The Connection Between the Appetite-Regulatory Peptides Ghrelin and GLP-1 and Alcohol Use Disorder.

The body-brain connection is well-established, further evidenced by studies on the orexigenic peptide ghrelin and the anorexigenic peptide glucagon-like peptide-1 (GLP-1). The ghrelin pathway consists of several substrates, which has been studied in relation to alcohol-related responses. Preclinical studies have found that central ghrelin infusions elevate alcohol intake, whereas suppression of the ghrelin receptors (GHSR) attenuates alcohol-related responses. On a similar note, the endogenous GHSR inverse agonist, LEAP2, and the precursor of ghrelin, DAG, block the stimulatory properties of alcohol and reduce alcohol intake. GLP-1 receptor agonists are currently approved for the treatment of type 2 diabetes and obesity. Recent advances in rodents have extended the pharmacological relevance of these GLP-1 receptor agonists as they mitigate alcohol-related responses. Specifically, in animal models reflecting alcohol use disorder (AUD) all tested GLP-1 receptor agonists reduce alcohol intake, suppress the motivation to consume alcohol, and prevent relapse drinking, effects most likely driven by an attenuation of alcohol-induced reward. Additional experiments were conducted in attempts to define areas and circuits responsible for ghrelin and GLP-1 to control alcohol-related responses. Specifically, areas associated with reward were defined as important modulatory areas. In summary, the ghrelin pathway and GLP-1 participate in the pathophysiology of AUD, thereby providing tentative treatment targets.