ArticleBehavioural brain research2020
Increasing doses of ketamine curtail antidepressant responses and suppress associated synaptic signaling pathways.
Article in Behavioural brain research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Pooled it
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine or esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial.Trends in psychiatry and psychotherapy · 2025Trial
- Enhancing plasticity to treat depression and other central nervous system diseases using event-driven pharmacology.Journal of psychopharmacology (Oxford, England) · 2026Review
- Kappa-Opioid Receptor Antagonism Prolongs the Antidepressant Effects of Ketamine in Adult Mice with Depression-like Behavior Induced by Adolescent Chronic Unpredictable Stress.International journal of molecular sciences · 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
- The hippocampus as a central hub in ketamine's antidepressant action: from molecules to circuit rewiring.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Review
- Ketamine enhances neurological function through neuronal and plasticity-related protein changes in rats with permanent middle cerebral artery occlusion.Metabolic brain disease · 2025Article
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity.Science (New York, N.Y.) · 2025Article
- Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage.International journal of molecular sciences · 2025Article
- Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Ketamine induced synaptic plasticity operates independently of long-term potentiation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Jnk1 and downstream signalling hubs regulate anxiety-like behaviours in a zebrafish larvae phenotypic screen.Scientific reports · 2024Article
- Targeting metaplasticity mechanisms to promote sustained antidepressant actions.Molecular psychiatry · 2024Review
- The therapeutic potential of traditional Chinese medicine in depression: focused on the modulation of neuroplasticity.Frontiers in pharmacology · 2024Review
- The role of neurotrophic factors in novel, rapid psychiatric treatments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- The effect of ketamine on synaptic mistuning induced by impaired glutamate reuptake.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Clinical findings show that a single subanesthetic dose of ketamine elicits rapid antidepressant effects. Accumulating data suggests that ketamine blocks the N-methyl-D-aspartate receptor and results in specific effects on intracellular signaling including increased brain-derived neurotrophic factor (BDNF) protein expression, which augments synaptic responses required for rapid antidepressant effects. To further investigate this potential mechanism for ketamine's antidepressant action, we examined the effect of increasing ketamine doses on intracellular signaling, synaptic plasticity, and rapid antidepressant effects. Given that ketamine is often used at 2.5-10 mg/kg to examine antidepressant effects and 20-50 mg/kg to model schizophrenia, we compared effects at 5, 20 and 50 mg/kg. We found that intraperitoneal (i.p.) injection of low dose (5 mg/kg) ketamine produces rapid antidepressant effects, which were not observed at 20 or 50 mg/kg. At 5 mg/kg ketamine significantly increased the level of BDNF, a protein necessary for the rapid antidepressant effects, while 20 and 50 mg/kg ketamine did not alter BDNF levels in the hippocampus. Low concentration ketamine also evoked the highest synaptic potentiation in the hippocampal CA1, while higher concentrations significantly decreased the synaptic effects. Our results suggest low dose ketamine produces antidepressant effects and has independent behavioral and synaptic effects compared to higher doses of ketamine that are used to model schizophrenia. These findings strengthen our knowledge on specific signaling associated with ketamine's rapid antidepressant effects.
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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.