2. Academic Validation
  3. NE contribution to rebooting unconsciousness caused by midazolam

NE contribution to rebooting unconsciousness caused by midazolam

  • Elife. 2024 Nov 20:13:RP97954. doi: 10.7554/eLife.97954.
LeYuan Gu # 1 2,  WeiHui Shao # 2,  Lu Liu # 1,  Qing Xu # 1,  YuLing Wang # 2,  JiaXuan Gu # 2,  Yue Yang 2,  ZhuoYue Zhang 1,  YaXuan Wu 2,  Yue Shen 3,  Qian Yu 2,  XiTing Lian 1,  HaiXiang Ma 4,  YuanLi Zhang 2,  HongHai Zhang 1 2 3 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3 Department of Anesthesiology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
  • 4 Medical College of Jining Medical University, Shandong, China.
  • 5 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
  • # Contributed equally.
PMID: 39565190 DOI: 10.7554/eLife.97954
Abstract

The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.

Keywords

C57BL/6J mice female; C57BL/6J mice male; GABAA-R knockdown C57BL/6J mice; medicine; mouse; neuroscience.

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