Effect of sildenafil on anxiety in the plus-maze test in mice

Several studies have shown a role of nitric oxide/cyclic guanosine monophosphate signaling pathway in the regulation of anxiety. The effects of the phosphodiesterase (PDE) 5 inhibitors on anxiety are not fully understood. The aim of present study was to investigate the possible role of sildenafil, an inhibitor of cyclic GMP-specific phosphodiesterase, on anxiety in the plus-maze test in mice. Sildenafil at a dose of 0.5 mg/kg had no significant effect on the behavior in the plus-maze test but at doses of 1 and 3 mg/kg induced an anxiogenic effect. The combination of sildenafil (1 mg/kg, i.p.) and methylene blue (1 mg/kg, i.p.) abolished the anxiogenic-like effect of sildenafil. The combination of sildenafil (1 mg/kg, i.p.) and L-arginine (50 mg/kg, i.p.) decreased the percentage of time spent in open arms compared to saline-treated group. Diazepam at a dose of 2 mg/kg significantly increased the percentage of time spent in open arms (p < 0.05). Sildenafil at a dose of 3 mg/kg and the combination of L-arginine (50 mg/kg, i.p.) and sildenafil (1 mg/kg, i.p.) significantly decreased the locomotor activity (p < 0.05). These results suggest that a nitric oxide-cGMP pathway seems to play an important role in sildenafil-induced anxiogenic-like effect.