title: Tramadol: Effects on sexual behavior in male rats are mainly caused by its 5-HT reuptake blocking effects.
abstract: Tramadol is a well-known and effective analgesic. Recently it was shown that tramadol is also effective in human premature ejaculation. The inhibitory effect of tramadol on the ejaculation latency is probably due to its mechanism of action as a μ-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake inhibitor. In order to test this speculation, we tested several doses of tramadol in a rat model of male sexual behavior and investigated two types of drugs interfering with the μ-opioid and the 5-HT system. First the μ-opioid receptor agonist properties of tramadol were tested with naloxone, a μ-opioid receptor antagonist. Second, the effects of WAY100,635, a 5-HT1Areceptor antagonist, were tested on the behavioral effects of tramadol. Finally the effects of paroxetine, a selective serotonin reuptake inhibitor, combined with naloxone or WAY100,635 treatment, were compared to the effects of tramadol combined with these drugs. Results showed that naloxone, at a sexually inactive dose, could only partially antagonize the inhibitory effect of tramadol. Moreover, low and behaviorally inactive doses of WAY100,635, strongly decreased sexual behavior when combined with a behaviorally inactive dose of tramadol. Finally we showed that the effects of paroxetine on sexual behavior resembled the effects of tramadol, indicating that tramadol's inhibitory effects on sexual behavior are primarily and mainly caused by its SSRI properties and that its μ-opioid receptor agonistic activity only contributes marginally. These findings support the hypothesis that tramadol exerts inhibition of premature ejaculations in men by its 5-HT reuptake inhibiting properties.
authors.affiliation: Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. Electronic address: j.d.a.olivier@rug.nl.
authors.forename: Jocelien D A
authors.initials: JD
authors.lastname: Olivier
authors.affiliation: Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; PhD Program in Biomedical Sciences, National Autonomous University of Mexico, Mexico City 04510, Mexico; Department of Cell Biology and Physiology, Biomedical Research Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Esquivel Franco
authors.affiliation: Dept. of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Oosting
authors.affiliation: Dept. of Pharmacology & Physiology, College of Medicine, Drexel University, Philadelphia, PA, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Waldinger
authors.affiliation: Laboratory of Psychiatric Neuroscience, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Sarnyai
authors.affiliation: Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Dept. of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004542:Ejaculation / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D014147:Tramadol / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D009270:Naloxone; D009292:Narcotic Antagonists; D017374:Paroxetine; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D017450:Receptors, Opioid, mu; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014147:Tramadol; C485765:Oprm1 protein, rat; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: 5-HT(1A) receptor; Male sexual behavior; Naloxone; SSRI; Tramadol