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Synergistic Effect Between Citalopram and Citicoline on Anxiolytic Effect in Non-Sensitized and Morphine-Sensitized Mice: An Isobologram Analysis Publisher Pubmed



Nejati S1 ; Khakpai F2 ; Zarrindast MR3, 4, 5, 6
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology and Toxicology, Islamic Azad University, Pharmaceutical Science Branch (IAUPS), Tehran, Iran
  2. 2. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  3. 3. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  6. 6. Department of Neuroendocrinology, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Brain Research Published:2020


Abstract

In the present study, the effects of intraperitoneal (i.p.) injections of citalopram and citicoline on morphine-induced anxiolytic effects were investigated in non-sensitized and morphine-sensitized mice using elevated plus-maze (EPM). Subcutaneous (s.c.) administration morphine (5 mg/kg) increased the percentage of open arm time (%OAT, in morphine-sensitized mice), and open arm entries (%OAE, in non-sensitized mice), but not a locomotor activity, indicating an anxiolytic response to morphine. On the other hand, i.p. administration of naloxone decreased %OAT (morphine-sensitized mice), and %OAE (non-sensitized and morphine-sensitized mice), but not a locomotor activity, showing an anxiogenic effect to naloxone. Moreover, i.p.co-administration of citalopram (5 and 10 mg/kg) and citicoline (75 mg/kg) induced the anxiolytic effect. Interestingly, i.p. co-administration of low doses of citalopram (0.5, 1 and 2.5 mg/kg) and citicoline (25 mg/kg) significantly increased %OAT and %OAE in non-sensitized as well as %OAT in morphine-sensitized mice, indicating an anxiolytic effect. An isobolographic analysis of data was performed, presenting a synergistic interaction between citalopram and citicoline upon the production of anxiolytic effect in non-sensitized and morphine-sensitized mice. In conclusion, it seems that (1) morphine sensitization affects the anxiety behavior in the EPM, (2) μ-opioid receptors play an important role in morphine anxiolytic effect, (3) citalopram and citicoline induced anti-anxiety effect, (4) a synergistic effect of citalopram and citicoline upon induction of anti-anxiety behavior in non-sensitized and morphine-sensitized mice. © 2020
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