Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance
Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance
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DOI：
10.1016/j.bbr.2015.07.026
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发表时间：
2015-10
影响因子：
2.7
通讯作者：
A. Walker;Brittany M. Foley;S. Sutor;J. McGillivray;M. Frye;S. Tye
中科院分区：
文献类型：
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作者：
A. Walker;Brittany M. Foley;S. Sutor;J. McGillivray;M. Frye;S. Tye
氯胺酮，n -甲基-d-天冬氨酸（NMDA）受体拮抗剂和抗炎剂，对一些顽固性抑郁症患者有快速的治疗效果。在临床和临床前抑郁症研究中，已报道了不规则的促炎细胞因子和急性反应蛋白水平。我们在抗抑郁药抵抗模型中探讨了氯胺酮的快速抗抑郁样作用与外周促炎谱之间的关系。雄性Wistar大鼠分别给予ACTH-(1-24) 100 μg/d或生理盐水（0.9%）预处理14 d。采用强迫游泳试验（FST）评估抗抑郁样作用。氯胺酮（10 mg/kg）显著减少经盐水预处理的对照动物的静止时间。相比之下，在acth预处理的抗抑郁药耐药动物中观察到不同的反应，50%有反应，50%无反应。采用酶联免疫吸附法（ELISA）检测血浆中白细胞介素6 （IL-6）、肿瘤坏死因子α (tnf - α)和c反应蛋白（CRP）。CRP和TNFα水平可区分氯胺酮反应者和无反应者。
Ketamine,N-methyl-d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100 μg/d or saline (0.9%) for 14 d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10 mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a divergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders.