The predator odor avoidance model of post-traumatic stress disorder in rats

Abstract

Individuals with post-traumatic stress disorder avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal axis response at the time of trauma. Our laboratory uses predator odor (i.e. bobcat urine) stress to divide adult Wistar rats into groups that exhibit high (avoiders) or low (nonavoiders) avoidance of a predator odor-paired context, modeling the fact that not all humans exposed to traumatic events develop psychiatric conditions. Male avoiders exhibit lower body weight gain after stress, as well as extinction-resistant avoidance that persists after a second stress exposure. These animals also show attenuated hypothalamic-pituitary-adrenal axis response to predator odor that predicts subsequent avoidance of the odor-paired context. Avoiders exhibit unique brain activation profiles relative to nonavoiders and controls (as measured by Fos immunoreactivity), and higher corticotropin-releasing factor levels in multiple brain regions. Furthermore, avoider rats exhibit escalated and compulsive-like alcohol self-administration after traumatic stress. Here, we review the predator odor avoidance model of post-traumatic stress disorder and its utility for tracking behavior and measuring biological outcomes predicted by avoidance. The major strengths of this model are (i) etiological validity with exposure to a single intense stressor, (ii) established approach distinguishing individual differences in stress reactivity, and (iii) robust behavioral and biological phenotypes during and after trauma.

Figure 1.

Schematic representation of bobcat urine conditioned place aversion procedure. On day 1, rats are allowed free movement between the three chambers for 5 min. The chamber in which each rat exhibits the most deviant time score (i.e., highly preferred or highly avoided) is excluded from all future sessions for that rat. On day 2, rats are allowed to explore the two non-excluded conditioning chambers for 5 min. On day 3, rats are placed in one of the chambers with the guillotine door shut without odor for 15 min. On day 4, rats are placed in the alternative chamber with the guillotine door shut and a bobcat urine soaked-sponge under the floor for 15 min, or no odor for control animals. On day 5, rats are again allowed to explore the two conditioning chambers for 5 min. Avoidance is calculated as a difference score between time spent in odor-paired context (day 5) and pre-conditioning time spent in odor-paired context (day 2). Rats that displayed a > 10 s decrease in time spent in odor-paired context are classified as Avoiders. Rats that displayed a < 10 s decrease in time spent in the predator odor-paired chamber are classified as Non-Avoiders.