An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking.

ABSTRACT: Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate cocaine seeking. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1-producing neurons in the nucleus tractus solitarius that project to the ventral tegmental area (VTA) decreased cocaine seeking. Single-nuclei transcriptomics and FISH studies revealed that GLP-1Rs are expressed primarily on GABA neurons in the VTA. Using in vivo fiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with i

SUBMITTER: Merkel R 

PROVIDER: S-EPMC11864183 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature