Differential effects of vilazodone versus citalopram and paroxetine on sexual behaviors and serotonin transporter and receptors in male rats

RATIONALE: Sexual side effects are commonly associated with selective serotonin reuptake inhibitor (SSRI) treatment. Some evidence suggest that activation of 5-HT(1A) receptors attenuates SSRI-induced sexual dysfunction. OBJECTIVE: This study in male rats compared the effects of vilazodone, an antidepressant with SSRI and 5-HT(1A) receptor partial agonist activity, with other prototypical SSRIs (citalopram and paroxetine) on sexual behaviors and 5-HT receptors (5-HT(1A) and 5-HT(2A)) and transporter (5-HT(T)) 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-HT(1A) receptor levels in cortical and hippocampal regions, while the SSRIs increased levels of this receptor in similar regions. All chronic treatments reduced 5-HT(T) 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-HT(1A) receptor and 5-HT(T) levels relative to conventional SSRIs.