ACTIVATION OF DOPAMINERGIC D-1 RECEPTORS PROMOTES MORPHOGENESIS OF DEVELOPING STRIATAL NEURONS

The early dopaminergic input from the midbrain may play an important r ole in the development of the basal ganglia. We therefore investigated whether and how dopamine affects the morphogenesis of striatal target neurons. Dissociated cell cultures of embryonic day 17 rat striatum w ere raised for seven days. Cells were then incubated with dopamine or various receptor-specific ligands for 1 h. At various times after term ination of the treatment, cells were immunostained for growth-associat ed protein-43. Morphological parameters including numbers of growth co nes, length of neurites, number of bifurcations, and neuronal soma siz e were assessed by means of a computer-based morphometric device. Trea tment with dopamine in low concentrations as well as with the D-1-like receptor agonist SKF 38393 increased the numbers of growth cones and neurite length and arborization. The morphogenetic effect took several hours to evolve and remained stable for at least 24 h. It could be bl ocked by the D-1-like receptor antagonist SCH 23390 or by cycloheximid e but not by pretreatment of the cultures with tetrodotoxin. The D-2-l ike receptor agonist quinpirole had no effect on the morphological par ameters and did not contribute to that of SKF 38393. Dopamine and SKF 38393 but not quinpirole also induced an increase in the number of neu rons immunoreactive for Fos-like proteins. However, this effect was re stricted to growth-associated protein-43-negative neurons. This is the first observation of a positive regulatory effect of D-1-like recepto rs on neuronal morphogenesis. We conclude that the changes reflect tru e differentiation rather than short-term modulation of cellular proper ties and that c-fos induction is not an obligatory step in the transdu ction pathway coupling D-1-like receptors to neurite outgrowth. Our re sults suggest that the differentiation of embryonic striatal neurons i s promoted by the dopaminergic nigrostriatal projection through D-1-li ke receptors. Copyright (C) 1996 IBRO. Published by Elsevier Science L td.