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Aim: We have previously demonstrated that a chronic treatment with sildenafil, a potent phosphodiesterase-5 inhibitor (PDE5-I) used to treat erectile dysfunction, improved motor performance in mouse models of physiological aging. Because of these findings, and considered that the NO/cGMP pathway is involved in muscle contraction, metabolism and vascularization, here we aimed to investigate whether sildenafil might affect morphological and functional properties of skeletal muscles, anxiety-like behavior and BDNF brain levels, which are known to be linked to exercise. Methods: We used males and females C57Bl/6J wild type mice aged 3-6 months treated with daily i.p. injections of sildenafil (3mg/kg) or vehicle for 3 weeks. We measured muscle strength by grip strength test and weights test, and anxiety-like behavior by elevated plus maze. Muscle hypertrophy was assessed by histological analyses on gastrocnemius. BDNF levels were analyzed by Western Blot on brain extracts. Results: We found that sildenafil induced an increase of both muscular mass and functional strength. Moreover, treated mice showed an improvement of anxiety-like behavior (more time and number of entries in the open arms), and an increase of BDNF brain levels. These results were more evident in a group of mice trained with a moderate exercise by forced treadmill running. Conclusions: Our data suggest that the increase in cGMP by PDE5-I might improve motor performance. These findings might be useful to enhance sport performance or in diseases characterized by an impairment of muscular strength.

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