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Effectiveness of Memantine on Depression-Like Behavior, Memory Deficits and Brain Mrna Levels of Bdnf and Trkb in Rats Subjected to Repeated Unpredictable Stress Publisher Pubmed



Amidfar M1 ; Kim YK2 ; Wiborg O3
Authors
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Authors Affiliations
  1. 1. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Psychiatry, College of Medicine, Korea University, Ansan Hospital, South Korea
  3. 3. Department of Health Science and Technology, Aalborg University, Aalborg, Denmark

Source: Pharmacological Reports Published:2018


Abstract

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. © 2017 Institute of Pharmacology, Polish Academy of Sciences
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