mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists

Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS · 2010 · Science · Atlas ID LIX2010

What this study shows

Ketamine's rapid antidepressant action requires mTOR-dependent synaptogenesis in prefrontal cortex.

Abstract

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The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Rat); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Rat
Journal	Science
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.1190287 · PMID 20724638 · Free full text (PMC3116441)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Ketamine (NMDA-receptor antagonist)
Target	mTOR
Model	Rat
Effect	mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists (ketamine)
Dose	Ketamine 5-10 mg/kg (systemic); Ro 25-6981 10 mg/kg (systemic); Rapamycin, U0126, LY294002 (ICV infusion)
Sample size	not stated
Effect size	Ketamine (5-10 mg/kg) rapidly activated mTOR signaling, increased synaptic proteins (PSD95, GluR1, synapsin I), increased spine density, significantly increased EPSC frequency and amplitude, and produced rapid antidepressant effects in FST, LH, and NSFT. These effects were blocked by rapamycin. Ro 25-6981 (10 mg/kg) showed similar effects.
Limitations	The mechanisms underlying the induction of mTOR signaling are unclear. Ketamine is a psychotomimetic drug with abuse potential, and a more selective agent would be desirable for clinical antidepressant use.

In the Atlas

Cite this paper

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Li, N., Lee, B., Liu, R. J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X. Y., Aghajanian, G., & Duman, R. S. (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. https://doi.org/10.1126/science.1190287

@article{LIX2010,
  author       = {Li, N. and Lee, B. and Liu, R. J. and Banasr, M. and Dwyer, J. M. and Iwata, M. and Li, X. Y. and Aghajanian, G. and Duman, R. S.},
  title        = {{mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists}},
  journal      = {Science},
  year         = {2010},
  doi          = {10.1126/science.1190287},
  note         = {PMID: 20724638},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record LIX2010) [Data set]. https://mtor-atlas.org/study/LIX2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LIX2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LIX2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LIX2010/},
  doi          = {10.5281/zenodo.22059963}
}

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