{"title":"Preclinical evidence for the anxiolytic- and antidepressant-like effects of citicoline and imipramine in the sciatic nerve-ligated mice","authors":"Mohammad-Reza Zarrindast , Bardia Hajikarimloo , Nastaran Raissi-Dehkordi , Negar Raissi-Dehkordi , Fatemeh Khakpai","doi":"10.1016/j.ibneur.2024.10.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 364-371"},"PeriodicalIF":2.0000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"IBRO Neuroscience Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667242124000939","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.