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

INSERM U. 710, Montpellier, France.
Chemico-Biological Interactions (Impact Factor: 2.58). 05/2008; 175(1-3):131-4. DOI: 10.1016/j.cbi.2008.04.001
Source: PubMed


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.

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