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A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment
Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR v...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cambridge University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198175/ https://www.ncbi.nlm.nih.gov/pubmed/21320392 http://dx.doi.org/10.1017/S1461145711000058 |
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author | Gaburro, Stefano Stiedl, Oliver Giusti, Pietro Sartori, Simone B. Landgraf, Rainer Singewald, Nicolas |
author_facet | Gaburro, Stefano Stiedl, Oliver Giusti, Pietro Sartori, Simone B. Landgraf, Rainer Singewald, Nicolas |
author_sort | Gaburro, Stefano |
collection | PubMed |
description | Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments. |
format | Online Article Text |
id | pubmed-3198175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31981752011-11-03 A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment Gaburro, Stefano Stiedl, Oliver Giusti, Pietro Sartori, Simone B. Landgraf, Rainer Singewald, Nicolas Int J Neuropsychopharmacol Research Article Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments. Cambridge University Press 2011-11 2011-02-15 /pmc/articles/PMC3198175/ /pubmed/21320392 http://dx.doi.org/10.1017/S1461145711000058 Text en © CINP and Cambridge University Press 2011 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use. http://creativecommons.org/licenses/by-nc-sa/2.5/ The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. (http://creativecommons.org/licenses/by-nc-sa/2.5/>) The written permission of Cambridge University Press must be obtained for commercial re-use. |
spellingShingle | Research Article Gaburro, Stefano Stiedl, Oliver Giusti, Pietro Sartori, Simone B. Landgraf, Rainer Singewald, Nicolas A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
title | A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
title_full | A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
title_fullStr | A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
title_full_unstemmed | A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
title_short | A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
title_sort | mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198175/ https://www.ncbi.nlm.nih.gov/pubmed/21320392 http://dx.doi.org/10.1017/S1461145711000058 |
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