Being Suckled in a Large Litter Mitigates the Effects of Early‐Life Stress on Hypothalamic‐Pituitary‐Adrenal Axis Function in the Male Rat

Abstract

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.

Sex differences in adult rat insulin and glucose responses to arginine: programming effects of neonatal separation, hypoxia, and hypothermia

“…; Clarke et al. ). Although brief periods of maternal separation of the dam from the pups in their nest is normal in the wild for rat species (Calhoun ), there does not seem to be a general consensus for how maternal separation should be performed in experimental animals.…”

Effects of mild calorie restriction on anxiety and hypothalamic-pituitary-adrenal axis responses to stress in the male rat

“…Conversely, weight loss in obese populations can ameliorate HPA axis stress responses (Yanovski et al 1997). We have also seen CR in early life, as in rat pups suckled in large litters, leads to a long-term attenuation of HPA axis responses to stress (Bulfin et al 2011;Clarke et al 2013). On the other hand, severe CR, such as with an involuntary starvation diet or anorexia nervosa, exacerbates stress responses (Fichter and Pirke 1986;Connan et al 2007).…”

“…; Clarke et al. ). On the other hand, severe CR, such as with an involuntary starvation diet or anorexia nervosa, exacerbates stress responses (Fichter and Pirke ; Connan et al.…”

Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

“…However, the EPM was not sensitive to ELS (Hulshof et al, 2011; Lajud et al, 2012), and the effects are dependent on the basal levels of the anxiety of the strain studied (Neumann et al, 2005). Regarding the FST, maternal separation increases active behavior (Rüedi-Bettschen et al, 2006), although other studies did not observe changes (Wang et al, 2011; Clarke et al, 2013) or describe increased passive coping strategies (Herpfer et al, 2012; Lajud et al, 2012; Martisova et al, 2012). Interestingly, the effects of ELS on the FST appear to be strain-dependent (Binder et al, 2011).…”