Cocaine use disorder (CUD) continues to be a prevalent health issue in the United States with 4.8 million people aged 12 or older using cocaine in 2021. Yet, to this day, there is no FDA-approved pharmacotherapy to treat CUD. Evidence from our lab suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists, which are FDA-approved for treating type II diabetes and obesity, could be repurposed for treating CUD. 

GLP-1 is a neuropeptide that plays a critical role in reward behaviors, specifically with food and drugs of abuse via activation of GLP-1Rs that expressed in the mesolimbic reward system. GLP-1Rs are highly expressed in the central amygdala (CeA), and our lab’s preliminary data have suggested administration of GLP-1R agonist Exendin-4 (Ex-4) directly into the CeAattenuates cocaine reinstatement in rodents. Further studies identified a subpopulation of CeA GLP-1R-expressing GABA neurons that project to the nucleus accumbens, a brain region know to play a role in cocaine seeking. While our pilot studies indicate that CeA GLP-1R-expressing neurons are implicated in cocaine seeking, the cellular and molecular consequences of central GLP-1R activation are unknown. Accordingly, no studies have explored the influence of cocaine on CeA neuron dynamics. Thus, this study aimed to characterize the effects of systemic Ex-4 pretreatment on CeA GABA neurons during cocaine seeking.