HALOPERIDOL INTERACTS WITH THE STRYCHNINE-INSENSITIVE GLYCINE SITE ATTHE NMDA RECEPTOR IN CULTURED MOUSE HIPPOCAMPAL-NEURONS

N-Methyl-D-aspartate (NMDA)-evoked responses in voltage-clamped hippoc ampal neurones in culture were reversibly, but not completely, attenua ted on superfusion with micromolar concentrations (0.1-100 muM) of hal operidol with an IC50 (+/- S.E.M.) value of 1.9 +/- 0.2 muM (n = 7). I n contrast, kainate- and pha-amino-3-hydroxy-5-methylisoxazole-4-propi onate (AMPA)-evoked responses were relatively unaffected on applicatio n of 50 muM haloperidol. The NMDA receptor antagonist action of halope ridol was neither competitive in nature nor voltage-dependent but was reduced upon elevation of the extracellular concentration of glycine. Furthermore, in the absence of added glycine haloperidol (at 0.1 muM) frequently potentiated NMDA-evoked responses. Haloperidol thus appears to be a partial agonist for the strychnine-insensitive glycine site a ssociated with the NMDA receptor-channel complex.