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Tramadol's Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats.

Diana C Esquivel-Franco1,2,3, Berend Olivier1,4,5, Marcel D Waldinger6

  • 1Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands.

Frontiers in Pharmacology
|July 13, 2018
PubMed
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Tramadol

Area of Science:

  • Neuroscience
  • Pharmacology
  • Urology

Background:

  • Premature ejaculation (PE) is a common male sexual dysfunction.
  • Tramadol is an effective treatment for PE.
  • The exact mechanism of tramadol's action in PE is not fully understood.

Purpose of the Study:

  • To investigate the role of serotonin transporter (SERT) inhibition in tramadol's effects on sexual behavior.
  • To explore the involvement of 5-HT1A receptors and μ-opioid receptors in tramadol's inhibitory action.

Main Methods:

  • Dose-response effects of tramadol on sexual behavior were tested in rats with varying serotonin transporter (SERT) gene expression (wild type, heterozygous, and knockout).
  • The effects of a 5-HT1A receptor antagonist (WAY100,635) and a μ-opioid receptor antagonist (naloxone) were evaluated alone and in combination with tramadol.
Keywords:
5-HT1A receptorSSRIratserotonin transportersexual behaviortramadolμ-opioid receptor

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Main Results:

  • Tramadol dose-dependently reduced sexual activity in all rat groups.
  • WAY100,635 and naloxone alone had minimal effects, but in combination with tramadol, they significantly reduced sexual activity, especially in SERT knockout rats.
  • Combined administration of tramadol, WAY100,635, and naloxone completely eliminated sexual activity.

Conclusions:

  • Tramadol's inhibitory effects on male sexual behavior are primarily mediated by SERT inhibition and involve 5-HT1A receptors.
  • Unlike SSRIs requiring chronic administration, tramadol's mechanism suggests potential for on-demand therapy for premature ejaculation.