Therapeutic potential of GHSR-1A antagonism in alcohol dependence, a review

Life Sci. 2022 Feb 15:291:120316. doi: 10.1016/j.lfs.2022.120316. Epub 2022 Jan 10.

Abstract

Growth hormone secretagogue receptor type 1A (GHSR-1A) is a functional receptor of orexigenic peptide ghrelin and is highly expressed in mesolimbic dopaminergic systems that regulate incentive value of artificial reward in substance abuse. Interestingly, GHSR-1A has also shown ligand-independent constitutive activity. Alcohol use disorder (AUD) is one of the growing concerns worldwide as it involves complex neuro-psycho-endocrinological interactions. Positive correlation of acylated ghrelin and alcohol-induced human brain response in the right and left ventral striatum are evident. In the last decade, the beneficial effects of ghrelin receptor (GHSR-1A) antagonism to suppress artificial reward circuitries and induce self-control for alcohol consumption have drawn significant attention from researchers. In this updated review, we summarize the available recent preclinical, clinical, and experimental data to discuss functional, molecular actions of central ghrelin-GHSR-1A signaling in different craving levels for alcohol as well as to promote "GHSR-1A antagonism" as one of the potential therapies in early abstinence.

Keywords: Addiction; Alcohol dependence; Artificial-reward enhancement; GHSR-1A blocker; Ghrelin.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking
  • Alcoholism / metabolism*
  • Alcoholism / therapy
  • Animals
  • Brain / metabolism
  • Craving
  • Disease Models, Animal
  • Ghrelin / metabolism*
  • Humans
  • Ligands
  • Receptors, Ghrelin / antagonists & inhibitors
  • Receptors, Ghrelin / metabolism*
  • Signal Transduction / physiology

Substances

  • GHRL protein, human
  • Ghrelin
  • Ghsr1a protein, human
  • Ligands
  • Receptors, Ghrelin