The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence

• DOI: 10.1038/tp.2015.68
• Publication Date: 2015-06-16T13:45:29Z
• Authors: P Suchankova; J Yan; M L Schwandt; B L Stangl; E C Caparelli; R Momenan; E Jerlhag; J A Engel; C A Hodgkinson; M Egli; M F Lopez; H C Becker; D Goldman; M Heilig; V A Ramchandani; L Leggio
• Keywords: Alcohol use disorder; Alcohol Dependence; Acamprosate; Self-administration

Abstract The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. present translational study is based on four human genetic association studies one preclinical providing data that support hypothesis GLP-1R may have a role pathophysiology use disorder (AUD). Case–control analysis ( N =908) was performed sample individuals enrolled National Institute Alcohol Abuse Alcoholism (NIAAA) intramural research program. Study Addiction: Genetics Environment (SAGE) =3803) used for confirmation purposes. Post hoc analyses were carried out from laboratory intravenous self-administration (IV-ASA; =81) social drinkers functional magnetic resonance imaging alcohol-dependent =22) subjected to Monetary Incentive Delay task. In study, agonist evaluated mouse model dependence demonstrate consumption. previously reported allele 168Ser (rs6923761) nominally associated with AUD P =0.004) NIAAA sample, which partially replicated males SAGE =0.033). 168Ser/Ser genotype further increased administration breath measures IV-ASA experiment higher BOLD response right globus pallidus when receiving notification outcome high monetary reward. Finally, agonism significantly reduced consumption dependence. These convergent findings suggest be an attractive target personalized pharmacotherapy treatment AUD.