Chronic aspirin ingestion improves spatial learning in adult and aged rats

Abstract

Epidemiological evidence suggests that nonsteroidal, anti-inflammatory drugs (NSAIDs) may retard the progression of Alzheimer's disease (AD). In the present study, we have chronically treated adult (4¿5 months old) and aged (20+ months) rats with water adulterated with aspirin, and examined spatial learning in a swim maze. Adult rats (n=40) and aged rats (n=20) were divided into separate groups assigned to receive either normal drinking water or water with 2 mg/ml of aspirin dissolved in it. For 6 weeks, we monitored daily water and/or drug intake before testing all rats in a standard swim maze over an 8-day period. On average, each rat drank approximately 25 ml of water/day with no apparent control versus aspirin group differences. There was no effect of aspirin in young adult rats except during a visible platform trial where aspirin-treated rats performed better than controls. In contrast, aspirin markedly improved performance in the aged rats during hidden and visible platform trials. Such group differences abated by the eighth test day when all rats performed equally well. The improvements in performance were not correlated with changes in swim speeds indicating that the enhancement was not due to facilitated motor output. These data reveal that a modest, 6-week treatment regimen with aspirin in aged rats is sufficient to induce improvements in both speed of learning and strength of the learned response. We have yet to address the key question as to underlying physiological mechanism(s) that might underpin this augmented cognitive performance. Moreover, it would be useful to ascertain whether or not chronic NSAID treatment might reduce the extent of learning impairments in aged, cognitively impaired animals.