ArticleMolecular psychiatry2021
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05181527 (Repurposing of Dextromethorphan as an Adjunct Therapy in Patients With Major Depressive Disorder), which is not on this map. Cited by 70 papers.
What it found
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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.
Repurposing of Dextromethorphan as an Adjunct Therapy in Patients With Major Depressive Disorder: A Randomized, Group Sequential, Adaptive Design, Controlled Clinical Trial
Who cites it
70 citing papers in PubMed, 111 citations in OpenAlex.
- Enhancement of hippocampal synaptic AMPA receptor function by the antidepressant tianeptine and by opioid peptides.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Parvalbumin interneurons under stress: converging mechanisms of vulnerability.The international journal of neuropsychopharmacology · 2026Review
- Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota-Gut-Brain Axis's Neural, Immune, and Metabolic Routes.Biomolecules · 2026Review
- Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine.Cell reports · 2026Article
- Contributions of dorsal medial prefrontal cortex GABAergic mu opioid receptors on acute restraint stress-induced anxiety-like behavior.Biology direct · 2026Article
- From Efference Copy to Emotional State: Insular Cortex Somatostatin Neurons Buffer Adaptive Responses to Physical Stress.Biological psychiatry global open science · 2026Article
- Treadmill exercise relieves cortical interneuron hyperactivation to prevent stress-induced anxiety-like behaviors in male mice.Communications biology · 2026Article
- Knockout of α-Synuclein Is Associated with Depression-like Behaviors by Altered Excitability of Medial Prefrontal Cortex Neurons in Mice.International journal of molecular sciences · 2026Article
- Psychobiotic Effects of Postbiotics in Depression, Psychosis and Mania.Health promotion perspectives · 2026Review
- Somatostatin-expressing neurons in the zona incerta regulate chronic stress response and modulate depression-like behaviors.Molecular psychiatry · 2026Article
- A modified tail suspension test for the assessment of behavioral despair in mice after stroke.Acta pharmacologica Sinica · 2026Article
- Microbiota-Derived SCFAs Mediate the Synergistic Antidepressant Effects of Dajianzhong Decoction and Ketamine via FFAR2-NLRP3-IL-1β Signaling.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Non-Invasive Temporal Interference Electrical Stimulation Modulates Neurotransmitter Release and Improves Aberrant Neural Oscillations in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Role of neural oscillations in depression: highlights on gamma oscillations.Translational psychiatry · 2026Review
- Semaphorin 3A-mediated perineuronal nets formation incubates depressive-like behaviors in male mice via activating parvalbumin-expressing interneurons.Molecular psychiatry · 2026Article
- Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Rapid and long-lasting antidepressant-like effects of the pituitary adenylate cyclase-activating polypeptide receptor antagonist PA-915 in chronic stress mouse models.Molecular psychiatry · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- GluN2A-NMDA receptor inhibition disinhibits the prefrontal cortex, reduces forced swim immobility, and impairs sensorimotor gating.Acta pharmacologica Sinica · 2026Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Major depressive disorder (MDD) is associated with alterations of GABAergic interneurons, notably somatostatin (Sst) as well as parvalbumin (Pvalb), in cortical brain areas. In addition, the antidepressant effects of rapid-acting drugs are thought to occur via inhibition of GABA interneurons. However, the impact of these interneuron subtypes in affective behaviors as well as in the effects of rapid-acting antidepressants remains to be determined. Here, we used a Cre-dependent DREADD-chemogenetic approach to determine if inhibition of GABA interneurons in the mPFC of male mice is sufficient to produce antidepressant actions, and conversely if activation of these interneurons blocks the rapid and sustained antidepressant effects of scopolamine, a nonselective acetylcholine muscarinic receptor antagonist. Chemogenetic inhibition of all GABA interneurons (Gad1+), as well as Sst+ and Pvalb+ subtypes in the mPFC produced dose and time-dependent antidepressant effects in the forced swim and novelty suppressed feeding tests, and increased synaptic plasticity. In contrast, stimulation of Gad1, Sst, or Pvalb interneurons in mPFC abolished the effects of scopolamine and prevented scopolamine induction of synaptic plasticity. The results demonstrate that transient inhibition of GABA interneurons promotes synaptic plasticity that underlies rapid antidepressant responses.
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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.