Featured Paper of the Month – September 2021
Published in Addiction Biology by Sara Deschaine, Mehdi Farokhnia and Lorenzo Leggio et al. in the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.
Growing evidence shows that ghrelin, a gastric-derived peptide hormone, is involved in regulation of alcohol seeking behavior. Accordingly, the ghrelin system is being studies as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The reverse side of this bidirectional link, i.e., the effects that alcohol may have on the ghrelin system, is not well understood. In a series of preclinical and clinical experiments, the present study aimed to investigate the impact of alcohol on different elements of the ghrelin system. It was found that peripheral ghrelin levels decreased following acute alcohol administration in humans, but AUD was not associated with changes in central expression of ghrelin system genes in post-mortem tissue. In rats, alcohol decreased acyl-ghrelin, but not des-acyl-ghrelin, and this effect was not dependent on the ghrelin receptor. No dose-dependent effects of alcohol were observed on acyl-ghrelin secretion from gastric mucosa cells or on ghrelin-O-acyltransferase (GOAT) acylation activity. Lastly, alcohol and sucrose produced distinct effects on ghrelin in rats despite equivalent caloric value. These findings suggest that alcohol acutely decreases peripheral ghrelin concentrations in vivo, but not in proportion to alcohol’s caloric value or through direct interaction with ghrelin-secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme.