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Hassan M, Flanagan TW, Eshaq AM, Altamimi OK, Altalag H, Alsharif M, Alshammari N, Alkhalidi T, Boulifa A, El Jamal SM, Haikel Y, Megahed M. Reduction of Prostate Cancer Risk: Role of Frequent Ejaculation-Associated Mechanisms. Cancers (Basel) 2025; 17:843. [PMID: 40075690 PMCID: PMC11898507 DOI: 10.3390/cancers17050843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/21/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Prostate cancer (PCa) accounts for roughly 15% of diagnosed cancers among men, with disease incidence increasing worldwide. Age, family history and ethnicity, diet, physical activity, and chemoprevention all play a role in reducing PCa risk. The prostate is an exocrine gland that is characterized by its multi-functionality, being involved in reproductive aspects such as male ejaculation and orgasmic ecstasy, as well as playing key roles in the regulation of local and systemic concentrations of 5α-dihydrotestosterone. The increase in androgen receptors at the ventral prostate is the first elevated response induced by copulation. The regulation of prostate growth and function is mediated by an androgen-dependent mechanism. Binding 5-DHT to androgen receptors (AR) results in the formation of a 5α-DHT:AR complex. The interaction of the 5α-DHT:AR complex with the specific DNA enhancer element of androgen-regulated genes leads to the regulation of androgen-specific target genes to maintain prostate homeostasis. Consequently, ejaculation may play a significant role in the reduction of PCa risk. Thus, frequent ejaculation in the absence of risky sexual behavior is a possible approach for the prevention of PCa. In this review, we provide an insight into possible mechanisms regulating the impact of frequent ejaculation on reducing PCa risk.
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Affiliation(s)
- Mohamed Hassan
- Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France;
- Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
- Research Laboratory of Surgery-Oncology, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA;
| | - Thomas W. Flanagan
- Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, USA;
| | - Abdulaziz M. Eshaq
- Research Laboratory of Surgery-Oncology, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA;
- Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA
| | - Osama K. Altamimi
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (O.K.A.); (H.A.); (M.A.); (N.A.); (T.A.)
| | - Hassan Altalag
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (O.K.A.); (H.A.); (M.A.); (N.A.); (T.A.)
| | - Mohamed Alsharif
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (O.K.A.); (H.A.); (M.A.); (N.A.); (T.A.)
| | - Nouf Alshammari
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (O.K.A.); (H.A.); (M.A.); (N.A.); (T.A.)
| | - Tamadhir Alkhalidi
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (O.K.A.); (H.A.); (M.A.); (N.A.); (T.A.)
| | - Abdelhadi Boulifa
- Berlin Institute of Health, Charité University Hospital, 10117 Berlin, Germany;
- Competence Center of Immuno-Oncology and Translational Cell Therapy (KITZ), Charité-University Hospital, 10117 Berlin, Germany
| | - Siraj M. El Jamal
- Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA;
| | - Youssef Haikel
- Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France;
- Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
- Pôle de Médecine et Chirurgie Bucco-Dentaire, Hôpital Civil, Hôpitaux Universitaire de Strasbourg, 67000 Strasbourg, France
| | - Mossad Megahed
- Clinic of Dermatology, University Hospital of Aachen, 52074 Aachen, Germany;
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Argiolas A, Argiolas FM, Argiolas G, Melis MR. Erectile Dysfunction: Treatments, Advances and New Therapeutic Strategies. Brain Sci 2023; 13:802. [PMID: 37239274 PMCID: PMC10216368 DOI: 10.3390/brainsci13050802] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/08/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D4 receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients.
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Affiliation(s)
- Antonio Argiolas
- Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, Italy; (F.M.A.); (M.R.M.)
| | - Francesco Mario Argiolas
- Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, Italy; (F.M.A.); (M.R.M.)
| | - Giacomo Argiolas
- General Medicine Unit, Hospital San Michele, ARNAS“G. Brotzu”, Piazzale Ricchi 1, 09100 Cagliari, Italy;
| | - Maria Rosaria Melis
- Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, Italy; (F.M.A.); (M.R.M.)
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Masugi-Tokita M, Kubota S, Kobayashi K, Yoshida T, Kageyama S, Sakamoto H, Kawauchi A. Spinal Transection Switches the Effect of Metabotropic Glutamate Receptor Subtype 7 from the Facilitation to Inhibition of Ejaculation. Neuroscience 2023; 509:10-19. [PMID: 36403690 DOI: 10.1016/j.neuroscience.2022.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/03/2022] [Accepted: 11/13/2022] [Indexed: 11/18/2022]
Abstract
Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which localize to presynaptic active zones of the central nervous system. We previously reported that mGluR7 knockout (KO) mice exhibit ejaculatory disorders, although they have normal sexual motivation. We hypothesized that mGluR7 regulates ejaculation by potentiating the excitability of the neural circuit in the lumbosacral spinal cord, because administration of the mGluR7-selective antagonist into that region inhibits drug-induced ejaculation. In the present study, to elucidate the mechanism of impaired ejaculation in mGluR7 KO mice, we eliminated the influence of the brain by spinal transection (spinalization). Unexpectedly, sexual responses of male mGluR7 KO mice were stronger than those of wild-type mice after spinalization. Histological examination indicated that mGluR7 controls sympathetic neurons as well as parasympathetic neurons. In view of the complexity of its synaptic regulation, mGluR7 might control ejaculation by multi-level and multi-modal mechanisms. Our study provides insight into the mechanism of ejaculation as well as a strategy for future therapies to treat ejaculatory disorders in humans.
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Affiliation(s)
- Miwako Masugi-Tokita
- Department of Urology, Shiga University of Medical Science, Otsu, Japan; World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
| | - Shigehisa Kubota
- Department of Urology, Shiga University of Medical Science, Otsu, Japan
| | - Kenichi Kobayashi
- Department of Urology, Shiga University of Medical Science, Otsu, Japan
| | - Tetsuya Yoshida
- Department of Urology, Shiga University of Medical Science, Otsu, Japan
| | - Susumu Kageyama
- Department of Urology, Shiga University of Medical Science, Otsu, Japan
| | - Hirotaka Sakamoto
- Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Setouchi, Japan
| | - Akihiro Kawauchi
- Department of Urology, Shiga University of Medical Science, Otsu, Japan
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Melis MR, Argiolas A. Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System. Biomolecules 2021; 11:biom11121866. [PMID: 34944510 PMCID: PMC8699072 DOI: 10.3390/biom11121866] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 12/06/2021] [Accepted: 12/08/2021] [Indexed: 12/21/2022] Open
Abstract
Nitric oxide (NO), the neuromodulator/neurotransmitter formed from l-arginine by neuronal, endothelial and inducible NO synthases, is involved in numerous functions across the body, from the control of arterial blood pressure to penile erection, and at central level from energy homeostasis regulation to memory, learning and sexual behavior. The aim of this work is to review earlier studies showing that NO plays a role in erectile function and sexual behavior in the hypothalamus and its paraventricular nucleus and the medial preoptic area, and integrate these findings with those of recent studies on this matter. This revisitation shows that NO influences erectile function and sexual behavior in males and females by acting not only in the paraventricular nucleus and medial preoptic area but also in extrahypothalamic brain areas, often with different mechanisms. Most importantly, since these areas are strictly interconnected with the paraventricular nucleus and medial preoptic area, send to and receive neural projections from the spinal cord, in which sexual communication between brain and genital apparatus takes place, this review reveals that central NO participates in concert with neurotransmitters/neuropeptides to a neural circuit controlling both the consummatory (penile erection, copulation, lordosis) and appetitive components (sexual motivation, arousal, reward) of sexual behavior.
