Region-specific loss of alpha 1-adrenergic receptors in rat brain with aging: a quantitative autoradiographic study

The effects of aging on the density and affinity of alpha 1-adrenergic receptors (alpha 1-ARs) were studied in several circumscribed areas of the Fischer 344 male rat brain. Computer-assisted quantitative autoradiography was used to analyze saturation binding isotherms of [125I]BE-2254, a selective alpha 1-AR antagonist. Significant decreases in receptor density of 15 and 29% were observed in the thalamus at 16-18 and 24-28 months of age, respectively, when compared to 3-4-month-old controls. Progressive declines in receptor density of 24 and 44% were also found in the olfactory tubercle. In the cerebral cortex, a significant 26% loss in receptors occurred only in the oldest age group. No changes were found in any of the other brain areas investigated, including the cerebellum, brainstem, caudate-putamen, and several subregional areas of the hippocampal formation. Kd values ranged from 12 +/- 1.8 pM in the brainstem to 23 +/- 1.6 pM in the thalamus and were not affected by aging in any area examined. It is concluded that the density of alpha 1-ARs in the Fischer 344 rat brain is diminished with aging in a region-specific manner and that loss of these receptors may account for age-related functional deficits only in a few brain areas.