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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2018.00229

Effect of ketamine on LTP and NMDAR EPSC in hippocampus of the Chronic Social Defeat Stress Mice Model of Depression

 Yu Yang1*, Weina Ju1, Haining Zhang1 and Li Sun1
  • 1Department of Neurology and Neuroscience Center, First Hospital, Jilin University, China

Depression is a common mental disorder that is associated with memory dysfunction. Ketamine has recently been demonstrated to be a rapid antidepressant. The mechanisms underlying how depression induces memory dysfunction and how ketamine relieves depressive symptoms remain poorly understood.
In this work, we have three groups of male C57BL/6J mice: mice exposed to chronic social defeat stress (CSDS) to induce a depression-like phenotype (depression-like mice), depression-like mice treated with ketamine (depression-like mice with ketamine), and control mice that were not exposed to CSDS or treated with ketamine. Spatial working memory and long term memory were assessed by spontaneous alternation Y-maze and fear conditioning tests, respectively. We used western blot to analyze the expression levels of NMDAR subunits in the hippocampus. We recorded long term potentials (LTP) and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal slices.
We observed that compared with control mice, depression-like mice had significant reductions in spatial working memory and contextual fear memory. The level of NR2B, LTP, and NMDA receptor-mediated EPSCs of depression-like mice were decreased. Ketamine treatment attenuated the memory impairment, and increased protein expression of NR2B, LTP, and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice.
In conclusion, depression-like mice have deficits in working memory and contextual fear memory. The decrease of NR2B, LTP induction, and NMDA receptor-mediated EPSCs in the hippocampus may be involved in this process. Ketamine can improve expression of NR2B, LTP induction, and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice, which is part of the reason why ketamine can alleviate the memory dysfunction induced by depression.

Keywords: Ketamine, Depression, Mice, LTP, EPSC

Received: 29 Jan 2018; Accepted: 12 Sep 2018.

Edited by:

João J. Cerqueira, Escola de Medicina, Universidade do Minho, Portugal

Reviewed by:

Yasuyuki Ishikawa, Maebashi Institute of Technology, Japan
Rodrigo A. Cunha, Faculdade de Medicina, Universidade de Coimbra, Portugal
Kenji Hashimoto, Chiba University, Japan
Avi Avital, Department of Physiology, Biophysics and Systems Biology, Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Israel  

Copyright: © 2018 Yang, Ju, Zhang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yu Yang, First Hospital, Jilin University, Department of Neurology and Neuroscience Center, Changchun, China, m15754306093@163.com