Effects of 5-HT1A-receptor agonist, 8-OH-DPAT, and GABAB-receptor agonist, baclofen, on lordosis in female rats with lesions in either the dorsal raphe nucleus or septum.

The inhibitory effects of 8-OH-DPAT, a 5-HT1A-receptor agonist, and baclofen, a GABAB-receptor agonist, on lordosis were examined in estrogen and progesterone-treated ovariectomized rats with lesions in either the dorsal raphe nucleus (DRN) or septum and in rats with either sham lesions or no lesions. The first behavior test series was carried out 6 days after implantation of the rats with silicon tubes containing estradiol. Four hours after injection with 0.5 mg progesterone, behavioral tests were performed before and 30 min after an injection with 1 mg/kg body weight 8-OH-DPAT. As a result, the mean lordosis quotient (LQ)s were changed from 100 to less than 20 before and after the injection in all groups. These results suggest that 8-OH-DPAT acts on areas other than the DRN and the septum, leading to a decrease in lordosis. Two weeks after implantation with estradiol, the next behavioral test series was carried out after injection with progesterone. Behavioral tests were performed before and after an injection with 10 mg baclofen. The results showed that the mean LQs decreased after the injection in all groups, but the mean LQ in the DRN lesion group was higher than that in the sham groups. These results indicate that baclofen may act partially on the DRN in inhibiting lordosis in female rats.

Suppressive effect of neonatal treatment with a phytoestrogen, coumestrol, on lordosis and estrous cycle in female rats.

The neural control systems for the ovulatory cycle and lordosis behavior are sexually differentiated by estrogen during the perinatal period in rats. In the present study, the effects of a single neonatal injection with the phytoestrogen, coumestrol, on female reproductive functions were investigated. Female rats were injected subcutaneously with 1 or 3mg coumestrol (CM1, CM3), 1mg genistein (GS1), 1mg estradiol (E2), or oil at day 5 after birth (birth day=day 1) and an estrous cycle check and lordosis behavior test were performed. As a result, vaginal opening was advanced in CM1-, CM3- or E2-treated females. A vaginal smear check indicated that oil- or GS1-treated females showed a constant 4- or 5-day estrous cycle, whereas CM1-, CM3- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovary weights in the CM1-, CM3- or E2-treated groups were lower than those in the oil- and GS1-treated groups and no corpora lutea were found in any rats of these three groups, except for two E2-treated rats. Behavioral tests were carried out after implantation of E2-tubes. All rats in the CM1-, GS1-treated groups showed a high lordosis quotient (LQ), being comparable to that in the oil-treated females. On the other hand, LQs in the CM3, E2 or male groups were lower than that in the control female group. These results suggest that a single neonatal injection of 3 mg coumestrol was effective in suppressing the functions of ovulation-inducing mechanisms and the induction of lordosis, but 1mg coumestrol was effective in only the estrous cycle of female rats.

Facilitatory effects of WAY-100635, a 5-HT1A receptor antagonist, on lordosis in female rats.

Effects of the serotonin (5-HT) receptor 1A antagonist, WAY-100635, on lordosis in female rats were examined. Ovariectomized rats were implanted with a silicon tube containing estradiol and behavioral tests were performed. Next, 5, 10 or 20 mg/kg bw WAY-100635 or saline was injected subcutaneously in female rats with a lordosis quotient (LQ) from 10 to 30 and the behavioral test was performed again. As a result, the mean LQs in 10 or 20 mg WAY-100635-treated groups were higher than in the saline-treated group (P < 0.01 and P < 0.05, 10 or 20 mg groups versus saline, respectively). In the experiment on the time-course of change in LQ after injection with 10 mg WAY-100635, the mean LQ was increased (P < 0.01, versus saline) 15 min after the injection and high levels persisted for 1 h. This finding shows that WAY-100635 has the potency to enhance lordosis behavior acutely in female rats with a low estrous state. In order to investigate relationships between the 5-HT(1A) receptor and the GABA(B) receptor in regulating lordosis, 10 mg baclofen, a GABA(B) receptor agonist, was injected and this was followed 1 h later by the injection of 10 mg/kg WAY-100635. Mean LQ decreased after the injection of baclofen (P < 0.0001, versus placebo-treated control), but the decrease in LQs was not reversed by injection with WAY-100635.

Effects of highly or relatively selective 5-HT1A receptor agonists on lordosis in female rats.

To investigate the role of serotonin (5-HT) receptor 1A or 7 in regulating lordosis behavior in female rats, ovariectomized rats were treated with 3 kinds of receptor agonists and lordosis behavior was observed. The injected agents were the selective 5-HT1A receptor agonist, buspirone (BUS), the highly selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT), and the 5-HT1A and 5-HT7 receptor agonist, (R)-8-hydroxy-2-(di-n-propylamino)tetralin ((+)8-OH-DPAT). A behavioral test was performed after ovariectomy and subcutaneous implantation of a silicon tube containing estradiol. Female rats in which the lordosis quotient (LQ) was over 70 were intraperitoneally injected with several doses of these agents. As a result, in the BUS group, the dose of 3 mg/kg bw, but not 1 mg/kg was effective for suppressing lordosis. On the other hand, an inhibitory effect was observed from 0.25 mg/kg and 0.5 mg/kg in the (+)8-OH-DPAT and (+/-)8-OH-DPAT groups, respectively. In the time-course experiment, in all drug-treated groups, LQ decreased to lower than 20 after 15 min and low LQ continued for 1 hr at least. Measurement of locomotor activity using an infrared sensor system showed no relation between the decrease in lordosis by these agents and spontaneous locomotion. These results indicate that 5-HT1A is strongly involved in the lordosis-inhibiting circuit of the serotonin neurons.

Effects of neonatal treatment with phytoestrogens, genistein and daidzein, on sex difference in female rat brain function: estrous cycle and lordosis.

It is well known that neonatal exposure to estrogen induces masculinization or defeminization of the brain. In this study, the effects of neonatal treatment with two kinds of soybean isoflavone aglycone, genistein (GS) and daidzein (DZ), on the estrous cycle and lordosis behavior were investigated. Female rats were injected subcutaneously with 1 mg GS, 1 mg DZ, 100 microg estradiol (E2), or oil daily for 5 days from birth. As a result, vaginal opening was advanced in GS- or E2-treated females. A vaginal smear check indicated that oil- or DZ-treated females showed a constant 4- or 5-day estrous cycle, whereas GS- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovaries in the GS- or E2-treated groups were smaller than those in the oil- and DZ-treated groups and contained no corpora lutea. In the DZ group, although corpora lutea were seen, ovaries were smaller than that of control females. Behavioral tests were carried out after implantation of E2-tubes. All of the oil- or DZ-treated females showed lordosis with a high lordosis quotient (LQ). On the other hand, as male rats, LQs were extremely low in the E2-treated group, when compared to the oil-treated group. In the GS-treated group, the mean LQ was lower than that in the oil-treated group, but higher than those in the E2-treated female or male groups. These results suggest that genistein acts as an estrogen in the sexual differentiation of the brain and causes defeminization of the brain in regulating lordosis and the estrous cycle in rats. In addition, neonatal daidzein also has some influence on ovarian function.