{"doi":"10.1126/sciadv.abo1440","title":"A red nucleus–VTA glutamate pathway underlies exercise reward and the therapeutic effect of exercise on cocaine use","abstract":"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.","journal":"Science Advances","year":2022,"id":250100,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":268059,"name":"Graziella Madeo","orcid":"0000-0001-7557-471X","position":1,"is_corresponding":false},{"id":373359,"name":"Ying Liang","orcid":"0000-0002-6216-4743","position":2,"is_corresponding":false},{"id":781395,"name":"Cindy Zhang","orcid":"0000-0002-0243-7842","position":3,"is_corresponding":false},{"id":481358,"name":"Briana J. Hempel","orcid":"0000-0002-0419-7459","position":4,"is_corresponding":false},{"id":321579,"name":"Xiaojie Liu","orcid":"0000-0001-9843-1674","position":5,"is_corresponding":false},{"id":497464,"name":"Lianwei Mu","orcid":"0000-0001-9453-1045","position":6,"is_corresponding":false},{"id":892259,"name":"Shui Liu","orcid":null,"position":7,"is_corresponding":false},{"id":283712,"name":"Guo‐Hua Bi","orcid":null,"position":8,"is_corresponding":false},{"id":282566,"name":"Ewa Galaj","orcid":"0000-0002-7180-4378","position":9,"is_corresponding":false},{"id":684975,"name":"Hai‐Ying Zhang","orcid":"0000-0003-0593-5940","position":10,"is_corresponding":false},{"id":282568,"name":"Hui Shen","orcid":"0000-0002-9508-0562","position":11,"is_corresponding":false},{"id":323570,"name":"Ross A. McDevitt","orcid":"0000-0003-3722-9047","position":12,"is_corresponding":false},{"id":393279,"name":"Eliot L. Gardner","orcid":"0000-0003-1541-3249","position":13,"is_corresponding":false},{"id":321581,"name":"Qing-song Liu","orcid":"0000-0003-1858-1504","position":14,"is_corresponding":false},{"id":282571,"name":"Zheng‐Xiong Xi","orcid":"0000-0001-6482-8104","position":15,"is_corresponding":false},{"id":282570,"name":"Yi He","orcid":"0000-0002-9503-0565","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:24:28.242323Z","pmid":"36054363","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}