Lack of antidepressant effects of low-voltage-sensitive T-type calcium channel blocker ethosuximide in a chronic social defeat stress model: Comparison with (R)-ketamine
Z. Ryan Tian, Chao Dong, Kai Zhang, Lijia Chang, Kenji Hashimoto
The International Journal of Neuropsychopharmacology August 4, 2018 DOI: 10.1093/ijnp/pyy072 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Chronic social defeat stress-susceptible mice |
| Interventions | Ethosuximide (R)-ketamine saline |
| Dose | Ethosuximide 100, 200, or 400 mg/kg; (R)-ketamine 10 mg/kg |
| Measures | locomotion test, tail suspension test, forced swimming test, 1% sucrose preference test |
| Topics | Esketamine Ketamine |
| Citations | 18 |
| Key points | (R)-ketamine (10 mg/kg) showed rapid and long-lasting antidepressant actions in chronic social defeat stress-susceptible mice, whereas ethosuximide at 100, 200, or 400 mg/kg did not reduce immobility in the tail suspension or forced swimming tests and did not improve sucrose preference. The authors conclude that low-voltage-sensitive T-type calcium channel inhibitors are unlikely to have ketamine-like antidepressant actions. |
Abstract
Background: A recent study demonstrated that low-voltage-sensitive T-type calcium channel blocker ethosuximide shows rapid antidepressant actions. This study was conducted to compare the antidepressant actions of ethosuximide and (R)-ketamine in a chronic social defeat stress model.
Methods: Ethosuximide (100, 200, or 400 mg/kg), (R)-ketamine (10 mg/kg), or saline was administered i.p. to chronic social defeat stress-susceptible mice. Subsequently, locomotion test, tail suspension test, forced swimming test, and 1% sucrose preference test were performed.
Results: (R)-ketamine showed rapid and long-lasting antidepressant actions in chronic social defeat stress-susceptible mice. In contrast, ethosuximide did not attenuate the increased immobility time of tail suspension test and forced swimming test in chronic social defeat stress-susceptible mice. In the sucrose preference test, ethosuximide did not improve decreased sucrose preference in chronic social defeat stress-susceptible mice.
Conclusions: Unlike (R)-ketamine, ethosuximide did not show rapid and sustained antidepressant effects in a chronic social defeat stress model. Therefore, it is unlikely that low-voltage-sensitive T-type calcium channel inhibitors may have ketamine-like robust antidepressant actions.
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
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Ketamine: A tale of two enantiomers Journal of Psychopharmacology November 6, 2020
- A historical review of antidepressant effects of ketamine and its enantiomers. Pharmacology, Biochemistry, and Behavior February 5, 2020
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- (R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress The International Journal of Neuropsychopharmacology August 28, 2019
and 2 more in the library
Cites 11
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions Proceedings of the National Academy of Sciences June 8, 2015
- Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model. Biological Psychiatry 2018
and 6 more in the library