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Neurosci."],"published-print":{"date-parts":[[2008,4,23]]},"abstract":"<jats:p>Chronic<jats:sc>l<\/jats:sc>-3,4-dihydroxyphenylalanine (<jats:sc>l<\/jats:sc>-DOPA) treatment of Parkinson's disease (PD) often leads to debilitating involuntary movements, termed<jats:sc>l<\/jats:sc>-DOPA-induced dyskinesia (LID), about which the rodent analog, the abnormal involuntary movements (AIMs), has been associated consistently with an activation of the Ras-extracellular signal-regulated kinase 1\/2 (ERK1\/2) mitogen-activated protein kinase signaling pathway. Previous studies have shown that lovastatin, a specific inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, can also inhibit Ras isoprenylation and activity and subsequently the phosphorylation of ERK1\/2 (pERK1\/2). We hypothesized that lovastatin treatment-commenced previous<jats:sc>l<\/jats:sc>-DOPA exposure could reduce AIM incidence and severity in the 6-hydroxydopamine (6-OHDA) rat model of PD by secondarily preventing the<jats:sc>l<\/jats:sc>-DOPA\/Benserazide-induced increase in pERK1 levels. The lovastatin-<jats:sc>l<\/jats:sc>-DOPA\/Benserazide-treated 6-OHDA animals displayed less severe rotational behavior as well as a dramatic reduction in AIM severity than the<jats:sc>l<\/jats:sc>-DOPA\/Benserazide-treated ones. Such lower AIM severity was associated with a decrease in<jats:sc>l<\/jats:sc>-DOPA-induced increase in the following: (1) striatal pERK1 and (2) \u0394FosB levels, and (3) theta\/\u03b1 oscillations of substantia nigra pas reticulata (SNr) neurons as well as (4) a normalization of SNr firing frequency. Those results strongly suggest that lovastatin might represent a treatment option for managing LID in PD.<\/jats:p>","DOI":"10.1523\/jneurosci.4720-07.2008","type":"journal-article","created":{"date-parts":[[2008,4,23]],"date-time":"2008-04-23T16:56:20Z","timestamp":1208969780000},"page":"4311-4316","source":"Crossref","is-referenced-by-count":84,"title":["The 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitor Lovastatin Reduces Severity of l-DOPA-Induced Abnormal Involuntary Movements in Experimental Parkinson's Disease"],"prefix":"10.1523","volume":"28","author":[{"given":"Stefan","family":"Schuster","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Nadjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun 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