Age-associated changes in the densities of presynaptic monoamine transporters in different regions of the rat brain from early juvenile life to late adulthood.

The binding parameters of highly selective ligands of serotonin (5-HT) transporters ([3H]paroxetine), noradrenaline (NE) transporters ([3H]nisoxetine), and of dopamine (DA) transporters ([3H]GBR-12935) were determined on membrane preparations from frontal cortex, striatum, midbrain and brain stem of Wistar rats on postnatal days 25, 50, 90 and 240, i.e., from the time of weaning till late adulthood. No age-dependent alterations in the affinity-parameters (K(D)-values) of all three monoamine transporters were observed. Age-associated changes in B(max)-values of the binding of all three specific ligands were most pronounced in the phylogenetically younger, late maturing brain regions (frontal cortex, striatum). Most likely, these changes reflect age-related changes in 5-HT, NE and DA-innervation densities. In the frontal cortex, 5-HT-transporter density increased steadily from weaning (day 25) till late adulthood, whereas the density of NE-transporters was highest at weaning, declined till puberty (day 50) and remained at this level until old age. DA-transporter density in the frontal cortex was not reliably measurable by [3H]GBR-binding assays. In the striatum, DA-transporter density increased till puberty and declined thereafter considerably and steadily to about one-fourth of the pubertal values at old age. No such age-associated changes in DA-transporter density were seen in the midbrain. Densities of 5-HT and NE remained at the level reached already at weaning until old age in the striatum, midbrain and brain stem. These findings provide the first comprehensive description of the normally occurring changes in the densities of all three presynaptically located monoamine transporters in the rat brain throughout the life span from weaning to late adulthood.