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Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood

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Abstract

Rationale

Adverse events during early developmental stages can induce persistent changes in central stress circuits, leading to increased stress sensitivity in adulthood, as is apparent in the maternally separated (MS) rat model. It is widely accepted that the stress peptide corticotropin-releasing factor (CRF) by binding to CRF1 and 2 receptors (CRFR1 and CRFR2) is key to these phenotypic changes.

Objectives

These studies aim to investigate the effects of maternal separation on central expression of CRFR1 and CRFR2 under basal conditions and following an acute psychological stressor in adulthood.

Methods

Western blotting techniques were employed to examine changes in receptor expression in the hypothalamus, pre-frontal and frontal cortices, amygdala and hippocampus of MS rats as compared to controls. Additionally, the effects of an acute psychological stressor (open field exposure) on these changes were assessed.

Results

Under basal conditions, CRFR1 was elevated in the hypothalamus of MS rats. Exposure to an acute stress had limited effects in non-separated animals but induced significant changes in CRFR1 in the hypothalamus, pre-frontal cortex and hippocampus of MS rats. Additionally, stress-induced increases in CRFR2 were observed in the amygdala of MS rats.

Conclusions

These data demonstrate the discrete and significant alterations in how the brain CRF system responds to acute stress following maternal separation. These studies illustrate that early life perturbations induce persistent changes in central CRF receptor expression and increased sensitivity to stress, which may contribute to the stress-related behavioural changes observed in these animals.

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Acknowledgements

We wish to express our gratitude to Dr. Sinead Gibney for inducing the OF stress and thank Patrick Fitzgerald and Dr. Marcela Julio-Pieper for their technical expertise. All experiments were in full accordance with the principles of the European Community Council Directive (86/609/EEC) and the local ethical committee (University College Cork). The authors and their work were supported by a Science Foundation Ireland (grant nos. 02/CE/B124 and 07/CE/B1368) and GlaxoSmithKline. JFC is funded by European Community’s Seventh Framework Programme; grant number FP7/2007-2013, grant agreement 201714.

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Authors and Affiliations

  1. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

    Dervla O’Malley, Timothy G. Dinan & John F. Cryan

  2. Department of Psychiatry, University College Cork, Cork, Ireland

    Timothy G. Dinan

  3. Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland

    John F. Cryan

  4. School of Pharmacy, University College Cork, Cavanagh Pharmacy Building, Cork, Ireland

    John F. Cryan

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  1. Dervla O’Malley
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Correspondence to John F. Cryan.

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O’Malley, D., Dinan, T.G. & Cryan, J.F. Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood. Psychopharmacology 214, 221–229 (2011). https://doi.org/10.1007/s00213-010-1885-9

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  • DOI: https://doi.org/10.1007/s00213-010-1885-9

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