Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-β1.
Dan Xu, Guilin Liu, Mingming Zhao, Xiayun Wan, Youge Qu, Rumi Murayama, Kenji Hashimoto
Journal of Affective Disorders December 15, 2024 DOI: 10.1016/j.jad.2024.08.222 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice exposed to chronic restraint stress |
| Interventions | Arketamine RepSox TGF-β1 |
| Dose | 10 mg/kg |
| Topics | Depression Ketamine |
| Keywords | Antidepressant Chronic stress Demyelination Tgf-β1 Mental health Psychopharmacology Brain research Stress disorders |
| Citations | 21 |
| Key findings | Arketamine improved depression-like behaviors and demyelination in the corpus callosum of stressed mice through a TGF-β1-dependent mechanism. |
Abstract
Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, the relationship between these depression-like behaviors and demyelination remains unclear. Arketamine, the (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects in CRS-exposed mice. We examined whether arketamine can improve both depression-like behaviors and demyelination in the brains of CRS-exposed mice. Additionally, we investigated the role of transforming growth factor β1 (TGF-β1) in the beneficial effects of arketamine. A single dose of arketamine (10 mg/kg) improved both depression-like behavior and demyelination in the corpus callosum of CRS-exposed mice. Correlations were found between depression-like behaviors and demyelination in this region. Furthermore, pretreatment with RepSox, an inhibitor of TGF-β1 receptor, significantly blocked the beneficial effects of arketamine on depression-like behaviors and demyelination in CRS-exposed mice. Finally, a single intranasal administration of TGF-β1 ameliorated both depression-like behaviors and demyelination in CRS-exposed mice. The precise mechanisms by which TGF-β1 contributes to the effects of arketamine remain unclear. These data suggest that CRS-induced demyelination in the corpus callosum may contribute to depression-like behaviors, and that arketamine can mitigate these changes through a TGF-β1-dependent mechanism.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 9
- Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice. European Journal of Pharmacology December 15, 2024
- Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice. European Journal of Pharmacology March 15, 2025
- Lessons learned from the regulatory alignment in ketamine, esketamine and arketamine clinical trials: A cross-sectional analysis of protocols from ClinicalTrials.gov. Psychiatry Research August 1, 2025
- Arketamine alleviates cognitive impairments and demyelination in mice with postoperative cognitive dysfunction via TGF-β1 activation. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers. Journal of Anesthesia and Translational Medicine September 1, 2025
and 4 more in the library
Cites 24
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
and 19 more in the library