Chronic memantine administration prevents ouabain-induced hyperactivity in mice via maintenance of Na+, K+-ATPase activity in the hippocampus

Abstract We have previously reported that mice received intracerebroventricular injection of ouabain, an inhibitor of Na + , K + -ATPase, exhibited hyperactivity via overactivation of glutamatergic neurons. Here we investigated the effects of memantine, a blocker of N -methyl- d -aspartate receptors, on ouabain-induced hyperactivity. In mice that received ouabain injection, chronic memantine administration prevented the hyperactivity and the decrease in the Na + , K + -ATPase activity in the hippocampus. Memantine also protected neurons without affecting glial activation in the hippocampus of these mice. Our results suggest that memantine improves hyperactivity via the maintenance of Na + , K + -ATPase activity and neurons in the hippocampus in this mouse model.