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Berend Olivier - One of the best experts on this subject based on the ideXlab platform.
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the serotonin transporter plays an important role in male sexual behavior a study in serotonin transporter knockout rats
The Journal of Sexual Medicine, 2011Co-Authors: Johnny S W Chan, Edwin Cuppen, Berend Olivier, Eelke M.s. Snoeren, Marcel D. Waldinger, Ronald S. OostingAbstract:ABSTRACT Introduction Serotonin (5‐HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/−) serotonin transporter (SERT) rats and SERT knockout rats (−/−) have serotonergic disturbances with significant elevations of basal extracellular 5‐HT levels. Aim To investigate the putative role of the SERT in male sexual behavior. Methods After extensive sexual training, the effects of the 5‐HT 1A/7 receptor agonist ±8‐OH‐DPAT, the 5‐HT 1A receptor antagonist WAY100 635 and a combination of both on sexual behaviors of SERT −/− and SERT +/− knockout and wildtype (SERT +/+ ) male Wistar rats were examined. Main Outcome Measures Male rat sexual behaviors of mounts, intromissions, and Ejaculations. Results SERT −/− had lower basal Ejaculation frequencies than SERT +/− and SERT +/+ animals. ±8‐OH‐DPAT enhanced sexual performance in all three genotypes to the same extent. WAY100635 dose‐dependently inhibited sexual behavior in all three genotypes with significant dose to genotype interactions. WAY100635 exerted the strongest effects in SERT −/− animals. The combination of a dose range of ±8‐OH‐DPAT and a selected dose of WAY100635 revealed only partial antagonism by ±8‐OH‐DPAT of the sexual inhibitory effects of WAY100635. Conclusions. Absence of the serotonin transporter reduces basal ejaculatory performance in male rats. Pharmacological experiments suggest that separate pools of 5‐HT 1A receptors regulate different aspects of sexual performance in male rats. 5‐HT 7 receptors may play a minor role in the partial recovery of sexual behavior after combination of ±8‐OH‐DPAT and WAY100635. The SERT −/− rat may be a model for chronic SSRI treatment, delayed Ejaculation, anorgasmia, and/or low libido. Chan JSW, Snoeren EMS, Cuppen E, Waldinger MD, Olivier B, and Oosting RS. The serotonin transporter plays an important role in male sexual behavior: A study in serotonin transporter knockout rats.
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clavulanic acid stimulates sexual behaviour in male rats
European Journal of Pharmacology, 2009Co-Authors: Johnny S W Chan, Berend Olivier, Ronald S. Oosting, Deog Joong Kim, Chang Ho AhnAbstract:Sexual behaviour in rats can be used to predict putative effects on human sexual behaviour. Anecdotic reports exist, that the beta-lactamase inhibitor, clavulanic acid exerts sexual stimulating activities in monkeys. To characterize these pro-sexual activities, clavulanic acid was tested in three doses and compared to one dose of a sexually inhibitory dose of the selective serotonin reuptake inhibitor, paroxetine, in sexually-experienced male rats, selected for a moderate level of sexual performance in a standard 30-min test with an oestrus female. After acute administration, clavulanic acid had minor sexual stimulating effects at the highest dose in the number of intromissions and in the first Ejaculation series. After sub-chronic 7-days treatment, clavulanic acid increased the number of Ejaculations at all three doses and reduced the number of intromissions in the 1st series at the highest dose. After chronic 14 days treatment, a similar but stronger pro-sexual profile was observed. The sexual side effects of paroxetine were as expected, including slight sexual inhibitory effects after acute administration, but somewhat stronger overall inhibitory effects after 7 and 14-days pretreatment, particularly notable in the decreasing number of animals contributing to the 2nd Ejaculation series, which was even stronger after 14-days treatment. One week after cessation of treatment, the paroxetine group had completely recovered, whereas the highest dose-group of clavulanic acid still showed some pro-sexual effects. This remarkable pro-sexual activity of clavulanic acid cannot readily be explained by its mechanism of action as a beta-lactamase inhibitor but could be due to unexpected central activity of the compound.
