Regulation Of Female Sexual Behavior Research Articles

Hormonal and circuit mechanisms controlling female sexual behavior.

Sexual behavior is crucial for reproduction in many animals. In many vertebrates, females exhibit sexual behavior only during a brief period surrounding ovulation. Over the decades, studies have identified the roles of ovarian sex hormones, which peak in levels around the time of ovulation, and the critical brain regions involved in the regulation of female sexual behavior. Modern technical innovations have enabled a deeper understanding of the neural circuit mechanisms controlling this behavior. In this review, I summarize our current knowledge and discuss the neural circuit mechanisms by which female sexual behavior occurs in association with the ovulatory phase of their cycle.

Regulation of female sexual behavior and possibilities of drug therapy

Female sexual behavior is under the complex influence of psycho-emotional, neuroendocrine and social factors. The realization of normal sexual activity in women is possible if many conditions are met and, first of all, ensuring a positive psycho-emotional background, safety, a satisfactory state of health, as well as comfortable interpersonal relationships for most women. In addition to significant psychological and social impact, accumulated modern scientific data confirm the important role of neuro-hormonal regulation of sexual behavior and suggest the potential effectiveness of pharmacological therapy. Unfortunately, however, medical strategies for correcting female sexual disorders are limited. Currently, in some countries, several drugs that increase female sexual activity are allowed for use, however, all of them are not registered and are not approved for use on the territory of the Russian Federation. The article briefly describes the neural mechanisms of the main areas of the central nervous system underlying receptivity and sexual attraction, namely the olfactory and limbic systems, the neocortex. The main attention is paid to the function of neurotransmitters and hormones that are critically involved in the modulation of emotions and sexual behavior, including the inhibitory mediator of gamma aminobutyric acid (GABA), estrogens, testosterone, and the excitatory mediator glutamate. The stages of development, the results of experimental and clinical studies to assess the effectiveness and safety of the unique Russian neuropeptide drug Desirex, which is a stimulant of sexual behavior due to the mechanism of reversible suppression of the GABAergic system, nonspecific stimulation of the dopaminergic system of motivation and reinforcement of positive emotions and disinhibition of the controlling function of the neocortex, are presented in detail.

Female Reproductive Behavior.

Reproductive behavior is the behavior related to the production of offspring and includes all aspects from the establishment of mating systems, courtship, sexual behavior, and parturition to the care of young. In this chapter, I outline the hormonal regulation of the estrous cycle, followed by a description of the neural regulation of female sexual behavior. Ovarian hormones play an important role in the induction of ovulation and behavioral estrus, in which they interact closely with several neurotransmitters and neuropeptides to induce sexual behavior. This chapter discusses the latest research on the role of estrogen, progesterone, serotonin, dopamine, noradrenaline, oxytocin, and GABA in female mating behavior. In addition, the most relevant brain areas, such as the preoptic area and the ventromedial nucleus of the hypothalamus, in which these regulations take place, are discussed.

Fezf1 is a novel regulator of female sex behavior in mice

Female sexual behavior is a complex process regulated by multiple brain circuits and influenced by sex steroid hormones acting in the brain. Several regions in the hypothalamus have been implicated in the regulation of female sexual behavior although a complete circuitry involved in female sexual behavior is not understood. Fez family zinc finger 1 (Fezf1) gene is a brain specific gene that has been mostly studied in the context of olfactory development, although in a recent study, FEZF1 has been identified as one of the genes responsible for the development of Kallman syndrome. In the present study, we utilized shRNA approach to downregulate Fezf1 in the ventromedial nucleus of the hypothalamus (VMN) with the aim to explore the role of this gene. Adult female mice were stereotaxically injected with lentiviral vectors encoding shRNA against Fezf1 gene. Mice injected with shRNA against Fezf1 had significantly reduced female sexual behavior, presumably due to the downregulation of estrogen receptor alpha (ERα), as the number of ERα-immunoreactive cells in the VMN of Fezf1 mice was significantly lower in comparison to controls. However, no effect on body weight or physical activity was observed in mice with downregulated Fezf1, suggesting that the role of Fezf1 in the VMN is limited to the regulation of sexual behavior. Significance statementFezf1 gene has been identified in the present study as a regulator of female sexual behavior in mice. Regulation of the female sexual behavior could be through the regulation of estrogen receptor alpha expression in the ventromedial nucleus of the hypothalamus, as the expression of this receptor was reduced in mice with downregulated Fezf1. As expression of Fezf1 is very specific in the brain, this gene could present a potential target for the development of novel drugs regulating hypoactive sexual desire disorder in women, if similar function of FEZF1 will be confirmed in humans.

