Gut-brain axis and addictive disorders: A review with focus on alcohol and drugs of abuse

Due to the limited efficacy of existing medications for addictive disorders including alcohol use disorder (AUD), the need for additional medications is substantial. Potential new medications for addiction can be identified through investigation of the neurochemical substrates mediating the ability of drugs of abuse such as alcohol to activate the mesolimbic dopamine system. Interestingly, recent studies implicate neuropeptides of the gut-brain axis as modulators of reward and addiction processes. The present review therefore summarizes the current studies investigating the ability of the gut-brain peptides ghrelin, glucagon-like peptide-1 (GLP-1), amylin and neuromedin U (NMU) to modulate alcohol- and drug-related behaviors in rodents and humans. Extensive literature demonstrates that ghrelin, the only known orexigenic neuropeptide to date, enhances reward as well as the intake of alcohol, and other drugs of abuse, while ghrelin receptor antagonism has the opposite effects. On the other hand, the anorexigenic peptides GLP-1, amylin and NMU independently inhibits reward from alcohol and drugs of abuse in rodents. Collectively, these rodent and human studies imply that central ghrelin, GLP-1, amylin and NMU signaling may contribute to addiction processes. Therefore, the need for randomized clinical trials investigating the effects of agents targeting these aforementioned systems on drug/alcohol use is substantial.