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We previously determined that ubiquitin-protein ligase parkin is involved in the regulation of METH addictive behaviors in rat models of MUD. Parkin is not yet a \u201cdruggable\u201d drug target; therefore, this study aimed to determine which biological processes, pathways, and proteins downstream of parkin are likely drug targets against MUD. Employing young adult Long Evans male rats with parkin deficit or excess in the nucleus accumbens (NAc), label-free proteomics, and molecular biology, we determined that the pathways downstream of parkin that are candidates for regulating METH addictive behaviors in young adult male rats are mitochondrial respiration, oxidative stress, AMPA receptor trafficking, GABAergic neurotransmission, and actin cytoskeleton dynamics.<\/jats:p>","DOI":"10.3390\/biom15070958","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T06:01:33Z","timestamp":1751522493000},"page":"958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder"],"prefix":"10.3390","volume":"15","author":[{"given":"Akhil","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Atasi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7162-7360","authenticated-orcid":false,"given":"Florine","family":"Collin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA"},{"name":"Keck Mass Spectrometry & Proteomics Resource, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA"},{"name":"Keck Mass Spectrometry & Proteomics Resource, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4850-3462","authenticated-orcid":false,"given":"TuKiet T.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA"},{"name":"Keck Mass Spectrometry & Proteomics Resource, Yale School of Medicine, New Haven, CT 06520, USA"},{"name":"Yale\/NIDA Neuroproteomics Center, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1557-566X","authenticated-orcid":false,"given":"Rolando","family":"Garcia-Milian","sequence":"additional","affiliation":[{"name":"Harvey Cushing\/John Hay Whitney Medical Library, Yale University, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9644-3494","authenticated-orcid":false,"given":"Tasnim","family":"Arroum","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0872-4843","authenticated-orcid":false,"given":"Lucynda","family":"Pham","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6310-7081","authenticated-orcid":false,"given":"Maik","family":"H\u00fcttemann","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-2318","authenticated-orcid":false,"given":"Anna","family":"Moszczynska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaau1184","DOI":"10.1126\/science.aau1184","article-title":"Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016","volume":"361","author":"Jalal","year":"2018","journal-title":"Science"},{"key":"ref_2","unstructured":"NIDA (2023). 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