Ketamine: Neuroprotective or Neurotoxic?

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist used clinically as an anesthetic since the 1970s.
• Recent research highlights ketamine's rapid antidepressant effects and potential for treating neuropsychiatric disorders.

Purpose of the Study:

• To summarize preclinical findings on ketamine's dual neurotoxic and neuroprotective properties.
• To explore the complex intracellular signaling pathways modulated by ketamine.

Main Methods:

• Review of preclinical studies investigating ketamine's effects.
• Analysis of context-dependent neurotoxic and neuroprotective actions.

Main Results:

• Anesthetic doses of ketamine during neurodevelopment can promote inflammation, autophagy, apoptosis, and oxidative stress.
• Subanesthetic ketamine doses activate neurotrophic signaling cascades, offering neuroprotection independent of NMDAR activity.

Conclusions:

• Ketamine's effects on the brain are complex and dose-dependent, exhibiting both harmful and beneficial properties.
• Understanding these contrasting effects is crucial for its therapeutic applications in neuropsychiatric conditions.