Ketamine: Neuroprotective or Neurotoxic?

Authors

Divya Choudhury
Anita E Autry
Kimberley F Tolias
Vaishnav Krishnan

Publication Date

1-1-2021

Journal

Frontiers in Neuroscience

DOI

10.3389/fnins.2021.672526

PMID

34566558

PMCID

PMC8461018

PubMedCentral® Posted Date

9-10-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

ketamine mechanism, neuroprotection, ketamine-induced neurotoxicity, BDNF, NMDA receptor, AMPA receptor, antidepressant

Abstract

Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, has been employed clinically as an intravenous anesthetic since the 1970s. More recently, ketamine has received attention for its rapid antidepressant effects and is actively being explored as a treatment for a wide range of neuropsychiatric syndromes. In model systems, ketamine appears to display a combination of neurotoxic and neuroprotective properties that are context dependent. At anesthetic doses applied during neurodevelopmental windows, ketamine contributes to inflammation, autophagy, apoptosis, and enhances levels of reactive oxygen species. At the same time, subanesthetic dose ketamine is a powerful activator of multiple parallel neurotrophic signaling cascades with neuroprotective actions that are not always NMDAR-dependent. Here, we summarize results from an array of preclinical studies that highlight a complex landscape of intracellular signaling pathways modulated by ketamine and juxtapose the somewhat contrasting neuroprotective and neurotoxic features of this drug.