On the role of brain aromatase in females: why are estrogens produced locally when they are available systemically?

The ovaries are often thought of as the main and only source of estrogens involved in the regulation of female behavior. However, aromatase, the key enzyme for estrogen synthesis, although it is more abundant in males, is expressed and active in the brain of females where it is regulated by similar mechanisms as in males. Early work had shown that estrogens produced in the ventromedial hypothalamus are involved in the regulation of female sexual behavior in musk shrews. However, the question of the role of central aromatase in general had not received much attention until recently. Here, I will review the emerging concept that central aromatization plays a role in the regulation of physiological and behavioral endpoints in females. The data support the notion that in females, brain aromatase is not simply a non-functional evolutionary vestige, and provide support for the importance of locally produced estrogens for brain function in females. These observations should also have an impact for clinical research.

The role of adrenoceptors in the central nervous system in male and female rat sexual behavior

Three different phases can be distinguished in rats’ sexual cycle, the introductory (precopulatory), the copulatory and the executive (ejaculatory) phases. In this review, a new analysis of existing pharmacological data is made, both in male and female rats, in which the different aspects of sexual behavior are taken into account. An effort is made to distinguish pharmacological effects on sexual behavior from a possible physiological role of noradrenaline. In addition, new data on the role of α2-adrenoceptors on female sexual behavior is presented.The new analysis suggests that noradrenaline has a stimulatory role on the executive phase of male sexual behavior, while the introductory and copulatory phases remain unaffected. Adrenoceptors play a role in the regulation of sexual behavior in the medial preoptic area and the lateral septum. In female rats, noradrenaline also does not play a vital role in the introductory phase. Only the lordosis behavior of the copulatory phase is sometimes affected by adrenergic agents, but only under a certain hormonal condition. The medial preoptic area, the ventromedial nucleus, the arcuate ventromedial nucleus and median eminence are involved in the regulation of female sexual behavior. The new data suggest that α2-adrenoceptors play no major role on any indices of female sexual behavior.

Effects of sex steroids and estrogen receptor agonists on the expression of estrogen receptor alpha in the principal division of the bed nucleus of the stria terminalis of female rats

Estrogen actions on neurons of the principal division of the bed nucleus of the stria terminalis (BNSTpr) are essential for the regulation of female sexual behavior. However, little is known about the effects of estradiol and progesterone (P) on estrogen receptor alpha (ERα) expression in this nucleus. To study this subject, we used stereological methods to estimate the total number of ERα-immunoreactive (ERα-ir) neurons in the BNSTpr of female rats at each stage of the estrous cycle and of ovariectomized rats after administration of estradiol benzoate (EB) and/or P. To ascertain the percentage of ERα-positive neurons in the BNSTpr, the total number of neurons in this nucleus was also estimated. In order to identify the specific role played by the selective activation of each ER in the expression of ERα, ovariectomized rats were injected with the ERα agonist, propyl-pyrazole triol (PPT), or the ERβ agonist, diaryl-propionitrile (DPN). Data show that ERα is expressed in 40–60% of the BNSTpr neurons and that the number of ERα-ir neurons is lowest at proestrus. This value is paralleled by the administration of EB. The number of ERα-ir neurons was not modified by P. PPT induced no changes in the number of ERα-ir neurons. Contrariwise, DPN induced a decrease in the total number of ERα-ir neurons to values similar to those of EB-treated rats. These results show that P has no effect in the modulation of ERα expression and demonstrate that estradiol regulation of ERα in BNSTpr neurons is mediated by activation of ERβ.

