Endocannabinoid signaling regulates the reinforcing and psychostimulant effects of ketamine in mice.
Endocannabinoid signaling regulates the reinforcing and psychostimulant effects of ketamine in mice.
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内源性大麻素信号传导调节氯胺酮对小鼠的强化和精神兴奋作用
DOI：
10.1038/s41467-020-19780-z
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发表时间：
2020-11-24
影响因子：
16.6
通讯作者：
Cen X
中科院分区：
文献类型：
--
作者：
Xu W;Li H;Wang L;Zhang J;Liu C;Wan X;Liu X;Hu Y;Fang Q;Xiao Y;Bu Q;Wang H;Tian J;Zhao Y;Cen X
The abuse potential of ketamine limits its clinical application, but the precise mechanism remains largely unclear. Here we discovered that ketamine significantly remodels the endocannabinoid-related lipidome and activates 2-arachidonoylglycerol (2-AG) signaling in the dorsal striatum (caudate nucleus and putamen, CPu) of mice. Elevated 2-AG in the CPu is essential for the psychostimulant and reinforcing effects of ketamine, whereas blockade of the cannabinoid CB1 receptor, a predominant 2-AG receptor, attenuates ketamine-induced remodeling of neuronal dendrite structure and neurobehaviors. Ketamine represses the transcription of the monoacylglycerol lipase (MAGL) gene by promoting the expression of PRDM5, a negative transcription factor of the MAGL gene, leading to increased 2-AG production. Genetic overexpression of MAGL or silencing of PRDM5 expression in the CPu robustly reduces 2-AG production and ketamine effects. Collectively, endocannabinoid signaling plays a critical role in mediating the psychostimulant and reinforcing properties of ketamine.
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DOI：
10.1016/j.pnpbp.2013.12.002
发表时间：
2014-04-03
影响因子：
5.6
作者：
Bystrowska, Beata;Smaga, Irena;Filip, Malgorzata
通讯作者：
Filip, Malgorzata
DOI：
10.1073/pnas.0808488105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Aubry, Laetitia;Bugi, Aurore;Perrier, Anselme L.
通讯作者：
Perrier, Anselme L.
影响因子：
5.3
作者：
Duan, Zhijun;Person, Richard E.;Horwitz, Marshall S.
通讯作者：
Horwitz, Marshall S.
影响因子：
4.7
作者：
Fattore, L;Spano, S;Fratta, W
通讯作者：
Fratta, W
影响因子：
3.6
作者：
Botanas, Chrislean Jun;de la Pena, June Bryan;Cheong, Jae Hoon
通讯作者：
Cheong, Jae Hoon