title: Chronic treatment with the uncompetitive NMDA receptor antagonist memantine influences the polyamine and glycine binding sites of the NMDA receptor complex in aged rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Merz + Co. GmbH & Co., Frankfurt/Main, Federal Republic of Germany.
authors.forename: I
authors.initials: I
authors.lastname: Bresink
authors.forename: W
authors.initials: W
authors.lastname: Danysz
authors.forename: C G
authors.initials: CG
authors.lastname: Parsons
authors.forename: P
authors.initials: P
authors.lastname: Tiedtke
authors.forename: E
authors.initials: E
authors.lastname: Mutschler
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008559:Memantine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013095:Spermidine / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D018696:Neuroprotective Agents; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D005998:Glycine; D013095:Spermidine; D008559:Memantine