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Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances. Int J Mol Sci 2021; 22:ijms221910376. [PMID: 34638719 PMCID: PMC8509000 DOI: 10.3390/ijms221910376] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 09/20/2021] [Accepted: 09/23/2021] [Indexed: 12/30/2022] Open
Abstract
A continuously increasing amount of research shows that oxytocin is involved in numerous central functions. Among the functions in which oxytocin is thought to be involved are those that play a role in social and sexual behaviors, and the involvement of central oxytocin in erectile function and sexual behavior was indeed one of the first to be discovered in laboratory animals in the 1980s. The first part of this review summarizes the results of studies done in laboratory animals that support a facilitatory role of oxytocin in male and female sexual behavior and reveal mechanisms through which this ancient neuropeptide participates in concert with other neurotransmitters and neuropeptides in this complex function, which is fundamental for the species reproduction. The second part summarizes the results of studies done mainly with intranasal oxytocin in men and women with the aim to translate the results found in laboratory animals to humans. Unexpectedly, the results of these studies do not appear to confirm the facilitatory role of oxytocin found in male and female sexual behavior in animals, both in men and women. Possible explanations for the failure of oxytocin to improve sexual behavior in men and women and strategies to attempt to overcome this impasse are considered.
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Spontaneous Ejaculation: A Focused Review for the Clinicians. Sex Med Rev 2020; 9:406-422. [PMID: 33262094 DOI: 10.1016/j.sxmr.2020.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/25/2020] [Accepted: 11/01/2020] [Indexed: 01/23/2023]
Abstract
INTRODUCTION The process of ejaculation has important meanings not only for its association with orgasm but also for the timing to ejaculate in the context of sexual activity. Spontaneous (involuntary) ejaculation (SE) without any sexual stimulation is a distressing symptom. Our understanding of SE is limited. Unfortunately, many physicians are not aware of these cases. OBJECTIVES The objective of this study is to describe the etiopathogenesis, clinical features, diagnosis, and treatment options for SE. METHODS We searched the literature for publications on "SE," "spontaneous emission" or "involuntary ejaculation," and factors influencing SE in the PUBMED/MEDLINE, Scopus, Cochrane Library, EMBASE, PsycINFO, ProQuest, Academic Search Complete database, Google Scholar, and CINAHL databases from inception to August 2020. RESULTS The literature search yielded 36 relevant publications reporting on 43 patients with SE. Attempts to explain the cause of pathologic SE have included 4 etiological groups (spinal cord lesions, psychological causes, rabies, and drug-induced). The underlying mechanisms responsible for induction of SE may include increased adrenergic activity, overactivity in dopaminergic system, decreased serotonergic activity, damage of descending inhibitory pathway, or penile hyperexcitability. SE may occur in the absence of an identifiable trigger or may be triggered by non-sexual circumstances (micturition, defecation, glans touch, anxiety, panic attack, or school examinations). Treatment options include psychoanalytic treatment, paroxetine, citalopram, sertraline, silodosin, and anxiolytics. In drug-induced SE, dose reduction and drug withdrawal with or without switching to another drug may relief SE. CONCLUSIONS SE is one of the least reported ejaculatory dysfunction. The key feature shared in common by these men is SE without any sexual thoughts or fantasies, may be triggered by non-sexual contexts, rarely associated with orgasm or erection. Treatment by psychoanalytic treatment and pharmacotherapy may be helpful. Further research might explore the definite underlying mechanisms. Abdel-Hamid IA, Ali OI. Spontaneous Ejaculation: A Focused Review for the Clinicians. Sex Med Rev 2021;9:406-422.
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Hull EM, Dominguez JM. Neuroendocrine Regulation of Male Sexual Behavior. Compr Physiol 2019; 9:1383-1410. [DOI: 10.1002/cphy.c180018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Wiggins JW, Kozyrev N, Sledd JE, Wilson GG, Coolen LM. Chronic Spinal Cord Injury Reduces Gastrin-Releasing Peptide in the Spinal Ejaculation Generator in Male Rats. J Neurotrauma 2019; 36:3378-3393. [PMID: 31111794 DOI: 10.1089/neu.2019.6509] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Spinal cord injury (SCI) causes sexual dysfunction, including anejaculation in men. Likewise, chronic mid-thoracic contusion injury impairs ejaculatory reflexes in male rats. Ejaculation is controlled by a spinal ejaculation generator (SEG) comprised of a population of lumbar spinothalamic (LSt) neurons. LSt neurons co-express four neuropeptides, including gastrin-releasing peptide (GRP) and galanin and control ejaculation via release of these peptides in lumbar and sacral autonomic and motor nuclei. Here, we tested the hypothesis that contusion injury causes a disruption of the neuropeptides that are expressed in LSt cell bodies and axon terminals, thereby causing ejaculatory dysfunction. Male Sprague Dawley rats received contusion or sham surgery at spinal levels T6-7. Five to six weeks later, animals were perfused and spinal cords were immunoprocessed for galanin and GRP. Results showed that numbers of cells immunoreactive for galanin were not altered by SCI, suggesting that LSt cells are not ablated by SCI. In contrast, GRP immunoreactivity was decreased in LSt cells following SCI, evidenced by fewer GRP and galanin/GRP dual labeled cells. However, SCI did not affect efferent connections of LSt, cells as axon terminals containing galanin or GRP in contact with autonomic cells were not reduced following SCI. Finally, no changes in testosterone plasma levels or androgen receptor expression were noted after SCI. In conclusion, chronic contusion injury decreased immunoreactivity for GRP in LSt cell soma, but did not affect LSt neurons per se or LSt connections within the SEG. Since GRP is essential for triggering ejaculation, such loss may contribute to ejaculatory dysfunction following SCI.
