Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function.

Sarah M Dinces,Akaysha C Tang,Bruce S Mcewen,Russell D Romeo

doi:10.3389/fnbeh.2014.00204

Abstract

In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1–21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54–63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal HPA regulation.

Highlights

Life experiences can have powerful, long-lasting impacts on adult function (Bowlby, 1969; Ainsworth et al, 1979; Rutter, 1981)
The neonatal novelty exposure procedure captures one particular element shared between the neonatal handling and enriched environment paradigms, that is an increase in the novelty of the environment
Notice that the Ns and ns for CORT response (CORTE) are smaller than the Ns and ns for CORTB and CORTS because a missing value of either CORTB or CORTS will result in the loss of CORTE

Summary

Introduction

Life experiences can have powerful, long-lasting impacts on adult function (Bowlby, 1969; Ainsworth et al, 1979; Rutter, 1981). Building upon the earlier experimental paradigms of neonatal handling (Levine, 1960; Denenberg, 1964) and enriched environment (Rosenzweig, 1966; Weiler et al, 1995), we developed neonatal novelty exposure, an early life intervention that induced consistent and positive consequences across a wide range of functional domains, multiple levels of analysis, and multiple development stages (Tang and Zou, 2002; Tang et al, 2003b, 2006, 2008, 2012a,b, 2014; Akers et al, 2008). Programming offspring HPA regulation by novelty environment; the standard laboratory-rearing environment is augmented with more complex, and changing stimuli. In both cases, the manipulation involves repeated environmental changes without which there would be no novelty. An organism’s response to novelty at behavioral and physiological levels are thought to contribute to individual differences in both physical and mental resilience or vulnerability to environmental challenge (Karatsoreos and McEwen, 2013)

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Conclusion