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      Glucocorticoid Abnormalities in Female Rats Exposed to a Predator-Based Psychosocial Stress Model of PTSD

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          Abstract

          People with post-traumatic stress disorder (PTSD) exhibit heightened anxiety and enhanced negative feedback of the hypothalamus-pituitary-adrenal (HPA) axis. We previously reported that male rats exposed to a predator-based psychosocial stress model of PTSD exhibited comparable changes in anxiety-like behavior and HPA axis activity, including lower baseline levels of corticosterone and a greater suppression of corticosterone after dexamethasone administration. Here, we assessed whether we would observe similar effects in female rats exposed to this model. Adult female Sprague-Dawley rats were exposed to a cat on two occasions (separated by 10 days), in combination with chronic social instability. Three weeks after the second cat exposure, we assessed anxiety-like behavior on an elevated plus maze (EPM) and collected blood samples from rats in the absence or presence of dexamethasone to quantify serum corticosterone levels. Although stressed females did not display heightened anxiety on the EPM, they exhibited significantly lower overall corticosterone levels and a greater suppression of corticosterone after dexamethasone administration. The observation of significantly lower overall corticosterone levels in stressed females was replicated in a separate, independent experiment. These findings suggest that the predator-based psychosocial stress model of PTSD may be useful for studying mechanisms that underlie changes in HPA axis function in females exposed to trauma.

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          Most cited references31

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          Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis.

          Post-traumatic stress disorder (PTSD) has inconsistently been associated with lower levels of cortisol. To compare basal cortisol levels in adults with current PTSD and in people without psychiatric disorder. Systematic review and meta-analysis. Standardised mean differences (SMD) in basal cortisol levels were calculated and random-effects models using inverse variance weighting were applied. Across 37 studies, 828 people with PTSD and 800 controls did not differ in cortisol levels (pooled SMD=-0.12, 95% CI=-0.32 to 0.080). Subgroup analyses revealed that studies assessing plasma or serum showed significantly lower levels in people with PTSD than in controls not exposed to trauma. Lower levels were also found in people with PTSD when females were included, in studies on physical or sexual abuse, and in afternoon samples. Low cortisol levels in PTSD are only found under certain conditions. Future research should elucidate whether low cortisol is related to gender or abuse and depends on the measurement methods used.
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            Sex differences in animal tests of anxiety.

            To explore further the meaning of sexually dimorphic behavior in the open-field test, male and female hooded Lister rats were tested in three tests of anxiety. In the social interaction test, the social interaction scores of the female rats were lower and did not increase as readily following familiarization to the apparatus as those of the male rats. In the elevated plus-maze test, female rats showed a reduced aversion to the open arms compared to male rats; and in a modified Vogel conflict test, the punished licking rates of the female rats were lower than those of the male rats. It is concluded that the behavior of male and female rats differs in these tests, but that firm conclusions concerning sex differences in anxiety levels cannot be made because all three tests did not lead to predictions which were in the same direction. It is also suggested that cautious interpretation is necessary because these tests may measure different variables in male and female rats and they may not be valid tests of anxiety for female rats.
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              Current status on behavioral and biological markers of PTSD: a search for clarity in a conflicting literature.

              Extensive research has identified stereotypic behavioral and biological abnormalities in post-traumatic stress disorder (PTSD), such as heightened autonomic activity, an exaggerated startle response, reduced basal cortisol levels and cognitive impairments. We have reviewed primary research in this area, noting that factors involved in the susceptibility and expression of PTSD symptoms are more complex and heterogeneous than is commonly stated, with extensive findings which are inconsistent with the stereotypic behavioral and biological profile of the PTSD patient. A thorough assessment of the literature indicates that interactions among myriad susceptibility factors, including social support, early life stress, sex, age, peri- and post-traumatic dissociation, cognitive appraisal of trauma, neuroendocrine abnormalities and gene polymorphisms, in conjunction with the inconsistent expression of the disorder across studies, confounds attempts to characterize PTSD as a monolithic disorder. Overall, our assessment of the literature addresses the great challenge in developing a behavioral and biomarker-based diagnosis of PTSD. Published by Elsevier Ltd.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                18 June 2021
                2021
                : 15
                : 675206
                Affiliations
                [1] 1Psychology Program, The School of Health and Behavioral Sciences, Ohio Northern University, Ada , Ohio, OH, United States
                [2] 2Department of Pharmaceutical Sciences, Marshall University School of Pharmacy , Huntington, WV, United States
                Author notes

                Edited by: Dayan Kessler Knox, University of Delaware, United States

                Reviewed by: Robert Spencer, University of Colorado Boulder, United States; Debra A. Bangasser, Temple University, United States

                *Correspondence: Phillip R. Zoladz p-zoladz@ 123456onu.edu

                This article was submitted to Emotion Regulation and Processing, a section of the journal Frontiers in Behavioral Neuroscience

                Article
                10.3389/fnbeh.2021.675206
                8249699
                34220463
                ffc8a07f-2062-4e8f-a765-849053ddf9d9
                Copyright © 2021 Zoladz, Del Valle, Smith, Goodman, Dodson, Elmouhawesse, Kasler and Rorabaugh.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 March 2021
                : 24 May 2021
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 31, Pages: 10, Words: 7149
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R15HL132322
                Categories
                Behavioral Neuroscience
                Original Research

                Neurosciences
                corticosterone,females,ptsd,animal model,hpa axis,anxiety
                Neurosciences
                corticosterone, females, ptsd, animal model, hpa axis, anxiety

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