Male Sexual Behavior Research Articles

Cell assembly analysis of neural circuits for innate behavior in Drosophila melanogaster using an immediate early gene stripe/egr-1

Innate behavior, such as courtship behavior, is controlled by a genetically defined set of neurons. To date, it remains challenging to visualize and artificially control the neural population that is active during innate behavior in a whole-brain scale. Immediate early genes (IEGs), whose expression is induced by neural activity, can serve as powerful tools to map neural activity in the animal brain. We screened for IEGs in vinegar fly Drosophila melanogaster and identified stripe/egr-1 as a potent neural activity marker. Focusing on male courtship as a model of innate behavior, we demonstrate that stripe-GAL4-mediated reporter expression can label fruitless (fru)-expressing neurons involved in courtship in an activity (experience)-dependent manner. Optogenetic reactivation of the labeled neurons elicited sexual behavior in males, whereas silencing of the labeled neurons suppressed courtship and copulation. Further, by combining stripe-GAL4-mediated reporter expression and detection of endogenous Stripe expression, we established methods that can label neurons activated under different contexts in separate time windows in the same animal. The cell assembly analysis of fru neural population in males revealed that distinct groups of neurons are activated during interactions with a female or another male. These methods will contribute to building a deeper understanding of neural circuit mechanisms underlying innate insect behavior.

A neural circuit for male sexual behavior and reward

Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTprTac1 neurons are upstream of POATacr1 neurons, and BNSTprTac1-released substance P following mate recognition potentiates activation of POATacr1 neurons through Tacr1 to initiate mating. Experimental activation of POATacr1 neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexualbehavior: motor displays, drive, and reward.

Neuropeptidergic control circuits in the spinal cord for male sexual behaviour: Oxytocin-gastrin-releasing peptide systems.

The neuropeptidergic mechanisms controlling socio-sexual behaviours consist of complex neuronal circuitry systems in widely distributed areas of the brain and spinal cord. At the organismal level, it is now becoming clear that "hormonal regulations" play an important role, in addition to the activation of neuronal circuits. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the "spinal ejaculation generator (SEG)." Oxytocin, long known as a neurohypophyseal hormone, is now known to be involved in the regulation of socio-sexual behaviors in mammals, ranging from social bonding to empathy. However, the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system remains unclear. Oxytocin is known to be synthesised mainly in hypothalamic neurons and released from the posterior pituitary into the circulation. Oxytocin is also released from the dendrites of the neurons into the hypothalamus where they have important roles in social behaviours via non-synaptic volume transmission. Because the most familiar functions of oxytocin are to regulate female reproductive functions including parturition, milk ejection, and maternal behaviour, oxytocin is often thought of as a "feminine" hormone. However, there is evidence that a group of parvocellular oxytocin neurons project to the lower spinal cord and control male sexual function in rats. In this report, we review the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system and effects of these neuropeptides on male sexual behaviour. Furthermore, we discuss the finding of a recently identified, localised "volume transmission" role of oxytocin in the spinal cord. Findings from our studies suggest that the newly discovered "oxytocin-mediated spinal control of male sexual function" may be useful in the treatment of erectile and ejaculatory dysfunction.

Effects of postnatal exposure to cadmium on male sexual incentive motivation and copulatory behavior: Estrogen and androgen receptors expression in adult brain rat

There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1–56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -β), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.

Behavior, Neural Structure, and Metabolism in Adult Male Mice Exposed to Environmentally Relevant Doses of Di(2-ethylhexyl) Phthalate Alone or in a Phthalate Mixture.

