Chronic nicotine improves working and reference memory performance and reduces hippocampal NGF in aged female rats

The cholinergic system is involved in cognition and several forms of dementia, including Alzheimer's disease, and nicotine administration has been shown to improve cognitive performance in both humans and rodents. While experiments with humans have shown that nicotine improves the ability to handle an increasing working memory load, little work has been done in animal models evaluating nicotine effects on performance as working memory load increases. In this report, we demonstrate that in aged rats nicotine improved the ability to handle an increasing working memory load as well as enhanced performance on the reference memory component of the water radial arm maze task. The dose required to exert these effects (0.3 mg/kg/day) was much lower than doses shown to be effective in young rats and appears to be a lower maintenance dose than is seen in light to moderate smokers. In addition, our study reports a nicotine-induced reduction in nerve growth factor (NGF) protein levels in the hippocampus of the aged rat. The effects of nicotine on hippocampal NGF levels are discussed as a potential mechanism of nicotine-induced improvements in working and reference memory.