Pharmacology Biochemistry & Behavior, Vol. 18, pp. 535-539, 1983. ©Ankho InternationalInc. Printed in the U.S.A. Facilitation of Estrogen-Induced Receptivity Through Metyrapone Administration in Ovariectomized Rats DENYS DE CATANZARO, RANDOLPH P. KNIPPING AND STEPHEN W. WIGMORE Department of Psychology, McMaster University, Hamilton, Ontario L8S 4K1, Canada Received 27 February 1982 DE CATANZARO, D., R. P. KNIPPING AND S. W. WIGMORE. Facilitation of estrogen-induced receptivity through metyrapone administration in ovariectomized rats. PHARMACOL BIOCHEM BEHAV 18(4) 535-539, 1983.--Previously it has been established that adrenalectomy facilitates lordosis in estrogen-primed ovariectomized female rats and that corticosterone administration restores lordosis to preadrenalectomy levels. The present study examined the effects of an inhibitor of the synthesis of corticosterone, metyrapone, upon lordosis in ovariectomized females. In Experiment 1, chronic administration of moderate doses of metyrapone was found to facilitate lordosis. In Experiment 2, a single metyrapone administration at various doses and time intervals before testing had a mild facilitatory effect on lordosis. Experiment 3 compared the effects of metyrapone on ovariectomized and adrenalectomized-ovariectomizedfemales. The absence of a facilitatory effect in adrenalectomized females suggests that the drug's effect on lordosis is mediated by its established inhibitory effects on 1lfl-hydroxylation in the adrenal. These data are consistent with indications that cortico- sterone titer modulates female receptivity. Metyrapone Corticosterone Lordosis Adrenalectomy Female sexual behavior Estrogen THERE is growing evidence that activity of the pituitary- adrenal system can influence estrogen-induced sexual re- ceptivity in female rodents. Several studies [9, 10, 11, 14, 15] have indicated that adrenalectomized-ovariectomized females show higher lordosis quotients in response to estro- gen administration than do adrenally-intact ovariectomized females. Chronic peripheral corticosterone or dex- amethasone administration, but not administration of progesterone or desoxycorticosterone, inhibits estrogen- induced lordosis in adrenalectomized-ovariectomized females [I0,12]. Despite the fact that adrenaicorticotrophic hormone (ACTH) levels rise following adrenalectomy and are lowered by corticosterone administration [8,17] and evi- dence that peripheral ACTH administration can facilitate lordosis [10,11], the effects of corticosterone and adrenaiec- tomy on lordosis do not appear to be mediated by ACTH [11]. However, under a variety of dosage regimens cortico- sterone level consistently influences female receptivity through some unknown mechanism [12]. The drug metyrapone is reported to be a potent inhibitor of adrenal synthesis of corticosterone, blocking action of the enzyme 1 lfl-hydroxylase that produces this hormone from its precursor, 11-desoxycorticosterone [6, 13, 21, 31]. There appears to have been very little study of the behavioral ef- fects of this substance. If corticosterone does indeed play a specific inhibitory role in the control of female sexual receptiv- ity, it should be possible to facilitate lordosis by administering metyrapone to adrenally-intact females. Previously [12], the inference that corticosterone may have an inhibitory effect on lordosis was based primarily upon comparison of adrenalectomized-ovariectomized rats given various re- placement doses of corticosterone. In the present study, ovariectomized but adrenally-intact animals were examined under varied acute and chronic regimens of metyrapone administration. This accordingly tests the generality of find- ings across physiological preparations, which should help to confirm or disconfirm a specific role of corticosterone in modulating female receptivity. The first two experiments demonstrate that metyrapone does indeed influence lordosis in manners consistent with such a modulatory role of corti- costerone. The third experiment verifies the involvement of the adrenal gland in these effects of metyrapone by compar- ing its action in adrenalectomized-ovariectomized and ovariectomized females. EXPERIMENT 1 In the first experiment, the effect of chronic administra- tion of various doses of metyrapone was studied in ovariec- tomized females given either of two doses of estrogen. A chronic regimen was employed first because previous data have indicated that sustained variations in corticosterone titer most reliably influence estrogen-induced female recep- tivity [10,12]. The dose range was based upon dosages ad- ministered in vivo to adult rats in studies demonstrating al- teration of adrenal functioning by this drug. For example, Malendowicz [22] administered 30 mg/animal daily for 5 days, demonstrating marked changes in adrenal histology, whereas Parvez and Parvez [24] administered 75 mg/animal daily for 1, 7; or 10 days, demonstrating a number of biochemical effects consistent with glucocorticoid suppres- sion. 535