Inhibition Of Lordosis Research Articles

Optogenetic Activation of β-Endorphin Terminals in the Medial Preoptic Nucleus Regulates Female Sexual Receptivity.

Estrogen and progesterone (P4) act in neural circuits to elicit lordosis, the stereotypical female sexual receptivity behavior. Estradiol acts through membrane receptors to rapidly activate a limbic-hypothalamic circuit consisting of the arcuate (ARH), medial preoptic (MPN), and ventromedial (VMH) nuclei of the hypothalamus. This initial activation results in a transient but necessary inhibition of lordosis, which appears to be a result of the release of β-endorphin (β-End) from proopiomelanocortin (POMC) terminals onto cells containing the µ-opioid receptor (MOR) in the MPN. To functionally examine the role of the MOR in the hypothalamic lordosis circuit, we transfected a channelrhodopsin (ChR2) adeno-associated virus into POMC cell bodies in the ARH and photostimulated POMC/β-End axon terminals in the MPN in sexually receptive female Pomc-cre mice. Following estrogen and P4 priming, sexual receptivity was assessed by measuring the lordosis quotient (LQ). Following an initial trial for sexual receptivity, mice were photostimulated during behavioral testing, and brains were processed for MOR immunohistochemistry (IHC). Photostimulation decreased the LQ only in ChR2-expressing Pomc-cre mice. Furthermore, photostimulation of ChR2 in POMC/β-End axon terminals in the MPN resulted in the internalization of MOR, indicating activation of the receptor. Our results suggest that the activation of the MOR in the MPN is sufficient to attenuate lordosis behavior in a hormone-primed, sexually receptive female mouse. These data support a central role of MOR in female sexual behavior, and provide further insight into the hypothalamus control of sexual receptivity.

Participation of progesterone receptors in facilitation and sequential inhibition of lordosis response induced by ring A-reduced progesterone metabolites in female mice.

Sexual receptivity in female rodents induced by the sequential injection of estrogen and progesterone is followed by a period in which females do not respond behaviorally to a second administration of progesterone (P); this is known as sequential inhibition. It has been proposed that the induction of sequential inhibition by progesterone in rats depends on down regulation of the progesterone receptor (PR) in brain areas involved in the expression of female sexual receptivity. P is rapidly metabolized to a variety of 5α- or 5β-ring A-reduced progestins (RPrg). These RPrg have little or no affinity for the PR. They stimulate sexual receptivity (lordosis) more potently than P itself in estrogen-primed rats and do not induce sequential inhibition. The purpose of the current study was to test the role of the PR in the facilitation of lordosis and sequential inhibition induced by P and the following RPrg: 5α-pregnandione (5α-DHP), 5α,3β-pregnanolone (5α,3β-Pgl), 5β-pregnanedione (5β-DHP), and 5β,3α-pregnanolone (5β,3α-Pgl) in ovariectomized (ovx) female mice primed with estradiol benzoate. The RPrg were tested in C57BL/6 mice and in a strain lacking the progesterone receptor expression (PRKO). Our results show that both facilitation and sequential inhibition of lordosis induced by progesterone require the presence of the progesterone receptor. Interestingly, some RPrg facilitate lordosis but do not induce sequential inhibition in female mice. Sexual receptivity induced by RPrg does not require the progesterone receptor. Thus, RPrg induce sexual receptivity, but they probably exert their effects through a different cellular mechanism that does not involve the progesterone receptor. (PsycINFO Database Record

