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Author Notes:

Correspondence should be addressed to Yan Xu; xuyanwxf@126.com and Xuebing Cao; caoxuebing@126.com

Huan Du and Shuke Nie contributed equally to this work.

None of the authors has any type of conflict of interests with this report.

Subject:

Research Funding:

This research was supported by the National Natural Science Foundation of China (NSFC Project No. 81171193 and No. 370700881).

SMP is supported by NIH grants NS045962, NS073994, NCRR RR000165 and ORIP/OD OD011132.

Dr. Papa has received research support from NIH, Michael J. Fox Foundation, Pfizer, Inc., EnVivo Pharmaceuticals, Inc., Forum Pharmaceuticals, Inc., GeneGraft, LTD, and Key Neurosciences. She is a consultant for Teva Neuroscience.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • LEVODOPA-INDUCED DYSKINESIA
  • INDUCED MOTOR COMPLICATIONS
  • PARKINSONS-DISEASE
  • DELTA-FOSB
  • RECEPTOR SUPERSENSITIVITY
  • INVOLUNTARY MOVEMENTS
  • MODEL
  • D1
  • MECHANISMS
  • PHOSPHORYLATION

Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum

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Journal Title:

Parkinson's Disease

Volume:

Volume 2015

Publisher:

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2015 Huan Du et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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