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

Abstract

Evaluation of: Li N, Lee B, Liu RJ et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329, 959–964 (2010).

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.

Keywords::

• AMPA receptor
• brain-derived neurotrophic factor (BDNF)
• cancer
• ketamine
• mTOR
• NMDA receptor
• protein synthesis
• σ-1 receptor
• treatment-resistant depression

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.