Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging.

The density of D-1 and D-2 dopamine receptors in human caudate nucleus and putamen, obtained postmortem, were studied throughout the adult lifespan using [3H]fluphenazine as the dopamine receptor ligand. The D-1 subtype increased progressively with age in both regions, while the D-2 subtype declined in caudate nucleus. The ratio of D-1/D-2 Bmax in both regions increased from approximately 1 at age 20 to 2 by age 75. The dopamine content in putamen declined with age and was inversely correlated with D-1 receptor density. We suggest that D-1 receptor density is up-regulated by loss of dopamine during aging. The D-2 receptor density in caudate nucleus was positively correlated with choline acetyltransferase activity, suggesting that loss of intrastriatal neurons with age may contribute to the decrease in D-2 sites. These divergent changes in dopamine receptor subtypes with age result in an altered complement of dopamine receptors in older humans and may provide a basis for selective pharmacotherapy in disorders of the basal ganglia.