Exogenous ghrelin administration affects alcohol self-administration and brain activity in heavy-drinking alcohol-dependent individuals: A human laboratory study

Authors

• M Farokhnia
• EN Grodin
• MR Lee
• EN Oot
• AN Blackburn
• BL Stangl
• ML Schwandt
• LA Farinelli
• R Momenan
• VA Ramchandani
• L Leggio

Abstract

Ghrelin, a hormone synthesized by the stomach, increases appetite by acting on the arcuate nucleus of hypothalamus. In addition, ghrelin modulates central reward and stress pathways that contribute to drug-seeking behaviors. Ghrelin administration in rodents enhances alcohol motivation and intake. Studies in humans suggest a positive relationship between endogenous ghrelin levels and alcohol craving and relapse. The present double-blind, placebo-controlled, crossover study investigated the effects of intravenous (IV) ghrelin on alcohol self-administration (ASA) and brain activity in heavy-drinking alcohol-dependent individuals. Participants underwent two experiments: 1) IV-ASA via the computerized alcohol infusion system (CAIS), 2) Brain functional magnetic resonance imaging (fMRI). Each experiment included two sessions during which a loading dose (3 mcg/kg) of IV ghrelin or placebo followed by a continuous ghrelin or placebo infusion (16.9 ng/kg/min) were administered. Results showed that participants self-administered higher number of alcohol infusions during the ghrelin than placebo session (mean increase: 24.97%, p=0.04). They also started pressing the button sooner (p=0.01) and received the first infusion earlier (p=0.03) during the ghrelin session. In regards to fMRI blood oxygen level dependent (BOLD) signal, IV ghrelin increased the alcohol- and food-related BOLD signal, respectively in left amygdala (p=0.01) and left nucleus accumbens (p=0.08). In addition, IV ghrelin decreased food-related BOLD signal in right medial orbitofrontal cortex (p=0.01). In conclusion, ghrelin administration increased alcohol self-administration and modulated brain activity in this sample. These data suggest that ghrelin signaling influences the neural correlates of alcohol consumption and can be considered as a therapeutic target for alcohol use disorder.

Scientific Focus Area: Neuroscience

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