Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint I. Role of progesterone receptors.
ABSTRACT Progestins and antiprogestins are widely used therapeutic agents in humans. In many cases, these are indicated for the treatment of reproductive activities. However, progesterone has widespread physiological effects including a reduction of the response to stress. We have reported that 5 min of restraint reduced lordosis behavior of ovariectomized rats hormonally primed with estradiol benzoate. When ovariectomized rats received both estradiol benzoate and progesterone priming, restraint had minimal effects on lordosis. Progesterone influences behavior through classical intracellular progesterone receptor-mediated nuclear events as well as extranuclear events. How these multiple events contribute to the response to stress is unclear. The current project was designed to initiate examination of the mechanisms responsible for progesterone's ability to protect against the effects of the restraint. In the first experiment, ovariectomized rats, primed with 10 μg estradiol benzoate, received 500 μg progesterone 4 h, 1 h, or 30 min before restraint. When progesterone was injected 4h before restraint, progesterone eliminated the effects of restraint. In contrast, progesterone 30 min before restraint offered no protection. Effects of progesterone 1h before restraint were equivocal allowing the suggestion that less than 4h of progesterone priming might be sufficient. In the second experiment, the synthetic progestin, medroxyprogesterone, was shown to mimic effects of progesterone in preventing effects of restraint. Finally, the progesterone receptor antagonist, RU486, attenuated progesterone's protection against restraint. These findings offer evidence that ligand-activated progesterone receptor mechanisms contribute to the maintenance of lordosis behavior in the presence of mild stress.
Article: Intracerebral actions of the 5-HT1A agonists, 8-OH-DPAT and buspirone and of the 5-HT1A partial agonist/antagonist, NAN-190, on female sexual behavior.[show abstract] [hide abstract]
ABSTRACT: Proestrous rats were infused intracerebrally with 50-1000 ng 8-OH-DPAT, 500 or 2000 ng buspirone or 125-500 ng NAN-190. For each drug, bilateral infusions into the mediobasal hypothalamus inhibited female lordosis behavior and proceptivity and initiated resistive behavior. The effects of the drugs were evident within 5-20 min of infusion and generally lasted for 1-2 hr. The effective sites for 5-HT1A-mediated inhibition of sexual behavior were most concentrated in the ventromedial nucleus of the hypothalamus. Cannulae sites anterior, posterior or dorsal to the ventromedial nucleus or clearly within the IIIrd ventricle were less effective at disrupting lordosis behavior. The inhibition of sexual behavior, following 8-OH-DPAT occurred in a dose-dependent manner and appeared to include the loss of motivation of the female to mate. Buspirone produced similar, but quantitatively smaller, effects on lordosis behavior. NAN-190 slightly, but significantly, suppressed lordosis behavior after either intracerebral or intraperitoneal injection and substantially increased resistive behavior. These results suggest that the inhibition of lordosis behavior, following treatment with 5-HT1A agonists, include an action within the ventromedial nucleus. Moreover, 5-HT1A receptors in this area appear to play a functionally important role in the modulation of the female's "willingness" to mate.Neuropharmacology 11/1992; 31(10):969-81. · 4.81 Impact Factor
Article: Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and of mild restraint on lordosis behavior.[show abstract] [hide abstract]
ABSTRACT: Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 microg EB 7 days before a second priming with 10 microg EB followed 48 h later with 500 microg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen's protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT(1A) receptor modulation of lordosis behavior.Brain Research 07/2003; 974(1-2):202-11. · 2.73 Impact Factor