[H-3]MK-801 BINDING AND THE MESSENGER-RNA FOR THE NMDAR1 SUBUNIT OF THE NMDA RECEPTOR ARE DIFFERENTIALLY DISTRIBUTED IN HUMAN AND RAT FOREBRAIN

The distributions of [H-3]MK-801 binding and the NMDA NR1 subunit mRNA were studied using receptor autoradiography and in-situ hybridization in rat and human brain whole-hemisphere coronal sections. Receptor pr otein detected by radioligand autoradiography and the mRNA for the key subunit of the receptor presented similar distributions in the forebr ain, with a few areas showing an imbalance between the levels of mRNA and receptor protein. Human frontal cortex showed a relative abundance of NMDAR1 mRNA as compared to [H-3]MK-801 binding. The same area in r at brain did not show any difference in the two distributions. In comp arison, the rat claustrum presented a relative excess of NMDAR1 mRNA w hich was not detected in human sections. Human caudate nucleus exhibit ed relatively high levels of [H-3]MK-801 binding that were unmatched i n rat caudate. The hippocampi of either species presented similar leve ls of [H-3]MK-801 binding and NMDAR1 mRNA, but when the two signals we re measured in specific subfields of the hippocampal formation, the di fferential distribution of the two signals reflected the anatomy of hi ppocampal connections assuming a preferential dendritic distribution f or MK-801 binding. Interestingly, rat and human hippocampi also showed some important species-dependent difference in the relative distribut ion of the receptor protein and mRNA. The data presented show an overa ll good correlation between the mRNA for the key subunit of the NMDA r eceptor and the functional receptor detected with radioligand binding and highlight the presence of local differences in their ratio. This m ay reflect different splicing of the mRNA for the NMDAR1 subunit in sp ecific brain areas of rat and human. The species-dependent differences in the relative distribution of the mRNA for the key subunit of the N MDA receptor and that of a marker of functional receptors also highlig hts important differences in the NMDA function in rat and human brain. (C) 1998 Elsevier Science B.V.