Preclinical evidence for the anxiolytic- and antidepressant-like effects of citicoline and imipramine in the sciatic nerve-ligated mice

Background: Neuropathic pain is a usual condition followed by nerve injury. Experimental neuropathy is linked with delayed behavioral variations correlated to anxiety and depression behaviors. Imipramine is a tricyclic antidepressant that can diminish anxiety- and depressive-like behaviors. Also, citicoline as a dietary supplement has antidepressant and anxiolytic effects. Methods: We sought to investigate citicoline's effect on anxiety-like (by elevated plus-maze (EPM)) and depression-like (by tail suspension test (TST)) responses as well as its potential to increase imipramine antidepressant properties in nerve-ligated mice. Results: The results showed that induction of neuropathic pain through sciatic nerve ligation caused anxious- and depressant-like behaviors in male mice. On the other hand, intraperitoneal (i.p.) injections of moderate (50 mg/ kg) and high (100 mg/kg) doses of citicoline and high dose of imipramine (5 mg/kg) significantly reduced anxiety- and depression-like behaviors induced by sciatic nerve ligation in male mice. Additionally, a low (25 mg/kg) dose of citicoline potentiated the anxiolytic- and antidepressant-like effects of different doses of imipramine when they co-injected in nerve-ligated mice. Isobolographic analysis indicated an additive effect of imipramine and citicoline on the occurrence of anxiolytic- and antidepressant-like behaviors in nerve-ligated mice. Our results showed that citicoline alone reduces anxiety- and depression-like behaviors. Furthermore, when co-administered with imipramine, citicoline potentiates imipramine effects. Conclusions: Injection of citicoline (as a dietary supplement) along with imipramine improved the effectiveness of imipramine for the management of anxiety- and depressive-like responses in nerve-ligated mice.