ABSTRACT
Chronic social defeat can inhibit the reproductive system of subordinate males and causes behavioral deficits. Sildenafil treatment increases mice testosterone levels through its effects on Leydig cells of mice and it has been found to work as an antidepressant drug both in humans and in animal models. Since previous findings showed that sildenafil can counteract the inhibitory effects of chronic social defeat on agonistic, reproductive and anxiety-like behaviors of subordinate male mice, we investigated whether these behavioral outcomes can be explained by Sildenafil stimulation of testosterone. CD1 mice underwent an intruder-resident paradigm. After the fifth day of test, subordinate mice were injected with either a 10 mg/kg Sildenafil or a saline solution for 4 weeks. The results of the present study showed that Sildenafil treatment increased counterattacking behaviors and sexual motivation of subordinate males in addition to limiting the increase in body weight often observed in subordinate mice following chronic psychosocial stress. Moreover, sildenafil treated mice showed a pattern of behaviors reflecting lower anxiety. In agreement with previous studies, Sildenafil also increased testosterone levels. These data demonstrate that sildenafil can counteract the effects of chronic stress, possibly through its stimulatory effects on Leydig cells. These data demonstrate that sildenafil might counteract the effects of chronic psychosocial stress through centrally and peripherally mediated mechanisms.
Subject(s)
Sildenafil Citrate/pharmacology , Stress, Psychological/drug therapy , Aggression/drug effects , Animals , Anxiety/drug therapy , Anxiety/metabolism , Disease Models, Animal , Male , Mice , Motivation/drug effects , Sildenafil Citrate/adverse effects , Social Defeat , Stress, Psychological/physiopathology , Testosterone/metabolism , Testosterone/pharmacologyABSTRACT
Selective phosphodiesterases (PDEs) inhibitors have been widely studied as therapeutic agents for treatment of various human diseases, including cardiotonics, vasodilators, smooth muscle relaxants, antidepressants, antithrombotics, antiasthmatics, and agents for improving learning and memory. Although Sildenafil(®) and Vardenafil(®) have similar chemical formulae, the same target and interact with many of the same residues at the active site of phosphodiesterse-5 (PDE-5), they exhibit both in vitro and in vivo some important functional differences that could differentially affect behavior. Therefore we assessed whether repeated and chronic administration of Vardenafil and Sildenafil at a dose based upon human treatment can differentially affect aggressive, social, emotional and sexual behavior. To this aim, the effects of Sildenafil (10mg/kg) or Vardenafil (2mg/kg) (t.i.w., for 5 weeks) were observed in CD1 subordinate male mice in a low aggression and social subordination context. The results show that Sildenafil increased competitive aggression, environmental and social exploration, and reduced anxiety like behaviors as compared to controls, whereas Vardenafil had a significant major effect on appetitive and consummatory aspect of sexual behavior. This demonstrates that Sildenafil and Vardenafil, although being structurally and functionally similar, are characterized by different neuro-behavioral actions and can have differential therapeutic potentials.