Development of substance P-containing neurons in the central nervous system in mice: an immunocytochemical study

The embryonic development of substance P (SP) in the central nervous system (CNS) of mice has been studied with the use of peroxidase antiperoxidase (PAP) immunocytochemistry. Immature SP-positive cells initially appear at embryonic day 12 (E12) in the epithalamus and in a column of cells extending from the myelencephalon throughout the length of the neural tube. By E13, SP-positive cells appear in the amygdaloid nuclear complex, the bed nucleus of the stria terminalis, and in the caudal medulla. Fibers are first detected in the stria terminalis at this age. Over the next 48 hours, a plethora of SP-positive cells appears throughout the CNS, notably in the septal area, diagonal band nucleus, piriform cortex, accumbens nucleus, hypothalamus, rostral striatum, superior and inferior colliculi, intercollicular nucleus, substantia nigra, interpeduncular nucleus, vestibular nuclei, spinal nucleus of the trigeminal, and the nucleus of the tractus solitarii. Subsequently, SP-positive neurons and fibers increase in number and staining intensity except in the medullary raphe where the apparent number of SP-positive neurons decreases after E16. Whereas the pattern of SP staining is quite similar in mice and rats, the time of initial detection of SP-like immunoreactivity in specific nuclei is 1-4 days earlier in mice than that reported in rats with different antisera.