Ivermectin reduces sexual behavior in female rats

Ivermectin (IVM) is an antiparasitic drug that is widely used in domestic animals. In mammals, IVM acts as a γ-aminobutyric acid (GABA) receptor agonist. This neurotransmitter plays an important role in the regulation of female sexual behavior. The present study investigated the effects of therapeutic (0.2mg/kg) and high (1.0mg/kg) IVM doses on female sexual behavior in physiological and pharmacological conditions. Female rats in estrus or treated with estradiol valerate to induce sexual behavior 24h before the experiments were used. Ivermectin was administered 15min before the sexual observations. The number of lordosis events in 10 mounts was recorded to calculate the lordosis quotient. The intensity of lordosis (0 [no lordosis], 1 [low lordosis], 2 [normal lordosis] and 3 [exaggerated lordosis]) was scored. In estrus and hormonal treated female rats, both IVM doses decreased the intensity of the lordosis reflex and the percentage of females that presented high levels of lordosis (exaggerated lordosis). However, the number of females that presented lordosis was unaltered. We conclude that in both hormonal conditions, 0.2mg/kg IVM treatment reduced female sexual behavior and the execution of the lordosis reflex. The present results may be useful for avoiding the side effects of this drug in veterinary practice.

Central genomic regulation of the expression of oestrous behaviour in dairy cows: a review

The expression of oestrous behaviour in Holstein Friesian dairy cows has progressively decreased over the past 50 years. Reduced oestrus expression is one of the factors contributing to the current suboptimal reproductive efficiency in dairy farming. Variation between and within cows in the expression of oestrous behaviour is associated with variation in peripheral blood oestradiol concentrations during oestrus. In addition, there is evidence for a priming role of progesterone for the full display of oestrous behaviour. A higher rate of metabolic clearance of ovarian steroids could be one of the factors leading to lower peripheral blood concentrations of oestradiol and progesterone in high-producing dairy cows. Oestradiol acts on the brain by genomic, non-genomic and growth factor-dependent mechanisms. A firm base of understanding of the ovarian steroid-driven central genomic regulation of female sexual behaviour has been obtained from studies on rodents. These studies have resulted in the definition of five modules of oestradiol-activated genes in the brain, referred to as the GAPPS modules. In a recent series of studies, gene expression in the anterior pituitary and four brain areas (amygdala, hippocampus, dorsal hypothalamus and ventral hypothalamus) in oestrous and luteal phase cows, respectively, has been measured, and the relation with oestrous behaviour of these cows was analysed. These studies identified a number of genes of which the expression was associated with the intensity of oestrous behaviour. These genes could be grouped according to the GAPPS modules, suggesting close similarity of the regulation of oestrous behaviour in cows and female sexual behaviour in rodents. A better understanding of the central genomic regulation of the expression of oestrous behaviour in dairy cows may in due time contribute to improved (genomic) selection strategies for appropriate oestrus expression in high-producing dairy cows.

Gonadotropin-inhibitory hormone reduces sexual motivation but not lordosis behavior in female Syrian hamsters (Mesocricetus auratus)

