Spatio-temporal effects of acute alcohol intoxication on endocannabinoid system in rat brain and blood

The endocannabinoid system (ECS) has been shown 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 the ECS and alcohol administration due to different experimental procedures. The present study aims at clarifying the time course effects of acute alcohol consumption on the ECS in the peripheral circulatory systems and central nervous systems of the same cohort of subjects. We have closely monitored the critical indicators reflecting changes of the ECS during the entire process from alcohol absorption to its metabolization, after acute alcohol (4.5 g/kg) intake by intragastric administration, including two key endocannabinoids (arachidonoylethanolamide and 2-arachidonoylglycerol) and their hydrolytic enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) in blood and three brain regions, as well as a crucial and abundant receptor (cannabinoid 1 receptor) of the ECS in the three brain regions. Our results indicate that acute alcohol consumption inhibits endocannabinoid (eCB) production in the blood and in the prefrontal cortex of the brain, whereas the reverse was observed in the brain regions of the hippocampus and striatum. The variation between levels of two hydrolytic enzymes in the blood and in the three brain regions failed to reach statistical significance. After acute alcohol consumption, CB1R levels in striatum, hippocampus, and prefrontal cortex showed a similar trend of increasing, while the significant changes occurred at different time points. The present findings reveal different ligand-receptor changing patterns in the blood and in different brain regions, supporting the notion that the ECS plays a vital role in acute alcohol intoxication. Additionally, the temporal effects of alcohol on key elements of the ECS of blood and different brain nuclei were different. Our investigation may lead to a deeper understanding of the effect of acute alcohol consumption on the ECS.