Subanesthetic ketamine reverses neuronal and astroglial metabolic activity deficits in a social defeat model of depression.
Pravin K Mishra, Arvind Kumar, Kevin L. Behar, Anant B Patel
Journal of Neurochemistry September 2018 DOI: 10.1111/jnc.14544 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | C57BL/6 mice subjected to a social defeat paradigm |
| Intervention | Ketamine |
| Dose | 10 mg/kg, intraperitoneal |
| Duration | 5 min social defeat per day for 10 consecutive days; ketamine for two consecutive days after the last defeat stress |
| Measures | sucrose preference, social interaction, immobility time, proton-observed carbon-edited nuclear magnetic resonance spectroscopy |
| Topics | Depression Esketamine Ketamine |
| Keywords | Glutamate Glutamine Neuron-glia interaction Neurotransmission Γ-amino butyric acid |
| Key findings | Ketamine (10 mg/kg for two days) restored sucrose preference, social interaction, and immobility time to control values in socially defeated mice and returned carbon-13 labeling of amino acids from glucose and acetate to control levels, suggesting that its fast antidepressant action is linked to re-established neuronal and astroglial TCA cycle and neurotransmitter cycling. |
Abstract
Depression is one of the most debilitating neuropsychiatric disorders. Most of the current antidepressants have long remission time and low recovery rate. This study explores the impact of ketamine on neuronal and astroglial metabolic activity in prefrontal cortex in a social defeat (SD) model of depression. C57BL/6 mice were subjected to a social defeat paradigm for 5 min a day for 10 consecutive days. Ketamine (10 mg/kg, intraperitoneal) was administered to mice for two consecutive days following the last defeat stress. Mice were infused with [1,6-13 C2 ]glucose or [2-13 C]acetate to assess neuronal and astroglial metabolic activity, respectively, together with proton-observed carbon-edited nuclear magnetic resonance spectroscopy in prefrontal cortex tissue extract. The 13 C labeling of amino acids from glucose and acetate was decreased in SD mice. Ketamine treatment in SD mice restored sucrose preference, social interaction and immobility time to control values. Acute subanesthetic ketamine restored the 13 C labeling of brain amino acids from glucose as well as acetate in SD mice to the respective control values, suggesting that rates of neuronal and astroglial tricarboxylic acid (TCA) cycle and neurotransmitter cycling were re-established to normal levels. The finding of improved energy metabolism in SD mice suggests that fast anti-depressant action of ketamine is linked with improved neurotransmitter cycling.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 5
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Astroglia and depression: A Gliocentric perspective from rodent models to therapeutic insights. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 27, 2026
- Investigation of Potential Therapeutic Effects of New Rapid-Acting Antidepressant Drugs (RAADs) Using Stress-Based Models of Depression Biomolecules August 24, 2026
- Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway Scientific Reports September 13, 2021
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