Mehdi Farokhnia1,2,3, Kelly M Abshire1, Aaron Hammer1, Sara L Deschaine1, Anitha Saravanakumar4, Enoch Cobbina, Zhi-Bing You5, Carolina L Haass-Koffler1,6,7, Mary R Lee1, Fatemeh Akhlaghi4, Lorenzo Leggio1,2,7,8,9,10. 1. Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland, USA. 2. Center on Compulsive Behaviors, National Institutes of Health, Bethesda, Maryland, USA. 3. Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. 4. Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island. 5. Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA. 6. Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island. 7. Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, Rhode Island. 8. Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA. 9. Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. 10. Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA.
Abstract
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. 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 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. RESULTS: 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. CONCLUSION: 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. Published by Oxford University Press on behalf of CINP 2021.
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. 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 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. RESULTS: 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. CONCLUSION: 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. Published by Oxford University Press on behalf of CINP 2021.
Authors: C I Messini; K Dafopoulos; N Chalvatzas; P Georgoulias; G Anifandis; I E Messinis Journal: J Endocrinol Invest Date: 2010-06-04 Impact factor: 4.256
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