N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.
Jen-Cheng Lin, Ming‐huan Chan, Mei-Yi Lee, Yi-Chyan Chen, Hwei‐hsien Chen
Progress in Neuro-Psychopharmacology and Biological Psychiatry November 3, 2016 DOI: 10.1016/j.pnpbp.2016.06.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | N N-dimethylglycine (DMG) ketamine |
| Measures | rotarod performance, novel location test, novel object recognition test, prepulse inhibition, forced swim test |
| Topics | Esketamine Ketamine |
| Keywords | Anesthesia Forced swimming Glycine Nmda receptor Prepulse inhibition |
| Key points | DMG pretreatment reversed ketamine-induced locomotor hyperactivity, rotarod impairment, novel location and novel object recognition deficits, and prepulse inhibition disruption in mice, while not affecting ketamine anesthesia. DMG alone showed antidepressant-like effects in the forced swim test and produced additive antidepressant-like effects with ketamine, suggesting possible antipsychotic potential as an add-on therapy. |
Abstract
Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine. The present study determined the effects of DMG on the ketamine-induced psychotomimetic, anesthetic and antidepressant-like effects in mice. DMG pretreatment reversed the ketamine-induced locomotor hyperactivity and impairment in the rotarod performance, novel location and novel object recognition tests, and prepulse inhibition. In addition, DMG alone exhibited antidepressant-like effects in the forced swim test and produced additive effects when combined with ketamine. However, DMG did not affect ketamine-induced anesthesia. These results reveal that DMG could antagonize ketamine's psychotomimetic effects, yet produce additive antidepressant-like effects with ketamine, suggesting that DMG might have antipsychotic potential and be suitable as an add-on therapy to ketamine for patients with treatment-resistant depression.
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 5
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Molecular Brain June 16, 2020
- Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice. Biomedicines June 25, 2023
- Gastrodin Mitigates Ketamine-Induced Inhibition of F-Actin Remodeling and Cell Migration by Regulating the Rho Signaling Pathway. Biomedicines March 6, 2025
- Biological variations in ketamine sensitivity: insights from hyperlocomotion to psychotomimetic features in genetically diverse mouse strains. Psychiatry Research April 1, 2026
- Stereochemical and structural effects of (2R,6R)-hydroxynorketamine on the mitochondrial metabolome in PC-12 cells. Biochimica et biophysica acta. General subjects June 2018
Cites 11
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- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic Journal of Psychopharmacology June 1, 2014
and 6 more in the library