Antidepressants and sexual dysfunctions:A translational perspective

Antidepressants including selective serotonin re-uptake inhibitors (SSRIs) have sexual side effects contributing to treatment cessation. Animal models predicting such effects are needed to develop better antidepressants. Models of normal male rat sexual behavior and a genetic model simulating chronic SSRI-treatment, the serotonin transporter (SERT)–knockout rat, have been developed. Our goal was to use both models to improve prediction of antidepressants without sexual side effects.Recent FindingsMale rats tested weekly for sexual behavior develop a stable sexual phenotype. Normal ejaculating males were used to test antidepressants, and results fit the typical human profile: SSRIs only exert inhibiting effects after chronic administration of antidepressants. Novel SSRI-antidepressants (vilazodone, vortioxetine) with additional serotonergic mechanisms lack inhibition of sexual behavior in line with human data. SERT-KO rats display lower basal sexual behavior than wildtypes at a level comparable with chronic SSRI-treated rats.SummaryThe wild-type model generates results highly translatable to human sexual behavior. The SERT-KO model provides possibilities to study non-SSRI mechanisms in antidepressants