Background
Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder (AUD). Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals.
Methods
This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included two experimental alcohol administration paradigms: intravenous alcohol self-administration (IV-ASA) and intravenous alcohol clamp (IV-AC). Each paradigm consisted of two counterbalanced sessions of IV ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), gastric inhibitory peptide (GIP), insulin, insulin-like growth factor-1 (IGF-1), cortisol, prolactin, and aldosterone.
Results
Despite some statistical differences, findings were consistent across the two alcohol administration paradigms: IV ghrelin, compared to placebo, increased blood concentrations of GLP-1, PP, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin versus placebo session.
Conclusion
These findings, gathered from a clinically relevant sample of heavy-drinking individuals with AUD, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.