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Expert Rev Neurother. 2011 Jan;11(1):33-6. doi: 10.1586/ern.10.176.

Role of the mTOR signaling pathway in the rapid antidepressant action of ketamine.

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Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.


Some patients with major depressive disorder remain resistant to antidepressant medication. A randomized, placebo-controlled, double-blind trial demonstrated that a single subanesthetic dose (0.5 mg/kg) of the N-methyl-D-aspartate receptor antagonist ketamine caused a rapid antidepressant effect within hours in treatment-resistant patients with major depressive disorder. However, the precise cellular mechanisms underlying ketamine's rapid antidepressant actions were unclear, although it is proposed that the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor might be involved in these mechanisms. Recently, Li et al. reported the role of the mammalian target of rapamycin (mTOR) signaling pathway, a ubiquitous protein kinase involved in protein synthesis and synaptic plasticity, in ketamine's rapid antidepressant effects. Here, these findings are put into context and their significance is discussed.

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