Sex Differences in Freezing Behavior and Extinction Learning Among Wistar Rats Exposed to Social Isolation and 15 cGy GCRsim Space Radiation Both Alone and in Combination

Long-term space missions traveling beyond the Earth’s magnetosphere will expose astronauts to prolonged periods of social isolation (SI) and exposure to space radiation (SR). Throughout these missions, astronauts will have to cope with these stressors and adapt to their environment to carry out mission objectives. It is known that SI and SR can impact mission performance and overall health. Additionally, behavioral stress responses can differ between sexes. However, the independent and interactive effects of SI and SR on fear behavior and extinction learning between sexes is unknown. This study compared freezing behavior and stress-induced hyperthermia (SIH) in female and male Wistar rats using a conditioned fear (CF) paradigm. Comparisons were made in SHAM-treated rats and in ground-based models of SI and SR alone and in combination (dual flight stressors (DFSs)). SHAM and SI females froze significantly more during shock training (ST), context re-exposure (CTX) and extinction learning (EXT) compared to their male counterparts, suggesting sex differences in fear learning and memory. There were minimal changes in freezing behavior between sexes in SR and DFS animals; however, SR and DFS females had significantly lower temperatures than their male counterparts. These findings suggest the presence of sex differences in stress responses, and that stress-based learning and memory can be differentially impacted by spaceflight hazards. Baseline differences suggest that males and female rats may have sex-specific characteristics attuned to their behavioral capacities or needs, whereas differences after exposure to spaceflight hazards suggest differences in stress vulnerability. In general, these data suggest that understanding within-sex alterations will be important for assessing the effects of spaceflight hazards on performance and developing mitigation strategies that may need to be tailored for males and females.