Hyposensitivity to the amnesic effects of scopolamine or amyloid beta(25-35) peptide in heterozygous acetylcholinesterase knockout (AChE(+/-)) mice

Chem Biol Interact. 2008 Sep 25;175(1-3):131-4. doi: 10.1016/j.cbi.2008.04.001. Epub 2008 Apr 10.


We examined the sensitivity of AChE(+/-) mice to the amnesic effects of scopolamine and amyloid beta peptide. AChE(+/-) and AChE(+/+) littermates, tested at 5-9 weeks of age, failed to show any difference in locomotion, exploration and anxiety in the open-field test, or in-place learning in the water-maze. However, when treated with the muscarinic receptor antagonist scopolamine (0.5, 5mg/kg s.c.) 20 min before each water-maze training session, learning impairments were observed at both doses in AChE(+/+) mice, but only at the highest dose in AChE(+/-) mice. The central injection of Abeta(25-35) peptide (9 nmol) induced learning deficits only in AChE(+/+) but not in AChE(+/-) mice. Therefore, the hyper-activity of cholinergic systems in AChE(+/-) mice did not result in increased memory abilities, but prevented the deleterious effects of muscarinic blockade or amyloid toxicity.

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism*
  • Amnesia / chemically induced*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Heterozygote*
  • Maze Learning
  • Mice
  • Mice, Knockout
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Peptides / pharmacology*
  • Scopolamine / pharmacology*


  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptides
  • amyloid beta-protein (25-35)
  • Scopolamine
  • Acetylcholinesterase