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

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. 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. 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. 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.