REGION-SPECIFIC AND STAGE-SPECIFIC PATTERNS OF MELANOCORTIN RECEPTOR ONTOGENY IN RAT CENTRAL-NERVOUS-SYSTEM, CRANIAL NERVE GANGLIA AND SYMPATHETIC-GANGLIA

Observations on developmental actions of melanotropic peptides in nerv ous system have been difficult to interpret in the absence of data on receptor ontogeny. We investigated binding of [I-125]Nle(4),D-Phe(7)-a lpha-MSH ([I-125]NDP) in developing Long Evans rats from gestational d ay (E) 13 by quantitative autoradiography. Regional [I-125]NDP binding characteristics were assessed by competition experiments in early pos tnatal brain. The study revealed region- and stage-specific, often tra nsient ontogenetic patterns. Sympathetic ganglia exhibit high [I-125]N DP binding from E13, with a peak in superior cervical ganglion at E16- E18. The first central [I-125]NDP binding sites transiently appear in parts of thalamus between E13 and E15. The early fetal period is chara cterized by prominent peaks of receptor density in somatosensory and v iscerosensory nuclei (trigeminal sensory nuclei, solitary tract nucleu s), paralleled by receptor expression in 5th, 7th, 9th and 10th crania l nerve ganglia. During late fetal life, receptor density peaks in dor sal motor nucleus of vagus and inferior olive; binding sites transient ly appear in cerebellum. Caudate-putamen, nucleus accumbens, olfactory tubercle and septohippocampal nucleus show a high perinatal maximum. Starting with late fetal piriform cortex, [I-125]NDP binding peaks seq uentially in cerebral cortical areas, with highest levels in entorhina l cortex. Preoptic, septal, hypothalamic and amygdaloid areas known fo r elevated receptor densities in adulthood, exhibit a slow, peri- and postnatal receptor ontogeny. Temporal relations to regional developmen tal processes support the idea of a role of melanocortins during ontog eny.