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The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model

OBJECTIVE: The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regardin...

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Autores principales: Ketenci, Sema, Acet, Nazife Gökçe, Sarıdoğan, Gökçe Elif, Aydın, Banu, Cabadak, Hülya, Gören, Mehmet Zafer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean College of Neuropsychopharmacology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242110/
https://www.ncbi.nlm.nih.gov/pubmed/32329303
http://dx.doi.org/10.9758/cpn.2020.18.2.219
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author Ketenci, Sema
Acet, Nazife Gökçe
Sarıdoğan, Gökçe Elif
Aydın, Banu
Cabadak, Hülya
Gören, Mehmet Zafer
author_facet Ketenci, Sema
Acet, Nazife Gökçe
Sarıdoğan, Gökçe Elif
Aydın, Banu
Cabadak, Hülya
Gören, Mehmet Zafer
author_sort Ketenci, Sema
collection PubMed
description OBJECTIVE: The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regarding the role of prazosin in traumatic stress are controversial. METHODS: In this study, we examined the effects of prazosin and the noradrenergic system in fear conditioning in a predator stress rat model. We evaluated the direct or indirect effects of stress and prazosin on noradrenaline (NA), gamma-aminobuytyric acid (GABA), glutamate, glycine levels and choline esterase activity in the amygdaloid complex, the dorsal hippocampus, the prefrontal cortex and the rostral pons. RESULTS: Our results demonstrated that prazosin might alleviate defensive behaviors and traumatic stress symptoms when given during the traumatic cue presentation in the stressed rats. However prazosin administration resulted in higher anxiety levels in non stressed rats when the neutral cue was presented. CONCLUSION: Prazosin should be used in PTSD with caution because prazosin might exacerbate anxiety in non-traumatized subjects. However prazosin might as well alleviate stress responses very effectively. Stress induced changes included increased NA and GABA levels in the amygdaloid complex in our study, attributing noradrenaline a possible inhibitory role on fear acquisition. Acetylcholine also has a role in memory modulation in the brain. We also demonstrated increased choline esterase acitivity. Cholinergic modulation might be another target for indirect prazosin action which needs to be further studied.
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spelling pubmed-72421102020-05-31 The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model Ketenci, Sema Acet, Nazife Gökçe Sarıdoğan, Gökçe Elif Aydın, Banu Cabadak, Hülya Gören, Mehmet Zafer Clin Psychopharmacol Neurosci Original Article OBJECTIVE: The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regarding the role of prazosin in traumatic stress are controversial. METHODS: In this study, we examined the effects of prazosin and the noradrenergic system in fear conditioning in a predator stress rat model. We evaluated the direct or indirect effects of stress and prazosin on noradrenaline (NA), gamma-aminobuytyric acid (GABA), glutamate, glycine levels and choline esterase activity in the amygdaloid complex, the dorsal hippocampus, the prefrontal cortex and the rostral pons. RESULTS: Our results demonstrated that prazosin might alleviate defensive behaviors and traumatic stress symptoms when given during the traumatic cue presentation in the stressed rats. However prazosin administration resulted in higher anxiety levels in non stressed rats when the neutral cue was presented. CONCLUSION: Prazosin should be used in PTSD with caution because prazosin might exacerbate anxiety in non-traumatized subjects. However prazosin might as well alleviate stress responses very effectively. Stress induced changes included increased NA and GABA levels in the amygdaloid complex in our study, attributing noradrenaline a possible inhibitory role on fear acquisition. Acetylcholine also has a role in memory modulation in the brain. We also demonstrated increased choline esterase acitivity. Cholinergic modulation might be another target for indirect prazosin action which needs to be further studied. Korean College of Neuropsychopharmacology 2020-05-31 2020-05-31 /pmc/articles/PMC7242110/ /pubmed/32329303 http://dx.doi.org/10.9758/cpn.2020.18.2.219 Text en Copyright © 2020, Korean College of Neuropsychopharmacology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Ketenci, Sema
Acet, Nazife Gökçe
Sarıdoğan, Gökçe Elif
Aydın, Banu
Cabadak, Hülya
Gören, Mehmet Zafer
The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model
title The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model
title_full The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model
title_fullStr The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model
title_full_unstemmed The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model
title_short The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model
title_sort neurochemical effects of prazosin treatment on fear circuitry in a rat traumatic stress model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242110/
https://www.ncbi.nlm.nih.gov/pubmed/32329303
http://dx.doi.org/10.9758/cpn.2020.18.2.219
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