Cargando…
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 involved in the extinction of fear memories. The present work aims to investigate the role of 5HT3 rece...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mashhad University of Medical Sciences
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487606/ https://www.ncbi.nlm.nih.gov/pubmed/34630955 http://dx.doi.org/10.22038/ijbms.2021.54299.12197 |
_version_ | 1784577992119287808 |
---|---|
author | Mohammadi-Farani, Ahmad Taghadosi, Mahdi Raziee, Sara Samimi, Zahra |
author_facet | Mohammadi-Farani, Ahmad Taghadosi, Mahdi Raziee, Sara Samimi, Zahra |
author_sort | Mohammadi-Farani, Ahmad |
collection | PubMed |
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 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. |
format | Online Article Text |
id | pubmed-8487606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Mashhad University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-84876062021-10-08 In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD Mohammadi-Farani, Ahmad Taghadosi, Mahdi Raziee, Sara Samimi, Zahra Iran J Basic Med Sci Original Article 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 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. Mashhad University of Medical Sciences 2021-06 /pmc/articles/PMC8487606/ /pubmed/34630955 http://dx.doi.org/10.22038/ijbms.2021.54299.12197 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Mohammadi-Farani, Ahmad Taghadosi, Mahdi Raziee, Sara Samimi, Zahra In vivo blockade of 5HT3 receptors in the infralimbic medial prefrontal cortex enhances fear extinction in a rat model of PTSD |
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 | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487606/ https://www.ncbi.nlm.nih.gov/pubmed/34630955 http://dx.doi.org/10.22038/ijbms.2021.54299.12197 |
work_keys_str_mv | AT mohammadifaraniahmad invivoblockadeof5ht3receptorsintheinfralimbicmedialprefrontalcortexenhancesfearextinctioninaratmodelofptsd AT taghadosimahdi invivoblockadeof5ht3receptorsintheinfralimbicmedialprefrontalcortexenhancesfearextinctioninaratmodelofptsd AT razieesara invivoblockadeof5ht3receptorsintheinfralimbicmedialprefrontalcortexenhancesfearextinctioninaratmodelofptsd AT samimizahra invivoblockadeof5ht3receptorsintheinfralimbicmedialprefrontalcortexenhancesfearextinctioninaratmodelofptsd |