We have previously shown that chronic exposure of adult male mice to low doses of di(2-ethylhexyl) phthalate (DEHP) altered male sexual behavior and induced down-regulation of the androgen receptor (AR) in the neural circuitry controlling this behavior. The cellular mechanisms induced by chronic exposure of adult male mice to low doses of DEHP alone or in an environmental phthalate mixture were studied. Two-month-old C57BL/6J males were exposed orally for 8 wk to DEHP alone (0, 5, or ) or to DEHP () in a phthalate mixture. Behavior, dendritic density per length, pre-/postsynaptic markers, synapse ultrastructure, and bioenergetic activity were analyzed. Mice exposed to DEHP either alone or in a phthalate mixture differed in mating, emission of ultrasonic vocalizations, and the ability to attract receptive females in urinary preference tests from control mice. Analyses in the medial preoptic area, the key hypothalamic region involved in male sexual behavior, showed lower dendritic spine density and protein levels of glutamate receptors and differences in other postsynaptic components and presynaptic markers between the treated groups. Ultrastructural observation of dendritic synapses by electron microscopy showed comparable morphology between the treated groups. Metabolic analyses highlighted differences in hypothalamic metabolites of males exposed to DEHP alone or in a phthalate mixture compared to control mice. These differences included lower tryptophan and higher levels, respectively, a precursor and end product of the kynurenine pathway of tryptophan metabolism. The protein amounts of the xenobiotic aryl hydrocarbon receptor, one of the targets of this metabolic pathway and known negative regulator of the AR, were higher in the medial preoptic area of exposed male mice. Differences in behavior of male mice exposed to environmental doses of phthalates were associated with differences in neural structure and metabolism, with possibly a key role of the kynurenine pathway of tryptophan metabolism in the effects mediated by these substances. https://doi.org/10.1289/EHP11514.

The endogenous cannabinoid system modulates male sexual behavior expression.

The endocannabinoid system (ECS) plays a key neuromodulatory role in the brain. Main features of endocannabinoids (eCBs) are that they are produced on demand, in response to enhanced neuronal activity, act as retrograde messengers, and participate in the induction of brain plasticity processes. Sexual activity is a motivated behavior and therefore, the mesolimbic dopaminergic system (MSL) plays a central role in the control of its appetitive component (drive to engage in copulation). In turn, copulation activates mesolimbic dopamine neurons and repeated copulation produces the continuous activation of the MSL system. Sustained sexual activity leads to the achievement of sexual satiety, which main outcome is the transient transformation of sexually active male rats into sexually inhibited animals. Thus, 24 h after copulation to satiety, the sexually satiated males exhibit a decreased sexual motivation and do not respond to the presence of a sexually receptive female with sexual activity. Interestingly, blockade of cannabinoid receptor 1 (CB1R) during the copulation to satiety process, interferes with both the appearance of the long-lasting sexual inhibition and the decrease in sexual motivation in the sexually satiated males. This effect is reproduced when blocking CB1R at the ventral tegmental area evidencing the involvement of MSL eCBs in the induction of this sexual inhibitory state. Here we review the available evidence regarding the effects of cannabinoids, including exogenously administered eCBs, on male rodent sexual behavior of both sexually competent animals and rat sub populations spontaneously showing copulatory deficits, considered useful to model some human male sexual dysfunctions. We also include the effects of cannabis preparations on human male sexual activity. Finally, we review the role played by the ECS in the control of male sexual behavior expression with the aid of the sexual satiety phenomenon. Sexual satiety appears as a suitable model for the study of the relationship between eCB signaling, MSL synaptic plasticity and the modulation of male sexual motivation under physiological conditions that might be useful for the understanding of MSL functioning, eCB-mediated plasticity and their relationship with motivational processes.

Effects of the aqueous extract of Pycnanthus angolensis (Myristicaceae) on male rat sexual behavior and nitric oxide release

Erectile dysfunction is a major public health problem leading to harmful consequences for couples. Hence the need to find adequate treatments using medicinal plants such as Pycnanthus angolensis, a Cameroonian plant used to treat erectile dysfunction. The effects of aqueous extract of Pycnanthus angolensis wood were evaluated on male rat sexual behavior and nitric oxide release. Adult male Wistar rats were divided into 4 groups of 5 each that included a group receiving orally: distilled water (10 ml/Kg BW), plant extract treatment (43 or 86 or 172 mg/kg BW). Sexual behaviors were monitored on days 1, 4, 7, and 14 by pairing male rats to receptive females and nitric oxide levels were assessed in penile homogenate. At the end of the 14 days of treatment, rats were killed and sexual organs weighed. No significant effect was observed on sexual organs weights. When administered at a dose of 43 mg/Kg, body weight; the plant extract significantly increased (p<0.05) the sexual performance as well as the libido of male rats. Nitric oxide release was significantly increased (p<0.05) in that group of extract-treated rats, while compared to the control group. The study demonstrates that Pycnanthus angolensis is a medicinal plant which can enhance the sexual behaviors of male rat. Hence, it can be used for the management of erectile dysfunction, mainly at a dose of 43 mg/Kg, body weight.

