Despite significant morbidity and mortality burdens, there are still no FDA-approved medications to treat cocaine use disorder. The development of effective pharmacotherapies requires an improved understanding of the neurobiological mechanisms underlying cocaine use and relapse. 

Our lab has demonstrated that glucagon-like peptide-1 (GLP-1), a satiation hormone, is an effective pharmacotherapy for reducing cocaine taking and seeking in rats. GLP-1 regulates food intake via modulation of the brain’s reward system. Medications that target GLP-1 receptors (GLP-1R) are FDA-approved for diabetes and obesity. We traced the effects of GLP-1 on cocaine-mediated behaviors to regions of the brain’s reward system including the ventral tegmental area (VTA), a region highly implicated in cocaine seeking. 

To advance our knowledge of the mechanisms by which GLP-1R agonists attenuate cocaine-mediated behaviors, we are studying the effects of cocaine and GLP-1R activation on neuronal activity. Here, we utilized fiber photometry techniques to record population-level signals from calcium sensors selectively expressed in VTA dopamine neurons. We explored the effects of systemic cocaine and pretreatment with GLP-1R agonist Exendin-4 on changes in fluorescent calcium in these neurons. We found that pretreatment with Exendin-4 blocked the effects of cocaine on calcium dynamics. These findings suggest that GLP-1R activation modulates the effects of cocaine on the neuronal dynamics of VTA dopamine neurons