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Ibotenic acid-induced lesion of the peripeduncular area does not impair the lordosis reflex in the cyclic female rat.

In the ovariectomized, hormone-primed rat the peripeduncular area (PPA) has been reported to play a key role in sexual receptivity by integrating the sensory and endocrine inputs necessary for the elicitation of the lordosis reflex. The present study was undertaken to investigate the effect of bilateral peripeduncular lesions induced by ibotenic acid on the lordosis behavior of the normal, cyclic rat. Sexually unexperienced females received a bilateral microinjection of either ibotenic acid (n = 14; lesion group) or phosphate buffer (n = 8; sham-operated group) in the PPA. Following recovery, the receptivity expressed as the lordosis quotient was controlled in the presence of a sexually active male. The results indicate that in both groups the females display a high lordosis quotient (LQ greater than 90%). Therefore, in the cyclic female rat, the manifestation of sexual receptivity does not seem to be affected following bilateral destruction of the PPA.

Animals↗

Naloxone and initial estrogen action to induce lordosis in ovariectomized rats: the effect of a cut between the septum and preoptic area.

The effects of intra-third-ventricular (ITV) injection of naloxone (NLX), an opioid receptor antagonist, on lordosis behavior were studied in ovariectomized female rats given a horizontal half-circle cut located just above the anterior commissure (ARD) and subcutaneously (s.c.) treated with estradiol benzoate (EB) and progesterone (Prog). In ARD-sham control animals, lordosis quotient (LQ) was 78.8 +/- 4.2% (SE,n = 8). LQ (48.3 +/- 7.2%, SE, n = 8) in the ARD-sham rats significantly decreased with the ITV injection of NLX at the time of s.c. EB-priming. In contrast, lordosis reflex in the ARD-operated animals was maximally facilitated (sham versus ARD, P < 0.01). LQ in the ARD-operated rats did not decrease with the ITV injection of NLX at the s.c. EB-priming. The present results suggest that the opioidergic systems modulate an initial phase of estrogen action to induce lordosis and play a part in neural input from the forebrain structures to regulate female sexual receptivity.

Animals↗

Coordination of hamster lordosis and flank marking behavior: role of arginine vasopressin within the medial preoptic-anterior hypothalamus.

The role of arginine vasopressin (AVP) within the medial preoptic area-anterior hypothalamus (MPOA-AH) in the neural coordination of lordosis and flank marking was investigated. AVP, but not saline, microinjected into the MPOA-AH of ovariectomized hamsters not given hormone replacement therapy stimulated high levels of flank marking when tested with a sexually experienced male, or when tested alone. In contrast, AVP microinjected into the MPOA-AH of ovariectomized hamsters given estradiol benzoate (EB) and progesterone did not stimulate flank marking or inhibit lordosis during tests with a sexually experienced male. However these same females exhibited high levels of flank marking in response to AVP when tested alone. A second experiment demonstrated that progesterone was not required for inhibition of AVP-induced flank marking in ovariectomized females given EB replacement and tested with sexually experienced males. The present study provides no evidence that AVP acts within the MPOA-AH to inhibit hamster lordosis, but demonstrates that ovarian hormones and male social contact block the induction of flank marking by AVP microinjected into the MPOA-AH. These data suggest that one component in the neural coordination of lordosis and flank marking is inhibition of the response of the MPOA-AH to AVP.

Animals↗

A substance P projection from the VMH to the dorsal midbrain central gray: implication for lordosis.

Substance P has been implicated in the modulation of lordosis behavior at the level of the dorsal midbrain central gray (dMCG). Bilateral injections of substance P into the dMCG facilitate estrogen-induced lordosis behavior in ovariectomized female rats. Input from the ventromedial nucleus of the hypothalamus (VMH) to the dMCG is a vital link in the central nervous system control that mediates the expression of lordosis behavior. Substance P-containing cells have been localized in the VMH and substance P binding sites are localized in the dMCG; this suggested to us that substance P neurons originating in the VMH may terminate in the dMCG. The present study examined the projection of substance P-immunoreactive neurons (SP-IR) in the VMH to the dMCG. The present study examined the projection of substance P-immunoreactive neurons (SP-IR) in the VMH to the dMCG. The retrograde tract tracer fluorogold revealed cell bodies throughout the extent of the VMH and sP immunofluorescence labelled a subpopulation of these cells particularly in the ventrolateral part of the VMH. The majority of sP-projection cells was localized in the caudal two-thirds of the VMH. Thirteen percent of the sP-IR cells were observed to project to the dMCG, while approximately 17% of the sP-IR cells of the ventrolateral part of the VMH projected to the dMCG. These results provide morphological evidence for a substance P projection from the VMH to an area where substance P has been demonstrated to facilitate lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Progestin-facilitated lordosis of hamsters may involve dopamine-like type 1 receptors in the ventral tegmental area.

