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Cabeza L, Ramadan B, Giustiniani J, et al. Chronic exposure to glucocorticoids induces suboptimal decision-making in mice. Eur Neuropsychopharmacol. 2021;46:56-67doi: 10.1016/j.euroneuro.2021.01.094.
Cabeza, L., Ramadan, B., Giustiniani, J., Houdayer, C., Pellequer, Y., Gabriel, D., Fauconnet, S., Haffen, E., Risold, P. Y., Fellmann, D., Belin, D., & Peterschmitt, Y. (2021). Chronic exposure to glucocorticoids induces suboptimal decision-making in mice. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 4656-67. https://doi.org/10.1016/j.euroneuro.2021.01.094
Cabeza, Lidia, et al. "Chronic exposure to glucocorticoids induces suboptimal decision-making in mice." European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology vol. 46 (2021): 56-67. doi: https://doi.org/10.1016/j.euroneuro.2021.01.094
Cabeza L, Ramadan B, Giustiniani J, Houdayer C, Pellequer Y, Gabriel D, Fauconnet S, Haffen E, Risold PY, Fellmann D, Belin D, Peterschmitt Y. Chronic exposure to glucocorticoids induces suboptimal decision-making in mice. Eur Neuropsychopharmacol. 2021 May;46:56-67. doi: 10.1016/j.euroneuro.2021.01.094. Epub 2021 Jan 30. PMID: 33531260.
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Eur Neuropsychopharmacol. 2021 May;46:56-67. doi: 10.1016/j.euroneuro.2021.01.094. Epub 2021 Jan 30.

Chronic exposure to glucocorticoids induces suboptimal decision-making in mice.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Lidia Cabeza, Bahrie Ramadan, Julie Giustiniani, Christophe Houdayer, Yann Pellequer, Damien Gabriel, Sylvie Fauconnet, Emmanuel Haffen, Pierre-Yves Risold, Dominique Fellmann, David Belin, Yvan Peterschmitt

Affiliations

  1. Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne - Franche-Comté, Besançon, France. Electronic address: [email protected].
  2. Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne - Franche-Comté, Besançon, France.
  3. Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne - Franche-Comté, Besançon, France; Clinical Psychiatry, Hôpital Universitaire CHRU, Besançon, France; Hôpital Universitaire CHRU, CIC-INSERM-1431, Besançon, France.
  4. PEPITE EA-4267, Université de Bourgogne - Franche-Comté, Besançon, France.
  5. Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne - Franche-Comté, Besançon, France; Hôpital Universitaire CHRU, CIC-INSERM-1431, Besançon, France.
  6. Hôpital Universitaire CHRU, CIC-INSERM-1431, Besançon, France; Laboratoire de Carcinogenèse associée aux HPV EA-3181, Université de Bourgogne - Franche-Comté, Besançon, France; Urologie, andrologie et transplantation rénale, Hôpital Universitaire CHRU, Besançon, France.
  7. Department of Psychology, University of Cambridge, Cambridge, United Kingdom.
  8. Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne - Franche-Comté, Besançon, France. Electronic address: [email protected].

PMID: 33531260 DOI: 10.1016/j.euroneuro.2021.01.094

Abstract

Anxio-depressive symptoms as well as severe cognitive dysfunction including aberrant decision-making (DM) are documented in neuropsychiatric patients with hypercortisolaemia. Yet, the influence of the hypothalamo-pituitary-adrenal (HPA) axis on DM processes remains poorly understood. As a tractable mean to approach this human condition, adult male C57BL/6JRj mice were chronically treated with corticosterone (CORT) prior to behavioural, physiological and neurobiological evaluation. The behavioural data indicate that chronic CORT delays the acquisition of contingencies required to orient responding towards optimal DM performance in a mouse Gambling Task (mGT). Specifically, CORT-treated animals show a longer exploration and a delayed onset of the optimal DM performance. Remarkably, the proportion of individuals performing suboptimally in the mGT is increased in the CORT condition. This variability seems to be better accounted for by variations in sensitivity to negative rather than to positive outcome. Besides, CORT-treated animals perform worse than control animals in a spatial working memory (WM) paradigm and in a motor learning task. Finally, Western blotting neurobiological analyses show that chronic CORT downregulates glucocorticoid receptor expression in the medial Prefrontal Cortex (mPFC). Besides, corticotropin-releasing factor signalling in the mPFC of CORT individuals negatively correlates with their DM performance. Collectively, this study describes how chronic exposure to glucocorticoids induces suboptimal DM under uncertainty in a mGT, hampers WM and motor learning processes, thus affecting specific emotional, motor, cognitive and neurobiological endophenotypic dimensions relevant for precision medicine in biological psychiatry.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Corticosterone; Decision-making; Gambling task

Conflict of interest statement

Conflicts of Interest All authors declare no conflicts of interest.

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