Reproductive success is maximized when female sexual motivation and behavior coincide with the time of optimal fertility. Both processes depend upon coordinated hormonal events, beginning with signaling by the gonadotropin-releasing hormone (GnRH) neuronal system. Two neuropeptidergic systems that lie upstream of GnRH, gonadotropin-inhibitory hormone (GnIH; also known as RFamide related peptide-3) and kisspeptin, are potent inhibitory and excitatory modulators of GnRH, respectively, that participate in the timing of the preovulatory luteinizing hormone (LH) surge and ovulation. Whether these neuropeptides serve as neuromodulators to coordinate female sexual behavior with the limited window of fertility has not been thoroughly explored. In the present study, either intact or ovariectomized, hormone-treated female hamsters were implanted for fifteen days with chronic release osmotic pumps filled with GnIH or saline. The effect of GnIH on sexual motivation, vaginal scent marking, and lordosis was examined. Following mating, FOS activation was quantified in brain regions implicated in the regulation of female sexual behavior. Intracerebroventricular administration of GnIH reduced sexual motivation and vaginal scent marking, but not lordosis behavior. GnIH administration altered FOS expression in key neural loci implicated in female reproductive behavior, including the medial preoptic area, medial amygdala and bed nucleus of the stria terminalis, independent of changes in circulating gonadal steroids and kisspeptin cell activation. Together, these data point to GnIH as an important modulator of female proceptive sexual behavior and motivation, independent of downstream alterations in sex steroid production.

Brain RegionSpecific Transcriptomic Markers of Serotonin1A Receptor Agonist Action Mediating Sexual Rejection and Aggression in Female Marmoset Monkeys

IntroductionIn a marmoset model of hypoactive female sexual function, we have shown that repeated administration of the serotonin (5HT)1A agonist R(+)8hydroxy2(diNpropylamino)tetralin (8OHDPAT) inhibits sexual receptivity in female marmoset monkeys and increases aggression toward the male pairmate. AimThe aims of this study are to investigate gene expression changes induced by 8OHDPAT in lasermicrodissected brain areas that regulate female sexual function and to identify genes, functional gene classes, and pathways associated with 8OHDPATmediated inhibition of female sexual receptivity. MethodsGene expression was measured in the medial prefrontal cortex (mPFC), medial preoptic area (mPOA), cornu ammonis1 (CA1) area of the hippocampus (CA1), and dorsal raphé nucleus (DRN) of four 8OHDPATtreated (0.1 mg/kg; daily administration for 16 weeks) and four vehicletreated female marmosets using a marmosetspecific microarray (European Marmoset Microarray [EUMAMA]) and validated by realtime quantitative polymerase chain reaction (RTqPCR). Enriched functional gene classes were determined. In a parallel candidate gene approach, the expression of serotonergic candidate genes, i.e., the 5HT1A, 5HT2A, and 5HT7 receptors and the 5HT transporter (5HTT), was measured by RTqPCR. Main Outcome MeasuresThe main outcome is the differential expression of genes between 8OHDPAT and vehicletreated marmosets. Results8OHDPAT affected the gene classes important to neural development (mPFC, mPOA, and DRN), neurotransmission (mPOA), energy production (mPFC and mPOA), learning and memory (CA1), and intracellular signal transduction (DRN). Oxytocin (OXT) in the mPOA and 5HTT in the DRN were strongly increased by 8OHDPAT. 5HT1A tended to increase in the mPFC, while 5HT7 was decreased in the CA1. ConclusionsBrain regionspecific alterations of gene expression regulating neural circuitries, energy demands, and learning processes are associated with 8OHDPATinduced decrease in female sexual receptivity and increase in pairmate aggression. The role of OXT in the serotonergic regulation of female sexual behavior and partner interactions warrants attention in future studies.

Role of estrogen receptor α and β in the induction of progesterone receptors in hypothalamic ventromedial neurons

The estrogen induction of progesterone receptors (PRs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is critical for the regulation of female sexual behavior. VMNvl neurons express PRs and both types of estrogen receptors (ERα and ERβ), and their sequential activation initiates the molecular mechanisms underlying sexual behavior. To assess the relative importance of each ER subtype in the induction of PRs, we have estimated the total number of PR-immunoreactive neurons and quantified the total amount of PR protein in the VMNvl of adult ovariectomized rats that were injected with either estradiol benzoate (EB) or the specific agonists of the ERα, propyl-pyrazole triol (PPT), and of the ERβ, diaryl-propionitrile (DPN), in different doses and schedules. The administration of EB and of PPT alone, but not of DPN alone, increased the total number of PR-immunoreactive neurons and PR protein levels. When the specific agonists were administered sequentially, the total number of PR-immunoreactive neurons also increased, particularly when PPT was administered before DPN. Conversely, the concomitant administration of PPT and DPN did not increase the number of PR-immunoreactive neurons.The observation that PPT increases the number of PR-immunoreactive neurons and the levels of PR protein far less than EB shows that the estradiol induction of PRs in the VMNvl does not involve solely the activation of the ERα and suggests that it might also implicate the activation of membrane receptors. The present results also show that ERβ activation averts the action of ERα in the induction of PRs.

