Agmatine selectively improves behavioural function in aged male Sprague-Dawley rats

L-arginine, a semi-essential amino acid, can be metabolized to form a number of bioactive molecules. Nitric oxide (NO), generated by NO synthase (NOS) from L-arginine, has been strongly implicated in the aging process. Agmatine, decarboxylated arginine, regulates the production of NO and other metabolites of L-arginine, modulates behavioural function, and has anti-inflammatory and neuroprotective effects. The present study investigated whether agmatine supplementation could improve behavioural function in aged male Sprague-Dawley rats, and could attenuate age-related changes in NOS activity and protein expression in memory-related structures. Aged rats treated with saline displayed significantly reduced exploratory activity and impaired spatial reference and working memory and object recognition memory. Agmatine (40 mg/kg) administered intraperitoneally significantly improved spatial working memory and object recognition memory in aged rats, suppressed age-related elevation in total NOS activity, and restored endothelial NOS protein to the normal level. However, agmatine supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings suggest that exogenous agmatine selectively improves behavioural function in aged rats under the present experimental condition, and merit future investigation of its therapeutic potential in cognitive decline during aging.