title: Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder.
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.
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Israel; The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Israel. Electronic address: zivardi@gmail.com.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ardi
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Israel; The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Israel.
authors.forename: Anne
authors.initials: A
authors.lastname: Albrecht
authors.affiliation: The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Richter-Levin
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Israel; The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Israel.
authors.forename: Rinki
authors.initials: R
authors.lastname: Saha
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Israel; The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Israel; Psychology Department, University of Haifa, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Richter-Levin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D008124:Locomotion; D008297:Male; D018782:Maze Learning / Q000502:physiology; D001523:Mental Disorders / Q000209:etiology* / Q000378:metabolism*; D009812:Odorants; D011569:Psychiatric Status Rating Scales; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000150:complications* / Q000473:pathology
chemical_list: D011963:Receptors, GABA-A
keywords: Animal models; Behavioral profiling; GABA A receptor; Hippocampus; PTSD; Resilience; Risk factors