Hyposensitivity to the amnesic effects of scopolamine or amyloid beta(25-35) peptide in heterozygous acetylcholinesterase knockout (AChE(+/-)) mice.
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.
INSERM U. 710, Montpellier, France.
Julie
J
Espallergues
Laurie
L
Galvan
Laurence
L
Lepourry
Béatrice
B
Bonafos
Tangui
T
Maurice
Arnaud
A
Chatonnet
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000647:Amnesia / Q000139:chemically induced*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006579:Heterozygote; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C074636:amyloid beta-protein (25-35); D012601:Scopolamine; D000110:Acetylcholinesterase