Access through your institution Buy or subscribe ARISING FROM P. Zanos _et al_. _Nature_ 533, 481–486 (2016); doi:10.1038/nature17998 Clinical data have demonstrated rapid and sustained

antidepressant effects of ketamine, a noncompetitive NMDAR (_N_-methyl-d-aspartate receptor) antagonist1. Recently, Zanos _et al_.2 claimed that the ketamine metabolite

(2_R_,6_R_)-hydroxynorketamine (HNK) is essential for the antidepressant effects of ketamine in mice in an NMDAR-independent manner, although no alternative mechanism was proposed, beyond

unspecific activation of AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor)2. Here we report that (2_R_,6_R_)-HNK blocks synaptic NMDARs in a similar manner to its parent

http://dx.doi.org/10.1038/nature22085 (2017). This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other

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are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Berman, R. M. et al.

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(Lond.)_ 587, 4589–4604 (2009) Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Neuroscience, University of Texas Southwestern

Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390-9111, Texas, USA Kanzo Suzuki, Elena Nosyreva, Ege T. Kavalali & Lisa M. Monteggia * Biopharmaceutical Product Development,

University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390-9111, Texas, USA Kevin W. Hunt Authors * Kanzo Suzuki View author publications You can also search

for this author inPubMed Google Scholar * Elena Nosyreva View author publications You can also search for this author inPubMed Google Scholar * Kevin W. Hunt View author publications You can

also search for this author inPubMed Google Scholar * Ege T. Kavalali View author publications You can also search for this author inPubMed Google Scholar * Lisa M. Monteggia View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Lisa M. Monteggia. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare

no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains Supplementary Methods. (PDF 94 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1

POWERPOINT SLIDE FOR FIG. 2 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Suzuki, K., Nosyreva, E., Hunt, K. _et al._ Effects of a ketamine metabolite

on synaptic NMDAR function. _Nature_ 546, E1–E3 (2017). https://doi.org/10.1038/nature22084 Download citation * Received: 10 November 2016 * Accepted: 23 February 2017 * Published: 21 June

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