Role of nitric oxide in the effect of aging on spatial memory in rats.

Since there is evidence that nitric oxide (NO) plays an important role as a diffusible messenger in learning and memory, we examined the role played by NO in the effect of aging on spatial memory in rats. The performance of aged rats (30 months old) in a radial-arm maze task was significantly impaired compared to that of adult rats (3 months old). The number of neurons containing NADPH-diaphorase (NADPH-d) reactivity in the cerebral cortex and striatum of aged rats was significantly less than that in the adult rats. The daily administration of NG-nitro-L-arginine methyl ester (L-NAME; 10-60 mg/kg, i.p.) resulted in a dose-dependent impairment of acquisition in the radial-arm maze task, while it failed to affect previously acquired performance, i.e., retention, in the adult rats. The content of 5-hydroxyindoleacetic acid in the hippocampus and of 3,4-dihydroxyphenylacetic acid in the striatum was significantly decreased and increased, respectively, in the L-NAME (60 mg/kg/day)-treated adult rats compared with that in controls. These findings demonstrate that NO production in the brain may be decreased in aged rats, suggesting that this alteration may be involved in memory processes, especially in the acquisition, but not in the retention, of spatial learning in rats, and further, that endogenous NO may be involved in the regulation of dopamine and 5-hydroxytryptamine metabolism.