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psychopharmacology of male rat sexual behavior modeling human sexual dysfunctions
International Journal of Impotence Research, 2006Co-Authors: Johnny S W Chan, Berend Olivier, Ronald S. Oosting, Tommy Pattij, Jan G Veening, T R De Jong, Marcel D. WaldingerAbstract:Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of Ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded Ejaculation (slow rats). Psychopharmacology in these endophenotypes helps to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. These preclinical studies and models contribute to a better understanding of the neurobiology of Ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded Ejaculation.
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proposal for a definition of lifelong premature Ejaculation based on epidemiological stopwatch data
The Journal of Sexual Medicine, 2005Co-Authors: Marcel D. Waldinger, Berend Olivier, Aeilko H. Zwinderman, Dave H. SchweitzerAbstract:ABSTRACT Introduction Consensus on a definition of premature Ejaculation has not yet been reached because of debates based on subjective authority opinions and nonstandardized assessment methods to measure Ejaculation time and Ejaculation control. Aim To provide a definition for lifelong premature Ejaculation that is based on epidemiological evidence including the neurobiological and psychological approach. Methods We used the 0.5 and 2.5 percentiles as accepted standards of disease definition in a skewed distribution. We applied these percentiles in a stopwatch‐determined intravaginal Ejaculation latency time (IELT) distribution of 491 nonselected men from five different countries. The practical consequences of 0.5% and 2.5% cutoff points for disease definition were taken into consideration by reviewing current knowledge of feelings of control and satisfaction in relation to ejaculatory performance of the general male population. Main Outcome Measures Literature arguments to be used in a proposed consensus on a definition of premature Ejaculation. Results The stopwatch‐determined IELT distribution is positively skewed. The 0.5 percentile equates to an IELT of 0.9 minute and the 2.5 percentile an IELT of 1.3 minutes. However, there are no available data in the literature on feelings of control or satisfaction in relation to ejaculatory latency time in the general male population. Random male cohort studies are needed to end all speculation on this subject. Exact stopwatch time assessment of IELT in a multinational study led us to propose that all men with an IELT of less than 1 minute (belonging to the 0.5 percentile) have “definite” premature Ejaculation, while men with IELTs between 1 and 1.5 minutes (between 0.5 and 2.5 percentile) have “probable” premature Ejaculation. Severity of premature Ejaculation (nonsymptomatic, mild, moderate, severe) should be defined in terms of associated psychological problems. Conclusion We define lifelong premature Ejaculation as a neurobiological dysfunction with an unacceptable increase of risk to develop sexual and psychological problems anywhere in a lifetime. By defining premature Ejaculation from an authority‐defined disorder into a dysfunction based on epidemiological evidence it is possible to establish consensus based on epidemiological evidence. Additional epidemiological stopwatch studies are needed for a final decision of IELT values at both percentile cutoff points.
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original research ejaculatory disorders on demand ssri treatment of premature Ejaculation pharmacodynamic limitations for relevant Ejaculation delay and consequent solutions
The Journal of Sexual Medicine, 2005Co-Authors: Marcel D. Waldinger, Dave H. Schweitzer, Berend OlivierAbstract:ABSTRACT Introduction Recently, the idea has emerged that on‐demand use of serotonin reuptake inhibitors (SSRIs), particularly short half‐life, should be equally effective in delaying Ejaculation as daily SSRI treatment of premature Ejaculation. Aim To provide evidence that SSRI‐induced Ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5‐hydroxytryptamine (5‐HT) receptor antagonism leads acutely to stronger Ejaculation delay than acute SSRI monoadministration. Methods We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5‐HT 1A receptor antagonists. In addition, we critically reviewed existing on‐demand SSRI treatments publications and the current debate on a definition of premature Ejaculation. Main Outcome Measures Intravaginal Ejaculation latency time (IELT). Results Acute SSRI administration leads to only a mild or no increase of 5‐HT neurotransmission and concomitant stimulation of postsynaptic 5‐HT receptors. Existing on‐demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high‐fold increases of Ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5‐HT 1A receptor antagonists significantly increases the Ejaculation time acutely compared to acute SSRI monoadministration. Conclusion On‐demand SSRI treatment has less Ejaculation‐delaying effects than daily SSRI treatment. SSRIs with a short half‐life are likely leading to much less Ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5‐HT 1A receptor antagonists increases the likelihood of clinically relevant Ejaculation delay after on‐demand treatment. On‐demand SSRIs with short half‐life that insufficiently delay Ejaculation in men with IELTs less than 1 minute should be called Ejaculation‐delaying drugs rather than drugs against premature Ejaculation.
