A comparison of stress reactivity between BTBR and C57BL/6J mice: an impact of early-life stress

Early-life stress (ELS) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and can increase the risk of psychiatric disorders later in life. The aim of this study was to investigate the influence of ELS on baseline HPA axis functioning and on the response to additional stress in adolescent male mice of strains C57BL/6J and BTBR. As a model of ELS, prolonged separation of pups from their mothers (for 3 h once a day: maternal separation [MS]) was implemented. To evaluate HPA axis activity, we assessed serum corticosterone levels and mRNA expression of corticotropin-releasing hormone (Crh) in the hypothalamus, of steroidogenesis genes in adrenal glands, and of an immediate early gene (c-Fos) in both tissues at baseline and immediately after 1 h of restraint stress. HPA axis activity at baseline did not depend on the history of ELS in mice of both strains. After the exposure to the acute restraint stress, C57BL/6J-MS mice showed less pronounced upregulation of Crh and of corticosterone concentration as compared to the control, indicating a decrease in stress reactivity. By contrast, BTBR-MS mice showed stronger upregulation of c-Fos in the hypothalamus and adrenal glands as compared to controls, thus pointing to greater activation of these organs in response to the acute restraint stress. In addition, we noted that BTBR mice are more stress reactive (than C57BL/6J mice) because they exhibited greater upregulation of corticosterone, c-Fos, and Cyp11a1 in response to the acute restraint stress. Taken together, these results indicate strain-specific and situation-dependent effects of ELS on HPA axis functioning and on c-Fos expression.