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) tran sporters ([H-3]paroxetine), noradrenaline (NE) transporters ([H-3]nisoxetin e), and of dopamine (DA) transporters ([H-3]GBR-12935) were determined on m embrane 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 o f 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 specifi c ligands were most pronounced in the phylogenetically younger, late maturi ng brain regions (frontal cortex, striatum). Most likely, these changes ref lect age-related changes in 5-HT, NE and DA-innervation densities. In the f rontal cortex, 5-HT-transporter density increased steadily from weaning (da y 25) till late adulthood, whereas the density of NE-transporters was highe st at weaning, declined till puberty (day 50) and remained at this level un til old age. DA-transporter density in the frontal cortex was not reliably measurable by [H-3]GBR-binding assays. In the striatum, DA-transporter dens ity increased till puberty and declined thereafter considerably and steadil y to about one-fourth of the pubertal values at old age. No such age-associ ated 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 fi rst comprehensive description of the normally occurring changes in the dens ities of all three presynaptically located monoamine transporters in the ra t brain throughout the life span from weaning to late adulthood. (C) 2000 E lsevier Science B.V. All rights reserved.