Age-related effects of rolipram on [3H]quinuclidinyl benzilate and [3H]phorbol 12,13-dibutyrate binding in the rat brain.

Abstract

Cholinergic neurotransmission and protein kinase C (PKC) in the brain play important roles in the processes of cognitive function. In this study, we examined the effect of chronic treatment with rolipram, a 3',5'-cyclic adenosine monophosphate (cyclic AMP)-selective phosphodiesterase inhibitor, on age-related changes in [3H]quinuclidinyl benzilate (QNB) and [3H]phorbol 12,13-dibutyrate (PDBu) binding, which labeled brain muscarinic cholinergic receptors and PKC, respectively. Rolipram was administered per os to young (15 weeks old) and old (80 weeks old) Wistar rats at dosage of 0.01 mg/kg and 0.1 mg/kg once a day over 4 weeks. Then, quantitative in vitro autoradiography was performed. Control old rats showed elevations in [3H]PDBu binding in the hippocampus and the cerebellum compared to young rats, but [3H]QNB binding was largely unchanged. Chronic treatment of the old rats with the higher dose of rolipram led to reductions in [3H]QNB and [3H]PDBu binding in many brain regions. However, the same treatment of the young rats induced no or minimal effect. Thus, the response of the brain to rolipram was different between young and old rats. These results suggest that the cyclic AMP-selective phosphodiesterase system in the brain is modified during aging, modulating subsequently cholinergic neurotransmission and PKC activity exclusively in old rat brains.