Hamsters are highly-dependent upon the central actions of progesterone (P) to facilitate sexual behavior. P has membrane mechanisms of action in the ventral tegmental area (VTA) to facilitate sexual receptivity of rodents. The present experiments examined whether P's membrane actions in the VTA include dopamine (DA) type 1 (D(1)) or dopamine type 2 (D(2)) receptors. Ovariectomized (ovx), estradiol (E(2))- and P-primed hamsters were infused with D(1) (Experiment 1) or D(2) (Experiment 2) antagonists or agonists (0 or 100 ng) to the VTA and tested 30 min later. The D(1) agonist, SKF38393, enhanced P-facilitated lordosis. The D(1) antagonist, SCH23390, attenuated P-facilitated lordosis. The D(2) agonist, quinpirole and the D(2) antagonist, sulpiride, had no significant effects on P-facilitated lordosis. These data suggest that, in hamsters, P's actions for lordosis may involve D(1) receptors in the VTA.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

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.

Animals↗

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.

Animals↗

Induction of pseudopregnancy using artificial VCS: importance of lordosis intensity and prestimulus estrous cycle length.

In cycling female rats, vaginocervical stimulation (VCS) received naturally during mating or by artificial mechanical stimulation induces neuroendocrine and behavioral responses that are critical for reproduction, including bi-circadian prolactin surges which result in pregnancy or an 8-14-day diestrous period called pseudopregnancy (PSP). Following mating, the incidence of PSP is higher when females receive high (10) as opposed to low (3-5) numbers of intromissions. Therefore, a threshold level of VCS must be exceeded before hypothalamic changes required for PSP can occur. This study characterized the threshold curve for PSP induction for artificial VCS (VCS-a). Proestrous females were given 1, 2, 3, 4, or 8 VCS-a applied with a glass rod using 200 g of force for 2 s, with an 8-min interval between stimulations. The lordosis response (LR) to the stimulus was measured on a scale of increasing intensity from 0 to 3, and the occurrence of PSP was measured by daily vaginal lavage. In contrast to previous findings, VCS-a induced robust lordosis responses without concurrent flank and perineal stimulation. The frequency of PSP induction did not increase in females as a function of amounts of VCS-a. However, the occurrence of PSP was strongly tied to the maximum lordosis response (LR(max)) observed. PSP was observed only among multiply stimulated females that showed the highest LR(max) (3.0) to at least one of the stimulations. Multiply stimulated females that showed a LR(max) < 3.0 or females that received only one VCS-a never became PSP. PSP and a stronger LR(max) were more likely to occur in females that had 5-day compared to 4-day prestimulus estrous cycle lengths. We conclude that central mechanisms important for VCS-induced PSP and lordosis may be potentiated by estradiol's actions in estrogen-concentrating forebrain areas.

Analysis of Variance↗

Differential effect of kinase A and C blockers on lordosis facilitation by progesterone and its metabolites in ovariectomized estrogen-primed rats.

Dose response curves for lordosis behavior was obtained for progesterone (P) and its two ring A-reduced metabolites: 5alpha-pregnanedione (alpha-DHP) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl) by infusing these progestins in the right lateral ventricle (rlv) of ovariectomized (ovx) estradiol-treated rats (2 microg estradiol benzoate; EB), 40 h before intracerebro-ventricular (icv) injection. Effective doses 50 (ED50) revealed that ring A-reduced progestins were more potent than P itself to induce lordosis behavior. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (ED50-ED60), were selected for testing the capacity of RpAMPS, a kinase A blocker, and H7, a kinase C blocker, to modify the response to the three progestins. rlv injection of RpAMPS significantly depressed the lordosis response to the two dose levels of P and alpha-DHP but failed to significantly inhibit that of 5alpha,3alpha-Pgl. The administration of H7 prevented the effect of both 5alpha-reduced progestins without affecting the response to P. The results suggest that P and its ring A-reduced metabolites stimulate lordosis behavior through different cellular mechanisms: P acting mainly through the cAMP-kinase system; alpha-DHP through both kinase A and kinase C signaling pathways and 5alpha,3alpha-Pgl through the kinase C system.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Attenuation of the lordosis-inhibiting effects of 8-OH-DPAT by TFMPP and quipazine.

