Cited by 537Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchTryptophan and brain disorders

Signaling pathways underlying the rapid antidepressant actions of ketamine

Open access
Duman, Ronald S., Li, Nanxin, Liu, Rong-Jian, Duric, Vanja, Aghajanian, George·2012·Neuropharmacology

Abstract

Currently available medications have significant limitations, most notably low response rate and time lag for treatment response. Recent clinical studies have demonstrated that ketamine, an NMDA receptor antagonist produces a rapid antidepressant response (within hours) and is effective in treatment resistant depressed patients. Molecular and cellular studies in rodent models demonstrate that ketamine rapidly increases synaptogenesis, including increased density and function of spine synapses, in the prefrontal cortex (PFC). Ketamine also produces rapid antidepressant actions in behavioral models of depression, and reverses the deficits in synapse number and behavior resulting from chronic stress exposure. These effects of ketamine are accompanied by stimulation of the mammalian target of rapamycin (mTOR), and increased levels of synaptic proteins. Together these studies indicate that ketamine rapidly reverses the atrophy of spines in the PFC and thereby causes a functional reconnection of neurons that underlies the rapid behavioral responses. These findings identify new targets for rapid acting antidepressants that are safer than ketamine. This article is part of a Special Issue entitled 'Anxiety and Depression'.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neuropharm.2011.08.044

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Ketamine administration reverses synaptic loss and depressive-like behavior induced by chronic stress in preclinical models.

    “Pioneering preclinical work carried out by Duman et al. indicates that administration of ketamine reverses the synaptic loss and depressive-like behavior induced by chronic stress 15,29,30 .”
  • mTOR is a serine/threonine kinase that regulates neurogenesis, dendritic spine growth, protein translation initiation, and protein synthesis via phosphorylation of p70S6 kinase and repression of 4E binding proteins.

    “Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates neurogenesis, dendritic spine growth, protein translation initiation, and protein synthesis via a phosphorylation of p70S6 kinase and repression of 4E binding proteins (4EBP 173–175).”

    From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [173]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Duman, R. S., Li, N., Liu, R.-J., Duric, V., & Aghajanian, G.
Affiliations
Yale University (US)
Corresponding author
Duman, Ronald S.
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2012-01
Volume
62
Issue
1
Pages
35-41
ISSN
0028-3908 (ISSN-L)
OpenAlex
W1964466640
Cited by
537
References
61
Citations by year
2026: 14 · 2025: 24 · 2024: 24 · 2023: 25 · 2022: 38 · 2021: 39 · 2020: 50 · 2019: 28 · 2018: 38 · 2017: 41 · 2016: 48 · 2015: 51 · 2014: 45 · 2013: 41 · 2012: 25
FWCI
4.60
Type
journal article
Language
en
Open access
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH093897)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
ketamine, rapid-acting antidepressants, NMDA receptor antagonism, treatment-resistant depression, synaptogenesis, dendritic spine plasticity, prefrontal cortex, mTOR signaling, chronic stress, synaptic proteins
MeSH terms
Animals, Antidepressive Agents, Depression, Gene Expression Regulation, Humans, Ketamine, Models, Biological, Neurons, Synapses, Signal Transduction, Neurogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review