Chronic mild stress-induced changes of risk assessment behaviors in mice are prevented by chronic treatment with fluoxetine but not diazepam

• CMS exposure increases risk assessment behaviors using ethological measures.
• CMS abolishes the correlations between risk assessment and decision making.
• Repeated diazepam treatment fails to reverse CMS-induced changes of risk assessment.
• Repeated fluoxetine treatment reverses the impacts of CMS on risk assessment.

As an important part of risk-related defensive behavior and central element of anxiety, risk assessment in rodents is particularly sensitive to psychosocial stress and may consequently influence the following decision-making and behavioral output. In this study, using a mouse-test battery, we evaluated the possible impacts of chronic mild stress (CMS) on risk assessment behaviors and action selections. For non-stressed control animals, a close relationship between risk assessment and choice behavior was observed in EPM and LDT. For stressed animals, however, 5 weeks of CMS exposure not only increased risk assessment behaviors, but also abolished the correlations between risk assessment and action selection. Pharmacological intervention with GABA-A receptor modulator diazepam (0.25–4 mg/kg) blocked the alterations of conventional spatiotemporal behaviors in response to CMS, but had no effect on the CMS-induced risk assessment behavioral changes. In contrast, 4-weeks of chronic treatment with fluoxetine (4–20 mg/kg), a selective serotonin reuptake inhibitor, not only ameliorated the CMS-affected risk-assessment behaviors, but also restored the CMS-impaired correlations between risk assessment and decision making-related action selection. The present findings may shed new light on the better understanding of emotional reactivity and decision making under stressful situations. These results also indicate a differential pharmacological sensitivity in CMS-affected emotional response and risk-assessment behaviors.