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. However, the progesterone metabolite, allopregnanolone (3α-hydroxy-5α-pregnan-20-one), also prevents lordosis inhibition after restraint. In a prior study, we reported that the progestin receptor antagonist, RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), attenuated the effect of allopregnanolone. Because RU486 can also block the glucocorticoid receptor, in the current studies, we evaluated the effect of the progestin receptor antagonist, CDB-4124 (17α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione), which is relatively devoid of antiglucocorticoid activity. Ovariectomized, Fischer rats were injected with 10μg estradiol benzoate. Two days later, rats received either 60mg/kg CDB-4124 or 20% DMSO/propylene glycol vehicle 1h before injection with 4mg/kg allopregnanolone. After a pretest to confirm sexual receptivity, rats were restrained for 5min and immediately tested for sexual behavior. Lordosis behavior was reduced by the restraint and attenuated by allopregnanolone. Pretreatment with CDB-4124 reduced allopregnanolone's effect. These findings support prior suggestions that allopreganolone reduces the response to restraint by mechanisms that require activation of the intracellular progesterone receptor.

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

The selective serotonin reuptake inhibitor (SSRI), fluoxetine (Prozac®), is an effective antidepressant that is also prescribed for other disorders (e.g. anorexia, bulimia, and premenstrual dysphoria) that are prevalent in females. However, fluoxetine also produces sexual side effects that may lead patients to discontinue treatment. The current studies were designed to evaluate several predictions arising from the hypothesis that serotonin 1A (5-HT 1A) receptors contribute to fluoxetine-induced sexual dysfunction. In rodent models, 5-HT 1A receptors are potent negative modulators of female rat sexual behavior. Three distinct experiments were designed to evaluate the contribution of 5-HT 1A receptors to the effects of fluoxetine. In the first experiment, the ability of the 5-HT 1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-2-pyridinylcyclohexanecarboxamide (WAY100635), to prevent fluoxetine-induced lordosis inhibition was examined. In the second experiment, the effects of prior treatment with fluoxetine on the lordosis inhibitory effect of the 5-HT 1A receptor agonist, (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT), were studied. In the third experiment, the ability of progesterone to reduce the acute response to fluoxetine was evaluated. WAY100635 attenuated the effect of fluoxetine; prior treatment with fluoxetine decreased 8-OH-DPAT's potency in reducing lordosis behavior; and progesterone shifted fluoxetine's dose–response curve to the right. These findings are consistent with the hypothesis that 5-HT 1A receptors contribute to fluoxetine-induced sexual side effects.

Alpha and beta noradrenergic mediation of NMDA glutamatergic effects on lordosis behaviour and plasmatic LH concentrations in the primed female rat

In previous studies we have found that blockade of NMDA (N-Methyl-D-Aspartic-Acid)-type glutamatergic receptor with intracerebroventricular (ICV) selective drugs induces an inhibition of lordosis in ovariectomized (OVX) estrogen primed rats receiving progesterone or luteinizing hormone releasing hormone (LHRH). By the opposite way, stimulation with NMDA in OVX estrogen primed rats induced a significant increase of lordosis. In the present study the action of an alpha1-noradrenergic antagonist, HEAT (BE 2254/2-beta-4-Hydroxyphenyl-Ethyl-Aminomethyl-1-Tetralone), and Metoprolol, a beta-noradrenergic antagonist, were studied injecting them ICV previously to NMDA administration in treated OVX estrogen primed rats. In experiment 1, the enhancing effect on lordosis induced by NMDA at high dose (1 microg) was abolished by HEAT administration (P < 0.001 for 3 and 6 microg), and the LH plasma levels were decreased only with the higher dose (P < 0.05), suggesting that behavioral effects are quite more sensitive to the alpha-blockade than hormonal effects. In experiment 2, enhancing effects on lordosis behavior were not observed with neither the NMDA at low dose (0.5 microg) nor the metoprolol alone (5.71 microg), but a synergism was observed when both were simultaneously administered (P < 0.001). The LH plasma levels were increased by Metoprolol alone (P < 0.05), and powered by the combination with NMDA at low dose (P < 0.01 vs. SAL and NMDA alone); no differences were observed with Metoprolol. LH increase was observed with Metoprolol even without behavioural modifications. These findings strongly suggest that facilitatory and inhibitory effects of NMDA in this model are mediated by alpha- and beta-adrenergic transmission in both, behavioral and hormonal effects.

