Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade
Frontiers in Molecular Neuroscience September 11, 2015 Elena Enosyreva, Anita E Autry, Ege Ekavalali et al. 51 citations
Ketamine, an NMDA receptor antagonist, produces rapid antidepressant effects in adults with major depressive disorder by blocking NMDA receptors, which inhibits eukaryotic elongation factor 2 kinase, leading to increased protein synthesis and synaptic potentiation in the hippocampus. In juvenile animals, ketamine failed to produce an antidepressant response in the novelty suppressed feeding and forced swim tests and did not trigger synaptic potentiation in hippocampal slices, unlike in slices from older animals (6–9 weeks old). The NMDA receptor antagonist AP5 similarly triggered synaptic potentiation in mature hippocampus, indicating that global competitive blockade of NMDA receptors is sufficient for this effect. These findings suggest that global NMDA receptor blockade in developmentally mature hippocampal synapses is necessary for ketamine's antidepressant efficacy.