Interval-dependent Neurotoxicity After Multiple Ketamine Injections in Late Postnatal Mice

Overview

Journal J Anesth

Specialty Anesthesiology

Date 2020 Nov 24

PMID 33231772

Citations 2

Authors

Yulim Lee

Ann Misun Youn

Xianshu Ju

Jianchen Cui

Boohwi Hong

Sangwon Yun

Youngkwon Ko

Yoon Hee Kim

Jun Young Heo

Woosuk Chung

Affiliations

Soon will be listed here.

Abstract

Purpose: Measuring the neurotoxic effects of multiple anesthetic exposures during neurodevelopment is complex due to the numerous factors that can affect the outcome. While we recently discovered that the interval between multiple sevoflurane exposures can affect the level of neurotoxicity, the significance of interval for other anesthetic agents is unknown. Thus, we evaluated the significance of dosing interval in the neurotoxic effects of multiple ketamine injections in postnatal day (PND) 17 mice.

Methods: PND17 mice of both sexes were intraperitoneally injected with ketamine (35 mg/kg) three times at short (2 h) or long (24 h) intervals. Changes in synaptic transmission were measured in hippocampal pyramidal neurons 5 days after the last injection, and behavioral changes were assessed at the age of 8 weeks. Values are presented as mean ± SD.

Results: Whereas short-interval ketamine injections enhanced excitatory synaptic transmission, as evidenced by an increased frequency of miniature excitatory postsynaptic currents (mEPSCs; ketamine, 0.09 ± 0.07 Hz; control, 0.06 ± 0.03 Hz), long-interval ketamine injections did not; instead, they decreased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs; ketamine, 47.72 ± 6.90 pA; control, 51.21 ± 7.65 pA,). However, only long-interval ketamine injections induced long-term changes in anxiety behavioral in the open-field test (decrease in center duration; ketamine, 400.1 ± 162.8 s; control, 613.3 ± 312.7 s).

Conclusions: Multiple ketamine injections induce interval-dependent, long-lasting synaptic changes and behavioral impairments. Future studies should carefully consider the dosing interval as a significant factor when studying the neurotoxic effects of multiple anesthetic exposures.

Citing Articles

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice.

Cui J, Ju X, Lee Y, Hong B, Kang H, Han K Commun Biol. 2022; 5(1):709.

PMID: 35840630 PMC: 9287305. DOI: 10.1038/s42003-022-03667-4.

Neonatal anesthesia and dysregulation of the epigenome†.

Cabrera O, Useinovic N, Jevtovic-Todorovic V Biol Reprod. 2021; 105(3):720-734.

PMID: 34258621 PMC: 8444668. DOI: 10.1093/biolre/ioab136.

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