Repeated estradiol benzoate treatment protects against the lordosis-inhibitory effects of restraint and prevents effects of the antiprogestin, RU486.

The following experiment was designed to test two specific questions: (1) Does the antiprogestin, RU486, reduce emergence of lordosis behavior and/or proceptivity in rats given repeated treatment with 10μg estradiol benzoate (EB) and/or a single high dose (40μg) of EB? (2) Does RU486 accentuate the effects of a 5min restraint experience on sexual behaviors in rats given repeated treatment with estradiol benzoate (EB) and/or a high dose of EB? RU486 was used to determine if a high dose and/or repeated treatment with EB enhanced proceptivity and reduced the response to mild stress through an intracellular progesterone receptor-mediated process. Ovariectomized Fischer rats were injected with a single dose of 10 or 40μg estradiol benzoate (EB) or received 4consecutiveweeks of treatment with 10μg EB. Forty-eight hours after the last treatment with EB, rats were injected with 5mg/kg of the antiprogestin, RU486, or the RU486 vehicle.

Allopregnanolone's attenuation of the lordosis-inhibiting effects of restraint is blocked by the antiprogestin, CDB-4124.

A brief restraint experience reduces lordosis behavior in ovariectomized females that have been hormonally primed with estradiol benzoate. The addition of progesterone to the priming prevents the lordosis inhibition. Based on prior studies with an inhibitor of progesterone metabolism, we have implicated the intracellular progesterone receptor, rather than progesterone metabolites, as responsible for this protection.

Comparison of female Fischer and Sprague-Dawley rats in the response to ketanserin.

The effects of the 5-HT2A/2C receptor antagonist, ketanserin, on lordosis behavior were examined in hormonally primed, ovariectomized Fischer and Sprague-Dawley females. Rats were primed with 0.067μg/g body weight estradiol benzoate and 3.

Prior hormonal treatment, but not sexual experience, reduces the negative effects of restraint on female sexual behavior.

These experiments were designed to determine if prior sexual experience reduced the negative effect of mild stress on female sexual behavior. In the first experiment, ovariectomized rats were hormonally primed with estradiol benzoate and progesterone for 3 consecutive weeks during which they received six mating experiences in a male's home cage or received no sexual experience. The next week, females were primed with 10 μg estradiol benzoate two days before a 5 min restraint.

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-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione) (60 mg/kg), or vehicle (20% DMSO+propylene glycol).

Sprague-Dawley and Fischer female rats differ in acute effects of fluoxetine on sexual behavior.

Introduction: The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT(1A) receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT(1A) receptors holds for other rat strains is not known.

RU486 blocks effects of allopregnanolone on the response to restraint stress.

These experiments were designed to provide information about the potential involvement of progesterone receptors in the ability of allopregnanolone (3α-hydroxy-5α-pregnan-20-one) to reduce the lordosis-inhibiting effects of restraint stress. Ovariectomized Fischer rats were hormonally primed with 10 μg estradiol benzoate and 4 mg/kg allopregnanolone or vehicle. One hour before allopregnanolone, rats were injected with the progesterone receptor antagonist, RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), or vehicle.

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint I. Role of progesterone receptors.

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.

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint II. Role of progesterone metabolites.

When ovariectomized Fischer female rats are hormonally primed with 10 μg estradiol benzoate, a 5 min restraint experience rapidly inhibits lordosis behavior. Addition of progesterone to the hormonal priming prevents this restraint-induced inhibition. In prior work, we reported evidence that progesterone receptors (PR) may contribute to this protective effect of progesterone.

Tropisetron increases the inhibitory effect of mild restraint on lordosis behavior of hormonally primed, ovariectomized rats.

Ovariectomized rats, hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone are resistant to the lordosis-inhibiting effects of a 5 min restraint experience. However, modulation of the serotonergic (5-HT) system alters this resistance to stress. In the following experiment, ovariectomized Fischer inbred rats were hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone.

Progesterone reduces the inhibitory effect of a serotonin 1B receptor agonist on lordosis behavior.

Ovariectomized Fischer inbred rats were hormonally primed with 10μg estradiol benzoate and sesame seed oil (EO rats) or with estradiol benzoate and 500μg progesterone (EP rats). Four to six hours after progesterone or oil, rats were pretested for sexual behavior and then infused bilaterally into the ventromedial nucleus of the hypothalamus with 0, 50, 100 or 200ng of the 5-HT(1B) receptor agonist, 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrol[3,2-bi]pyridin-5-one-dihydrochloride (CP 93129). Sexual receptivity was monitored by the lordosis to mount (L/M) ratio.

Role of 5-HT(1A) receptors in fluoxetine-induced lordosis inhibition.

The selective serotonin reuptake inhibitor (SSRI), fluoxetine (Prozac(R)), is an effective antidepressant that is also prescribed for other disorders (e.g. anorexia, bulimia, and premenstrual dysphoria) that are prevalent in females.

Progesterone reduces the effect of the serotonin 1B/1D receptor antagonist, GR 127935, on lordosis behavior.

Ovariectomized rats were hormonally primed with 10 microg estradiol benzoate or with estradiol benzoate plus 500 microg progesterone. Rats received a bilateral infusion with 200 ng of the 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1'-biphenyl-4-carboxamide hydrochloride (GR 127935), into the ventromedial nucleus of the hypothalamus (VMN), followed by a 5 min restraint or home cage experience. In estrogen-primed females that had experienced minimal handling between ovariectomy and use in the experiment, infusion with the water vehicle transiently inhibited lordosis behavior, and the 5-HT(1B/1D) receptor antagonist amplified this inhibition.

Daily male exposure attenuates estrous cycle disruption by fluoxetine.

Fluoxetine (Prozac) produces sexual dysfunction in a substantial number of patients. In the few animal studies designed to address this sexual dysfunction in females, data have been inconsistent. Some investigators report that the drug disrupts sexual behavior without affecting the estrous cycle while we have reported robust effects of fluoxetine on the estrous cycle.

Serotonin receptor involvement in effects of restraint on female rat lordosis behavior.

Ovariectomized Fischer (CDF-344) rats, with bilateral cannulae in the mediobasal hypothalamus (MBH) near the ventromedial nucleus of the hypothalamus (VMN), were used to test the hypothesis that serotonin receptors in the VMN contribute to the lordosis-inhibiting effects of mild restraint. Rats were hormonally primed with 10 microg estradiol benzoate (EB) followed 48 h later with sesame seed oil. Four to six hours later (during the dark portion of the light-dark cycle), rats were pretested for sexual behavior.

Restraint accentuates the effects of 5-HT2 receptor antagonists and a 5-HT1A receptor agonist on lordosis behavior.

The effect of restraint on lordosis behavior was examined in proestrous and ovariectomized, hormone-primed rats. Restraint durations from 5 to 60 min had no effect on lordosis behavior of proestrous rats. There was also no effect of 5 min restraint on lordosis behavior of ovariectomized rats hormonally primed with 10 microg estradiol benzoate and 500 microg progesterone.

Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and of mild restraint on lordosis behavior.

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.