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Rationale: Drug and natural rewarding stimuli activate the mesolimbic dopaminergic system. Both methamphetamine (Meth) and copulation to satiety importantly increase dopamine (DA) release in the nucleus accumbens (NAc), but with differences in magnitude. This paper analyzes the interaction between Meth administration and the intense sexual activity associated with sexual satiety. Objectives: To evaluate possible changes in Meth-induced behavioral effects and striatal DA-related protein expression due to sexual satiety. Methods: Meth-induced locomotor activity and conditioned place preference (CPP) were tested in sexually experienced male rats that copulated to satiety (S–S) or ejaculated once (1E) the day before or displayed no sexual activity (control group; C). DA receptors and DA transporter expression were determined by western blot in the striatum of animals of all sexual conditions treated with specific Meth doses. Results: Meth's locomotor and rewarding effects were exacerbated in S–S animals, while in 1E rats, only locomotor effects were enhanced. Sexual activity, by itself, modified DA-related protein expression in the NAc core and in the caudate-putamen (CPu), while Meth treatment alone changed their expression only in the NAc shell. Meth-induced changes in the NAc shell turned in the opposite direction when animals had sexual activity, and additional changes appeared in the NAc core and CPu of S–S rats. Conclusion: Sexual satiety sensitizes rats to Meth's behavioral effects and the Meth-induced striatal DA-related protein adaptations are modified by sexual activity, evidencing cross-sensitization between both stimuli. [ABSTRACT FROM AUTHOR]

Rationale: Exposure of male rats to an inaccessible receptive female and copulation increases dopamine (DA) levels in the nucleus accumbens (NAcc). Males copulating to satiety become sexually inhibited and most of them do not display sexual activity when presented with a sexually receptive female 24 h later. This inhibitory state can be pharmacologically reversed. There are no studies exploring NAcc DA levels during this sexual inhibitory state. Objectives: To characterize changes in NAcc DA and its metabolites' levels during sexual satiety development, during the well-established sexual inhibitory state 24 h later, and during its pharmacological reversal. Methods: Changes in NAcc DA and its metabolites were measured in sexually experienced male rats, using in vivo microdialysis, during copulation to satiety, when presented to a new sexually receptive female 24 h later, and during the pharmacological reversal of the sexual inhibition by anandamide. Results: NAcc DA levels remained increased during copulation to satiety. DA basal levels were significantly reduced 24 h after copulation to satiety, as compared to the initial basal levels. Presenting a receptive female behind a barrier 24 h after satiety did not induce the typical NAcc DA elevation in the sexually satiated males but there was a decrease that persisted when they got access to the female, with which they did not copulate. Anandamide injection slightly increased NAcc DA levels coinciding with sexual satiety reversal. Conclusions: Reduced NAcc DA concentrations coincide with the inhibition of an instinctive, natural rewarding behavior suggesting that there might be a DA concentration threshold needed to be responsive to a rewarding stimulus. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) has been shown to be an effective nutritional intervention for increasing longevity in some animal species. The objective of this study was to evaluate CR's effects on metabolic and reproductive parameters in 12-month-old male Wistar rats. The rats were distributed in three groups: control, CR at 15%, and CR at 35% for 6 (up to 18 months of age) and 12 months (up to 24 months of age). At the end of CR treatment, we evaluated reproductive (male sexual behavior (MSB), sperm quality) and biochemical parameters (plasma glucose, glucose-regulating hormone, and sex steroid levels), and quantified annexin V in the seminiferous epithelium. Results showed that MSB and sperm quality were improved after 6 months of CR associated with increases in plasma testosterone and decrease annexin V in the seminiferous epithelium of the testicles compared to their control group. The metabolic profile of the CR rats also improved compared to controls. However, these effects of CR on reproductive parameters were not maintained after 12 months of CR. Findings suggest that beginning CR at the age of maturity reestablishes the behavioral sexual response and reproductive function in older animals after 6 months of CR and improves endocrine functioning during aging. [ABSTRACT FROM AUTHOR]

Kisspeptin has an indispensable role in gonadotropin-releasing hormone/gonadotropin secretion in mammals. In rodents, kisspeptin neurons are located in distinct brain regions, namely the anteroventral periventricular nucleus-periventricular nucleus continuum (AVPV/PeN), arcuate nucleus (ARC), and medial amygdala (MeA). Among them, the physiological role of AVPV/PeN kisspeptin neurons in males has not been clarified yet. The present study aims to investigate the acute effects of the olfactory and/or mating stimulus with a female rat on hypothalamic and MeA Kiss1 mRNA expression, plasma luteinizing hormone (LH) and testosterone levels in male rats. Intact male rats were exposed to the following stimuli: exposure to clean bedding; exposure to female-soiled bedding as a female-olfactory stimulus; exposure to female-soiled bedding and mating stimulus with a female rat. The mating stimulus significantly increased the number of the AVPV/PeN Kiss1 mRNA-expressing cells in males within 5 minutes after the exposure, and significantly increased LH and testosterone levels, followed by an increase in male sexual behavior. Whereas, the males exposed to female-soiled bedding showed a moderate increase in LH levels and no significant change in testosterone levels and the number of the AVPV/PeN Kiss1 mRNA-expressing cells. Importantly, none of the stimuli affected the number of Kiss1 mRNA-expressing cells in the ARC and MeA. These results suggest that the mating-induced increase in AVPV/PeN Kiss1 mRNA expression may be, at least partly, involved in stimulating LH and testosterone release, and might consequently ensure male mating behavior. This study would be the first report suggesting that the AVPV/PeN kisspeptin neurons in males may play a physiological role in ensuring male reproductive performance.

