Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has attracted attention for its acute and sustained antidepressant effects in patients with depression. Hydroxynorketamine (HNK), a metabolite of ketamine, exerts antidepressant effects without exerting ketamine's side effects and has attracted much attention in recent years. However, the detailed pharmacological mechanism of action...
Background: The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine exerts rapid and sustained antidepressant effects in depressed patients. Ketamine is a racemic mixture of equal amounts of enantiomers, (R)-ketamine and (S)-ketamine. The neural mechanisms that underlie different effects of these enantiomers remain unclear.
We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D-KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The...