Beneficial effects of arketamine on the reduced bone mineral density in susceptible mice after chronic social defeat stress: Role of the gut-microbiota-bone-brain axis.
Xiayun Wan, Akifumi Eguchi, Lijia Chang, Chisato Mori, Kenji Hashimoto
Neuropharmacology May 1, 2023 DOI: 10.1016/j.neuropharm.2023.109466 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Chronic social defeat stress susceptible mice |
| Intervention | Arketamine |
| Dose | 10 mg/kg |
| Duration | Single administration |
| Topics | Ketamine |
| Keywords | Bone mineral density Gut microbiota Metabolites |
| Key findings | Arketamine ameliorated anhedonia-like behavior and reduced femoral neck cortical and total bone mineral density in CSDS susceptible mice, with changes linked to gut microbiota and plasma metabolites. |
Abstract
Patients with depression exhibit reduced bone mineral density (BMD). We previously reported that the new antidepressant arketamine improved the reduced BMD seen in chronic social defeat stress (CSDS) susceptible mice and ovariectomized mice. Considering the role of the gut microbiota in maintaining bone health, the current study investigated whether the gut microbiota, along with metabolites derived from the microbiome, play a role in the beneficial actions of arketamine with respect to the anhedonia-like behavior and reduced BMD seen in CSDS susceptible mice. A single administration of arketamine (10 mg/kg) ameliorated anhedonia-like behavior and decreased femoral neck cortical (and total) BMD in CSDS susceptible mice. There was a negative correlation between anhedonia-like behavior and BMD. Furthermore, significant differences in the abundance of microbiota (and plasma metabolites) were found between the CSDS + saline and CSDS + arketamine groups. Correlations were observed between the abundance of certain microbiota (and plasma metabolites) and cortical (and total) BMD. These data suggest that, in addition to its anti-anhedonia effect, arketamine might ameliorate the reduced cortical (and total) BMD seen in CSDS susceptible mice through the gut-microbiota-bone-brain axis. Therefore, arketamine could serve as a drug therapy for depressed patients with low BMD. This article is part of the Special Issue on "Ketamine and its Metabolites".
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 7
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions Journal of Anesthesia and Translational Medicine July 11, 2024
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications. Frontiers in Pharmacology 2024
- A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress. Pharmacology, Biochemistry, and Behavior May 1, 2024
- Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: a role for oral microbiota. Translational Psychiatry November 24, 2025
and 2 more in the library
Cites 17
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Intravenous arketamine for treatment-resistant depression: open-label pilot study European Archives of Psychiatry and Clinical Neuroscience February 20, 2020
- 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
and 12 more in the library