CSC counteracts l-DOPA-induced overactivity of the corticostriatal synaptic ultrastructure and function in 6-OHDA-lesioned rats.

Yi-Xian Huang, Wei-Feng Luo, Dan Li, Wei-Dong Hu, Chun-Feng Liu

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Brain research 2011 Feb 28

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l-DOPA remains the gold-standard treatment for Parkinson's disease (PD). However, the emergence of l-DOPA-induced dyskinesia (LID) and motor fluctuations represents a major clinical problem in PD. The selective localization of adenosine A(2A) receptors to the basal ganglia and specifically to the indirect output pathway appear to be crucial both in the pathogenesis of PD and in the development of LID. In this study, we investigated the effects of a 3-week treatment with l-DOPA (50mg/kg/day+benserazide 12.5mg/kg/day, twice daily, i.p.) alone or combined with adenosine A(2A) receptor antagonist 8-(3-Chlorostyryl)caffeine (CSC) (5mg/kg/day, twice daily), on the rotational motor response duration, abnormal involuntary movements (AIM) and the associated striatal expression of adenosine A(2A) receptor in rats with a nigrostriatal lesion. CSC treatment ameliorated the shortening of the rotational motor response duration, partly attenuated dyskinesia and reduced striatal expression of adenosine A(2A) receptor induced by l-DOPA. Electron microscopy technique results showed that the postsynapse density depth was much thicker, synapse cleft width was narrower and the ratio of perforated synapses significantly increased in the l-DOPA-treated rats, while systemic coadministration of CSC with l-DOPA attenuated the overactivity of corticostriatal synaptic ultrastructure and function induced by l-DOPA. In conclusion, CSC by means of its dual action as A(2A) receptor antagonist and MAO-B inhibitor ameliorated the changed behavior, expression of adenosine A(2A) receptor and postsynaptic effects, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of LID. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Citation

Yi-Xian Huang, Wei-Feng Luo, Dan Li, Wei-Dong Hu, Chun-Feng Liu. CSC counteracts l-DOPA-induced overactivity of the corticostriatal synaptic ultrastructure and function in 6-OHDA-lesioned rats. Brain research. 2011 Feb 28;1376:113-21