{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:46Z","timestamp":1787028526862,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH Avenir Award","doi-asserted-by":"publisher","award":["DP1-DA044359"],"award-info":[{"award-number":["DP1-DA044359"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH Avenir Award","doi-asserted-by":"publisher","award":["F31 DA053128-01"],"award-info":[{"award-number":["F31 DA053128-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Ruth L. Kirschstein Research Award","doi-asserted-by":"publisher","award":["DP1-DA044359"],"award-info":[{"award-number":["DP1-DA044359"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Ruth L. Kirschstein Research Award","doi-asserted-by":"publisher","award":["F31 DA053128-01"],"award-info":[{"award-number":["F31 DA053128-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dopamine signaling in the adult ventral forebrain regulates behavior, stress response, and memory formation and in neurodevelopment regulates neural differentiation and cell migration. Excessive dopamine levels, including those due to cocaine use in utero and in adults, could lead to long-term adverse consequences. The mechanisms underlying both homeostatic and pathological changes remain unclear, in part due to the diverse cellular responses elicited by dopamine and the reliance on animal models that exhibit species-specific differences in dopamine signaling. In this study, we use the human-derived ventral forebrain organoid model of Xiang\u2013Tanaka and characterize their response to cocaine or dopamine. We explore dosing regimens of dopamine or cocaine to simulate acute or chronic exposure. We then use calcium imaging, cAMP imaging, and bulk RNA-sequencing to measure responses to cocaine or dopamine exposure. We observe an upregulation of inflammatory pathways in addition to indicators of oxidative stress following exposure. Using inhibitors of reactive oxygen species (ROS), we then show ROS to be necessary for multiple transcriptional responses of cocaine exposure. These results highlight novel response pathways and validate the potential of cerebral organoids as in vitro human models for studying complex biological processes in the brain.<\/jats:p>","DOI":"10.3390\/ijms242216474","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T07:33:18Z","timestamp":1700292798000},"page":"16474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reactive Oxygen Species Mediate Transcriptional Responses to Dopamine and Cocaine in Human Cerebral Organoids"],"prefix":"10.3390","volume":"24","author":[{"given":"Thomas T.","family":"Rudibaugh","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-0384","authenticated-orcid":false,"given":"Samantha R.","family":"Stuppy","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8958-1232","authenticated-orcid":false,"given":"Albert J.","family":"Keung","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.biocel.2004.09.009","article-title":"Dopaminergic neurons","volume":"37","author":"Chinta","year":"2005","journal-title":"Int. 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