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 μM, is well tolerated and improves cognition. Here we tested the effects of chronic oral administration of memantine (10, 30 and 100 mg/kg per day) producing steady state plasma drug levels ranging between ∼0.5and 6 μM 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.