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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Susceptible mice after chronic social defeat stress |
| Interventions | (R)-ketamine lanicemine |
| Topics | Ketamine Depression Esketamine |
| Keywords | Social defeat Antidepressant Gut flora Antagonist Pharmacology Nmda receptor Endocrinology Immunology Hippocampus |
| Citations | 126 |
| Key points | (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.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 40
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Translational Psychiatry November 7, 2019
- A historical review of antidepressant effects of ketamine and its enantiomers. Pharmacology, Biochemistry, and Behavior February 5, 2020
and 35 more in the library
Cites 24
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
and 19 more in the library