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Preclinical Evidence for the Anxiolytic- and Antidepressant-Like Effects of Citicoline and Imipramine in the Sciatic Nerve-Ligated Mice Publisher



Zarrindast MR1, 2, 3 ; Hajikarimloo B4 ; Raissidehkordi N4 ; Raissidehkordi N4 ; Khakpai F5, 6
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  4. 4. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  6. 6. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

Source: IBRO Neuroscience Reports Published:2024


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. © 2024 The Authors