• P De Maricourt, T Jay, P Goncalvès, H Lôo, and R Gaillard.
• Service hospitalo-universitaire de santé mentale et de thérapeutique, hôpital Sainte-Anne, université Paris Descartes, centre hospitalier Sainte-Anne, 1, rue Cabanis, 75014 Paris, France; Inserm UMR 894, centre de psychiatrie et neurosciences, université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
• Encephale. 2014 Feb 1; 40 (1): 48-55.

BackgroundIn recent years, discovery of ketamine's fast and powerful antidepressant effects for treatment-resistant depression (TRD) has led to rethinking of the pathophysiology of depression. Numerous studies in humans and animals have focused on mechanisms of action underlying this effect, producing a number of explanatory pathways.MethodThe aim of this article is to summarize the various hypotheses underlying rapid antidepressant action of ketamine and therefore to better understand the mechanisms underlying depression and antidepressant action.ResultsKetamine unique antidepressant properties have led to many studies on its neurobiological grounds. Intracellular signaling pathways such as mTOR, GSK3 or eEF2 seem to play a key role and are associated with an increased synaptic plasticity. Other hypotheses are discussed such as ketamine effects on neuro-inflammation, the role of anterior cingulate cortex in brain changes induced by ketamine, and the potential benefits of analgesic properties of ketamine in depressive disorders.ConclusionOur review highlights the potential role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Understanding which pathways underlie the fast antidepressant effect of ketamine paves the way for the development of new antidepressants.Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

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