Distribution of tritium label in the neonate rat brain following intracisternal or subcutaneous administration of [3H]6-OHDA. An autoradiographic study.

The present report describes the distribution of tritium label after injection of newborn rats with [3H]6-hydroxydopamine ([3H]6-OHDA). The animals were injected either intracisternally (i.c.) or subcutaneously (s.c.), with or without pretreatment with nomifensine, which blocks the high-affinity uptake of both noradrenaline (NA) and dopamine (DA), and sacrificed at intervals from 40 min to 24 h post-injection (p.i.). In i.c. injected animals, tritium label is demonstrable as early as 40 min p.i. in neurons of all known NA and DA cell groups. In NA neurons, it is taken up into cell body, dendrites, preterminal and terminal axons. The intensity of neuronal labeling is highest within the first 4 h p.i. and decreases in most neurons with longer postinjection intervals. A significant proportion of both NA and DA neurons degenerate beginning 6 h p.i., the majority show morphological signs of the axon reaction 24 h p.i. Uptake of [3H]6-OHDA into serotonergic and non-catecholaminergic neurons is not demonstrable. [3H]6-OHDA is accumulated by the following extraneuronal cells of the CNS: ependymal cells, epithelial cells of the choroid plexus, subependymal macrophages, smooth muscle cells in the wall of large intraparenchymal blood vessels, meningeal cells and glial cells. The time course of accumulation and disappearance of the label varies among these extraneuronal elements. The meningeal cells show the highest labeling intensity and degenerate within 24 h p.i. After pretreatment of the animals with nomifensine, the uptake of [3H]6-OHDA into NA and DA neurons is totally blocked; by contrast uptake of the labeled drug into extraneuronal cells is not prevented. These findings show that [3H]6-OHDA is not only accumulated by neurons possessing the high-affinity uptake for NA or DA, but by numerous other, extraneuronal cells which also participate in the metabolism of catecholamines.