EFFECT OF ROLIPRAM ON AGE-RELATED-CHANGES IN CYCLIC AMP-SELECTIVE PHOSPHODIESTERASE IN THE RAT-BRAIN - AN AUTORADIOGRAPHIC STUDY

Rolipram is a clinically effective antidepressant with cyclic AMP-sele ctive phosphodiesterase (cyciic-AMP PDE) inhibiting action. In this st udy we investigated the effect of chronic treatment with rolipram on a ge-related changes in cyclic-AMP PDE in the mt brain visualized and qu antitated by in vitro [H-3]rolipram autoradiography. Rolipram (0.01 mg /kg and 0.1 mg/kg) or its vehicle was administered orally to 15-week-o ld (young) and 80-week-old (aged) Wistar rats once a day for 4 weeks. In control young rats, high [H-3]rolipram binding was seen in the hipp ocampus, the cerebellum and the neocortex. In control aged rats, the [ H-3]rolipram binding decreased strikingly in almost all brain regions. Chronic treatment of the young rats with rolipram reduced the [H-3]ro lipram binding in a dose-dependent manner. By contrast, the same treat ment of the aged rats induced no or minimal changes. These results sug gest that 1) cyclic-AMP PDE in the rat brain is subject to age-associa ted decline and 2) the response to rolipram treatment is different bet ween young and aged rats. (C) 1998 Prous Science. All rights reserved.