Sertraline reverses depressive-like behaviors in males and females following early life hypoxic brain injury

INTRODUCTION: Later-life behavioral deficits associated with neonatal hypoxic brain injury remain without definitive treatment options. We have previously shown that a one-week course of sertraline prevents depressive-like behaviors but worsens anxiety in males using a rat model of early-life hypoxic seizures. Here, we examined whether a more extended sertraline course has a more favorable effect on later-life emotional behaviors of both males and females in this model. METHOD: Postnatal day 10 (P10) Sprague Dawley male and female rat pups were subjected to global hypoxia. The open field test (OFT) and forced swim test (FST) were performed at P50-52 and P53-54, respectively. Sertraline was administered from P22 to P55. RESULTS: All groups were comparable in the OFT. Hypoxic seizures resulted in increased immobility in the FST in both genders, but to a greater extent in females. Sertraline mitigated these hypoxic brain injury-induced depressive-like behaviors in both genders without anxiogenic side effects. Histological analyses at P55 revealed comparable hippocampal neuronal densities in all groups. CONCLUSIONS: These findings suggest that adolescent females are more susceptible to depression associated with early-life hypoxic brain injury and that chronic sertraline treatment is beneficial in both genders. Further mechanistic studies are warranted to elucidate underlying pathways.