Human caudate nucleus, putamen, substantia nigra, and nucleus accumbens were analyzed for the effects of age on dopaminergic binding sites. Decreases in the number of dopaminergic binding sites were detected with age in caudate nucleus (44 specimens from three sample groups) and substantia nigra (n = 12). In caudate nucleus, the decline in [3H]2-amino-6, 7-dehydroxy-1, 2, 3, 4-tetrahydronaphthalene sites was three times greater than for [3H]spiperone, but age changes were significant in only two of the three sampling groups. No age changes in binding were detected in the putamen (n = 44) or nucleus accumbens. Age, sex, and tissue source all significantly contributed to variance. However, cause of death, time from death to tissue freezing, and length of storage did not influence dopaminergic binding in the caudate nucleus or putamen. Relative to the life-span, the age-correlated decrease in dopaminergic binding sites of human brain approximates that in aging rodent striatum. Comparisons of altered dopaminergic binding with other age-correlated changes suggest that neuronal loss may not be involved in the loss of binding sites before midlife.

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Aging was associated with an increase in the density of specific binding sites for [3H]imipramine in postmortem specimens of human hypothalamus, frontal cortex, and parietal cortex. In general, [3H]imipramine binding was not affected by factors considered difficult to control in postmortem studies, i.e., time from death to autopsy and cause of death. The in vitro regulation of [3H]imipramine binding by sodium was impaired with age in hypothalamic homogenates. In vitro regulation of [3H]imipramine binding by chloride was intact. Determination of the concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid in hypothalamus and frontal cortex indicated no apparent age-related changes in indole metabolism. The age-related increase in brain [3H]imipramine binding and impairment in the in vitro regulation of binding by ions are similar to changes observed previously in aged mouse brain. The increase in brain antidepressant binding sites is discussed in relationship to other indices of brain serotonergic function in aging and to the relationship of [3H]imipramine binding and depression.

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