Effects of a ketamine metabolite on synaptic NMDAR function

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: (2R,6R)-HNK blocks NMDAR-mEPSCs and decreases eEF2 phosphorylation in hippocampal neurons.
Figure 2: (2R,6R)-HNK acts as open channel NMDAR blocker.

References

  1. 1

    Berman, R. M. et al. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry 47, 351–354 (2000)

    Article  CAS  Google Scholar 

  2. 2

    Zanos, P. et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533, 481–486 (2016)

    ADS  Article  CAS  Google Scholar 

  3. 3

    Autry, A. E. et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475, 91–95 (2011)

    Article  CAS  Google Scholar 

  4. 4

    Nosyreva, E. et al. Acute suppression of spontaneous neurotransmission drives synaptic potentiation. J. Neurosci. 33, 6990–7002 (2013)

    Article  CAS  Google Scholar 

  5. 5

    Nosyreva, E., Autry, A. E., Kavalali, E. T. & Monteggia, L. M. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade. Front. Mol. Neurosci. 7, 94 (2014)

    Article  Google Scholar 

  6. 6

    Atasoy, D. et al. Spontaneous and evoked glutamate release activates two populations of NMDA receptors with limited overlap. J. Neurosci. 28, 10151–10166 (2008)

    Article  CAS  Google Scholar 

  7. 7

    Gideons, E. S., Kavalali, E. T. & Monteggia, L. M. Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses. Proc. Natl Acad. Sci. USA 111, 8649–8654 (2014)

    ADS  Article  CAS  Google Scholar 

  8. 8

    Lukas, G., Brindle, S. D. & Greengard, P. The route of absorption of intraperitoneally administered compounds. J. Pharmacol. Exp. Ther. 178, 562–564 (1971)

    PubMed  CAS  Google Scholar 

  9. 9

    Collingridge, G.L. et al. Antidepressant actions of ketamine versus hydroxynorketamine. Biol. Psychiatry 81, e65–e67 (2016)

    Article  CAS  Google Scholar 

  10. 10

    Zanos, P. et al. Reply to: antidepressant actions of ketamine versus hydroxynorketamine. Biol. Psychiatry 81, e69–e71 (2016)

    Article  CAS  Google Scholar 

  11. 11

    Singh, J. B. et al. Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol. Psychiatry 80, 424–431 (2016)

    Article  CAS  Google Scholar 

  12. 12

    Moaddel, R. et al. Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors. Eur. J. Pharmacol. 698, 228–234 (2013)

    Article  CAS  Google Scholar 

  13. 13

    Kotermanski, S. E., Wood, J. T. & Johnson, J. W. Memantine binding to a superficial site on NMDA receptors contributes to partial trapping. J. Physiol. (Lond.) 587, 4589–4604 (2009)

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.