Oxytocinergic neurons, but not oxytocin, are crucial for male penile erection

The cumulative evidence suggests that oxytocin is involved in the male sexual behaviors. However, no significant sexual impairments were observed in oxytocin gene knock-out (KO) mice, suggesting that oxytocin is not necessary for sexual behavior in male mice. To better understand the role of oxytocin in male erection, two types of oxytocin gene KO mice were created. In the first type, the oxytocin gene was deleted in the zygote, while in the second type, the oxytocin gene was mutated in adulthood by injecting the CRISPR/Cas9 AAVs. The results showed that disrupting the oxytocin gene at either the embryonic or adult stage did not affect erection, indicating that oxytocin is not necessary for penile erection. Pharmacologically, injecting oxytocin receptor agonist Carbetocin into the VTA of the oxytocin gene KO mice still evoked penile erection. By employing the Oxt-Ires-Cre mice, we found that specifically activating oxytocinergic neurons through chemogenetics strongly induced penile erection, while inhibiting these neurons blocked the erection responses. Furthermore, ablating PVN oxytocinergic neurons abolished the male erection response. In conclusion, although the neuropeptide oxytocin is not essential for male erection, the activity of oxytocinergic neurons is required. Our results might reflect the redundancy in the central nerve system in the sense that many signals contribute to the activation of oxytocinergic neurons to evoke penile erection during sexual behaviors.

Chronic corticosterone exposure evokes itch hypersensitivity and sexual dysfunction in male rats: Relationship between the two distinct gastrin-releasing peptide systems in the spinal cord

In today’s society, people are subjected to many social stressors, and excessive chronic stress causes functional disruption of the neuroendocrine system and many diseases. Although the exacerbation of atopic dermatitis with symptoms of itching and erectile dysfunction is induced by chronic stress, the details of the mechanisms are unknown. Here, we examined the effects of chronic stress on itch sensation and male sexual function at the behavioral and molecular levels, focusing on two distinct gastrin-releasing peptide (GRP) systems that independently regulate itch transmission, i.e., the somatosensory GRP system, and male sexual function, i.e., the lumbosacral autonomic GRP system, in the spinal cord. In a rat model of chronic stress induced by chronic corticosterone (CORT) administration, we observed increased plasma CORT concentrations, decreased body weight, and increased anxiety-like behavior, similar to that observed in humans. Chronic CORT exposure induced hypersensitivity to itch and increased the Grp mRNA level in the spinal somatosensory system, but there was no change in pain or tactile sensitivity. Antagonists of the somatosensory GRP receptor, an itch-specific mediator, suppressed itch hypersensitivity induced by chronic CORT exposure. In contrast, chronic CORT exposure decreased male sexual behavior, ejaculated semen volume, vesicular gland weight, and plasma testosterone levels. However, there were no effects on the expression of Grp mRNA or protein in the lumbosacral autonomic GRP system, which regulates male sexual function. In summary, chronic stress model rats showed itch hypersensitivity and impaired sexual function in males, and the involvement of the spinal GRP systems was apparent in itch hypersensitivity.

Indonesian medicinal plants that have the potential to affect testicular function: A Review

The testes are two glandular organs in the male reproductive system responsible for producing gametes called sperm and synthesizing androgen hormone called testosterone. The two functions of the testes are used as parameters for fertility and sexual performance in males. This paper presents the results of research to find plant-derived ingredients that are potential to treat disorders related to testicular function carried out in Indonesia in the last two decades. The inclusions criteria of the papers compiled are: containing the results of research conducted in Indonesia, by Indonesian researchers; have been published both in national and international journals that can be accessed using Google search engine. The results indicated there are numerous plant species that were revealed to have potentials to be developed as contraceptive or anti-fertility agent, pro-fertility ingredient and sexual activity enhancer herbs in males. Given fertility, infertility, and sexual behavior in males are all determined by the function of testes, it can be concluded that the Indonesian medicinal plants studied are containing active substance that have an effect on the testes.

Social experience and pheromone receptor activity reprogram gene expression in sensory neurons.