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

Ovariectomized rats were hormonally primed with 10 μg estradiol benzoate or with estradiol benzoate plus 500 μg 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. There were no effects in rats hormonally primed with estrogen and progesterone. Handling for two days before the experiment reduced the effects of the infusions in estrogen-primed rats. However, when a 5 min restraint experience followed infusion with GR 127935, there was a significant decline in lordosis behavior that persisted for 10 to 15 min after the experience. Regardless of the prior experience or type of infusion, the addition of progesterone to the hormonal priming completely prevented the lordosis inhibition. These findings are consistent with prior evidence that progesterone protects against the inhibitory effects of a 5 min restraint experience on lordosis behavior. Moreover, these are the first experiments to demonstrate an inhibitory effect of a selective 5-HT 1B/1D receptor antagonist in the VMN on lordosis behavior of estrogen primed, but not estrogen and progesterone primed, ovariectomized rats.

The effects of partial and complete masculinization on the sexual differentiation of nuclei that control lordotic behavior in the male rat

Male rats, under certain experimental conditions, may show lordosis, the typical expression of female sexual receptivity. This work studies the sexual morphological pattern of facilitatory and inhibitory structures that control lordosis. Three groups of males were neonatally subjected to a gradient of androgen exposure (castrated plus injected oil (GxM + oil); castrated plus androstenedione treated (GxM + AND); and sham operated [CM]); a group of control females (CF) was also added. Lordotic response after these different hormonal and neonatal surgical treatments, as well as the volume or number of neurons in facilitatory (ventromedial nucleus of the hypothalamus [VMN]) and inhibitory (the intermediate region of the lateral septum [LSi] and accessory olfactory bulb [AOB]) nuclei involved in lordosis was studied in adults. The inhibition of lordosis in the males seems to be associated to the neonatal presence of testosterone and the consequent masculinization of the VMN, VMNvl, LSi and AOB. It is suggested that one of the functions of the sex differences consistently seen in these structures might be to inhibit the lordosis response in the male.

Environmental-Like Exposure to Low Levels of Estrogen Affects Sexual Behavior and Physiology of Female Rats

Xenoestrogens are endocrine-disrupting chemicals that mimic the action of endogenous estrogen hormones. Effects of xenoestrogen on aquatic wildlife are well documented, whereas the experimental evidence for impairment of reproductive behavior and physiology in mammals after exposure to xenoestrogens has been debated. The strongest arguments against such studies have been that the route, time course, and intensity of exposure did not simulate environmental exposure and that the chemicals tested have additional nonestrogenic toxic effects, hindering generalization of actual xenoestrogenic effects. Here we show that environmental-like exposure to the pure estrogen 17alpha-ethinylestradiol during development alters reproductive behavior and physiology in adult female Sprague-Dawley rats. We simulated environmental exposure by giving low doses (0.4 and 0.004 microg/kg.d) of 17alpha-ethinylestradiol orally to pregnant females from conception to weaning of the pups, which continued to receive the treatment until puberty. We studied the sexual behavior, estrous cycle, and estradiol plasma levels of intact female rats when they reached 3 months of age. Exposure to the higher dose strongly affected female sexual behavior and physiology, with suppression of lordosis and the estrous cycle and enhanced aggression toward males. The lower dose disrupted appetitive components of sexual behavior that influence the rate of copulation. Estradiol plasma levels were not affected by the treatment. Our study revealed that exposure to low oral doses of a pure estrogen during development alters female sexual behavior and physiology. These results suggest potential risks of reproductive failure from xenoestrogen exposure in realistic ecological conditions.

