Receptor binding studies on rat cortical membranes were used to characterize the NMDA receptor in aged rats (22 months) treated for 20 months with a memantine containing diet delivering 30 mg/kg/day in comparison to aged and young/adult rats treated with control-diet. Spatial memory impairing effects of (+)-MK-801 (0.16 mg/kg) in the radial maze was not altered within the course of memantine-treatment (up to 16 months). However, chronic memantine-treatment significantly increased the number of [3H]MK-801 binding sites and the affinity of [3H]glycine. A non-significant trend to such changes was also seen in aged-control rats. Glycine-dependent [3H]MK-801 binding (functional binding under non-equilibrium conditions at a fixed L-glutamate concentration) revealed that a decreased ability of glycine to stimulate channel opening in aged rats was partially attenuated by the long-term memantine treatment. Furthermore, an increased ability of spermidine to enhance [3H]MK-801 binding in aged-control rats was even more pronounced in the aged memantine-treated group. Together these findings may indicate that changes in functional receptor-channel properties during the process of aging occur prior to a detectable loss of binding sites and that memantine enhances an endogenous compensatory mechanism triggered by glutamatergic hypofunction which is suggested to take place in aging.