Social experience and pheromone signaling in olfactory neurons affect neuronal responses and male courtship behaviors in Drosophila. We previously showed that social experience and pheromone signaling modulate chromatin around behavioral switch gene fruitless, which encodes a transcription factor necessary and sufficient for male sexual behaviors. Fruitless drives social experience-dependent modulation of courtship behaviors and physiological sensory neuron responses to pheromone; however, the molecular mechanisms underlying this modulation of neural responses remain less clear. To identify the molecular mechanisms driving social experience-dependent changes in neuronal responses, we performed RNA-seq from antennal samples of mutants in pheromone receptors and fruitless, as well as grouped or isolated wild-type males. Genes affecting neuronal physiology and function, such as neurotransmitter receptors, ion channels, ion and membrane transporters, and odorant binding proteins are differentially regulated by social context and pheromone signaling. While we found that loss of pheromone detection only has small effects on differential promoter and exon usage within fruitless gene, many of the differentially regulated genes have Fruitless-binding sites or are bound by Fruitless in the nervous system. Recent studies showed that social experience and juvenile hormone signaling co-regulate fruitless chromatin to modify pheromone responses in olfactory neurons. Interestingly, genes involved in juvenile hormone metabolism are also misregulated in different social contexts and mutant backgrounds. Our results suggest that modulation of neuronal activity and behaviors in response to social experience and pheromone signaling likely arise due to large-scale changes in transcriptional programs for neuronal function downstream of behavioral switch gene function.

Psychopathological aspects of compulsive sexual behavior in males

The article is devoted to the study of the clinical picture of compulsive sexual disorders in men as a manifestation of various mental disorders. The authors compare and analyze psychopathological features in patients with compulsive behavioral disorders in the form of compulsive masturbation within four different clinical groups. Concurrently, the presence and clinical and psychopathological features of such a phenomenon as a compulsive sexual disorder are considered not only as an important diagnostic criterion for the qualification of mental disorder, but also for the development of adequate therapeutic measures. The article proposes a program of effective therapy and rehabilitation for these disorders.

Aphrodisiac potentials of the aqueous extract of Hibiscus asper Hook. f. leaves (Malvaceae) in male Wistar rats

Introduction: In general medicine, male sexual dysfunction is a major source of worry and consultation. Finding alternative substances like plants to regulate these disturbances is motivated by the side effects of standard aphrodisiac medicines. In the current investigation, male rats were used to test the aphrodisiac effects of an aqueous extract of Hibiscus asper leaves. Methodology: Aphrodisiac effect of the extract was evaluated following a single daily administration of Hibiscus asper at doses of 50, 100 and 200 mg/kg respectively. Sexual behavioural parameters such as mounting and intromission frequencies, mounting, intromission and ejaculatory latencies, sexual motivation were monitored on days 1, 4 and 8. At the end of the experiment, the grapping test was assessed, after which the animals were sacrificed and blood collected for the evaluation of cholesterol, fructose, proteins, acid phosphatase, testosterone, and other androgen-dependent enzymes. Some androgen-dependent organs, such as the testis, epididymis, seminal vesicle, prostate, and levator ani muscle, were also removed for biochemical and histological analysis. Results: The administration of the aqueous extract of H. asper leaves had a significant impact on sexual behaviour, increasing mounting frequency (MF), intromission frequency (IF), and ejaculatory latency (EL), and reducing mounting latency (ML), intromission latency (IL), and post-ejaculatory interval (PEI). There was also an enhancement in orientational activities, libido, arousal and potency. Cholesterol, acid phosphatase, vesicular fructose, proteins, nitric oxide and testosterone levels were all significantly increased in treated animals. Conclusion: These findings support the traditional use of H. asper leaves to enhance male sexual behavior by demonstrating the aphrodisiac potential of these plants.

Effect of Fruit Volatiles from Native Host Plants on the Sexual Performance of Anastrepha fraterculus sp. 1 Males.

Anastrepha fraterculus sp.1 males are sexually stimulated by the aroma of fruit of its native host Psidium guajava (guava). Other hosts, which are exotic to A. fraterculus, do not enhance male sexual behavior. Here we evaluate the effects of fruit volatile exposure on male A. fraterculus sp. 1 sexual performance using other native hosts, under the hypothesis that male improvement derives from a common evolutionary history between A. fraterculus sp. 1 and its native hosts. Four species were evaluated: Eugenia myrcianthes, Juglans australis, Psidium cattleianum, and Acca sellowiana. Guava was used as a positive control. Males were exposed to fruit from 12:00 pm to 4:00 pm, from day 8 to day 11 post-emergence. On day 12, we evaluated their calling behavior and mating success. Both guava and P. cattleianum enhanced calling behavior. Mating success was enhanced only by guava and a trend was found for P. cattleianum. Interestingly, the two hosts belong to the Psidium genus. A volatile analysis is planned to identify the compounds responsible for this phenomenon. The other native fruits did not improve the sexual behavior of males. Implications of our findings in the management of A. fraterculus sp. 1 are discussed.

