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Chronic Social Defeat Stress in Early Adolescent Male Mice
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Lack of Antidepressant Effects of Low-Voltage-Sensitive T-Type Calcium Channel Blocker Ethosuximide in a Chronic
Zheng Tian1, Chao Dong1, Kai Zhang1
1Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
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.
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