Targeting Peripheral CB₁ Receptors Reduces Ethanol Intake via a Gut-Brain Axis.

ABSTRACT: Endocannabinoids acting on the cannabinoid-1 receptor (CB₁R) or ghrelin acting on its receptor (GHS-R_1A) both promote alcohol-seeking behavior, but an interaction between the two signaling systems has not been explored. Here, we report that the peripheral CB₁R inverse agonist JD5037 reduces ethanol drinking in wild-type mice but not in mice lacking CB₁R, ghrelin peptide or GHS-R_1A. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid β-oxidation. Blocking gastric vagal affe

SUBMITTER: Godlewski G 

PROVIDER: S-EPMC6551287 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature