Vaginocervical Stimulation Research Articles

In vivo spontaneous activity and coital-evoked inhibition of mouse accessory olfactory bulb output neurons

Little is known about estrous effects on brain microcircuits. We examined the accessory olfactory bulb (AOB) invivo, in anesthetized naturally cycling females, as model microcircuit receiving coital somatosensory information. Whole-cell recordings demonstrate that output neurons are relatively hyperpolarized in estrus and unexpectedly fire high frequency bursts of action potentials. To mimic coitus, a calibrated artificial vagino-cervical stimulation (aVCS) protocol was devised. aVCS evoked stimulus-locked local field responses in the interneuron layer independent of estrous stage. The response is sensitive to α1-adrenergic receptor blockade, as expected since aVCS increases norepinephrine release in AOB. Intriguingly, only in estrus does aVCS inhibit AOB spike output. Estrus-specific output reduction coincides with prolonged aVCS activation of inhibitory interneurons. Accordingly, in estrus the AOB microcircuit sets the stage for coital stimulation to inhibit the output neurons, possibly via high frequency bursting-dependent enhancement of reciprocal synapse efficacy between inter- and output neurons.

Sperm utilize tumor necrosis factor alpha to shut down a 2-methoxyestradiol nongenomic pathway that accelerates oviductal egg transport in the rat.

Mating shuts down the 2-methoxyestradiol (2ME) nongenomic pathway that accelerates oviductal egg transport in the rat. This study shows that sperm cells, but not vaginocervical stimulation, utilize TNF-α to shut down this 2ME nongenomic pathway. The transport of oocytes or embryos throughout the oviduct to the implantation site in the uterus is defined as egg transport. In the rat, 2-methoxyestradiol (2ME) accelerates egg transport through the oviduct via a nongenomic pathway. Mating is known to shut down this 2ME pathway and then trigger an estradiol genomic pathway that accelerates egg transport. Here, we tested whether intrauterine insemination (IUI) or vaginocervical stimulation (VCS) shuts down the 2ME nongenomic pathway that accelerates egg transport, and if these mating components require tumor necrosis factor alpha (TNF-α). Levels of TNF-α and the mRNA for TNF-α receptors were measured in the oviduct of IUI or VCS rats. The tissue distribution of TNF-α receptor proteins and the concentration of the mRNA for catechol-O-methyl transferase (Comt) and 2ME were also analyzed in the oviduct. Finally, we assessed whether 2ME accelerates egg transport in IUI or VCS rats previously treated with the TNF-α antagonist W9P9QY. Results show that IUI, but not VCS, increased TNF-α and their receptors in the oviduct. IUI and VCS did not change the tissue distribution of TNF-α receptors; however, both decreased the oviductal concentration of Comt and 2ME. IUI and VCS each blocked the 2ME-induced egg transport acceleration; however, only the IUI was antagonized by the TNF-α antagonist. We concluded that IUI and VCS inhibit the 2ME nongenomic pathway that accelerates egg transport; however, the vias of action are distinct, with a TNF-α increase on spermatozoa presence being required for the shutdown of the 2ME pathway.

Neurobiology of Maternal Behavior in Nonhuman Mammals: Acceptance, Recognition, Motivation, and Rejection.

Among the different species of mammals, the expression of maternal behavior varies considerably, although the end points of nurturance and protection are the same. Females may display passive or active responses of acceptance, recognition, rejection/fear, or motivation to care for the offspring. Each type of response may indicate different levels of neural activation. Different natural stimuli can trigger the expression of maternal and paternal behavior in both pregnant or virgin females and males, such as hormone priming during pregnancy, vagino-cervical stimulation during parturition, mating, exposure to pups, previous experience, or environmental enrichment. Herein, we discuss how the olfactory pathways and the interconnections of the medial preoptic area (mPOA) with structures such as nucleus accumbens, ventral tegmental area, amygdala, and bed nucleus of stria terminalis mediate maternal behavior. We also discuss how the triggering stimuli activate oxytocin, vasopressin, dopamine, galanin, and opioids in neurocircuitries that mediate acceptance, recognition, maternal motivation, and rejection/fear.

