Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons' activity

Shaolei Jiang; Dengyun Ge; Bo Song; Xiaofei Deng; Zhongdong Liu; Jian He; Jing Sun; Zhi Zhu; Zhiqiang Meng; Yingjie Zhu

doi:10.1016/j.neuropharm.2024.110264

Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons' activity

Neuropharmacology. 2024 Dec 13:265:110264. doi: 10.1016/j.neuropharm.2024.110264. Online ahead of print.

Authors

Shaolei Jiang¹, Dengyun Ge², Bo Song³, Xiaofei Deng², Zhongdong Liu⁴, Jian He⁵, Jing Sun⁶, Zhi Zhu⁷, Zhiqiang Meng⁸, Yingjie Zhu⁹

Affiliations

¹ School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China; Shenzhen Key Lab of Drug Addiction, Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, 518055, China.
² Shenzhen Key Lab of Drug Addiction, Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, 518055, China.
³ School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
⁴ Grain College, Henan University of Technology, Zhengzhou, 450001, China.
⁵ Department of Anesthesiology, The First People's Hospital of Foshan, Foshan City, 528000, China.
⁶ Department of Anesthesiology, Shenzhen Futian District Maternity & Child Healthcare Hospital, No. 2002 Jintian Road, Futian District, Shenzhen, 518000, China.
⁷ School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China. Electronic address: [email protected].
⁸ Shenzhen Key Lab of Drug Addiction, Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, 518055, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China. Electronic address: [email protected].
⁹ Shenzhen Key Lab of Drug Addiction, Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, 518055, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China. Electronic address: [email protected].

PMID: 39675464
DOI: 10.1016/j.neuropharm.2024.110264

Abstract

Anxiety, a common mental disorder, imposes significant clinical and economic burdens. Previous studies indicate that propofol has anxiolytic effects at anesthetic doses. However, the risks associated with general anesthesia limit its application in anxiety treatment. The feasibility of using subanesthetic doses of propofol to alleviate chronic stress-induced anxiety and the underlying neural mechanisms remain unknown. Here, we found that subanesthetic dose (20 mg/kg and 40 mg/kg) of propofol alleviated anxiety-like behaviors induced by chronic unpredictable mild stress (CUMS) in mice, and the anxiolytic effects were maintained for at least 6 h. In vivo calcium imaging study showed that propofol significantly enhanced Ca²⁺ signals in ventral tegmental area dopaminergic (VTA^DA) neurons. Whole-cell patch-clamp recordings confirmed that subanesthetic propofol increased the excitability of VTA^DA neurons while inhibiting VTA GABAergic (VTA^GABA) neurons. Propofol suppressed spontaneous inhibitory postsynaptic currents (sIPSCs) in VTA^DA neurons, accompanied by a decline in the ability of GABAergic neurons to transmit inhibitory signals. These findings suggests that a subanesthetic dose of propofol enhances the excitability of VTA^DA neurons through disinhibition, demonstrating its potential for the treatment of CUMS-associated anxiety-like behaviors.

Keywords: Anxiety; Disinhibition; Dopaminergic neurons; Propofol; Subanesthetic dose.