Developmental stress has sex-specific effects on contextual and cued fear conditioning in adulthood.

Stress-induced deviations in central nervous system development has long-term effects on adult mental health. Previous research in humans demonstrates that prenatal or adolescent stress increases the risk for psychiatric disorders. Animal models investigating the effects of stress during prenatal or adolescent development produces behavioral outcomes analogous to those observed in humans. However, whether adolescent stress exposure potentiates the effects of prenatal stress is currently unknown. Thus, the current study tested whether adolescent stress increases the impact of prenatal stress on contextual and cued fear memory in adulthood. Male and female Sprague Dawley rats were exposed to a chronic variable stress schedule during the last week of gestation, during adolescence, or during both developmental periods before undergoing fear conditioning training in adulthood. Our hypothesis predicted that the combined effects of prenatal and adolescent stress on contextual and cued fear memory would be greater than the effects of stress during either time period alone. In contrast to our hypothesis, however, we found independent effects of prenatal and adolescent stress on contextual and cued fear memory in both sexes, with no additional combined impact of stress exposure during both developmental phases. In males, developmental stress increased freezing behavior during contextual and cued testing regardless of whether stress exposure was prenatal, adolescent, or combined prenatal and adolescent stress exposure. In contrast, the effects of developmental stress in females were both test- and ovarian hormone status-dependent. During cued testing, nonstressed female freezing behavior depended on estrous cycle phase, whereas freezing behavior in stressed females did not, suggesting that developmental stress interferes with hormone-dependent cued fear memory. No effects of developmental stress or estrous cycle phase were observed for contextual fear memory in females. The results of the current study suggest that the effects of prenatal and adolescent stress on contextual and cued fear memory are not cumulative, but the effects of developmental stress on associative memory differ between males and females.