The Onset of Maternal Behavior in Sheep and Goats: Endocrine, Sensory, Neural, and Experiential Mechanisms.

In sheep and goats, the onset of maternal behavior at parturition is characterized by a first phase called maternal responsiveness during which the mother is attracted to any newborn. In a second phase, called maternal selectivity, the mother establishes a selective bond with her young so that she only accepts it at suckling. After a description of the behavioral expression of both phases, this chapter reviews the physiological, sensory, and neural mechanisms involved. These two behavioral processes are synchronized with parturition by the vaginocervical stimulation induced by the expulsion of the newborn. Olfactory cues provided by the neonate are involved in maternal responsiveness and selectivity. Oxytocin supported by estrogens is the key factor for maternal responsiveness. The neural network involved in maternal responsiveness is mainly hypothalamic and is different from the circuitry involved in selectivity, which mainly concerns olfactory processing regions. Visual and auditory cues are necessary for offspring recognition at a distance. This multisensory recognition suggests that mothers form a mental image of their young. Maternal experience renders mothers more responsive to maternally relevant physiology and to young-related sensory inputs.

Regulation of maternal behavior, social isolation responses, and postpartum estrus by steroid hormones and vaginocervical stimulation in sheep

Periparturient ewes display several activities in addition to maternal behavior per se. They isolate themselves from the flock and, contrary to other mammals, do not show postpartum estrus. We investigated the possibility of a common hormonal control of maternal behavior, prepartum social isolation responses, and absence of postpartum estrus. We quantified responses to flockmate separation and incidence of sexual receptivity at several reproductive stages in intact ewes (Experiment 1). Responses to social isolation were lowest in preparturient ewes and at pregnancy day 149, intermediate at pregnancy day 147 and highest at day 136 and in non-pregnant ewes (P < 0.05 between the 3 levels). In a second experiment, we quantified the same parameters and maternal behavior in 1) ovariectomized ewes receiving medroxyprogesterone acetate only (ovxMPA); 2) ovariectomized ewes receiving MPA + estradiol benzoate (ovxSHORT); 3) intact ewes receiving a longer MPA + estradiol dipropionate treatment, before and after vaginocervical stimulation (VCS). Before VCS no steroid treatments decreased social isolation responses and maternal behavior was scarce or absent. Following VCS and interaction with lamb, maternal responses in the ovxSHORT group increased while social isolation responses decreased. Sexual receptivity occurred in non-pregnant ewes and in ovxSHORT group. Conclusion: some hormonal treatments +VCS can effectively induce maternal behavior and reduce social isolation responses. Long-term progestin treatment can inhibit postpartum estrus.

Artificial vagino-cervical stimulation modifies the frequency of uterine contractions during the estrous cycle of the female rat

Las contracciones uterinas (CU) pueden participar en importantes procesos reproductivos, como el transporte de espermatozoides y el parto. La evidencia indica que las CU pueden ser inducidas por hormonas y estimulación vaginocervical (EVC) a través de vías neuroendocrinas, incluida la actividad de las glándulas pituitaria y ovarios. Evaluamos la frecuencia de CU después de la EVC en diferentes fases del ciclo estral (CE) en ratas hembras adultas. Treinta y seis ratas hembras fueron anestesiadas, y sus cuernos uterinos fueron expuestos a través de una incisión abdominal. La EVC incluyó intromisiones vaginocervicales (IVC) y distensión vaginal mediante la inserción de un tapón de silicón para imitar los efectos del tapón posteyaculatorio. El número de CU se midió: 1) antes y después de las IVC, 2) durante la distensión vaginal por el tapón de silicón, y después de que se retiró. Comparamos el efecto de la EVC en la cantidad de CU durante las diferentes etapas de la CE de ratas. Los resultados indicaron que la frecuencia de la CU basal fue mayor durante el proestro tardío y menor durante el diestro. Además, las intromisiones dieron como resultado una mayor actividad uterina. La EVC aumentó el número de contracciones durante todas las fases de la CE, excepto durante el diestro. Discutimos el papel de las hormonas y la estimulación sexual en la CU, y su posible implicación en los procesos reproductivos de las hembras.

