Repeated administration of a selective dopamine D2 receptor agonist to 6-OHDA-lesioned rats does not affect the survival and outgrowth of intrastriatal fetal mesencephalic grafts

The objective of the present study was to investigate the effects of chronic activation of dopamine D2 receptors on the development of grafted fetal rat mesencephalic dopaminergic neurons. Therefore, unilaterally 6-hydroxydopamine - lesioned rats received intrastriatal mesencephalic cell suspension grafts and were subsequently chronically treated with the selective dopamine D2 receptor agonist LY 171555 (Quinpirole). After treatment for 6 consecutive weeks, the rats were processed for tyrosine-hydroxylase immunocytochemistry to assess the survival and outgrowth from grafted dopaminergic neurons. morphological analysis revealed that, like the volume and morphology of the graft, neither the number nor the cell area of grafted dopaminergic neurons was significantly different between vehicle- and LY 171555-treated animals. To obtain a quantitative estimate of the graft-derived dopaminergic reinnervation, a computerized image analysis system was used. Using this procedure, which was based on the densitometric measurement of tyrosine hydroxylase immunoreactivity in the area adjacent to the grafted tissue, it was found that the extent of graft-derived outgrowth also appeared to be unaffected upon chronic treatment with LY 171555. It is concluded that long-term concurrent administration of a dopamine D2 receptor agonist for 6 consecutive weeks does not impair the survival and outgrowth of grafted rat fetal mesencephalic dopaminergic neurons