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However, the impact of chronic in\u00a0vivo meth administration on SNc mitochondria is unclear. We therefore examined the impact of chronic meth administration on the expression of mitochondrial fission 1 (FIS1) and Dynamin\u2010related protein 1 (DRP1), proteins involved in mitophagy, as well as mitochondrial density and mitochondrial function in the SNc. Male C57BL\/6J mice received saline or meth (5\u2009mg\/kg; i.p.) for 28\u2009days; chronic meth administration decreased SNc expression of both DRP1 and FIS1 proteins, suggesting impaired mitophagy. Consistent with this, mitochondrial density in SNc dopamine neurons was also increased. Moreover, this increase in mitochondrial density was MAO\u2010dependent, suggesting that chronic meth\u2010induced SNc degeneration is associated with an increase in mitochondrial density. To determine whether mitochondria were functional, high\u2010resolution respirometry assessments were conducted using SNc tissue from mice treated with either chronic meth or saline. Results indicate that chronic in\u00a0vivo meth administration decreased mitochondrial complex I as well as complex I\u2009+\u2009II oxidative phosphorylation capacities and coupling efficiencies in the SNc. Presented data suggest that chronic in\u00a0vivo meth administration results in an accumulation of functionally compromised mitochondria in the SNc, which is associated with and may potentially contribute to chronic meth\u2010induced neurodegeneration.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70554-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70554","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:00:57Z","timestamp":1790316057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Methamphetamine Administration Increases Mitochondrial Density and Impairs Mitochondrial Function in the Substantia Nigra Pars Compacta"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2584-5765","authenticated-orcid":false,"given":"Aishwarya","family":"Bhowmik","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Wilking","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4314-9721","authenticated-orcid":false,"given":"Duha","family":"Alshareef","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-1617","authenticated-orcid":false,"given":"Steven M.","family":"Graves","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/cdd.2012.81","article-title":"The Pathways of Mitophagy for Quality Control and Clearance of Mitochondria","volume":"20","author":"Ashrafi G.","year":"2013","journal-title":"Cell Death and Differentiation"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23010363","article-title":"Dopamine and Methamphetamine Differentially Affect Electron Transport Chain Complexes and Parkin in Rat Striatum: New Insight Into Methamphetamine Neurotoxicity","volume":"23","author":"Bazylianska V.","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1089\/ars.2007.2000","article-title":"Ultrastructure of the Mitochondrion and Its Bearing on Function and Bioenergetics","volume":"10","author":"Benard G.","year":"2008","journal-title":"Antioxidants & Redox Signaling"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1471-4159.2005.03379.x","article-title":"Methamphetamine\u2010Induced Inhibition of Mitochondrial Complex II: Roles of Glutamate and Peroxynitrite","volume":"95","author":"Brown J. 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