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 | ||
| مقاله 9، دوره 24، شماره 6، شهریور 2021، صفحه 776-786 اصل مقاله (681.24 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2021.54299.12197 | ||
| نویسندگان | ||
| Ahmad Mohammadi-Farani* 1، 2؛ Mahdi Taghadosi3؛ Sara Raziee4؛ Zahra Samimi3 | ||
| 1Pharmaceutical Sciences Research Centre, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 2Department of Pharmacology and Toxicology, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 3Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 4Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| چکیده | ||
| 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. | ||
| کلیدواژهها | ||
| Fear extinction؛ Infralimbic medial prefrontal cortex؛ PTSD؛ Single prolonged stress؛ 5HT3 receptor | ||
| مراجع | ||
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