ABSTRACT: Introduction: The COVID-19 pandemic drastically altered the way of life around the world. Due to social distancing measures, contact restrictions and fears of infection, social life has changed significantly. These measures along with the stressors associated with the current worldwide situation, will inevitably have an effect on people's interpersonal and personal behaviors. Aim: This study evaluates the effect the COVID-19 pandemic and nationwide German lockdown had on the sexual behavior of cis men. Methods: An anonymous nationwide web-based questionnaire was conducted among cis men in Germany during the first COVID-19 home isolation (April 20, 2020–July 20, 2020). The questionnaire was distributed via e-mail, online chats and social-media platforms. Main Outcome Measures: Data was collected on general characteristics including demographics and socio-economic backgrounds. To evaluate sexual health, questions from the Sexual Behavior Questionnaire were included. Results: 523 cis male participated. 414 met the inclusion criteria. Most were heterosexual (n = 248, 59.9%; vs homosexual n = 97, 23.4%; vs bisexual n = 69, 16.7%). 243 (59%) were employed, 153 (37.1%) were students and 16 (3.9%) were unemployed. Most of the participants reported an annual income lower than 75.000€. During the lockdown, average weekly frequency of sexual intercourse and masturbation was increased in all groups. Consistently, a significant rise of higher satisfaction with the frequency of sexual contacts during the quarantine was observed (P < .05). Furthermore, the level of sexual arousal increased significantly in all groups (P < .0005). Capability to enjoy sexual intercourse or masturbation increased significantly in heterosexual (P < .0005) and homosexual men (P < .005). Bisexual participants showed a significant increase in general satisfaction with sexual life (P < .05) and a significant decrease in satisfaction in relationship or single life (P < .05). Positive confounders in the changing of sexual behavior during the COVID-19 pandemic were: Being in a relationship or being single, parenthood and being employed. Conclusion: Our study firstly describes how COVID-19 pandemic related restrictions and social distancing measurements altered sexual behavior amongst cis male in Germany. Further studies, including sexual minorities specifically, are needed to clarify if the behavior in the first German nationwide quarantine has persisted or transformed as the pandemic proceeded. Mumm J-N, Vilsmaier T, Schuetz JM, et al. How the COVID-19 Pandemic Affects Sexual Behavior of Hetero-, Homo-, and Bisexual Males in Germany. Sex Med 2021;9:100380.

The preoptic area (POA) has long been recognized as a sleep center, first proposed by von Economo. The POA, especially the medial POA (MPOA), is also involved in the regulation of various innate functions such as sexual and parental behaviors. Consistent with its many roles, the MPOA is composed of subregions that are identified by different gene and protein expressions. This review addresses the current understanding of the molecular and cellular architecture of POA neurons in relation to sleep and reproductive behavior. Optogenetic and pharmacogenetic studies have revealed a diverse group of neurons within the POA that exhibit different neural activity patterns depending on vigilance states and whose activity can enhance or suppress wake, non-rapid eye movement (NREM) sleep, or rapid eye movement (REM) sleep. These sleep-regulating neurons are not restricted to the ventrolateral POA (VLPO) region but are widespread in the lateral MPOA and LPOA as well. Neurons expressing galanin also express gonadal steroid receptors and regulate motivational aspects of reproductive behaviors. Moxd1, a novel marker of sexually dimorphic nuclei (SDN), visualizes the SDN of the POA (SDN-POA). The role of the POA in sleep and other innate behaviors has been addressed separately; more integrated observation will be necessary to obtain physiologically relevant insight that penetrates the different dimensions of animal behavior.

The preoptic area (POA) has long been recognized as a sleep center, first proposed by von Economo. The POA, especially the medial POA (MPOA), is also involved in the regulation of various innate functions such as sexual and parental behaviors. Consistent with its many roles, the MPOA is composed of subregions that are identified by different gene and protein expressions. This review addresses the current understanding of the molecular and cellular architecture of POA neurons in relation to sleep and reproductive behavior. Optogenetic and pharmacogenetic studies have revealed a diverse group of neurons within the POA that exhibit different neural activity patterns depending on vigilance states and whose activity can enhance or suppress wake, non-rapid eye movement (NREM) sleep, or rapid eye movement (REM) sleep. These sleep-regulating neurons are not restricted to the ventrolateral POA (VLPO) region but are widespread in the lateral MPOA and LPOA as well. Neurons expressing galanin also express gonadal steroid receptors and regulate motivational aspects of reproductive behaviors. Moxd1, a novel marker of sexually dimorphic nuclei (SDN), visualizes the SDN of the POA (SDN-POA). The role of the POA in sleep and other innate behaviors has been addressed separately; more integrated observation will be necessary to obtain physiologically relevant insight that penetrates the different dimensions of animal behavior. [ABSTRACT FROM AUTHOR]

Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT1A receptors in rats facilitate ejaculatory behavior. However, the relative contribution of 5-HT1A somatodendritic autoreceptors and heteroreceptors in this pro-sexual behavior is unclear. Moreover, it is unclear whether the contribution of somatodendritic 5-HT1A autoreceptors and postsynaptic 5-HT1A heteroreceptors alter when extracellular 5-HT levels are chronically increased. Serotonin transporter knockout (SERT–/–) rats exhibit enhanced extracellular 5-HT levels and desensitized 5-HT1A receptors. These rats model neurochemical changes underlying chronic SSRI-induced sexual dysfunction. We want to determine the role of presynaptic versus postsynaptic 5-HT1A receptors in the pro-sexual effects of 5-HT1A receptor agonists in SERT+/+ and in SERT–/– rats. Therefore, acute effects of the biased 5-HT1A receptor agonists F-13714, a preferential 5-HT1A autoreceptor agonist, or F-15599, a preferential 5-HT1A heteroreceptor agonist, and S15535 a mixed 5-HT1A autoreceptor agonist/heteroreceptor antagonist, on male sexual behavior were assessed. A clear and stable genotype effect was found after training where SERT+/+ performed sexual behavior at a higher level than SERT–/– rats. Both F-15599 and F-13714 induced pro-sexual activity in SERT+/+ and SERT–/– animals. Compared to SERT+/+, the F13714-dose-response curve in SERT–/– rats was shifted to the right. SERT+/+ and SERT–/– rats responded similar to F15599. Within both SERT+/+ and SERT–/– rats the potency of F-13714 was much stronger compared to F-15599. S15535 had no effect on sexual behavior in either genotype. In SERT+/+ and SERT–/– rats that were selected on comparable low sexual activity (SERT+/+ 3 or less ejaculations and SERT–/– 5 or less ejaculations in 10 weeks) S15535 also did not influence sexual behavior. The two biased compounds with differential effects on 5-HT1A auto- and hetero-receptors, exerted pro-sexual activity in both SERT+/+ and SERT–/– rats. Applying these specific pharmacological tools has not solved whether pre- or post-synaptic 5-HT1A receptors are involved in pro-sexual activity. Moreover, the inactivity of S15535 in male sexual behavior in either genotype was unexpected. The question is whether the in vivo pharmacological profile of the different 5-HT1A receptor ligands used, is sufficient to differentiate pre- and/or post-synaptic 5-HT1A receptor contributions in male rat sexual behavior.

