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Preservation of N-Methyl-D-Aspartate Receptor Binding Sites With Age in Rat Neocortex

^a Departments of Psychiatry and Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania

Alan M. Palmer, Vernalis Research Limited, 613 Reading Road, Winnersh, Wokingham, RG41 5UA, UK E-mail: a.palmer{at}vernalis.com.

Decision Editor: Jay Roberts, PhD

This study used [³H]dizocilpine ([³H]MK-801) binding to examine glycine, polyamine, and zinc subsites of the N-methyl-D-aspartate (NMDA) receptor in well-washed membranes derived from the neocortex of Fischer 344/Norwegian brown rats aged 3, 12, 24 and 37 months. [³H]dizocilpine binding in the presence of 100 µM glutamate was enhanced by the addition of 30 µM glycine. Binding in the presence of both glutamate and glutamate plus glycine were unaffected by age. The competitive polyamine site antagonist arcaine inhibited [³H]dizocilpine binding in a dose-dependent fashion and 50 µM spermidine caused a rightward shift in this dose response curve. IC₅₀ values derived from these plots were not significantly affected by age. Similarly, zinc inhibited binding in a dose-dependent fashion and was also unaffected by age. These data indicate that the NMDA receptor is spared in aging.