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Mechanisms of ketamine on mice hippocampi shown by gas chromatography-mass spectrometry-based metabolomic analysis.

Bin Lian, Jinjun Xia, Xun Yang, Chanjuan Zhou, Xue Gong, Siwen Gui, Qiang Mao, Ling Wang, Pengfei Li, Cheng Huang, Xunzhong Qi, Peng Xie

Neuroreport June 13, 2018 DOI: 10.1097/wnr.0000000000001020 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Animal metabolomics study Peer reviewed
Population Mice hippocampi
Interventions Ketamine NBQX
Topics Esketamine Ketamine
Key points The authors report that ketamine altered 14 hippocampal metabolites in mice, and that after NBQX administration six metabolites remained differentially expressed between ketamine and ketamine-plus-NBQX groups while eight did not. They propose that ketamine exerts antidepressant effects through both an AMPA-receptor-inhibition-dependent mechanism and a mechanism not affected by AMPA inhibition.

Abstract

In the present study, we used a gas chromatography-mass spectrometry-based metabolomics method to evaluate the effects of ketamine on mice hippocampi. Multivariate statistical analysis and ingenuity pathway analysis were then used to identify and explore the potential mechanisms and biofunction of ketamine. Compared with the control (CON) group, 14 differential metabolites that involved amino acid metabolism, energy metabolism, and oxidative stress metabolism were identified. After combination with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) administration, six of the 14 metabolites remained significantly differentially expressed between the ketamine (KET) and KET+NBQX groups, including glycine, alanine, glutamine, aspartic acid, myoinositol, and ascorbate, whereas no difference was found in the levels of the other eight metabolites between the KET and KET+NBQX groups, including phosphate, 4-aminobutyric acid, urea, creatine, L-malic acid, galactinol, inosine, and aminomalonic. Our findings indicate that ketamine exerts antidepressant effects through an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid inhibition-dependent mechanism and a mechanism not affected by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid inhibition. Which provides further insight into the therapeutic mechanisms of ketamine in the hippocampus.

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

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