title: Differential effects of vilazodone versus citalopram and paroxetine on sexual behaviors and serotonin transporter and receptors in male rats.
abstract: BACKGROUND
  Sexual side effects are commonly associated with selective serotonin reuptake inhibitor (SSRI) treatment. Some evidence suggest that activation of 5-HT1A receptors attenuates SSRI-induced sexual dysfunction.
  
  
  OBJECTIVE
  This study in male rats compared the effects of vilazodone, an antidepressant with SSRI and 5-HT1A receptor partial agonist activity, with other prototypical SSRIs (citalopram and paroxetine) on sexual behaviors and 5-HT receptors (5-HT1A and 5-HT2A) and transporter (5-HTT) levels in select forebrain regions of the limbic system using quantitative autoradiography.
  
  
  METHODS
  Rats received vilazodone (1, 3, and 10 mg/kg), citalopram (10 and 30 mg/kg), or paroxetine (10 mg/kg) treatment for 14 days. Sexual behaviors (frequency and latency of mounts, intromissions, and ejaculations) were measured in the presence of an estrous female rat on days 1 (acute), 7 (subchronic), and 14 (chronic).
  
  
  RESULTS
  Vilazodone-treated rats exhibited no sexual dysfunction compared with controls; in contrast, the citalopram- and paroxetine-treated rats exhibited impaired copulatory and ejaculatory behaviors after subchronic and chronic treatments. Chronic vilazodone treatment markedly decreased 5-HT1A receptor levels in cortical and hippocampal regions, while the SSRIs increased levels of this receptor in similar regions. All chronic treatments reduced 5-HTT levels across the forebrain; however, the magnitude of the decrease was considerably smaller for vilazodone than for the SSRIs.
  
  
  CONCLUSIONS
  The current studies showed that chronic treatment with vilazodone, in contrast to citalopram and paroxetine, was not associated with diminished sexual behaviors in male rats, which may be related to the differential effects of vilazodone on 5-HT1A receptor and 5-HTT levels relative to conventional SSRIs.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. R.S.Oosting@uu.nl.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Johnny S
authors.initials: JS
authors.lastname: Chan
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: Department of Psychiatry and Neuroscience Harvard Medical School and McLean Hospital, Belmont, MA, USA.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Department of Psychiatry and Neuroscience Harvard Medical School and McLean Hospital, Belmont, MA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Tarazi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology*; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012725:Sexual Behavior / Q000187:drug effects*; D000069503:Vilazodone Hydrochloride / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D017374:Paroxetine; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride
keywords: 5-HT; 5-HT1A; 5-HT2A; 5-HTT; Citalopram; Ejaculatory behavior; Paroxetine; SSRI; Sexual behavior; Vilazodone