Sex Specific Effects of Adolescent Intermittent Ethanol on GLP-1R-Mediated Anxiety-Like Behavior And Central Amygdala Gene Expression

Authors: Greg Voce , Ellery McClenathan

Field of Study: Biological Sciences

Program Affiliation: Varodayan Neuroscience Lab

Faculty Mentors: Paige Marsland, Florence Varodayan

Easel: 19

Timeslot: Morning

Abstract: Adolescent alcohol exposure increases the risk of developing alcohol use disorder (AUD) in adulthood. Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging AUD therapies, but the effects of adolescent alcohol exposure on GLP-1R systems remain unclear. The central amygdala (CeA) expresses GLP-1R and mediates negative affective states associated with AUD. Male and female Sprague-Dawley rats underwent adolescent intermittent ethanol (AIE) exposures (4 g/kg ethanol i.g.; 2 days on/off, 14 total exposures) beginning P28. Adult animals received Exendin-4 (GLP-1R agonist) injections (Ex-4, 0.1 mg/kg i.p.) and anxiety-like behaviors were assessed using the Elevated Plus Maze. Ex-4 decreased anxiety-like behavior in males but increased it in AIE-exposed females. Preliminary RNA sequencing of male CeA tissue identified increased expression of genes Nrxn2, Oxr1, Pxn, and Dnm1l in AIE-exposed males following Ex-4 injection. These findings suggest sex-specific GLP-1R modulation of affective behavior following adolescent alcohol exposure.