Additive inhibition of lordosis by simultaneous treatments with GABA A and GABA B receptor agonists, muscimol and baclofen, in female rats

In order to investigate the relationship between GABA A and GABA B receptors in the induction of lordosis behavior, agonists of these receptor subtypes were injected simultaneously to estrogen-treated ovariectomized rats and lordosis behavior was observed before and after the injections. The GABA A receptor agonist, muscimol (MUS), at a dose in the range from 1.0 to 1.4 mg/kg body weight (bw) or the GABA B receptor agonist, baclofen (BAC) at a dose in the range from 1 to 10 mg/kg bw, was injected intraperitoneally. The lordosis quotient (LQ) decreased after treatments with MUS or BAC and a dose-dependent decrease of LQ was observed in MUS or BAC-treated rats. When 1.2 mg/kg bw MUS and 5 mg/kg bw BAC were injected simultaneously, the mean LQ decreased strongly and was significantly lower than the values obtained after single injections of the agonists at these doses ( P < 0.05). In addition, to ascertain the time-course of changes, a behavioral test was carried out 7 times from 15 to 180 min after the injection of agonists. The low LQ in the rats injected with both MUS and BAC continued longer than in rats given single injections. These results indicate that both GABA A and GABA B receptors are involved in lordosis-inhibiting mechanisms by the GABA neuron and operate independently.

Sex Differences in Serotonergic But Not γ-Aminobutyric Acidergic (GABA) Projections to the Rat Ventromedial Nucleus of the Hypothalamus

Hormonal conditions that elicit lordosis in female rats are ineffective in males, suggesting that this behavior is actively suppressed in males. Previous studies theorize that serotonergic and gamma-aminobutyric acidergic (GABA) inputs to the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMNvl) may contribute to lordosis inhibition in males. Using triple-label immunofluorescent techniques, the present studies explored potential sex differences in the density of these projections within three hypothalamic sites: the VMNvl, the arcuate nucleus (ARC), and the dorsomedial nucleus of the hypothalamus. Antibodies directed against HuC/D, estrogen receptor (ER)-alpha and either serotonin (5-HT) or the gamma-aminobutyric acid synthetic enzyme glutamic acid decarboxylase-65 were used to compare the densities of glutamic acid decarboxylase (GAD)-65- and 5-HT-containing fibers in each brain area, the percentage of VMNvl HuC/D immunoreactive (ir) neurons that contained ERalpha, and the percentage of HuC/D and ERalpha double-labeled cells receiving apparent contacts from 5-HT fibers between adult, gonadectomized male and female rats. The densities of VMNvl and ARC 5-HT immunolabeled fibers were significantly higher in the males, and the percentage of VMNvl HuC/D-ir neurons containing ERalpha was significantly higher in the females. The percentage of HuC/D-ir cells contacted by 5-HT fibers was significantly higher in the males, compared with the females, but there was no sex difference in the proportion of those cells receiving contacts that were ERalpha-ir. Neonatal administration of estradiol but not genistein masculinized 5-HT content in the adult female VMNvl, but the percentage of HuC/D-ir cells colabeled with ERalpha was not significantly affected by treatment. A similar, but not statistically significant, pattern was observed in the ARC. These findings suggest that the development of serotonergic inputs to the male VMNvl is orchestrated by neonatal estradiol exposure. The hormone-dependent organization of these 5-HT projection patterns may be an important developmental mechanism accounting for sex-specific behaviors in adulthood.

Role of glutamate receptors in the ventromedial hypothalamus in the regulation of female rat sexual behaviors: I. Behavioral effects of glutamate and its selective receptor agonists AMPA, NMDA and kainate

Bilateral infusions of glutamate or kainate to the ventromedial hypothalamus (VMH) have been shown previously to produce a rapid inhibition of lordosis in estrogen-primed female rats induced by manual flank stimulation. The present study examined whether glutamate or selective ionotrophic glutamate receptor agonists can disrupt appetitive and consummatory sexual behaviors following bilateral infusions to the VMH of females during copulation with male rats. Ovariectomized, sexually experienced female rats were implanted bilaterally with guide cannulae aimed at the ventrolateral VMH. After recovery from surgery, females were primed with estradiol benzoate and progesterone and infused with different doses of glutamate, AMPA, NMDA or kainate ( n = 9–10 in each dose group) 3 min prior to a test with sexually vigorous males in bilevel chambers. Glutamate infusions decreased the display of hops and darts and produced a trend toward decreased lordosis. AMPA infusions decreased the display of solicitations, hops and darts, and lordosis. NMDA infusions decreased lordosis and increased defensive behaviors and pacing. Kainate infusions decreased solicitations, hops and darts, and lordosis, and increased defensive behaviors and pacing. These data indicate that the activation of glutamate receptors in the VMH is inhibitory for both appetitive and consummatory aspects of sexual behavior in the female rat.

