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Brain-corticosteroid hormone dialogue: Slow and persistent

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Summary

1. The stress response system is shaped by genetic factors and life experiences, of which the effect of a neonatal life event is among the most persistent. Here we report studies focused on the “nature-nurture” question using rat lines genetically selected for extreme differences in dopamine phenotype as well as rats exposed as infants to the traumatic experience of maternal deprivation.

2. As key to the endocrine and behavioural adaptations occurring in these two animal models the hormone corticosterone (CORT) is considered. The stress hormone exerts slow and persistent genomic control over neuronal activity underlying the stress response system via high affinity mineralocorticoid (MR) and glucocorticoid receptors (GR). This action is exerted in a coordinate manner and involves after stress due to the rising CORT levels progressive activation of both receptor types.

3. Short periods of maternal separation (neonatal handling) trigger subsequently enhanced maternal care and sensory stimulation. However, a prolonged period (24h) of depriving the infant of maternal care disrupts the stress hyporesponsive period (SHRP) and causes an inappropriate rise in CORT. During development exposure to CORT and to sensory stimulation has long-lasting consequences for organization of the stress response system.

4. We find that these factors embodied by mother-pup interaction are critical for dopamine phenotype, CORT receptor dynamics and neuroendocrine regulation in adult life. The findings provide a conceptual framework to study dopamine-related psychopathology against a background of genetic predisposition, early life events, stress hormones and brain development.

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Authors and Affiliations

  1. Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Leiden, The Netherlands

    E. Ronald de Kloet & Nynke Y. Rots

  2. Department of Psychoneuropharmacology, Catholic University of Nijmegen, Nijmegen, The Netherlands

    Alexander R. Cools

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  1. E. Ronald de Kloet
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  2. Nynke Y. Rots
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  3. Alexander R. Cools
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Ronald de Kloet, E., Rots, N.Y. & Cools, A.R. Brain-corticosteroid hormone dialogue: Slow and persistent. Cell Mol Neurobiol 16, 345–356 (1996). https://doi.org/10.1007/BF02088100

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