Effect of Ketamine on LTP and NMDAR EPSC in Hippocampus of the Chronic Social Defeat Stress Mice Model of Depression
Yu Yang, Weina Ju, Haining Zhang, Li Sun
Frontiers in Behavioral Neuroscience October 9, 2018 DOI: 10.3389/fnbeh.2018.00229 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled laboratory experiment Peer reviewed |
|---|---|
| Population | Male C57BL/6J mice |
| Intervention | Ketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Long-term potentiation Nmda receptor Hippocampus Social defeat Hippocampal formation Ltp induction Excitatory postsynaptic potential Glutamate receptor Long-term depression Antidepressant Inhibitory postsynaptic potential Ampa receptor |
| Citations | 80 |
| Key findings | Depression-like mice had deficits in working and contextual fear memory, with decreased hippocampal NR2B, LTP, and NMDA receptor-mediated EPSCs; ketamine treatment reversed these memory impairments and restored the molecular and electrophysiological measures. |
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.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study | |
| Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression Susceptible mice in the social defeat stress model | 2016 | Animal experimental study | |
| Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Wistar-Kyoto (WKY) rats and Wistar control rats | 2020 | Preclinical study | |
| Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice Mice | 2022 | Experimental study |