Membrane-Initiated Estradiol Signaling Induces Spinogenesis Required for Female Sexual Receptivity

Estrogens have profound actions on the structure of the nervous system during development and in adulthood. One of the signature actions of estradiol is to alter the morphology of neural processes. In the hippocampus, estradiol modulates spines and cellular excitability that affect cognitive behaviors. In the hypothalamus, estradiol increases spine density in mediobasal hypothalamic nuclei that regulate reproduction. The hypothalamic arcuate nucleus (ARH), an important site for modulation of female sexual receptivity, has a sexual dimorphism in dendritic spine density that favors females. In the present study, we used both β-actin immunostaining and Golgi staining to visualize estradiol-induced changes in spine density in Long-Evans rats. Golgi impregnation was used to visualize spine shape, and then β-actin immunoreactivity was used as a semiquantitative measure of spine plasticity since actin forms the core of dendritic spines. At 4 h after estradiol treatment, both β-actin immunofluorescence and filopodial spines were increased (from 70.57 ± 1.09% to 78.01 ± 1.05%, p < 0.05). Disruption of estradiol-induced β-actin polymerization with cytochalasin D attenuated lordosis behavior, indicating the importance of estradiol-mediated spinogenesis for female sexual receptivity (81.43 ± 7.05 to 35.00 ± 11.76, p < 0.05). Deactivation of cofilin, an actin depolymerizing factor is required for spinogenesis. Membrane-initiated estradiol signaling involving the metabotropic glutamate receptor 1a was responsible for the phosphorylation and thereby deactivation of cofilin. These data demonstrate that estradiol-induced spinogenesis in the ARH is an important cellular mechanism for the regulation of female sexual behavior.

Long-term effects of pubertal stressors on female sexual receptivity and estrogen receptor-α expression in CD-1 female mice

Exposure to stress during puberty can lead to long-term behavioral alterations. Female mice, of the inbred C57BL/6 strain, have been shown to display lower levels of sexual receptivity in adulthood when exposed to shipping stress or to an immune challenge during puberty. The present study investigated whether this effect can be extended to CD1 outbred mice and examined a possible mechanism through which exposure to stressors could suppress sexual receptivity. The results revealed that CD1 mice injected with lipopolysaccharide (LPS) or exposed to shipping stress at 6 weeks old display lower levels of sexual receptivity in response to estradiol and progesterone in adulthood than control mice. Moreover, mice exposed to shipping stress at 8 weeks old also displayed reduced sexual receptivity, but those injected with LPS at that time showed slightly reduced effects, suggesting that the sensitive pubertal period extends to 8 weeks of age in this strain of mice. The examination of estrogen receptor-α (ER-α) expression revealed that mice exposed to shipping stress during the sensitive period (6 weeks) display lower levels of ER-α expression in the medial preoptic area and the ventromedial nucleus and the arcuate nucleus of the hypothalamus than mice shipped at a younger age. These findings support the prediction that exposure to shipping stress or LPS during puberty decreases behavioral responsiveness to estradiol and progesterone in adulthood in an outbred strain of mice through enduring suppression of ER-α expression in some brain areas involved in the regulation of female sexual behavior.