Marcel D. Waldinger - One of the best experts on this subject based on the ideXlab platform.
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Disorders of Orgasm and Ejaculation in Menjsm_1782 1668..1686
2016Co-Authors: David Rowl, Marcel D. Waldinger, Chris G Mcmahon, Carmita Abdo, Juza Chen, Emmanuele Jannini, Tai Young AhnAbstract:Introduction. Ejaculatory/orgasmic disorders are common male sexual dysfunctions, and include premature ejacu-lation (PE), inhibited Ejaculation, anEjaculation, retrograde Ejaculation, and anorgasmia. Aim. To provide recommendations and guidelines concerning current state-of-the-art knowledge for management of Ejaculation/orgasmic disorders in men. Methods. An international consultation in collaboration with the major urology and sexual medicine association
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the pathophysiology of lifelong premature Ejaculation
Translational Andrology and Urology, 2016Co-Authors: Marcel D. WaldingerAbstract:In 2008, lifelong premature Ejaculation (PE) was defined by the ISSM as an Ejaculation that occurs within about 1 min, and as an inability to delay Ejaculation and with negative personal consequences. The neurophysiology of Ejaculation in lifelong PE is intact. However, the core problem in lifelong PE is the timing of Ejaculation, which is presumably associated with a dysfunction in the central serotonergic modulation of the spinal Ejaculation reflex. This central serotonergic modulation is influenced by genetic polymorphisms of serotonergic neurotransmission and specific serotonergic receptors. As there are four PE subtypes, each with its own clinical characteristics, etiology and pathogenesis, it is assumed that the pathophysiology of lifelong PE is different from the pathophysiology of the other PE subtypes. For a full understanding of the pathophysiology of lifelong PE, there are still many questions that need to be answered by evidence-based human and animal research.
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ejaculatio praecox erectio praecox and detumescentia praecox as symptoms of a hypertonic state in lifelong premature Ejaculation a new hypothesis
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Marcel D. WaldingerAbstract:Abstract In the last two decades, in vivo animal research and human neurobiological, genetic and pharmacological research of lifelong premature Ejaculation (PE) have much contributed to a better understanding of the role of the central and peripheral nervous systems in mediating Ejaculation. Research of genetic polymorphisms in men with lifelong PE and clinical research of the validity of the classification into four PE subtypes have provided a better insight into lifelong PE and its distinction from the three other PE subtypes. Nevertheless, a number of symptoms of lifelong PE and its treatment by SSRIs are still not well understood. In the current article, it will be argued that lifelong PE is characterized not only by early Ejaculations (ejaculatio praecox), a diminished control over Ejaculation, and negative personal consequences, but also by early erections (erectio praecox) and an immediately occurring detumescence of the penis after Ejaculation (detumescentia praecox) as symptoms of an (sub)acute hypertonic or hypererotic physical state when making love. Based on animal research it is postulated that the facilitated erection, facilitated Ejaculation and facilitated penile detumescence are associated with centrally and peripherally increased oxytocin release. In addition, it is postulated that mechano- and thermosensory activity of transient receptor potential (TRP) ion channels, located in skin receptors of the glans penis, are associated with lifelong PE. Research into the three characteristics of the (sub)acute hypererotic state will presumably contribute to a better phenomenological description of and better neurobiological understanding of lifelong PE and its delineation to the three other PE subtypes.
