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

Julie Espallergues (1) , Laurie Galvan (2) , Laurence Lepourry (3) , Béatrice Bonafos (3) , Tangui Tm Maurice (4) , Arnaud Chatonnet (3)

1 IGF - Institut de Génomique Fonctionnelle
2 Center for Neurobehavioral Genetics, Semel Institute
3 DCC - Différenciation Cellulaire et Croissance
4 MMDN - Mécanismes moléculaires dans les démences neurodégénératives

We examined the sensitivity of AChE(+/-) mice to the amnesic effects of scopolamine and amyloid 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 A beta(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.

Mots clés: LEARNING AND MEMORY; FORCED SWIMMING; ACETYLCHOLINESTERASE; KNOCKOUT MOUSE

Mots clés: SCOPOLAMINE; AMYLOID PEPTIDE; APPRENTISSAGE

Domaines: Neurosciences [q-bio.NC]

Julie Espallergues, Laurie Galvan, Laurence Lepourry, Béatrice Bonafos, Tangui Tm Maurice, et al.. Hyposensitivity to the amnesic effects of scopolamine or amyloid β25–35 peptide in heterozygous acetylcholinesterase knockout (AChE+/−) mice. Chemico-Biological Interactions, 2008, 175 (1-3), pp.131-134. ⟨10.1016/j.cbi.2008.04.001⟩. ⟨hal-02459753⟩