A new stress model by predatory sound produces persistent anxiety-like behaviours in male SD rats but not ICR mice

Abstract

The animal models of anxiety are beneficial to developing new medications for their treatment and understanding the mechanisms underlying anxiety disorders. However, current available animal models for the anxiety disorders are inadequate. Here, we develop a model of anxiety by predatory sound stress in rodents, which would probably benefit the experimental effectiveness and animal welfare. Specifically, a feline predatory sound (PS) at 60 or 80 dB played during the open-field test (OFT) and elevated-plus maze (EPM) in 5 min was used to elicit anxiety-like behaviour in adult male ICR mice or SD rats. We then attempted to pharmacologically validate this model in rats by testing 0.5 or 1 mg/kg doses of diazepam on these behavioural outcomes in OFT and EPM. To assess the potential long-lasting effects induced by acute PS stress, the rats were divided into five groups exposed to BG, PS, BG, PS or WN for 5 min on day 1, and then BG, BG, PS, PS or WN during the EPM test on day 8, accordingly and sequentially, which were abbreviated as BG-BG, PS-BG, BG-PS, PS-PS or WN-WN group, respectively. After the behavioural test, their plasma noradrenaline (NA), adrenaline (A), adrenocorticotropin (ACTH) and corticosterone (CORT) were measured by ELISA assays. During the period of acute PS exposure, mice did not alter the OFT or EPM behaviours; while rats significantly increased the anxiety-like responses in OFT or EPM, which were inhibited by diazepam. Relative to BG-BG group, PS-BG group increased anxiety-like behaviours and circulating NA, A, ACTH and CORT levels comparable to these by BG-PS or PS-PS group, indicating that the PS-induced anxiogenic effect persisted for at least 7 days; WN-WN group failed to produce significant effects. Therefore, this easily-handled and validated stress model produces persistent anxious effects and improves the animal welfare, which may provide the possibility of screening novel anxiolytics and exploring neurological mechanism in anxiety disorders.