Cannabinoid Modulation of Monoamine Levels in Mouse Brain:Unveiling Neurochemical Dynamics through an Innovative High‑performance Liquid Chromatography‑Fluorescence Detection Bioanalysis  

作　　者：Fonseca Carla Cunha Susana Ferreira Ricardo Lapo Pais Mariana Goncalves Joana Camins Antoni Ettcheto Miren Barbosa Rui Fortuna Ana 

机构地区：[1]Laboratory of Pharmacology,Faculty of Pharmacy,University of Coimbra,Polo das Ciencias da Saude,Azinhaga de Santa Comba,Coimbra 3000‑548,Portugal [2]CIBIT/ICNAS-Coimbra Institute for Biomedical Imaging and Translational Research,University of Coimbra,Coimbra 3000‑548,Portugal [3]Department of Pharmacology,Toxicology and Therapeutic Chemistry,Faculty of Pharmacy and Food Science,Universitat de Barcelona,Barcelona 08028,Spain [4]Institute of Neurosciences,Universitat de Barcelona,Barcelona 08035,Spain [5]Faculty of Sciences and Technology,Doctoral Program in Biomedical Engineering,University of Coimbra,Coimbra 3004‑516,Portugal [6]Biomedical Research Networking Centre in Neurodegenerative Diseases(CIBERNED),Carlos Ⅲ Health Institute,Madrid 28031,Spain [7]Institut d’Investigacio Sanitaria Pere Virgili(IISPV),Reus 43204,Spain [8]CNC-Center for Neuroscience and Cell Biology,University of Coimbra,Coimbra 3004-504,Portugal

出　　处：《Journal of Analysis and Testing》2024年第3期300-314,共15页分析检测（英文）

基　　金：supported by funds from Fundacao para a Ciencia e a Tecnologia(FCT),Portugal,European Union,MCTES,and Fundo Social Europeu(FSE)in the scope of the Centro 2020 Regional Operational Programme(Carla’s PhD research grant 2021.06135;BD and Mariana’s PhD research grant 2020.6582.BD);supported by FCT Exploratory Project 2022.01066.PTDC,COMPETE and FEDER funds,FCT,Portugal.Figures 1 and 2 were created with BioRender.com.

摘　　要：Homeostasis of monoaminergic pathways is compromised in aging and neurodegenerative/neurological diseases such as Alzheimer’s disease and depression.On the other hand,their modulation has also been linked to the mechanism of action of several drugs.Therefore,monitoring the levels of noradrenaline(NA),adrenaline(AD),dopamine(DA),and serotonin(5-HT),as well as those of tryptophan(TRYP),the precursor of 5-HT,and DA metabolites,namely 3,4-dihydroxyphenylacetic acid(DOPAC)and homovanillic acid(HVA),is fundamental for assessing disease severity and progression.This work aimed to develop and validate the first High-Performance Liquid Chromatography(HPLC)coupled with fluorescence detector(FLD)method that simultaneously and accurately quantifies NA,AD,DA,DOPAC,HVA,5-HT and TRYP in mouse brain and prefrontal cortex(PFC)matrices.Previous sample preparation by protein precipitation was required to extract the compounds.Calibration curves were plotted using the background subtraction approach to reduce the interference of the endogenous analytes.Intra and inter-day accuracy and precision were within the ranges defined by ICH(The International Council for Harmonisation)guideline for bioanalytical method validation.Following validation,the impact of cannabidiol(CBD),cannabigerol(CBG),and cannabidivarin(CBDV)was explored in mice brains post-administration,revealing significant alterations in specific neurotransmitter levels upon cannabinoid exposure and shedding light on the complex modulation of neurochemical dynamics by cannabinoids.This research highlights the fit-for-purpose of the HPLC-FLD method and provides insights into potential mechanisms underlying phytocannabinoid actions in the central nervous system(CNS).

关 键 词：NEUROTRANSMITTER HPLC Mice Brain Prefrontal cortex CANNABINOID 

分 类 号：O657.72[理学—分析化学] R285.5[理学—化学]