The perinatal environment influences stress responses in the long-term, as does body composition. Male rats suckled in large litters, where they have reduced access to milk and attention from the dam, are less anxious and have attenuated hypothalamic-pituitary-adrenal (HPA) axis responses to stress compared to rats from control litters. In the present study, we investigated whether this early-life environment can also ameliorate anxiety and HPA axis function in rats prone to be stress-sensitive. We conducted these experiments in male rats from control litters (n = 12) or large litters (n = 20). Half were given 24 h of maternal separation on postnatal day 10 to induce HPA axis hyperactivity; the remainder staying undisturbed with their dam. When the rats reached adulthood, we examined behavioural indices of anxiety (elevated plus maze) and depression (Porsolt's forced swim test) under basal conditions and after 15 min of restraint stress. We also examined neuronal activation in the paraventricular nucleus of the hypothalamus (PVN) as an index of HPA axis function. Being suckled in a large litter led to a significantly attenuated PVN response to stress in adulthood. Maternal separation strongly exacerbated the stress-induced increase in PVN neuronal activation in control rats but did not affect the PVN response in large-litter rats. Immobility in the forced swim after restraint was also exacerbated in neonatally maternally separated control rats but not in those from large litters. Our findings show that being suckled in large litters mitigates the effects of early-life stress on HPA axis function and indices of depression in the rat.

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