Evaluation of antidepressant and anxiolytic activity of phosphodiesterase 3 inhibitor - Cilostazol

Abstract

Background: Cyclic nucleotide Phosphodiesterases (PDEs) are ubiquitously distributed in mammalian tissues and play a major role in cell signaling by hydrolyzing cyclic Adenosine Monophosphate (cAMP) and cyclic Guanosine Monophosphate (cGMP). Impairments in signal transduction have been implicated as possible mechanism of reduced plasticity and neuronal survival in major depressive disorders. PDE inhibitors possess a potentially powerful means to manipulate secondary messengers involved in learning, memory and mood. Cilostazol is an antiplatelet agent indicated for the treatment of intermittent claudication with peripheral artery occlusion and for the prevention of ischemic stroke worldwide. Various animal studies have reported neuroprotective, anti apoptotic, cognition and cerebral blood flow improvement properties of cilostazol. Materials and Methods: In this study, the antidepressant and anxiolytic effects of cilostazol were evaluated in mice using behavioral tests sensitive to clinically effective antidepressant compound. Results: Cilostazol, administered intraperitoneally (20 mg/kg), decreased immobility time of mice when subjected to forced swim test and tail suspension test as compared to standard fluoxetine (20 mg/kg). Cilostazol also produced significant decrease in the number of marbles buried as compared to fluoxetine in marble burying model. Conclusion: The present study suggests that cilostazol possesses potential antidepressant and anxiolytic activity, which could be of therapeutic interest for use in patients with depressive disorders.

Keywords

• Cilostazol
• forced swim test
• marble burying behavior model
• PDE3 inhibitor
• tail suspension test