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dc.contributor.authorFredduzzi, S.-
dc.contributor.authorMoratalla, Rosario-
dc.contributor.authorMonopoli, A.-
dc.contributor.authorCuellar, B.-
dc.contributor.authorXu, K.-
dc.contributor.authorOngini, E.-
dc.contributor.authorImpagnatiello, F.-
dc.contributor.authorSchwarzschild, M.A.-
dc.contributor.authorChen, J.-F.-
dc.identifier.citationJournal of Neuroscience 22: 1054- 1062 (2002)-
dc.description.abstractTo investigate the role of A2A adenosine receptors in adaptive responses to chronic intermittent dopamine receptor stimulation, we compared the behavioral sensitization elicited by repeated L-DOPA treatment in hemiparkinsonian wild-type (WT) and A2A adenosine receptor knock-out (A2A KO) mice. Although the unilateral nigrostriatal lesion produced by intrastriatal injection of 6-hydroxydopamine was indistinguishable between WT and A2A KO mice, they developed strikingly different patterns of behavioral sensitization after daily treatment with low doses of L-DOPA for 3 weeks. WT mice initially displayed modest contralateral rotational responses and then developed progressively greater responses that reached a maximum within 1 week and persisted for the duration of the treatment. In contrast, any rotational behavioral sensitization in A2A KO mice was transient and completely reversed within 2 weeks. Similarly, the time to reach the peak rotation was progressively shortened in WT mice but remained unchanged in A2A KO mice. Furthermore, daily L-DOPA treatment produced gradually sensitized grooming in WT mice but failed to induce any sensitized grooming in A2A KO mice. Finally, repeated L-DOPA treatment reversed the 6-OHDA-induced reduction of striatal dynorphin mRNA in WT but not A2A KO mice, raising the possibility that the A2A receptor may contribute to L-DOPA-induced behavioral sensitization by facilitating adaptations within the dynorphin-expressing striatonigral pathway. Together these results demonstrate that the A2A receptor plays a critical role in the development and particularly the persistence of behavioral sensitization to repeated L-DOPA treatment. Furthermore, they raise the possibility that the maladaptive dyskinetic responses to chronic L-DOPA treatment in Parkinson's disease may be attenuated by A2A receptor inactivation.-
dc.publisherSociety for Neuroscience-
dc.subjectParkinson's disease-
dc.subjectBehavioral sensitization-
dc.subjectA2A adenosine receptor-
dc.titlePersistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors-
dc.description.versionPeer Reviewed-
item.fulltextWith Fulltext-
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