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-induced lesion of the mesostriatal dopaminergic pathway on substance P and enkephalin mRNA expression in the rat neostriatum. This was done by means of quantitative in situ hybridization histochemistry. As reported previously, the unilateral dopaminergic lesion induced a significant and homogeneous decrease in striatal substance P mRNA expression and a marked increase in enkephalin mRNA expression in the ipsilateral neostriatum which was more pronounced in the dorsolateral than ventromedial part of the structure. Long-term L-DOPA treatment alone had no significant effects on the two striatal peptide mRNA levels. The chronic L-DOPA treatment in 6-hydroxydopamine-lesioned rats was found to partially reverse the lesion-induced down-regulation of substance P mRNA expression, without significantly affect the up-regulation of enkephalin when considering the neostriatum as a whole. Topographical analysis revealed that long-term L-DOPA treatment reversed, in fact, both post-lesional enkephalin and substance P responses to 6-hydroxydopamine lesion, in the ventromedial neostriatum, without significantly modified these peptide responses in the dorsolateral neostriatum. These findings provide new evidence that prolonged L-DOPA treatment differentially affects the post-lesional peptide responses in the ventromedial and dorsolateral parts of the neostriatum, suggesting regional cellular mechanisms in the neostriatum underlying the benefit and/or side-effects of L-DOPA treatment in parkinsonian patients.
Salin
P
P
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, UPR9013, CNRS, Marseille, France.
Dziewczapolski
G
G
Gershanik
O S
OS
Nieoullon
A
A
Raisman-Vozari
R
R
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004745:Enkephalins / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D011498:Protein Precursors / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015320:Tachykinins / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D004745:Enkephalins; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D007980:Levodopa; D016627:Oxidopamine; C033660:preproenkephalin