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Affiliation(s)
- J Walker Wiggins
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.,Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, Mississippi
| | - Natalie Kozyrev
- Robarts Institute, Western University, London, Ontario, Canada
| | - Jonathan E Sledd
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
| | - George G Wilson
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
| | - Lique M Coolen
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.,Department of Biological Sciences, Kent State University, Kent, Ohio
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Seizert CA. The neurobiology of the male sexual refractory period. Neurosci Biobehav Rev 2018; 92:350-377. [DOI: 10.1016/j.neubiorev.2018.06.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 04/03/2018] [Accepted: 06/13/2018] [Indexed: 02/07/2023]
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Kozyrev N, Staudt MD, Brown A, Coolen LM. Chronic Contusion Spinal Cord Injury Impairs Ejaculatory Reflexes in Male Rats: Partial Recovery by Systemic Infusions of Dopamine D3 Receptor Agonist 7OHDPAT. J Neurotrauma 2016; 33:943-53. [DOI: 10.1089/neu.2015.4232] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Natalie Kozyrev
- Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada
- Department of Physiology, University of Michigan, Ann Arbor, Michigan
| | - Michael D. Staudt
- Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada
| | - Arthur Brown
- Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada
- Robarts Research Institute, Western University, London, Ontario, Canada
| | - Lique M. Coolen
- Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada
- Department of Physiology, University of Michigan, Ann Arbor, Michigan
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi
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Steadman CJ, Hubscher CH. Sexual Function after Spinal Cord Injury: Innervation, Assessment, and Treatment. CURRENT SEXUAL HEALTH REPORTS 2016. [DOI: 10.1007/s11930-016-0067-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Alexander MS, Kozyrev N, Bosma RL, Figley CR, Richards JS, Stroman PW. fMRI Localization of Spinal Cord Processing Underlying Female Sexual Arousal. JOURNAL OF SEX & MARITAL THERAPY 2016; 42:36-47. [PMID: 25635474 DOI: 10.1080/0092623x.2015.1010674] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Using functional magnetic resonance imaging, the authors aimed to determine the roles of the human spinal cord in mediating sexual responses in women. Functional magnetic resonance imaging of the entire lower thoracic, lumbar, and sacral spinal cord was performed using a sexual stimulation paradigm designed to elicit psychological and physical components of sexual arousal. Responses were measured in 9 healthy adult women during 3 consecutive conditions: (a) erotic audiovisual, (b) manual clitoral, and (c) audiovisual plus manual stimulation. Functional magnetic resonance imaging results in healthy subjects demonstrate that this method is sensitive for mapping sexual function in the spinal cord, and identify several key regions involved in human sexual response, including the intermediolateral cell column, the dorsal commissural nucleus, and the sacral parasympathetic nucleus. Using spinal functional magnetic resonance imaging, this study identified many of the spinal cord regions involved in female sexual responses. Results from audiovisual and manual clitoral stimulation correspond with previous data regarding lumbar and sacral neurologic changes during sexual arousal. This study provides the first characterization of neural activity in the human spinal cord underlying healthy female sexual responses and sets a foundation for future studies aimed at mapping changes that result from sexual dysfunction, spinal cord trauma or disease.
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Affiliation(s)
- Marcalee S Alexander
- a Department of Physical Medicine and Rehabilitation , University of Alabama at Birmingham , Birmingham , Alabama , USA
| | - Natalie Kozyrev
- b Centre for Neuroscience Studies , Queen's University , Kingston , Ontario , Canada
| | - Rachael L Bosma
- b Centre for Neuroscience Studies , Queen's University , Kingston , Ontario , Canada
| | - Chase R Figley
- b Centre for Neuroscience Studies , Queen's University , Kingston , Ontario , Canada
| | - J Scott Richards
- a Department of Physical Medicine and Rehabilitation , University of Alabama at Birmingham , Birmingham , Alabama , USA
| | - Patrick W Stroman
- b Centre for Neuroscience Studies , Queen's University , Kingston , Ontario , Canada
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Hawksworth DJ, Burnett AL. Pharmacotherapeutic management of erectile dysfunction. Clin Pharmacol Ther 2015; 98:602-10. [DOI: 10.1002/cpt.261] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 09/03/2015] [Indexed: 11/05/2022]
Affiliation(s)
- DJ Hawksworth
- Department of Urology; Fort Belvoir Community Hospital; Fort Belvoir Virginia USA
| | - AL Burnett
- Department of Urology; Johns Hopkins Medical Institutions; Baltimore Maryland USA
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Normal male sexual function: emphasis on orgasm and ejaculation. Fertil Steril 2015; 104:1051-60. [PMID: 26385403 DOI: 10.1016/j.fertnstert.2015.08.033] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 08/17/2015] [Accepted: 08/26/2015] [Indexed: 12/31/2022]
Abstract
Orgasm and ejaculation are two separate physiological processes that are sometimes difficult to distinguish. Orgasm is an intense transient peak sensation of intense pleasure creating an altered state of consciousness associated with reported physical changes. Antegrade ejaculation is a complex physiological process that is composed of two phases (emission and expulsion), and is influenced by intricate neurological and hormonal pathways. Despite the many published research projects dealing with the physiology of orgasm and ejaculation, much about this topic is still unknown. Ejaculatory dysfunction is a common disorder, and currently has no definitive cure. Understanding the complex physiology of orgasm and ejaculation allows the development of therapeutic targets for ejaculatory dysfunction. In this article, we summarize the current literature on the physiology of orgasm and ejaculation, starting with a brief description of the anatomy of sex organs and the physiology of erection. Then, we describe the physiology of orgasm and ejaculation detailing the neuronal, neurochemical, and hormonal control of the ejaculation process.
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Rubio-Casillas A, Rodríguez-Quintero C, Rodríguez-Manzo G, Fernández-Guasti A. Unraveling the modulatory actions of serotonin on male rat sexual responses. Neurosci Biobehav Rev 2015; 55:234-46. [DOI: 10.1016/j.neubiorev.2015.05.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 03/25/2015] [Accepted: 05/04/2015] [Indexed: 12/29/2022]
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Gur S, Sikka SC. The characterization, current medications, and promising therapeutics targets for premature ejaculation. Andrology 2015; 3:424-42. [DOI: 10.1111/andr.12032] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Revised: 02/03/2015] [Accepted: 02/21/2015] [Indexed: 01/06/2023]
Affiliation(s)
- S. Gur
- Department of Pharmacology; School of Pharmacy; Ankara University; Ankara Turkey
- Department of Urology; Tulane University Health Sciences Center; New Orleans LA USA
| | - S. C. Sikka
- Department of Urology; Tulane University Health Sciences Center; New Orleans LA USA
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Rodríguez-Manzo G, Canseco-Alba A. Anandamide reduces the ejaculatory threshold of sexually sluggish male rats: possible relevance for human lifelong delayed ejaculation disorder. J Sex Med 2015; 12:1128-35. [PMID: 25808995 DOI: 10.1111/jsm.12866] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The sexually sluggish (SLG) male rat has been proposed as an animal model for the study of lifelong delayed ejaculation, a sexual dysfunction for which no treatment is available. Low endocannabinoid anandamide (AEA) doses facilitate sexual behavior display in normal sexually active and in noncopulating male rats through the activation of CB1 receptors. AIM To establish whether low AEA doses reduced the ejaculatory threshold of SLG male rats by acting at CB1 receptors. METHODS SLG male rats were intraperitoneally injected with different doses of AEA (0.1-3.0 mg/kg), the CB1 receptor antagonist AM251 (0.1-3.0 mg/kg), or their vehicles and tested for copulatory behavior during 60 minutes. Animals receiving AEA effective doses were subjected to a second sexual behavior test, 7 days later under drug-free conditions. To determine the participation of CB1 receptors in AEA-induced actions, SLG rats were pretreated with AM251 prior to AEA. MAIN OUTCOME MEASURES The sexual parameters, intromission latency, number of mounts and intromissions, ejaculation latency, and interintromission interval. RESULTS All sexual behavior parameters of SLG rats were significantly increased when compared with normal sexually experienced animals. Low AEA doses (0.3 and 1 mg/kg) significantly lowered the ejaculatory threshold of SLG rats, reducing the number of pre-ejaculatory intromissions and ejaculation latency. IL, M number, and locomotor activity were unaffected by AEA. Facilitation of the ejaculatory response of SLG rats disappeared 7 days after AEA injection. AM251 lacked an effect on copulation of SLG rats but blocked the AEA-induced lowering of the ejaculatory threshold. CONCLUSIONS AEA appears to specifically target the ejaculatory threshold of SLG rats through the activation of CB1 receptors. This specificity along with the fact that AEA's effects are exerted acutely and at low doses makes this drug emerge as a promising treatment for the improvement of the ejaculatory response in men with primary delayed ejaculation.
