Time dependent changes in DA uptake sites, D1 and D2 receptor binding and mRNA after 6-OHDA lesions of the medial forebrain bundle in the rat brain.

Quantitative receptor autoradiography and in situ hybridization techniques were used to examine the temporal pattern of changes in dopamine uptake sites, D1 and D2 receptors and their transcripts in the striata of animals lesioned with 6-hydroxydopamine. Animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4, 6, 8, and 16 weeks postlesion. Degeneration of the nigrostriatal pathway induced a significant loss of dopamine uptake sites in the ipsilateral caudate putamen of all lesioned animals. D1 receptor binding was significantly increased in the caudate putamen on the lesioned side from 1 week to 16 weeks postlesion, whereas the expression of D1 receptor mRNA did not show any change during this period. There was a significant upregulation of D2 receptor binding as well as D2 mRNA from 2 weeks to 8 weeks postlesion. However, at 16 weeks postlesion, D2 receptor binding continued to increase, whereas the mRNA appeared to compensate. These studies show that a different regulatory mechanism may exist between these two DA receptor subtypes. D1 receptor changes occur at the post-transcriptional or translational level, whereas D2 alterations occur by both transcriptional and translational processes. These studies also indicate that the postsynaptic supersensitivity observed in D1 receptors may not be accompanied by a corresponding increase in D1 receptor mRNA.