ArticleBiological psychiatry2021
Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms.
Article in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- Acute subanesthetic ketamine-induced effects on the mismatch negativity and their relationship to early and sustained treatment response in major depressive disorder.Journal of psychopharmacology (Oxford, England) · 2025Trial
- The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study.Molecular psychiatry · 2022Trial
- Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026Review
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- The Emerging Neurobiology of Psychedelics: Critical Periods, Metaplasticity, and Extracellular Matrix Remodeling.Annual review of neuroscience · 2026Review
- Disruption of psychostimulant-associated memories by single, low dose ketamine in rats.Neuropharmacology · 2026Article
- Cell-type targeted CRISPR/Cas9 Clock knockdown in mouse VTA dopamine neurons alter sleep, behavior, and cellular excitability.bioRxiv : the preprint server for biology · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Disrupted synapses: prefrontal cortex-reward circuit dysfunction in stress-induced depression-like behaviors.Frontiers in cellular neuroscience · 2026Review
- Patterned wireless transcranial optogenetics generates artificial perception.Nature neuroscience · 2026Article
- Innovative Approaches to Depression Therapy: The Antidepressant Efficacy and Mechanisms of General Anesthetics.Current neuropharmacology · 2026Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- Analysis and management of thermal loads generated in vivo by miniaturized optoelectronic implantable devices.Device · 2025Article
- Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker.International journal of molecular sciences · 2025Review
- Ketamine Alters Specific Gene Expression Profiles by Transcriptome-Wide Responses in a Ketamine-Induced Schizophrenia-Like Mouse Model.Molecular neurobiology · 2025Article
- Review
- Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance.Neuron · 2025Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundKetamine elicits rapid onset antidepressant effects in patients with clinical depression through mechanisms hypothesized to involve the genesis of neocortical dendritic spines and synapses. Yet, the observed changes in dendritic spine morphology usually emerge well after ketamine clearance, raising questions about the link between rapid behavioral effects of ketamine and plasticity.
methodsHere, we used two-photon glutamate uncaging/imaging to focally induce spinogenesis in the medial prefrontal cortex, directly interrogating baseline and ketamine-associated plasticity of deep layer pyramidal neurons in C57BL/6 mice. We combined pharmacological, genetic, optogenetic, and chemogenetic manipulations to interrogate dopaminergic mechanisms underlying ketamine-induced rapid enhancement in evoked plasticity and associated behavioral changes.
resultsWe found that ketamine rapidly enhances glutamate-evoked spinogenesis in the medial prefrontal cortex, with timing that matches the onset of its behavioral efficacy and precedes changes in dendritic spine density. Ketamine increases evoked cortical spinogenesis through dopamine Drd1 receptor (Drd1) activation that requires dopamine release, compensating blunted plasticity in a learned helplessness paradigm. The enhancement in evoked spinogenesis after Drd1 activation or ketamine treatment depends on postsynaptic protein kinase A activity. Furthermore, ketamine's behavioral effects are blocked by chemogenetic inhibition of dopamine release and mimicked by activating presynaptic dopaminergic terminals or postsynaptic Gα
conclusionsOur findings highlight dopaminergic mediation of rapid enhancement in activity-dependent dendritic spinogenesis and behavioral effects induced by ketamine.
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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.