Testosterone aromatization into estrogens in the preoptic area (POA) is critical for the activation of male sexual behavior in many vertebrates. Yet, the cellular mechanisms mediating actions of neuroestrogens on sexual behavior remain largely unknown. We investigated in male and female Japanese quail by dual‐label fluorescent in situ hybridization (FISH) whether aromatase‐positive (ARO) neurons express glutamic acid decarboxylase 67 (GAD67), the rate‐limiting enzyme in GABA biosynthesis. ARO cells and ARO cells double labeled with GAD67 (ARO‐GAD67) were counted at standardized locations in the medial preoptic nucleus (POM) and the medial bed nucleus of the stria terminalis (BST) to produce three‐dimensional distribution maps. Overall, males had more ARO cells than females in POM and BST. The number of double‐labeled ARO‐GAD67 cells was also higher in males than in females and greatly varied as a function of the specific position in these nuclei. Significant sex differences were however present only in the most caudal part of POM. Although both ARO and GAD67 were expressed in the VMN, no colocalization between these markers was detected. Together, these data show that a high proportion of estrogen‐synthesizing neurons in POM and BST are inhibitory and the colocalization of GAD67 with ARO exhibits a high degree of anatomical specificity as well as localized sex differences. The fact that many preoptic ARO neurons project to the periaqueductal gray in male quail suggests possible mechanisms through which locally produced estrogens could activate male sexual behavior. [ABSTRACT FROM AUTHOR]

Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT1A receptors in rats facilitate ejaculatory behavior. However, the relative contribution of 5-HT1A somatodendritic autoreceptors and heteroreceptors in this pro-sexual behavior is unclear. Moreover, it is unclear whether the contribution of somatodendritic 5-HT1A autoreceptors and postsynaptic 5-HT1A heteroreceptors alter when extracellular 5-HT levels are chronically increased. Serotonin transporter knockout (SERT–/–) rats exhibit enhanced extracellular 5-HT levels and desensitized 5-HT1A receptors. These rats model neurochemical changes underlying chronic SSRI-induced sexual dysfunction. We want to determine the role of presynaptic versus postsynaptic 5-HT1A receptors in the pro-sexual effects of 5-HT1A receptor agonists in SERT+/+ and in SERT–/– rats. Therefore, acute effects of the biased 5-HT1A receptor agonists F-13714, a preferential 5-HT1A autoreceptor agonist, or F-15599, a preferential 5-HT1A heteroreceptor agonist, and S15535 a mixed 5-HT1A autoreceptor agonist/heteroreceptor antagonist, on male sexual behavior were assessed. A clear and stable genotype effect was found after training where SERT+/+ performed sexual behavior at a higher level than SERT–/– rats. Both F-15599 and F-13714 induced pro-sexual activity in SERT+/+ and SERT–/– animals. Compared to SERT+/+, the F13714-dose-response curve in SERT–/– rats was shifted to the right. SERT+/+ and SERT–/– rats responded similar to F15599. Within both SERT+/+ and SERT–/– rats the potency of F-13714 was much stronger compared to F-15599. S15535 had no effect on sexual behavior in either genotype. In SERT+/+ and SERT–/– rats that were selected on comparable low sexual activity (SERT+/+ 3 or less ejaculations and SERT–/– 5 or less ejaculations in 10 weeks) S15535 also did not influence sexual behavior. The two biased compounds with differential effects on 5-HT1A auto- and hetero-receptors, exerted pro-sexual activity in both SERT+/+ and SERT–/– rats. Applying these specific pharmacological tools has not solved whether pre- or post-synaptic 5-HT1A receptors are involved in pro-sexual activity. Moreover, the inactivity of S15535 in male sexual behavior in either genotype was unexpected. The question is whether the in vivo pharmacological profile of the different 5-HT1A receptor ligands used, is sufficient to differentiate pre- and/or post-synaptic 5-HT1A receptor contributions in male rat sexual behavior. [ABSTRACT FROM AUTHOR]

Administering clomipramine during the early days of life induced several behavioral and neurochemical alterations in adult male rats, which resemble major depression disorder. The alterations included poor sexual performance, which is considered a reward-seeking behavior regulated by dopaminergic system. Given that estrogen receptors are expressed in different areas of the brain involved in regulating reproductive behavior, motivation and mood. The objective of this study was to analyze the effect of a non-selective dopamine agonist (apomorphine) on sexual incentive motivation in rats exposed to clomipramine (CMI) in the neonatal period. In addition, we evaluated the expression of mRNA ERα and ERβ in nucleus accumbens (NAcc) and septum of CMI rats. We found that only a few rats subjected to neonatal CMI treatment performed mounts, intromissions and ejaculations. Also, those rats spent less time exploring the sexual incentive zone and had lower preference scores; this effect was reverted by administering 0.1 mg/kg of apomorphine. Finally, the CMI rats presented higher levels of mRNA ERα and ERβ, only in septum area. These data indicate that neonatal treatment with CMI altered the expression of mRNA ERα and ERβ in the septum, which participates in regulating the motivational component of sexual behavior. • Clomipramine administration during neonatal period alters the masculine sexual behavior. • The administration of apomorphine increases the sexual motivation in both control and clomipramine rats. • Clomipramine neonatal treatment in female rats impairs the expression of ER alpha and beta in septum. [ABSTRACT FROM AUTHOR]

