Modulation of Anxiety-Like Behavior in Sildenafil Citrate-Treated Mice Placed in an Elevated Plus-Maze

Introduction: Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor, may have various effects on the central nervous system via the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Preclinical studies have shown the controversial effect of sildenafil on anxiety-like behavior in animals. This study was undertaken to investigate the acute effect of sildenafil on anxiety-like behavior in mice. Methods: Male mice were intraperitoneally (i.p.) administrated sildenafil (1, 2, or 10 mg/kg), and the control group was given the vehicle 15 min before the plus-maze test. The number of entries into the open arms of the plus-maze, the time spent in the open arms, and the total numbers of entries into the arms were recorded. Results: The results indicated that compared to the control group, the sildenafil-treated mice spent more time in the open arms and had a greater number of entries into open arms. The total number of entries into the arms did not significantly differ between the sildenafil-treated groups and the control group. Discussion: Acute administration of sildenafil could have anxiolytic effects on male mice. This effect might be mediated in a time-dependent manner by the NO/ cGMP/PDE5 pathway.