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This enhanced vulnerability likely relates to the toxic effects of <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content> that overlap with <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> pathology, for example, aberrant functioning of \u03b1\u2010synuclein and parkin. In <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, peripheral factors are thought to contribute to central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) degeneration. For example, \u03b1\u2010synuclein levels in the enteric nervous system (<jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content>) are elevated, and this precedes the onset of motor symptoms. It remains unclear whether neurons of the <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content>, particularly catecholaminergic neurons, exhibit signs of <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content>\u2010induced toxicity as seen in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>. The aim of this study was to determine whether self\u2010administered <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content> altered the levels of \u03b1\u2010synuclein, parkin, tyrosine hydroxylase (<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>), and dopamine\u2010\u03b2\u2010hydroxylase (D\u03b2H) in the myenteric plexus of the distal colon <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content>. Young adult male Sprague\u2010Dawley rats self\u2010administered <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content> for 3\u00a0h per day for 14\u00a0days and controls were saline\u2010yoked. Distal colon tissue was collected at 1, 14, or 56\u00a0days after the last operant session. Levels of \u03b1\u2010synuclein were increased, while levels of parkin, <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>, and D\u03b2H were decreased in the myenteric plexus in the <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content>\u2010exposed rats at 1\u00a0day following the last operant session and returned to the control levels after 14 or 56\u00a0days of forced abstinence. The changes were not confined to neurofilament\u2010positive neurons. These results suggest that colon biomarkers may provide early indications of <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content>\u2010induced neurotoxicity, particularly in young chronic <jats:styled-content style=\"fixed-case\">METH<\/jats:styled-content> users who may be more susceptible to progression to <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> later in life.<\/jats:p>","DOI":"10.1111\/ejn.13630","type":"journal-article","created":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T09:47:06Z","timestamp":1498729626000},"page":"1918-1932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Self\u2010administration of methamphetamine alters gut biomarkers of toxicity"],"prefix":"10.1111","volume":"46","author":[{"given":"Amanda","family":"Flack","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Wayne State University Eugene Applebaum College of Pharmaceutical Sciences Detroit MI 48201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda L.","family":"Persons","sequence":"additional","affiliation":[{"name":"Center for Compulsive Behavior and Addiction Rush University Medical Center Chicago IL USA"},{"name":"Department of Pharmacology Rush University Medial Center Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharanya M.","family":"Kousik","sequence":"additional","affiliation":[{"name":"Center for Compulsive Behavior and Addiction Rush University Medical Center Chicago IL USA"},{"name":"Department of Pharmacology Rush University Medial Center Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Celeste Napier","sequence":"additional","affiliation":[{"name":"Center for Compulsive Behavior and Addiction Rush University Medical Center Chicago IL USA"},{"name":"Department of Pharmacology Rush University Medial Center Chicago IL USA"},{"name":"Department of Psychiatry Rush University Medical Center Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Moszczynska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Wayne State University Eugene Applebaum College of Pharmaceutical Sciences Detroit MI 48201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.05.010"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10599"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000243"},{"key":"e_1_2_11_5_1","first-page":"879","article-title":"Aggregation of alpha\u2010synuclein in Lewy bodies","volume":"152","author":"Baba M.","year":"1998","journal-title":"Am. 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