Medial preoptic area δ-opioid receptors inhibit lordosis

Endogenous opioid peptides that activate the δ-opioid receptor (DOR) are thought to facilitate female receptive behavior. This facilitation of lordosis has been demonstrated by intracerebroventricular infusions and injection of DOR-active ligands into the ventromedial hypothalamic nucleus, an area with robust DOR binding. However, DOR binding is distributed throughout the hypothalamus, and the role of DOR in other areas of the hypothalamus has not been examined. In the current study, we demonstrated DOR immunoreactivity in the medial preoptic area (MPO), in particular medial preoptic nucleus (MPN) of the preoptic area. DOR immunoreactive processes were sparsely distributed in the medial and lateral parts of the MPN. Larger DOR immunoreactive fibers were localized in the ventrolateral aspect of the lateral MPN. The MPN is involved in the modulation of female sexual receptivity and the distribution of DOR in this area suggested to us that DOR may regulate lordosis. Ovariectomized rats with unilateral cannulae aimed at the MPN were given 5 μg 17β-estradiol benzoate (EB), once every 4 days and tested for lordosis. [D-Pen 2, D-Pen 5]-enkephalin (DPDPE), a DOR agonist, microinfused into the MPO, 52–54 h after EB-priming, inhibited lordosis when compared with the aCSF (vehicle) control ( P ≤ 0.05). The inhibitory effects of DPDPE were reversed by microinjection of naltrindole, a DOR antagonist ( P ≤ 0.05). Interestingly, the DOR inhibition of lordosis is similar to the μ-opioid receptor inhibition of lordosis in the MPN. These results indicate that DOR in the MPO, particularly in the MPNm, plays an important role in the regulation of lordosis.

Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats.

The endogenous peptides beta-endorphin (beta-END) and neuropeptide Y (NPY) have been implicated in regulating sexual receptivity. Both beta-END and NPY systems are activated by estrogen and inhibit female sexual receptivity. The initial estrogen-induced sexual nonreceptivity is correlated with the activation and internalization of mu-opioid receptors (MORs), in the medial preoptic nucleus (MPN). Progesterone reverses the estrogen-induced activation/internalization of MOR and induces the sexual receptive behavior lordosis. To determine whether NPY and endogenous opioids interact, we tested the hypothesis that estrogen-induced MOR activation is mediated through NPY-Y1 receptor (Y1R) activation. Retrograde tract tracing demonstrated Y1Ron beta-END neurons that projected to the MPN. Sex steroid modulation of MOR in the MPN acts through NPY and the Y1R. Estradiol administration or intracerebroventricular injection of NPY activated/internalized Y1R in the arcuate nucleus and MOR in the MPN of ovariectomized (OVX) rats. Moreover, the selective Y1R agonist [Leu31, Pro34]-Neuropeptide Y (LPNY) internalized MOR in the MPN of OVX rats. The Y1R antagonist (Cys31, Nva34)-Neuropeptide Y (27-36)2 prevented estrogen-induced Y1R and MOR activation/internalization. NPY reversed the progesterone blockade of estradiol-induced Y1R and MOR internalization in the arcuate nucleus and MPN, respectively. Behaviorally, LPNY inhibited estrogen plus progesterone-induced lordosis, and the MOR-selective antagonist D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr amide reversed LPNY-induced inhibition of lordosis. These results suggest that a sequential sex steroid activation of NPY and MOR circuits regulates sexual receptivity.

