Editors' ChoiceNeuroscience

Antidepressant Action of Ketamine

Sci. Signal.  24 Aug 2010:
Vol. 3, Issue 136, pp. ec259
DOI: 10.1126/scisignal.3136ec259

In contrast to the weeks or months of treatment required for standard antidepressant medication, ketamine administration produces an antidepressant response within 4 to 6 hours in depressed patients. What lies behind the rapid actions of ketamine? Li et al. (see the Perspective by Cryan and O'Leary) found that ketamine administration resulted in fast activation of mammalian target of rapamycin (mTOR) signaling and increased levels of synaptic proteins in the rat prefrontal cortex. Ketamine rapidly increased the density and function of the dendritic spines of layer V pyramidal neurons in the prefrontal cortex. Thus, the behavioral actions of ketamine in models of depression and antidepressant response are dependent on mTOR signaling.

N. Li, B. Lee, R.-J. Liu, M. Banasr, J. M. Dwyer, M. Iwata, X.-Y. Li, G. Aghajanian, R. S. Duman, mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329, 959–964 (2010). [Abstract] [Full Text]

J. F. Cryan, O. F. O'Leary, A glutamate pathway to faster-acting antidepressants? Science, 329, 913–914 (2010). [Summary] [Full Text]

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