Prolactin gene expression in the pituitary of rats subjected to vaginocervical stimulation requires Erk-1/2 signaling

Vaginocervical stimulation (VCS) induces twice-daily prolactin (PRL) surges resulting in pseudopregnancy in the rat. Furthermore, activation of the extracellular signal-regulated kinase-1/2 (Erk-1/2) is involved in the effect of estradiol (E2) on the Prl gene expression in pituitary cells. Herein, we investigated whether Erk-1/2 signaling is involved in the control of Prl expression in the pituitary of VCS rats and whether VCS regulates the effect of E2 on Erk-1/2 and Prl in the pituitary. Estrous rats were assigned as control or VCS groups and 0, 6, 12 or 24h later the levels and localization of phosphorylated Erk-1/2 (p-Erk-1/2) were analyzed in the pituitary. The effect of an Erk-1/2 inhibitor PD98059 on the Prl level in the pituitary of control or VCS rats was also analyzed. Other control or VCS rats were treated with E2 and the level of p-Erk-1/2 and Prl were measured in the pituitary. In control rats, p-Erk-1/2 decreased at 6 and 12h and increased at 24h while Erk-1/2 was phosphorylated at all time points in VCS rats. p-Erk-1/2 was localized only in the anterior pituitary. PD98059 decreased Prl level in VCS, but not in control rats. Estradiol decreased Erk-1/2 phosphorylation although did not change Prl level in the pituitary of control or VCS rats. These findings show that prolonged activation of Erk-1/2 is necessary to induce Prl expression in the pituitary of VCS rats; however, VCS does not influence the role of E2 on the activation of Erk-1/2 and Prl expression the pituitary.

Electroencephalographic coupling in the amygdala and prefrontal cortex in relation to the estrous cycle and duration of vaginocervical stimulation in the rat

The influence of the duration of vaginocervical stimulation (VCS) on the electroencephalographic activity (EEG) of medial amygdala (MeA) and prefrontal cortex (PFC) in rats during proestrus-estrus (P-E) and diestrus (D) was examined. Using a glass syringe plunger, a constant force of 300g was exerted against the cervix during 60s. Relative power (RP) and correlation of three EEG band frequencies were compared between the first and last 30s intervals of VCS. A higher RP of the 4–7Hz band and a lower RP of the fast frequencies were observed in the MeA and PFC in P-E females during the first 30s of VCS as compared to the last 30s. Only during P-E, a higher interamygdaline correlation in the 8–12Hz band and a lower correlation in the 13–21Hz band during the first 30s were observed. Similarly, a higher interamygdaline correlation in the 8–12Hz band was observed during the first 30s of VCS during P-E as compared to D. During the last 30s of VCS there was no difference between phases. The VCS evoked EEG changes in the MeA that varied between phases of the estrous cycle and depended on the duration of the stimulation. These effects could be associated with the quantification processes of VCS that has been proposed to occur in the amygdala. These findings show differential responsiveness of the MeA and PFC according to the amount of VCS received, and that the response varies according to the estrous cycle.

Neuroendocrine control of maternal behavior in non-human and human mammals

Mammalian parental care is essentially provided by the mother and it occupies most of the reproductive period for female. The synchronization of maternal behavior with parturition and lactation ensures that the mother responds to the needs of the young at the appropriate time. This temporal synchrony is accomplished by hormonal changes that underly both the onset of maternal behavior and of parturition and lactation. The aim of this review is to describe and compare the hormonal mechanisms that regulate the onset of maternal behavior across a variety of mammals, including humans, that represent different behavioral strategies. Are involved the steroid hormones, estradiol and progesterone synthesized by the ovaries which primed the future mother to repond maternally. In response to these steroids, oxytocin release induced by vaginocervical stimulation and prolactin release affect the maternal brain. The medial preoptic area integrates the hormonal signals to regulate maternal behavior. The hormonal cocktail that stimulates maternal behavior varies across mammalian species. Because most of the studies in humans are correlative and because human environment is complex, direct causality between hormones and maternal behavior is unclear. However, one can reasonably think that hormones create a positive bias towards the baby increasing the occurrence of maternal behavior.

