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 the brain of young-adult (3 months old), aged (11 moths old) and nimodipine-administered (11 months old) senescence-accelerated mouse (SAM), of which SAMP8 sub-strain is inferior in acquisition of learning and has 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 SAMP8, NOS activity was increased compared with that of young-adult SAMP8. Though nimodipine did not alter the contents of NO in any brain regions compared with those in aged SAMP8, nimodipine increased NOS activity in the aged cerebellum. Our data suggest that nimodipine may increase NOS activity through elevation of testosterone level, as testosterone increases NOS only in the cerebellum, although further work is clearly needed to ascertain effects of nimodipine on testosterone metabolism and maintenance in the acquisition of learning.