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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 |
| Topics | Ketamine |
| Keywords | Chronic restrain stress Gut microbiota Metabolites Prophylactic effect: resilience Mental-health Psychopharmacology Gut-brain-axis Stress-resilience Metabolomics |
| Citations | 11 |
| Key points | 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.