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

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