Abnormal corticosterone regulation in an immature rat model of continuous chronic stress

Linda Schultz,E E Gilles,T Z Baram

doi:10.1016/0887-8994(96)00153-1

Linda Schultz, E E Gilles + Show 1 more

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https://doi.org/10.1016/0887-8994(96)00153-1

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Journal: Pediatric Neurology	Publication Date: Sep 1, 1996
Citations: 175	License type: cc-by

Affiliation: University of California, Irvine

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.

Highlights

Exaggerated activity of the hypothalamic-pituitary-adrenal axis (HPA) is a neurobiologic correlate of adult depression and anxiety [1,2]
Animal models provide a critical tool for delineating the effects of chronic stress on the neuroendocrine system regulating the stress response
This neuroendocrine system in infant rats is similar to that of humans; e.g., corticotropin-releasing hormone (CRH) is identical in both species

Summary

Introduction

Exaggerated activity of the hypothalamic-pituitary-adrenal axis (HPA) is a neurobiologic correlate of adult depression and anxiety [1,2]. About the ontogeny and function of the neuroendocrine system of neglected infants and its contribution to abnormal development, growth failure, or depression [1,2,5,8]. Maternal separation and daily handling in the rat are two paradigms known to alter the development of the stress response and the responses to acute stressors experienced as adults [15,16,17,18,19]; e.g., extended periods of as much as 24 hours of maternal separation after 7 days of age increases plasma corticosterone (CORT) response to novelty [12,16,18,19]. Handling of the preweanling rat for even short periods (15 min) results in an HPA system that is hypo responsive to acute stressors and remains so for the duration of the animal’s life [14,15]

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