Central GLP-1 Signaling Integrates Metabolic and Reward Pathways, Dampening Appetite and Substance-Seeking Behaviors

Obesity and Substance Use Disorders (SUDs) represent significant global health challenges, contributing substantially to mortality and morbidity. Current pharmacotherapies for SUDs, including alcohol, nicotine, and opioid addictions, often demonstrate only moderate efficacy, are plagued by inconsistent patient compliance, and frequently result in relapse, underscoring an urgent need for novel treatment strategies. Similarly, while progress has been made in obesity management, the chronic and recurrent nature of the disease necessitates diverse therapeutic approaches. The central glucagon-like peptide-1 (GLP-1) system, with its widespread expression of GLP-1 receptors (GLP-1Rs) across critical brain regions involved in both metabolism and reward, is uniquely positioned to integrate physiological state with motivated behaviors. This system offers a promising avenue to address the underlying neurobiological mechanisms contributing to both overeating and compulsive drug-seeking.