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Synergistic Effect Between Imipramine and Citicoline Upon Induction of Analgesic and Antidepressant Effects in Mice Publisher Pubmed



Khakpai F1 ; Ramezanikhah M2 ; Valizadegan F2 ; Zarrindast MR3
Authors
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Authors Affiliations
  1. 1. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Neuroscience Letters Published:2021


Abstract

Imipramine is a tricyclic antidepressant (TCA) drug that is sometimes used to treat neuropathic pain. Citicoline is a dietary supplement that has been used as a neuroprotective agent for neurological disorders. Probable interaction between imipramine and citicoline on pain and depression behaviors was examined in mice using a tail-flick test, open field test (OFT), forced swimming test (FST), and tail suspension test (TST). The results indicated that the intraperitoneal (i.p.) administration of citicoline (50 mg/kg) induced analgesic and antidepressant-like behaviors in mice. Similarly, i.p. injection of imipramine (5 mg/kg) induced dose-dependent anti-nociceptive and anti-depressive effects. Co-administration of different doses of imipramine (1.25, 2.5, and 5 mg/kg) along with an ineffective dose of citicoline (6.25 mg/kg) increased tail-flick latency and decreased immobility time in the FST, suggesting an analgesic and antidepressant-like behaviors. Interestingly, there is a synergistic effect between imipramine and citicoline upon the induction of analgesic and antidepressant effects. All doses of the drugs had no significant effect on the locomotor activity. Based on these results, it can be concluded that the administration of citicoline (as an adjuvant drug) in combination with imipramine increased the efficacy of TCA drugs for modulation of pain and depression behaviors. © 2021 Elsevier B.V.