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. To this day, there is no FDA-approved pharmacotherapy to treat CUD, and thus promoting long-term abstinence and preventing cocaine relapse remain the greatest challenges to successfully treating CUD. An emerging body of evidence from our laboratory suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists, which are FDA-approved for treating diabetes type II and obesity, could be re-purposed for treating CUD. Our lab's preliminary data indicate that intra-central amygdala (CeA) injection of GLP-1R agonist Exendin-4 (Ex-4) dose-dependently attenuates the reinstatement of cocaine-seeking behavior in male rats. However, the efficacy of the GLP-1R agonist to reduce cocaine seeking in female rats remains to be determined.

Emerging literature highlights important sex differences in clinical and preclinical studies of CUD. For example, females acquire cocaine taking faster, consume higher amounts of cocaine, and relapse quicker than males. These sex-dependent behaviors are also modeled in rats self-administering cocaine. Of relevance to this study, a recent study found lower membrane capacity in GLP-1R-expressing CeA neurons, which may alter the efficacy of GLP-1R agonists. Thus, in this study we aim to identify doses of intra-CeA Ex-4 that reduce cocaine seeking and are well-tolerated in female rats.