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Investigating the anti-anxiety effects of the combined administration of alprazolam and citicoline on anxiety behaviors following stress in mice
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Parnian Pakzad   , Seyyedeh Elaheh Mousavi , Seyyed Mahdi Rezayat , Amir Hossein Abdolghaffari |
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Abstract: (239 Views) |
Introduction: Considering the high prevalence of anxiety disorders in society, the identification of neurobiological and neurotransmitter systems related to anxiety can be useful in controlling and treating these disorders. Benzodiazepines such as alprazolam bind to the molecular components of the GABAA receptor in the nerve membrane in the central nervous system and facilitate the opening of this channel, thereby strengthening inhibition by GABA at all nerve levels. Citicoline is an exogenous source for acetylcholine synthesis. It stimulates the biosynthesis of structural phospholipids of nerve membranes such as phosphatidyl-choline, increases brain metabolism, and affects the levels of various neurotransmitters. It has also been determined that citicoline reduces anxiety behaviors in the Elevated plus Maze (EPM) test. The aim of the present study is to investigate the simultaneous use of citicoline and benzodiazepines on behavioral functions in the anxiety model.
Methods and Materials: In this study, 42 male mice weighing 2±52 grams were used and the mice were randomly divided into 7 groups of 6 each. Contains, the control group with normal saline, the group under stress for 3 days, the group receiving citicoline 25 mg/kg, the group receiving citicoline 75 mg/kg, the group receiving alprazolam 0.5 mg/kg, the group receiving alprazolam mg/kg 1 kg, the group receiving citicoline 25 mg/kg and alprazolam 0.5 mg/kg simultaneously. It should be noted that all groups receiving citicoline and alprazolam, received the drug intraperitoneally for 14 days after stress. Restrainer was also used to induce stress. After 3 days of creating anxiety, rats were given intraperitoneal injections of citicoline and alprazolam for 14 days. At the end of the experiment, OFT and EPM behavioral tests were used as a model to investigate anxiety behaviors.
Results: In the present study, the group receiving citicoline and alprazolam and the alprazolam 1 mg/kg group respectively had the highest number of admissions to the open arm (OAE) compared to total admissions. Also, the time spent in the open arm (OAT) in the EPM test in the group receiving citicoline and alprazolam simultaneously, citicoline group 25 mg/kg (P<0.0001) and alprazolam group (0.5 mg/kg) P<0.01) was significantly higher compared to the stressed group. The number of crossing the square in the OFT test in the group receiving citicoline 25 mg/kg and alprazolam 0.5 mg/kg (P<0.05) and the alprazolam group 1 mg/kg (P<0.01) Compared to the group of rats under stress, it was significantly less.
Conclusion: In the present study, the group receiving citicoline and alprazolam and the alprazolam group showed the highest anti-anxiety effect in the EPM and OFT tests. Therefore, according to the toxicity, tolerance and dependence caused by alprazolam and the slight toxicity of citicoline, with the simultaneous administration of these two drugs, the synergistic effect of the simultaneous administration of these two drugs can be used in order to reduce the dosage, increase the efficiency and reduce the side effects caused by it.
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| Keywords: Alprazolam, Citicoline, Anti-anxiety behaviors of mice |
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Full-Text [PDF 434 kb]
(33 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/23 | Accepted: 2023/08/1 | Published: 2023/08/1
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