[Ketamine: a neuropsychotropic drug with an innovative mechanism of action].

Autor:	Guilloux JP; Laboratoire de Neuropharmacologie, Université Paris-Saclay, Faculté de Pharmacie, Inserm CESP/UMR 1018, Équipe MOODS, F-91400 Orsay, France., Nguyen TML; Laboratoire de Neuropharmacologie, Université Paris-Saclay, Faculté de Pharmacie, Inserm CESP/UMR 1018, Équipe MOODS, F-91400 Orsay, France., Gardier AM; Laboratoire de Neuropharmacologie, Université Paris-Saclay, Faculté de Pharmacie, Inserm CESP/UMR 1018, Équipe MOODS, F-91400 Orsay, France.
Jazyk:	francouzština
Zdroj:	Biologie aujourd'hui [Biol Aujourdhui] 2023; Vol. 217 (3-4), pp. 133-144. Date of Electronic Publication: 2023 Nov 29.
DOI:	10.1051/jbio/2023026
Abstrakt:	Ketamine, a non-competitive antagonist of the N-methyl-D-aspartate-glutamate receptor (R-NMDA), has a rapid (from 24 h post-dose) and prolonged (up to one week) antidepressant effect in treatment resistant depression and in rodent models of anxiety/depression. Arguments regarding its cellular and molecular mechanisms underlying its antidepressant activity mainly come from animal studies. However, debates still persist on the structural remodeling of frontocortical/hippocampal neurons and the role of excitatory/inhibitory neurotransmitters involved in its behavioral effect. Neurochemical and behavioral changes are maintained 24 h after administration of ketamine, well beyond its plasma elimination half-life. The glutamatergic pyramidal cells of the medial prefrontal cortex are primarily implicated in the therapeutic effects of ketamine. Advances in knowledge of the consequences of R-NMDA blockade allowed to specify the underlying mechanisms involving the activation of AMPA glutamate receptors, which triggers a cascade of intracellular events dependent on the mechanistic target of rapamycin, brain-derived neurotrophic factor, and synaptic protein synthesis facilitating synaptic plasticity (number of dendritic spines, synaptogenesis). This review focuses on abnormalities of neurotransmitter systems involved in major depressive disorders, their potential impact on neural circuitry and beneficial effects of ketamine. Recent preclinical data pave the way for future studies to better clarify the mechanism of action of fast-acting antidepressant drugs for the development of novel, more effective therapies. (© Société de Biologie, 2023.)
Databáze:	MEDLINE
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