Region- and stage-specific patterns of melanocortin receptor ontogeny in rat central nervous system, cranial nerve ganglia and sympathetic ganglia

Abstract

Observations on developmental actions of melanotropic peptides in nervous system have been difficult to interpret in the absence of data on receptor ontogeny. We investigated binding of [ 125I]Nle 4, d-Phe 7-α-MSH ([ 125I]NDP) in developing Long Evans rats from gestational day (E) 13 by quantitative autoradiography. Regional [ 125I]NDP binding characteristics were assessed by competition experiments in early postnatal brain. The study revealed region- and stage-specific, often transient ontogenetic patterns. Sympathetic ganglia exhibit high [ 125I]NDP binding from E13, with a peak in superior cervical ganglion at E16–E18. The first central [ 125I]NDP binding sites transiently appear in parts of thalamus between E13 and E15. The early fetal period is characterized by prominent peaks of receptor density in somatosensory and viscerosensory nuclei (trigeminal sensory nuclei, solitary tract nucleus), paralleled by receptor expression in 5th, 7th, 9th and 10th cranial nerve ganglia. During late fetal life, receptor density peaks in dorsal motor nucleus of vagus and inferior olive; binding sites transiently appear in cerebellum. Caudate-putamen, nucleus accumbens, olfactory tubercle and septohippocampal nucleus show a high perinatal maximum. Starting with late fetal piriform cortex, [ 125I]NDP binding peaks sequentially in cerebral cortical areas, with highest levels in entorhinal cortex. Preoptic, septal, hypothalamic and amygdaloid areas known for elevated receptor densities in adulthood, exhibit a slow, peri- and postnatal receptor ontogeny. Temporal relations to regional developmental processes support the idea of a role of melanocortins during ontogeny.