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Prior Stress and Fear Conditioning Intensity Interact to Generate Sex-, and Strain-Specific Enhanced or Attenuated Fear Memory

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In humans, posttraumatic stress disorder (PTSD) is co-morbid with major depressive disorder. Individuals who are exposed to stress prior to a traumatic event have an increased likelihood of developing PTSD. To study this increased vulnerability, a rat model was developed using the Stress Enhanced Fear Learning (SEFL) paradigm. This study aims to show how SEFL’s consequences can differ depending on the sex, stress-reactivity of the animal, and intensity of fear conditioning. Wistar Kyoto (WKY) rats were bred based on their extremes in a test used to measure depression-like behavior. WKY More Immobile (WMI) strain mirrors human major depressive disorder, and the isogenic WKY Less Immobile (WLI) strain acts as a control. In the study, 16 groups of rats were used, strains (2) by sex (2) by stress (2) by shock intensity (2) with 7-8 animals in each group. Rats in the stress group received acute restraint stress 48 hours prior to contextual fear conditioning (CFC). During CFC, WLI and WMI rats received either 0.6 mA or 0.8 mA intensity foot shocks and their freezing response was measured. WLI rats showed no effect due to SEFL, while WMI males exhibit enhanced fear memory after greater intensity CFC. In contrast, WMI females show enhanced memory after 0.6 mA, but attenuated fear memory after 0.8 mA intensity CFC. Expression of target genes in the blood and brains of these animals could identify biomarkers aligned to the behavior, with potential to identify mechanisms underlying the modulation of SEFL.

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  • 06/03/2019
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