CHRONIC TREATMENT WITH THE UNCOMPETITIVE NMDA RECEPTOR ANTAGONIST MEMANTINE INFLUENCES THE POLYAMINE AND GLYCINE BINDING-SITES OF THE NMDA RECEPTOR COMPLEX IN AGED RATS

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