THE INFLUENCE OF INTERMITTENT L-DOPA TREATMENT ONSTRIATAL MOLECULAR MARKERS IN HEMIPARKINSONIANRATS*
Abstract
Motor complications after chronic l-DOPA treatment in patients with Parkinson’s diseasemay be caused by the fluctuations of l-DOPA availability in the brain that provokes thesensitization of striatal output neurons of dopamine-depleted striatum. The aim of thisstudy was to analyze the effects of intermittent l-DOPA/carbidopa treatment schedule(injection of l-DOPA/carbidopa every fourth day, 6-treatments) on the development oflocomotor sensitization of hemiparkinsonian rats to l-DOPA, and on the development ofdopaminergic sensitization of striatal output neurons of the indirect and direct pathways.The development of locomotor sensitization was verified by the increased intensity ofcontralateral turning behavior after the last l-DOPA injection. It is well known that PPTmRNA is expressed predominantly by the neurons of the direct pathway, PENK mRNAby the neurons of the indirect pathway, while GAD67 mRNA is expressed in the neuronsof both pathways. Dopaminergic sensitization of striatal output neurons of dopaminedepleted striatum was thus assessed by the analysis of changes of striatal preprotachykinin(PPT), proenkephalin (PENK) and GAD 67 mRNA levels 4 and 12 hours after the lastl-DOPA injection. We found, that chronic dopamine depletion by itself down-regulates theexpression of striatal PPT mRNA and up-regulates GAD67 and PENK mRNAs. These changesof basal expression were not reversed by the intermittent l-DOPA/carbidopa treatment.However, in dopamine-depleted striatum, the intermittent treatment with l-DOPA inducedincreased responsiveness of striatal PPT and GAD67, but not PENK mRNA expression, tol-DOPA. Our results are in agreement with the hypothesis, that intermittent l-DOPA treatment induces locomotor sensitization that may be linked to the increased dopaminergicresponsiveness of striatonigral neurons of the direct pathway, within dopamine-depletedstriatum.Downloads
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