Developmental maturation of the N-methyl-d-aspartic acid receptor channel complex in postnatal rat brain

Abstract

The N-methyl-d-aspartate (NMDA) receptor plays an important role in developmental plasticity. Previous studies have reported differences between the NMDA receptor-channel complex in the rat pup brain and the adult brain. In the present study, modulation of the NMDA channel complex as a function of age was measured to determine when the temporal switching of the NMDA receptor from the immature form to the adult mature form takes place. [3H]MK-801 binding was measured in the rat forebrain from postnatal day 1 to day 21. Our data suggest the presence of two types of NMDA receptors — an immature type and a mature type. The immature NMDA receptor, seen during the early postnatal period (day 1–day 14) is highly sensitive to spermidine, l-glutamate alone potentiates [3H]MK-801 binding, and glycine failed to potentiate an l-glutamate-induced increase in [3H]MK-801 binding. During the late postnatal period (after day 14) spermidine alone did not increase [3H]MK-801 binding as potently as it did during the early postnatal period, high-affinity [3H]MK-801 binding was not seen in the presence of l-glutamate alone, and l-glutamate and glycine or l-glutamate and spermidine or l-glutamate, glycine and spermidine together, significantly increased [3H]MK-801 binding in a manner similar to that reported in the adult brain. Together, the pharmacology of the NMDA receptor during the early postnatal period differs from the adult-like receptor seen during the late postnatal period, and that in rats the apparent switching of the NMDA receptor from the immature type to the mature type takes place after the second postnatal week.