Sexual experience modulates partner preference and mPOA nitric oxide synthase in female rats.

Sexually experienced female rats return to the male more quickly after intromissions, exhibit shorter interintromission intervals, and spend more time with the male rat during a test of paced mating behavior in comparison to naïve rats. The present study tested whether these changes reflect heightened sexual motivation independent of receipt of vaginocervical stimulation and/or neurochemical changes in the medial preoptic area (mPOA). Ovariectomized, female rats were given estradiol benzoate and progesterone, and then received either 6 paced mating encounters (experienced) or 6 control exposures to an empty paced mating arena (naïve). Experienced and naïve rats received a no-contact partner preference test under oil vehicle and then under hormone on a different day. Hormonal status and sexual experience led to significantly higher preference for the male. Brains were collected 1 hr after both experienced and naïve rats received paced mating to compare mPOA levels of Fos, a marker of neural activity, in response to copulation and nitric oxide synthase (NOS), the enzyme responsible for production of nitric oxide (NO). Expression of NOS was higher in experienced relative to naïve rats, whereas Fos was comparable between the groups. The data are consistent with the idea that both sexual motivation and changes to the mPOA contribute to the shift in paced mating behavior induced by sexual experience. (PsycINFO Database Record

Vaginocervical stimulation attenuates the sensitization of appetitive sexual behaviors by estradiol benzoate in the ovariectomized rat

The acute administration of estradiol benzoate (EB) to the ovariectomized (OVX) rat induces low levels of lordosis while sexually appetitive behaviors (e.g., hops, darts, solicitations) are absent, yet the repeated administration of EB results in a behavioral sensitization in which lordosis is potentiated and sexually appetitive behaviors are induced. We have shown that repeated copulation attenuates the sensitization of appetitive sexual behaviors. Here, we assessed which component of male stimulation during copulation is involved in the attenuation. On 8 occasions, sexually experienced OVX Long–Evans rats were treated with 10μgEB and 48h later assigned to one of six groups that differed in their experience on intermediates tests (2–7). One was given repeated access to a male (EB/Male), and another was placed in the copulation chamber alone (EB/Alone) on intermediate tests. Three groups were given one of three somatosensory stimuli by the experimenter: manual flank stimulation (FLS), clitoral stimulation (CLS), or vaginocervical stimulation (VCS). Finally, the control group was left undisturbed in the animal care facility (ACF). Sexual behaviors were measured on Tests 1 and 8. VCS received from the experimenter (VCS) or from the male during copulation (EB/Male) attenuated the magnitude of the sensitization of appetitive sexual behaviors compared with those that were not brought to the testing rooms (ACF), and the effect was most pronounced on sexual solicitations. These results suggest that VCS received during penile intromission inhibits the sensitization of sexually appetitive behaviors by repeated administration of EB. As such, repeated administration of EB may oppose those mechanisms that induce estrous termination, perhaps by sensitizing inhibitory processes within the ventromedial hypothalamus that typically prevent the display of sexual behaviors (i.e., by facilitating disinhibition).

Female rats express a conditioned object preference for receipt of sexual stimulation

Female rats alternately approach and avoid the male rat during copulation, potentially reflecting appetitive and aversive aspects of mating, respectively. We developed a novel classical conditioning procedure, conditioned object preference (COP), to test whether female rats show increased approach toward a conditioned stimulus associated directly with receipt of sexual stimulation. During conditioning, one scented object was paired with an appetitive stimulus and a different object plus scent was paired with a control stimulus on a separate day. After conditioning, preference for each object was evaluated with a choice task. Experiment 1 was conducted to verify the procedure. Rats exhibited a significant COP for 1mg/kg amphetamine, indicating that the conditioned object preference procedure is an effective tool for evaluating the rewarding nature of a treatment. In Experiment 2, paced mating to one ejaculation and experimenter-delivered artificial vaginocervical stimulation (aVCS) each induced a COP. The robust COPs for paced mating and aVCS support the notion that female rats experience a reward state during receipt of sexual stimulation. Moreover, the data suggest that any aversive aspects of receipt of sexual stimulation do not overshadow the appetitive effects.

