2020
DOI: 10.1038/s41467-020-19780-z
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Endocannabinoid signaling regulates the reinforcing and psychostimulant effects of ketamine in mice

Abstract: 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, attenua… Show more

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Cited by 22 publications
(15 citation statements)
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“…Recent studies have highlighted the association of PRDM5 with the progression of human cancers [ 19 , 33 , 34 ]. PRDM5 is a sequence-specific transcriptional repressor [ 35 ]. It has been shown that PRDM5 is silenced by promoter methylation in multiple cancers [ 36 ].…”
Section: Discussionmentioning
confidence: 99%
“…Recent studies have highlighted the association of PRDM5 with the progression of human cancers [ 19 , 33 , 34 ]. PRDM5 is a sequence-specific transcriptional repressor [ 35 ]. It has been shown that PRDM5 is silenced by promoter methylation in multiple cancers [ 36 ].…”
Section: Discussionmentioning
confidence: 99%
“…However, 2-AG concentrations were increased in CPu and NAcc, but decreased in PFC. Moreover, MGLL mRNA levels were reduced in CPu and PFC, although only MAGL protein expression in CPu was reduced [188]. Acute postnatal administration of PCP in mice reduced CB1R levels in the PFC, while increasing it in the dental gyrus of Hipp [189].…”
Section: Gene and Protein Function/expression Changes Of Ecs Componentsmentioning
confidence: 92%
“…Brain tissue was collected immediately following cocaine preference testing and was prepared by using an ethyl acetate/hexane (9:1, v/v) extraction method adapted from a previously published study [ 21 ]. Tissues were spiked with ethyl acetate/hexane and internal standards (d4-AEA (10011178, Cayman) at 10 μg/mL; d5-2-AG (362,162, Cayman) at 100 μg/mL; 2 μL of mixed internal standards for each sample) and ultrasonicated in an ice-cold water bath.…”
Section: Methodsmentioning
confidence: 99%
“…Beginning 30 min before cocaine or saline administration, rimonabant and AM6545 (0.6 μg/μL, 1 μL/side, 0.5 μL/min) [ 21 ] as well as URB597 (10 ng/μL, 1 μL/side, 0.5 μL/min) [ 22 ] were administered bilaterally with a micro-injector. Beginning 15 min before cocaine or saline treatment, AEA (10 μM/side, 0.5 μL/min) was injected.…”
Section: Methodsmentioning
confidence: 99%