title: Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum.
abstract: L-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson's disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators of LID in rats with 6-hydroxydopamine (6-OHDA) lesions. Following chronic administration of L-DOPA (12 mg/kg, twice daily for 14 days), rats developed abnormal involuntary movements (AIMs), but co-administration of levetiracetam (15, 30, and 60 mg/kg) with equivalent L-DOPA dosing significantly reduced AIMs scores in a dose dependent manner. The effects of levetiracetam were associated with changes in striatal expression of ΔFosB, phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and phosphorylated cAMP-regulated phosphoprotein of 32 kDa (p-DARPP-32). These data support that levetiracetam acts at multiple sites in the pathogenetic cascade of LID, and that further understanding of these actions of antiepileptics may contribute to developing new LID therapies.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China ; Department of Neurology, Sanmenxia Central Hospital, Sanmenxia 472000, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
authors.forename: Shuke
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, Renmin Hospital, Wuhan University, Wuhan 430060, China.
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Yerkes National Primate Research Center, Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Papa
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Cao