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Affiliation(s)
| | - Ana Canseco-Alba
- Departamento de Farmacobiología, Cinvestav-Sede Sur, México, México
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Clement P, Giuliano F. Anatomy and physiology of genital organs - men. HANDBOOK OF CLINICAL NEUROLOGY 2015; 130:19-37. [PMID: 26003237 DOI: 10.1016/b978-0-444-63247-0.00003-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Male sexual functions involve a number of organs and structures in genitalia whose role is to produce fertilizing gametes and to allow female-partner insemination. The testes belong to the reproductive and endocrine systems as they synthesize spermatozoa and androgens, and are under finely regulated hormonal control by the hypothalamopituitary axis. Sexual responses are controlled by a complex and coordinated interplay of both the somatic and the autonomic nervous system in multiple components of the brain, spinal cord, and relevant peripheral organs. Erectile bodies are an essential element of the penis and engorgement of the penis with blood leads to penile tumescence. Blood engorgement is due to relaxation of smooth-muscle cells of erectile tissue and endothelium of the penile arteries. The penis gains additional rigidity when the ischiocavernosus muscles contract. Stimuli from peripheral and/or central origins activate particular spinal nuclei, causing penile erection. Ejaculation consists of two phases, emission and expulsion, which correspond, respectively, to secretion of the different components of the semen by sex glands and forceful expulsion of semen due to rhythmic contractions of the bulbospongiosus muscle. A spinal generator of ejaculation integrates genital stimuli and sexual cues and, when the excitatory threshold is reached, triggers ejaculation by orchestrating the activation of autonomic and somatic pathways commanding the peripheral events of ejaculation.
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Affiliation(s)
- Pierre Clement
- School of Health Sciences, University of Versailles-St. Quentin en Yvelines, Montigny le Bretonneux, France; Pelvipharm Laboratories, Montigny le Bretonneux, France
| | - François Giuliano
- School of Health Sciences, University of Versailles-St. Quentin en Yvelines, Montigny le Bretonneux, France; Pelvipharm Laboratories, Montigny le Bretonneux, France; Neuro-Uro-Andrology, Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France.
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LeBoeuf B, Correa P, Jee C, García LR. Caenorhabditis elegans male sensory-motor neurons and dopaminergic support cells couple ejaculation and post-ejaculatory behaviors. eLife 2014; 3. [PMID: 24915976 PMCID: PMC4103683 DOI: 10.7554/elife.02938] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Accepted: 06/09/2014] [Indexed: 12/03/2022] Open
Abstract
The circuit structure and function underlying post-coital male behaviors remain poorly understood. Using mutant analysis, laser ablation, optogenetics, and Ca2+ imaging, we observed that following C. elegans male copulation, the duration of post-coital lethargy is coupled to cellular events involved in ejaculation. We show that the SPV and SPD spicule-associated sensory neurons and the spicule socket neuronal support cells function with intromission circuit components, including the cholinergic SPC and PCB and the glutamatergic PCA sensory-motor neurons, to coordinate sex muscle contractions with initiation and continuation of sperm movement. Our observations suggest that the SPV and SPD and their associated dopamine-containing socket cells sense the intrauterine environment through cellular endings exposed at the spicule tips and regulate both sperm release into the hermaphrodite and the recovery from post-coital lethargy. DOI:http://dx.doi.org/10.7554/eLife.02938.001 The nematode worm, C. elegans, is roughly 1 mm long, made up of around 1000 cells and has two sexes: male and hermaphrodite. Hermaphrodite worms produce both eggs and sperm and can self-fertilize to generate around 300 offspring each time. Fertilization by a male, on the other hand, results in three times as many progeny and introduces genetic diversity into the population. However, it also reduces the lifespan of the hermaphrodite. Mating also incurs a cost for males: it requires a lot of energy, which prevents male works from engaging in other activities, such as feeding, and it also increases their risk of predation. In many species, including C. elegans, the frequency with which a male can mate is limited by a period of reduced mating drive and ability that follows each instance of successful mating. However, the molecular and cellular basis of this ‘refractory period’ remains largely unclear. Using a range of techniques, LeBoeuf et al. have now identified the circuits that regulate male mating behavior in C. elegans. When male worms were introduced into a Petri dish containing 15 hermaphrodites, most males initiated mating within about 2 min. The length of the refractory period varied between worms, but averaged roughly 12 min. This consisted of a period of disinterest, in which males did not approach hermaphrodites, followed by a period in which males attempted mating but were slower and less efficient, suggesting that the neural circuits controlling mating behaviors had yet to recover completely. Males with longer refractory periods produced more progeny in their second mating than those with shorter refractory periods, suggesting that the interval also enables males to replenish their sperm levels. Further experiments revealed that a chemical transmitter called dopamine promotes ejaculation and then immediately reduces the worm's activity levels, giving rise to the refractory period. By enforcing a delay between matings, the refractory period may also increase the likelihood that successive matings will be with different hermaphrodites, helping to maximize the number and diversity of offspring. Some aspects of the neural circuitry that controls the refractory period in C. elegans resemble those seen in mammals, suggesting that insights gained from an animal with 1000 cells could also be relevant to more complex species. DOI:http://dx.doi.org/10.7554/eLife.02938.002
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Affiliation(s)
- Brigitte LeBoeuf
- Department of Biology, Howard Hughes Medical Institute, Texas A&M University, College Station, United States
| | - Paola Correa
- Department of Biology, Howard Hughes Medical Institute, Texas A&M University, College Station, United States
| | - Changhoon Jee
- Department of Biology, Howard Hughes Medical Institute, Texas A&M University, College Station, United States
| | - L René García
- Department of Biology, Howard Hughes Medical Institute, Texas A&M University, College Station, United States
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Snoeren EM, Veening JG, Olivier B, Oosting RS. Serotonin 1A receptors and sexual behavior in male rats: A review. Pharmacol Biochem Behav 2014; 121:102-14. [DOI: 10.1016/j.pbb.2013.11.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 10/08/2013] [Accepted: 11/07/2013] [Indexed: 12/21/2022]
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Veening J, Coolen L. Neural mechanisms of sexual behavior in the male rat: Emphasis on ejaculation-related circuits. Pharmacol Biochem Behav 2014; 121:170-83. [DOI: 10.1016/j.pbb.2013.12.017] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 12/12/2013] [Accepted: 12/16/2013] [Indexed: 01/20/2023]
