{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:09:37Z","timestamp":1791252577004,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,1,11]]},"abstract":"<jats:p>\n                    Treatment of Parkinson disease (PD) with\n                    <jats:sc>l<\/jats:sc>\n                    -3,4-dihydroxyphenylalanine (\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA) dramatically relieves associated motor deficits, but\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA\u2013induced dyskinesias (LID) limit the therapeutic benefit over time. Previous investigations have noted changes in striatal medium spiny neurons, including abnormal activation of extracellular signal-regulated kinase1\/2 (ERK). Using two PD models, the traditional 6-hydroxydopamine toxic lesion and a genetic model with nigrostriatal dopaminergic deficits, we found that acute dopamine challenge induces ERK activation in medium spiny neurons in denervated striatum. After repeated\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA treatment, however, ERK activation diminishes in medium spiny neurons and increases in striatal cholinergic interneurons. ERK activation leads to enhanced basal firing rate and stronger excitatory responses to dopamine in striatal cholinergic neurons. Pharmacological blockers of ERK activation inhibit\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA\u2013induced changes in ERK phosphorylation, neuronal excitability, and the behavioral manifestation of LID. In addition, a muscarinic receptor antagonist reduces LID. These data indicate that increased dopamine sensitivity of striatal cholinergic neurons contributes to the expression of LID, which suggests novel therapeutic targets for LID.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1006511108","type":"journal-article","created":{"date-parts":[[2010,12,27]],"date-time":"2010-12-27T20:45:14Z","timestamp":1293482714000},"page":"840-845","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":182,"title":["Enhanced striatal cholinergic neuronal activity mediates\n                    <scp>l<\/scp>\n                    -DOPA\u2013induced dyskinesia in parkinsonian mice"],"prefix":"10.1073","volume":"108","author":[{"given":"Yunmin","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Britt","sequence":"additional","affiliation":[{"name":"Committee on Neurobiology, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean Austin O.","family":"Lim","sequence":"additional","affiliation":[{"name":"Committee on Neurobiology, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"McGehee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, and"},{"name":"Committee on Neurobiology, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Un Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology,"},{"name":"Committee on Neurobiology, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,12,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(01)00024-4"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1999.0259"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.05.044"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0852-07.2007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-12-05042.2002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.11.032"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012322"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4720-07.2008"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0230529100"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00464"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(03)00162-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3718-04.2005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.07.018"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.08.032"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/ana.21947","article-title":"Dopamine-dependent motor learning: Insight into levodopa's long-duration response","volume":"67","author":"Beeler JA","year":"2010","unstructured":"JA Beeler, et al., Dopamine-dependent motor learning: Insight into levodopa's long-duration response. 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