A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress.
Li Ma, Akifumi Eguchi, Guilin Liu, Youge Qu, Xiayun Wan, Rumi Murayama, Chisato Mori, Kenji Hashimoto
Pharmacology, biochemistry, and behavior May 1, 2024 DOI: 10.1016/j.pbb.2024.173736 via PubMed
Summary
AI-generated from the abstractPretreatment with the antidepressant arketamine prevented stress-induced body weight loss, increased behavioral despair, decreased sucrose preference, and reduced synaptic protein expression in the prefrontal cortex of male mice exposed to chronic restraint stress. Gut microbiota analysis indicated that arketamine may restore stress-related changes in microbial abundance. Metabolomics identified four blood metabolites altered between stress-exposed and arketamine-pretreated mice. Network analysis linked synaptic proteins in the prefrontal cortex with specific gut microbes and blood metabolites. These findings suggest that the gut-brain axis, including microbial metabolites, may partly underlie the sustained prophylactic effects of arketamine.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Male mice |
| Intervention | Arketamine |
| Dose | 10 mg/kg |
| Duration | 7-day chronic restraint stress model; arketamine given 1 day prior to stress onset |
| Keywords | Chronic restrain stress Gut microbiota Metabolites Prophylactic effect: resilience Mental-health |
| Citations | 11 |
| Key finding | Pretreatment with arketamine prevented stress-induced behavioral and molecular changes, and the gut-brain axis may partially contribute to its prophylactic effects. |
Abstract
The gut-brain axis, which includes gut microbiota and microbiome-derived metabolites, might be implicated in depression. We reported the sustained prophylactic effects of a new antidepressant arketamine in chronic restrain stress (CRS) model of depression. In this study, we investigated the role of gut-brain axis on the prophylactic effects of arketamine in the CRS (7 days) model. Pretreatment with arketamine (10 mg/kg, 1 day prior to the CRS onset) significantly prevented CRS-induced body weight loss, increased immobility time of forced swimming test, decreased sucrose preference of sucrose preference test, and reduced expressions of synaptic proteins (GluA1 and PSD-95) in the prefrontal cortex (PFC) in the male mice. Gut microbiota analysis showed that pretreatment with arketamine might restore altered abundance of gut microbiota in CRS-exposed mice. An untargeted metabolomics analysis revealed four metabolites (e.g., L-leucine, N-acetyl-l-glutamine, 2-(2,4-dichlorophenyl)-3-[4-(dimethylamino)phenyl]acrylonitrile, L-threonine amide) that were altered between control and CRS group; however, there were found to be altered between the saline + CRS group and the arketamine + CRS group. Network analysis demonstrated correlations among synaptic proteins in the PFC and certain microbiota, and blood metabolites. These findings suggest that gut-brain axis, including its metabolites, might partially contribute to the persistent prophylactic effects of arketamine in the CRS model.