NMDA-induced responses are modulated by mGluR compounds in the absence of exogenously expressed mGluRs (A). Whole-cell responses from HEK293 cells transfected with NR1–1a and NR2A NMDA receptor subunits. Currents are induced by application of 30 μM NMDA (N) and 10 μM glycine (G) before, during, and after coapplication of DHPG (D) (100 μM), to cells voltage clamped at −70 mV. (B) Whole-cell response induced by 50 μM NMDA and 10 μM glycine from a Xenopus oocyte injected with NR1–1a/NR2A RNAs. NMDA currents were recorded before, during and after coapplication of DHPG (100 μM). (C) Responses from oocytes due to coapplication of various mGluR agonists and antagonists with 50 μM NMDA and 10 μM glycine expressed as a percentage of the control response. The concentrations of the drugs tested were: (S)-MCPG, 100 μM; (RS)-DHPG, 100 μM; (S)-3-HPG, 100 μM; (1S, 3R)-ACPD, 100 μM; trans-ADA, 100 μM; dl-AP4, 1 mM; AIDA, 200 μM. (D–F) Responses from coapplication of the mGluR compounds at these concentrations with NMDA and glycine at the concentrations indicated. See Table 1 for number of observations (asterisks denote significance using a one-sample Student’s t test: ∗, P < 0.05; ∗∗, P < 0.01; ∗∗∗, P < 0.001).