Impaired Recovery of Alpha1-and Alpha2-adrenergic Receptors in Brain Tissue of Aged Rats

Abstract

The influence of age on the rate of recovery of alpha 1- and alpha 2-adrenergic receptors was determined in rat brain following their irreversible inhibition by phenoxybenzamine (PBZ). Fischer 344 rats (3- or 24-months old) were administered two doses of vehicle or PBZ at 12-hour intervals. At various times after the last dose of PBZ, alpha-adrenergic receptors were quantified in washed membranes of cerebral cortex and hypothalamus, using [3H]prazosin and [3H]rauwolscine to label alpha 1- and alpha 2-adrenergic receptors, respectively. Recovery of prazosin binding sites in cortex and hypothalamus and of rauwolscine binding sites in cortex was significantly delayed in aged versus young rats. Administration of [3H]PBZ to young and aged rats revealed no apparent differences in the concentration or rate of disappearance of PBZ or its metabolites that could account for these age-related changes. These data suggest that the synthesis of both alpha 1- and alpha 2-adrenergic receptors is impaired in brain tissue from aged rats.