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ejaculatio praecox erectio praecox and detumescentia praecox as symptoms of a hypertonic state in lifelong premature Ejaculation a new hypothesis
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Marcel D. WaldingerAbstract:In the last two decades, in vivo animal research and human neurobiological, genetic and pharmacological research of lifelong premature Ejaculation (PE) have much contributed to a better understanding of the role of the central and peripheral nervous systems in mediating Ejaculation. Research of genetic polymorphisms in men with lifelong PE and clinical research of the validity of the classification into four PE subtypes have provided a better insight into lifelong PE and its distinction from the three other PE subtypes. Nevertheless, a number of symptoms of lifelong PE and its treatment by SSRIs are still not well understood. In the current article, it will be argued that lifelong PE is characterized not only by early Ejaculations (ejaculatio praecox), a diminished control over Ejaculation, and negative personal consequences, but also by early erections (erectio praecox) and an immediately occurring detumescence of the penis after Ejaculation (detumescentia praecox) as symptoms of an (sub)acute hypertonic or hypererotic physical state when making love. Based on animal research it is postulated that the facilitated erection, facilitated Ejaculation and facilitated penile detumescence are associated with centrally and peripherally increased oxytocin release. In addition, it is postulated that mechano- and thermosensory activity of transient receptor potential (TRP) ion channels, located in skin receptors of the glans penis, are associated with lifelong PE. Research into the three characteristics of the (sub)acute hypererotic state will presumably contribute to a better phenomenological description of and better neurobiological understanding of lifelong PE and its delineation to the three other PE subtypes.
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Summary of Committee. For the complete report please refer to Sexual Medicine: Sexual Dysfunctions in Men and
2013Co-Authors: Michael A Perelman, Marcel D. Waldinger, David Rowl, Zhong Cheng Xin, Edited T. F. Lue, R. Basson, R. Rosen, F. Giuliano, S. Khoury, F. MontorsiAbstract:Introduction. Ejaculatory/orgasmic disorders, common male sexual dysfunctions, include premature Ejaculation, inhibited Ejaculation, anEjaculation, retrograde Ejaculation and anorgasmia. Aim. To provide recommendations/guidelines concerning state-of-the-art knowledge for management of Ejaculation/orgasmic disorders in men. Methods. An International Consultation in collaboration with the major urology and sexual medicin
Lique M Coolen - One of the best experts on this subject based on the ideXlab platform.
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chronic contusion spinal cord injury impairs ejaculatory reflexes in male rats partial recovery by systemic infusions of dopamine d3 receptor agonist 7ohdpat
Journal of Neurotrauma, 2016Co-Authors: Michael D Staudt, Natalie Kozyrev, Arthur Brown, Lique M CoolenAbstract:Abstract Chronic spinal cord injury (SCI) causes major disruption of ejaculatory function in men. Ejaculation is a reflex and the spinal generator for ejaculatory reflexes in the rat has been located in the lumbosacral spinal cord. The effects of SCI on the rat spinal Ejaculation generator and ejaculatory reflexes remain understudied. The first goal of the current study was to establish the effects of chronic SCI on the function of the spinal Ejaculation generator. Male rats received a contusion injury of the spinal cord at spinal level T6–T7. Ejaculatory reflexes elicited by electrical stimulation of the dorsal penile nerve (DPN) were evaluated in injured and control rats at 4–6 weeks following SCI. SCI males demonstrated significant reductions in bursting of the bulbocavernosus muscle (BCM), an indicator for expulsion phase of Ejaculation, and in seminal vesicle pressure (SVP) increases, an indicator for the emission phase of Ejaculation, following DPN stimulation. Thus, contusion SCI resulted in long-t...
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activation of mu or delta opioid receptors in the lumbosacral spinal cord is essential for ejaculatory reflexes in male rats
PLOS ONE, 2015Co-Authors: Natalie Kozyrev, Lique M CoolenAbstract:Ejaculation is controlled by a spinal Ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates Ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls Ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered Ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of Ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for Ejaculation, while MOR activation is sufficient to trigger Ejaculation in the absence of sensory stimulation.
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neural mechanisms of sexual behavior in the male rat emphasis on Ejaculation related circuits
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Jan G Veening, Lique M CoolenAbstract: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.
