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

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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, 5weeks 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 (0.25–4mg/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 (4–20mg/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.