{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:43:58Z","timestamp":1793742238054,"version":"4.6.1"},"posted":{"date-parts":[[2025,10,9]]},"group-title":"Neuroscience","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Glucagon-like peptide-1 receptor (GLP-1R) agonists have recently emerged as powerful tools for the treatment of obesity through their ability to suppress food intake. However, their effects on non-ingestive motivated behaviors remain incompletely understood. Here, we show that the long-acting GLP-1R agonist semaglutide (SG) suppresses voluntary wheel running in both lean and diet-induced obese mice. Importantly, this suppression of activity was not caused by hypophagia and was accompanied by decreased motivation, with SG-treated mice displaying reduced effort for wheel access in a progressive ratio task. Real-time measurements of dopamine via fiber photometry revealed specific dopamine changes in the nucleus accumbens at both the beginning and end of running bouts, with SG-treated animals showing amplified dopamine dynamics at these key behavioral timepoints. Collectively, these data reveal important non-ingestive behavioral effects of GLP-1R agonism and suggest a role for dopamine circuits in mediating reductions of volitional activity following SG treatment.<\/jats:p>","DOI":"10.1101\/2025.10.08.681212","type":"posted-content","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:05:38Z","timestamp":1760043938000},"source":"Crossref","is-referenced-by-count":4,"title":["The GLP-1R Agonist Semaglutide Reduces Motivated Running and Alters Dopamine Dynamics in the Nucleus Accumbens"],"prefix":"10.64898","author":[{"given":"Ethan P.","family":"Foscue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Trinko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaysen 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