An updated animal model capturing both the cognitive and emotional features of post-traumatic stress disorder (PTSD)

Abstract

The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines post-traumatic stress disorder (PTSD) as a "trauma and stressor-related disorder". PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e., social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffering effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets of the pathology.

Keywords: animal models of PTSD; footshock; memory; predator odor; rats; social behavior; stress; trauma.

Figure 1

Schematic representation of the cat odor and footshock exposure PTSD models.

Figure 2

(A) Percentage of time spent in freezing and (B) number of crossings of rats exposed to an unworn (unexposed) or to a worn (exposed) cat collar during the exposure session (left plot) (EXP, UNEXP: n = 12) and re-exposure sessions performed 1, 7, or 14 days after the exposure to the stressor (right plots) (1D EXP n = 8, UNEXP n = 7; 7D EXP, UNEXP n = 9; 14D EXP n = 9, UNEXP n = 8). Data are expressed as mean + SEM (* p < 0.05; ** p < 0.01; *** p < 0.001; EXP vs. UNEXP).

Figure 3

Percentage of time spent in freezing of rats exposed to the context and not shocked (unexposed) or exposed to the context and given five inescapable footshocks (exposed) during the re-exposure sessions performed 1, 7, 14, 21 and 54 days after the exposure (n = 8–11). (A) Isolated, (B) social-housed animals. Data are expressed as mean + SEM (* p < 0.05; ** p < 0.01; EXP vs. UNEXP).

Figure 4

(A,D) Percentage of time in the open arms, (B,E) percentage of open arm entries and (C,F) closed arms entries of rats unexposed or exposed to the footshock in the EPM 1, 7, 14, 21 days after exposure to the stressor (n = 8–11). Data are expressed as mean + SEM (* p < 0.05; ** p < 0.01).

Figure 5

Time spent in social interaction of unexposed and exposed rats 1, 7, 14, 21 and 54 days the exposure to the stressor (n = 8–11). (A) Isolated, (B) social-housed animals. Data are expressed as mean + SEM (* p < 0.05; ** p < 0.01).