Program

PO1-1-137

Potassium channels mediate the antidepressant-like effect of nitrazepam in forced swimming test and tail suspension test in mice

[Speaker] Vahid Nikoui:1
[Co-author] Muhammad Imran Khan:2, Azam Bakhtiarian:3,4, Mohammad Yahya Karimi:1, Pardis Azhand:5, Saeed Mehrzadi:1, Mehrdad Foroohandeh:6, Ahmad-Reza Dehpour:3,4, Mohamad-Reza Aghanoori:7,8
1:Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran, 2:Department of Pharmacy, Kohat University of Science and Technology, 26000 Kohat, KPK, Pakistan, 3:Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, 4:Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran, 5:School of Pharmacy, International Campus of Tehran University of Medical Sciences, Tehran, Iran, 6:Department of Oral Pathology, Dental School, Isfahan University of Medical Science, Isfahan, Iran, 7:Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada, 8:Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada

Background: Evidence show that gamma-aminobutyric acid (GABA) receptors are involved in depression, so the aim of this study was to investigate the effect of GABAA receptors agonist, nitrazepam on depression in male mice and the role of potassium channel this response.
Methods: For this purpose, we studied the antidepressant-like properties of fluoxetine, nitrazepam, glibenclamide, and cromakalim by both forced swimming test (FST) and tail suspension test (TST). Animals were injected by various doses of nitrazepam (0.05, 0.1, and 0.5 mg/kg). For multiple comparisons, one-way ANOVA followed by Tukey`s post-hoc test was carried out. P-values less than 0.05 were considered statistically significant.
Results: Nitrazepam at dose of 0.5 mg/kg significantly decreased the immobility time compared to control group in both FST and TST (P<0.05). Fluoxetine also showed comparable response. Co-administration of subeffective dose of nitrazepam (0.05 mg/kg) with glibenclamide (1 mg/kg) also exerted antidepressant-like effect in TST (P<0.05). Moreover, cromakalim (0.1 mg/kg) could reverse the antidepressant-like effect of nitrazepam (0.5 mg/kg) in both FST (P<0.05) and TST (P<0.01), while cromakalim and glibenclamide alone could not change the immobility time compared to control group (P>0.05).
Conclusions: The results of this study revealed that nitrazepam might possess antidepressant-like properties through modulation of potassium channels in mice.

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