Antidepressant-like effect of sildenafil through oxytocin-dependent cyclic AMP response element-binding protein phosphorylation

H. Matsushita, M. Matsuzaki, X. J. Han, T. I. Nishiki, I. Ohmori, H. Michiue, H. Matsui, K. Tomizawa

Research output: Contribution to journalArticle

22 Citations (Scopus)


Oxytocin (OT) levels in plasma increase during sexual response and are significantly lower in patients with depression. A drug for the treatment of sexual dysfunction, sildenafil, enhances the electrically evoked release of OT from the posterior pituitary. In this study, we showed that sildenafil had an antidepressant-like effect through activation of an OT signaling pathway. Application of sildenafil reduced depression-related behavior in male mice. The antidepressant-like effect was blocked by an OT receptor (OTR) antagonist and was absent in OTR knockout (KO) mice. Sildenafil increased the phosphorylation of cAMP response element-binding protein (CREB) in the hippocampus. The OTR antagonist inhibited sildenafil-induced CREB phosphorylation and sildenafil had no effect on CREB phosphorylation in OTR KO mice. These results suggest sildenafil to have an antidepressant-like effect through the activation of OT signaling and to be a promising drug for the treatment of depression.

Original languageEnglish
Pages (from-to)13-18
Number of pages6
Publication statusPublished - Jan 3 2012



  • Anxiety
  • CREB
  • Depression
  • MAP kinase
  • Oxytocin
  • Sildenafil

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this