文章基本信息

标题：Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model
本地全文：下载
作者：Youge Qu ; Chun Yang ; Qian Ren 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
页码：15725
DOI：10.1038/s41598-017-16060-7
语种：English
出版社：Springer Nature
摘要：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.