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central regulation of Ejaculation
Physiology & Behavior, 2004Co-Authors: Lique M Coolen, Julien Allard, William A Truitt, Kevin E MckennaAbstract:Ejaculation is a reflex mediated by a spinal control center, referred to as a spinal Ejaculation generator. This spinal Ejaculation generator coordinates sympathetic, parasympathetic and motor outflow to induce the two phases of Ejaculation, i.e., emission and expulsion. In addition, the spinal Ejaculation generator integrates this outflow with inputs that are related to the summation of sexual activity prior to Ejaculation that are required to trigger Ejaculation. Recently, a group of spinothalamic neurons in the lumbar spinal cord (LSt cells) were demonstrated to comprise an integral part of the spinal Ejaculation generator. Specifically, lesions of LSt cells completely ablate ejaculatory function. Moreover, LSt cells are activated following Ejaculation, but not following other components of sexual behavior. Furthermore, based on their relationship with autonomic nuclei, motoneurons and genital sensory inputs, LSt cells are also in the ideal anatomical position to integrate sensory inputs and autonomic and motor outflow. Additionally, the spinal Ejaculation generator is under inhibitory and excitatory influence of supraspinal sites, including the nucleus paragigantocellularis (nPGi), the paraventricular nucleus of the hypothalamus (PVN) and the medial preoptic area (MPOA). Finally, sensory information related to Ejaculation is processed in the spinal cord and brain, possibly contributing to the rewarding properties of Ejaculation. One candidate pathway for relay of Ejaculation-related cues consists of LSt cells and their projections to the parvocellular subparafascicular thalamic nucleus. Moreover, neural activation specifically related to Ejaculation is observed in the brain and may reflect of processing of Ejaculation-related sensory cues.
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the selective serotonin re uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment
Psychopharmacology, 2002Co-Authors: Marcel D. Waldinger, Afke Van De Plas, Tommy Pattij, Ruud Van Oorschot, Lique M Coolen, Jan G Veening, Berend OlivierAbstract:Rationale: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and Ejaculation in men. In men with rapid Ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in Ejaculation and fluvoxamine the weakest. Objectives: In the present study, we compared the acute and chronic effects of fluvoxamine and paroxetine on sexual behavior in the male rat in order to compare their differential inhibitory effects on sexual behavior. Methods: During a 4-week period, 48 male Wistar rats, selected on the basis of their sexual performance, were repeatedly tested for sexual behavior. All male rats received vehicle (saline, n=12), fluvoxamine (30 mg/kg, n=12), or paroxetine (10 mg/kg, n=12) daily for 2 weeks. Sexual behavioral tests were performed on days 1 (acute), 7, and 14. Results: After acute oral administration, fluvoxamine and paroxetine did not inhibit sexual behavior. After 7 days and 14 days treatment, fluvoxamine mildly inhibited certain parameters of sexual behavior but Ejaculation was never delayed. In contrast, paroxetine, after 7 days and particularly after 14 days treatment, strongly inhibited sexual behavior, including Ejaculation. Conclusions: These results strongly concur with clinical data, suggesting that paroxetine, but not fluvoxamine, delays Ejaculation. Because fluvoxamine does not delay Ejaculation it may serve as an optimal treatment for depressive illness when sexual side effects, such as a delayed Ejaculation, are undesired. The mechanisms whereby paroxetine and fluvoxamine, both being selective serotonin uptake inhibitors, differentially inhibit sexual behavior are unclear.
Francois Giuliano - One of the best experts on this subject based on the ideXlab platform.
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physiology and pharmacology of Ejaculation
Basic & Clinical Pharmacology & Toxicology, 2016Co-Authors: Pierre Clement, Francois GiulianoAbstract:Ejaculation is the final stage of coitus in mammalian male and is mandatory for natural procreation. Two synchronized phases, emission and expulsion, form the ejaculatory response and involve specific organs and anatomical structures. The peripheral events leading to Ejaculation are commanded by autonomic (sympathetic and parasympathetic) and somatic divisions of the nervous system. The autonomic and somatic motor efferents originate in spinal nuclei located in thoracolumbar and lumbosacral segments. Co-ordinated activation of autonomic and somatic spinal nuclei is orchestrated by a group of lumbar spinal interneurons defined as the spinal generator of Ejaculation. The generator of Ejaculation together with the autonomic and somatic spinal nuclei constitutes a spinal network that is under the strong influence of stimulating or inhibiting genital sensory and supraspinal inputs. A brain circuitry dedicated to Ejaculation has been delineated that is part of a more global network controlling other aspects of the sexual response. This circuitry includes discrete neuronal populations distributed in all divisions of the brain. The corollary to the expanded CNS network is the variety of neurotransmitter systems participating in the ejaculatory process. Among them, serotonin neurotransmission plays a key role and its targeting led to the development of the first registered pharmacological treatment of premature Ejaculation in human beings. Critical gaps remain in the understanding of neurophysiopharmacology of Ejaculation and management of ejaculatory disorders in human beings needs improvement. Because the ejaculatory response in laboratory animals and in human beings shares many similarities, the use of animal models will certainly provide further advances in the field.
