N-METHYL-D-ASPARTATE (NMDA) AND NON-NMDA BINDING-SITES IN DEVELOPING HUMAN FRONTAL-CORTEX

The binding levels of [H-3]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [H-3]kainate and [H-3](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10 -1min (MK-801) were examined in human frontal cortex homogenates ranging from 24 weeks gestation to old age. Different developmental profiles were revealed for each ligand. [H-3]kainate binding peaked sharply in the neonate, declining precipitantly during the first year and returning to foetal levels by the first or second decade, with no further decline. [H-3]AMPA binding was also highest in the neonate, declining by the first decade to foetal levels and showing little or no further decline. [H-3]MK-801 binding in the presence of glutamate, glycine and spermidine rose sharply from the foetal and neonatal stages to peak from about 3 months of age, with elevated binding until the first or second decade and a subsequent decline throughout the whole age range. The pronounced developmental peak in [H-3]kainate binding implicates this receptor in the organisation of neuronal pathways, and in vulnerability to hypoxia and ischaemia at birth.