[3H]MK-801 binding and the mRNA for the NMDAR1 subunit of the NMDA receptor are differentially distributed in human and rat forebrain

The distributions of [3H]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 protein detected by radioligand autoradiography and the mRNA for the key subunit of the receptor presented similar distributions in the forebrain, 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 [3H]MK-801 binding. The same area in rat brain did not show any difference in the two distributions. In comparison, the rat claustrum presented a relative excess of NMDAR1 mRNA which was not detected in human sections. Human caudate nucleus exhibited relatively high levels of [3H]MK-801 binding that were unmatched in rat caudate. The hippocampi of either species presented similar levels of [3H]MK-801 binding and NMDAR1 mRNA, but when the two signals were measured in specific subfields of the hippocampal formation, the differential distribution of the two signals reflected the anatomy of hippocampal connections assuming a preferential dendritic distribution for MK-801 binding. Interestingly, rat and human hippocampi also showed some important species-dependent difference in the relative distribution of the receptor protein and mRNA. The data presented show an overall good correlation between the mRNA for the key subunit of the NMDA receptor and the functional receptor detected with radioligand binding and highlight the presence of local differences in their ratio. This may reflect different splicing of the mRNA for the NMDAR1 subunit in specific brain areas of rat and human. The species-dependent differences in the relative distribution of the mRNA for the key subunit of the NMDA receptor and that of a marker of functional receptors also highlights important differences in the NMDA function in rat and human brain.