ANTIDEPRESSANT-LIKE EFFECT OF SILDENAFIL THROUGH OXYTOCIN-DEPENDENT CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN PHOSPHORYLATION

作者：Matsushita H; Matsuzaki M; Han X J; Nishiki T I; Ohmori I; Michiue H; Matsui H; Tomizawa K^*

来源：Neuroscience, 2012, 200: 13-18.

DOI：10.1016/j.neuroscience.2011.11.001

• oxytocin
• depression
• CREB
• sildenafil
• anxiety
• MAP kinase

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.

• 出版日期2012-1-3