Modification of the N-methyl-D-aspartate response by antidepressant sigma receptor ligands

Sertraline, a selective serotonin reuptake inhibitor, and clorgyline, a monoamine oxidase inhibitor, both of which have high affinity for sigma receptors, were assessed in an electrophysiological model. In keeping with previous data obtained with other sigma receptor ligands, low doses of sertraline and of clorgyline potentiated selectively with a bell-shaped dose-response curve the effect of N-methyl-D-aspartate (NMDA) on pyramidal neurons in the CA3 region of the rat dorsal hippocampus. This potentiation was reversed by the sigma receptor ligands haloperidol and BMY-14802. The selective serotonin reuptake inhibitor paroxetine and the monoamine oxidase inhibitor tranylcypromine, both devoid of affinity for sigma receptors, had no effects on the NMDA response. These data suggest that the effects of sertraline and clorgyline on the NMDA response are due to their affinity for sigma receptors.