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Dobberfuhl AD, Oti T, Sakamoto H, Marson L. Identification of CNS neurons innervating the levator ani and ventral bulbospongiosus muscles in male rats. J Sex Med 2013; 11:664-77. [PMID: 24373488 DOI: 10.1111/jsm.12418] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The pelvic striated muscles play an important role in mediating erections and ejaculation, and together these muscles compose a tightly coordinated neuromuscular system that is androgen sensitive and sexually dimorphic. AIM To identify spinal and brains neurons involved in the control of the levator ani (LA) and bulbospongiosus (BS) in the male adult and preadolescent rat. METHODS Rats were anesthetized, and the transsynaptic retrograde tracer pseudorabies virus (PRV) was injected into the LA muscle of adults or the ventral BS muscle in 30-day-old rats. After 3-5 days rats were sacrificed, and PRV-labeled neurons in the spinal cords and brains were identified using immunohistochemistry. The presence of gastrin-releasing peptide (GRP) in the lumbar spinal neurons was examined. MAIN OUTCOMES MEASURES The location and number of PRV-labeled neurons in the spinal cord and brain and GRP colocalization in the lumbar spinal cord. RESULTS PRV-labeled spinal interneurons were found distributed throughout T11-S1 of the spinal cord, subsequent to dorsal medial motoneuron infection. The majority of spinal interneurons were found in the lumbosacral spinal cord in the region of the dorsal gray commissure and parasympathetic preganglionic neurons. Preadolescent rats had more PRV-labeled spinal interneurons at L5-S1 where the motoneurons were located but relatively less spread rostrally in the spinal cord compared with adults. Lumbar spinothalmic neurons in medial gray of L3-L4 co-localized PRV and GRP. In the brain consistent labeling was seen in areas known to be involved in male sexual behavior including the ventrolateral medulla, hypothalamic paraventricular nucleus, and medial preoptic area. CONCLUSION Common spinal and brain pathways project to the LA and BS muscles in the rat suggesting that these muscles act together to coordinate male sexual reflexes. Differences may exist in the amount of synaptic connections/neuronal pathways in adolescents compared with adults.
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Affiliation(s)
- Amy D Dobberfuhl
- Division of Urology, Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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23
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Huynh HK, Willemsen AT, Lovick TA, Holstege G. Pontine Control of Ejaculation and Female Orgasm. J Sex Med 2013; 10:3038-48. [DOI: 10.1111/jsm.12300] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Azadzoi KM, Yang J, Siroky MB. Neural regulation of sexual function in men. World J Clin Urol 2013; 2:32-41. [PMID: 34707982 PMCID: PMC8547275 DOI: 10.5410/wjcu.v2.i3.32] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/30/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
Male sexual response is controlled by a series of neurally mediated phenomena regulating libido, motivation, arousal and genital responses such as penile erection and ejaculation. These neural events that occur in a hormonally defined milieu involve different neurophysiological, neurochemical, and neuropsychological parameters controlled by central mechanisms, spinal reflexes and peripheral nervous system. Epidemiologic studies have suggested the high prevalence of male sexual dysfunction worldwide with significant impact on the quality of life of patients suffering from this problem. The incidence of sexual dysfunction is particularly high among men with neurologic disorders. Sexual dysfunction in men, such as loss of sexual desire, erectile dysfunction (ED), changes in arousal, and disturbances in orgasm and ejaculation may involve organic causes, psychological problems, or both. Organic male sexual disorders include a wide variety of neurologic, vasculogenic, neurovascular or hormonal factors that interfere with libido, erection, ejaculation and orgasm. Neurogenic sexual dysfunction may result from a specific neurologic problem or it could be the presenting symptom of a developing neurologic disease. Neurologic ED could result from complications of chronic neurologic disorders, trauma, surgical injury or iatrogenic causes. These etiologic factors and the underlying pathophysiologic conditions could overlap, which should be considered when making a diagnosis and selecting a treatment. A detailed history of physical examination, neurologic disorders, as well as any past history of psychological and psychiatric disturbances, and a thorough neurological examination will provide better understanding of the underlying causes of neurogenic sexual dysfunction. In patients with spinal cord injury, the location of the lesion and the time of onset of injury should be determined. Therapeutic strategies against erectile dysfunction are initiated with the least invasive options using the phosphodiesterase inhibitors. When oral medication options are exhausted, intraurethral and intracavernosal therapies and ultimately vacuum constriction devices and penile implants are considered. Recent basic research has suggested the potential role of stem cell-based therapeutic strategies to protect penile neural integrity and reverse cavernosal neurodegeneration in experimental models. Further insight into the central, spinal and peripheral neural mechanisms of male sexual response may help precise diagnosis and better management of neurogenic sexual dysfunction in men.
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Ishigami T, Yoshioka K, Karicheti V, Marson L. A Role for Peripheral 5-HT2 Receptors in Serotonin-Induced Facilitation of the Expulsion Phase of Ejaculation in Male Rats. J Sex Med 2013; 10:2688-702. [DOI: 10.1111/jsm.12306] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Bijlsma EY, Chan JSW, Olivier B, Veening JG, Millan MJ, Waldinger MD, Oosting RS. Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release? Pharmacol Biochem Behav 2013; 121:88-101. [PMID: 24128918 DOI: 10.1016/j.pbb.2013.10.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2013] [Accepted: 10/04/2013] [Indexed: 01/26/2023]
Abstract
Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling.
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Affiliation(s)
- Elisabeth Y Bijlsma
- Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Universiteitsweg 99, 3584 CGUtrecht, The Netherlands
| | - Johnny S W Chan
- Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Universiteitsweg 99, 3584 CGUtrecht, The Netherlands
| | - Berend Olivier
- Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Universiteitsweg 99, 3584 CGUtrecht, The Netherlands
| | - Jan G Veening
- Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Universiteitsweg 99, 3584 CGUtrecht, The Netherlands; Department of Anatomy, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - Mark J Millan
- Institut de Recherches Servier, Psychopharmacology Department, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France
| | - Marcel D Waldinger
- Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Universiteitsweg 99, 3584 CGUtrecht, The Netherlands
| | - Ronald S Oosting
- Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Universiteitsweg 99, 3584 CGUtrecht, The Netherlands
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27
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Abstract
Ejaculatory dysfunction may occur after many different disorders ranging from traumatic spinal cord injury to diabetes mellitus. With an understanding of the many facets and nuances of the ejaculatory apparatus, both anatomic and neurologic, the well-versed clinician can proceed along a safe, efficient, and appropriate treatment algorithm to help affected men and their partners achieve parenthood.
