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.
Citations in the library
Cited by 20
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Molecular Brain June 16, 2020
- Targeting metaplasticity mechanisms to promote sustained antidepressant actions. Molecular Psychiatry April 1, 2024
- Ketamine induced synaptic plasticity operates independently of long-term potentiation. Neuropsychopharmacology October 1, 2024
- Both Ketamine and NBQX Attenuate Alcohol-Withdrawal Induced Depression in Male Rats Journal of Drug and Alcohol Research 2018
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. Psychopharmacology June 1, 2025
and 15 more in the library
Cites 11
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- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 23, 2012
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial The International Journal of Neuropsychopharmacology March 17, 2009
- Intravenous ketamine therapy in a patient with a treatment-resistant major depression Swiss Medical Weekly April 21, 2007
and 6 more in the library