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Neuropsychopharmacological profiling of scoparone in mice.
- Source :
-
Scientific reports [Sci Rep] 2022 Jan 17; Vol. 12 (1), pp. 822. Date of Electronic Publication: 2022 Jan 17. - Publication Year :
- 2022
-
Abstract
- Scoparone (6,7-dimethoxycoumarin) is a simple coumarin from botanical drugs of Artemisia species used in Traditional Chinese Medicine and Génépi liquor. However, its bioavailability to the brain and potential central effects remain unexplored. We profiled the neuropharmacological effects of scoparone upon acute and subchronic intraperitoneal administration (2.5-25 mg/kg) in Swiss mice and determined its brain concentrations and its effects on the endocannabinoid system (ECS) and related lipids using LC-ESI-MS/MS. Scoparone showed no effect in the forced swimming test (FST) but, administered acutely, led to a bell-shaped anxiogenic-like behavior in the elevated plus-maze test and bell-shaped procognitive effects in the passive avoidance test when given subchronically and acutely. Scoparone rapidly but moderately accumulated in the brain (Cmax < 15 min) with an apparent first-order elimination (95% eliminated at 1 h). Acute scoparone administration (5 mg/kg) significantly increased brain arachidonic acid, prostaglandins, and N-acylethanolamines (NAEs) in the FST. Conversely, subchronic scoparone treatment (2.5 mg/kg) decreased NAEs and increased 2-arachidonoylglycerol. Scoparone differentially impacted ECS lipid remodeling in the brain independent of serine hydrolase modulation. Overall, the unexpectedly potent central effects of scoparone observed in mice could have toxicopharmacological implications for humans.<br /> (© 2022. The Author(s).)
- Subjects :
- Animals
Arachidonic Acid metabolism
Arachidonic Acids metabolism
Avoidance Learning drug effects
Behavior, Animal drug effects
Biological Availability
Cognition drug effects
Coumarins administration & dosage
Coumarins pharmacokinetics
Endocannabinoids metabolism
Ethanolamines metabolism
Glycerides metabolism
Infusions, Parenteral
Lipid Metabolism
Male
Maze Learning drug effects
Mice
Prostaglandins metabolism
Brain metabolism
Coumarins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 35039558
- Full Text :
- https://doi.org/10.1038/s41598-021-04741-3