Development of the norepinephrine transporter in the rat CNS.

The norepinephrine transporter (NET) plays a major role in regulating the actions of norepinephrine by removing norepinephrine from the synapse. Many studies suggest norepinephrine plays an important role in regulating development of the CNS, pointing to NET as an important factor in this process. We examined the ontogeny of NET expression in rat brain at 5, 10, 15, 20 and 25 days postnatally (PND) and in adults, using quantitative autoradiography with [3H]nisoxetine as ligand. At PND 5 and 10 most forebrain areas had low NET expression (1-2 fmol/mg tissue). By PND 15 most forebrain areas increased NET expression approximately five-fold compared with PND 10, levels generally similar to those found in the adult brain. In contrast, NET development in the brainstem exhibited elevated densities at PND 5, 10 and 20 that decreased in the adult. The locus coeruleus, in particular, had very high NET expression in the early postnatal period that decreased dramatically in the adult brain. These data illustrate a dynamic ontogenic profile for NET, characterized by developmental increases in forebrain structures and contrasting decreases in the brainstem. The early postnatal expression of NET in brainstem and the subsequent decrease or loss of NET expression with maturation suggest an important role for this transporter and for norepinephrine in the development of many brain regions. These studies also have important implications for use of drugs targeting the noradrenergic system in children and adolescents, such as antidepressants and drugs of abuse.