Inhibition of Lordosis Behavior in Male and Female Rats by Androgens and Progesterone

Several studies suggest that when manipulated experimentally in adulthood, the lordosis response to estrogen can be increased dramatically in male rats. Because adult-gonadectomized (Gx) animals were used in these studies, the lack of testicular hormones in adulthood may have been a factor. To examine this possibility, adult-Gx rats were implanted with blank (Bk)-, testosterone (T)-, 5α-dihydrotestosterone (DHT)-, or progesterone (P)-filled capsules, alone or in combination. We report a new finding, that a combined treatment of T plus P (T+P) at physiological doses for the male, but not T or P alone, reduced lordosis significantly in males, with and without estrogen priming. T+P did not inhibit lordosis in females, nor did this specific treatment affect open field, aggressive, and male copulatory behaviors. In confirming studies done with much higher doses, DHT reduced lordosis in both sexes. DHT and T+P also reduced lordosis in adrenalectomized/Gx males. Mechanisms responsible for the T+P inhibition of lordosis in males are not known, but they may include an upregulation of androgen receptors by P, and this possibility is discussed.

Facilitatory and Inhibitory Effects of β-Endorphin on Lordosis in Female Rats: Relation to Time of Administration

The purpose of the present study was to investigate the effect of time of β-endorphin (β-EP) administration on lordosis in ovariectomized female rats injected subcutaneously (sc) with estradiol benzoate (EB) and progesterone (Prog). Intracerebroventricular (icv) injections of β-EP and naloxone (NLX), an opioid receptor antagonist, were administered at the various stages of sc steroid hormone priming. Facilitation of lordosis induced by 10 μg β-EP was observed exclusively within the initial 6 h of estrogen action, after which inhibition of lordosis occurred. At 12 h after EB priming, at the time of sc Prog treatment (or 43 h after EB priming), icv injection of 10 μg β-EP significantly inhibited lordosis. Lordosis was significantly facilitated by icv injections of 1 and 10 μg β-EP at the time of sc EB priming, but not by 0.1 μg β-EP. A dose–response relationship was identified for lordosis in experimental animals receiving icv injection of β-EP. Lordosis was inhibited by icv injections of 1 and 10 μg β-EP at 1 h before the test (or 47 h after EB priming). Lordosis was significantly inhibited by icv injection of NLX at all stages. From the present results, it seems that two different mechanisms are involved in endorphinergic modulation of rats' sexual receptivity: (a) the endorphinergic system at the initial stages of estrogen action facilitates the estrogen activation of lordosis; (b) the endorphinergic system at the final stages of steroid action inhibits lordosis. Moreover, there exists a critical time between 6 and 12 h after estrogen priming for endorphinergic mediation to modulate estrogen action.

Gonadal steroid-dependent GAL-IR cells within the medial preoptic nucleus (MPN) and the stimulatory effects of GAL within the MPN on sexual behaviors.

More GAL-I cells exist within sexually dimorphic cell groups of the medial preoptic nucleus (MPN) in male rate than females, a large percentage of estrogen-concentrating cells within MPN cell groups are also GAL-immunoreactive (GAL-IR), and significantly more GAL-IR cells are visible with estrogen or its precursor, testosterone. Gonadal steroids also increase the size (diameter) of MPN GAL-IR cells and the number of GAL-IR cell processes within a portion of the MPN called the "GAL-IR MPOA plexus," which exists in males only. GAL microinjected into the MPN stimulated male-typical sexual behaviors, with more testosterone required in females than males. Immunoneutralization with anti-GAL serum inhibited male-typical sexual behavior, indicating a role for endogenous GAL within the MPN. Microinjection of GAL into the MPN also stimulated female-typical sexual behaviors in estrogen-treated females and males, and GAL within the MPN dramatically overrode an inhibition of lordosis by dihydrotestosterone in rats of both sexes.

