Since its discovery, the gut
hormone,
ghrelin, has been implicated in diverse functional roles in the central nervous system. Central and peripheral interactions between
ghrelin and other
hormones, including the stress-response
hormone cortisol, govern complex behavioral responses to external cues and internal states. By acting at ventral tegmental area dopaminergic projections and other areas involved in reward processing,
ghrelin can induce both general and directed motivation for rewards, including craving for alcohol and other alcohol-seeking behaviors. Stress-induced increases in
cortisol seem to increase
ghrelin in the periphery, suggesting a pathway by which
ghrelin influences how stressful life events trigger motivation for rewards. However, in some states,
ghrelin may be protective against the anxiogenic effects of stressors. This critical review brings together a dynamic and growing literature, that is, at times inconsistent, on the relationships between
ghrelin, central reward-motivation pathways, and central and peripheral stress responses, with a special focus on its emerging role in the context of
alcohol use disorder.