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the spinal control of Ejaculation revisited a systematic review and meta analysis of anEjaculation in spinal cord injured patients
Human Reproduction Update, 2013Co-Authors: C Chehensse, Pierre Clement, Stephane Bahrami, P Denys, J Bernabe, Francois GiulianoAbstract:BACKGROUND After spinal cord injury (SCI), most men cannot ejaculate without medical assistance. A major advance in the knowledge of the spinal control of Ejaculation has been achieved with the discovery of a spinal generator of Ejaculation (SGE) in the rat. The aim of this report was to review studies about Ejaculation after SCI in order to revisit the spinal control of Ejaculation and especially to assess the existence of an SGE in man. METHODS Studies were identified from Embase, PubMed, EBSCOhost and Cochrane Library. Studies were eligible when they specify the occurrence of antegrade Ejaculation as a function of the neurological characterization of SCI. Studies were excluded when Ejaculation was elicited by rectal electrical stimulation or when Ejaculation could not be discriminated from climax. Meta-analyses were performed to assess the reference Ejaculation rates for each procedure used to elicit Ejaculation, i.e. masturbation or coitus, penile vibratory stimulation (PVS) or acetylcholine esterase (AchE) inhibitors prior to masturbation. Subgroup analyses were performed according to the procedure used to elicit Ejaculation on (i) the completeness of the SCI and (ii) the upper and lower limits of the SCI. To assess the existence of an SGE, the effect of concurrent lesions of different spinal segments was assessed by means of a stratified bivariate analysis. RESULTS From 523 studies, 45 were selected (n = 3851). Ejaculation occurred in response to masturbation or coitus, PVS or AchE inhibitors followed by masturbation in, respectively, 11.8% (n = 1161), 47.4% (n = 597) and 54.7% (n = 309) of patients with complete SCI and in, respectively, 33.2% (n = 343), 52.8% (n = 305) and 78.1% (n = 32) of patients with incomplete SCI. Ejaculation, in the case of complete lesion of the sympathetic centres (T12 to L2), of the parasympathetic and somatic centres (S2-S4) or of all spinal Ejaculation centres (T12 to S5) occurred in response to PVS in none of the patients (respectively, n = 5, n = 4 and n = 21) and in response to AchE inhibitors followed by masturbation in 4.9% (n = 61), 30.8% (n = 26) and 0% (n = 16) of the patients, respectively. Ejaculation in response to PVS or AchE inhibitors prior to masturbation was rhythmic forceful in 97.9% (n = 48) of the patients with complete lesion strictly above Onuf's nucleus (segments S2-S4). Complete lesion of the S2-S4 segments precluded the occurrence of rhythmic forceful Ejaculation (n = 5). Controlling for the number of the injured segments between T12 and L2, the Ejaculation rate sharply decreased when the lesion extended to the L3 segment and below. CONCLUSIONS The results reinforce the crucial roles of the spinal sympathetic and parasympathetic centres for emission and the somatic centre for expulsion. The spinal segments between L2 and S2 is more than a pathway to connect the Ejaculation centres and likely harbours an SGE in man located in the L3, L4 and L5 segments.
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pharmacology for the treatment of premature Ejaculation
Pharmacological Reviews, 2012Co-Authors: Francois Giuliano, Pierre ClementAbstract:Male sexual response comprises four phases: excitement, including erection; plateau; Ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of Ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature Ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay Ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the Ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of Ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to Ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying Ejaculation.
