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Review
. 2021 Sep 10:15:672526.
doi: 10.3389/fnins.2021.672526. eCollection 2021.

Ketamine: Neuroprotective or Neurotoxic?

Divya Choudhury  1 , Anita E Autry  2   3 , Kimberley F Tolias  4 , Vaishnav Krishnan  4   5   6
Affiliations
Review

Ketamine: Neuroprotective or Neurotoxic?

Divya Choudhury et al. Front Neurosci. .

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.

Keywords: AMPA receptor; BDNF; NMDA receptor; antidepressant; ketamine mechanism; ketamine-induced neurotoxicity; neuroprotection.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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