Survival and Differentiation of Cultured Dopaminergic Neurons Are Not Impaired by Chronic Stimulation of DA D-2 Autoreceptors

Replacement of the degenerated dopamin-ergic input by grafted dopamine (DA) producing cells has been proposed as an effective therapy for Parkinson's disease (PD). However, results from clinical application of fetal DA grafts were rather disappointing since transplantation resulted only in slight functional improvement/1/. Prolonged treatment with L-dopa or DA agonists might, via stimulation of DA D-2 auto-receptors, impair survival and/or differentiation of grafted neurons. Chronic treatment with L-dopa has been reported to impair survival and neurite outgrowth of cultured dopaminergic neurons/2/. It is tempting to speculate that D-2 receptors are involved since D-2 receptor activation not only leads to a decrease in the firing rate of dopaminergic neurons but also to an inhibition of the synthesis and release of DA. To investigate the role of D-2 receptors in the effect of L-dopa and the development of fetal dopaminergic neurons in general, knowledge about the expression of D-2 receptors on these neurons is a prerequisite. Therefore cultures were prepared from fetal rat ventral mesen-cephalon on gestational day 15. Cultured dopaminergic neurons (identified by tyrosine hydroxylase [TH] immunocytochemistry) became more differentiated in the course of time and exhibited specific high-affinity uptake for