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Bridging rapid and sustained antidepressant effects of ketamine

Ji-Woon Kim, Kanzo Suzuki, Ege T Kavalali, Lisa M Monteggia

Trends in molecular medicine March 1, 2023 DOI: 10.1016/j.molmed.2023.02.003 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Intervention Ketamine
Topics Esketamine Ketamine
Key findings The authors propose that ketamine's blockade of NMDA receptors triggers intracellular signaling that induces a novel form of hippocampal synaptic plasticity responsible for rapid antidepressant effects, while subsequent downstream transcriptional changes are proposed to sustain those effects over days to more than a week.

Abstract

Acute (R,S)-ketamine (ketamine) administration produces rapid antidepressant effects that in some patients can be sustained for several days to more than week. Ketamine blocks NMDA receptors to elicit specific downstream signaling that induces a novel form of synaptic plasticity in the hippocampus that has been linked to the rapid antidepressant action. These signaling events lead to subsequent downstream transcriptional changes that are involved in the sustained antidepressant effects. Here we review how ketamine triggers this intracellular signaling pathway to mediate synaptic plasticity which underlies the rapid antidepressant effects and links it to downstream signaling and the sustained antidepressant effects.

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