Zaprinast, a phosphodiesterase 5 inhibitor, overcomes sexual dysfunction produced by fluoxetine, a selective serotonin reuptake inhibitor in hamsters

Abstract

A high incidence of sexualdys function among women is reported in the clinicalliterature. Little experimental investigation has been initiated on the ability of phosphodiesterase (PDE) inhibitors to overcome deficits in sexual functioning because of selective serotonin reuptake inhibitors (SSRIs). The effects of fluoxetine, an SSRI, and zaprinast, a PDE-5 inhibitor, on the lateral displacement response (used as a measure of sensitivity to reproductively relevant stimuli) of hamsters in behavioral estrus were investigated. In Experiment 1, hamsters that were maximally sensitive to reproductively relevant stimuli because they were at the peak of behavioral estrus were administered fluoxetine (10mg/kg, i.p.); they had significantly decreased lateral displacement responses compared to vehicle-administered hamsters. In Experiment 2, hamsters that were relatively less sensitive to sexualstimuli because they were at the termination of behavioral estrus were administered zaprinast (3 mg/kg; i.p.); they had significantly enhanced lateral displacement responses compared to responses seen following vehicle administration. In Experiment 3, fluoxetine-induced deficits in the lateral displacement of hamsters at the peak of behavioral estrus were overcome by the coadministration of zaprinast. These data confirm previous findings that sexual dys function can be induced by SSRIs and extend the current knowledge to suggest that administration of a PDE-5 inhibitor can override SSRI-induced deficits in sexual functioning. © 2003 Nature Publishing Group.