Cognitive deficits in aged rats correlate with levels of l-arginine, not with nNOS expression or 3,4-DAP-evoked transmitter release in the frontoparietal cortex

Aging is associated with altered neurotransmitter function in the brain. In this study, we measured release parameters for acetylcholine (ACh), norepinephrine and serotonin in the frontoparietal cortex of young and aged rats. We also determined cortical amino acid concentrations and nitric oxide (NO) synthase function. Prior to sacrifice, the rats had been tested for Morris water-maze performance. In aged, compared with young rats, we observed a reduction in both uptake of choline and acetylcholine release. Serotonin release and l-arginine concentrations (a precursor of NO) showed an aging-related increase; however, l-citrulline/l-arginine ratios were decreased in aged rats. Moreover, while most age-related changes in transmitter release or neurochemical markers were not related to the learning performance, l-arginine concentrations were positively correlated to cognitive deficits. NO synthase concentrations were not affected by aging. It is suggested that events related to l-arginine-to-l-citrulline/NO metabolism in the frontoparietal cortex may take part in age-related cognitive deficits.