ArticleMolecular psychiatry2016
Activation of a ventral hippocampus-medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 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
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Meta-analysis of cortical thickness abnormalities in medication-free patients with major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Pooled it
- Assessing the Effects of Continuous Theta Burst Stimulation Over the Dorsolateral Prefrontal Cortex on Human Cognition: A Systematic Review.Frontiers in integrative neuroscience · 2020Pooled it
- Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals.Translational psychiatry · 2023Trial
- A randomized placebo-controlled PET study of ketamine´s effect on serotoninTranslational psychiatry · 2020Trial
- Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- Ketamine preserves perineuronal nets in chronic stressed mice brain through the inhibition of microglia activation.IBRO neuroscience reports · 2026Article
- The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response.Nature communications · 2026Article
- Coadministration of scopolamine and mGlu2 NAM VU6001966 as a novel antidepressant approach: Lowering effective dose and reducing cognitive side effects.Psychopharmacology · 2026Article
- The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data from the Hippocampus and Cortex.bioRxiv : the preprint server for biology · 2026Article
- TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.Science advances · 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
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- Efficacy of Venlafaxine and Deep Brain Stimulation Against the Effects of Hippocampal Lesion with Ibotenic Acid in Animals Exposed to the Chronic Mild Stress Model of Depression.Current neuropharmacology · 2026Article
- Disrupted synapses: prefrontal cortex-reward circuit dysfunction in stress-induced depression-like behaviors.Frontiers in cellular neuroscience · 2026Review
- Review
- Ketamine Reverses Chronic Stress-Induced Behavioral Changes via the Expression of CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.European archives of psychiatry and clinical neuroscience · 2025Review
- Resting-state fMRI reveals altered functional connectivity associated with resilience and susceptibility to chronic social defeat stress in mouse brain.Molecular psychiatry · 2025Article
- Prophylactic (R,S)-Ketamine and (2S,6S)-Hydroxynorketamine Decrease Fear Expression by Differentially Modulating Fear Neural Ensembles.Biological psychiatry · 2025Article
- Layer-specific input to medial prefrontal cortex is linked to stress susceptibility.Translational psychiatry · 2025Article
60 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
Abstract
A single sub-anesthetic dose of ketamine exerts rapid and sustained antidepressant effects. Here, we examined the role of the ventral hippocampus (vHipp)-medial prefrontal cortex (mPFC) pathway in ketamine's antidepressant response. Inactivation of the vHipp with lidocaine prevented the sustained, but not acute, antidepressant-like effect of ketamine as measured by the forced swim test (FST). Moreover, optogenetic as well as pharmacogenetic specific activation of the vHipp-mPFC pathway using DREADDs (designer receptors exclusively activated by designer drugs) mimicked the antidepressant-like response to ketamine; importantly, this was pathway specific, in that activation of a vHipp to nucleus accumbens circuit did not do this. Furthermore, optogenetic inactivation of the vHipp/mPFC pathway at the time of FST completely reversed ketamine's antidepressant response. In addition, we found that a transient increase in TrkB receptor phosphorylation in the vHipp contributes to ketamine's sustained antidepressant response. These data demonstrate that activity in the vHipp-mPFC pathway is both necessary and sufficient for the antidepressant-like effect of ketamine.
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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.