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Additive Anxiolytic-Like Effect of Citicoline and Acpa in the Non-Acute Restraint Stress (Nars) and Acute Restraint Stress (Ars) Mice Publisher Pubmed



Amnzade A1 ; Zarrindast MR2, 3, 4 ; Khakpai F5
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  5. 5. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

Source: Physiology and Behavior Published:2024


Abstract

The cannabinoid system plays a key role in stress-related emotional symptoms such as anxiety. Citicoline is a supplemental substance with neuroprotective properties that alleviates anxiety-related behaviors. There is a relation between the actions of cannabinoids and cholinergic systems. So, we decided to evaluate the effects of intracerebroventricular (i.c.v.) infusion of cannabinoid CB1 receptor agents on citicoline-produced response to anxiety-like behaviors in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. For i.c.v. microinjection of drugs, a guide cannula was inserted in the left lateral ventricle. ARS was induced by movement restraint for 4 h. Anxiety-related behaviors were assessed using an elevated plus maze (EPM). The results showed that induction of ARS for 4 h decreased the percentage of time spent in the open arms (%OAT) and the percentage of entries to the open arms (%OAE) without affecting locomotor activity, showing anxiogenic-like behaviors. i.c.v. infusion of ACPA (1 µg/mouse) induced an anxiolytic-like effect due to the enhancement of %OAT in the NARS and ARS mice. Nonetheless, i.c.v. microinjection of AM251 (1 µg/mouse) decreased %OAT in the NARS and ARS mice which suggested an anxiogenic-like response. Intraperitoneal (i.p.) administration of citicoline (80 mg/kg) induced an anxiolytic-like effect by the augmentation of %OAT in the ARS mice. Furthermore, when ACPA and citicoline were co-administrated, ACPA potentiated the anxiolytic-like effect induced by citicoline in the NARS and ARS mice. On the other hand, when AM251 and the citicoline were co-injected, AM251 reversed the anxiolytic-like response induced by the citicoline in the NARS and ARS mice. The results of this research exhibited an additive effect between citicoline and ACPA on the induction of anxiolytic-like response in the NARS and ARS mice. Our results indicated an interaction between citicoline and cannabinoid CB1 receptor drugs on the control of anxiety-like behaviors in the NARS and ARS mice. © 2024 Elsevier Inc.
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