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Affiliation(s)
- Elizabeth Phillips
- Division of Urology, Boston University School of Medicine, Shapiro Center, Suite 3B, 715 Albany Street, Boston, MA 02118, USA
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28
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Bowman BR, Kumar NN, Hassan SF, McMullan S, Goodchild AK. Brain sources of inhibitory input to the rat rostral ventrolateral medulla. J Comp Neurol 2013; 521:213-32. [PMID: 22740031 DOI: 10.1002/cne.23175] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 05/02/2012] [Accepted: 06/20/2012] [Indexed: 12/19/2022]
Abstract
The rostral ventrolateral medulla (RVLM) contains neurons critical for cardiovascular, respiratory, metabolic, and motor control. The activity of these neurons is controlled by inputs from multiple identified brain regions; however, the neurochemistry of these inputs is largely unknown. Gamma-aminobutyric acid (GABA) and enkephalin tonically inhibit neurons within the RVLM. The aim of this study was to identify all brain regions that provide GABAergic or enkephalinergic input to the rat RVLM. Neurons immunoreactive for cholera toxin B (CTB-ir), retrogradely transported from the RVLM, were assessed for expression of glutamic acid decarboxylase (GAD67) or preproenkephalin (PPE) mRNA using in situ hybridization. GAD67 mRNA was expressed in CTB-ir neurons in the following regions: the nucleus of the solitary tract (NTS, 6% of CTB-ir neurons), area postrema (AP, 8%), caudal ventrolateral medulla (17%), midline raphe (40%), ventrolateral periaqueductal gray (VLPAG, 15%), lateral hypothalamic area (LHA, 25%), central nucleus of the amygdala (CeA, 77%), sublenticular extended amygdala (SLEA, 86%), interstitial nucleus of the posterior limb of the anterior commissure (IPAC, 56%), bed nucleus of the stria terminals (BNST, 59%), and medial preoptic area (MPA, 53%). PPE mRNA was expressed in CTB-ir neurons in the following regions: the NTS (14% of CTB-ir neurons), midline raphe (26%), LHA (22%), zona incerta (ZI, 15%), CeA (5%), paraventricular nucleus (PVN, 13%), SLEA (66%), and MPA (26%). Thus, limited brain regions contribute GABAergic and/or enkephalinergic input to the RVLM. Multiple neurochemically distinct pathways originate from these brain regions projecting to the RVLM.
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Affiliation(s)
- Belinda R Bowman
- Australian School of Advanced Medicine, Macquarie University, 2109, NSW Australia
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Abstract
The male refractory period (MRP) continues to be a topic of discussion and debate within the field of sexual medicine. To date explanations rely on central descending (efferent) influences involving specific neurotransmitter systems. Herein we explore the issue of the male refractory period, identifying problems with current explanations, specifying the parameters of an adequate model, and suggesting possible mechanisms mediating this phenomenon. We review the literature regarding existing explanations for the MRP and look to other systems of physiological regulation that might provide a model for the conceptualization of the MRP. Our approach differs from traditional explanations in that it emphasizes the possible roles of various peripheral, rather than central, feedback (afferent) systems that affect peripheral autonomic functioning and response. Yet our approach is consistent with other peripheral regulatory feedback systems controlling autonomic response related to such processes as heart rate, respiration, and gut motility. Although direct empirical research supporting our approach is lacking, sufficient evidence exists to support the idea that such processes are not only possible but likely with respect to the male refractory period. We suggest several lines of research that might provide empirical support for this approach.
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Affiliation(s)
- Kenneth R Turley
- Department of Psychology, Valparaiso University, Valparaiso, IN, USA.
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30
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Effect of dexmedetomidine on ejaculatory behavior and sexual motivation in intact male rats. Pharmacol Biochem Behav 2012; 103:345-52. [DOI: 10.1016/j.pbb.2012.09.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2012] [Revised: 08/29/2012] [Accepted: 09/08/2012] [Indexed: 01/07/2023]
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31
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Soga T, Wong D, Putteeraj M, Song K, Parhar I. Early-life citalopram-induced impairments in sexual behavior and the role of androgen receptor. Neuroscience 2012; 225:172-84. [DOI: 10.1016/j.neuroscience.2012.08.061] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Revised: 08/28/2012] [Accepted: 08/28/2012] [Indexed: 01/27/2023]
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Estrogen dependent activation function of ERβ is essential for the sexual behavior of mouse females. Proc Natl Acad Sci U S A 2012; 58:e41. [PMID: 23150547 DOI: 10.1073/pnas.1217668109] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 11/05/2019] [Indexed: 12/26/2022] Open
Abstract
We previously generated and characterized a genuine estrogen receptor (ER) β-null mouse line (named ERβ(ST)(L-/L-)) and showed that ERβ(ST)(L-/L-) mice were sterile, due to an ovulation impairment in females and to an unknown reason in males, as their reproductive organs and spermatozoid motility appeared normal. We report here an assessment of the sexual behavior of ERβ(ST)(L-/L-) null mice. We found that ERβ(ST)(L-/L-) males display mildly impaired sexual behavior and that ERβ(ST)(L-/L-) females are significantly less receptive and less attractive than wild-type (WT) females. Decreased attractivity is also exhibited by ERβAF2(0) but not by ERβAF1(0) mutant females (females devoid of either AF2 or AF1 activation function of ERβ). Interestingly, by using an odor preference test, we have determined that the low attractiveness of ERβ(ST)(L-/L-) and ERβAF2(0) females is related to a deficiency of a volatile chemosignal.
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Abstract
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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Affiliation(s)
- François Giuliano
- Service de Médecine Physique et de Réadaptation, Hôpital Raymond Poincaré, 104 bd Raymond Poincaré, 92380 Garches, France.
