{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:00:12Z","timestamp":1762160412531,"version":"build-2065373602"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,11,4]],"date-time":"2004-11-04T00:00:00Z","timestamp":1099526400000},"content-version":"vor","delay-in-days":2805,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[1997,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Therapeutic treatment of parkinsonian monkeys by chronic administration of levodopa (1\u2010DOPA) leads to the development of dyskinesias and other motor fluctuations. It is unclear whether there are alterations in the dopamine system that are related to the induction of dyskinesias by 1\u2010DOPA, but recent attention has focused on the D<jats:sub>1<\/jats:sub> receptor system. The present study assessed the consequences of chronic 1\u2010DOPA treatment in monkeys made parkinsonian with 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) on indices of the pre\u2010 and post\u2010synaptic dopamine (DA) system. Treatment with therapeutic doses of 1\u2010DOPA led to the induction of dyskinesias in the MPTP\u2010treated monkeys. High\u2010pressure liquid chromatography was used for measurement of tissue levels of DA and its metabolites, and quantitative autoradiography was used to examine the regional integrity of the presynaptic DA system (by measuring [<jats:sup>3<\/jats:sup>H]mazindol binding to DA uptake sites). Quantitative autoradiography was used to measure the number of postsynaptic D<jats:sub>1<\/jats:sub> receptors (using [<jats:sup>3<\/jats:sup>H] SCH 23390) in the striatum and pallidum of normal, MPTP alone, and MPTP monkeys treated chronically with 1\u2010DOPA. In both MPTP\u2010treated monkeys, levels of DA and metabolites as well as [<jats:sup>3<\/jats:sup>H]mazindol binding were greatly reduced in the caudate and putamen, slightly more in dorsal than in ventral areas. However, the lack of increase in striatal DA levels along with higher [<jats:sup>3<\/jats:sup>H]mazindol binding in MPTP\u2010plus\u20101\u2010DOPA\u2010treated monkeys suggested differences in the way DA was used after 1\u2010DOPA treatment. In MPTP\u2010treated monkeys, a significant increase (141\u2013170% of normals) of D<jats:sub>1<\/jats:sub> receptor numbers was observed in putamen and dorsal caudate. With 1\u2010DOPA treatment, the number of D<jats:sub>1<\/jats:sub> receptor numbers was further elevated in caudal putamen (119\u2013123%), dorsal caudate (110\u2013130%), and in the internal segment of the globus pallidus (GPi; 164% of normals) of MPTP\u2010treated monkeys as compared with MPTP treatment alone. This suggested that in MPTP\u2010treated monkeys made dyskinetic by chronic pulsatile delivery of 1\u2010DOPA, there was enhanced production of D<jats:sub>1<\/jats:sub> receptors in the direct striatal output to the GPi.<\/jats:p>","DOI":"10.1002\/mds.870120204","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T20:21:54Z","timestamp":1117311714000},"page":"148-158","source":"Crossref","is-referenced-by-count":43,"title":["The effects of chronic levodopa treatment on pre\u2010 and postsynaptic markers of dopaminergic function in striatum of parkinsonian monkeys"],"prefix":"10.1002","volume":"12","author":[{"given":"Lise","family":"Rioux","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.","family":"Frohna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey 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