C57BL/6J and C57BL/6N mice exhibit different neuro-behaviors and sensitivity to midazolam- and propofol-induced anesthesia

Jiali Peng; Xiaofan Ma; Yelin Chen; Jia Yan; Hong Jiang

doi:10.1016/j.physbeh.2023.114146

C57BL/6J and C57BL/6N mice exhibit different neuro-behaviors and sensitivity to midazolam- and propofol-induced anesthesia

Physiol Behav. 2023 May 15:264:114146. doi: 10.1016/j.physbeh.2023.114146. Epub 2023 Mar 6.

Authors

Jiali Peng¹, Xiaofan Ma¹, Yelin Chen², Jia Yan³, Hong Jiang⁴

Affiliations

¹ Department of Anaesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
³ Department of Anaesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: mzkyanj@163.com.
⁴ Department of Anaesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: dr_jianghong@163.com.

PMID: 36889487
DOI: 10.1016/j.physbeh.2023.114146

Abstract

Phenotypes of inbred mice are strain-dependent, indicating the important influence of genetic background in biomedical research. C57BL/6 is one of the most commonly used inbred mouse strains, and its two closely related substrains, C57BL/6J and C57BL/6N, have been separated for only about 70 years. These two substrains have accumulated genetic variations and exhibit different phenotypes, but it remains unclear whether they respond to anesthetics differently. In this study, commercially acquired wildtype C57BL/6J or C57BL/6N mice from two different sources were analyzed and compared for their response to a spectrum of anesthetics (midazolam, propofol, esketamine or isoflurane anesthesia) and their performance in a series of behavioral tests associated with neurological functions including open field test (OFT), elevated plus maze (EPM), Y maze, prepulse inhibition (PPI), tail strain test (TST) and forced swimming test (FST). Loss of the righting reflex (LORR) is used to measure the anesthetic effects. Our results suggested that the anesthesia induction time induced by either of the four anesthetics were comparable for the C57BL/6J and C57BL/6N mice. However, C57BL/6J or C57BL/6N mice do exhibit different sensitivity to midazolam and propofol. The anesthesia duration of midazolam of C57BL/6J mice was about 60% shorter than that of the C57BL/6N mice, while the LORR duration induced by propofol in C57BL/6J mice was 51% longer than that of the C57BL/6N. In comparison, the two substrains were anesthetized by esketamine or isoflurane similarly. In the behavioral analysis, the C57BL/6J mice exhibited a lower level of anxiety- and depression-like behaviors in OFT, EPM, FST and TST than the C57BL/6N mice. Locomotor activity and sensorimotor gating of these two substrains remained comparable. Our results stress the point that when selecting inbred mice for allele mutation or behavioral testing, the influence of even subtle differences in genetic background should be fully considered.

Keywords: Anesthesia; C57BL/6J; C57BL/6N; Midazolam; Propofol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anesthesia*
Anesthetics*
Animals
Isoflurane* / pharmacology
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Midazolam / pharmacology
Propofol* / pharmacology

Substances

Propofol
Midazolam
Esketamine
Isoflurane
Anesthetics