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NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses

Author

Listed:
  • Anita E. Autry

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Megumi Adachi

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Elena Nosyreva

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Elisa S. Na

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Maarten F. Los

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Peng-fei Cheng

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Ege T. Kavalali

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

  • Lisa M. Monteggia

    (University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard)

Abstract

Route to fast antidepressants? Antidepressants such as selective serotonin re-uptake inhibitors can take months to take effect, but small doses of ketamine, a glutamatergic N-methyl-D-aspartate receptor (NMDAR) agonist, can have antidepressant effects within hours. The antidepressant mechanism of ketamine is not well understood. Work in mice shows that antidepressant-like effects of ketamine depend on rapid synthesis of brain-derived neurotrophic factor (BDNF). Ketamine-mediated NMDAR blockade deactivates eukaryotic elongation factor 2 (eEF2) kinase, resulting in reduced eEF2 phosphorylation and de-suppression of BDNF translation. These findings raise the possibility of this pathway as a therapeutic target for fast-acting antidepressants.

Suggested Citation

  • Anita E. Autry & Megumi Adachi & Elena Nosyreva & Elisa S. Na & Maarten F. Los & Peng-fei Cheng & Ege T. Kavalali & Lisa M. Monteggia, 2011. "NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses," Nature, Nature, vol. 475(7354), pages 91-95, July.
    • Handle: RePEc:nat:nature:v:475:y:2011:i:7354:d:10.1038_nature10130
    DOI: 10.1038/nature10130
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    Citations

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    Cited by:

    1. Radhika Rawat & Elif Tunc-Ozcan & Tammy L. McGuire & Chian-Yu Peng & John A. Kessler, 2022. "Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Jackie Zhu & Elisa Hawkins & Kristin Phillips & Laxmikant S. Deshpande, 2020. "Assessment of Ketamine and its Enantiomers in an Organophosphate-Based Rat Model for Features of Gulf War Illness," IJERPH, MDPI, vol. 17(13), pages 1-16, June.
    3. David H. Sarrazin & Wilf Gardner & Carole Marchese & Martin Balzinger & Chockalingam Ramanathan & Marion Schott & Stanislav Rozov & Maxime Veleanu & Stefan Vestring & Claus Normann & Tomi Rantamäki & , 2024. "Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Ruchi Lohia & Reza Salari & Grace Brannigan, 2019. "Sequence specificity despite intrinsic disorder: How a disease-associated Val/Met polymorphism rearranges tertiary interactions in a long disordered protein," PLOS Computational Biology, Public Library of Science, vol. 15(10), pages 1-29, October.
    5. Tommaso Ianni & Sedona N. Ewbank & Marjorie R. Levinstein & Matine M. Azadian & Reece C. Budinich & Michael Michaelides & Raag D. Airan, 2024. "Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Patrick R. Smith & Sarah Loerch & Nikesh Kunder & Alexander D. Stanowick & Tzu-Fang Lou & Zachary T. Campbell, 2021. "Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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