The combination of a glucagon-like peptide-1 and amylin receptor agonists reduces alcohol consumption in both male and female rats

Objective: Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 may be of potential interest as they individually reduce alcohol intake in rodents. While the combination of amylin receptor (AMYR) and glucagon-like peptide-1 receptor (GLP-1R) agonists have been found to decrease feeding and body weight in obese male rats synergistically, their combined impact on alcohol intake is unknown. Methods: Therefore, the effect of the combination of an AMYR (salmon calcitonin (sCT)) and a GLP-1R (dulaglutide) agonist on alcohol intake in rats of both sexes was explored in two separate alcohol-drinking experiments. The first alcohol-drinking experiment evaluated the potential of adding sCT to an ongoing dulaglutide treatment, whereas the second alcohol-drinking experiment examined the effect when adding sCT and dulaglutide simultaneously. Results: When adding sCT to an ongoing dulaglutide treatment, a reduction in alcohol intake was observed in both male and female rats. However, when combining sCT and dulaglutide simultaneously, an initial reduction in alcohol intake was observed in rats of both sexes, whereas tolerance towards treatment was observed. In both alcohol-drinking experiments, this treatment combination consistently decreased food consumption and body weight in males and females. While the treatment combination did not affect inflammatory mediators, the gene expression of AMYR or GLP-1R, it changed fat tissue morphology. Conclusions: Further investigation needs to be done on the combination of AMYR and GLP-1R agonists to assess their combined effects on alcohol intake.