The onset of cell differentiation in the locus coeruleus, dorsal and medial raphe nuclei, and substantia nigra (zona compacta) was studied using the technique of long-survival H3-thymidine autoradiography to date neurogenesis. Pregnant female rats were injected with isotope on day 10, 11, 12, 13, 14, 15, 16 or 17 of gestation. Litters were born on day 22 and allowed to survive for 30 days. Brains were prepared for the fluorescence histochemical demonstration of monoamines or fixed by formalin perfusion. Autoradiography was carried out on sections adjacent to those in which monoamine-nuclear groups were identified by the fluorescence method and also on sections from perfused brains, which were used to facilitate cell counting. The norepinephrine cells of the locus coeruleus began to differentiate (presence of heavily labelled cells) on days 10–13 of gestation, with a peak of heavy labelling on day 12, whereas the 5-HT cells of the raphe nuclei and the dopamine cells of the substantia nigra began differentiating on days 11–15. In the dorsal raphe nucleus, the peak of heavy labelling occurred on day 14, whereas in the medial nucleus this took place on days 13–14. The substantia nigra, on the other hand, peaked on day 13.
Cell differentiation was also studied in the cerebellar Purkinje cells and hippocampal macroneurons (pyramidal and polymorph cells) of areas CA3 and CA4, to which the locus coeruleus has been reported to project. Differentiation of these cells commenced on days 14–15 (Purkinje cells) and 13–18 (hippocampal cells), with both cell types peaking on day 15, a full three days after the peak of heavy labelling in the locus coeruleus.
Evidence is discussed for the possible neurotrophic role of monoamine neurons in the neurogenesis of monoaminergic receptive cells.