TY - JOUR

T1 - Chronic corticosterone improves perseverative behavior in mice during sequential reversal learning

AU - Odland, Anna U.

AU - Sandahl, Rune

AU - Andreasen, Jesper T.

N1 - Funding Information: This research was supported by Lundbeckfonden [grant R263–2017–3000 ] for the PhD project of A.U.O. The funding source had no influence on the design, analysis, or reporting of the study. The authors declare no conflicts of interest. Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - Background: Stressful life events can both trigger development of psychiatric disorders and promote positive behavioral changes in response to adversities. The relationship between stress and cognitive flexibility is complex, and conflicting effects of stress manifest in both humans and laboratory animals. Objective: To mirror the clinical situation where stressful life events impair mental health or promote behavioral change, we examined the post-exposure effects of stress on cognitive flexibility in mice. Methods: We tested female C57BL/6JOlaHsd mice in the touchscreen-based sequential reversal learning test. Corticosterone (CORT) was used as a model of stress and was administered in the drinking water for two weeks before reversal learning. Control animals received drinking water without CORT. Behaviors in supplementary tests were included to exclude non-specific confounding effects of CORT and improve interpretation of the results. Results: CORT-treated mice were similar to controls on all touchscreen parameters before reversal. During the low accuracy phase of reversal learning, CORT reduced perseveration index, a measure of perseverative responding, but did not affect acquisition of the new reward contingency. This effect was not related to non-specific deficits in chamber activity. CORT increased anxiety-like behavior in the elevated zero maze test and repetitive digging in the marble burying test, reduced locomotor activity, but did not affect spontaneous alternation behavior. Conclusion: CORT improved cognitive flexibility in the reversal learning test by extinguishing prepotent responses that were no longer rewarded, an effect possibly related to a stress-mediated increase in sensitivity to negative feedback that should be confirmed in a larger study.

AB - Background: Stressful life events can both trigger development of psychiatric disorders and promote positive behavioral changes in response to adversities. The relationship between stress and cognitive flexibility is complex, and conflicting effects of stress manifest in both humans and laboratory animals. Objective: To mirror the clinical situation where stressful life events impair mental health or promote behavioral change, we examined the post-exposure effects of stress on cognitive flexibility in mice. Methods: We tested female C57BL/6JOlaHsd mice in the touchscreen-based sequential reversal learning test. Corticosterone (CORT) was used as a model of stress and was administered in the drinking water for two weeks before reversal learning. Control animals received drinking water without CORT. Behaviors in supplementary tests were included to exclude non-specific confounding effects of CORT and improve interpretation of the results. Results: CORT-treated mice were similar to controls on all touchscreen parameters before reversal. During the low accuracy phase of reversal learning, CORT reduced perseveration index, a measure of perseverative responding, but did not affect acquisition of the new reward contingency. This effect was not related to non-specific deficits in chamber activity. CORT increased anxiety-like behavior in the elevated zero maze test and repetitive digging in the marble burying test, reduced locomotor activity, but did not affect spontaneous alternation behavior. Conclusion: CORT improved cognitive flexibility in the reversal learning test by extinguishing prepotent responses that were no longer rewarded, an effect possibly related to a stress-mediated increase in sensitivity to negative feedback that should be confirmed in a larger study.

KW - Cognitive flexibility

KW - Corticosterone

KW - Extinction learning

KW - Mouse behavior

KW - Reversal learning

KW - Stress

U2 - 10.1016/j.bbr.2023.114479

DO - 10.1016/j.bbr.2023.114479

M3 - Journal article

C2 - 37169127

AN - SCOPUS:85159637076

VL - 450

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

M1 - 114479

ER -