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Subsequently, animals were killed and the brains harvested at 1, 7, 28 or 56\u00a0days of abstinence.<jats:italic>Post mortem<\/jats:italic>, tyrosine hydroxylase (<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>) immunostaining in the dorsal striatum progressively decreased throughout abstinence, reaching a 50% loss at 56\u00a0days. In the substantia nigra, there was marked reduction of<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>+ cells, and Fluorogold (retrograde tracer) transport from the striatum to the nigra, at 28 and 56\u00a0days after Meth. Thus, Meth\u2010induced progressive nigrostriatal damage occurred retrogradely, similar to<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>pathology. The mesolimbic dopamine pathway [i.e. ventral tegmental area (<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>) and nucleus accumbens (<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c)], critical for Meth\u2010induced reward, was also evaluated.<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>immunostaining was decreased in the<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c\u2010core at 28 and 56\u00a0days of forced abstinence, while staining in the dorsomedial<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c\u2010shell was preserved. Accordingly,<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>+ cell loss was evident in the lateral<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>, the origin of projections to the<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c\u2010core, but not the medial<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>where<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c\u2010shell projections originate. Thus, after Meth\u2010taking ceased, a time\u2010dependent, progressive degeneration occurred within nigrostriatal projections that eventually engulfed lateral mesolimbic projections. This pathological pattern is consistent with a trajectory for developing<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>; therefore, these findings provide preclinical support for Meth abuse to increase vulnerability to developing<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/ejn.12628","type":"journal-article","created":{"date-parts":[[2014,5,30]],"date-time":"2014-05-30T06:34:28Z","timestamp":1401431668000},"page":"2707-2714","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Methamphetamine self\u2010administration results in persistent dopaminergic pathology: implications for Parkinson's disease risk and reward\u2010seeking"],"prefix":"10.1111","volume":"40","author":[{"given":"Sharanya M.","family":"Kousik","sequence":"first","affiliation":[{"name":"Center for Compulsive Behavior and Addiction Rush University Medical Center Chicago IL USA"},{"name":"Department of Pharmacology Rush University Medical Center Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Carvey","sequence":"additional","affiliation":[{"name":"Center for Compulsive Behavior and Addiction Rush University Medical Center Chicago IL USA"},{"name":"Department of Pharmacology Rush University Medical Center Chicago IL USA"},{"name":"Department of Neurological Sciences Rush University Medical Center Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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