TIME-COURSE OF CHANGES IN STRIATAL LEVELS OF DA UPTAKE SITES, DA D(2) RECEPTOR AND PREPROENKEPHALIN MESSENGER-RNAS AFTER NIGROSTRIATAL DOPAMINERGIC DENERVATION IN THE RAT

Changes in striatal dopamine uptake sites, D2 receptor and preproenkephalin (PPE) mRNA levels provoked by unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic (DA) pathway were studied by quantitative autoradiography and in situ hybridization (ISH) in rats sacrificed at different post-lesion delays. The disappearance of DA terminals as visualized with the labelling of dopamine uptake sites with [H-3]GBR 12935 became significant 36 h after the lesion and was almost complete at a delay of 7 days. PPE mRNA amounts significantly increase + 24%) already at the shortest delay studied (9 h after the lesion) while the labelling of the uptake sites on DA terminals was not affected. The time course increase of PPE mRNA levels was progressive until 21 days post-lesion where it reached its maximum (+ 132%) and remained stable up to the latest delay studied (60 days). Conversely D2 mRNA contents remained unchanged up to 5 days post-surgery and then increased relatively quickly since at 7 days post-lesion their levels were near (+21%) the maximum observed which was reached at 21 days post-lesion (+ 32%). This study suggests a time-dependent differential sensitivity to the degree of DA denervation of both major components implicated in the striatopallidal output.