• Br J Anaesth · Feb 2025

    Striatal neurones expressing D1 dopamine receptors modulate consciousness in sevoflurane but not propofol anaesthesia in mice.

    • Kang Zhou, Zi-Jun Hou, Xu-Liang Jiang, Yu-Jie Xiao, Lin-Chen Zhang, Wei Xu, Bo Xiong, Wei-Min Qu, Yu-Guang Huang, Zhi-Li Huang, and Lu Wang.
    • Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Joint International Research Laboratory of Sleep, Fudan University, Shanghai, China; Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
    • Br J Anaesth. 2025 Feb 5.

    BackgroundSevoflurane and propofol are the most widely used inhaled and i.v. general anaesthetics, respectively. The mechanisms by which sevoflurane and propofol induce loss of consciousness (LOC) remain unclear. Recent studies implicate the brain dopaminergic circuit in anaesthetic-induced LOC and the cortical-striatal-thalamic-cortical loop in decoding consciousness. We investigated the contribution of the dorsal striatum, which is a critical interface between the dopaminergic circuit and the cortical-striatal-thalamic-cortical loop, in sevoflurane and propofol anaesthesia.MethodsElectroencephalography and electromyography recordings and righting reflex tests were used to determine LOC and recovery of consciousness (ROC). The activity of D1 dopamine receptor (D1R)-expressing neurones in the dorsal striatum was monitored using fibre photometry, and regulated using optogenetic and chemogenetic methods in D1R-Cre mice.ResultsPopulation activities of striatal D1R neurones began to decrease before LOC and gradually returned after ROC. During sevoflurane anaesthesia, optogenetic activation of striatal D1R neurones induced ROC at cortical and behavioural levels in steady-state anaesthesia and promoted cortical activation in deep burst suppression anaesthesia. Chemogenetic inhibition of striatal D1R neurones accelerated induction (from 242.0 [46.1] to 194.0 [26.9] s; P=0.010) and delayed emergence (from 93.5 [21.2] to 133.5 [33.9] s; P=0.005), whereas chemogenetic activation of these neurones accelerated emergence (from 107 [23.7] to 81.3 [16.1] s; P=0.011). However, neither optogenetic nor chemogenetic manipulation of striatal D1R neurones had any effects on propofol anaesthesia.ConclusionsStriatal D1R neurones modulate the state of consciousness in sevoflurane anaesthesia, but not in propofol anaesthesia.Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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