N-methyl-D-aspartate-induced neuronal activation is selectively modulated by σ receptors

The effects of two high-affinity σ ligands, DTG (1,3-di(2-tolyl)guanidine) and haloperidol, on the activation of dorsal hippocampus pyramidal neurons induced by microiontopheretic application of N-methyl-D-aspartate (NMDA) were assessed electrophysiologically. Low doses of DTG (0.5–3 μg/kg i.v.) potentiated the NMDA response. This effect of DTG was blocked by haloperidol (10 μg/kg i.v.), but not by spiperone, a potent dopamine antagonist with low affinity for σ receptors. These results suggest that σ receptors modulate the NMDA-induced neuronal activation.