Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

Featured Paper of the Month – July 2021

Published in International Journal of Neuropsychopharmacology by Mehdi Farokhnia and Lorenzo Leggio , et al. in the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.

Summary

Evidence from preclinical and clinical studies suggest that the orexigenic hormone ghrelin modulates alcohol-seeking behaviors. Accordingly, the ghrelin system is being studied as a potential pharmacotherapeutic target for alcohol use disorder (AUD). Both ghrelin and alcohol interact with a variety of endocrine pathways, especially those related to appetite, metabolism, and stress. To better understand the complex interplay between ghrelin and other hormones in the context of alcohol use, the present study examined neuroendocrine response to a supraphysiological challenge with exogenous ghrelin, combined with alcohol, in a clinically relevant sample of heavy-drinking individuals with AUD. Results found that intravenous ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, 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 vs placebo session. This study provides a comprehensive picture of neuroendocrine response to ghrelin plus alcohol and provides a deeper insight into the interplay between ghrelin and appetitive, metabolic, and stress-related hormones in the context of alcohol use.

Publication Information

Farokhnia, Mehdi; Abshire, Kelly M; Hammer, Aaron; Deschaine, Sara L; Saravanakumar, Anitha; Cobbina, Enoch; You, Zhi-Bing; Haass-Koffler, Carolina L; Lee, Mary R; Akhlaghi, Fatemeh; Leggio, Lorenzo

Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study Journal Article

In: International Journal of Neuropsychopharmacology, 2021, ISSN: 1461-1457, (pyab004).

Abstract | Links

@article{10.1093/ijnp/pyab004,

title = {Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study},

author = {Mehdi Farokhnia and Kelly M Abshire and Aaron Hammer and Sara L Deschaine and Anitha Saravanakumar and Enoch Cobbina and Zhi-Bing You and Carolina L Haass-Koffler and Mary R Lee and Fatemeh Akhlaghi and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/33560411/},

doi = {10.1093/ijnp/pyab004},

issn = {1461-1457},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {International Journal of Neuropsychopharmacology},

abstract = {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. 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. This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. 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, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, 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 vs placebo session. These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.},

note = {pyab004},

keywords = {},

pubstate = {published},

tppubtype = {article}

}