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.
Kurt
Mehmet
M
Department of Pharmacology, University of Ondokuz Mayis, Samsun, 55139, Turkey.
Bilge
Sirri S
SS
Aksoz
Elif
E
Kukula
Osman
O
Celik
Suleyman
S
Kesim
Yuksel
Y
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced / Q000517:prevention & control*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity*; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
D014151:Anti-Anxiety Agents; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D003975:Diazepam; D008751:Methylene Blue