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去甲哈尔明增强丙咪嗪和西酞普兰诱导的抗焦虑和抗抑郁样反应:等辐射分析。

Norharmane potentiated anxiolytic- and antidepressant-like responses induced by imipramine and citalopram: an isobologram analysis.

机构信息

Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University.

Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Behav Pharmacol. 2024 Dec 1;35(8):432-441. doi: 10.1097/FBP.0000000000000794. Epub 2024 Oct 4.

DOI:10.1097/FBP.0000000000000794
PMID:39361265
Abstract

β-carboline compounds display a therapeutic property for treating depression and anxiety behaviors. Imipramine and citalopram play an important role in the modulation of anxiety and depression behaviors. We investigated the effects of norharmane, imipramine, and citalopram on anxiety- and depression-like effects and their interactions. Elevated plus maze and forced swimming test were used for the assessment of anxiety- and depression-like behaviors in male mice. The results revealed that intraperitoneal (i.p.) administration of norharmane (10 mg/kg) increased percentage of open arm time (%OAT) in the elevated plus maze test and decreased immobility time in the forced swimming test, proposing anxiolytic- and antidepressant-like effects. Injection of imipramine (5 mg/kg; i.p.) enhanced %OAT and decreased immobility time, suggesting anxiolytic- and antidepressant-like effects. Moreover, norharmane potentiated the anxiolytic- and antidepressant-like responses induced by imipramine by increasing %OAT and decreasing immobility time. The results revealed additive anxiolytic- and antidepressant-like effects between norharmane and imipramine in mice. Alone, the administration of citalopram (5 mg/kg; i.p.) enhanced %OAT and reduced immobility time, causing anxiolytic- and antidepressant-like effects. When citalopram and norharmane were coinjected, norharmane augmented the anxiolytic- and antidepressant-like effects induced by citalopram by increasing %OAT and reducing immobility time. These results indicated additive anxiolytic- and antidepressant-like effects between norharmane and antidepressant drugs such as imipramine and citalopram on the modulation of anxiety and depression processes in mice.

摘要

β-咔啉类化合物具有治疗抑郁和焦虑行为的治疗特性。丙咪嗪和西酞普兰在调节焦虑和抑郁行为方面发挥着重要作用。我们研究了去甲哈尔明、丙咪嗪和西酞普兰对焦虑和抑郁样效应的影响及其相互作用。高架十字迷宫和强迫游泳试验用于评估雄性小鼠的焦虑和抑郁样行为。结果表明,腹腔注射去甲哈尔明(10mg/kg)增加了高架十字迷宫试验中开放臂时间的百分比(%OAT),减少了强迫游泳试验中的不动时间,提示具有抗焦虑和抗抑郁样作用。注射丙咪嗪(5mg/kg;腹腔内)增强了%OAT,减少了不动时间,提示具有抗焦虑和抗抑郁样作用。此外,去甲哈尔明通过增加%OAT 和减少不动时间,增强了丙咪嗪引起的抗焦虑和抗抑郁样反应,提示两者之间存在相加的抗焦虑和抗抑郁样作用。单独给予西酞普兰(5mg/kg;腹腔内)可增强%OAT 并减少不动时间,产生抗焦虑和抗抑郁样作用。当西酞普兰和去甲哈尔明同时注射时,去甲哈尔明通过增加%OAT 和减少不动时间,增强了西酞普兰引起的抗焦虑和抗抑郁样作用。这些结果表明,去甲哈尔明与丙咪嗪和西酞普兰等抗抑郁药之间存在相加的抗焦虑和抗抑郁样作用,可调节小鼠的焦虑和抑郁过程。

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