ArticleThe Journal of clinical investigation2020
GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 6 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
199 citing papers in PubMed, 6 syntheses or guidelines pooled it, 334 citations in OpenAlex.
- Effect of ketamine on reward processing in depressive disorders: a systematic review of neuroimaging studies.CNS spectrums · 2026Pooled it
- Ketamine/esketamine treatment for resistant depression in children and adolescents: a PRISMA systematic review.European child & adolescent psychiatry · 2026Pooled it
- Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?European psychiatry : the journal of the Association of European Psychiatrists · 2026Pooled it
- A scientometric analysis of research on the role of NMDA receptor in the treatment of depression.Frontiers in pharmacology · 2024Pooled it
- Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.Neuroscience and biobehavioral reviews · 2023Pooled it
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.eLife · 2024Trial
- Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults.Psychopharmacology · 2022Trial
- NMDA subunit 2B-selective negative allosteric modulator satoprodil (BI 1569912) as mono- and adjunctive therapy in patients with major depressive disorder: results from two phase 2 randomized, controlled trials.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Parvalbumin interneurons under stress: converging mechanisms of vulnerability.The international journal of neuropsychopharmacology · 2026Review
- Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026Review
- The effects of low-dose ketamine and (2R,6R)-Hydroxynorketamine on affective behaviors associated with protracted oxycodone withdrawal.Psychopharmacology · 2026Article
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine.Cell reports · 2026Article
- Disruption of psychostimulant-associated memories by single, low dose ketamine in rats.Neuropharmacology · 2026Article
- From synapse to strategy: a bibliometric map of ionotropic glutamate receptors in depression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Treadmill exercise relieves cortical interneuron hyperactivation to prevent stress-induced anxiety-like behaviors in male mice.Communications biology · 2026Article
- Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.The international journal of neuropsychopharmacology · 2026Article
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Effect of Perioperative Ketamine on Early Postpartum Depressive Symptoms Following Cesarean Section: A Meta-Analysis.Cureus · 2026Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
A single subanesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates this increase and ketamine's behavioral actions has not been identified. To address this question, we used a combination of viral shRNA and conditional mutation to produce cell-specific knockdown or deletion of a key NMDAR subunit, GluN2B, implicated in the actions of ketamine. The results demonstrated that the antidepressant actions of ketamine were blocked by GluN2B-NMDAR knockdown on GABA (Gad1) interneurons, as well as subtypes expressing somatostatin (Sst) or parvalbumin (Pvalb), but not glutamate principle neurons in the medial prefrontal cortex (mPFC). Further analysis of GABA subtypes showed that cell-specific knockdown or deletion of GluN2B in Sst interneurons blocked or occluded the antidepressant actions of ketamine and revealed sex-specific differences that are associated with excitatory postsynaptic currents on mPFC principle neurons. These findings demonstrate that GluN2B-NMDARs on GABA interneurons are the initial cellular trigger for the rapid antidepressant actions of ketamine and show sex-specific adaptive mechanisms to GluN2B modulation.
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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.