Epididymectomy as a novel surgical procedure; application in the domestic cat

Feline overpopulation raises issues concerning health, ecology, economy, and ethics. Procedures to limit overpopulation should carefully address animal welfare, efficiency, costs, and feasibility. Vasectomy in unowned cats is suggested as preferable to standard neutering as it maintains male sexual behaviour which may induce ovulation and pseudopregnancy in intact females and may prevent immigration of other males. Vasectomy is not performed routinely because it is fastidious, time consuming and requires more material than standard neutering. We describe epididymectomy as an alternative. In a first experiment, we analysed semen, testosterone, behaviour and pain in six experimental cats before and after epididymectomy, and after castration two months later. Excised tissues were analysed histologically. Testosterone concentrations did not differ significantly between intact and epididymectomised animals but were significantly different after castration. Sexual behaviour and testicular spermatogenesis persisted after epididymectomy, but with a marked drop in the semen count after 7 days. The Glasgow pain scores did not differ significantly after epididymectomy and castration. In a subsequent experiment, 20 privately owned cats were epididymectomised and castrated immediately afterwards, to analyse the learning curve and perioperative complications. The time required for an epididymectomy was significantly shorter than for castration. The study confirms that epididymectomy is quicker and less invasive than castration, it is associated with minimal risks and post-operative pain while easy to learn and inexpensive. Further field studies are required to test its efficiency for feline feral population control or in other species such as in bears, lions or deer, where infertility is required and castration not wanted.

The effect of phenotypic heterogeneity on behaviours linked to invasive success

AbstractWhile most introduced species fail to become invasive, those that succeed are a major threat to global biodiversity. To improve the management of invasive species, a predictive understanding of invasion risk is needed. There is strong evidence that invasive success is linked to specific traits of the introduced species, and it is well recognised that phenotypic trait heterogeneity is linked to population viability. However, the effects of population‐level traits, and the contribution of trait heterogeneity to invasive success, remain poorly addressed in invasion biology. Here, we address this gap by quantifying the contribution of founding population phenotypic heterogeneity to reproductive success (a proxy for invasion success). Namely, we use the Trinidadian guppy (Poecilia reticulata) to test the prediction that founding populations composed of phenotypically heterogeneous males produce larger broods of more viable offspring than founding populations of reduced male heterogeneity. We found that founding populations of greater male phenotypic heterogeneity produced larger broods. Furthermore, whilst male sexual behaviour was an important predictor of brood size for all groups of reduced male heterogeneity, this was not observed for phenotypically heterogeneous populations. Taken together, our results provide strong support for the key role phenotypic heterogeneity plays in the invasion process.

Role of the hypothalamus in ghrelin effects on reproduction: sperm function and sexual behavior in male mice.

Ghrelin signals to the hypothalamus inhibit reproduction during times of food scarcity. In this study, we demonstrate that ghrelin impairs sperm quality in male mice. Ghrelin (GHRL) is an orexigenic peptide that has been investigated as one of the signals responsible for the reproductive performance of mammals under fluctuating metabolic conditions. Central GHRL administration impairs spermatogenesis in mice by regulating the hypothalamic-pituitary-gonadal axis function. In the present study, the hypothalamus role as a mediator of GHRL effects on sperm fertilizing capacity and male sexual behavior was evaluated. After 42 days of hypothalamic GHRL infusion or artificial cerebrospinal fluid, in vitro and in vivo sperm fertilizing capacity, testicular α-tubulin, speriolin gene expression and spermatic α-tubulin protein were evaluated. Hypothalamic expression of genes Kiss1, Gpr54 and Gnrh was also studied. The second group of animals was infused with one time only GHRL or artificial cerebrospinal fluid into the hypothalamus to evaluate the effects on sexual behavior. Results demonstrated that chronic GHRL administration to male mice significantly increased the percentages of pre-implantation embryo loss and the number of post-implantation embryo loss. In relation to the gene expression, our results show a relative decrease of Kiss1, Gpr54 and Spatc1. Although no significant differences were observed in the quantitative expression of α-tubulin protein, qualitative changes in its expression pattern were observed. In addition, a dual effect on sexual behavior was observed: 40% of the treated animals showed a significant reduction in the number of mounts and intromissions, while a 60% showed a significant decrease in ejaculation latency vs control animals. In conclusion, our results provide evidence that central GHRL administration possibly induces failure in embryo development and/or implantation in the females mated with treated males, possibly because of a negative effect in the α-tubulin pattern.

