Time-course of changes in striatal levels of DA uptake sites, DA D2 receptor and preproenkephalin mRNAs after nigrostriatal dopaminergic denervation in the rat.

ABSTRACT

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 [3H]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.