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Mol Psychiatry. 2018 Oct;23(10):2029-2038. doi: 10.1038/mp.2017.226. Epub 2017 Nov 14.

Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals.

Author information

1
Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
2
Clinical NeuroImaging Research Core, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
3
Department of Neuroscience, Brown University, Providence, RI, USA.
4
Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
5
Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
6
Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. lorenzo.leggio@nih.gov.
7
Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA. lorenzo.leggio@nih.gov.

Abstract

Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg-1) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97±10.65, P=0.04, Cohen's d=0.74). Participants were also significantly faster to initiate alcohol self-administration when they received ghrelin, compared to placebo (P=0.03). The relationships between breath alcohol concentration and subjective effects of alcohol were also moderated by ghrelin administration. Neuroimaging data showed that ghrelin increased the alcohol-related signal in the amygdala (P=0.01) and modulated the food-related signal in the medial orbitofrontal cortex (P=0.01) and nucleus accumbens (P=0.08). These data indicate that ghrelin signaling affects alcohol seeking in humans and should be further investigated as a promising target for developing novel medications for alcohol use disorder.

PMID:
29133954
DOI:
10.1038/mp.2017.226
[Indexed for MEDLINE]

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