Repeated administration of estradiol promotes mechanisms of sexual excitation and inhibition: Glutamate signaling in the ventromedial hypothalamus attenuates excitation

Repeated administration of 10μg of estradiol benzoate (EB) every 4 days to the ovariectomized (OVX) rat induces a behavioral sensitization of sexual behaviors. Repeated copulation or the receipt of vaginocervical stimulation (VCS) attenuates the sensitization of appetitive sexual behaviors, suggesting that VCS acts in opposition to the mechanisms that induce the sensitization. It is known that VCS accelerates the onset of estrous termination (characterized by a decrease in appetitive sexual behaviors, and an increase in defensive behaviors prior to the decline in lordosis), and glutamate transmission in the ventromedial hypothalamus (VMH), particularly via AMPA receptor signaling, is an important regulator of this effect. Thus, the current studies examined whether mechanisms of estrous termination are involved in the attenuated sensitization to EB that occurs with repeated copulation. In the first study, OVX rats received infusions of AMPA to the VMH on tests 2–4, and sexual behavior was measured on tests 1 and 5. Appetitive sexual behaviors were lower in females that received AMPA infusions in place of copulation compared to saline, suggesting that AMPA receptor activation by VCS may be playing a role in the attenuation of sensitization. In the second study, females that were not given the opportunity to copulate on tests 2–4 fell out of behavioral estrus faster than those that did, suggesting that both excitatory and inhibitory mechanisms of sexual behavior become sensitized with repeated administration of EB. Together these findings extend our hypothesis that repeated episodes of heat sensitize the activation of sexual behaviors to increase the probability of eventual fertilization.

Estrogen receptors regulate the estrous behavior induced by progestins, peptides, and prostaglandin E2

The role of classical estrogen receptors (ERs) in priming female reproductive behavior has been studied previously; however, the participation of this receptor during activation of estrous behavior has not been extensively studied. The purpose of this work was to test the possibility that the facilitation of lordosis behavior in estrogen-primed rats by progesterone (P) and its 5α- and 5β-reduced metabolites, gonadotropin-releasing hormone (GnRH), leptin, prostaglandin E2 (PGE2) and vagino-cervical stimulation (VCS) involves interactions with classical ERs by using the selective ER modulator, tamoxifen. To further assess the role of ERs, we also explored the effects of the pure ER antagonist, ICI182780 (ICI), on estrous behavior induced by P and GnRH. Ovariectomized, estrogen-primed rats (5μg estradiol benzoate 40h earlier) were injected intraventricularly with the above-mentioned compounds, or they received VCS. All compounds and VCS effectively facilitated estrous behavior when tested at 60, 120 or 240min after infusion or application of VCS. Intraventricular infusion of tamoxifen (5μg), 30min before, significantly attenuated estrous behaviors induced in estradiol-primed rats by P, most of its 5α- and 5β-reduced metabolites, GnRH, and PGE2, but not by VCS. Although there was a trend for reduction, tamoxifen did not significantly decrease lordosis in females treated with 5β-pregnan-3,20-dione. ICI also inhibited lordosis behavior induced by P and GnRH at some testing intervals. These results suggest that activation of classical ERs participates in the triggering effects on estrous behavior induced by agents with different chemical structures that do not bind directly to ERs.

