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Psychiatric disorders

GluN2B mediates ketamine's antidepressant effect

The cellular mechanisms underlying the rapid antidepressant effects of the NMDA receptor (NMDAR) antagonist ketamine are not well understood. Miller et al. showed that mice lacking the NMDAR subunit GluN2B from principal cortical neurons showed reduced despair-like behaviour and that ketamine had no antidepressant effects in these mice. Ketamine increased excitatory synaptic transmission in prefrontal cortex slices from control mice; this effect was mimicked in untreated slices lacking GluN2B, and ketamine had no additional effect on synaptic transmission in these slices. Furthermore, the authors showed that GluN2B-containing NMDARs are tonically activated by ambient glutamate, which could explain why the nonselective NMDAR antagonist ketamine seems to have a GluN2B-selective effect. These data indicate that a suppression of tonic GluN2B activation in cortical neurons could underlie the antidepressant effects of ketamine.


  1. Miller, O. H. et al. GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine. eLife (2014)

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Welberg, L. GluN2B mediates ketamine's antidepressant effect. Nat Rev Neurosci 15, 769 (2014).

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