{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:21:42Z","timestamp":1791105702274,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,7,20]]},"abstract":"<jats:p>Drug-induced dyskinesias in dopamine-denervated animals are known to depend on both pre- and postsynaptic changes of the nigrostriatal circuitry. In lesion models used thus far, changes occur in both of these compartments and, therefore, it has not been possible to dissect the individual contribution of each compartment in the pathophysiology of dyskinesias. Here we silenced the nigrostriatal dopamine neurotransmission without affecting the anatomical integrity of the presynaptic terminals using a short-hairpin RNA-mediated knockdown of tyrosine hydroxylase enzyme (shTH). This treatment resulted in significant reduction (by about 70%) in extracellular dopamine concentration in the striatum as measured by on-line microdialysis. Under these conditions, the animals remained nondyskinetic after chronic L-DOPA treatment, whereas partial intrastriatal 6-hydoxydopamine lesioned rats with comparable reduction in extracellular dopamine levels developed dyskinesias. On the other hand, apomorphine caused moderate to severe dyskinesias in both groups. Importantly, single-dose L-DOPA challenge in apomorphine-primed shTH animals failed to activate the already established abnormal postsynaptic responses. Taken together, these data provide direct evidence that the status of the presynaptic, DA releasing compartment is a critical determinant of both the induction and maintenance of L-DOPA\u2013induced dyskinesias.<\/jats:p>","DOI":"10.1073\/pnas.1003432107","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T22:23:58Z","timestamp":1278455038000},"page":"13159-13164","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Presynaptic dopaminergic compartment determines the susceptibility to L-DOPA\u2013induced dyskinesia in rats"],"prefix":"10.1073","volume":"107","author":[{"given":"Ayse","family":"Ulusoy","sequence":"first","affiliation":[{"name":"Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, BMC D11, 22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurdal","family":"Sahin","sequence":"additional","affiliation":[{"name":"Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, BMC D11, 22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Kirik","sequence":"additional","affiliation":[{"name":"Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, BMC D11, 22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,7,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-1931(00)00031-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.1090"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04124.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.1.141"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.1.137"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh229"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/156652308786847996"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.035"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.09.011"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2009.05.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm964"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.142"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2002.0499"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01843.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2008.09.013"},{"key":"e_1_3_3_16_2","first-page":"S115","article-title":"Nigrostriatal system plasticity in Parkinson's disease: Effect of dopaminergic denervation and treatment","volume":"47","author":"Hirsch EC","year":"2000","unstructured":"EC Hirsch, Nigrostriatal system plasticity in Parkinson's disease: Effect of dopaminergic denervation and treatment. 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