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      Pulsed electromagnetic field attenuated PTSD-induced failure of conditioned fear extinction

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          Abstract

          Objective(s):

          This study aimed to determine whether exposure to pulsed electromagnetic field (PEMF) can impair behavioral failure as induced by PTSD, and also its possible effects on hippocampal neurogenesis. PEMF was used as a non-invasive therapeutic tool in psychiatry.

          Materials and Methods:

          Male rats were divided into Control-Sham exposed, Control-PEMF, PTSD-Sham exposed, and PTSD-PEMF groups. PTSD rats were conducted by the single prolonged stress procedures and then conditioned by the contextual fear conditioning apparatus. Control rats were only conditioned. Experimental rats were submitted to daily PEMF (7 mT, 30 Hz for 16 min/day, 14 days). Sham-exposed groups were submitted to the turned off PEMF apparatus. Fear extinction, sensitized fear and anxiety, cell density in the hippocampus, and proliferation and survival rate of BrdU-labeled cells were evaluated.

          Results:

          Freezing of PTSD-PEMF rats was significantly lower than PTSD-Sham exposed. In the PTSD-PEMF, center and total crossing in open field, also the percentage of open arms entry and time in the elevated plus maze, significantly increased as compared with PTSD-Sham exposed ( P<0.001). Numbers of CA1, CA3, and DG cells in PTSD-PEMF and Control-Sham exposed groups were significantly more than PTSD-Sham exposed ( P<0.001). There were more BrdU-positive cells in the DG of the PTSD-PEMF as compared with the PTSD-Sham exposed. Qualitative observations showed an increased number of surviving BrdU-positive cells in the PTSD-PEMF as compared with PTSD-Sham exposed.

          Conclusion:

          Using 14-day PEM attenuates the PTSD-induced failure of conditioned fear extinction and exaggerated sensitized fear, and this might be related to the neuroprotective effects of magnetic fields on the hippocampus.

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          Most cited references44

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          Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells.

          Chronic treatments with selective serotonin reuptake inhibitors (SSRIs) have been shown to increase hippocampal neurogenesis. However, it is not known whether SSRIs impact the maturation and functional integration of newborn neurons. Here we examined the effects of subchronic and chronic fluoxetine on the structural and physiological properties of young granule cells. Our results show that doublecortin-positive immature neurons displayed increased dendritic arborization after chronic fluoxetine treatment. In addition, chronic but not subchronic fluoxetine elicited a decrease in the number of newborn neurons expressing immature markers and a corresponding increase in those expressing mature markers. These results suggest that chronic fluoxetine accelerates the maturation of immature neurons. We also investigated the effects of fluoxetine on a form of neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus. This form of LTP was enhanced by chronic fluoxetine, and ablation of neurogenesis with x-irradiation completely blocked the effects of chronic fluoxetine on LTP. Finally, we demonstrated that the behavioral effect of fluoxetine in the novelty-suppressed feeding test requires chronic administration and is blocked by x-irradiation. These results show that the effects of fluoxetine on LTP and behavior both require neurogenesis and follow a similar delayed time course. The effects of chronic fluoxetine on the maturation and functional properties of young neurons may therefore be necessary for its anxiolytic/antidepressant activity and contribute to its delayed onset of therapeutic efficacy.
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            Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses.

            Aversive conditioning has been proposed as an important factor involved in the etiology of posttraumatic stress disorder (PTSD). However, it is not yet fully understood exactly which learning mechanisms are characteristic for PTSD. PTSD patients (n=36), and healthy individuals with and without trauma exposure (TE group, n=21; nTE group, n=34), underwent a differential fear conditioning experiment consisting of habituation, acquisition, and extinction phases. An electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures as conditioned stimuli (CS+, paired; CS-, unpaired). Conditioned responses were quantified by skin conductance responses (SCRs), subjective ratings of CS valence and US-expectancy, and a behavioural test. In contrast to the nTE group, PTSD patients showed delayed extinction of SCRs to the CS+. Online ratings of valence and US-expectancy as well as the behavioural test confirmed this pattern. These findings point to a deficit in extinction learning and highlight the role of affective valence appraisals and cognitive biases in PTSD. In addition, there was some evidence that a subgroup of PTSD patients had difficulties in learning the CS-US contingency, thereby providing preliminary evidence of reduced discrimination learning.
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              Stress-restress: effects on ACTH and fast feedback.

              Glucocorticoid secretion is tightly regulated by negative feedback. Glucocorticoid feedback has been found to be altered in depression and post-traumatic stress disorder (PTSD). While hyposensitive glucocorticoid feedback has been found in depression, hypersensitive or enhanced negative feedback was described in PTSD. Enhanced negative feedback, can be seen as a sensitization of the inhibitory elements of HPA axis, and stress-restress or time dependent sensitization (TDS) model, has been suggested as an animal model for PTSD. We have studied the effects of this model on the HPA axis to determine whether it will produce increased sensitivity to negative feedback as found in PTSD patients. Adult Sprague-Dawley male rats were exposed to a single session of prolonged stress (restraint followed by a forced swim and exposure to ether vapors) and briefly restressed 7 days later. The effects of single prolonged stress on plasma ACTH and corticosterone responses (0, 5, and 30 min) and on glucocorticoid fast feedback (cortisol vs. saline pretreatment) were assessed in two studies. Animals exposed to single prolonged stress showed enhanced negative feedback in comparison to naive animals (F = 4.6371, df = 3, p = .0107), but there was no difference in ACTH or corticosterone responses during the restress. Pretreatment with cortisol, in the first stress session, did not prevent the development of the enhanced fast feedback when restressed. This can be seen as a sensitization of the inhibitory elements of HPA axis, suggesting that stress-restress paradigm might serve as a good animal model for HPA abnormalities found in PTSD patients.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                June 2019
                : 22
                : 6
                : 650-659
                Affiliations
                [1 ]School of Biology, Damghan University, Damghan, Semnan, Iran
                [2 ]Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
                Author notes
                [* ]Corresponding author: Kataneh Abrari. School of Biology, Damghan University, Damghan, Iran. Tel: +98-23 35220242; Fax: +98-2335220223; Email: abrari@du.ac.ir
                Article
                10.22038/ijbms.2019.32576.7797
                6570745
                12c73900-e524-45f1-996a-528dac45147d

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 June 2018
                : 12 December 2018
                Categories
                Original Article

                classical conditioning electromagnetic fields,hippocampus,neurogenesis,post-traumatic stress - disorder

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