Endocannabinoid system (ECS) has been proved to play a critical role in the regulation of alcohol intake and alcohol-related behaviors. However, there are discrepancies between studies examining the interaction of ECS and alcohol administration due to different experiment procedures. The present study aims at clarifying the time course effects of acute alcohol consumption on ECS in peripheral and central nervous system of the same cohort of subjects. We have closely monitored the critical indicators reflecting changes of ECS during the whole process from alcohol absorption to its metabolization after acute alcohol (4.5 g/kg) intake by intragastric administration, including two key endocannabinoids (AEA and 2-AG) and their hydrolytic enzymes (FAAH and MAGL), as well as two crucial receptors (CB1R and CB2R) of ECS in blood and three brain regions. Our results indicate that acute alcohol consumption inhibits eCBs production in blood and prefrontal cortex of brain, whereas the reverse was observed in brain regions of hippocampus and striatum. The variation between levels of two hydrolytic enzymes in blood and in three brain regions failed to reach statistical significance. The levels of CB1R and CB2R in striatum showed similar tendency of increasing at 4h, which was consistent with the peak time of non-oxidative ethanol metabolite. However, the levels of CB1R and CB2R showed opposite tendencies in hippocampus at 8 h that CB1R expression increased while CB2R decreased. The expression of CB1R and CB2R in prefrontal cortex were elevated after alcohol consumption. The present findings reveal different ligand-receptor changing patterns in blood and in different brain regions, supporting the notion that ECS plays a vital role in acute alcohol intoxication. Additionally, the effect temporality of alcohol on key elements of ECS of blood and different brain nuclei were different. Our investigation may lead to a deeper understanding of the effect on ECS after acute alcohol consumption.
Keywords: Alcohol, Cannabinoid receptors (CBRs), Endocannabinoids (eCBs), Fatty acid amide hydrolase (FAAH), Monoacylglycerol lipase (MAGL)
Copyright © 2020 Elsevier Inc. All rights reserved.