Simultaneous determination of binding of a variety of radioligands related to ionotropic excitatory amino acid receptors in fetal and neonatal rat brains

Expression of ionotropic excitatory amino acid receptors was assessed by membrane binding assays using a variety of radioligands in fetal and neonatal rat brains. In fetal rat brain, receptors sensitive to N-methyl-D-aspartate (NMDA) exhibited delayed onset of expression during the last 7 days before birth as compared with those insensitive to NMDA. In addition, developmental increases in agonist-preferring sites preceded those in antagonist-preferring sites within the first 7 postnatal days in particular brain structures with respect to each domain on the NMDA receptor complex. Growth of animals led to drastic increments of [H-3](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cSicIohepten-5,1 0-imine (MK-801) binding to the NMDA channel in telencephalic regions until 21 to 28 days after birth, with concomitant desensitization to inhibition by protons of [H-3]MK-801 binding in cortical membranes. By contrast, three different agonists were invariably effective in more potently potentiating [H-3]MK-801 binding in cortical membranes of 14- and 28-days-old rats than in those of 5-day-old rats. These results suggest that the NMDA-sensitive subclass may play more critical roles in mechanisms underlying postnatal development of rat telencephalon than do the NMDA-insensitive subclasses.