title: [Ketamine's antidepressant effect: focus on ketamine mechanisms of action].
abstract: BACKGROUND
  In 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Ketamine 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: 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.
authors.forename: P
authors.initials: P
authors.lastname: De Maricourt
authors.affiliation: Inserm UMR 894, centre de psychiatrie et neurosciences, université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Jay
authors.affiliation: Clinique du Bois Bondy, 93G11 EPS Ville Evrard, 93140 Bondy, France.
authors.forename: P
authors.initials: P
authors.lastname: Goncalvès
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Lôo
authors.affiliation: 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. Electronic address: raphael.gaillard@normalesup.org.
authors.forename: R
authors.initials: R
authors.lastname: Gaillard
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D054736:Elongation Factor 2 Kinase / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D017981:Receptors, Neurotransmitter; C069474:glutamine receptor; D007649:Ketamine; C546842:MTOR protein, human; C517689:EEF2K protein, human; D058570:TOR Serine-Threonine Kinases; D054736:Elongation Factor 2 Kinase; D038362:Glycogen Synthase Kinase 3
keywords: Dépression; Dépression résistante; Glutamate; Ketamine; Kétamine; Major depressive disorder; NMDA; NMDA receptors; Treatment-resistant depression