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

Summary

Depression-like mice exhibited significant reductions in spatial working memory and contextual fear memory compared to control mice. Specifically, levels of NR2B, long-term potentiation (LTP), and NMDA receptor-mediated excitatory postsynaptic currents were decreased in these mice. Ketamine treatment improved memory impairment and increased NR2B expression, LTP, and NMDA receptor-mediated EPSCs in the hippocampus, suggesting that these changes contribute to ketamine's ability to alleviate memory dysfunction associated with depression.

Study at a glance

Abstract

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.

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