Aims: Pediatric patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Mechanistically, radiation-induced injury to the hippocampi could play an important role in this debilitating condition, by inducing loss of neural stem/progenitor cells and neuroinflammation within this region. Noradrenergic (NA) agonists can potentially mitigate this radiation-induced cognitive decline by reducing cell death and inflammation. Therefore, we hypothesize that boosting NA through drugs will attenuate radiation-induced impairments in neurogenesis and decrease neuroinflammation, resulting in decreased memory dysfunction. Methods: Mice were irradiated with a single fraction of 10 Gy at P22. NA agonists, Reboxetine and Atipamezole, were delivered as 7 daily intraperitoneal injections starting immediately after radiation. At 6 hours and 1 month post-radiation, radiation-induced hippocampal injury and inflammation was investigated with histology. Cognitive deficits were investigated by a behavioral test battery at 1 month post-irradiation. Results: We report that Reboxetine and Atipamezole significantly mitigate radiation-induced toxicity in the hippocampi. At 6 hours post-irradiation, NA agonists reduce radiation-induced apoptosis and microglial inflammation compared to sham treatment. Moreover, the deleterious effect of 10 Gy irradiation on neurogenesis at 1 month post-irradiation was mitigated in both groups. Behavioral testing revealed that treatment with Reboxetine after radiotherapy was able to successfully mitigate radiation-induced deficits in working memory.Conclusion: Present findings document the marked benefits of NA treatment against radiation-induced hippocampal injury. Additionally, we demonstrate that Reboxetine is able to mitigate radiation-induced memory dysfunction, which highlights the potential of NA treatment for resolving long-standing complications faced by pediatric brain tumor survivors.