Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol

• Published in: Neuropharmacology 2024-10, Vol.257, p.110032, Article 110032
• Main Authors: Zhou, Yue, Dong, Wei, Qiu, Yong-Kang, Shao, Ke-Jie, Zhang, Zi-Xin, Yao, Jia-Qi, Chen, Tian-Qi, Li, Zi-Yi, Zhou, Chen-Rui, Jiao, Xin-Hao, Chen, Yu, Lu, Han, Wu, Yu-Qing
• Format: Article
• Language: English
• Subjects: Anesthesia, General - methods; Anesthetics, Intravenous - pharmacology; Animals; Basal Forebrain - drug effects; GABAergic neurons; GABAergic Neurons - drug effects; GABAergic Neurons - metabolism; General anesthesia; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Propofol; Propofol - pharmacology; Proto-Oncogene Proteins c-fos - metabolism; Reflex, Righting - drug effects; Reflex, Righting - physiology; Righting reflex; Ventral pallidum; Vesicular Inhibitory Amino Acid Transport Proteins; Wakefulness - drug effects; Wakefulness - physiology
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2024.110032

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia. •GABAergic neurons in VP are involved in anesthesia effects of propofol.•Propofol anesthesia inhibits the activity of VP GABAergic neurons.•Activating VP GABAergic neurons attenuates anesthesia effects of propofol.•Inhibiting VP GABAergic neurons enhances anesthesia effects of propofol.