Effect of rolipram on age-related changes in cyclic AMP-selective phosphodiesterase in the rat brain: an...

Rolipram is a clinically effective antidepressant with cyclic AMP-selective phosphodiesterase (cyclic-AMP PDE) inhibiting action. In this study, we investigated the effect of chronic treatment with rolipram on age-related changes in cyclic-AMP PDE in the rat brain visualized and quantitated by in vitro [3H]rolipram autoradiography. Rolipram (0.01 mg/kg and 0.1 mg/kg) or its vehicle was administered orally to 15-week-old (young) and 80-week-old (aged) Wistar rats once a day for 4 weeks. In control young rats, high [3H]rolipram binding was seen in the hippocampus, the cerebellum and the neocortex. In control aged rats, the [3H]rolipram binding decreased strikingly in almost all brain regions. Chronic treatment of the young rats with rolipram reduced the [3H]rolipram binding in a dose-dependent manner. By contrast, the same treatment of the aged rats induced no or minimal changes. These results suggest that 1) cyclic-AMP PDE in the rat brain is subject to age-associated decline, and 2) the response to rolipram treatment is different between young and aged rats.