THE EFFECTS OF CHRONIC ADMINISTRATION OF NIMODIPINE ON AGE-RELATED-CHANGES IN NITRIC-OXIDE AND ITS SYNTHASE IN SENESCENCE-ACCELERATED MOUSE-BRAIN

The levels of nitric oxide (NO) and NO synthase (NOS) activities in th e brain of young-adult (3 months old), aged (11 moths old) and nimodip ine-administered (11 months old) senescence-accelerated mouse (SAM), o f which SAMP8 sub-strain is inferior in acquisition of learning and ha s a lower content in testosterone, were compared. Nimodipine, which is L-type calcium ion channel blocker and has memory-enhancing effects, was administered orally for 5 months. In the cerebral cortex of aged S AMP8, NOS activity was increased compared with that of young-adult SAM P8. Though nimodipine did not alter the contents of NO in any brain re gions compared with those in aged SAMP8, nimodipine increased NOS acti vity in the aged cerebellum. Our data suggest that nimodipine may incr ease NOS activity through elevation of testosterone level, as testoste rone increases NOS only in the cerebellum, although further work is cl early needed to ascertain effects of nimodipine on testosterone metabo lism and maintenance in the acquisition of learning.