Prenatal development of mesencephalic and diencephalic dopaminergic systems in the male and female rat

Abstract

Previous results had suggested mesencephalic dopaminergic neurons in cultures of gestational day (GD) 14 rat embryonic brains to be characterized by an early maturation and acquisition of sex-related differences in transmitter uptake. Therefore development of dopaminergic systems was reexamined in the rat in vivo with special emphasis on the prenatal period, mesencephalo-hypothalamic relationships, and possible sex differences. Perfusion-fixed brains of GD 14, 17, 20, 21 and newborn rats were sectioned or processed as whole-mounts and immunostained for tyrosine hydroxylase (TH). Total numbers of mesencephalic TH-immunoreactive cell bodies as assessed by a stereological method rose between GD 14 and 17 and fell again between GD 17 and 21. As early as GD 14, a prominent mesencephalo-hypothalamic projection was observed coming off the medial forebrain bundle and terminating in the retrochiasmatic region. Two additional TH-immunoreactive fiber bundles leaving the medial forebrain bundle, one rostral and one caudal to the former, and terminating in the paraventricular and premammillary region, respectively, were noticed on GD 17. Careful examination of developing TH-immunoreactive neurons in the lower brainstem ascertained that there was no interference from ascending catecholaminergic fibers other than dopaminergic of mesencephalic origin during this early prenatal period. All 3 mesencephalo-hypothalamic projections had largely disappeared by GD 20 and were no longer detectable as distinct fiber bundles thereafter. There were subtle sex differences in numbers and distribution of both mesencephalic and diencephalic TH-immunoreactive neurons present at GD 17, which thus occurred prior to manifestation of other well-known sexual dimorphisms of the rat brain. The transient nature of the mesencephalo-hypothalamic projections strongly suggest mesencephalic dopaminergic neurons to assume a role in directing development of some hypothalamic target areas.