start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=1 article-no= start-page=103 end-page=114.e5 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the gspinal ejaculation generator (SEG).h We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion?a localized volume transmission?to reach oxytocin receptors on GRP neurons and facilitate male sexual function. en-copyright= kn-copyright= en-aut-name=OtiTakumi en-aut-sei=Oti en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatohKeita en-aut-sei=Satoh en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UtaDaisuke en-aut-sei=Uta en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagafuchiJunta en-aut-sei=Nagafuchi en-aut-mei=Junta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TateishiSayaka en-aut-sei=Tateishi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaRyota en-aut-sei=Ueda en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakanamiKeiko en-aut-sei=Takanami en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoungLarry J. en-aut-sei=Young en-aut-mei=Larry J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GalioneAntony en-aut-sei=Galione en-aut-mei=Antony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorrisJohn F. en-aut-sei=Morris en-aut-mei=John F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama kn-affil= affil-num=4 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Center for Translational Social Neuroscience, Silvio O. Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University kn-affil= affil-num=9 en-affil=Department of Pharmacology, University of Oxford kn-affil= affil-num=10 en-affil=Department of Physiology, Anatomy & Genetics, University of Oxford kn-affil= affil-num=11 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=oxytocin kn-keyword=oxytocin en-keyword=localized volume transmission kn-keyword=localized volume transmission en-keyword=spinal cord kn-keyword=spinal cord en-keyword=male sexual activity kn-keyword=male sexual activity en-keyword=gastrin-releasing peptide kn-keyword=gastrin-releasing peptide en-keyword=spinal ejaculation generator kn-keyword=spinal ejaculation generator END