Combined pre- and postnatal environmental enrichment programs the HPA axis differentially in male and female rats

Summary

Experimental environmental enrichment (EE) is usually applied in adulthood or immediately after weaning, with robust effects on physiology and behaviour. To investigate the effects of EE earlier in life, female rats were maintained under moderate enrichment during pregnancy and, together with their pups, during lactation until weaning. A separate group of dams housed under standard conditions during pregnancy and lactation served as controls. Dams housed under EE exhibited fewer nursing episodes and were off the nest more often, but the frequency of pup licking was not affected on postnatal days 3–5. EE effects on hypothalamus–pituitary–adrenal (HPA) axis responses to an acute stressor were determined in adult male and female offspring with and without previous exposure to the chronic stressor of constant light. In female offspring, chronic stress significantly increased basal corticosterone (CORT) levels, but not if rats had been exposed to early EE. Furthermore, while control females exposed to chronic stress showed a greatly reduced adrenocorticotropin (ACTH) response to an acute stressor, EE females did not display this desensitization. There was no significant effect of EE on basal ACTH and CORT levels in adult male offspring, nor did it alter their response to acute stress. Maternal licking frequency was moderately but significantly correlated with net corticosterone increases in response to acute stress, the direction of the correlation crucially depending on the offspring's sex and stress conditions. This study shows that EE during pregnancy and lactation has long-lasting effects on reactivity to acute and chronic stress in offspring and that these effects are dependent on the offspring's sex but not greatly on early postpartum maternal behaviour.

Introduction

A wealth of evidence has shown that environmental conditions early in life have profound influence on adult behaviour and vulnerability to stress (Heim et al., 2001, Ladd et al., 2000, Liu et al., 1997). The mechanisms by which this occurs are being explored in studies evaluating physiology and brain function in animals reared under aversive as well as enriched environmental conditions (Larsson et al., 2002, Moncek et al., 2004, Pham et al., 1999). In this regard, environmental enrichment (EE) usually involves housing several rats or mice together in a larger-than-usual cage that contains toys, tubes and/or a running wheel. The effects of EE can be roughly divided into three categories: consequences of EE per se on neurogenesis, neurochemistry and behaviour (Brown et al., 2003, van Praag et al., 1999, Kempermann et al., 2002, Lee et al., 2003); prevention by EE of lesion effects or symptoms associated with aging (Frick et al., 2003, Pham et al., 1999, Saito et al., 1994); and reversal by EE of changes induced by environmental impacts, lesions or genetic manipulation (van Rijzingen et al., 1997, Wagner et al., 2002).

Many EE studies have been performed in juvenile rats during the period immediately after weaning, a procedure sometimes referred to as ‘EE rearing’. The brain during this period is particularly sensitive to environmental changes, as shown in studies of isolation rearing (Hall, 1998). EE during the post-weaning period has many effects (Fernandez-Teruel et al., 2002), notably on neuronal structure and survival (Berman et al., 1996, Young et al., 1999). EE during adolescence can also reverse the effects of an adverse early-life environment. Thus, the prolonged corticosterone (CORT) release in response to stress observed in prenatally stressed rats (Morley-Fletcher et al., 2003) or in rats exposed to repeated maternal separations during lactation (Francis et al., 2002) is normalized if these rats are reared under enriched conditions.

Notwithstanding the numerous effects of EE applied during adolescence or in adulthood, the perinatal period, during which rapid brain development takes place, is arguably even more susceptible to environmental manipulations. Indeed, both prenatal stress and repeated pup-mother separations during lactation have permanent ‘programming’ effects on offspring's sensitivity to stress later in life (for reviews see Ladd et al., 2000, Welberg and Seckl, 2001). Most animal studies investigating manipulations of the early life environment apply such treatments selectively prenatally or postnatally. In reality, it is likely that a particular milieu during pregnancy will remain the same during the postpartum period. Thus, in the study described here, female rats were environmentally enriched—to a moderate degree—during pregnancy and, together with their pups, during lactation until weaning. We determined the effects of EE on maternal behaviour and on hypothalamus–pituitary–adrenal (HPA) axis responses to an acute stressor in adult male and female offspring with and without previous exposure to chronic stress.