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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002421:Caudate Nucleus / Q000032:analysis* / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004298:Dopamine / Q000032:analysis; D005260:Female; D005476:Fluphenazine / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000032:analysis* / Q000201:enzymology; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000032:analysis*; D013134:Spiperone / Q000378:metabolism
D011954:Receptors, Dopamine; D013134:Spiperone; D002795:Choline O-Acetyltransferase; D005476:Fluphenazine; D004298:Dopamine