Effects of nicotine on spatial memory deficits in rats with septal lesions

Impaired septohippocampal function has been implicated in the memory deficits associated with Alzheimer's disease (AD), and septal lesions have been used to model the cognitive deficits associated with AD. In this study, we assessed the effects of systemic administration of nicotine on lesion-induced deficits in the acquisition of a spatial discrimination version of the Morris water maze. Rats with radiofrequency lesions of the medial septum were required to learn which of two visible platforms in a pool of water provided a means of escape. On each of the first 4 days of training, the rats received an injection of (-)nicotine (0, 0.1 or 0.3 mg/kg, i.p.) before training. Nicotine markedly improved the performance of septal rats. This enhanced performance was maintained in rats subsequently tested 1 and 15 days later without additional drug treatment. Septal rats initially trained under nicotine were impaired, however, when the platform locations were reversed and training was conducted under saline. Our findings suggest that nicotinic receptor stimulation might be useful in the treatment of cognitive deficits.