Cognition-enhancing and anxiolytic effects of memantine.
Memantine, a moderate-affinity NMDA receptor antagonist, is clinically used for the treatment of Alzheimer's disease (AD). Both clinical and preclinical studies have shown that memantine, at doses producing a steady-state plasma level of 0.5-1 microM, is well tolerated and improves cognition. Here we tested the effects of chronic oral administration of memantine (10, 30 and 100mg/kg per day) producing steady state plasma drug levels ranging between approximately 0.5 and 6 microM on motor, social, emotional and cognitive behavior in normal C57BL/6J mice. Memantine dose-dependently reduced escape latency (hidden platform) and decreased wall swimming tendency in the Morris water maze test, increased time spent in open arms in the elevated plus-maze test, and reduced the number of isolation-induced aggressive attacks, but did not affect exploratory activity in the open field. These data indicate that high, stable doses of memantine improved cognition and exhibited a potential anxiolytic response in normal mice.
Minkeviciene
Rimante
R
Department of Neurobiology, A.I.Virtanen Institute for Molecular sciences, University of Kuopio, Kuopio, Finland.
Banerjee
Pradeep
P
Tanila
Heikki
H
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008559:Memantine / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011930:Reaction Time / Q000187:drug effects; D012934:Social Isolation; D013997:Time Factors
D014151:Anti-Anxiety Agents; D008559:Memantine