Glutamate release in the ventromedial hypothalamus of the female rat during copulation: Modulation by estradiol

Binding of glutamate or its ionotropic receptor agonists in the ventromedial hypothalamus (VMH) of female rats inhibits both appetitive and consummatory aspects of sexual behavior. Because vaginocervical stimulation activates glutamate neurons in the VMH, and administration of estradiol benzoate (EB) and progesterone (P) delays this effect, the present study examined the effects of hormonal priming on glutamate release within the VMH of female rats paired with sexually vigorous males. Ovariectomized, sexually experienced rats were implanted with guide cannula aimed at the ventrolateral VMH, through which microdialysis probes were inserted prior to testing. Females were assigned randomly to one of three hormone treatment conditions: EB+P, EB alone, or the oil vehicle. Testing was conducted over 5h, including a 120-min period of habituation to the testing chamber, a 60-min period of baseline sample collection, and a 120-min period during which a sexually vigorous male was introduced into the testing chamber. Dialysates were collected every 20min during the test and were analyzed for glutamate using HPLC. Females primed with oil had large and significant increases in glutamate release from baseline once the male was introduced to the chamber. Treatment with EB alone decreased glutamate release in response to male cues. Although treatment with EB+P did not differ significantly from EB alone, the degree of reduced glutamate release was less than with EB alone. These results indicate that priming with EB reduces glutamate transmission in the VMH in response to male cues. Taken together with our previous findings, estradiol blunts the activation of glutamate neurons in the VMH thus allowing female rats to copulate.

Sexual experience blocks the ability of clitoral stimulation to induce a conditioned place preference in the rat

We have previously established the rewarding value of clitoral stimulation (CLS) through the demonstration that manual, distributed, CLS induces a significant conditioned place preference (CPP) and conditioned partner preference in naïve, hormonally primed and non-hormonally primed rats. The present experiment asks whether previous sexual experience might inhibit the ability of clitoral stimulation to induce a conditioned place preference.Female Long–Evans rats were ovariectomized and treated with 10μg of estradiol benzoate (EB) 48h and 500μg of progesterone (P) 4h prior to receiving either 0, 1, or 5 consecutive copulatory sessions with a sexually vigorous male. Each copulatory session ended when females received at least 1 ejaculation. Females then experienced 10 alternating trials of distributed CLS or no CLS paired with one side of a non-biased CPP box under the same hormone-priming regimen. Females that experienced 5 consecutive copulatory sessions did not develop a significant place preference indicated by both a preference score (the proportion of time spent in the reinforced chamber) and a difference score (time in the non-reinforced chamber minus the time in the reinforced chamber) compared prior to and following the 10 conditioning trials. This suggests that repeated copulatory experience might induce a desensitization of the genitosensory circuit since copulation includes both clitoral, and vaginocervical stimulation from mounts plus intromissions. Alternatively, repeated sexual experience prior to conditioning may generate a UCS pre-exposure effect that cannot be altered when manual clitoral stimulation is paired with a new environment.

Src kinase signaling mediates estrous behavior induced by 5β-reduced progestins, GnRH, prostaglandin E2 and vaginocervical stimulation in estrogen-primed rats

The progesterone receptor (PR) is a dual function protein that acts in the nucleus as a transcriptional factor and at the cytoplasm as a scaffold for the Src–MAPK signaling pathway. Several agents lacking affinity for the PR, such as 5β-reduced progestins, GnRH or prostaglandin E2 (PGE2) facilitate estrous behavior in ovariectomized (ovx), estrogen-primed rats yet their action is blocked by the antiprogestin RU486. We hypothesize that these agents act by using the PR–Src–mitogen activated protein kinase alternative pathway. To test this hypothesis we used PP2, a specific inhibitor of the Src kinase family. Intraventricular infusion of 30μg of PP2, 30min before behavioral testing, significantly attenuated estrous behaviors induced in estradiol benzoate (E2B)-primed rats by 5β-dihydroprogesterone (5β-DHP), 5β-pregnan-3β-ol-20-one (5β,3β-Pgl), GnRH, PGE2 and by manual flank/vaginocervical stimulation. These results suggest that the Src signaling system, by activating mitogen-activated protein kinases, participates in the facilitation of estrous behavior in E2B-primed rats induced by agents lacking affinity for the PR.

