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Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice
Yulim Lee1, Ann Misun Youn2, Xianshu Ju1
1Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.
Journal of Anesthesia
|November 24, 2020
Summary
The interval between ketamine injections significantly impacts neurotoxicity. Short intervals enhanced excitatory transmission, while long intervals impaired inhibitory transmission and caused anxiety-like behaviors in mice.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Toxicology
Background:
- Assessing anesthetic neurotoxicity is complex, with factors like dosing intervals influencing outcomes.
- Previous research highlighted the impact of intervals for sevoflurane, but this remains unknown for other anesthetics.
Purpose of the Study:
- To investigate the significance of dosing interval on the neurotoxic effects of multiple ketamine injections.
- To evaluate interval-dependent synaptic and behavioral changes following ketamine exposure in developing mice.
Main Methods:
- Postnatal day 17 mice received three ketamine injections (35 mg/kg) at either short (2-hour) or long (24-hour) intervals.
- Synaptic transmission in hippocampal neurons was assessed 5 days post-injection.
- Behavioral changes were evaluated at 8 weeks of age.
Main Results:
- Short-interval ketamine enhanced excitatory synaptic transmission (increased mEPSC frequency).
- Long-interval ketamine decreased inhibitory synaptic transmission (decreased mIPSC amplitude) and induced long-term anxiety-like behaviors.
Conclusions:
- The dosing interval is a critical factor in ketamine-induced neurotoxicity.
- Future research on multiple anesthetic exposures must carefully consider the dosing interval to accurately assess neurotoxic effects.
