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Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later

In basic research, the etiology of fear-related pathologies, such as post-traumatic stress disorder (PTSD), is conceptualized using fear-conditioning protocols that pair environmental stimuli (that is, a conditioned stimulus—CS) with an aversive, unconditioned stimulus (US) to elicit an assessable c...

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Autores principales: Ritov, G, Richter-Levin, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545737/
https://www.ncbi.nlm.nih.gov/pubmed/28072410
http://dx.doi.org/10.1038/tp.2016.277
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author Ritov, G
Richter-Levin, G
author_facet Ritov, G
Richter-Levin, G
author_sort Ritov, G
collection PubMed
description In basic research, the etiology of fear-related pathologies, such as post-traumatic stress disorder (PTSD), is conceptualized using fear-conditioning protocols that pair environmental stimuli (that is, a conditioned stimulus—CS) with an aversive, unconditioned stimulus (US) to elicit an assessable conditioned fear response. Although pathophysiological models agree that regulatory dysfunctions in this associative process may instigate fear-related pathology, current opinions differ in regard to the nature of these dysfunctions. Primarily derived from studies in rodents, the prevailing perspective proposes that pathological fear-reactions develop from intensified and overly consolidated CS-US associations. Alternatively, models derived from studies in humans suggest that tempospatial inaccuracies in representations of associative fear might precipitate pathology by engendering failure to differentiate present experiences and past memories of threat. To test this concept in rodents, we administered rats with cognition enhancing doses of Methylphenidate before or after fear conditioning and measured long-term alterations in their conditioned fear behaviors and PTSD-like reactions. The administration of Methylphenidate before fear-memory formation indeed reduced anxious-like responses during fear-memory retrieval one month later. An individual profiling analysis revealed that Methylphenidate onset had opposing effects on the risk for PTSD-like classification. The modulation of initial learning and formation of associative fear normalized the risk for developing PTSD-like reaction. In contrast, when the effects of Methylphenidate were exerted only over later consolidation this risk increased markedly. When examined under current psychiatric and neuropharmacologic literature, these results reveal a possible strategy of using low-dose Methylphenidate for the prevention of PTSD in high risk populations.
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spelling pubmed-55457372017-08-07 Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later Ritov, G Richter-Levin, G Transl Psychiatry Original Article In basic research, the etiology of fear-related pathologies, such as post-traumatic stress disorder (PTSD), is conceptualized using fear-conditioning protocols that pair environmental stimuli (that is, a conditioned stimulus—CS) with an aversive, unconditioned stimulus (US) to elicit an assessable conditioned fear response. Although pathophysiological models agree that regulatory dysfunctions in this associative process may instigate fear-related pathology, current opinions differ in regard to the nature of these dysfunctions. Primarily derived from studies in rodents, the prevailing perspective proposes that pathological fear-reactions develop from intensified and overly consolidated CS-US associations. Alternatively, models derived from studies in humans suggest that tempospatial inaccuracies in representations of associative fear might precipitate pathology by engendering failure to differentiate present experiences and past memories of threat. To test this concept in rodents, we administered rats with cognition enhancing doses of Methylphenidate before or after fear conditioning and measured long-term alterations in their conditioned fear behaviors and PTSD-like reactions. The administration of Methylphenidate before fear-memory formation indeed reduced anxious-like responses during fear-memory retrieval one month later. An individual profiling analysis revealed that Methylphenidate onset had opposing effects on the risk for PTSD-like classification. The modulation of initial learning and formation of associative fear normalized the risk for developing PTSD-like reaction. In contrast, when the effects of Methylphenidate were exerted only over later consolidation this risk increased markedly. When examined under current psychiatric and neuropharmacologic literature, these results reveal a possible strategy of using low-dose Methylphenidate for the prevention of PTSD in high risk populations. Nature Publishing Group 2017-01 2017-01-10 /pmc/articles/PMC5545737/ /pubmed/28072410 http://dx.doi.org/10.1038/tp.2016.277 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Ritov, G
Richter-Levin, G
Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later
title Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later
title_full Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later
title_fullStr Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later
title_full_unstemmed Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later
title_short Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later
title_sort pre-trauma methylphenidate in rats reduces ptsd-like reactions one month later
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545737/
https://www.ncbi.nlm.nih.gov/pubmed/28072410
http://dx.doi.org/10.1038/tp.2016.277
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