Ghrelin, a hormone synthesized by endocrine cells of the stomach, may be a new promising target developing novel medications for alcohol use disorder, according to a recent study.
The hormone ghrelin affects alcohol-seeking behavior. Image credit: Michal Jarmoluk.
Ghrelin is known as the ‘hunger hormone’ given its role in increasing appetite, meal initiation and food intake.
“Preclinical studies have shown that ghrelin has complex interactions with the brain, including the brain’s reward and stress pathways,” said study senior author Dr. Lorenzo Leggio, from the National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health.
“While studies in animals have pointed to ghrelin’s possible role in alcohol-seeking behavior, its impact on alcohol intake by humans has been unclear.”
Dr. Leggio and colleagues conducted a proof-of-concept human laboratory study consisting of two experiments: alcohol self-administration and brain functional magnetic resonance imaging (fMRI).
The goal was to investigate, for the first time, the effects of ghrelin on alcohol self-administration and brain function in regions associated with alcohol-related behaviors.
Participants were alcohol-dependent heavy-drinking (>15 and >20 standard drinks/week for women and men, respectively) individuals. They received either ghrelin or placebo.
In the alcohol self-administration experiment, they could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System.
In another experiment, brain fMRI was conducted while they performed a task to gain points for alcohol, food or no reward.
The scientist found that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered.
Participants were also significantly faster to initiate alcohol self-administration when they received ghrelin.
The relationships between breath alcohol concentration and subjective effects of alcohol were also moderated by ghrelin administration.
fMRI data showed that ghrelin increased the alcohol-related signal in the amygdala and modulated the food-related signal in the medial orbitofrontal cortex and nucleus accumbens.
“These data indicate that ghrelin signaling affects alcohol seeking in humans,” Dr. Leggio and co-authors said.
The study was published in the journal Molecular Psychiatry.
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M. Farokhnia et al. Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Molecular Psychiatry, published online November 14, 2018; doi: 10.1038/mp.2017.226