STUDY OF SOME REPRODUCTIVE PARAMETERS AND SEXUAL BEHAVIOR IN AWASSI RAMS: A REVIEW

Reproductive efficiency represented by sexual desire, semen quality, testicular dimensions, and level of sex hormones are among the main components of ram fertility, which affect the fertility and productivity of the herd. Since the development of the testicles is related to reproductive activity and the ability to fertilize, so measuring the dimensions of the testicles is important in evaluating the reproductive capacity of rams. In addition, the concentration of testosterone is reflected in most of the characteristics of male sexual behavior, as it is positively and significantly correlated with ejaculate volume, mass motility, and sperm concentration. The high level of testosterone hormone in the blood plasma during reproductive season leads to an increase in male sexual desire and an improvement in the quality of semen through direct influence in the process of sperm formation and the volume ejaculate, density and vitality of semen. In addition to reproductive traits are also affected by age, body weight, season and herd management, as well as the impact of the environmental conditions, which are temperature, humidity, level of nutrition, quantity and quality, and length of the photoperiod, which is one of the most important factors affecting the reproductive performance of rams.

A new approach for on-demand premature ejaculation

For quite some time, off-label use of selective serotonin reuptake inhibitors (SSRIs) is the primary choice of pharmacological treatment of lifelong premature ejaculation (PE). Unfortunately these treatments do not exert on-demand effects and have to be taken chronically. Although several new approaches have been introduced the last decade, on-demand treatment appears a big bottleneck (Olivier and Olivier, 2019). In our research on sexual behavior in male rats, we developed a model for male sexual behavior that is able to replicate the effects of SSRIs in men with lifelong premature ejaculation. After extensive weekly sexual training of large cohorts of male Wistar rats, a portion of them displays stable and high levels of sexual behavior in 30-min. tests with an estrus female, presented by very stable levels of high ejaculation frequencies and short ejaculation latencies. These fast-ejaculating rats are used for drug testing. SSRIs exert the profile as shown in men with lifelong PE, no acute effects but only sexual inhibition after chronic administration. We found that adding a very selective 5-HT1A receptor antagonist Atlas987 (10-mg/kg IP) to the SSRI paroxetine (5-mg/kg IP) led to acute (on-demand) inhibition of sexual behavior in male rats, evidenced by a strong reduction in the ejaculation frequency and doubling of ejaculation latency. A similar profile was found with the reference 5-HT1A-receptor antagonist WAY100,635 (0.3 mg/kg IP) plus 5 mg/kg paroxetine. Based on these and additional findings we are in the process of developing a new approach to treat lifelong premature ejaculation with an on-demand medication: Enduro, which is a combination of an SSRI (paroxetine) with a 5-HT1A-receptor antagonist (Atlas987). Olivier JDA,Olivier B. Antidepressants and sexual dysfunction; translational aspects. Current Sexual Health Reports, 11: 156-166, 2019 No conflicts of interest

Androgen receptors immunoreactivity in the rat brain of males with same-sex preference

Androgen receptors (AR) are crucial in the control of male sexual behavior and sex preference. AR are particularly concentrated in areas related with the neuroendocrine control of sex preference including the medial amygdala (MeA), the ventromedial nucleus of the hypothalamus (VMH), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA), the nucleus accumbens (Acb), the suprachiasmatic (SCh) and supraoptic (SO) nuclei, but also seem to be important for the control of reproductive processes in the hippocampus (CA1-CA4 and dentate gyrus, DG). In the present study we analyzed the density of AR in these brain areas of adult male rats with sexual preference (established in a three-compartment box). Same-sex preference was produced in male rats by the prenatal administration of the aromatase inhibitor, letrozole (0.56 μg/kg/ml s.c. G10-22) that usually produces 1–2 animals per litter with same sex preference, while the others retain a female sex preference. We also included a group of proestrus females that had a clear preference for a sexually active male. AR were analyzed by immunocytochemistry using PG21 as primary antibody. We also measured total plasma testosterone concentrations by radioimmunoassay. In males with same sex preference there was a specific AR overexpression in CA3 and CA4 that suggests a feminized pattern because females in proestrus trend to show a higher density of AR in these hippocampal areas. Sex differences in AR density were found in the anterior cingulate cortex (ACg) and frontoparietal cortex (FrPa). Serum levels of testosterone did not differ between groups. Data are discussed based on the role of AR in the hippocampus.