Effectiveness of memantine on depression-like behavior, memory deficits and brain mRNA levels of BDNF and TrkB in rats subjected to repeated unpredictable stress
Effectiveness of memantine on depression-like behavior, memory deficits and brain mRNA levels of BDNF and TrkB in rats subjected to repeated unpredictable stress
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DOI：
10.1016/j.pharep.2017.12.007
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发表时间：
2018-06-01
影响因子：
4.4
通讯作者：
Wiborg, Ove
中科院分区：
文献类型：
--
作者：
Amidfar, Meysam;Kim, Yong-Ku;Wiborg, Ove
背景资料：先前的临床和临床前研究表明，N-甲基-D-天冬氨酸（NMDA）受体拮抗剂美金刚具有神经保护特性以及抗抑郁作用。本研究旨在探讨美金刚对反复不可预测应激（罗斯）大鼠行为学和分子生物学的影响。方法：将大鼠随机分为4组：对照+生理盐水组、对照+美金刚组、应激+生理盐水组和应激+美金刚组。在暴露于罗斯范例10天后，腹膜内（ip）给予大鼠美金刚胺（20 mg/kg）14天。分别通过强迫游泳试验和被动回避试验测量不动时间来评估抑郁样行为和记忆表现。结果：罗斯抑郁模型可引起大鼠抑郁样行为和记忆提取障碍。海马区BDNF和TrkB mRNA水平无明显变化，但前额叶皮质区TrkB mRNA水平明显下调。美金刚的管理逆转抑郁样行为和记忆障碍，并显着增加BDNF和TrkB mRNA水平在前额叶皮层和海马的应激exposedrats.Conclusions：我们的研究支持的假设，如美金刚的NMDA受体拮抗剂，可能是有效的治疗抑郁症的药物。我们的研究结果还表明，上调脑中BDNF和TrkB的mRNA水平可能是必不可少的抗抑郁剂样活性的美金刚在应激暴露大鼠。(c)2017年波兰科学院药理学研究所。出版社：Elsevier Sp. z o.o. All rights reserved.
Background: Previous clinical and preclinical studies have indicated that the N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, has neuroprotective properties as well as antidepressant effects. The present study was designed to examine behavioral and molecular effects of memantine administration in rats subjected to the repeated unpredictable stress (RUS) paradigm.Methods: Rats were split into four groups at random including control + saline, control + memantine, stressed + saline and stressed + memantine. After 10 days of exposure to the RUS paradigm, rats were administered memantine (20 mg/kg) intraperitoneally (ip) for 14 days. Depression-like behavior and memory performance were assessed by measuring immobility time in the forced swim test and passive avoidance test, respectively. The mRNA levels of BDNF and TrkB in the prefrontal cortex and hippocampus were measured by real-time quantitative PCR.Results: Our results demonstrated that the RUS paradigm caused depression-like behavior and impairment of memory retrieval in rats. We did not find significant changes in BDNF or TrkB mRNA levels in hippocampus, but mRNA levels of TrkB in the prefrontal cortex showed a significant downregulation. Administration of memantine reversed depression-like behavior and memory impairment and significantly increased BDNF and TrkB mRNA levels in both prefrontal cortex and hippocampus of stress exposed rats.Conclusions: Our study supports the hypothesis that drugs with antagonistic properties on the NMDA receptor, such as memantine, might be efficient in treatment of major depression. Our results also suggest that upregulated mRNA levels of BDNF and TrkB in the brain might be essential for antidepressant-like activity of memantine in stress exposed rats. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.