Appetitive maternal behavior in mice is resistant to perinatal chronic variable stress and perinatal chronic corticosterone treatment.

Perinatal stress is a risk factor for emotional and cognitive disturbances in both caregivers and their infants. Here, we compared the impact of two stressors, perinatal chronic variable stress (CVS) and perinatal chronic corticosterone treatment (C-CORT), on maternal exploratory behavior, maternal caregiving, and hypothalamic neural activity. We stressed mouse dams with each paradigm for 13 days starting at gestational day 11 (GD11). We examined open field exploration behavior on day 12 of stress (or post-partum day 3, PP3) and pup-directed behavior on day 13 of stress (PP4). We collected brains and serum 30 min after pup exposure to study circulating maternal corticosterone and the expression of the immediate-early gene Fos in hypothalamic neuropeptidergic cell populations. We found that perinatal CVS reduced distance moved and increased immobility in the open field, suggestive of a depression-like phenotype, while perinatal C-CORT reduced time spent in the center of the open field, suggestive of an anxiety-like phenotype. Dams exposed to both stressors showed intact appetitive maternal behavior. Importantly, we found that CVS in mated, unpregnant females led to hypoactivity in the open field and significantly increased pup retrieval latency. Both stressors led to reduced Fos colocalization with corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus (PVHCRF) after pup exposure. Perinatal C-CORT treatment increased Fos colocalization with urocortin-3 in the perifornical area of the hypothalamus (PeFAucn3). Together, these results suggest that adaptations in maternal physiology and brain function contribute to stress resistance, thereby protecting appetitive maternal behavior.