| Autor: |
Carta, Manolo, Lindgren, Hanna S., Lundblad, Martin, Stancampiano, Roberto, Fadda, Fabio, Cenci, M. A. |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Mar2006, Vol. 96 Issue 6, p1718-1727, 10p, 1 Diagram, 1 Chart, 4 Graphs |
| Abstrakt: |
We explored possible differences in the peripheral and central pharmacokinetics ofl-DOPA as a basis for individual variation in the liability to dyskinesia. Unilaterally, 6-hydroxydopamine (6-OHDA) lesioned rats were treated chronically withl-DOPA for an induction and monitoring of abnormal involuntary movements (AIMs). Comparisons between dyskinetic and non-dyskinetic cases were then carried out with regard to plasma and striatall-DOPA concentrations, tissue levels of dopamine (DA), DA metabolites, and serotonin. After a single intraperitoneal injection ofl-DOPA, plasmal-DOPA concentrations did not differ between dyskinetic and non-dyskinetic animals, whereas peak levels ofl-DOPA in the striatal extracellular fluid were about fivefold larger in the former compared with the latter group. Interestingly, the time course of the AIMs paralleled the surge in striatall-DOPA levels. Intrastriatal infusion ofl-DOPA by reverse dialysis concentration dependently induced AIMs in all 6-OHDA lesioned rats, regardless of a previous priming for dyskinesia. Steady-state levels of DA and its metabolites in striatal and cortical tissue did not differ between dyskinetic and non-dyskinetic animals, indicating that the observed difference in motor response tol-DOPA did not depend on the extent of lesion-induced DA depletion. These results show that an elevation ofl-DOPA levels in the striatal extracellular fluid is necessary and sufficient for the occurrence of dyskinesia. Individual differences in the central bioavailability ofl-DOPA may provide a clue to the varying susceptibility to dyskinesia in Parkinson's disease. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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