Stress, Motivation, and the Gut–Brain Axis: A Focus on the Ghrelin System and Alcohol Use Disorder

Abstract

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.

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

“…At the central nervous system level, it has been demonstrated to play a role in anxiety-like behavior through the activation of the CCK2 receptors in limbic regions [64]. Serum ghrelin, which is known for its adipogenic effects and for playing a role in response to stress (i.e., triggering motivation for rewards), has been shown to be associated with modification of certain gut bacteria strains, such as negatively correlated with the commensal Bifidobacterium and Lactobacillus strains, and directly with Bacteroides/Prevotella species [65]. Corticotropin-releasing factor (CRF) plays a key role in response to stress mediating the neural control of adrenocorticotropic hormone (ACTH) release from pituitary corticotrophs, which in turn regulate cortisol secretion acutely but may lead to the development of stress-related disorders (i.e., anxiety and depression) when exposed to chronic stress [66].…”

Ghrelin receptor deletion reduces binge‐like alcohol drinking in rats

“…Ghrelin is increasingly recognised for its significance in reward and stress regulation in relation to alcohol and drugs of abuse . A significant amount of rodent and human research suggests a role for ghrelin in AUD .…”

The metabolic mind: A role for leptin and ghrelin in affect and social cognition

“…For example, leptin administration in rodents increases self‐stimulating behaviors beyond food (e.g., pressing a lever that stimulates an implanted electrode), likely via interaction with dopaminergic systems (Carr, ; Fulton, Woodside, & Shizgal, ). A growing body of evidence in both rodents and humans implicates ghrelin and its receptors in drug‐related reward responses (e.g., Wenthur et al, ; Zallar et al, ; see also Morris, Voon, & Leggio, , for review). For example, in humans, individuals with higher fasting ghrelin appear to be more reward sensitive and report experiencing more intense, longer lasting subjective effects in response to intravenous alcohol administration relative to saline placebo (Ralevski et al, , ; this work used ethanol rather than alcohol ingestion, which contains carbohydrates, in order to disentangle the pleasure induced by ethanol from alcohol's caloric value).…”