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

Sertraline, a selective serotonin reuptake inhibitor, and clorgyline, a monoamine oxidase inhibitor, both of which have high affinity for σ receptors, were assessed in an electrophysiological model. In keeping with previous data obtained with other σ 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 σ receptor ligands haloperidol and BMY-14802. The selective serotonin reuptake inhibitor paroxetine and the monoamine oxidase inhibitor tranylcypromine, both devoid of affinity for σ 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 σ receptors.