaying greater analgesia than female rats and gonadectomy reducing analgesic magmtude 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 me-response functions of analgesia following intracerebroventrlcular adrmmstration of morphine as measured by the tail-flick and jump tests Sham-operated male rats displayed significantly greater magmtudes of peak and total analgesia following central morphine than sham-operated female rats on both nociceptive measures This striking effect was reflected both m terms of magmtude and EDso, while male rats displayed near-maxn-nal analgesia at a 5 p.g dose of morphine, female rats displayed moderate analgesia at doses as high as 40 p.g of morphine Castration produced small, but significant reductions in the magnitude of central morphine analgesia, the EDso of morphine analgesia, however, was not changed Although female rats m either procstrous or estrous displayed significantly greater magnitudes of analgesia than ovanectormzed rats or rats m a combined met-/dt-estrous phase at some doses, the EDso of morphine analgesia was not significantly altered as functions of estrous phase or ovanectomy The interaction of opiate receptors and gonadal steroid receptors is considered as one possible detemunant of gender differences observed in the magnitude and potency of central morphine analgesia Central morphine analgesia Gender differences Gonadectomy Estrous phases Pain Rats THE roles of gender and gonadal function m the medmtlon of opiold and nonoplold forms of pain inhlbmon have been recently elucidated [see review (7)]. Female rats display significantly lower shock thresholds than male rats (4,37) Whde androgenized female rats display shock thresholds similar to intact male rats, castrated male rats display shock thresholds smular to intact female rats (5). Female rats exhibit their greatest basal sensmvlty to shock during the estrous phase (12). The analgesic magmtudes of systemic morphine, oplold intermittent cold-water swims (ICWS) (6) and nonoplold continuous cold-water swims (CCWS) (6) are higher in intact male than female rats (2, 23, 40) Gonadectomy reduces each of these forms of analgesia relaUve to same sex controls (9,42), and steroid replacement therapy with testosterone reverses the swim analgesia deficits in gonadecto- mazed animals (41) While the phase of estrous fails to alter nonoploid CCWS analgesia (40), the greatest sensitivity to sys- termc morphine analgesia occurs dunng d~estrous m intact female rats (3). The s~te of action for these gender and gonadectomy effects upon analgemc processes has been presumed to be centrally mediated. The present study tested this hypothesm by evaluating the relative importance of three gender-related variables, gender differences, gonadectomy and estrous phase, upon the central analgesic effects of morplune following mtracerebroventncular administraUon [see review, (51)] Dose-response and ume-re- sponse actions of central morphine analgesm were evaluated in sham-operated male rats, castrated male rats, ovanectomized female rats, and sham-operated female rats during estrous, pro- IK L Kepler was a recipient of an Ommtech Travel Fellowship to the Society for Neuroscience meeting, 1988 Tins paper is based on the abstract subrmtted for the award The award winmng papers are published together m thlS Issue 2Requests for repnnts should be addressed to Dr R J Bodnar 119