Regularly cycling, proestrous female rats received infusions of 200 ng of the serotonin (5-HT) 1A receptor agonist, (+/-) 8-hydroxy 2-(di-n-propylamino) tetralin-HBr (8-OH-DPAT), or 200 ng 8-OH-DPAT and 1000 or 2000 ng of N-(3-trifluoro-methylphenyl) piperazine hydrochloride (TFMPP) or 2-(1-piperazinyl) quinoline dimaleate (quipazine). Infusions were made bilaterally into the ventromedial nucleus of the hypothalamus (VMN). Animals receiving 200 ng 8-OH-DPAT exhibited a decline in lordosis behavior following infusion. Rats receiving 8-OH-DPAT and 1000 or 2000 ng quipazine or TFMPP were protected from the lordosis-inhibiting effects of 8-OH-DPAT, alone. Although both quipazine and TFMPP act on multiple 5-HT receptors, they overlap in their agonist action at 5-HT2 receptors. Consequently, these results provide further evidence supporting the contention that within the VMN, both 5-HT1A and 5-HT2 receptor subtypes contribute to the modulation of lordosis behavior in the female rat. The data are discussed in terms of the relative potency of 5-HT at 5-HT receptors mediating inhibition and facilitation of lordosis behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

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.

Animals↗

Nervus terminalis lesions: II. Enhancement of lordosis induced by tactile stimulation in the hamster.

The involvement of the nervus terminalis in lordosis, induced by manual tactile stimulation, was investigated in the female hamster. Lordosis latencies were measured in response to manual lumbosacral tactile stimulation, which was performed at 5 different delay times after the previous lordotic response. Nervus terminalis lesion (TNX), control forebrain lesion (FBX), and sham (SH) surgeries were performed after preoperative data was collected, and animals were tested again postoperatively. Latencies to lordose were compared separately for each delay time between preoperative and postoperative tests. The TNX group showed small, but significant, decreases in lordosis latencies postoperatively. Lordosis latencies for the SH and FBX groups did not change. These results suggest that the nervus terminalis plays a minor role in mediating sensory processing during reproductive encounters.

Animals↗

Estrogen modulates 5-HT(1A) agonist inhibition of lordosis behavior but not binding of [(3)H]-8-OH-DPAT.

Previous studies showed that repeated estrogen treatment reduces the ability of the 5-HT(1A) receptor agonist, 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), to inhibit lordosis behavior of female rats. The present study evaluated the effects of repeated estrogen treatment on lordosis behavior and 5-HT(1A) receptor binding and coupling to G protein in the hypothalamus-preoptic area using the agonist ligand [3H]-8-OH-DPAT, which binds selectively to G-protein-coupled 5-HT(1A) receptors. Rats were injected twice with 25 or 50 microg of estradiol benzoate (EB) 7 days apart followed by 500 microg of progesterone (P) 48 h after the second EB injection. Controls received a single injection of 25 or 50 microg EB followed 48 h later by 500 microg of P. Four hours after P, 0.15 mg/kg 8-OH-DPAT was injected, and lordosis behavior examined for 30 min. Rats treated twice with EB showed significantly less 8-OH-DPAT inhibition of lordosis behavior than rats receiving a single EB injection. For receptor binding, rats received EB without P treatment. None of the estrogen treatments reduced [3H]-8-OH-DPAT binding density or affinity in the hypothalamus-preoptic area or hippocampus. These studies suggest that estrogen modulates 5-HT(1A) agonist potency without a measurable change in 5-HT(1A) receptor density or coupling to G protein.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Perinatal flutamide and mounting and lordosis behavior in adult female Wistar and Sprague-Dawley rats.

The present study was designed to investigate the possible role of perinatal androgens acting via the androgen receptor, as opposed to the estrogen receptor, for the differentiation of adult mounting and lordosis behavior in female rats. Female Wistar (W) and Sprague-Dawley (SD) rats were exposed to the anti-androgen flutamide prenatally (days 11-22 of pregnancy) and/or neonatally (days 1-10). The females were ovariectomized in adulthood and repeatedly tested for mounting and lordosis behavior. Flutamide, given both pre- and neonatally to SD rats, reduced adult T-induced female mounting. Flutamide administered only prenatally or only neonatally did not lower adult mounting behavior of SD rats. Mounting behavior of female W rats, following pre- and/or neonatal flutamide treatment was not affected. Lordosis behavior was also not altered by perinatal flutamide treatment of either strain. The results of the present study, no effect of prenatal flutamide, do not support the hypothesis that female rats require prenatal androgen receptor-mediated actions of testosterone in the organization of neural tissues for the occurrence of adult mounting and lordosis behavior. Only in SD rats androgenic organization of adult mounting behavior via the androgen receptor seems to occur both pre- and neonatally. Since clear behavioral effects of prenatal flutamide treatment have been published earlier in Long-Evans females, we suggest strain differences in sensitivity for perinatal androgenization in female rats. Future research into that possibility is needed.

Animals↗

GABA(A), D1, and D5, but not progestin receptor, antagonist and anti-sense oligonucleotide infusions to the ventral tegmental area of cycling rats and hamsters attenuate lordosis.

