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Psychiatric disorders

Ketamine modifies mood through mTOR

Nature Reviews Neuroscience volume 11, pages 666–667 (2010)Cite this article

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The authors showed that intraperitoneal administration of a low dose of ketamine in rats rapidly and transiently increased the phosphorylation and activation of eukaryotic initiation factor 4E-binding protein 1 (4EBP1), p70S6 kinase and mTOR — components of the mTOR signalling pathway — in PFC synaptoneurosomes. It also activated extracellular signal-regulated kinase 1 (ERK1) and ERK2 and protein kinase B (PKB; also known as Akt), which are known to activate mTOR.

In addition, ketamine administration increased levels of the synaptic proteins postsynaptic density 95 (PSD95), glutamate receptor 1 (GluR1) and synapsin I in the PFC, and this was associated with synapse formation: two-photon imaging showed that ketamine-treated rats had larger spines and a higher spine density in layer V PFC neurons than control rats. This resulted in synaptic strengthening, as indicated by increased excitatory postsynaptic currents (EPSCs) in response to serotonin or orexin in PFC slices of ketamine-treated rats. Intracerebroventricular (ICV) infusion of the mTOR inhibitor rapamycin prevented the effects of ketamine on synaptic protein levels, spine formation and EPSCs.

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References

ORIGINAL RESEARCH PAPER

  1. Li, N. et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329, 959–964 (2010)

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FURTHER READING

  1. Vollenweider, F. X. & Kometer, M. The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Rev. Neurosci. 11, 642–651 (2010)

    Article  CAS  Google Scholar 

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Authors
  1. Leonie Welberg
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Welberg, L. Ketamine modifies mood through mTOR. Nat Rev Neurosci 11, 666–667 (2010). https://doi.org/10.1038/nrn2916

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