Gestational and postpartum corticosterone exposure to the dam affects behavioral and endocrine outcome of the offspring in a sexually-dimorphic manner

Abstract

Exposure to high levels of glucocorticoids in utero and during the postpartum period has a detrimental effect on brain development. We created an animal model of postpartum stress/depression based on administering high levels of corticosterone (CORT) to the dams during the postpartum period which caused behavioral changes and reduced hippocampal cell proliferation in the offspring. As the consequences of early exposure to glucocorticoids may depend on the dose and the developmental stage of the offspring, the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on the outcome of the offspring. Male and female offspring were weighed throughout the experiment, tested in a series of behavioral tests (forced swim test, open field, elevated plus maze) and basal and restraint stress CORT levels were examined in adolescence or young adulthood. Results show that maternal CORT exposure, regardless of when administered, significantly attenuated body weight gain until adulthood in the offspring. Offspring exposed to low maternal CORT, but not high maternal CORT, during the postpartum had higher basal levels of CORT as young adults. Further, male and female offspring of dams exposed to high maternal CORT in utero showed more depressive-like behavior in the forced swim test, while males of dams exposed to high maternal CORT postpartum exhibited more anxiety-like behavior in the elevated plus maze. Taken together, maternal glucocorticoid exposure have long lasting effects on male and female offspring's behavioral and neuroendocrine measures in adolescence and adulthood depending on the time of exposure to glucocorticoids. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

“…However, dose and species differences could account for this discrepancy, as forced swim test outcomes differ between mice and rats (Slattery and Cryan, 2012). Our results confirm previous work with this model of PPD in which maternal postpartum CORT did not significantly affect depressivelike behavior of adult offspring in the forced swim test (Brummelte et al, 2006(Brummelte et al, , 2012. Our findings show that maternal postpartum fluoxetine exerts enduring changes in serotoninrelated behavior, which may manifest from disturbances to the developing serotonin system following developmental exposure to fluoxetine.…”

“…Previous work with using this model showed that after 1 h of restraint, maternal postpartum CORT did not significantly alter serum CORT concentrations in either adult male or female offspring (Brummelte et al, 2006(Brummelte et al, , 2012. This suggests that maternal postpartum CORT results in developmental disturbance specific to negative feedback of the HPA axis.…”

“…The dose was chosen because it reliably induces a depressive-like phenotype in dams, impairs maternal care, and affects offspring development (Brummelte et al, 2006Brummelte et al, 2012;Workman et al, 2013a). Fluoxetine (Sequoia Research Products, Pangbourne, UK) was prepared every 2e3 days by dissolving in dimethyl sulfoxide (DMSO; Sigma Aldrich) and adjusting with 0.9% saline to yield a final concentration of 10 mg/ml fluoxetine in saline with 10% DMSO.…”

“…The numbers of entries (all four paws entering an arm) into the open arm and closed arm as well as time (in seconds) spent in the open arm and closed arm were analyzed. Ratio of time spent in the closed arm versus the open arms and center was used as an index of anxiety as previously described (Brummelte et al, 2012).…”

“…Interestingly, maternal postpartum CORT decreases hippocampal cell proliferation in male offspring at weaning (Brummelte et al, 2006) and increases anxiety-like behavior in adolescent male, but not female, offspring (Brummelte et al, 2012). However, it is unclear whether these sex differences or effects on offspring brain and behavior persist when the dam is exposed to concurrent maternal antidepressant exposure.…”