The Depressant-Like Effect of Sildenafil in the Forced Swimming Test in Mice

Abstract

Phosphodiesterease type 5 (PDE5), nitric oxide synthase (NOS) and guanilate cyclase have shown high activity in areas responsible to behaviours in brain. It is alleged that PDE5 inhibitor sildenafil which is used in erectile disfunction passes blood brain barrier and can cause adverse effects related to behaviours. The aim of this study, to investigate the effect of sildenanil in depression by forced swimming test in mice. We administered sildenafil (1, 5, 10, 15, 20, 30 mg/kg), sertraline (20 mg/kg) and imipramine (30 mg/kg) with intraperitoneal (ip) injection. All drugs were injected 15 min. before testing. Sertraline and imiprarnine given alone and in combination with sildenafil. When combination with sildenafil and other drugs were employed, other drugs were administered 10 min. before sildenafil. The activity of each mice was recorded for 5 min. in an activity cage (Ugo Basile, 7430-Varese, Italy). Then immobility was measured during the last 4 min. of the 6 min. swim test. Increase immobility time in a swim test has been found to represent "depression- like" behaviour. Sildenafil at a dose of 10mg/kg increased the immobility time without affecting locomotor activity (p<0.05). imiprarnine and sertraline significantly decreased the immobility time (p<0.05). The depressant-like effect of sildenafil (10 mg/kg) was prevented by pretreatment with both sertraline and imiprarnine (p<0.05). These findings suggest that, sildenafil has a depressant-like effect on the forced swimming test and NO-cGMP pathway may play a role in depression.