Hyposensitivity to the amnesic effects of scopolamine or amyloid β25–35 peptide in heterozygous acetylcholinesterase knockout (AChE) mice

We examined the sensitivity of AChE^+/− mice to the amnesic effects of scopolamine and amyloid β 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, 5 mg/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 Aβ_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.