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

T. Noshita, N. Murayama, S. Nakamura

Asubio Pharma Co., Limited, Kobe, Japan. noshita.takafumi.eb@asubio.co.jp

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• Pharmacology

OBJECTIVE: The aim of the study was to investigate the effects of nicotine on learning and memory deficits induced by intracerebroventricular infusion of amyloid-β peptide (Aβ) in rats.

MATERIALS AND METHODS: Neuronal dysfunction in rats was induced by an infusion of Aβ1-42 (20 µg/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 Aβ 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 Aβ infusion induced significant learning and memory deficits in rats, judging from the behavioral tests. Treatment of the rats with nicotine significantly improved the Aβ-induced learning and memory deficits in water maze task. The Aβ 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 Aβ1-42-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.

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