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.