ArticleMolecular psychiatry2021
Chronic administration of ketamine induces cognitive deterioration by restraining synaptic signaling.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Efficacy and safety of S-ketamine in pain management for breast cancer patients undergoing modified radical mastectomy: a meta-analysis of randomized controlled trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Pooled it
- Alterations in brain synaptic proteins and mRNAs in mood disorders: a systematic review and meta-analysis of postmortem brain studies.Molecular psychiatry · 2022Pooled it
- Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review.Frontiers in neuroanatomy · 2022Pooled it
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review.Research square · 2026Article
- From Bench to Bedside: Understanding General Anesthetics' Impact on PTSD.Current neuropharmacology · 2026Review
- Novel pharmacotherapies for opioid use disorder and opioid withdrawal.Frontiers in psychiatry · 2026Review
- Inulin ameliorates chronic ketamine-induced anxiety-like behaviors and impairments in spatial learning and memory: involvement of gut microbiota, microbial metabolite short-chain fatty acids, and the BDNF-TrkB-ERK1/2-CREB pathway.Frontiers in microbiology · 2026Article
- Molecular Mechanisms Underlying Chronic High-Dose Ketamine-Induced Apoptosis in the Hippocampus: A Narrative Review.Neurochemical research · 2025Review
- Cerebrolysin ameliorates ketamine-mediated anxiety and cognitive impairments via modulation of mitochondrial function and CREB/PGC-1α pathway.Molecular brain · 2025Article
- Acute REM sleep deprivation alleviated depression-like behavior mediated by inhibiting VIP neurons in the mPFC.Science advances · 2025Article
- Psychoactive substances: novel molecular insights and therapeutic potential for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Repeated Levonorgestrel Administration Impairs Cognitive Function via Glutamatergic Transmission and CaMKII-PKA-BDNF Signaling in the Hippocampus of Female Wistar Rats.Journal of experimental pharmacology · 2025Article
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook.Frontiers in psychiatry · 2025Review
- Neurotoxicity mechanisms and clinical implications of six common recreational drugs.Frontiers in pharmacology · 2025Review
- The impact of ketamine on cognitive outcomes in geriatric anesthesia: a comprehensive review.Frontiers in psychiatry · 2025Review
- Poly I:C-induced maternal immune activation causes schizophrenia-like behaviors in the offspring of both sexes by regulating gut microbiota and tryptophan metabolism pathway.Frontiers in microbiology · 2025Article
- Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.Brain and behavior · 2024Article
- Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.Neuropharmacology · 2023Article
- Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.Frontiers in neuroscience · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery of the rapid antidepressant effects of ketamine has arguably been the most important advance in depression treatment. Recently, it was reported that repeated long-term ketamine administration is effective in preventing relapse of depression, which may broaden the clinical use of ketamine. However, long-term treatment with ketamine produces cognitive impairments, and the underlying molecular mechanisms for these impairments are largely unknown. Here, we found that chronic in vivo exposure to ketamine for 28 days led to decreased expression of the glutamate receptor subunits GluA1, GluA2, GluN2A, and GluN2B; decreased expression of the synaptic proteins Syn and PSD-95; decreased dendrite spine density; impairments in long-term potentiation (LTP) and synaptic transmission in the hippocampal CA1 area; and deterioration of learning and memory in mice. Furthermore, the reduced glutamate receptor subunit and synaptic protein expression and the LTP deficits were still observed on day 28 after the last injection of ketamine. We found that the expression and phosphorylation of CaMKIIβ, ERK1/2, CREB, and NF-κB were inhibited by ketamine. The reductions in glutamate receptor subunit expression and dendritic spine density and the deficits in LTP, synaptic transmission, and cognition were alleviated by overexpression of CaMKIIβ. Our study indicates that inhibition of CaMKIIβ-ERK1/2-CREB/NF-κB signaling may mediate chronic ketamine use-associated cognitive impairments by restraining synaptic signaling. Hypofunction of the glutamatergic system might be the underlying mechanism accounting for chronic ketamine use-associated cognitive impairments. Our findings may suggest possible strategies to alleviate ketamine use-associated cognitive deficits and broaden the clinical use of ketamine in depression treatment.
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Registered trials
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