DOPAMINE-RECEPTORS STATUS AFTER UNILATERAL NIGRAL 6-OHDA LESION - AUTORADIOGRAPHIC AND INSITU HYBRIDIZATION STUDY IN THE RAT-BRAIN

The physiological effects of dopamine (DA) are mediated by several dis tinct receptor subtypes. The effects of unilateral nigral 6-hydroxydop amine (6-OHDA) lesions on DA receptors were investigated by receptor a utoradiography using the D1 selective ligand [H-3]SCH 23390 as well as the D2 ligand [H-3]spiroperidol. mRNA distribution was studied by in situ hybridization. Lesioned rats were sacrificed at different time in tervals. Receptor binding studies were performed on tissue sections us ing selective ligands. [S-35]UTP labeled RNA probes were prepared from the different cDNA (D1, D2, D3) and used for in situ hybridization. A specific loss of receptor binding sites and mRNA hybridization was fo und in the lesioned substantia nigra pars compacta (SNc) at all times examined. Receptor binding studies revealed a different time-dependent increase in both D1 and D2 receptors. In situ hybridization showed th at only D1 receptor mRNA increased in the caudate-putamen (CPu) of the lesioned side 15 d after 6-OHDA. No changes were observed in D1 and D 1 receptor mRNA during the entire time-course.