Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expressions of NR2A, NR2B, nAChR alpha 7, alpha 4 and beta 2. Forty male rats (16-18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin + ascorbic acid-treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin + ascorbic acid group (p < 0.05). While 8-hydroxy-2-deoxyguanosine and malondialdehyde levels were significantly decreased, NR2B and nAChRa7 expressions were significantly increased in the aspirin + ascorbic acid group as compared to the control group (p < 0.05). Subchronic treatment with aspirin + ascorbic acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process. (C) 2014 Elsevier B.V. All rights reserved.