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Chronic Exposure to Glucocorticoids Induces Suboptimal Decision-Making in Mice

Lidia Cabeza, Bahrie Ramadan, View ORCID ProfileJulie Giustiniani, Christophe Houdayer, Yann Pellequer, View ORCID ProfileDamien Gabriel, View ORCID ProfileSylvie Fauconnet, View ORCID ProfileEmmanuel Haffen, View ORCID ProfilePierre-Yves Risold, View ORCID ProfileDominique Fellmann, View ORCID ProfileDavid Belin, View ORCID ProfileYvan Peterschmitt
doi: https://doi.org/10.1101/2020.09.11.293217
Lidia Cabeza
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
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  • For correspondence: lidia.cabeza_alvarez@edu.univ-fcomte.fr yvan.peterschmitt@univ-fcomte.fr
Bahrie Ramadan
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
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Julie Giustiniani
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
2Hôpital Universitaire CHRU, Clinical Psychiatry, Besançon, France
3Hôpital Universitaire CHRU, CIC-1431, Besançon, France
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Christophe Houdayer
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
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Yann Pellequer
4PEPITE EA-4267, Université de Bourgogne – Franche-Comté, Besançon, France
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Damien Gabriel
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
3Hôpital Universitaire CHRU, CIC-1431, Besançon, France
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Sylvie Fauconnet
5Laboratoire de Carcinogenèse associée aux HPV EA3-181, Université de Bourgogne – Franche-Comté, Besançon, France
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Emmanuel Haffen
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
2Hôpital Universitaire CHRU, Clinical Psychiatry, Besançon, France
3Hôpital Universitaire CHRU, CIC-1431, Besançon, France
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Pierre-Yves Risold
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
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Dominique Fellmann
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
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David Belin
6University of Cambridge, Department of Psychology, Cambridge, United Kingdom
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Yvan Peterschmitt
1Laboratoire de Neurosciences Intégratives et Cliniques EA-481, Université de Bourgogne – Franche-Comté, Besançon, France
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  • For correspondence: lidia.cabeza_alvarez@edu.univ-fcomte.fr yvan.peterschmitt@univ-fcomte.fr
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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.

Competing Interest Statement

The authors have declared no competing interest.

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Posted September 14, 2020.
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Chronic Exposure to Glucocorticoids Induces Suboptimal Decision-Making in Mice
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
bioRxiv 2020.09.11.293217; doi: https://doi.org/10.1101/2020.09.11.293217
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Chronic Exposure to Glucocorticoids Induces Suboptimal Decision-Making in Mice
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
bioRxiv 2020.09.11.293217; doi: https://doi.org/10.1101/2020.09.11.293217

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