Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine
Soichiro Ide, Yuiko Ikekubo, Masayoshi Mishina, Kenji Hashimoto, Kazutaka Ikeda
Journal of Pharmacological Sciences November 1, 2017 DOI: 10.1016/j.jphs.2017.11.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study (knockout mouse comparison) Peer reviewed |
|---|---|
| Population | GluN2D subunit knockout mice and wildtype mice subjected to restraint stress |
| Interventions | Ketamine (S)-ketamine (R)-ketamine |
| Duration | Assessed up to 96 h after injection |
| Measures | tail-suspension test |
| Topics | Esketamine Ketamine |
| Citations | 44 |
| Key findings | Ketamine and its enantiomers showed antidepressant effects in the tail-suspension test in both wildtype and GluN2D-knockout mice, and the effects of (RS)- and (S)-ketamine persisted 96 hours after injection in both groups. The sustained effect of (R)-ketamine was seen only in wildtype mice, which the authors interpret as indicating that the GluN2D subunit is critical for (R)-ketamine's lasting antidepressant action. |
Abstract
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 antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R)-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R)-ketamine.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 15
- Rapid-acting antidepressants. Advances in pharmacology (San Diego, Calif.) 2019
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions? American Journal of Psychiatry March 1, 2025
- Rapid-Acting Antidepressants Current Pharmaceutical Design October 19, 2018
- Is (R)-ketamine a Potential Therapeutic Agent for Treatment-Resistant Depression with Less Detrimental Side Effects? A Review of Molecular Mechanisms Underlying Ketamine and its Enantiomers. Biochemical Pharmacology February 1, 2022
and 10 more in the library
Cites 5
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model. Biological Psychiatry 2018
- GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine Elife October 23, 2014
- Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology Molecular Psychiatry January 3, 2012