In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD
Objective(s): Treatments that reverse deficits in fear extinction are promising for the management of post-traumatic stress disorder (PTSD). 5-Hydroxytryptamine type 3 (5-HT3) receptor is involved in the extinction of fear memories. The present work aims to investigate the role of 5HT3 receptors in...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2021-06-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_17979_3918f1f27287160626ec1f96d55d3c5a.pdf |
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| author | Ahmad Mohammadi-Farani Mahdi Taghadosi Sara Raziee Zahra Samimi |
| author_facet | Ahmad Mohammadi-Farani Mahdi Taghadosi Sara Raziee Zahra Samimi |
| author_sort | Ahmad Mohammadi-Farani |
| collection | DOAJ |
| description | Objective(s): Treatments that reverse deficits in fear extinction are promising for the management of post-traumatic stress disorder (PTSD). 5-Hydroxytryptamine type 3 (5-HT3) receptor is involved in the extinction of fear memories. The present work aims to investigate the role of 5HT3 receptors in the infralimbic part of the medial prefrontal cortex (IL-mPFC) in extinction of conditioned fear in the single prolonged stress (SPS) model of PTSD in rats.Materials and Methods: The effect of SPS administration was evaluated on the freezing behavior in contextual and cued fear conditioning models. After the behavioral tests, levels of 5HT3 transcription in IL-mPFC were also measured in the same animals using the real-time RT-PCR method. To evaluate the possible role of local 5HT3 receptors on fear extinction, conditioned freezing was evaluated in another cohort of animals that received local microinjections of ondansetron (a 5HT3 antagonist) and ondansetron plus a 5HT3 agonist (SR 57227A) after extinction sessions. Results: Our findings showed that exposure to SPS increased the freezing response in both contextual and cued fear models. We also found that SPS is associated with increased expression of 5HT3 receptors in the IL-mPFC region. Ondansetron enhanced the fear of extinction in these animals and the enhancement was blocked by the 5HT3 agonist, SR 57227A.Conclusion: It seems that up-regulation of 5HT3 receptors in IL-mPFC is an important factor in the neurobiology of PTSD and blockade of these receptors could be considered a potential treatment for this condition. |
| first_indexed | 2024-12-14T07:22:14Z |
| format | Article |
| id | doaj.art-6f951f349f5f41c09c6e4727d7a2494b |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-14T07:22:14Z |
| publishDate | 2021-06-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-6f951f349f5f41c09c6e4727d7a2494b2022-12-21T23:11:36ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742021-06-0124677678610.22038/ijbms.2021.54299.1219717979In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSDAhmad Mohammadi-Farani0Mahdi Taghadosi1Sara Raziee2Zahra Samimi3Pharmaceutical Sciences Research Centre, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, IranDepartment of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IranStudent Research Committee, Kermanshah University of Medical Sciences, Kermanshah, IranDepartment of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IranObjective(s): Treatments that reverse deficits in fear extinction are promising for the management of post-traumatic stress disorder (PTSD). 5-Hydroxytryptamine type 3 (5-HT3) receptor is involved in the extinction of fear memories. The present work aims to investigate the role of 5HT3 receptors in the infralimbic part of the medial prefrontal cortex (IL-mPFC) in extinction of conditioned fear in the single prolonged stress (SPS) model of PTSD in rats.Materials and Methods: The effect of SPS administration was evaluated on the freezing behavior in contextual and cued fear conditioning models. After the behavioral tests, levels of 5HT3 transcription in IL-mPFC were also measured in the same animals using the real-time RT-PCR method. To evaluate the possible role of local 5HT3 receptors on fear extinction, conditioned freezing was evaluated in another cohort of animals that received local microinjections of ondansetron (a 5HT3 antagonist) and ondansetron plus a 5HT3 agonist (SR 57227A) after extinction sessions. Results: Our findings showed that exposure to SPS increased the freezing response in both contextual and cued fear models. We also found that SPS is associated with increased expression of 5HT3 receptors in the IL-mPFC region. Ondansetron enhanced the fear of extinction in these animals and the enhancement was blocked by the 5HT3 agonist, SR 57227A.Conclusion: It seems that up-regulation of 5HT3 receptors in IL-mPFC is an important factor in the neurobiology of PTSD and blockade of these receptors could be considered a potential treatment for this condition.https://ijbms.mums.ac.ir/article_17979_3918f1f27287160626ec1f96d55d3c5a.pdffear extinctioninfralimbic medial prefrontal cortexptsdsingle prolonged stress5ht3 receptor |
| spellingShingle | Ahmad Mohammadi-Farani Mahdi Taghadosi Sara Raziee Zahra Samimi In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD Iranian Journal of Basic Medical Sciences fear extinction infralimbic medial prefrontal cortex ptsd single prolonged stress 5ht3 receptor |
| title | In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD |
| title_full | In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD |
| title_fullStr | In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD |
| title_full_unstemmed | In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD |
| title_short | In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD |
| title_sort | in vivo blockade of 5ht3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of ptsd |
| topic | fear extinction infralimbic medial prefrontal cortex ptsd single prolonged stress 5ht3 receptor |
| url | https://ijbms.mums.ac.ir/article_17979_3918f1f27287160626ec1f96d55d3c5a.pdf |
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