Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter

doi:10.1016/j.neuron.2023.02.017

	Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter
	Zhu, Xiao-Na1 ; Li, Jie 2; Qiu, Gao-Lin 3; Wang, Lin1 ; Lu, Chen1 ; Guo, Yi-Ge1 ; Yang, Ke-Xin1 ; Cai, Fang1 ; Xu, Tao 4; Yuan, Ti-Fei 2; Hu, Ji1
	2023-03-17
发表期刊	NEURON (IF:14.7[JCR-2023],16.9[5-Year])
ISSN	1097-4199
EISSN	1097-4199
卷号	111 期号:10
发表状态	已发表
DOI	10.1016/j.neuron.2023.02.017
摘要	Lasker's award-winning drug propofol is widely used in general anesthesia. The recreational use of propofol is reported to produce a well-rested feeling and euphoric state; yet, the neural mechanisms underlying such pleasant effects remain unelucidated. Here, we report that propofol actively and directly binds to the dopa-mine transporter (DAT), but not the serotonin transporter (SERT), which contributes to the rapid relief of anhe-donia. Then, we predict the binding mode of propofol by molecular docking and mutation of critical binding residues on the DAT. Fiber photometry recording on awake freely moving mice and [18F] FP-CIT-PET scan-ning further establishes that propofol administration evokes rapid and lasting dopamine accumulation in nucleus accumbens (NAc). The enhanced dopaminergic tone drives biased activation of dopamine -recep-tor-1-expressing medium spiny neurons (D1-MSNs) in NAc and reverses anhedonia in chronically stressed animals. Collectively, these findings suggest the therapeutic potential of propofol against anhedonia, which warrants future clinical investigations.
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Major Projects[KF2021006] ; National Natural Science Foundation of China["61890951","31922029","STI2030"] ; null[32192414] ; null[2021ZD0203900]
WOS研究方向	Neurosciences & Neurology
WOS类目	Neurosciences
WOS记录号	WOS:001005085400001
出版者	CELL PRESS
引用统计	被引频次：22[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/299865
专题	生命科学与技术学院生命科学与技术学院_PI研究组_胡霁组生命科学与技术学院_博士生
通讯作者	Xu, Tao; Yuan, Ti-Fei; Hu, Ji
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Shanghai Jiao Tong Univ, Brain Hlth Inst, Natl Ctr Mental Disorders, Shanghai Mental Hlth Ctr,Sch Med,Shanghai Key Lab, Shanghai 200030, Peoples R China 3.Anhui Med Univ, Dept Anesthesiol, Affiliated Hosp 1, Hefei 230022, Peoples R China 4.Shanghai Jiao Tong Univ, Affiliated Shanghai Peoples Hosp 6, Dept Anesthesiol, Sch Med, Shanghai 200233, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhu, Xiao-Na,Li, Jie,Qiu, Gao-Lin,et al. Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter[J]. NEURON,2023,111(10).
APA	Zhu, Xiao-Na.,Li, Jie.,Qiu, Gao-Lin.,Wang, Lin.,Lu, Chen.,...&Hu, Ji.(2023).Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter.NEURON,111(10).
MLA	Zhu, Xiao-Na,et al."Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter".NEURON 111.10(2023).