Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder

Ziv Ardi, Anne Albrecht, Alon Richter-Levin, Rinki Saha, Gal Richter-Levin

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Diagnosis of psychiatric disorders in humans is based on comparing individuals to the normal population. However, many animal models analyze averaged group effects, thus compromising their translational power. This discrepancy is particularly relevant in posttraumatic stress disorder (PTSD), where only a minority develop the disorder following a traumatic experience.In our PTSD rat model, we utilize a novel behavioral profiling approach that allows the classification of affected and unaffected individuals in a trauma-exposed population.Rats were exposed to underwater trauma (UWT) and four weeks later their individual performances in the open field and elevated plus maze were compared to those of the control group, allowing the identification of affected and resilient UWT-exposed rats.Behavioral profiling revealed that only a subset of the UWT-exposed rats developed long-lasting behavioral symptoms. The proportion of affected rats was further enhanced by pre-exposure to juvenile stress, a well-described risk factor of PTSD.For a biochemical proof of concept we analyzed the expression levels of the GABAA receptor subunits α1 and α2 in the ventral, dorsal hippocampus and basolateral amygdala. Increased expression, mainly of α1, was observed in ventral but not dorsal hippocampus of exposed animals, which would traditionally be interpreted as being associated with the exposure-resultant psychopathology. However, behavioral profiling revealed that this increased expression was confined to exposed-unaffected individuals, suggesting a resilience-associated expression regulation. The results provide evidence for the importance of employing behavioral profiling in animal models of PTSD, in order to better understand the neural basis of stress vulnerability and resilience.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalNeurobiology of Disease
Volume88
DOIs
StatePublished - 1 Apr 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

Funding

This research was funded by the German Israeli Project Cooperation (DIP) RI 1922/1-1 HE 1128/16-1 , to Gal Richter-Levin, and by a USAMRMC award ( 10071009 ) to Gal Richter-Levin.

FundersFunder number
DIPRI 1922/1-1 HE 1128/16-1
German Israeli Project Cooperation
Medical Research and Materiel Command10071009

    Keywords

    • Animal models
    • Behavioral profiling
    • GABA A receptor
    • Hippocampus
    • PTSD
    • Resilience
    • Risk factors

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