DIFFERENTIAL REGIONAL EFFECTS OF LONG-TERM L-DOPA TREATMENT ON PREPROENKEPHALIN AND PREPROTACHYKININ GENE-EXPRESSION IN THE STRIATUM OF 6-HYDROXYDOPAMINE-LESIONED RAT

The present study examined the effects of prolonged L-DOPA treatment ( 6 months) alone or in combination with unilateral 6-hydroxydopamine-in duced lesion of the mesostriatal dopaminergic pathway on substance P a nd enkephalin mRNA expression in the rat neostriatum, This was done by means of quantitative in situ hybridization histochemistry. As report ed previously, the unilateral dopaminergic lesion induced a significan t and homogeneous decrease in striatal substance P mRNA expression and a marked increase in enkephalin mRNA expression in the ipsilateral ne ostriatum which was more pronounced in the dorsolateral than ventromed ial part of the structure. Long-term L-DOPA treatment alone had no sig nificant effects on the two striatal peptide mRNA levels. The chronic L-DOPA treatment in 6-hydroxydopamine-lesioned rats was found to parti ally reverse the lesion-induced down-regulation of substance P mRNA ex pression, without significantly affect the up-regulation of enkephalin when considering the neostriatum as a whole. Topographical analysis r evealed that long-term L-DOPA treatment reversed, in fact, both post-l esional enkephalin and substance P responses to 6-hydroxydopamine lesi on, in the ventromedial neostriatum, without significantly modified th ese peptide responses in the dorsolateral neostriatum. These findings provide new evidence that prolonged L-DOPA treatment differentially af fects the post-lesional peptide responses in the ventromedial and dors olateral parts of the neostriatum, suggesting regional cellular mechan isms in the neostriatum underlying the benefit and/or side-effects of L-DOPA treatment in parkinsonian patients. (C) 1997 Elsevier Science B .V.