Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration
Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration
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DOI：
10.1016/j.jpsychires.2013.06.008
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发表时间：
2013-10-01
影响因子：
4.8
通讯作者：
Macedo, Danielle Silveira
中科院分区：
文献类型：
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作者：
Ferreira Mello, Bruna Stefania;Monte, Aline Santos;Macedo, Danielle Silveira
目前的证据支持炎症、氧化和氮应激以及脑源性神经营养因子（BDNF）信号机制在抑郁症病理生理学中具有重要意义。四环素类抗生素具有抗炎和抗氧化特性。初步证据表明米诺环素具有抗抑郁作用。与其他四环素同源物相比，强力霉素（DOXY）具有良好的药代动力学和安全性。DOXY的抗抑郁活性尚未得到充分研究。本研究评估了DOXY（25和50 mg/kg，i. p.）对LPS诱导的（0.5mg/kg，i. p.）类似抑郁的行为在LPS之前30分钟（LPS前）或LPS给药后1.5和23.5小时（LPS后）给药多西环素。内毒素给药后24小时，与对照组相比，LPS处理的动物在强迫游泳试验（FST）中的不动时间增加。与丙咪嗪（IMI-10 mg/kg，i. p.）类似，两种剂量的DOXY均能预防和逆转LPS诱导的FST改变。LPS注射后24 h，纹状体、海马和前额叶皮质中IL-1 β含量增加。IMI和DOXY预防和逆转LPS诱导的IL-1 β增加。IMI和DOXY还预防和逆转LPS诱导的亚硝酸盐含量和氧化应激参数（脂质过氧化和还原型谷胱甘肽水平）的改变。DOXY和IMI都能阻止LPS诱导的海马BDNF水平的降低。总之，我们的研究结果表明，DOXY在有效改善LPS诱导的抑郁样行为方面与IMI相当，为测试DOXY在人类中的抗抑郁功效提供了理论基础。(C)2013爱思唯尔有限公司保留所有权利。
Current evidences support inflammation, oxidative and nitrogen stress, as well as brain-derived neurotrophic factor (BDNF) signaling mechanisms as important in depression pathophysiology. Tetracycline antibiotics have anti-inflammatory and antioxidant properties. Preliminary evidence indicates that minocycline has antidepressant properties. Doxycycline (DOXY) has favorable pharmacokinetic and safety profiles when compared to other tetracycline congeners. The antidepressant activity of DOXY has not been adequately investigated. This study evaluated the effects of DOXY (25 and 50 mg/kg, i.p.) on LPS-induced (0.5 mg/kg, i.p.) depressive-like behavior. Doxycycline was administered 30 min before LPS (pre-LPS) or 1.5 and 23.5 h following LPS (post-LPS) administration in mice. LPS-treated animals presented an increase in immobility time in the forced swimming test (FST) when compared to controls 24 h after endotoxin administration. Similarly to imipramine (IMI-10 mg/kg, i.p.), DOXY at both doses prevented and reversed LPS-induced alterations in the FST. IL-1 beta content was increased 24 h after LPS administration in striatum, hippocampus and prefrontal cortex. IMI and DOXY prevented and reversed LPS-induced increase in IL-1 beta. IMI and DOXY also prevented and reversed LPS-induced alterations in nitrite content and oxidative stress parameters (lipid peroxidation and reduced glutathione levels). Both DOXY and IMI prevented LPS-induced decrease in hippocampal BDNF levels. Taken together, our results demonstrate that DOXY is comparable to IMI in effectively ameliorate LPS-induced depressive-like behavior, providing a rationale for testing DOXY's antidepressant efficacy in humans. (C) 2013 Elsevier Ltd. All rights reserved.