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Neurophysiology of Erection and Ejaculation
The Journal of Sexual Medicine, 2011Co-Authors: Francois GiulianoAbstract:ABSTRACT Introduction Penile erection and Ejaculation are closely associated during sexual intercourse. Erection is a central psychoneuroendocrine and peripheral neuro-vasculo-tissular event, resulting in blood filling the sinusoidal spaces of the corpora cavernosa and corpus spongiosum. Ejaculation represents the climax of the sexual cycle and comprises emission (secretion of semen) and expulsion (propulsion of semen) phases. Aim This article provides an overview of the proposed neurophysiology of erection and Ejaculation. Methods Review of the literature. Main Outcome Measures Current data on the neurophysiology of erection and Ejaculation. Results In terms of peripheral innervation, the pelvic plexus represents a junction for efferent nerves to the structures involved in erection and Ejaculation. At the spinal level, the spinal cord contains three sets of neurons (thoracolumbar sympathetic, sacral parasympathetic, and somatic) innervating the sexual organs involved in erection and Ejaculation. The presence of cerebral descending pathways to spinal erection and Ejaculation centers indicates that the brain has an excitatory or inhibitory effect on these processes. Brain structures that modulate spinal command of erection and Ejaculation are part of a larger network that is dedicated to regulating sexual responses. Neurophysiological and pharmacological research has elucidated that dopamine and serotonin have central roles in modulating erection and Ejaculation. Interestingly, erection is not a prerequisite for Ejaculation, and each of these sexual responses can exist without the other. Conclusion Despite the association between erection and Ejaculation during intercourse, these two processes can be considered distinct events from an anatomical, physiological, and pharmacological perspective. Giuliano F. Neurophysiology of erection and Ejaculation.
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the pharmacological treatment of premature Ejaculation
BJUI, 2008Co-Authors: Francois Giuliano, Wayne J G HellstromAbstract:Premature Ejaculation (PE) is a common sexual dysfunction in men that is characterized by a short time to Ejaculation, and a lack of control over Ejaculation, and is associated with distress for men and their partners. Lack of knowledge about the aetiology of PE and lack of approved treatments might contribute to its under-diagnosis and under-treatment. The organic factors involved in PE are not well understood but serotonin (5-hydroxytryptamine, 5-HT) is important at the level of the central nervous system in the complex regulatory mechanisms involved in Ejaculation. Selective serotonin reuptake inhibitor (SSRI) antidepressants (paroxetine, fluoxetine and sertraline) and the tricyclic antidepressant
Natalie Kozyrev - One of the best experts on this subject based on the ideXlab platform.
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chronic contusion spinal cord injury impairs ejaculatory reflexes in male rats partial recovery by systemic infusions of dopamine d3 receptor agonist 7ohdpat
Journal of Neurotrauma, 2016Co-Authors: Michael D Staudt, Natalie Kozyrev, Arthur Brown, Lique M CoolenAbstract:Abstract Chronic spinal cord injury (SCI) causes major disruption of ejaculatory function in men. Ejaculation is a reflex and the spinal generator for ejaculatory reflexes in the rat has been located in the lumbosacral spinal cord. The effects of SCI on the rat spinal Ejaculation generator and ejaculatory reflexes remain understudied. The first goal of the current study was to establish the effects of chronic SCI on the function of the spinal Ejaculation generator. Male rats received a contusion injury of the spinal cord at spinal level T6–T7. Ejaculatory reflexes elicited by electrical stimulation of the dorsal penile nerve (DPN) were evaluated in injured and control rats at 4–6 weeks following SCI. SCI males demonstrated significant reductions in bursting of the bulbocavernosus muscle (BCM), an indicator for expulsion phase of Ejaculation, and in seminal vesicle pressure (SVP) increases, an indicator for the emission phase of Ejaculation, following DPN stimulation. Thus, contusion SCI resulted in long-t...
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activation of mu or delta opioid receptors in the lumbosacral spinal cord is essential for ejaculatory reflexes in male rats
PLOS ONE, 2015Co-Authors: Natalie Kozyrev, Lique M CoolenAbstract:Ejaculation is controlled by a spinal Ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates Ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls Ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered Ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of Ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for Ejaculation, while MOR activation is sufficient to trigger Ejaculation in the absence of sensory stimulation.