Ability of aged rats to alter beta adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine.

Repeated administration of reserpine to 3-month-old rats produced dose-related increases in [3H]dihydroalprenolol (DHA) binding in pineal gland, cerebral cortex and cerebellum. Reserpine increased DHA binding by increasing the density of beta adrenergic receptors. Brain tissue from 24-month-old rats, however, had an impaired ability to increase receptor density in response to reserpine treatment, even in the pineal gland where the concentration of reserpine was nearly 7 times that found in the glands of young rats given the same dose on the basis of body weight. Repeated administration of desmethylimipramine decreased DHA binding in pineal glands by about 50% and in cerebral cortices by about 25%, but did not alter DHA binding in the cerebellum. The magnitude of these changes was similar in the 3- and 24-month-old rats, although the concentration of desmethylimipramine in the pineal glands and cerebral cortices of the aged rats was significantly higher than that of the young animals. The results indicate that the reserpine-induced decrease in noradrenergic input causes a compensatory increase in beta adrenergic receptor density in rat brain. They suggest further that although aged rats can decrease receptor density in response to increased adrenergic input, they have an impaired ability to increase beta adrenergic receptor density in response to decreased adrenergic input. This finding may explain the decreased density of beta adrenergic receptor found in aged rat brain.