[Abstract Title]. - Society for Neuroscience

1 EPHE, Univ. Montpellier II, INSERM U710, Montpellier, France; 2 INRA UMR 866,
Montpellier, France
Abstract: Decrease in acetylcholinesterase (AChE) expression or activity results in increased
cholinergic tonus in the brain or periphery, with concomittant regulations of nicotinic and
muscarinic receptors expression. We generated AChE knockout mice and characterized the
behavioral phenotype of heterozygous animals, particularly focusing on learning and memory
functions. Male and female, AChE+/- and AChE+/+ littermate controls (129/Sv strain), tested at
5-9 weeks of age, failed to show any difference in terms of locomotion, exploration and anxiety
parameters in the open-field test. Animals were then tested for place learning in the water-maze.
They were trained using a 'sustained acquisition' protocol (3 swims/day during 5 days) or a 'mild
acquisition' protocol (2 swims/day during 9 days) to locate an invisible platform in fixed position
(reference memory procedure). Then, during 3 days, they were trained to locate the platform in a
variable position (working memory procedure). Learning profiles and probe test performances
were unchanged in AChE+/- mice as compared with AChE+/+. Mice were then treated with the
muscarinic receptor antagonist scopolamine (0.5, 5 mg/kg sc) 20 min before each training
session (3 swims/day during 5 days). Scopolamine impaired learning at both doses in AChE+/+
mice, but only at the highest dose in AChE+/- mice. Moreover, the central injection of amyloid
beta25-35 peptide (9 nmol) 7 days before water-maze acquisition failed to induce learning
deficits in AChE+/- mice, contrarily to AChE+/+ controls. These behavioral study shows that the
increase in cholinergic tonus did not result in increased memory abilities in these heterozygous
AChE+/- mice, but allowed a significant prevention of the deleterious effects of muscarinic
blockade or amyloid toxicity. Major adaptations in the expression and activity of nicotinic and
muscarinic receptors have been observed in response to the chronic hypercholinergy in AChE-/-
mice, that have been suggested to contribute the limited efficacy of AChE inhibitors in
Alzheimer's disease. Our behavioral study suggest that such adaptations do not occur in
heterozygous mice.
This work is a project (#03) of the CompAn behavioral phenotyping facility (Montpellier,
France).
Disclosures: J. Espallergues , None; L. Galvan, None; L. lepourry, None; B. Bonnafos,
None; A. Chatonnet, None; T. Maurice, None.
Poster
290. Animal Cognition and Behavior: Learning and Memory: Pharmacology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 290.24/RR75
Topic: F.02.j. Learning and memory: Pharmacology