Co-administration of fluoxetine and Sildenafil has benefits in anxiety behavior in mice

Abstract

Fluoxetine, a selective serotonin reuptake inhibitor, has been widely prescribed drugs in psychiatry. However, it may produce controversial effects, including sexual dysfunction. Sildenafil, a phosphodiesterase inhibitor type 5, may reduce fluoxetine-induced behavior alterations, but its drug interaction profile has not been investigated. To evaluate the interaction between sildenafil and fluoxetine, we acutely or chronically administered adult male mice with intraperitoneal sildenafil (2 mg/kg); fluoxetine (10 mg/kg); a mixture of fluoxetine (10 mg/kg) and sildenafil (2 mg/kg); the anxiolytic benzodiazepine, diazepam (0.3 mg/kg); or saline, after which the mice were evaluated in an elevated plus-maze. The number of entries into the open arms, the time spent in the open arms, and the numbers of total entries into the arms were determined as measures of anxiety. Acute treatment with fluoxetine produced a behavioral profile consistent with anxiogenesis, while sildenafil produced an anxiolytic-like profile. Co-administration of fluoxetine with sildenafil reversed the anxiogenic effects of the former. In chronic treatment neither of drugs (alone) had any effects compared to controls. Their combination resulted in anxiolytic effect. These findings suggest that the anxiolytic sildenafil masked the effect of fluoxetine in the chronic experiment.