Regionally Distinct N -Methyl-D-Aspartate Receptors Distinguished by Quantitative Autoradiography of [ 3 H]MK-801 Binding in Rat Brain

Quantitative autoradiography of [ 3 H]MK-801 binding was used to characterize regional differences in N -methyl-d-aspartate (NMDA) receptor pharmacology in rat CNS. Regionally distinct populations of NMDA receptors were distinguished on the basis of regulation of [ 3 H]MK-801 binding by the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). CPP inhibited [ 3 H]MK-801 binding in outer cortex (OC) and medial cortex (MC) with apparent K i values of 0.32-0.48 Μ M , whereas in the medial striatum (MS), lateral striatum (LS), CA1, and dentate gyrus (DG) of hippocampus, apparent K i values were 1.1-1.6 Μ M . In medial thalamus (MT) and lateral thalamus (LT) the apparent K i values were 0.78 Μ M . In the presence of added glutamate (3 Μ M ), the relative differences in apparent K i values between regions maintained a similar relationship with the exception of the OC. Inhibition of [ 3 H]MK-801 binding by the glycine site antagonist 7-chlorokynurenic acid (7-ClKyn) distinguished at least two populations of NMDA receptors that differed from populations defined by CPP displacement. 7-ClKyn inhibited [ 3 H]MK-801 binding in OC, MC, MS, and LS with apparent K i values of 6.3-8.6 Μ M , whereas in CA1, DG, LT, and MT, K i values were 11.4-13.6 Μ M . In the presence of added glycine (1 Μ M ), the relative differences in apparent K i values were maintained. Under conditions of differential receptor activation, regional differences in NMDA receptor pharmacology can be detected using [ 3 H]MK-801 binding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65616/1/j.1471-4159.1993.tb03295.x.pd