AMPA/kainate receptors in the ventromedial hypothalamus mediate the effects of glutamate on estrus termination in the rat

Infusions of glutamate or its selective receptor agonists to the VMH of ovariectomized (OVX) female rats primed with estradiol benzoate (EB) and progesterone (P) inhibit both appetitive and consummatory aspects of sexual behavior whereas selective glutamate receptor antagonists facilitate these measures in females primed with EB alone. Because vaginocervical stimulation (VCS) activates glutamate neurons in the VMH, and induces a faster termination of estros behavior, the present study examined the effects of the AMPA/kainate receptor antagonist DNQX on the induction of estrus termination by manual VCS. Ovx, sexually-experienced rats were primed with EB and P and subsequently received either 1 or 50 distributed VCSs, over the course of an hour, 12h before a test with sexually vigorous males. Half of the females in each stimulus group received bilateral infusions of 1μl/side of either DNQX (19.8mmol/μl) or saline aimed at the VMH immediately prior to VCS or sham stimulation. Saline-infused females given VCS had lower lordosis quotients compared to females given sham stimulation. In contrast, females infused with DNQX prior to VCS displayed more appetitive behaviors and higher lordosis quotients and magnitudes compared to females infused with saline. These data indicate that activation of AMPA/kainate receptors in the VMH by increased glutamate transmission induced by VCS mediates estrus termination.

Prolactin secretory rhythm in women: immediate and long-term alterations after sexual contact

Prolactin (PRL) is one of the most versatile hormones in the mammalian body, affecting reproductive, sexual and other functions. In rats, mating or vaginocervical stimulation activates a characteristic PRL secretory pattern for several days, which is essential for successful reproduction. Although the underlying mechanisms appear to be different, PRL is also crucial for human fertility. We have detected a PRL increase in women induced by sexual intercourse. Extending these findings, the current study aimed at analyzing the PRL secretory rhythm after sexual contact, in order to elucidate whether human females also show long-term alterations of the PRL secretory pattern. In a pilot study, serial blood samples were taken from women (n= 7) in mid-cycle to assess changes in PRL secretory rhythm induced by sexual intercourse, during a period of 32 h. Compared with control condition, sexual intercourse with orgasm induced not only the well-established immediate PRL increase of ~300% but also an additional PRL elevation around noon of the next day (P< 0.05). These fluctuations were measured on top of the regular circadian rhythm of PRL, manifested as a surge early in the morning. We are able to demonstrate a long-term change in the PRL secretory rhythm after sexual intercourse with orgasm in females, suggesting memory effects. We hypothesize that the additionally secreted PRL could be beneficial for decidualization and implantation. Further studies with more participants are required to investigate in detail the implications of such effects on reproductive success in humans.

P-1456 - Neurobiologic correlates between sexual activity and women's mood

Introduction Vagino-cervical stimulation and orgasm may influence mood since sexual intercourse and orgasm physiologically stimulate the vagal nerve and increase the secretion of oxytocin. Objective To explain physiopathologic correlations between sexual intercourse and orgasm from one part and women's mood from another part. Methods A review of the literature published via MedLine is done without any restrictions, using the terms “vagino-cervical stimulation” or “orgasm” in association with “affect” or “mood” or “stress”. Results Vagal nerve bypasses the spinal cord in its course to the brain and constitute the afferent pathway stimulating orgasm. Vagal nerve stimulation is an adjunctive long-term treatment of chronic or recurrent depression. Epilepsy patients who have received vagal nerve stimulation have shown improvement in depressive symptoms. Vagal nerve stimulation may activate the release of oxytocin, noradrenalin and serotonin via the stimulation of the tractus solitaris. Vagino-cervical stimulation releases oxytocin into plasma via the Ferguson reflex. Oxytocin's origin is predominantly in neurons of the paraventricular nucleus of the hypothalamus that project axons into the posterior pituitary, where they release oxytocin into the systemic circulation in response to vagino-cervical stimulation and orgasm. Studies of brain imaging indicate increased activation at women's orgasm in the paraventricular nucleus of the hypothalamus, periaqueductal gray of the midbrain, hippocampus, and the cerebellum. There has been at least one clinical trial showing that daily intranasal oxytocin led to improvements in depressive symptoms and reactivity to stressful life events. Conclusion Orgasm and vagino-cervical stimulation affects mood level in women.