The early adolescent or “juvenile stress” translational animal model of posttraumatic stress disorder

The diagnosis of posttraumatic stress disorder (PTSD) requires exposure to a major traumatic event. This criterion has influenced the thinking about causes of the disorder, approaches to treatment, and also how to establish an effective animal model of the disorder. Accordingly, the focus in animal models of PTSD is on what would establish an effective traumatic exposure that would lead to PTSD-related symptoms in the studied animal. However, the prevalence of PTSD among individuals exposed to a traumatic event suggests that the exposure to the trauma is not sufficient to induce PTSD, since most exposed individuals will not develop the disorder. The emphasis in translational animal models of PTSD should thus be on inclusion of relevant risk factors, that together with the exposure to a traumatic event will lead to the development of PTSD. Epidemiological studies indicate that childhood trauma predisposes individuals to develop stress-related disorders later in life. As a result of this finding, we developed an animal model in which exposing rats to early adolescence (postweaning, prepubertal, juvenile) stress was also found to induce a predisposition to develop PTSD following an exposure to an additional stress in adulthood. Within these pre-exposed animals, dissociation could be caused among individuals that exhibited more anxious or more depressive symptoms. This dissociation, which has been recognized also in human patients, required the development of a behavioral profiling approach that enabled grouping animals according to their clusters of symptoms. Interestingly, this approach also enabled the identification of new data on the influence of sex on long-term consequences of “Juvenile Stress.” These data reveal that whilst both male and female rats showed behavioral changes following exposure to a stressor at juvenility, the profile of effects differed between the sexes. Collectively, these findings indicate that the model presented here is an effective translational model for understanding of the etiology of trauma-related disorders and of relevant predisposing factors.