An antiprogestin, CDB4124, blocks progesterone's attenuation of the negative effects of a mild stress on sexual behavior.

These experiments were designed to test the hypothesis that a progesterone receptor antagonist would block progesterone's ability to reduce the negative effects of a 5 min restraint on female rat sexual behavior. Ovariectomized Fischer rats were injected with 10 µg estradiol benzoate. Two days later, rats were injected subcutaneously (sc) with the progesterone receptor antagonist, CDB4124 (17α-acetoxy-21-methoxy-11ß-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione) (60 mg/kg), or vehicle (20% DMSO+propylene glycol). One hour later, rats were injected sc with 500 µg progesterone or vehicle (sesame seed oil). Rats were assigned to one of three different treatment conditions: (1) (ECV) estradiol benzoate, CDB4124, sesame seed oil vehicle, (2) (ECP) estradiol benzoate, CDB4124, progesterone, and (3) (EVP) estradiol benzoate, DMSO/propylene glycol vehicle, progesterone. That afternoon sexual behavior was examined before and after a 5 min restraint experience. Before restraint, lordosis behavior was comparable across treatment conditions but only progesterone-treated rats exhibited proceptive behavior. CDB4124 did not block progesterone's induction of proceptivity. However, after restraint, CDB4124 attenuated the positive effects of progesterone on all sexual behaviors examined. The restraint experience inhibited sexual behavior in rats treated with estradiol benzoate and CDB4124 and in rats treated with estradiol benzoate, CDB4124, and progesterone but not in rats given estradiol benzoate and progesterone without CDB4124. These findings are consistent with the hypothesis that progesterone receptors mediate progesterone's ability to reduce the negative sexual behavioral effects of a mild stressor.

8-OH-DPAT attenuates isoproterenol- but not forskolin-stimulated accumulation of cAMP in mediobasal hypothalamus.

Ovariectomized female rats were used to test the possibility that the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), inhibits cyclic AMP (cAMP) accumulation in the mediobasal hypothalamus. Tissue slices were incubated with forskolin or with the beta-adrenergic receptor agonist, isoproterenol, to stimulate accumulation of cAMP. Both compounds increased accumulation of cAMP. The 5-HT(1A) receptor agonist, 8-OH-DPAT, reduced cAMP accumulation after stimulation by isoproterenol, but not after forskolin stimulation. These findings are discussed in terms of putative differences in the mechanisms whereby 5-HT(1A) receptors are able to inhibit stimulation of adenylate cyclase. The potential significance of these findings to 5-HT(1A) receptor-mediated inhibition of female rat lordosis behavior is also discussed.