title: Effect of nicotine on neuronal dysfunction induced by intracerebroventricular infusion of amyloid-β peptide in rats.
abstract: 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.
  
  
  METHODS
  Neuronal dysfunction in rats was induced by an infusion of Aβ(1-42) (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 Aβ(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.
authors: Asubio Pharma Co., Limited, Kobe, Japan. noshita.takafumi.eb@asubio.co.jp.
authors: T
authors: T
authors: Noshita
authors: N
authors: N
authors: Murayama
authors: S
authors: S
authors: Nakamura
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016229:Amyloid beta-Peptides; D018722:Nicotinic Agonists; D009538:Nicotine; D002795:Choline O-Acetyltransferase