Effect of nicotine on neuronal dysfunction induced by intracerebroventricular infusion of amyloid-β peptide in rats

OBJECTIVE: The aim of the study was to investigate the effects of nicotine on learning and memory deficits induced by intracerebroventricular infusion of amyloid-beta peptide (A beta) in rats. MATERIALS AND METHODS: Neuronal dysfunction in rats was induced by an infusion of A beta(1-42) (20 mu g/body, over 3 days) into right ventricle. Nicotine was administered intraperitoneally to the rats at 0.2 mg/kg, once a day for 9 weeks beginning 3 weeks after the A beta infusion. Learning and memory functions were examined by behavioral tests including Morris water maze task performed on days 87-90. As biochemical analyses, choline acetyltransferase (ChAT) activity and hemicholinium-3 (HC-3) binding were measured in brain tissues after the behavioral examination. RESULTS: The A beta infusion induced significant learning and memory deficits in rats, judging from the behavioral tests. Treatment of the rats with nicotine significantly improved the A beta-induced learning and memory deficits in water maze task. The A beta infusion also decreased significantly not only the level of ChAT activity in posterior cortex and striatum, but the HC-3 binding in anterior cortex, posterior cortex, and hippocampus. The nicotine treatment did not reverse the level of ChAT but significantly inhibited the decrease in HC-3 binding, indicating improvement of cholinergic function without affecting the number of ACh terminals. CONCLUSIONS: Nicotine ameliorated learning and memory deficits in the A beta(1-42)-induced animal model, which is mediated, at least in part, by enhancement of cholinergic neurotransmission. nAChR ligands including nicotine is thought to be useful as a treatment for Alzheimer's disease.