A Novel Ghrelin Receptor Antagonist May Serve as a Therapeutic Target for Alcoholism: From Bench to Bedside, a Complete Translational Study

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAAA	PHARM-1

Authors

• A.H. Pilling
• J.D. Tapocik
• A. Pincus
• C. Frable
• F. Akhlaghi
• M. Heilig
• L. Leggio

Abstract

The goal of this project is to test the safety and efficacy of a ghrelin receptor antagonist (PF-05190457) as a treatment for alcoholism. Ghrelin is a peptide that stimulates appetite and food intake. Preclinical and human evidence suggests ghrelin activity correlates with increased alcohol craving and consumption. Antagonizing its receptor (GHSR1a) has been linked with decreased alcohol reward and use in preliminary studies in mice, an observation not translated yet in humans. The first phase of this study is currently being conducted in Wistar rats. After determining optimal doses and time of administration of the drug by measuring plasma and brain concentrations of PF-05190457, we measured how the drug affects ethanol sensitivity, and locomotion in rats via locomotor activity and loss of righting reflex (LORR) tests respectively. Our results confirm our hypothesis that PF-05190457 has no significant effect on any of these measures, thus supporting the safety of this compound for our planned human studies. Notably, we observed a non-significant trend toward decreased alcohol sensitivity in the higher doses of the drug (10mg/kg). After examining PF-05190457 effects on ethanol-induced ERK phosphorylation we will test its effect on alcohol rewarding properties using rats trained to self-administer 20% ethanol.

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