Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats
Tramadol is an effective pharmacological intervention in human premature ejaculation (PE). To investigate whether the inhibitory action of tramadol is primarily caused by its selective serotonin reuptake inhibitory (SSRI) effects we tested the dose–response effects of tramadol on sexual behavior in...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00676/full |
| _version_ | 1818216460061769728 |
|---|---|
| author | Diana C. Esquivel-Franco Diana C. Esquivel-Franco Diana C. Esquivel-Franco Berend Olivier Berend Olivier Berend Olivier Marcel D. Waldinger Gabriel Gutiérrez-Ospina Gabriel Gutiérrez-Ospina Jocelien D. A. Olivier |
| author_facet | Diana C. Esquivel-Franco Diana C. Esquivel-Franco Diana C. Esquivel-Franco Berend Olivier Berend Olivier Berend Olivier Marcel D. Waldinger Gabriel Gutiérrez-Ospina Gabriel Gutiérrez-Ospina Jocelien D. A. Olivier |
| author_sort | Diana C. Esquivel-Franco |
| collection | DOAJ |
| description | Tramadol is an effective pharmacological intervention in human premature ejaculation (PE). To investigate whether the inhibitory action of tramadol is primarily caused by its selective serotonin reuptake inhibitory (SSRI) effects we tested the dose–response effects of tramadol on sexual behavior in serotonin transporter wild type (SERT+/+), heterozygous (SERT+/-), and knockout (SERT-/-) rats. To investigate whether other mechanisms contribute to the inhibitory effects, WAY100,635, a 5-HT1A receptor antagonist and naloxone, a μ-opioid receptor antagonist, were tested on sexual behavior together with tramadol. Tramadol dose-dependently decreases sexual activity in all genotypes. In all studies, SERT+/- rats did not respond differently from SERT+/+ rats. WAY100,635 did not affect sexual activity in SERT+/+, but dose-dependently reduced sexual activity in SERT-/- rats. WAY100,635 (0.3 mg/kg) combined with tramadol (20 mg/kg) significantly reduced sexual activity in SERT+/+ and even stronger in SERT-/- rats. Naloxone did not affect sexual behavior consistently in SERT+/+ rats, while in SERT-/- rats all doses reduced ejaculation frequency mildly. Combining naloxone (20 mg/kg) and tramadol (20 mg/kg) decreased ejaculation frequencies in both genotypes. Interestingly, combining tramadol (20 mg/kg), WAY100,635 (0.3 mg/kg) and naloxone (20 mg/kg) led to complete elimination of all sexual activity in both SERT+/+ and SERT-/- rats. These findings suggest that the inhibitory effects of tramadol on male sexual behavior in SERT+/+ rats is mainly, if not exclusively, due to SERT inhibition, with an important role for 5-HT1A receptors, although influence of other systems (e.g., noradrenergic) cannot be excluded. As SSRIs exert their sexual inhibition after chronic administration, tramadol may be therapeutically attractive as “on demand” therapy for PE. |
| first_indexed | 2024-12-12T06:52:19Z |
| format | Article |
| id | doaj.art-6bb4b6c1e7a5437f9a17e83dc0542a38 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T06:52:19Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6bb4b6c1e7a5437f9a17e83dc0542a382022-12-22T00:34:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-06-01910.3389/fphar.2018.00676389550Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout RatsDiana C. Esquivel-Franco0Diana C. Esquivel-Franco1Diana C. Esquivel-Franco2Berend Olivier3Berend Olivier4Berend Olivier5Marcel D. Waldinger6Gabriel Gutiérrez-Ospina7Gabriel Gutiérrez-Ospina8Jocelien D. A. Olivier9Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, NetherlandsPrograma de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoNeurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, NetherlandsDepartment of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, NetherlandsDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Pharmacology & Physiology, College of Medicine, Drexel University, Philadelphia, PA, United StatesDepartamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoCoordinación de Psicobiología y Neurociencias, Facultad de Psicología, Universidad Nacional Autónoma de México, Mexico City, MexicoNeurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, NetherlandsTramadol is an effective pharmacological intervention in human premature ejaculation (PE). To investigate whether the inhibitory action of tramadol is primarily caused by its selective serotonin reuptake inhibitory (SSRI) effects we tested the dose–response effects of tramadol on sexual behavior in serotonin transporter wild type (SERT+/+), heterozygous (SERT+/-), and knockout (SERT-/-) rats. To investigate whether other mechanisms contribute to the inhibitory effects, WAY100,635, a 5-HT1A receptor antagonist and naloxone, a μ-opioid receptor antagonist, were tested on sexual behavior together with tramadol. Tramadol dose-dependently decreases sexual activity in all genotypes. In all studies, SERT+/- rats did not respond differently from SERT+/+ rats. WAY100,635 did not affect sexual activity in SERT+/+, but dose-dependently reduced sexual activity in SERT-/- rats. WAY100,635 (0.3 mg/kg) combined with tramadol (20 mg/kg) significantly reduced sexual activity in SERT+/+ and even stronger in SERT-/- rats. Naloxone did not affect sexual behavior consistently in SERT+/+ rats, while in SERT-/- rats all doses reduced ejaculation frequency mildly. Combining naloxone (20 mg/kg) and tramadol (20 mg/kg) decreased ejaculation frequencies in both genotypes. Interestingly, combining tramadol (20 mg/kg), WAY100,635 (0.3 mg/kg) and naloxone (20 mg/kg) led to complete elimination of all sexual activity in both SERT+/+ and SERT-/- rats. These findings suggest that the inhibitory effects of tramadol on male sexual behavior in SERT+/+ rats is mainly, if not exclusively, due to SERT inhibition, with an important role for 5-HT1A receptors, although influence of other systems (e.g., noradrenergic) cannot be excluded. As SSRIs exert their sexual inhibition after chronic administration, tramadol may be therapeutically attractive as “on demand” therapy for PE.https://www.frontiersin.org/article/10.3389/fphar.2018.00676/fullSSRIsexual behaviortramadolrat5-HT1A receptorμ-opioid receptor |
| spellingShingle | Diana C. Esquivel-Franco Diana C. Esquivel-Franco Diana C. Esquivel-Franco Berend Olivier Berend Olivier Berend Olivier Marcel D. Waldinger Gabriel Gutiérrez-Ospina Gabriel Gutiérrez-Ospina Jocelien D. A. Olivier Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats Frontiers in Pharmacology SSRI sexual behavior tramadol rat 5-HT1A receptor μ-opioid receptor |
| title | Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats |
| title_full | Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats |
| title_fullStr | Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats |
| title_full_unstemmed | Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats |
| title_short | Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats |
| title_sort | tramadol s inhibitory effects on sexual behavior pharmacological studies in serotonin transporter knockout rats |
| topic | SSRI sexual behavior tramadol rat 5-HT1A receptor μ-opioid receptor |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00676/full |
| work_keys_str_mv | AT dianacesquivelfranco tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT dianacesquivelfranco tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT dianacesquivelfranco tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT berendolivier tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT berendolivier tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT berendolivier tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT marceldwaldinger tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT gabrielgutierrezospina tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT gabrielgutierrezospina tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats AT joceliendaolivier tramadolsinhibitoryeffectsonsexualbehaviorpharmacologicalstudiesinserotonintransporterknockoutrats |