Highlights • Reviews the current status of the behavior system for sexual learning. • In addition to reviewing research with quail (which was the focus of prior paper), in this treatment research with rats is also incorporated into the characterization of the behavior system. • Unlike prior papers which dealt primarily with sexual learning in males, in this review we also discuss in detail sexual learning in females. • For the first time the characterization of the sexual learning system includes detailed information on how learning facilitates fertilization and reproductive success. • Although much progress has been made in characterizing the sexual learning system, we include an extensive section discussing areas for future research. • A new perspective on how sexual learning can contribute to evolutionary change is included. Abstract In this paper we review and update evidence relevant to formulating a behavior system for sexual learning. We emphasize behavioral rather than neurobiological evidence and mechanisms. Our analysis focuses on three types of responses or response modes: general search, focal search, and consummatory or copulatory behavior. We consider how these response modes are influenced by three categories of stimuli: spatially distributed contextual cues, arbitrary localized stimuli, and species-typical cues provided by the sexual partner. We characterize behavior control by these types of stimuli before and after various Pavlovian conditioning procedures in which the unconditioned stimulus is provided by copulation with a sexual partner. The results document extensive Pavlovian modifications of sexual behavior. These conditioning effects reflect new conditioned responses that come to be elicited by various categories of stimuli. In addition, the conditioning of contextual cues and localized stimuli facilitate sexual responding to species-typical cues. Thus, learning experiences enhance how the species-typical cues of a sexual partner stimulate sexual behavior. These modulatory conditioning effects not only produce significant behavioral changes but also increase rates of fertilization of eggs and numbers of offspring produced. These latter findings suggest that sexual learning can lead to differential reproductive success, which in turn can contribute to evolutionary change. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Piper auritum Kunth is employed as an aphrodisiac in the traditional medicine, but corroborative evidence for such effect is scarce. Aim of the study The pro-sexual effect of an aqueous extract of P. auritum and its possible mechanisms were analyzed in two paradigms of male sexual function. Material and methods Effects of an aqueous extract of P. auritum (PA, single administration) were investigated in the fictive ejaculation, and copulatory behavior paradigms in sexually sluggish male rats. WAY 100635 (antagonist of 5-HT 1A receptors), atosiban (antagonist of oxytocinergic receptors), L-NAME (inhibitor of the nitric oxide synthase) and baclofen (antagonist of GABA B receptors) were used as pre-treatments in order to investigate the role of different neurotransmitter systems in PA actions. Chemical profile of PA was determined by Gases Chromatography and Ultra Performance Chromatography-Electrospray Ionization-Masses Spectrometry (UPLC-ESI-MS). Results In males with retarded ejaculation, PA stimulated ejaculatory behavior and recovered electromyographic activity of pelvic musculature participating in seminal emission and ejaculation. All pre-treatments blocked stimulating effects of PA on the fictive ejaculation; additionally WAY 100635 interfered with PA actions on ejaculatory behavior. Safrol, apigenin dimethylether, myristicin, vaccihein A, sakuranin and sakuranetin flavonoids, were main constituents of PA, with possible participation in its pro-sexual effects. Conclusions Pro-sexual effects of P. auritum elicited at level of ejaculation were mediated by several neurotransmitter systems, among which serotonin and its 5-HT 1A receptors play an important role. Present findings support P. auritum reputation as an aphrodisiac, with potential use in delayed ejaculation disorder. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Sexual behavior is one of the biologically highly relevant types of behavior. Sexual arousal, or an initial stage of sexual behavior, is of particular interest since it triggers all the following events but still remains the least known element of this behavior. Sexual dysfunctions are caused by aging, stress, or side effects of psychotropic drugs; they are symptoms of a variety of neurological and psychiatric disorders. Therefore, the study of sexual behavior appears to be an important step in modeling various animal pathologies and the effects of psychotropic drugs. We have performed phenotyping of animals with hereditary predisposition to catalepsy using our previous development, a model of male sexual arousal, and examined the relationship between catalepsy and sexual arousal. The main gene for a high predisposition to catalepsy was shown to be associated with the expression of sexual motivation, but not with the hormonal component of sexual arousal (increase in plasma testosterone levels following exposure to a receptive female). ASC (Antidepressant Sensitive Catalepsy) mice, proposed as a model of depression, had a decreased manifestation of sexual motivation, while male GC (Genetic Catalepsy) strain rats had enhanced sexual motivation. Noteworthy, highly excitable GC strain animals corresponding to the manic pole of bipolar disorders prevail at the current stage of breeding. Our results are in a good agreement with clinical data that indicate reduced libido in depressed patients and hypersexuality in people with bipolar disorder.

Highlights • c-Fos expression in the MPNc increases after ejaculation in male rats. • c-Fos expression in non-calbindin MPNc neurons decreases with sexual experience. • The MPNc may change functionally with sexual experience. Abstract The medial preoptic area (MPN) plays an important role in the control of male sexual behavior. In rats, the central part of the MPN (MPNc) is sexually dimorphic and contains a sexually dimorphic nucleus composed of neurons expressing calbindin-D28 K (CALB-SDN). Although the functions of the MPNc are not well understood, surgical destruction of the MPNc adversely affects the performance of sexual behavior in sexually naive males, but not in sexually experienced males, supporting the notion that the MPNc changes functionally with sexual experience. In this study, we aimed to determine the effects of sexual experience on the neuronal activity of the MPNc and CALB-SDN. Sexual behavior in sexually inexperienced males that had no experience of ejaculation, and experienced males that had ejaculated once was observed. After they displayed sexual behavior, the brains were sampled, and immunohistochemical analysis of c-Fos, a neuronal activity marker, in the MPNc and CALB-SDN was performed. The numbers of c-Fos-immunopositive cells with or without calbindin-D28K-immunoreactivity increased significantly in the MPNc and CALB-SDN following ejaculation in both sexually inexperienced and experienced males, although the numbers did not change significantly with exposure to estrous female odors, the first mount, and the first intromission before and after the first ejaculation. We further found that the number of c-Fos-immunopositive and calbindin-D28K-immunonegative cells in the MPNc, but not in the CALB-SDN, was significantly smaller in sexually experienced males than in sexually inexperienced males. These results suggest that a population of MPNc neurons, which is located outside the CALB-SDN and do not express calbindin-D28 K, are activated during the first copulation and then silent after acquisition of sexual experience. [ABSTRACT FROM AUTHOR]

