Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model
Youge Qu, Chun Yang, Qian Ren, Min Ma, Chao Dong, Kenji Hashimoto
Scientific Reports November 10, 2017 DOI: 10.1038/s41598-017-16060-7 via OpenAlex
Summary
In a mouse model of depression induced by chronic social defeat stress, (R)-ketamine, but not the related NMDAR antagonist lanicemine, reversed depression-like behavior and partially restored the composition of gut bacteria, including Bacteroidales, Clostridiales, Ruminococcaceae, and Clostridium. The findings suggest that the antidepressant effects of (R)-ketamine may be partly mediated by its ability to normalize gut microbiota alterations.
Study at a glance
| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Susceptible mice after chronic social defeat stress |
| Interventions | (R)-ketamine lanicemine |
| Topics | Ketamine |
| Keywords | Social defeat Antidepressant Gut flora Antagonist |
| Citations | 126 |
| Key finding | (R)-ketamine, but not lanicemine, showed antidepressant effects and significantly attenuated altered levels of Bacteroidales, Clostridiales, and Ruminococcaceae in susceptible mice after chronic social defeat stress. |
Abstract
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.