The expression of GPCRs reduces NMDAR activity. Cortical cell cultures from WT and CNR1-/- mice were exposed to NMDA for 24 h. * Significant difference compared to WT cultured neurons, p < 0.05. Cell death induced by NMDA was also determined in cultures transfected with CNR1, serotonin receptor type 1A (5HT1AR), Mu-opioid receptor (MOR) and dopaminergic receptor type 2 (D2R). Φ Significant difference in the CNR1-/- cultured neurons that were not transfected with the corresponding GPCR, p < 0.05. The data shown represent the mean ± S.E.M. from 12 wells per experimental group. Inset to CNR1 group: Fluorescence photomicrograph of CNR1-/- cortical cell cultures showing the expression of transfected CNR1 using Abs against CNR1 (green) and MAP2 (red). The nuclei were counterstained with 4,6-diamidino-2-phenylindole. Bottom: The cells were immunolabelled with an anti-MAP2 Ab (green) and assayed following treatment with vehicle (A and D), 30 μM of NMDA (B and E) or 30 μM of NMDA plus 100 nM of WIN55,212-2 (C and F). The expression of HINT1 in the CNR1-/- cortical cell cultures is shown.