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Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model
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Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model
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Journal Article
Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model
2017
Overview
Accumulating evidence suggests a key role of the gut–microbiota–brain axis in the antidepressant actions of certain compounds. Ketamine, an
N
-methyl-D-aspartate receptor (NMDAR) antagonist, showed rapid and sustained antidepressant effects in treatment-resistant depressed patients. In contrast, another NMDAR antagonist, lanicemine, did not exhibit antidepressant effects in such patients. (
R
)-ketamine, the (
R
)-enantiomer of ketamine, has rapid-acting and long-lasting antidepressant effects in rodent models of depression. Here we compared the effects of (
R
)-ketamine and lanicemine on depression-like phenotype and the composition of the gut microbiota in susceptible mice after chronic social defeat stress (CSDS). In behavioral tests, (
R
)-ketamine showed antidepressant effects in the susceptible mice, whereas lanicemine did not. The 16S ribosomal RNA gene sequencing of feces demonstrated that (
R
)-ketamine, but not lanicemine, significantly attenuated the altered levels of
Bacteroidales
,
Clostridiales
and
Ruminococcaceae
in the susceptible mice after CSDS. At the genus level, (
R
)-ketamine significantly attenuated the marked increase of
Clostridium
in the susceptible mice. In contrast, the effects of lanicemine were less potent than those of (
R
)-ketamine. This study suggests that the antidepressant effects of (
R
)-ketamine might be partly mediated by the restoration of altered compositions of the gut microbiota in a CSDS model.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 64/60
/ Animals
/ Antidepressive Agents - therapeutic use
/ Bacteria
/ Gastrointestinal Microbiome - drug effects
/ Humanities and Social Sciences
/ Ketamine
/ Male
/ N-Methyl-D-aspartic acid receptors
/ Phenethylamines - pharmacology
/ Phenethylamines - therapeutic use
/ Principal Component Analysis
/ rRNA 16S
/ Science
