{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:12:23Z","timestamp":1787242343732,"version":"build-2736575974"},"reference-count":65,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"35","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,9,2]]},"abstract":"<jats:p>Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Anatomic and functional assays demonstrated that most RN magnocellular portion (RNm) neurons are glutamatergic. Wheel-running activates a subset of RNm glutamate neurons that project to ventral tegmental area (VTA) dopamine neurons. Optogenetic stimulation of this pathway was rewarding, as assessed by intracranial self-stimulation and conditioned place preference, whereas optical inhibition blocked wheel-running behavior. Running wheel access decreased cocaine self-administration and cocaine seeking during extinction. Last, optogenetic stimulation of the RNm-to-VTA glutamate pathway inhibited responding to cocaine. Together, these findings indicate that physical exercise activates a specific RNm-to-VTA glutamatergic pathway, producing exercise reward and reducing cocaine intake.<\/jats:p>","DOI":"10.1126\/sciadv.abo1440","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T13:58:24Z","timestamp":1662127104000},"source":"Crossref","is-referenced-by-count":29,"title":["A red nucleus\u2013VTA glutamate pathway underlies exercise reward and the therapeutic effect of exercise on cocaine use"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-0565","authenticated-orcid":true,"given":"Yi","family":"He","sequence":"first","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, 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