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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 6
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions Journal of Anesthesia and Translational Medicine July 11, 2024
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-β1. Journal of Affective Disorders December 15, 2024
- Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice. Pharmacology, Biochemistry, and Behavior December 1, 2024
- Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: a role for oral microbiota. Translational Psychiatry November 24, 2025
and 1 more in the library
Cites 38
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD) Molecular Psychiatry October 3, 2018
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
and 33 more in the library