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

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.