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34
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Kozyrev N, Lehman MN, Coolen LM. Activation of Gastrin‐releasing Peptide Receptors in the Lumbosacral Spinal Cord is Required for Ejaculation in Male Rats. J Sex Med 2012; 9:1303-18. [DOI: 10.1111/j.1743-6109.2012.02688.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Hueletl‐Soto ME, Carro‐Juárez M, Rodríguez‐Manzo G. Fluoxetine Chronic Treatment Inhibits Male Rat Sexual Behavior by Affecting Both Copulatory Behavior and the Genital Motor Pattern of Ejaculation. J Sex Med 2012; 9:1015-26. [DOI: 10.1111/j.1743-6109.2011.02339.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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36
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Brain–spinal cord neural circuits controlling male sexual function and behavior. Neurosci Res 2012; 72:103-16. [DOI: 10.1016/j.neures.2011.11.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Revised: 10/14/2011] [Accepted: 10/25/2011] [Indexed: 01/10/2023]
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37
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Staudt MD, Truitt WA, McKenna KE, de Oliveira CVR, Lehman MN, Coolen LM. A pivotal role of lumbar spinothalamic cells in the regulation of ejaculation via intraspinal connections. J Sex Med 2011; 9:2256-65. [PMID: 22189051 DOI: 10.1111/j.1743-6109.2011.02574.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
INTRODUCTION A population of lumbar spinothalamic cells (LSt cells) has been demonstrated to play a pivotal role in ejaculatory behavior and comprise a critical component of the spinal ejaculation generator. LSt cells are hypothesized to regulate ejaculation via their projections to autonomic and motor neurons in the lumbosacral spinal cord. AIM The current study tested the hypothesis that ejaculatory reflexes are dependent on LSt cells via projections within the lumbosacral spinal cord. METHODS Male rats received intraspinal injections of neurotoxin saporin conjugated to substance P analog, previously shown to selectively lesion LSt cells. Two weeks later, males were anesthetized and spinal cords were transected. Subsequently, males were subjected to ejaculatory reflex paradigms, including stimulation of the dorsal penile nerve (DPN), urethrogenital stimulation or administration of D3 agonist 7-OH-DPAT. Electromyographic recordings of the bulbocavernosus muscle (BCM) were analyzed for rhythmic bursting characteristic of the expulsion phase of ejaculation. In addition, a fourth commonly used paradigm for ejaculation and erections in unanesthetized, spinal-intact male rats was utilized: the ex copula reflex paradigm. MAIN OUTCOME MEASURES LSt cell lesions were predicted to prevent rhythmic bursting of BCM following DPN, urethral, or pharmacological stimulation, and emissions in the ex copula paradigm. In contrast, LSt cell lesions were not expected to abolish erectile function as measured in the ex copula paradigm. RESULTS LSt cell lesions prevented rhythmic contractions of the BCM induced by any of the ejaculatory reflex paradigms in spinalized rats. However, LSt cell lesions did not affect erectile function nor emissions determined in the ex copula reflex paradigm. CONCLUSIONS These data demonstrate that LSt cells are essential for ejaculatory, but not erectile reflexes, as previously reported for mating animals. Moreover, LSt cells mediate ejaculation via projections within the spinal cord, presumably to autonomic and motor neurons.
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Affiliation(s)
- Michael D Staudt
- Department of Anatomy & Cell Biology, The University of Western Ontario, London, Ontario, Canada
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38
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Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev 2011; 63:811-59. [PMID: 21880989 DOI: 10.1124/pr.111.004515] [Citation(s) in RCA: 239] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, both autonomic and somatic, and supraspinal influences from visual, olfactory, and imaginary stimuli. Several central transmitters are involved in the erectile control. Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as oxytocin and adrenocorticotropin/α-melanocyte-stimulating hormone, have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. The balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa (CC) and determines the functional state of the penis. Noradrenaline contracts both CC and penile vessels via stimulation of α₁-adrenoceptors. Neurogenic NO is considered the most important factor for relaxation of penile vessels and CC. The role of other mediators, released from nerves or endothelium, has not been definitely established. Erectile dysfunction (ED), defined as the "inability to achieve or maintain an erection adequate for sexual satisfaction," may have multiple causes and can be classified as psychogenic, vasculogenic or organic, neurologic, and endocrinologic. Many patients with ED respond well to the pharmacological treatments that are currently available, but there are still groups of patients in whom the response is unsatisfactory. The drugs used are able to substitute, partially or completely, the malfunctioning endogenous mechanisms that control penile erection. Most drugs have a direct action on penile tissue facilitating penile smooth muscle relaxation, including oral phosphodiesterase inhibitors and intracavernosal injections of prostaglandin E₁. Irrespective of the underlying cause, these drugs are effective in the majority of cases. Drugs with a central site of action have so far not been very successful. There is a need for therapeutic alternatives. This requires identification of new therapeutic targets and design of new approaches. Research in the field is expanding, and several promising new targets for future drugs have been identified.
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Affiliation(s)
- K-E Andersson
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA.
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Sweni S, Meenakshisundaram R, Senthilkumaran S, Thirumalaikolundusubramanian P. Propofol’s derivative: A potential drug for erectile dysfunction? Med Hypotheses 2011; 77:668-70. [DOI: 10.1016/j.mehy.2011.07.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2011] [Accepted: 07/04/2011] [Indexed: 11/17/2022]
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Yin TL, Yang J, Zhang B, Yan WJ, Xu WM, Li W, Yu L, Li SJ, Wu GX. Folic acid supplementation as adjunctive treatment premature ejaculation. Med Hypotheses 2011; 76:414-6. [DOI: 10.1016/j.mehy.2010.11.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Revised: 11/01/2010] [Accepted: 11/08/2010] [Indexed: 12/26/2022]
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Normandin JJ, Murphy AZ. Serotonergic lesions of the periaqueductal gray, a primary source of serotonin to the nucleus paragigantocellularis, facilitate sexual behavior in male rats. Pharmacol Biochem Behav 2011; 98:369-75. [PMID: 21296106 DOI: 10.1016/j.pbb.2011.01.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2010] [Revised: 01/21/2011] [Accepted: 01/28/2011] [Indexed: 10/18/2022]
Abstract
While selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anxiety and depression, they also produce profound disruptions of sexual function including delayed orgasm/ejaculation. The nucleus paragigantocellularis (nPGi), a primary source of inhibition of ejaculation in male rats, contains receptors for serotonin (5-HT). The ventrolateral periaqueductal gray (vlPAG) provides serotonin to this region, thus providing an anatomical and neurochemical basis for serotonergic regulation of the nPGi. We hypothesize that 5-HT acting at the nPGi could underlie the SSRI-induced inhibition of ejaculation in rodents. To this end, we produced 5-HT lesions of the source of 5-HT to the nPGi (the vlPAG) and examined sexual behavior. Removing the source of 5-HT to the nPGi facilitated genital reflexes, but not other aspects of sexual behavior, consistent with our hypothesis. Namely, 5-HT lesions produced a significant increase in the mean number of ejaculations and a significant decrease in ejaculation latency as compared to sham lesioned animals, while latency to mating and the post-ejaculatory interval did not differ. These data suggest that the serotonergic vlPAG-nPGi pathway is an important regulatory mechanism for the inhibition of ejaculation in rats and supports the hypothesis that this circuit contributes to SSRI-induced inhibition of ejaculation.
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Affiliation(s)
- Joseph J Normandin
- Department of Biology, Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30302-4010, USA
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Waldinger MD. Toward evidence-based genetic research on lifelong premature ejaculation: a critical evaluation of methodology. Korean J Urol 2011; 52:1-8. [PMID: 21344023 PMCID: PMC3037500 DOI: 10.4111/kju.2011.52.1.1] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2010] [Accepted: 12/16/2010] [Indexed: 01/21/2023] Open
Abstract
Recently, four premature ejaculation (PE) subtypes have been distinguished on the basis of the duration of the intravaginal ejaculation latency time (IELT). These four PE subtypes have different etiologies and pathogeneses. Genetic research on PE should consider the existence of these PE subtypes and the accurate measurement of the IELT with a stopwatch. Currently, three methods of genetic research on PE have been used. They differ in the investigated population, tool of measurement, study design, and variables of PE. From animal and human research, it is derived that the central serotonergic system "modulates" ejaculation, whereas the ejaculation (reflex) itself is probably not under direct influence of the serotonergic system, but rather under the influence of other neurotransmitter systems in the spinal cord. For genetic research on PE, it is important to take into account that the (serotonergic) modulation of the IELT is variable among men and may even be absent. This means that serotonergic genetic polymorphisms may only be found in men with PE who respond with an ejaculation delay treatment with a selective serotonin reuptake inhibitor.