Two inbred strains of Sprague-Dawley rats, known as the Hatano high- and lowavoidance animals (HAA and LAA respectively), have been selectively bred for high versus low rates of avoidance responses in a shuttle-box avoidance task. To investigate differences in the sexual behavior of Hatano rats, male HAA, LAA and SD rats were tested from 12 to 15 weeks of age. LAA rats exhibited more rapid and frequent sexual behavior than HAA or SD rats, and such differences increased with repeated sexual experience. Plasma testosterone levels tended to be lower in LAA rats than in HAA or SD rats, suggesting that active sexual behavior in LAA rats is not related to these levels. Strain differences in mating behavior between HAA and LAA rats may be caused by emotional responses to novelty. [ABSTRACT FROM AUTHOR]

The Coolidge effect is the renewal of sexual behavior after the presentation of a novel sexual partner and possibly occurs as the result of habituation and dishabituation processes. This re-motivation to copulate is well studied in males and is commonly related to sexual satiety, which involves several neurobiological changes in steroid receptors and their mRNA expression in the CNS. On the other hand, there are few reports studying sexual novelty in females and have been limited to behavioral aspects. Here we report that the levels of rat proceptive behavior, a sign of sexual motivation, declines after 4 h of continuous mating, particularly in females that were unable to regulate the time of mating. Such reduction was not accompanied by changes in lordosis, suggesting that they were not due to the vanishing of the endocrine optimal milieu necessary for the expression of both components of sexual behavior in the female rat. These and previous data support important differences between sexual behavior in both sexes that would result in natural divergences in the Coolidge effect expression. We here also review some reports in humans showing peculiarities between the pattern of habituation and dishabituation in women and men. This is a growing research field that needs emphasis in female subjects. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to endocrine‐disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3‐dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti‐androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25–250 mg kg–1 via oral administration over 28 consecutive days post‐birth) suppressed male sexual behavior and reduced testes size. These changes were dose‐dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life. [ABSTRACT FROM AUTHOR]

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 CdCl 2 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. • Postnatal exposure to Cd decreases sexual motivation and copulatory behavior. • Postnatal Cd exposure induced a decrease in the number of cells in mPOA. • AR and ER-α immunoreactivity decreases in mPOA and MeA with Cd exposure. [ABSTRACT FROM AUTHOR]

The sagittalis nucleus of the hypothalamus (SGN) is a small nucleus located in the interstitial area between the arcuate and ventromedial nuclei of the hypothalamus in rats. The SGN exhibits male-biased sexual dimorphism and expresses estrogen receptor α and calbindin-D28 K. This suggests a contribution of the SGN to sexually differentiated brain function, but its functional role is unknown. In this study, neuronal activation in the SGN during sexual behavior in male rats was examined by c-Fos immunohistochemistry. The number of c-Fos-immunoreactive (c-Fos-ir) cells was elevated with only exposure to chemosensory cues of estrous females and significantly increased after the first mount. The first intromission and ejaculation did not induce further increases in the number of c-Fos-ir cells in the SGN. These findings suggest that the SGN is involved in regulation of the early phase of male sexual behavior, including motivation. [ABSTRACT FROM AUTHOR]

Tramadol is a well-known and effective analgesic. Recently it was shown that tramadol is also effective in human premature ejaculation. The inhibitory effect of tramadol on the ejaculation latency is probably due to its mechanism of action as a μ-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake inhibitor. In order to test this speculation, we tested several doses of tramadol in a rat model of male sexual behavior and investigated two types of drugs interfering with the μ-opioid and the 5-HT system. First the μ-opioid receptor agonist properties of tramadol were tested with naloxone, a μ-opioid receptor antagonist. Second, the effects of WAY100,635, a 5-HT 1A receptor antagonist, were tested on the behavioral effects of tramadol. Finally the effects of paroxetine, a selective serotonin reuptake inhibitor, combined with naloxone or WAY100,635 treatment, were compared to the effects of tramadol combined with these drugs. Results showed that naloxone, at a sexually inactive dose, could only partially antagonize the inhibitory effect of tramadol. Moreover, low and behaviorally inactive doses of WAY100,635, strongly decreased sexual behavior when combined with a behaviorally inactive dose of tramadol. Finally we showed that the effects of paroxetine on sexual behavior resembled the effects of tramadol, indicating that tramadol's inhibitory effects on sexual behavior are primarily and mainly caused by its SSRI properties and that its μ-opioid receptor agonistic activity only contributes marginally. These findings support the hypothesis that tramadol exerts inhibition of premature ejaculations in men by its 5-HT reuptake inhibiting properties. [ABSTRACT FROM AUTHOR]

GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons’ activity. Blockade of VTA GABA A receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72 h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state. To test this hypothesis, in the present work we investigated the effect of GABA A receptor blockade in sexually exhausted males 24 h after copulation to satiety, once the sexual inhibitory state is established, and compared it with its effect in sexually experienced rats. Results showed that low doses of systemically administered bicuculline induced sexual behavior expression in sexually exhausted rats, but lacked an effect on copulation of sexually experienced animals. Intra-VTA bilateral infusion of bicuculline did not modify sexual behavior of sexually experienced rats, but induced sexual behavior expression in all the sexually exhausted males. Hence, GABA plays a role in the control of sexual behavior expression at the VTA. The role played by GABAergic transmission in male sexual behavior expression of animals with distinct sexual behavior conditions is discussed. [ABSTRACT FROM AUTHOR]

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 sexual behavior: motor displays, drive, and reward. [Display omitted] • A multisynaptic neural circuit that converts sensory input to male sexual behavior • An embedded molecular timer delays mating onset following mate recognition • This neural circuit elicits dopamine release and governs male sexual drive and reward • This neural circuit governs libido and motor displays of male sexual behavior Molecular genetics, neuronal activity monitoring, and circuit epistasis reveal a developmentally wired neural circuit for male sexual behavior that senses pheromones, recognizes mates, triggers mating, and governs sexual drive and reward. [ABSTRACT FROM AUTHOR]

Discoveries in the past two decades have continued to improve our understanding of the pathophysiology of erectile dysfunction disease and animal models have played a significant role to define the basic mechanisms of erectile dysfunction treatment. Both in vitro and in vivo models have been developed in the past years to study the aphrodisiac agents. Methods that are used in aphrodisiac study can be categorized into physical methods including male sexual behavior (mount frequency, mount latency, intromission frequency, intromission latency, ejaculation frequency, post-ejaculatory interval, couplatory rate, index of libido, computed male sexual behavior parameter), pendiculation study, orientation behavior, determination of hesitation time & attraction towards female, test of potency, test for libido, penile microcirculation study, Intracavernous pressure study and biochemical methods, histopathology, sperm count, Fructose content in seminal vesicles, sperm preservation, organ weight, hormonal determination, assay of nitric oxide synthase, In vitro nitric oxide release & androgen receptor protein. This review aims to highlight some of the new and currently used experimental models that are used for the evaluation of aphrodisiac agents.