Aflatoxin B 1 and Reproduction: I. Reproductive Performance in Female Rats

An experimental group of female rats was exposed to aflatoxin B1 at a dose of 7.5 mg/kg body weight daily for 14 days through oral intubation. A deleterious effect on the gonads and embryotoxicity in the experimental animals were observed. There were reductions in ovarian and uterine sizes, increases in fetal resorption, implantation loss, and intra-uterine death. The data showed significant disturbances in oestrus cycle, inhibition of lordosis, and reductions in the conception rates and litter sizes, suggesting severe impairment of fertility in the aflatoxin exposed rats. An aflatoxin blood level of 86.2 +/- 1.3 ppb was recovered in the experimental animals.

Leptin facilitates and inhibits sexual behavior in female hamsters.

Food deprivation decreases fertility in female mammals in part by inhibiting sexual behaviors. Genetically obese ob/ob mice, like food-deprived wild-type animals, are also infertile; treatment of ob/ob mice with leptin, the adipocyte-derived protein that they lack, corrects some of their reproductive deficiencies. We tested the hypothesis that leptin treatment would prevent the suppression of sexual receptivity that is caused by food deprivation in female Syrian hamsters. Instead, we found that treatment with murine leptin facilitated female sexual behavior in ad libitum-fed hamsters, but not in food-deprived animals. In food-deprived hamsters, leptin treatment actually intensified the inhibition of lordosis. Food deprivation decreased detectable estrogen receptor immunoreactivity (ERIR) in the ventromedial hypothalamus (VMH), but the leptin-induced changes in female sexual behavior were not accompanied by parallel changes in VMH ERIR. Thus leptin facilitates estrous behavior in hamsters, but it does not overcome the lordosis-inhibiting metabolic cues produced by acute food deprivation. Because circulating leptin levels are directly related to body fat content, an implication of these findings is that elevated levels of adipose tissue could have a positive influence on sexual responsiveness.

Inhibition of lordosis in female hamsters and rats by 8-OH-DPAT treatment

In the present experiments, the ability of the 5-HT 1A agonist, 8-OH-DPAT, to inhibit lordosis was determined in ovariectomized hamsters and rats under various hormonal conditions. Systemic administration of 8-OH-DPAT (0.25 mg/kg) significantly inhibited lordosis duration in ovariectomized hamsters treated on 3 consecutive wk with estradiol benzoate (3 or 10 μg) and progesterone (500 μg). Similarly, systemic administration of 8-OH-DPAT (0.25 mg/kg) significantly inhibited lordosis frequency in ovariectomized rats treated on 3 consecutive wk with estradiol benzoate (0.25, 0.5, or 25 μg for 3 days) and progesterone (500 μg), although females treated with the higher doses of estrogen were slightly less inhibited on the second and third wk of testing. Results indicate that the 5-HT 1A agonist, 8-OH-DPAT, effectively inhibited lordosis in female hamsters, as well as female rats, under varied hormonal conditions.

Effects of hormonal treatment and history on scopolamine inhibition of lordosis

The muscarinic receptor blocker, scopolamine, inhibits the display of lordosis behavior in female rats but its effectiveness depends on hormonal conditions. In these experiments, systemic administration of scopolamine (0.031–4 mg/kg) inhibited lordosis in ovariectomized rats brought into receptivity by treatment with a low dose of estradiol benzoate (EB, 0.25 μg for 3 days) with progesterone (P, 500 μg for 1 day), or a high dose of EB (25 μg for 3 days) with and without P. However, the effectiveness of scopolamine was reduced at the high dose of EB and with the addition of P. Furthermore, scopolamine failed to inhibit lordosis in females treated on a second week with the high dose of EB with or without P, unless an interval of at least 3 weeks separated the two sets of steroid treatments. The reduced effectiveness of scopolamine cannot be explained by peripheral mechanisms because its inhibitory effect on lordosis also was reduced following repeated hormonal exposure even when scopolamine was infused directly into the lateral ventricles.