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

Fiche publication

Date publication

janvier 2021

Journal

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FELLMANN Dominique , Pr HAFFEN Emmanuel , Dr FAUCONNET Sylvie

Tous les auteurs :
Cabeza L, Ramadan B, Giustiniani J, Houdayer C, Pellequer Y, Gabriel D, Fauconnet S, Haffen E, Risold PY, Fellmann D, Belin D, Peterschmitt Y

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33531260

Résumé

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.