The diabetes drug semaglutide lowers motivation to run and changes dopamine signals in the brain's reward area

The long-acting GLP-1R agonist semaglutide significantly suppresses voluntary wheel running in both lean and diet-induced obese mice.

• Semaglutide treatment did not lead to reduced food intake, indicating that its effects are independent of hypophagia.
• Mice treated with semaglutide showed decreased motivation, as evidenced by reduced effort to access the wheel in a progressive ratio task.
• Real-time measurements indicated specific changes in dopamine levels in the nucleus accumbens during running bouts in semaglutide-treated mice.
• Amplified dopamine dynamics were observed at both the beginning and end of running bouts following semaglutide administration.
• These findings suggest a role for dopamine circuits in mediating reductions in voluntary activity associated with GLP-1R agonism.

Simplified