Role of neural afferents as mediators of estrogen effects on the hypothalamic ventromedial nucleus

The effects of estrogens on the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) are essential for its role in the regulation of female sexual behavior. Enhanced synaptogenesis and induction of progesterone receptors (PRs) are hallmarks of the actions of estrogens on the VMNvl. To investigate the influence of neural afferents in mediating these effects, we estimated the number of spine and dendritic synapses per neuron and the total number of PR-immunoreactive neurons in ovariectomized rats treated with either estradiol benzoate or vehicle, after unilateral VMN deafferentation. The estimates were performed independently in the VMNvl of the deafferented and contralateral sides, and in the VMNvl of unoperated rats (controls). The administration of estradiol benzoate did not induce any increase in the number of synapses of the deafferented VMNvl. In the contralateral VMNvl, the synaptogenic effects of estrogen were apparent, but still reduced relative to the control VMNvl, where a 25% increase in the total number of synapses was observed after estrogenic stimulation. In the absence of estrogenic stimulation, i.e., in basal conditions, deafferentation reduced the number of dendritic and spine synapses, but particularly the latter. The reduction was also visible, but less marked, in the contralateral VMNvl. Contrary to synapses, the estrogen induction of PRs was unaffected by deafferentation, and the total number of PR-immunoreactive neurons was similar in the control, deafferented and contralateral VMNvl. The results show that estrogens enhance synaptogenesis in the VMNvl by acting through neural afferents and induce PR expression by acting directly upon VMN neurons.

Differential regulation of female sexual behaviour by dopamine agonists in the medial preoptic area

The medial preoptic area (mPOA) is a brain region critical in the control of male sexual behaviour, and the neurotransmitter dopamine (DA) plays an important role within it. However, both the roles of DA and the mPOA in female sexual behaviour are not fully understood, with few studies producing consistent data. The present study examined the function of DA within the mPOA on the full cascade of female sexual behaviour. Ovariectomized female rats were bilaterally cannulated into the mPOA and partially hormonally primed with estradiol benzoate (EB). Different doses of a nonselective DA receptor agonist, and selective DA D1 and D2 receptor agonists (apomorphine, SKF 38393 and quinpirole, respectively) were infused bilaterally to the mPOA. Copulatory behaviour was then immediately tested over a period of 30 min in a bilevel chamber with a sexually experienced male. Precopulatory behaviours were increased in females following infusions of a low dose (0.25 μg) of apomorphine and both a low (0.05 μg) and a high dose (0.2 μg) of quinpirole. However, hops and/or darts were decreased following infusion of a low dose (0.05 μg) of SKF 38393. These results suggest that the ratio of DA D1/D2 activity within the mPOA of female rats is critical for the expression of precopulatory behaviours, and may work with other brain areas responsible for stimulating lordosis to control the timing of female sexual behaviour.

1408 POSTER Identification of bipotential cells in both neuroblastic primary tumours and neuroblastoma bone marrow metastasis

Sexual behavior in female rats depends on the action of estradiol on estrogen receptors (ERs) found in particular brain regions. While hormonal regulation of female sexual behavior requires ERα, the possible functions of ERβ remain to be clarified. Mating stimulation has several behavioral and physiological consequences and induces Fos expression in many brain areas involved in the regulation of reproductive behavior and physiology. In addition, some cells in which mating induces Fos expression coexpress ERα. To determine whether cells in which Fos is induced by a particular mating stimulus coexpress ERα, ERβ, or both, we used a triple-label immunofluorescent technique to visualize ERα-, ERβ-, and mating-induced Fos-immunoreactivity (Fos-ir) in neurons in which mating stimulation reliably increases Fos expression. Ovariectomized, hormone-primed rats were either unmated, received 15 mounts, or received 15 intromissions. In the rostral medial preoptic area, Fos-ir was induced by mounts alone primarily in cells coexpressing ERα-ir, while Fos-ir was induced by intromissions mainly in cells coexpressing both ERα-ir and ERβ-ir (ERα/ERβ-ir). In the dorsal part of the posterodorsal medial amygdala, Fos-ir was induced by intromissions in cells coexpressing ERα-ir and ERα/ERβ-ir. However, in the ventral part of the posterodorsal medial amygdala, Fos-ir was induced by intromissions primarily in cells coexpressing only ERβ-ir. These data suggest that qualitatively different sexual stimuli may be integrated through distinct ER-containing circuits in the rostral medial preoptic area and posterodorsal medial amygdala. The diversity in coexpression of type of ER in cells in different brain areas after various mating stimuli suggests a role for both ERα and ERβ in the integration of hormonal information and information related to mating stimuli.

