Sex-dependent impact of different degrees of maternal separation experience on OFT behavioral performances after adult chronic unpredictable mild stress exposure in rats

Abstract

Early-life social-environmental factors are important for normal development, and different degrees of early-life stress experience have different impacts on adult behaviors and stress responsiveness. The aim of present study was to investigate the long-term effects of different degrees of maternal separation (MS) on male and female rats and subsequent responsiveness to chronic unpredictable mild stress (CUMS) exposure in adults. Sprague-Dawley (SD) newborn pups were exposed to either 15 min/day of MS (MS15), 360 min/day of MS (MS360) or no separation (NS) during postnatal day (PND)4-PND10. At PND56, behavioral tasks, including sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT), were used to explore depressive and anxiety-like behaviors. Then the rats received a series of CUMS for 28 days, behavioral tasks were recorded after CUMS. Prior to CUMS, the behavioral performances in male and female rats were consistent, MS360 led to increased immobile time in FST and decreased activity in OFT, while MS15 rats exhibited behavioral performances similar to NS group. After CUMS, sexual dimorphism was observed in the OFT behavioral responses to adult stress re-exposure, but no differences in FST were observed. CUMS male rats with MS360 experiences showed the worst behavioral performances in OFT compared to those of the other male rats groups, while CUMS female rats without MS experience showed the worst behavioral performances in OFT compared to those of the other female rats groups. Both CUMS male and female rats with MS15 experiences showed better trend in OFT performances than those of CUMS rats with MS360 experience and without MS experiences. These results suggest that brief MS experiences increase the OFT behavioral resilience of rats to adult stress re-exposure, and prolonged MS promotes OFT behavioral resilience of female rats to adult stress re-exposure, while increases vulnerability of male rats to adult stress re-exposure.

Keywords: Behavioral response; Chronic unpredictable mild stress; Maternal separation; Resilience; Sex differences; Vulnerability.