TIME-DEPENDENT CHANGES IN DA UPTAKE SITES, D1 AND D2 RECEPTOR-BINDINGAND MESSENGER-RNA AFTER 6-OHDA LESIONS OF THE MEDIAL FOREBRAIN-BUNDLEIN THE RAT-BRAIN

Quantitative receptor autoradiography and in situ hybridization techni ques were used to examine the temporal pattern of changes in dopamine uptake sites, D-1 and D-2 receptors and their transcripts in the stria ta of animals lesioned with 6-hydroxydopamine. Animals were unilateral ly lesioned in the medial forebrain bundle and the brains were analyze d at 1, 2, 4, 6, 8, and 16 weeks postlesion. Degeneration of the nigro striatal pathway induced a significant loss of dopamine uptake sites i n the ipsilateral caudate putamen of all lesioned animals. D-1 recepto r binding was significantly increased in the caudate putamen on the le sioned side from 1 week to 16 weeks postlesion, whereas the expression of D-1 receptor mRNA did not show any change during this period. Ther e was a significant upregulation of D-2 receptor binding as well as D- 2 mRNA from 2 weeks to 8 weeks postlesion. However, at 16 weeks postle sion, D-2 receptor binding continued to increase, whereas the mRNA app eared to compensate. These studies show that a different regulatory me chanism may exist between these two DA receptor subtypes. D-1 receptor changes occur at the post-transcriptional or translational level, whe reas D-2 alterations occur by both transcriptional and translational p rocesses. These studies also indicate that the postsynaptic supersensi tivity observed in D-1 receptors may not be accompanied by a correspon ding increase in D-1 receptor mRNA.