In hamsters, progesterone (P) in the hypothalamus and ventral tegmental area (VTA) is necessary for receptivity; in rats, hypothalamic P induces receptivity and midbrain P further enhances it. How P exerts its effects in the VTA on lordosis is of interest because few estrogen-induced P receptors (PRs) have been identified there. Sexual receptivity of rats and hamsters is enhanced when P's actions in the VTA are restricted to the membrane and when the gamma-aminobutyric acid (GABA)A agonist, muscimol, is infused into the VTA, but attenuated with infusions of the GABA(A) antagonist, bicuculline. The dopamine (DA) agonist. SKF38393, rapidly enhances receptivity when infused intravenously; this effect can be blocked by both DA receptor (DR) and PR antagonists. This study investigated the importance of PRs, glutamic acid decarboxylase (GAD), the enzyme responsible for GABA production, GABA(A) receptors (GBRs), and DRs in the VTA of cycling rats and hamsters for the expression of lordosis. Proestrous and diestrous animals implanted with bilateral VTA cannulae were pre-tested for receptivity, infused with either an antagonist (RU38486 (20 microg), bicuculline (100 ng), SCH23390 (100 ng)), anti-sense oligonucleotide (against PR (250 ng), GAD (500 ng), D1 (500 ng), D5 (250 ng)), or control infusions to each cannulae and re-tested. Vehicle and scrambled oligonucleotides were infused as controls and elicited similar effects. Antagonists of GBRs and DRs significantly reduced lordosis on post-tests compared to the PR antagonist and control conditions in rats and hamsters. Lordosis was significantly reduced, compared to controls, only by anti-sense oligonucleotides for GAD and D1- and D5-DR subtypes. These data suggest that in the VTA GABAergic and dopaminergic neurons may be more important in the mediation of sexual receptivity than neurons containing intracellular PRs.

Animals↗

Lordosis-inhibiting effect of progesterone in male and female rats with septal lesions.

The inhibitory role of progesterone (P) in regulating lordosis was investigated in male and female rats with septal lesions (SL). Male rats with SL showed lordosis quotients (LQ) as high as female rats with SL and female control rats without brain surgery after injection of 50 microg/kg estradiol benzoate (EB) followed by 0.5 mg P 44 h later. Even when primed with 5 mg P 1 h prior to the 50 microg EB-injection, the mean LQs were still high in all groups. When the dose of EB was decreased to 5 microg/kg, all rats showed high-score LQs. In contrast, all animals in both male and female in which 5 mg P was injected 1 h before 5 microg EB, showed low LQs. These results suggest that P is effective in suppressing lordosis enhanced by estrogen in either male rats or females. Furthermore, the high dose of estrogen overcomes the inhibitory action of P on lordosis in both sexes.

Animals↗

Estradiol benzoate facilitates lordosis and ear wiggling of 4- to 6-day-old rats.

The effects of exogenous and endogenous steroids on components of female sexual behavior of neonatal male and female rats were investigated. In Experiment 1, 4-day-old rats were treated with 0, 0.1, 1.0, 10, or 100 micrograms/10 g body weight estradiol benzoate (EB) and were tested 44 hr later. In Experiment 2, male rats castrated within 24 to 48 hr of birth were compared with sham operated controls and castrates given steroid replacement. The results indicated that most 6-day-old pups will display lordosis and ear wiggling; therefore, the display of these responses is not dependent upon exogenous steroids. However, a fine-grained behavioral analysis revealed that EB treatment increased the frequency, duration, and intensity of lordosis and the frequency of ear wiggling in infant females, and it increased lordosis duration in males. Castration of infant males decreased the likelihood that male infants would display lordosis, whereas testosterone replacement restored behavior to control levels. These data question the concept that organizational and activational actions of estrogens occur during completely separable times in development and should provide new insights into the development of estrogen receptor function and the process of sexual differentiation of brain and behavior.

Animals↗

Connections between the pontine central gray and the ventromedial hypothalamus are essential for lordosis in female rats.

Lesions and knife cuts were used to study central gray (CG) and ventromedial hypothalamic (VMH) mediation of sexual receptivity in female rats. Lesions of the midbrain-pontine CG eliminated lordosis in female rats. Bilateral sagittal knife cuts that bracketed the rostral pontine CG also eliminated lordosis, and an experiment with the retrograde tracer Fluoro-Gold confirmed the effectiveness of these cuts in severing the lateral connections linking the VMH and the CG. Finally, females with a unilateral hypothalamic cut combined with a contralateral CG transection almost never showed lordosis. Each cut, at a different level for each side of the brain, transected axons linking the VMH and the CG. The demonstration that this combination eliminated lordosis provides new evidence that the lateral connections between the VMH and the CG are essential for the display of sexual receptivity in female rats.

Afferent Pathways↗