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Challenge of Developing a Validated Animal Model of PTSD – Focus on Juvenile Stress Model

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Comprehensive Guide to Post-Traumatic Stress Disorder
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Abstract

Post-traumatic stress disorder may be triggered by exposure to one or more traumatic events, in particular if the trauma is extreme. When attempting to develop a translational animal model of PTSD, most studies focus on the type of 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 go on to develop the disorder. Clinical studies show that individuals vary dramatically in their susceptibility for developing PTSD, and several risk factors have been proposed. Thus, when attempting to develop an effective translational animal model of PTSD, these predisposing factors should be taken into consideration.

Epidemiological studies indicate that childhood trauma predisposes individuals to develop stress-related disorders later in life. In accordance, we developed an animal model in which exposing rats to prepubertal (“juvenile”) stress induces a predisposition to developing PTSD-related symptoms following an exposure to an additional stress in adulthood. The rationale behind the “juvenile stress” model is to induce long-term alterations in stress responsiveness by exposing rats to stressors early in life, in a period that models human childhood. When compared to a single exposure to a major stressor in adulthood, adding prior exposure to stressors in juvenility results in altered behavioral and physiological responses.

Within these preexposed animals, dissociation could be made between 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 while 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.

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Abbreviations

CBC:

Cutoff behavioral criteria

JVS:

Juvenile stress

UWT:

Underwater trauma

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Gal, RL., Orli, K., Shtoots, L., Ruchi, A. (2015). Challenge of Developing a Validated Animal Model of PTSD – Focus on Juvenile Stress Model. In: Martin, C., Preedy, V., Patel, V. (eds) Comprehensive Guide to Post-Traumatic Stress Disorder. Springer, Cham. https://doi.org/10.1007/978-3-319-08613-2_121-1

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