ArticleNature2018
Ketamine blocks bursting in the lateral habenula to rapidly relieve depression.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 550 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Evaluation of Schemes of Administration of Intravenous Ketamine in Treatment-resistant Depression: Clinical-neuroimaging Correlation
A Randomized, Parallel-group，Placebo-controlled, Double-blind Clinical Trial to Evaluate the Efficacy and Safety of Ethosuximide in Chinese Patients With Treatment-Resistant Depression.
Who cites it
550 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,027 citations in OpenAlex.
- Effect of perioperative esketamine administration on the incidence of postoperative delirium: a systematic review and meta-analysis.BMC anesthesiology · 2026Pooled it
- Investigation of habenula volume in mood disorders: A meta-analytic study.Psychological medicine · 2026Pooled it
- The habenula in mood disorders: A systematic review of human studies.Molecular psychiatry · 2025Pooled it
- Metabolomics in Depression: What We Learn from Preclinical and Clinical Evidences.Molecular neurobiology · 2025Pooled it
- The disappointment centre of the brain gets exciting: a systematic review of habenula dysfunction in depression.Translational psychiatry · 2024Pooled it
- Modulation of early non-rapid eye movement slow wave activity by ketamine in treatment-resistant depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Trial
- Impact of esketamine-based opioid-free anesthesia on quality of recovery after laparoscopic hysterectomy: a randomized controlled trial using the QoR-40 questionnaire.BMC anesthesiology · 2026Trial
- Brain functional network correlates and predictors of the perioperative antidepressant effect of esketamine in breast cancer patients: a double-blind randomized controlled trial using resting-state fMRI and graph theory.Translational psychiatry · 2026Trial
- Investigation of Esketamine Administration During Surgical Procedures for the Alleviation of Postoperative Anxiety and Depression in Adolescent Patients: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Entactogen Effects of Ketamine: A Reverse-Translational Study.The American journal of psychiatry · 2024Trial
- Discovery of novel Kir4.1 inhibitors based on serdemetan with potential therapy for glioblastoma-depression comorbidity.Pharmaceutical science advances · 2026Article
- Advances in calcium signalling research for the diagnosis and treatment of depression.Annals of medicine · 2026Review
- NgR-Dependent plasticity in a dCA3Molecular psychiatry · 2026Article
- Reframing stress adaptation as a dynamic system failure along a threat-response continuum: towards a phase-specific, mechanism-driven framework.Molecular psychiatry · 2026Article
- The multilevel exploration test, a novel paradigm to measure exploratory behavior in depression animal models and the involvement of the PL-ZI circuit.Acta pharmacologica Sinica · 2026Article
- The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response.Nature communications · 2026Article
- Impaired contingency judgement in mice under ketamine: an implication for an altered sense of agency in schizophrenia.Psychopharmacology · 2026Article
- A prefrontal cortex-piriform cortex circuit mediates diminished interest.Molecular psychiatry · 2026Article
- Dual regulatory mechanisms of the ZI-LHb circuit in SPS&S model mice: dissociable control of aversion and anxiety through distinct downstream targets.Molecular psychiatry · 2026Article
- Prefrontal-raphe-habenular circuit drives fear memory recall and updating.Nature communications · 2026Article
490 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.
Indexed as
Identifiers
What OpenQuestion holds
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.