title: Subchronic memantine administration on spatial learning, exploratory activity, and nest-building in an APP/PS1 mouse model of Alzheimer's disease.
abstract: Glutamate neurotoxicity has been proposed to be involved in Alzheimer pathogenesis, with clinical data supporting successful treatment with the NMDA receptor antagonist memantine. In the present study, the effects of subchronic memantine administration were assessed on spatial and non-spatial learning as well as exploratory activity and nest-building in APP/PS1 mutant mice. Memantine (10 mg/kg, i.p.) was better than placebo during the reversal phase of left-right discrimination, though equivalent to saline for Morris water maze and passive avoidance learning. The drug had no effect on non-learned behaviors in elevated plus-maze exploration and nest-building. These results support a specific action of the NMDA receptor antagonist on behavioral flexibility in mutant mice with amyloid pathology.
authors.affiliation: Laboratory of Endocrinology and Genomics, CHUQ Research Center and Department of Molecular Medicine, Laval University, 2705 Boulevard Laurier, Québec G1V 4G2, Canada. Mohammed.Filali@crchul.ulaval.ca
authors.forename: Mohammed
authors.initials: M
authors.lastname: Filali
authors.forename: Robert
authors.initials: R
authors.lastname: Lalonde
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009425:Nesting Behavior / Q000187:drug effects*; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; D018691:Excitatory Amino Acid Antagonists; D053764:Presenilin-1; D008559:Memantine