Modeling Posttraumatic Stress Disorder in a Genetic Rat Model of Depression

Lim PH; Redei EE; Sophia Jenz

doi:https://doi.org/10.21985/N25T4V

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Modeling Posttraumatic Stress Disorder in a Genetic Rat Model of Depression

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Posttraumatic stress disorder (PTSD) is an anxiety disorder characterized by flashbacks of the traumatic event and high comorbidity with major depressive disorder (MDD). Prior stress is known to increase the likelihood of developing PTSD after experiencing a traumatic event. Currently, PTSD is diagnosed clinically, its biological etiology is not known and there are few effective treatments. This study aimed to identify if a genetic animal model of depression shows PTSD-like behavior using the Stress-Enhanced Fear Learning (SEFL) paradigm, which has been used as a model for PTSD. Wistar Kyoto (WKY) rats were bi-directionally and selectively bred based on their extremes of depression-like behavior. The WKY More Immobile (WMI) strain mirror human MDD-specific traits, and the isogenic WKY Less Immobile (WLI) strain act as control without depression-like behavior. To test their SEFL, one group of WMI and WLI males and females received acute restraint stress forty-eight hours before Contextual Fear Conditioning (CFC), and a second group did not. Prior stress resulted in increased fear memory in WMI males, but not females, a finding similar to those obtained using CFC in human subjects. Plasma corticosterone differences between stressed and not-stressed WLI and WMI male and female animals immediately prior to fear conditioning paralleled SEFL results. Hippocampal expression of the glucocorticoid receptor, the nuclear receptor for corticosterone and a transcriptional factor, followed the expected pattern for being negatively regulated by its ligand. These results suggest the WMI as a model for studying the underlying neurobiology and genetics of PTSD and depression-like behavioral characteristics.

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