Sex-dependent effects of postweaning exposure to an enriched environment on visceral pain and anxiety- and depression-like behaviors induced by neonatal maternal separation

Background: Neonatal maternal separation (NMS) can lead to visceral pain and anxiety-and depression -like behaviors. An enriched environment (EE) can alleviate NMS-induced pain and mental disorders, but previous studies have mostly been performed in male animals. Therefore, the aim of this study was to investigate whether the effects of EE were sex dependent at different stages of development.Methods: Female and Male C57BL/6 J mice that had been subjected to NMS alone and those subjected to both NMS and exposed to EE were used in this study. The visceral pain threshold test (PTT), open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST) were conducted to evaluate visceral pain, anxiety-like behavior, and depression-like behavior in mice, respectively.Results: Compared with the male mice in the NMS group without EE exposure, those exposed to EE from postnatal day (P)21 to 41 showed an increase of the visceral pain threshold in the PTT, an increase of the central time and central distance in the OFT, an increase of the sucrose preference rate in the SPT, and a decrease of the time of immobility in the FST. Compared with both female and male mice in the NMS group without EE exposure, those exposed to EE from P21 to P61 had an increase of the visceral pain threshold in the PTT, an increase of the central time and central distance in the OFT, an increase in the sucrose preference rate in the SPT, and a decrease of the time of immobility in the FST.Conclusions: EE is more effective in male NMS mice, while longer EE is required in female NMS mice for positive effects.