{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:34:26Z","timestamp":1784302466255,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veterans Affairs","award":["1I21BX005850"],"award-info":[{"award-number":["1I21BX005850"]}]},{"name":"Department of Veterans Affairs","award":["1I01BX004757-01A1"],"award-info":[{"award-number":["1I01BX004757-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome\u2019s role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-treated (ABX) models. In GF mice, the absence of a microbiome blunted cocaine-induced psychomotor activation (p = 0.013), which was restored after conventionalization. GF mice also showed reduced cocaine-conditioned place preference (CPP) (p = 0.002), which normalized after conventionalization. Dopaminergic function, critical for psychomotor responses and reward, was microbiome-dependent, with increased dopamine levels (p = 0.009) and normalized turnover ratios after conventionalization. In the ABX model, microbiome depletion reduced both cocaine-induced locomotion and CPP responses (p \u2264 0.009), further supporting the role of gut microbes in modulating psychomotor and reward behaviors. ABX-treated mice also showed significant declines in microbial diversity, shifts in bacterial structure, and dysregulation in metabolic, immune, and neurotransmitter pathways (p \u2264 0.0001), including alterations in short-chain fatty acids and gamma-aminobutyric acid metabolism. These findings highlight the gut microbiome\u2019s critical role in regulating cocaine\u2019s psychomotor and rewarding effects, offering insights into potential therapeutic strategies for cocaine use disorder.<\/jats:p>","DOI":"10.3390\/microorganisms13010077","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T07:10:17Z","timestamp":1735888217000},"page":"77","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1439-9406","authenticated-orcid":false,"given":"Andrew D.","family":"Winters","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. Dingell VA Medical Center, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-746X","authenticated-orcid":false,"given":"Dina M.","family":"Francescutti","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. Dingell VA Medical Center, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kracht","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. Dingell VA Medical Center, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9236-7683","authenticated-orcid":false,"given":"Diptaraj S.","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. Dingell VA Medical Center, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislava","family":"Zagorac","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. 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