Various parameters of sexual behaviour were studied in ten male rabbits daily tested with sexually receptive females (ovariectomized, given estradiol benzoate s.c. 5 µg/day). The aim of this study was to analyse rabbit sexual behaviour during successive tests leading to sexual exhaustion. We allowed copulation ad libitum and determined if sexual satiety was reached within a day and sexual exhaustion across several days. The pair was allowed to copulate freely until the male failed to show sexual interest in that female for 30 minutes. The female was then removed and replaced by another; this procedure was repeated using as many does as needed, until the male showed no interest in any female for 2 hours. Scent-marking (chinning) was also recorded, before and after the copulation test. This whole procedure was repeated daily until the male showed no sexual behaviour at all on a given day. Within a test, copulation ad libitum led to a gradual increase in the time interval between successive mounts and ejaculations, regardless of the day of testing. Such increments predicted that the buck was reaching sexual satiety. The “miss” rate (i.e., the proportion of mounts that did not culminate in ejaculation) significantly increased from a median of 25 on the first day to 55 on the last day of testing. The mean time to reach copulatory inactivity decreased from 4 hrs on the first day to 1 hr on the last day. The total number of ejaculations within a test decreased from an average of 22 to 6 (first vs last day, respectively) and the number of chin marks was reduced by 69% compared with pre-mating values, regardless of the day of testing. All bucks eventually stopped copulating after a variable number of days (range=2-15 days). We concluded that, following copulation ad libitum with several females, male rabbits reach sexual satiety (i.e., they are unable to continue copulating on the same day) and, after several days, they also attain sexual exhaustion, a state in which copulation is totally arrested for at least 24 hours. Some behavioural parameters can be used as reliable predictors that a buck is approaching sexual satiety and sexual exhaustion.

Sexual behavior is a natural reward and the mesolimbic (MSL) system is involved in the processing of its motivational component and reinforcing properties. Endocannabinoids control rewarding behaviors through the modulation of MSL system's activity. The endocannabinoid anandamide (AEA), systemically administered, produces dose-based, biphasic effects on male rat copulation, facilitating its expression at low doses in both, sexually experienced and sexually exhausted male rats. We hypothesized that AEA's sexual facilitative effects might be exerted at the MSL circuit. Therefore, in this work different AEA doses were bilaterally infused into the VTA of sexually experienced or sexually exhausted animals and their copulatory behavior recorded. Results showed that the lowest AEA dose tested lacked an effect, intermediate doses facilitated specific sexual parameters, and the highest dose inhibited copulation of sexually experienced males. In sexually exhausted animals low AEA doses reversed the sexual inhibition that characterizes sexual satiety, but this effect was lost at higher doses. Together, these data show that the VTA is a target for AEA's biphasic sexual effects suggesting a role of the MLS system in the actions of endocannabinoids on male rat sexual behavior. [ABSTRACT FROM AUTHOR]

Mesquite ( Prosopis sp.) and Leucaena leucocephala are widespread legumes, widely used to feed several livestock species and as food source for human populations in several countries. Both mesquite and Leucaena contain several phytoestrogens which might have potential estrogenic effects. Thus, the aim of this study was to evaluate the effects of mesquite pod and Leucaena extracts on several aspects of behavior and reproductive physiology of the male rat. The effects of the extracts were compared with those of estradiol (E 2 ) and of two isoflavones: daidzein (DAI) and genistein (GEN). The following treatments were given to groups of intact male rats: vehicle; mesquite pod extract; Leucaena extract; E 2 ; DAI; GEN. The results indicate that mesquite pod and Leucaena extracts disrupt male sexual behavior in a similar way to DAI and GEN, but less than E 2 . The main disruptor of sexual behavior was E 2 , however after 40 and 50 days of administration, both extracts and phytoestrogens disrupted sexual behavior in a similar way to E 2 . The extracts also increased testicular germ cell apoptosis, decreased sperm quality, testicular weight, and testosterone levels, as phytoestrogens did, although these effects were less than those caused by estradiol. The number of seminiferous tubules with TUNEL-positive germ cells increased in extracts treated groups in a similar way to phytoestrogens groups, and E 2 caused the greatest effect. The number of TUNEL-positive cells per tubule increased only in Leucaena extract and E 2 groups, but not in mesquite- and phytoestrogens-treated groups. Spermatocytes and round spermatids were the TUNEL-positive cells observed in all experimental groups. This effect was associated with smaller testicular weights without atrophy in experimental groups compared with control. Testicular atrophy was only observed in estradiol-treated males. Testosterone decreased in males of all experimental groups, compared with control, this androgen was undetectable in E 2 treated males. These results suggest that mesquite pod and Leucaena extracts cause effects similar to those of phytoestrogens in male rat reproduction, these effects were lower than those caused by E 2 . [ABSTRACT FROM AUTHOR]

Sexual behavior is one of the biologically highly relevant types of behavior. Sexual arousal, or the initial stage of sexual behavior, is of particular interest since it triggers all the following events, but still remains the least known element of this behavior. Sexual dysfunctions are caused by aging, stress, or the side effects of psychotropic drugs; they are symptoms of a variety of neurological and psychiatric disorders. Therefore, the study of sexual behavior appears to be an important step in modeling various animal pathologies and the effects of psychotropic drugs. We have phenotyped animals with a hereditary predisposition to catalepsy using our previous development, a model of male sexual arousal, and examined the relationship between catalepsy and sexual arousal. The major gene for a high predisposition to catalepsy was shown to be associated with the expression of sexual motivation, but not with the hormonal component of sexual arousal (increase in the plasma testosterone levels following exposure to a receptive female). ASC (Antidepressant Sensitive Catalepsy) mice, proposed as a model of depression, had a decreased manifestation of sexual motivation, while male GC (Genetic Catalepsy) strain rats had enhanced sexual motivation. We note that the highly excitable GC strain animals corresponding to the manic pole of bipolar disorders prevail at the current stage of breeding. Our results are in good agreement with the clinical data that indicate reduced libido in depressed patients and hypersexuality in people with bipolar disorder. [ABSTRACT FROM AUTHOR]

