A tale of two receptors: simultaneous targeting of NMDARs and 5-HT Rs exerts additive effects against stress.

Background: Serotonin (5-HT) receptors and -methyl-D-aspartate receptors (NMDARs) have both been implicated in the pathophysiology of depression and anxiety disorders. Here, we evaluated whether targeting both receptors through combined dosing of ( , )-ketamine, an NMDAR antagonist, and prucalopride, a serotonin type IV receptor (5-HT R) agonist, would have additive effects, resulting in reductions in stress-induced fear, behavioral despair, and hyponeophagia.

Methods: A single injection of saline (Sal), ( , )-ketamine (K), prucalopride (P), or a combined dose of ( , )-ketamine and prucalopride (K+P) was administered before or after contextual fear conditioning (CFC) stress in both sexes.

Fluoroethylnormemantine, a Novel NMDA Receptor Antagonist, for the Prevention and Treatment of Stress-Induced Maladaptive Behavior.

Background: Major depressive disorder is a common, recurrent illness. Recent studies have implicated the NMDA receptor in the pathophysiology of major depressive disorder. (R,S)-ketamine, an NMDA receptor antagonist, is an effective antidepressant but has numerous side effects.