Rapid visualization of NMDA receptors in the brain: characterization of (+)-3-[125I]-iodo-MK-801 binding to thin sections of rat brain.

We have developed and characterized a method for the rapid autoradiographic determination of receptor sites for the non-competitive NMDA receptor antagonist, MK-801, using an iodinated form of the compound, (+)-3-[125I]-iodo-MK-801. The binding site was shown to exhibit those criteria necessary for its definition as a receptor site, i.e., the binding was saturable, of high affinity, easily reversible, and stereospecific. Saturation analysis of binding to thin brain sections revealed a Bmax of 108.1 +/- 10.5 fmol/mg protein and a Kd of 383 +/- 67 pM. The pharmacology of the interaction of the ligand with the binding site yielded good correlation between the potency of various substances to complete for the binding site and their ability to act as antagonists of NMDA. Autoradiographs of thin coronal brain sections using (+)-3-[125I]-iodo-MK-801 yielded high quality images in 24-48 h with a distribution of binding sites paralleling that reported for the tritiated form of the ligand, i.e., with high densities in the hippocampus, cerebral cortex and lateral septum. Other areas with significant binding included parts of the thalamus, the amygdala and the olfactory tubercules. Furthermore, due to its high specific activity, this ligand lends itself to the study of regions not rich in MK-801 binding sites, such as the diencephalon.