ArticleMolecular psychiatry2018
Ketamine enhances structural plasticity in mouse mesencephalic and human iPSC-derived dopaminergic neurons via AMPAR-driven BDNF and mTOR signaling.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.
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Who cites it
96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review.Molecular medicine (Cambridge, Mass.) · 2024Pooled it
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers.Clinical pharmacology and therapeutics · 2024Trial
- Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.The American journal of psychiatry · 2018Trial
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics.Molecular psychiatry · 2026Article
- Time-dependent effects of rapid-acting antidepressants in iPSC-derived neurons from treatment-resistant depression and healthy volunteers.Molecular psychiatry · 2026Article
- A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Clinical applications of esketamine: Current status and future perspectives.The Journal of international medical research · 2026Review
- Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers.Research square · 2026Article
- Insights into Dysregulated GABAergic Synapses and Depression: A Complex and Evolving Relationship.Advances in experimental medicine and biology · 2026Review
- From Monoamines to Systems Psychiatry: Rewiring Depression Science and Care (1960s-2025).Biomedicines · 2025Article
- Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.Translational psychiatry · 2025Article
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Sex-dependent preventive effects of prenatal N-acetyl-cysteine on neuronal, emotional and metabolic dysfunctions following exposure to maternal high-fat diet in mice.Translational psychiatry · 2025Article
- MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses.iScience · 2025Article
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.The international journal of neuropsychopharmacology · 2025Review
- Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.Journal of medicinal chemistry · 2025Review
- Harnessing neuroplasticity with psychoplastogens: the essential role of psychotherapy in psychedelic treatment optimization.Frontiers in psychiatry · 2025Article
- Effect of esketamine on postoperative pain relief and depressive status in patients with traumatic fractures.Frontiers in medicine · 2025Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons. Sixty minutes exposure to ketamine elicited concentration-dependent increases of dendritic arborization and soma size in both mouse and human cultures as measured 72 hours after application. These structural effects were blocked by mTOR complex/signaling inhibitors like rapamycin. Direct evidence of mTOR activation by ketamine was revealed by its induction of p70S6 kinase. All effects of ketamine were abolished by AMPA receptor antagonists and mimicked by the AMPA-positive allosteric modulator CX614. Inhibition of BDNF signaling prevented induction of structural plasticity by ketamine or CX614. Furthermore, the actions of ketamine required functionally intact dopamine D3 receptors (D3R), as its effects were abolished by selective D3R antagonists and absent in D3R knockout preparations. Finally, the ketamine metabolite (2R,6R)-hydroxynorketamine mimicked ketamine effects at sub-micromolar concentrations. These data indicate that ketamine elicits structural plasticity by recruitment of AMPAR, mTOR and BDNF signaling in both mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons. These observations are of likely relevance to the influence of ketamine upon mood and its other functional actions in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.