The effect of nitrazepam on depression and curiosity in behavioral tests in mice: The role of potassium channels.
Evidence show that gamma-aminobutyric acid (GABA) receptors are involved in depression, so the aim of this study was to investigate the effect of nitrazepam as agonist of GABAAreceptors on depression and curiosity in male mice and the role of potassium channel in antidepressant-like response. 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 0.5mg/kg). Nitrazepam at dose of 0.5mg/kg significantly decreased the immobility time compared to control group in both FST and TST. Fluoxetine also showed such a response. Co-administration of nitrazepam (0.05mg/kg) with glibenclamide in TST (1mg/kg) and in FST (0.3, 1mg/kg) also showed antidepressant-like response. Beside, cromakalim (0.1mg/kg) could reverse the antidepressant-like effect of nitrazepam (0.5mg/kg) in both FST and TST, while cromakalim and glibenclamide alone could not change the immobility time compared to control group (P>0.05). The hole-board test revealed that nitrazepam at doses of 0.5 and 0.1mg/kg could increase the activity of the animal's head-dipping and boost the curiosity and exploration behavior of mice. The results of this study revealed that nitrazepam may possess antidepressant-like properties and this effect is dependent to potassium channels in both FST and TST.
School of Pharmacy, International Campus, Tehran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Vahid
V
Nikoui
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Sattar
S
Ostadhadi
School of Pharmacy, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
Pardis
P
Azhand
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Samira
S
Zolfaghari
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Shayan
S
Amiri
Department of Oral Pathology, Dental School, Isfahan University of Medical Science, Isfahan, Iran.
Mehrdad
M
Foroohandeh
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Manijeh
M
Motevalian
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran; Tissue Engineering Group (TEG) and Research, National Orthopedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopedics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Ali Mohammad
AM
Sharifi
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: bakhtiar@tums.ac.ir.
Azam
A
Bakhtiarian
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D019806:Cromakalim / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D005106:Exploratory Behavior / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D051379:Mice; D009567:Nitrazepam / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000378:metabolism*
D000928:Antidepressive Agents; D015221:Potassium Channels; D019806:Cromakalim; D009567:Nitrazepam; D005905:Glyburide
Forced swimming test; Hole-board test; Mice; Nitrazepam; Potassium channel; Tail suspension test