Animals change their biological activities depending on their nutritional state. Reproductive functions, including sexual behavior, are suppressed under low-energy conditions; however, the underlying neuronal mechanism is poorly understood. Neuropeptide Y (NPY) is an orexigenic molecule released in response to low-energy conditions and has an inhibitory effect on sexual behavior. We examined how NPY is involved in energy state-dependent regulation of male sexual behavior. Mounting, intromission, and ejaculation were evaluated as parameters of sexual behavior. Almost all parameters indicated that fasting for 24 h suppressed male sexual behavior. Intracerebroventricular injection of NPY inhibited sexual behavior in males that free-fed for 8 h following 24-h fasting (fed males). We next examined whether the dorsal raphe nucleus (DRN), in which serotonergic (5-HT) neurons are distributed, is involved in NPY-mediated inhibition of male sexual behavior. NPY-positive processes immunoreactive for a presynaptic marker, synaptophysin, were distributed in the DRN of both fed and fasted males. Expression of the NPY Y1 receptor in 5-HT neurons was also observed. Direct injection of NPY or 8-OH-DPAT (a 5-HT 1A receptor agonist that inhibits the activity of 5-HT neurons) into the DRN inhibited male sexual behavior in fed males. In contrast, injection of BIBP-3226, a NPY Y1 receptor antagonist, or (+)-DOI hydrochloride (DOI), a 5-HT 2A/2C receptor agonist that activates 5-HT neurons, into the DRN partially recovered male sexual behavior in 24-h fasted males. These results suggest that NPY inhibits serotonergic neuronal activity via the Y1 receptor in the DRN, resulting in suppression of male sexual behavior in low-energy conditions. [ABSTRACT FROM AUTHOR]

Gonadal hormones have a developmental role in organization of the nervous system that regulates sexually dimorphic behavior. It is well known that androgen secreted from testes in the perinatal period is converted to estrogen by aromatase in rodent brain, and that estrogen and its receptor play a pivotal role in masculinization of brain structure and function. Treatment with flutamide, an androgen receptor (AR) antagonist, during the perinatal period inhibits development of malespecific brain structure and function, suggesting that androgen signaling via AR also influences brain masculinization. In this study, we investigated which stage during the postnatal period is critical for androgen signaling in brain masculinization. The postnatal period was designated as postnatal days (PD) 0–22, and divided into stages I (PD 0–7), II (PD 8–14), and III (PD 15–22). Newborn male rats were given flutamide subcutaneously in each stage. After adulthood, the effects of postnatal flutamide treatment on brain masculinization were evaluated byanalysis of male sexual behavior. Continuous inhibition of AR throughout stages I and II caused a robust reduction of the intromission ratio and ejaculation frequency compared with other groups. AR inhibition in stage I, II, or III did not cause any change. AR inhibition had no effect onmount behavior. These results show that stage-specific AR activation in the first two postnatal weeks may contribute to brain masculinization mediating male sexual behavior in adulthood. [ABSTRACT FROM AUTHOR]

Male sexual satiety has been associated with a decrease in dopamine levels. Spontaneous recovery of copulatory behavior begins at least 72 h after sexual satiety is reached or in the condition in which a sexually-satiated male is exposed to a new receptive female distinct from the one with which sexual satiety was reached. The aim of the present study was to explore whether dopaminergic activation by bromocriptine (BrCr) can reactivate copulatory behavior with the same sexual mate immediately after sexual satiety is reached. Male rats were divided into three groups exposed to one of the following three conditions: 1) administration of 2 mg/kg s.c. of BrCr and exposure to the same female with whom sexual satiety was previously reached; 2) administration of 0.3 mL s.c. of the vehicle solution with exposure to the same female with whom sexual satiety was reached; and, 3) exposure to a new receptive female after sexual satiety was reached. Results showed that BrCr significantly reactivated copulatory capability in sexually-satiated males with the same receptive female. In contrast, no males in the vehicle group ejaculated with the same female after reaching sexual exhaustion. Copulation was reactivated by BrCr in a way similar to that observed in untreated males exposed to a new receptive female ( i.e. , the Coolidge effect). The reversal of sexual satiety in the males treated with BrCr could be explained by its action on D2 family receptors, which promotes a reactivation of sexual motivation at a level sufficient to allow renewed copulation with the same female mate. [ABSTRACT FROM AUTHOR]

The medial preoptic nucleus (MPN) is a regulatory center for male sexual behavior. It consists of sexually dimorphic structures that are male biased, and these structures are found in the central part of the MPN (MPNc). The bed nucleus of the stria terminalis (BNST) also participates in male sexual behavior, and receives efferent neural projections from the MPNc. In this study, we examined if MPNc neurons projecting to the BNST are activated in male rats displaying sexual behavior. Fluoro-Gold (FG; a retrograde neural tracer) was injected into the BNST of male rats, which were separated into two groups: (1) those in contact with estrous female rats and displayed sexual behavior followed by ejaculation and (2) those without contact with estrous female rats. In both groups, protein expression of c-Fos (a neuronal activity marker) and calbindin (a location marker of the MPNc) were detected by fluorescent immunohistochemistry. The number of c-Fos-immunoreactive cells with or without FG labeling in the MPNc was also measured. The number of c-Fos-immunoreactive cells significantly increased following ejaculation. Approximately 10% of FG-labeled cells in ejaculation male rats were immunoreactive for c-Fos, and this percentage value was significantly higher in this group compared with control male rats. Overall, these results suggest that efferent projections from the MPNc to the BNST function to control sexual behavior in male rats. [ABSTRACT FROM AUTHOR]

