The States of Different 5-HT Receptors Located in the Dorsal Raphe Nucleus Are Crucial for Regulating the Awakening During General Anesthesia

General anesthesia is widely used in various clinical practices due to its ability to cause loss of consciousness. However, the exact mechanism of anesthesia-induced unconsciousness remains unclear. It is generally thought that arousal-related brain nuclei are involved. 5-Hydroxytryptamine (5-HT) is...

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Published in:Molecular neurobiology 2023-12, Vol.60 (12), p.6931-6948
Main Authors: Ma, HaiXiang, Gu, LeYuan, Wang, YuLing, Xu, Qing, Zhang, Yuanli, Shao, WeiHui, Yu, Qian, Lian, XiTing, Liu, Lu, Gu, JiaXuan, Ji, Na, Liu, XiaoLing, Nagayasu, Kazuki, Zhang, HongHai
Format: Article
Language:English
Subjects:
Anesthesia
Anesthesia, General
Animals
Arousal
Biomedical and Life Sciences
Biomedicine
Cell Biology
Dorsal Raphe Nucleus
General anesthesia
Mice
Neurobiology
Neurology
Neurons
Neurosciences
Optogenetics
Raphe nuclei
Receptor, Serotonin, 5-HT2A
Serotonin
Sevoflurane
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Summary:General anesthesia is widely used in various clinical practices due to its ability to cause loss of consciousness. However, the exact mechanism of anesthesia-induced unconsciousness remains unclear. It is generally thought that arousal-related brain nuclei are involved. 5-Hydroxytryptamine (5-HT) is closely associated with sleep arousal. Here, we explore the role of the 5-HT system in anesthetic awakening through pharmacological interventions and optogenetic techniques. Our data showed that exogenous administration of 5-hydroxytryptophan (5-HTP) and optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DR) could significantly shorten the emergence time of sevoflurane anesthesia in mice, suggesting that regulation of the 5-HT system using both endogenous and exogenous approaches could mediate delayed emergence. In addition, we first discovered that the different 5-HT receptors located in the DR, known as 5-HT autoreceptors, are essential for the regulation of general anesthetic awakening, with 5-HT1A and 5-HT2A/C receptors playing a regulatory role. These results can provide a reliable theoretical basis as well as potential targets for clinical intervention to prevent delayed emergence and some postoperative risks. Graphical Abstract
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-023-03519-0