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首页> 外文期刊>Steroids: An International Journal >Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice
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Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice

机译：新型5-HT3受体拮抗剂4i对皮质酮诱导的小鼠抑郁样行为和氧化应激的影响

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摘要

Stress in our daily life severely affects the normal physiology of the biological system. Dysregulation of hypothalamic pituitary adrenal (HPA) axis has been implicated in the development of depression-like behavior, which remains under diagnosed and poorly treated. Exogenous corticosterone (CORT) administration has been demonstrated to develop a depression model, which has shown to mimic HPA-axis induced depression-like state in rodents. In the present study, the effect of a novel 5HT(3) receptor, 4i was examined on CURT induced depression in mice. CURT (30 mg/kg, subcutaneously) was given for 4-weeks to mice in control group, while mice in drug treated group were given 4i (0.5-1 mg/kg, intraperitoneally)/fluoxetine (as a positive control, 10 mg/kg), for the last 2-weeks of CURT dosing. Repeated CURT dosing caused depression-like behavior in mice as indicated by increased despair effects in forced swim test (FST) and anhedonia in sucrose preference test. In addition, CURT administration induced oxidative load in the brain with significant increase in pro-oxidant (lipid peroxidation and nitrite levels) markers and a substantial decline in anti-oxidant defense (catalase and reduced glutathione levels) system, indicating a direct effect of stress hormones in the induction of the brain oxidative damage. On the other hand, 4i and fluoxetine treatment reversed the CURT induced depressive-like deficits. Furthermore, 4i and fluoxetine prevented CURT induced oxidative brain insults, which may plausibly demonstrate one of the key mechanisms for antidepressant-like effects of the compounds. Thus, the study suggests that 5HT(3) antagonist; 4i may be implicated as pharmacological intervention targeting depressive-like anomaly associated with HPA-axis dysregulation. (C) 2015 Elsevier Inc. All rights reserved.
机译：我们日常生活中的压力严重影响着生物系统的正常生理。下丘脑垂体肾上腺（HPA）轴失调已牵涉到抑郁样行为的发展，该行为仍在诊断和治疗不良中。已证明外源性皮质酮（CORT）给药可建立抑郁模型，该模型已证明可模仿HPA轴在啮齿动物中诱导的抑郁样状态。在本研究中，检查了新型5HT（3）受体4i对CURT诱导的小鼠抑郁的作用。对照组给予小鼠CURT（30 mg / kg，皮下）4周，而药物治疗组给予小鼠4i（0.5-1 mg / kg，腹膜内）/氟西汀（作为阳性对照，10 mg / kg），在CURT给药的最后2周内。反复进行CURT给药会在小鼠中引起抑郁样行为，如强迫游泳试验（FST）的绝望效应增加和蔗糖偏爱试验的快感缺乏症所表明。此外，CURT给药诱导了大脑的氧化负荷，促氧化剂（脂质过氧化和亚硝酸盐水平）标志物显着增加，抗氧化防御系统（过氧化氢酶和降低的谷胱甘肽水平）显着下降，表明压力的直接影响激素在诱导脑部氧化损伤中起作用。另一方面，4i和氟西汀治疗可逆转CURT诱发的抑郁样缺陷。此外，4i和氟西汀可预防CURT诱导的氧化性脑损伤，这有可能证明了该化合物具有抗抑郁样作用的关键机制之一。因此，该研究表明5HT（3）拮抗剂。 4i可能涉及针对与HPA轴异常相关的抑郁样异常的药理干预。 （C）2015 Elsevier Inc.保留所有权利。

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