Preclinical evaluation of the impact of cilostazol on anti-depressant activity of fluoxetine

Abstract

The current anti-depressant agents have limitations like the slow onset of action, moderate efficacy, withdrawal symptoms, incompliance of treatment, and instabilities in circadian rhythm. Their therapeutic use is quite restricted and produces inadequate or partial symptomatic relief of depression which may lead to treatment- resistance depression. In the view of a new strategy, second messengers (cAMP, cGMP) and their signalling pathways are emerging as novel targets for anti-depressants. The present study conducted to evaluate the augmentation property of cilostazol on the anti-depressant activity of fluoxetine. Traditional anti-depressant models like forced swimming test and tail suspension test were employed. Mice were randomly grouped into six groups, with six rats in each. Each group was treated, as mentioned in the study. The reduction in immobility period of each mouse was noted. These results were analysed by ordinary one way ANOVA followed by Tukey’s multiple comparison test. Cilostazol at a dose of 20 mg/kg i.p significantly reduced immobility period when compared to cilostazol 10 mg/kg i.p and normal saline. Cilostazol 10 mg/kg i.p also decreased immobility period significantly when compared to normal saline by forced swimming test. Fluoxetine 20 mg/kg i.p + cilostazol 20 mg/kg i.p produced a highly significant reduction in the immobility period in comparison with all groups except with fluoxetine 20 mg/kg i.p + cilostazol 10 mg/kg i.p in forced swimming test. This study concludes that cilostazol has produced dose-dependent anti-depressant activity. This study also emphasises cilostazol can augment the anti-depressant activity of fluoxetine.