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Abnormal corticosterone regulation in an immature rat model of continuous chronic stress
E E Gilles1, L Schultz, T Z Baram
1Department of Neurology, University of Southern California, USA.
Insights
Chronic stress in infant rats, induced by limited bedding, elevated corticosterone levels and reduced body weight. This new model mimics stress in neglected human infants without maternal separation.
Area of Science:
- Neuroendocrinology
- Developmental Psychology
- Stress Research
Background:
- Establishing neuroendocrine correlates of chronic stress in human infants is challenging.
- Existing animal models often involve maternal separation, which may not fully represent human infant stress.
- Understanding the impact of early-life stress on the developing hypothalamic-pituitary-adrenal (HPA) axis is crucial.
Purpose of the Study:
- To develop a novel animal model of continuous chronic stress in immature rats.
- To investigate the basal and stress-induced plasma corticosterone levels in this model.
- To examine the effects of early-life stress on HPA axis regulation.
Main Methods:
- Immature rat pups (postnatal days 2-9) were housed in three conditions: handled, not handled with ample bedding, and not handled with limited bedding.
- Limited bedding was used to induce chronic stress.
- On postnatal day 9, pups were exposed to acute cold-separation stress, with blood samples collected at intervals (90, 240, 360 min) for corticosterone analysis.
Main Results:
- The group with limited bedding showed elevated basal plasma corticosterone levels.
- This group also exhibited a sustained increase in plasma corticosterone following acute stress.
- Increased corticosterone interanimal variability and decreased body weight were observed, indicative of chronic stress.
Conclusions:
- A novel rat model of continuous chronic stress in infant rats was established without maternal separation.
- This model demonstrates HPA axis upregulation, mirroring chronic stress in neglected human infants.
- The findings provide insights into the neuroendocrine consequences of early-life adversity.
Abstract:
Neuroendocrine correlates of chronic stress in human infants have not been established. The goal of the present study was to create an animal model of continuous chronic stress using the immature rat to measure basal plasma corticosterone, and secretion of plasma corticosterone in response to an acute stress. This was achieved by modulation of the cage environment for rat pups and their mothers. During postnatal days 2-9, pups were maintained in three groups: (1) handled, (2) not handled and with ample bedding; and (3) not handled with limited bedding. On postnatal day 9, some pups from each group were subjected to acute cold-separation stress and were killed 90, 240, or 360 min later along with unstressed controls. The group not handled and with limited bedding manifested increased plasma corticosterone output even without cold exposure and a sustained increase of plasma corticosterone after cold-separation stress. Plasma corticosterone interanimal variability was increased and body weight was decreased in these pups, typical of a state of chronic stress. The first model of continuous stress in infant rats in which upregulation of hypothalamic-pituitary-adrenal axis is achieved without maternal separation is presented. This paradigm may more closely approximate the human situation of chronically stressed, neglected infants.