During late gestation and early infancy humans go HTS assay through a period of stress-induced adrenal quiescence. In rodents a similar period occurs, known as the stress hyporesponsive period (SHRP), that takes place from P4 to P14 in rats. During the SHRP, the adrenal response of the hypothalamic-pituitary-adrenal (HPA) axis is down-regulated resulting in lower circulating glucocorticoids to stressors. This period is hypothesized

to be protective to defend the developing brain from excitotoxicity produced by stress-induced elevations in corticosteroids [29] and [30]. Hence, the SHRP, while buffering the effects of stress has a finite capacity; chronic stress during this period may exceed this buffering capacity and result in adverse effects [31], [32], [33], [34] and [35]. The purpose of this study was to test the hypothesis that chronic stress alters the effects of MnOE during neonatal development in rodents. Accordingly, we combined MnOE with a model of developmental stress already shown to result in long-term effects, i.e., the barren cage model that uses cages without normal bedding [36]. This cage condition was used to mimic aspects found in impoverished low SES human environments [37], [38] and [39]. We previously used this model to assess developmental Epacadostat manufacturer lead exposure

in combination with barren cage rearing [40]. Because the effects of chronic stressors are not reliably reflected in basal corticosterone levels, we also used an acute stressor (shallow water stress) to induce an acute stress response to test

for differences in stress reactivity. The Mn-stress interaction exposure reported here is intended to be a model for future experiments on Mn in combination with other factors. All protocols were approved by the Institutional Animal Care and Use Committee. Animals were maintained in a AAALAC-accredited vivarium with regulated light cycles (14:10 h light:dark cycle, lights on at 600 h) and controlled temperature (19 ± 1 °C) and humidity (50 ± 10%). selleck chemicals Rats had access to NIH-07 rodent chow and reverse osmosis filtered, UV sterilized water provided ad libitum. The NIH-07 diet contains consistent levels of metals, minerals, and other nutrients, thus providing a consistent background nutritional formulation. Male and nulliparous female Sprague-Dawley CD (IGS) rats (strain 001, Charles River Laboratories, Raleigh, NC) were bred following acclimation to the facility for a minimum of 1 week. The morning a sperm plug was found was designated embryonic day 0 (E0). On E1 females were transferred to polycarbonate cages (46 cm × 24 cm × 20 cm) with woodchip bedding containing a stainless steel semicircular enclosure as partial environmental enrichment [41]. Birth was counted as P0. On P1, litters were culled to 12 pups (6 males and 6 females). If a litter had 10 or 11 pups, 1 or 2 pups from another litter with the same date of birth were fostered into the litter short of pups to achieve uniform litter sizes.