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氯苯那敏和艾司西酞普兰:在小鼠焦虑模型中具有相似的抗抑郁和降低一氧化氮的作用。

Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety.

作者信息

Gammoh Omar, Mayyas Fadia, Darwish Elhajji Feras

机构信息

Department of Pharmacy, American University of Madaba, Amman 11821, Jordan.

Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.

出版信息

Biomed Rep. 2017 Jun;6(6):675-680. doi: 10.3892/br.2017.901. Epub 2017 May 3.

Abstract

There is a crosstalk between mood disorders and oxidative stress. Chlorpheniramine (CPA), a first generation antihistamine, is hypothesized to have an anxiolytic role at high doses; however, its antidepressant and antioxidant roles have not previously been investigated. The aim of the current study was to evaluate the antidepressant and anxiolytic effects of CPA treatment in association with nitric oxide (NO) and super oxide dismutase (SOD) activity in a mouse model of anxiety. BALB/c mice were divided into unstressed (naïve), control, and CPA- (0.5 mg/kg) and escitalopram- (ESC; 10 mg/kg) treated groups for 3 weeks. Subsequently, they were immobilized for 6 h and subjected to behavioural paradigms as follows: The open field test, the elevated plus maze (EPM) and the forced swim test to investigate motor function, anxiety and depression, respectively. The mice were sacrificed and serum was obtained to detect NO and SOD activity. Compared with the control group, the CPA-treated group demonstrated an antidepressant effect similar to that of the ESC-treated group. In addition, CPA prevented stress-induced NO without affecting SOD activity. CPA did not improve anxiety-like behaviour in the EPM, nor did it improve stress-induced locomotion and rearing, as demonstrated by the OFT. Thus, to the best of our knowledge, this is the first study to evaluate the antidepressant role of CPA in association with NO metabolism. However, further studies are required to elucidate the underlying mechanism.

摘要

情绪障碍与氧化应激之间存在相互作用。氯苯那敏(CPA)是第一代抗组胺药,据推测在高剂量时有抗焦虑作用;然而,其抗抑郁和抗氧化作用此前尚未得到研究。本研究的目的是在焦虑小鼠模型中评估CPA治疗与一氧化氮(NO)和超氧化物歧化酶(SOD)活性相关的抗抑郁和抗焦虑作用。将BALB/c小鼠分为未应激(未处理)组、对照组、CPA(0.5mg/kg)处理组和艾司西酞普兰(ESC;10mg/kg)处理组,为期3周。随后,将它们固定6小时,并进行如下行为学实验:旷场试验、高架十字迷宫(EPM)和强迫游泳试验,分别用于研究运动功能、焦虑和抑郁。处死小鼠并获取血清以检测NO和SOD活性。与对照组相比,CPA处理组表现出与ESC处理组相似的抗抑郁作用。此外,CPA可预防应激诱导的NO产生,而不影响SOD活性。如旷场试验所示,CPA并未改善EPM中的焦虑样行为,也未改善应激诱导的运动和竖毛行为。因此,据我们所知,这是第一项评估CPA与NO代谢相关抗抑郁作用的研究。然而,需要进一步研究以阐明其潜在机制。

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