The 5HT 7 receptor subtype is involved in the regulation of female sexual behaviour in the rat

5-Hydroxytryptamine (5-HT) regulates sexual behaviour in the female rat via a number of its receptors. The role of the 5HT 7 receptor was investigated in ovariectomised rats primed with 10 μg oestradiol benzoate (OB) followed at 48 h by 0.5 mg progesterone, which induced receptivity in approximately half of the animals. These animals were treated with three agonists all effective at 5HT 1A and 5HT 7 receptors; 5-hydroxytryptophan, 8-hydroxy-2-(di- n-propylamino)tetralin 1-Br (8-OH DPAT) and 5-carboxy-aminotryptamine (5-CT) in the presence or absence of selective 5HT 1A and 5HT 7 antagonists: WAY 100135 and SB 269970-A. The three agonists inhibited lordosis in the receptive group, and this was prevented by both the selective 5HT 1A and 5HT 7 antagonists. When given alone, both WAY 100135 and SB 269970-A increased the lordosis in the non-receptive rats indicating that endogenous 5-HT acting on 5HT 1A and 5HT 7 receptors may have a tonic inhibitory effect on receptivity. A comparison of OB priming doses on the effect of serotoninergic agents showed that the higher OB doses attenuated the inhibitory effect of 8-OH DPAT and enhanced the stimulatory effect of WAY 100135, but did not affect the actions of 5-CT or SB 269970-A. The interaction between oestradiol and 5-HT activity on sexual behaviour may therefore be selective to the 5HT 1A pathway.

Sexual receptivity is reduced in the female mu-opioid receptor knockout mouse

Activation of mu-opioid receptors is critical to steroid regulation of female sexual behavior, lordosis, in rodents. Estrogen treatment activates mu-opioid receptors in the medial preoptic area inhibiting lordosis, but ultimately appears important for progesterone facilitation of lordosis. We investigated the role of mu-opioid receptors in the expression of sexual receptivity in mice lacking mu-opioid receptors. Although estrogen and progesterone facilitated lordosis in mu-opioid receptor knockout mice, they exhibited deficits in lordosis quotient and score compared with wild-type females, indicating reduced sexual receptivity. In contrast, wild-type and mu-opioid receptor knockout female mice did not differ in either active or passive avoidance of the male. These data are most consistent with the hypothesis that mu-opioid receptor activation is necessary for estrogen and progesterone to maximally facilitate lordosis.

Different roles of 5-HT 2A and 5-HT 2C receptors in regulation of female rat paced mating behaviour

Serotonin (5-HT) receptor 2A (5-HT 2A) and 2C (5-HT 2C) agonists have been reported to facilitate female rat lordosis behaviour. This study investigated the acute effects of the 5-HT 2A receptor agonist DOI ((±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and the 5-HT 2C receptor agonist MK-212 (2-chloro-6-(1-piperazinyl) pyrazine) on paced mating behaviour in a population of sexually receptive female rats in order to explore the role of 5-HT 2A and 5-HT 2C receptors in the mediation of female rat sexual motivation. DOI (0.5 and 1.0 mg/kg) increased female rat sexual motivation during the first of two consecutive copulatory series seen as a tendency towards a decrease in return latencies following ejaculation and decreased inter-intromission intervals. MK-212 generally increased approach latencies. 0.5 mg/kg MK-212 increased post-ejaculatory exit latency, while 1.0 and 2.0 mg/kg MK-212 increased both post-ejaculatory exit latencies and post-ejaculatory return latencies. The possibility that an increased level of anxiety confounded the effects of MK-212 on sexual motivation behaviour is discussed. The results may support the hypothesis that both 5-HT 2A and 5-HT 2C receptors are important in regulation of female sexual behaviour.