Neural circuits underlying male sexual function comprise several nuclei located in the brain and spinal cord. We have previously demonstrated in rats that the gastrin-releasing peptide (GRP) system influences spinal centers promoting penile reflexes. Moreover, a group of oxytocin (OXT) neurons, situated in the parvocellular part of the paraventricular nucleus of the hypothalamus, project into the spinal cord and control penile reflexes. Therefore, it has been hypothesized that OXT is transported by long descending paraventriculospinal pathways and activates proerectile spinal centers. Consequently, we have shown that in rats, axonal distribution of OXT in the lumbar spinal cord exhibits a male-dominant sexual dimorphism. Furthermore, OXT binding is observed in the spinal GRP neurons. Thus, OXT axons may secrete OXT from spinal axonal terminals and regulate male sexual function via an OXT receptor-mediated mechanism in spinal GRP neurons. Future studies should address the relationship between the hypothalamic OXT and spinal GRP systems. Identification of the male-specific brain-spinal cord neural circuit that regulates male sexual behavior may provide new avenues for therapeutic approaches to masculine reproductive dysfunction, including erectile dysfunction and/or ejaculation disorder. [ABSTRACT FROM AUTHOR]

While sexually experienced males copulate at a higher frequency than sexually inexperienced males, there is still a great deal of variability in their behavior. Within the medial preoptic area (mPOA) of the hypothalamus, glutamate modulates some of this variability. Glutamate levels, for example, increase during sexual activity, peaking with ejaculation and falling precipitously during the post-ejaculation interval. Whereas lower glutamate levels after ejaculation translates to longer post-ejaculatory intervals, administration of glutamate uptake inhibitors into the mPOA increases the number of ejaculations a male rat achieves over a mating bout, and reduces the latency to ejaculate once mating begins. Because astrocytes modulate the availability of neuronal glutamate, we hypothesized that differences in the number of GFAP-positive astrocytes in the mPOA may account for variability in sexual behavior. To this end, we examined whether the number of astrocytes in the mPOA related to ejaculation latency as well as to the duration of the post-ejaculatory interval (PEI) in sexually experienced and sexually inexperienced males. Results indicate that the number of astrocytes negatively correlated with latency to reach ejaculations in sexually inexperienced but not sexually experienced rats while the number of astrocytes and PEI were not related. Astrocyte numbers did not vary between inexperienced and experienced subjects indicating that astrocyte processes may differentially project to sex-relevant glutamatergic synapses or that glutamatergic innervation of the mPOA changes as a function of sexual experience. [ABSTRACT FROM AUTHOR]

Highlights: [•] SCH 23390 (D1 antagonist) blocks the conditioned place preference induced by ejaculation. [•] SCH 23390 does not modify locomotion and have a transient effect on sexual behavior. [•] SCH 23390 affects only the first coital interaction. [•] SKF 38393 (D1 agonist) induces a conditioned place preference and it is blocked by SCH 23390. [•] Our results suggest that dopamine is involved in the sexual reward induced by ejaculation. [ABSTRACT FROM AUTHOR]

Abstract: Sexual behavior of the male rat can be described as a ‘sequence’: a series of behavioral transitions eventually leading to a consummatory act: ejaculation. A ‘funnel-model’ is presented to describe the behavioral progression during the sexual sequence. The ejaculation itself is extensively controlled by the ‘spinal ejaculation generator’, consisting of several elements with afferent sources of genitosensory information, with ascending projection fibers to inform the brainstem and forebrain as well as with descending afferent fibers providing the supraspinal control mechanisms with the opportunity to restrict ejaculations to the optimal moments and circumstances. The messages ascending from the spinal cord reach several interconnected thalamic, hypothalamic and limbic brain areas and are integrated with olfactory information. These brain areas play a role in mechanisms like ‘sexual satiety’ or a temporary interruption of sexual activities (post-ejaculatory interval), but the exact facilitatory and inhibitory mechanisms involved have not been elucidated yet. In the ‘downward’ mechanisms controlling the spinal ‘release’ of an ejaculation, the medial preoptic nucleus plays an important role in cooperation with a number of brainstem areas. This nucleus is also explicitly involved in the rewarding experiences coming with an ejaculation. Finally, the role of several neurotransmitters and-peptides on male sexual behavior are discussed shortly, because sometimes they show remarkable effects on specific aspects of the behavioral sequence. We conclude that, despite our increased knowledge about the brain mechanisms involved in the control of ejaculation, we are still far away from a complete understanding and quite a few questions remain to be resolved. [Copyright &y& Elsevier]

Highlights: [•] Environmental chemicals that mimic hormones are termed endocrine disrupting chemicals (EDCs) [•] EDCs may interfere with developmental events, particularly sexual differentiation [•] Birds respond depending on the aryhl hydrocarbon receptor (AhR), which differs across species [•] Adverse Outcomes Pathways allows a functional construct of EDC actions; spanning molecular mechanisms to population impacts. [•] Birds are vulnerable to EDCs; precocial species impacted during embryonic development; altricial species may remain vulnerable throughout their lifespan. [Copyright &y& Elsevier]

Abstract: Several neurotransmitters, among them neuropeptides, have been implicated in the control of male sexual behavior. Opioids are involved in mediating the positive affective states generated by the execution of sexual behavior in both males and females. We have previously shown that intracerebroventricular administration of endomorphin-1 (EM-1), the specific ligand for the μ opioid receptor, increased the ejaculation latency and interintromission interval and reduced the number of ejaculations during the test. In the present study we evaluated the effect of EM-1 upon male sexual behavior and socio-sexual interactions when infused in the medial preoptic area (MPOA) or the medial amygdala (Me). The results indicate that the administration of EM-1 in the MPOA increased mount and intromission latencies while infusion in the Me increased the number of mounts before ejaculation as well as the ejaculation latency. With respect to socio-sexual interactions, the duration of pursuit was significantly increased after administration of EM-1 in the MPOA. The effects upon sexual behavior and socio-sexual interactions were blocked by administration of the opioid antagonist naloxone. These results indicate that EM-1 modulates the appetitive aspect of sexual behavior in the MPOA and the consummatory phase in the Me. [Copyright &y& Elsevier]