RT Journal Article SR Electronic T1 The 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitor Lovastatin Reduces Severity of l-DOPA-Induced Abnormal Involuntary Movements in Experimental Parkinson's Disease JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4311 OP 4316 DO 10.1523/JNEUROSCI.4720-07.2008 VO 28 IS 17 A1 Schuster, Stefan A1 Nadjar, Agnès A1 Guo, Jun Tang A1 Li, Qin A1 Ittrich, Carina A1 Hengerer, Bastian A1 Bezard, Erwan YR 2008 UL http://www.jneurosci.org/content/28/17/4311.abstract AB Chronic l-3,4-dihydroxyphenylalanine (l-DOPA) treatment of Parkinson's disease (PD) often leads to debilitating involuntary movements, termed l-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 l-DOPA exposure could reduce AIM incidence and severity in the 6-hydroxydopamine (6-OHDA) rat model of PD by secondarily preventing the l-DOPA/Benserazide-induced increase in pERK1 levels. The lovastatin-l-DOPA/Benserazide-treated 6-OHDA animals displayed less severe rotational behavior as well as a dramatic reduction in AIM severity than the l-DOPA/Benserazide-treated ones. Such lower AIM severity was associated with a decrease in l-DOPA-induced increase in the following: (1) striatal pERK1 and (2) ΔFosB levels, and (3) theta/α 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.