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A study of time- and sex-dependent effects of vortioxetine on rat sexual behavior: Possible roles of direct receptor modulation.

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 receptor agonist), CP-94253 (a 5-HT1B receptor agonist), or ondansetron (a 5-HT3 receptor 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.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Li Y,Pehrson AL,Oosting RS,Gulinello M,Olivier B,Sanchez C

doi

10.1016/j.neuropharm.2017.04.017

subject

Has Abstract

pub_date

2017-07-15 00:00:00

pages

89-99

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(17)30158-2

journal_volume

121

pub_type

杂志文章

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