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Research in the metal oxide nanoparticles and nanotechnology field is growing. Zinc oxide (ZnO) nanoparticles (NPs) have been widely used in the various products and industries. Regarding the probable toxicity of ZnO NPs on central nervous system (neurotoxicity), the current study was designed to investigate the effects of maternal exposure to ZnO NPs during pregnancy on depressive-like behaviors in mice offspring, using two validated animal models of depression. Thirty pregnant female mice were distributed into three groups (n = 10 for each group). The two experimental groups were injected subcutaneously at gestation day 5, 8, 11, 14, and 17 with 100 µl of ZnO NPs solution at doses of 0.5 and 1 mg/ml, respectively. The control group was treated with a similar subcutaneous injection of saline containing 0.05% Tween-80 as vehicle. Neurobehavioral tests including forced swimming test (FST) and tail suspension test (TST) were used to evaluate depressive-like behaviors in 3-week-old and 6-week-old male and female offspring (n = 10/group). The results of this study indicated that subcutaneous injection of ZnO NPs at 0.5 and 1 mg/ml dose dependently increased the immobility time in 3-week-old and 6-week-old mice in both the FST and TST (P < 0.05). Moreover, increasing age also significantly increased the duration of immobility in both the FST and TST (P < 0.05). In addition, sex differences were observed in behavioral responses, such as female mice were more immobile than male mice in both the FST and TST (P < 0.05). In conclusion, these findings demonstrated that the depressive-like effects of ZnO NPs may be due to its neurotoxic influences during neuronal development. [ABSTRACT FROM AUTHOR]