Cargando…

Examining the long-term effects of traumatic brain injury on fear extinction in male rats

There is a strong association between traumatic brain injuries (TBIs) and the development of psychiatric disorders, including post-traumatic stress disorder (PTSD). Exposure-based therapy is a first-line intervention for individuals who suffer from PTSD and other anxiety-related disorders; however,...

Descripción completa

Detalles Bibliográficos
Autores principales: Smith, K. A., Raskin, M. R., Donovan, M. H., Raghunath, V., Mansoorshahi, S., Telch, M. J., Shumake, J., Noble-Haeusslein, L. J., Monfils, M. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313105/
https://www.ncbi.nlm.nih.gov/pubmed/37397129
http://dx.doi.org/10.3389/fnbeh.2023.1206073
_version_ 1785067054136557568
author Smith, K. A.
Raskin, M. R.
Donovan, M. H.
Raghunath, V.
Mansoorshahi, S.
Telch, M. J.
Shumake, J.
Noble-Haeusslein, L. J.
Monfils, M. H.
author_facet Smith, K. A.
Raskin, M. R.
Donovan, M. H.
Raghunath, V.
Mansoorshahi, S.
Telch, M. J.
Shumake, J.
Noble-Haeusslein, L. J.
Monfils, M. H.
author_sort Smith, K. A.
collection PubMed
description There is a strong association between traumatic brain injuries (TBIs) and the development of psychiatric disorders, including post-traumatic stress disorder (PTSD). Exposure-based therapy is a first-line intervention for individuals who suffer from PTSD and other anxiety-related disorders; however, up to 50% of individuals with PTSD do not respond well to this approach. Fear extinction, a core mechanism underlying exposure-based therapy, is a procedure in which a repeated presentation of a conditioned stimulus in the absence of an unconditioned stimulus leads to a decrease in fear expression, and is a useful tool to better understand exposure-based therapy. Identifying predictors of extinction would be useful in developing alternative treatments for the non-responders. We recently found that CO(2) reactivity predicts extinction phenotypes in rats, likely through the activation of orexin receptors in the lateral hypothalamus. While studies have reported mixed results in extinction of fear after TBI, none have examined the long-term durability of this phenotype in the more chronically injured brain. Here we tested the hypothesis that TBI results in a long-term deficit in fear extinction, and that CO(2) reactivity would be predictive of this extinction phenotype. Isoflurane-anesthetized adult male rats received TBI (n = 59) (produced by a controlled cortical impactor) or sham surgery (n = 29). One month post-injury or sham surgery, rats underwent a CO(2) or air challenge, followed by fear conditioning, extinction, and fear expression testing. TBI rats exposed to CO(2) (TBI-CO(2)) showed no difference during extinction or fear expression relative to shams exposed to CO(2) (sham-CO(2)). However, TBI-CO(2) rats, showed significantly better fear expression than TBI rats exposed to air (TBI-air). In contrast to previous findings, we observed no relationship between CO(2) reactivity and post-extinction fear expression in either the sham or TBI rats. However, compared to the previously observed naïve sample, we observed more variability in post-extinction fear expression but a very similar distribution of CO(2) reactivity in the current sample. Isoflurane anesthesia may lead to interoceptive threat habituation, possibly via action on orexin receptors in the lateral hypothalamus, and may interact with CO(2) exposure, resulting in enhanced extinction. Future work will directly test this possibility.
format Online
Article
Text
id pubmed-10313105
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-103131052023-07-01 Examining the long-term effects of traumatic brain injury on fear extinction in male rats Smith, K. A. Raskin, M. R. Donovan, M. H. Raghunath, V. Mansoorshahi, S. Telch, M. J. Shumake, J. Noble-Haeusslein, L. J. Monfils, M. H. Front Behav Neurosci Neuroscience There is a strong association between traumatic brain injuries (TBIs) and the development of psychiatric disorders, including post-traumatic stress disorder (PTSD). Exposure-based therapy is a first-line intervention for individuals who suffer from PTSD and other anxiety-related disorders; however, up to 50% of individuals with PTSD do not respond well to this approach. Fear extinction, a core mechanism underlying exposure-based therapy, is a procedure in which a repeated presentation of a conditioned stimulus in the absence of an unconditioned stimulus leads to a decrease in fear expression, and is a useful tool to better understand exposure-based therapy. Identifying predictors of extinction would be useful in developing alternative treatments for the non-responders. We recently found that CO(2) reactivity predicts extinction phenotypes in rats, likely through the activation of orexin receptors in the lateral hypothalamus. While studies have reported mixed results in extinction of fear after TBI, none have examined the long-term durability of this phenotype in the more chronically injured brain. Here we tested the hypothesis that TBI results in a long-term deficit in fear extinction, and that CO(2) reactivity would be predictive of this extinction phenotype. Isoflurane-anesthetized adult male rats received TBI (n = 59) (produced by a controlled cortical impactor) or sham surgery (n = 29). One month post-injury or sham surgery, rats underwent a CO(2) or air challenge, followed by fear conditioning, extinction, and fear expression testing. TBI rats exposed to CO(2) (TBI-CO(2)) showed no difference during extinction or fear expression relative to shams exposed to CO(2) (sham-CO(2)). However, TBI-CO(2) rats, showed significantly better fear expression than TBI rats exposed to air (TBI-air). In contrast to previous findings, we observed no relationship between CO(2) reactivity and post-extinction fear expression in either the sham or TBI rats. However, compared to the previously observed naïve sample, we observed more variability in post-extinction fear expression but a very similar distribution of CO(2) reactivity in the current sample. Isoflurane anesthesia may lead to interoceptive threat habituation, possibly via action on orexin receptors in the lateral hypothalamus, and may interact with CO(2) exposure, resulting in enhanced extinction. Future work will directly test this possibility. Frontiers Media S.A. 2023-06-16 /pmc/articles/PMC10313105/ /pubmed/37397129 http://dx.doi.org/10.3389/fnbeh.2023.1206073 Text en Copyright © 2023 Smith, Raskin, Donovan, Raghunath, Mansoorshahi, Telch, Shumake, Noble-Haeusslein and Monfils. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Neuroscience
Smith, K. A.
Raskin, M. R.
Donovan, M. H.
Raghunath, V.
Mansoorshahi, S.
Telch, M. J.
Shumake, J.
Noble-Haeusslein, L. J.
Monfils, M. H.
Examining the long-term effects of traumatic brain injury on fear extinction in male rats
title Examining the long-term effects of traumatic brain injury on fear extinction in male rats
title_full Examining the long-term effects of traumatic brain injury on fear extinction in male rats
title_fullStr Examining the long-term effects of traumatic brain injury on fear extinction in male rats
title_full_unstemmed Examining the long-term effects of traumatic brain injury on fear extinction in male rats
title_short Examining the long-term effects of traumatic brain injury on fear extinction in male rats
title_sort examining the long-term effects of traumatic brain injury on fear extinction in male rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313105/
https://www.ncbi.nlm.nih.gov/pubmed/37397129
http://dx.doi.org/10.3389/fnbeh.2023.1206073
work_keys_str_mv AT smithka examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT raskinmr examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT donovanmh examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT raghunathv examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT mansoorshahis examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT telchmj examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT shumakej examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT noblehaeussleinlj examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats
AT monfilsmh examiningthelongtermeffectsoftraumaticbraininjuryonfearextinctioninmalerats