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Affiliation(s)
- Marcel D Waldinger
- Department of Psychiatry and Neurosexology, HagaHospital, The Hague, The Netherlands
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Melis MR, Argiolas A. Central control of penile erection: A re-visitation of the role of oxytocin and its interaction with dopamine and glutamic acid in male rats. Neurosci Biobehav Rev 2011; 35:939-55. [DOI: 10.1016/j.neubiorev.2010.10.014] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Revised: 10/08/2010] [Accepted: 10/26/2010] [Indexed: 11/28/2022]
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Normandin JJ, Murphy AZ. Excitotoxic lesions of the nucleus paragigantocellularis facilitate male sexual behavior but attenuate female sexual behavior in rats. Neuroscience 2010; 175:212-23. [PMID: 21144886 DOI: 10.1016/j.neuroscience.2010.11.030] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 11/11/2010] [Accepted: 11/13/2010] [Indexed: 01/23/2023]
Abstract
Little is known regarding the descending inhibitory control of genital reflexes such as ejaculation and vaginal contractions. The brainstem nucleus paragigantocellularis (nPGi) projects bilaterally to the lumbosacral motoneuron pools that innervate the genital musculature of both male and female rats. Electrolytic nPGi lesions facilitate ejaculation in males, leading to the hypothesis that the nPGi is the source of descending inhibition to genital reflexes. However, the function of the nPGi in female sexual behavior remains to be elucidated. To this end, male and female rats received bilateral excitotoxic fiber-sparing lesions of the nPGi, and sexual behavior and sexual behavior-induced Fos expression were examined. In males, nPGi lesions facilitated copulation, supporting the hypothesis that the nPGi, and not fibers-of-passage, is the source of descending inhibition of genital reflexes in male rats. nPGi lesions in males did not alter sexual behavior-induced Fos expression in any brain region examined. nPGi-lesioned females spent significantly less time mating with stimulus males and had significantly longer ejaculation-return latencies compared to baseline. These results did not significantly differ from control females, but this trend warranted further analysis of the reinforcing value of sexual behavior. Both lesioned and non-lesioned females formed a conditioned place preference (CPP) for artificial vaginocervical stimulation (aVCS). However, post-reinforcement, nPGi-lesioned females did not differ in the percentage of time spent in the non-reinforced chamber versus the reinforced chamber, suggesting a weakened CPP for aVCS. nPGi lesions in females reduced sexual behavior-induced Fos expression throughout the hypothalamus and amygdala. Taken together, these results suggest that while nPGi lesions in males facilitate copulation, such lesions in females attenuate several aspects of sexual behavior resulting in a reduction in the rewarding value of copulation that may be mediated by nPGi control of genital reflexes. This work has important implications for the understanding and treatment of sexual dysfunction in people including delayed/premature ejaculation, involuntary vaginal spasms, and pain during intercourse.
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Affiliation(s)
- J J Normandin
- Department of Biology, Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30302-4010, USA
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Chan JSW, Waldinger MD, Olivier B, Oosting RS. Drug-induced sexual dysfunction in rats. CURRENT PROTOCOLS IN NEUROSCIENCE 2010; Chapter 9:Unit 9.34. [PMID: 20938926 DOI: 10.1002/0471142301.ns0934s53] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
This unit describes the testing of sexual behaviors of male Wistar rats. The described test enables the detection of stimulatory and inhibitory profiles of compounds. The test includes four training sessions to reach a stable sexual performance, followed by acute and/or chronic administration of drugs. The main quantifiable sexual behaviors are number of mounts (no vaginal penetration), intromissions (vaginal penetration), and ejaculations. By comparing the test compound to reference compound(s), sexual (side) effects can be determined.
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MESH Headings
- Animals
- Behavior, Animal/drug effects
- Behavior, Animal/physiology
- Copulation/drug effects
- Copulation/physiology
- Disease Models, Animal
- Drug Evaluation, Preclinical/methods
- Female
- Genitalia, Male/drug effects
- Genitalia, Male/innervation
- Genitalia, Male/physiopathology
- Male
- Rats
- Rats, Wistar
- Serotonin/physiology
- Selective Serotonin Reuptake Inhibitors/adverse effects
- Selective Serotonin Reuptake Inhibitors/toxicity
- Sexual Behavior, Animal/drug effects
- Sexual Behavior, Animal/physiology
- Sexual Dysfunction, Physiological/chemically induced
- Sexual Dysfunction, Physiological/physiopathology
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Affiliation(s)
- Johnny S W Chan
- Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
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Keel CE, Dorsey PJ, Acker W, Hellstrom WJG. New Concepts in the Diagnosis and Treatment of Premature Ejaculation. Curr Urol Rep 2010; 11:414-20. [DOI: 10.1007/s11934-010-0144-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Carro‐Juárez M, Rodríguez‐Manzo G. Participation of Endogenous Opioids in the Inhibition of the Spinal Generator for Ejaculation in Rats. J Sex Med 2009; 6:3045-55. [DOI: 10.1111/j.1743-6109.2009.01470.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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5-HT(1A) receptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats. Int J Neuropsychopharmacol 2009; 12:1045-53. [PMID: 19435548 DOI: 10.1017/s1461145709000406] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapies. 5-HT(1A) antagonists have been suggested as beneficial adjunctive treatment in respect of antidepressant efficacy; however, the effects of 5-HT(1A) antagonism on antidepressant-induced side-effects has not been fully examined. The present study was conducted to evaluate the ability of acute or chronic treatment with 5-HT(1A) antagonists to alter chronic fluoxetine-induced impairments in sexual function. Chronic 14-d treatment with fluoxetine resulted in a marked reduction in the number of non-contact penile erections in sexually experienced male rats, relative to vehicle-treated controls. Acute administration of the 5-HT(1A) antagonist WAY-101405 resulted in a complete reversal of chronic fluoxetine-induced deficits on non-contact penile erections at doses that did not significantly alter baselines. Chronic co-administration of the 5-HT(1A) antagonists WAY-100635 or WAY-101405 with fluoxetine prevented fluoxetine-induced deficits in non-contact penile erections in sexually experienced male rats. Moreover, withdrawal of WAY-100635 from co-treatment with chonic fluoxetine, resulted in a time-dependent reinstatement of chronic fluoxetine-induced deficits in non-contact penile erections. Additionally, chronic administration of SSA-426, a molecule with dual activity as both a SSRI and 5-HT(1A) antagonist, did not produce deficits in non-contact penile erections at doses demonstrated to have antidepressant-like activity in the olfactory bulbectomy model. Taken together, these data suggest that 5-HT(1A) antagonist treatment may have utility for the management of SSRI-induced sexual dysfunction.
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Hellstrom WJ, Giuliano F, Rosen RC. Ejaculatory Dysfunction and Its Association With Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia and BPH Treatment. Urology 2009; 74:15-21. [DOI: 10.1016/j.urology.2008.06.048] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2008] [Revised: 06/09/2008] [Accepted: 06/25/2008] [Indexed: 11/24/2022]
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