Introduction: Oxytocin (OXT) has attracted attention as an effective treatment for anxiety and depression. It also can prevent 3-NP-induced anxiety and depression. However, the effects of OXT can be context-dependent. The objective of this investigation was to explore how prenatal stress (PS) context modulates the effectiveness of OXT in mitigating anxiety-and depression-like behaviors induced by 3-NP, as well as alterations in antioxidant levels.

Methods: The dams underwent PS or PS+3NP treatments, and the effects of OXT on the anxiety-like behavior, and depression-like behavior in these treatment groups were evaluated via elevated plus maze and forced swim test respectively. The reduced glutathione (GSH) level was also measured in the striatum, hippocampus, prefrontal cortex, and amygdala.

Results: We found that PS per se and 3-NP in the context of PS increased anxiety and depression. These groups also had lower GSH levels in the brain regions examined. OXT pretreatment markedly increased the behavioral changes in the PS group and ameliorated the antioxidant changes. However, OXT pretreatment could not improve 3-NP-induced behavioral and GSH level changes in the context of PS.

Conclusion: These findings indicate that OXT improves PS-induced anxiety and depression and the antioxidant level changes, but we found that PS per se thwarts the protective effects of OXT in the 3-NP-induced anxiety and depression