Antidepressant Effects of Ketamine on Depression-like Behavior in Juvenile Mice after Neonatal Dexamethasone Exposure

Objective: Pediatric depression is associated with significant functional impairment at school and at work. Recently, we reported on depression-like behavior in juvenile mice neonatally exposed to dexamethasone (DEX) as a potential animal model for pediatric depression. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has promoted rapid and long-lasting antidepressant effects in patients with treatment-resistant major depression. This study was conducted to examine whether ketamine had antidepressant effects in juvenile mice after neonatal DEX exposure. Methods: A single dose (10 mg/kg) of ketamine or vehicle was injected into juvenile mice at days 29-32 after neonatal DEX (or saline) exposure (days 1-3). The sucrose preference test, tail suspension test, and forced swimming test were performed 24, 40, and 46 hours, respectively, after injection of ketamine. Results: Ketamine (10 mg/kg) significantly improved depression-like behavior in DEX-treated juvenile mice. Conclusion: This finding suggests that ketamine confers antidepressant effects in an animal model of pediatric depression.