Differences in the neurotoxicity of simultaneous application of AMPA and IDRA-21 (A) or AMPA and cyclothiazide (B) in primary cultures of cerebellar granule cells. The ordinate shows % neuronal death (mean ± SEM = 6) measured 24 hrs after a 60 min exposure. Where indicated dizocilpine was added 5 min prior to the simultaneous application of AMPA and one of the two modulators. ∗, P < 0.01 when AMPA/IDRA-21- or AMPA/cyclothiazide-treated neurons were compared with control treated neurons or with neurons treated with IDRA-21 or cyclothiazide without AMPA. #, P < 0.01 when AMPA/IDRA-21- or AMPA/cyclothiazide-treated neurons in the presence of dizocilpine were compared with neurons receiving the same drug treatment combination without dizocilpine. a, P < 0.05 when AMPA/cyclothiazide/dizocilpine-treated neurons were compared with neurons treated with AMPA or with cyclothiazide without AMPA. Note that 50 μM AMPA, 10 or 25 μM cyclothiazide, and 100–250 μM IDRA-21 per se failed to produce a significant increase of neuronal death. Results similar to those reported in A and B were obtained in at least four other experiments with different batches of cerebellar granule cells.