A study of time- and sex-dependent effects of vortioxetine on rat sexual behavior

Possible roles of direct receptor modulation

Yan Li, Alan L. Pehrson, Ronald S. Oosting, Maria E. Gulinello, Berend Olivier, Connie Sanchez

Research output: Contribution to journalArticle

Abstract

Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT1A agonist), CP-94253 (a 5-HT1B agonist), or ondansetron (a 5-HT3 antagonist). These selective ligands were chosen to simulate vortioxetine's direct modulation of these receptors. Paroxetine was also included in the male study. Acute and repeated treatment with vortioxetine at doses corresponding to clinical levels (based on serotonin transporter occupancy) had minimal effects on sexual behavior in male and female rats. High dose vortioxetine plus flesinoxan (to mimic predicted clinical levels of 5-HT1A receptor occupancy by vortioxetine) facilitated male rat sexual behavior (acutely) while inhibiting female rat proceptive behavior (both acutely and after 14 days treatment). The selective serotonin reuptake inhibitor, paroxetine, inhibited male sexual behavior after repeated administration (7 and 14 days). Flesinoxan alone facilitated male sexual behavior acutely while inhibiting female rat proceptive behavior after repeated administration (7 and 14 days). CP-94253 inhibited sexual behavior in both male and female rats after repeated administration. Ondansetron had no effect on sexual behavior. These findings underline the complex serotonergic regulation of sexual behavior and indicate that the low sexual side effects of vortioxetine found in clinical studies are likely associated with its direct modulation of serotonin receptors.

Original languageEnglish (US)
Pages (from-to)89-99
Number of pages11
JournalNeuropharmacology
Volume121
DOIs
StatePublished - Jul 15 2017

Fingerprint

Sexual Behavior
Serotonin 5-HT1 Receptor Agonists
Ondansetron
Paroxetine
Antidepressive Agents
Serotonin 5-HT3 Receptor Antagonists
Serotonin Plasma Membrane Transport Proteins
Withholding Treatment
Receptor, Serotonin, 5-HT1A
vortioxetine
Serotonin Receptors
Serotonin Uptake Inhibitors
Therapeutics
Patient Compliance
Ligands
flesinoxan

Keywords

  • 5-HT
  • 5-HT
  • 5-HT
  • Female rat sexual behavior
  • Male rat sexual behavior
  • Vortioxetine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

A study of time- and sex-dependent effects of vortioxetine on rat sexual behavior : Possible roles of direct receptor modulation. / Li, Yan; Pehrson, Alan L.; Oosting, Ronald S.; Gulinello, Maria E.; Olivier, Berend; Sanchez, Connie.

In: Neuropharmacology, Vol. 121, 15.07.2017, p. 89-99.

Research output: Contribution to journalArticle

Li, Yan ; Pehrson, Alan L. ; Oosting, Ronald S. ; Gulinello, Maria E. ; Olivier, Berend ; Sanchez, Connie. / A study of time- and sex-dependent effects of vortioxetine on rat sexual behavior : Possible roles of direct receptor modulation. In: Neuropharmacology. 2017 ; Vol. 121. pp. 89-99.
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