Nikoui Vahid, Ostadhadi Sattar, Azhand Pardis, Zolfaghari Samira, Amiri Shayan, Foroohandeh Mehrdad, Motevalian Manijeh, Sharifi Ali Mohammad, Bakhtiarian Azam
School of Pharmacy, International Campus, Tehran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
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.
Eur J Pharmacol. 2016 Nov 15;791:369-376. doi: 10.1016/j.ejphar.2016.09.017. Epub 2016 Sep 9.
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 GABA receptors 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.
有证据表明γ-氨基丁酸（GABA）受体与抑郁症有关，因此本研究的目的是探讨硝西泮作为GABA受体激动剂对雄性小鼠抑郁和好奇心的影响以及钾通道在抗抑郁样反应中的作用。为此，我们通过强迫游泳试验（FST）和悬尾试验（TST）研究了氟西汀、硝西泮、格列本脲和克罗卡林的抗抑郁样特性。给动物注射不同剂量的硝西泮（0.05、0.1和0.5mg/kg）。在FST和TST中，0.5mg/kg剂量的硝西泮与对照组相比显著减少了不动时间。氟西汀也表现出这样的反应。在TST（1mg/kg）和FST（0.3、1mg/kg）中，硝西泮（0.05mg/kg）与格列本脲联合给药也表现出抗抑郁样反应。此外，克罗卡林（0.1mg/kg）可在FST和TST中逆转硝西泮（0.5mg/kg）的抗抑郁样作用，而单独的克罗卡林和格列本脲与对照组相比不能改变不动时间（P>0.05）。洞板试验显示，0.5和0.1mg/kg剂量的硝西泮可增加动物的探洞活动，并增强小鼠的好奇心和探索行为。本研究结果表明，硝西泮可能具有抗抑郁样特性，且在FST和TST中这种作用均依赖于钾通道。
