Two weeks of predatory stress induces anxiety-like behavior with co-morbid depressive-like behavior in adult male mice

Abstract

Psychological stress can have devastating and lasting effects on a variety of behaviors, especially those associated with mental illnesses such as anxiety and depression. Animal models of chronic stress are frequently used to elucidate the mechanisms underlying the relationship between stress and mental health disorders and to develop improved treatment options. The current study expands upon a novel chronic stress paradigm for mice: predatory stress. The predatory stress model incorporates the natural predator-prey relationship that exists among rats and mice and allows for greater interaction between the animals, in turn increasing the extent of the stressful experience. In this study, we evaluated the behavioral effects of exposure to 15 days of predatory stress on an array of behavioral indices. Up to 2 weeks after the end of stress, adult male mice showed an increase of anxiety-like behaviors as measured by the open field and social interaction tests. Animals also expressed an increase in depressive-like behavior in the sucrose preference test. Notably, performance on the novel object recognition task, a memory test, improved after predatory stress. Taken as a whole, our results indicate that 15 exposures to this innovative predatory stress paradigm are sufficient to elicit robust anxiety-like behaviors with evidence of co-morbid depressive-like behavior, as well as changes in cognitive behavior in male mice.

Keywords: Anxiety-like behavior; Depressive-like behavior; Mice; Predatory stress.

Fig. 1

Timeline of behavioral testing and predatory stress. Behavioral testing was conducted prior and following chronic stress in order to measure the effects of the stress paradigm on anxiety- and depressive-like behaviors, as well as on cognition. Behaviors were completed in the following order before and after stress: sucrose preference, open field, novel object, marble burying, and social interaction. Predatory stress lasted 15 days and post-behavioral testing began the day after the end of stress.

Fig. 2

Predatory stress increased affective behaviors. (a) Control mice travelled a greater distance in the open field during the second round. However, mice exposed to predatory stress did not alter the distance travelled between the two rounds of testing. (b) Stressed mice travelled significantly less distance in the center after predatory stress. (c) Total time spent in social contact was decreased by predatory stress but unaltered by repeated testing. (d) When compared to the control group, mice exposed to stress significantly increased their consumption of sucrose. Data shown are mean ± SEM; asterisk indicates significance at p < 0.05 in an unpaired two-tailed t-test.

Fig. 3

Behavior in the novel object test after the 24-h delay was altered by predatory stress. (a) Percentage of time spent with the novel object was unaltered by predatory stress during the no-delay task (p > 0.05). (b) Percentage of time spent with the novel object was unaltered by predatory stress during the hour-delay task (p > 0.05). (c) Chronic predatory stress increased the percentage of time spent with novel object in the 24-h delay task. Data shown are mean ± SEM; asterisk indicates significance at p < 0.05 in a paired two-tailed t-test.