Cargando…

A robust and reliable non-invasive test for stress responsivity in mice

Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutan...

Descripción completa

Detalles Bibliográficos
Autores principales: Zimprich, Annemarie, Garrett, Lillian, Deussing, Jan M., Wotjak, Carsten T., Fuchs, Helmut, Gailus-Durner, Valerie, de Angelis, Martin Hrabě, Wurst, Wolfgang, Hölter, Sabine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995076/
https://www.ncbi.nlm.nih.gov/pubmed/24782732
http://dx.doi.org/10.3389/fnbeh.2014.00125
_version_ 1782312821670805504
author Zimprich, Annemarie
Garrett, Lillian
Deussing, Jan M.
Wotjak, Carsten T.
Fuchs, Helmut
Gailus-Durner, Valerie
de Angelis, Martin Hrabě
Wurst, Wolfgang
Hölter, Sabine M.
author_facet Zimprich, Annemarie
Garrett, Lillian
Deussing, Jan M.
Wotjak, Carsten T.
Fuchs, Helmut
Gailus-Durner, Valerie
de Angelis, Martin Hrabě
Wurst, Wolfgang
Hölter, Sabine M.
author_sort Zimprich, Annemarie
collection PubMed
description Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutants for alterations in their stress responses. Here we present the determinants of a robust and reliable non-invasive test for stress-responsivity in mice. Stress is applied through restraining the mice in tubes and recording behavior in the Open Field 20 min after cessation of the stress. Two hours, but not 15 or 50 min of restraint lead to a robust and reproducible increase in distance traveled and number of rearings during the first 5 min in the Open Field in C57BL/6 mice. This behavioral response is blocked by the corticosterone synthesis inhibitor metyrapone, but not by RU486 treatment, indicating that it depends on corticosteroid secretion, but is not mediated via the glucocorticoid receptor type II. We assumed that with a stress duration of 15 min one could detect hyper-responsivity, and with a stress duration of 2 h hypo-responsivity in mutant mouse lines. This was validated with two mutant lines known to show opposing effects on corticosterone secretion after stress exposure, corticotropin-releasing hormone (CRH) over-expressing mice and CRH receptor 1 knockout (KO) mice. Both lines showed the expected phenotype, i.e., increased stress responsivity in the CRH over-expressing mouse line (after 15 min restraint stress) and decreased stress responsivity in the CRHR1-KO mouse line (after 2 h of restraint stress). It is possible to repeat the acute stress test several times without the stressed animal adapting to it, and the behavioral response can be robustly evoked at different ages, in both sexes and in different mouse strains. Thus, locomotor and rearing behavior in the Open Field after an acute stress challenge can be used as reliable, non-invasive indicators of stress responsivity and corticosterone secretion in mice.
format Online
Article
Text
id pubmed-3995076
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-39950762014-04-29 A robust and reliable non-invasive test for stress responsivity in mice Zimprich, Annemarie Garrett, Lillian Deussing, Jan M. Wotjak, Carsten T. Fuchs, Helmut Gailus-Durner, Valerie de Angelis, Martin Hrabě Wurst, Wolfgang Hölter, Sabine M. Front Behav Neurosci Neuroscience Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutants for alterations in their stress responses. Here we present the determinants of a robust and reliable non-invasive test for stress-responsivity in mice. Stress is applied through restraining the mice in tubes and recording behavior in the Open Field 20 min after cessation of the stress. Two hours, but not 15 or 50 min of restraint lead to a robust and reproducible increase in distance traveled and number of rearings during the first 5 min in the Open Field in C57BL/6 mice. This behavioral response is blocked by the corticosterone synthesis inhibitor metyrapone, but not by RU486 treatment, indicating that it depends on corticosteroid secretion, but is not mediated via the glucocorticoid receptor type II. We assumed that with a stress duration of 15 min one could detect hyper-responsivity, and with a stress duration of 2 h hypo-responsivity in mutant mouse lines. This was validated with two mutant lines known to show opposing effects on corticosterone secretion after stress exposure, corticotropin-releasing hormone (CRH) over-expressing mice and CRH receptor 1 knockout (KO) mice. Both lines showed the expected phenotype, i.e., increased stress responsivity in the CRH over-expressing mouse line (after 15 min restraint stress) and decreased stress responsivity in the CRHR1-KO mouse line (after 2 h of restraint stress). It is possible to repeat the acute stress test several times without the stressed animal adapting to it, and the behavioral response can be robustly evoked at different ages, in both sexes and in different mouse strains. Thus, locomotor and rearing behavior in the Open Field after an acute stress challenge can be used as reliable, non-invasive indicators of stress responsivity and corticosterone secretion in mice. Frontiers Media S.A. 2014-04-15 /pmc/articles/PMC3995076/ /pubmed/24782732 http://dx.doi.org/10.3389/fnbeh.2014.00125 Text en Copyright © 2014 Zimprich, Garrett, Deussing, Wotjak, Fuchs, Gailus-Durner, de Angelis, Wurst and Hölter. http://creativecommons.org/licenses/by/3.0/ 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) or licensor 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
Zimprich, Annemarie
Garrett, Lillian
Deussing, Jan M.
Wotjak, Carsten T.
Fuchs, Helmut
Gailus-Durner, Valerie
de Angelis, Martin Hrabě
Wurst, Wolfgang
Hölter, Sabine M.
A robust and reliable non-invasive test for stress responsivity in mice
title A robust and reliable non-invasive test for stress responsivity in mice
title_full A robust and reliable non-invasive test for stress responsivity in mice
title_fullStr A robust and reliable non-invasive test for stress responsivity in mice
title_full_unstemmed A robust and reliable non-invasive test for stress responsivity in mice
title_short A robust and reliable non-invasive test for stress responsivity in mice
title_sort robust and reliable non-invasive test for stress responsivity in mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995076/
https://www.ncbi.nlm.nih.gov/pubmed/24782732
http://dx.doi.org/10.3389/fnbeh.2014.00125
work_keys_str_mv AT zimprichannemarie arobustandreliablenoninvasivetestforstressresponsivityinmice
AT garrettlillian arobustandreliablenoninvasivetestforstressresponsivityinmice
AT deussingjanm arobustandreliablenoninvasivetestforstressresponsivityinmice
AT wotjakcarstent arobustandreliablenoninvasivetestforstressresponsivityinmice
AT fuchshelmut arobustandreliablenoninvasivetestforstressresponsivityinmice
AT gailusdurnervalerie arobustandreliablenoninvasivetestforstressresponsivityinmice
AT deangelismartinhrabe arobustandreliablenoninvasivetestforstressresponsivityinmice
AT wurstwolfgang arobustandreliablenoninvasivetestforstressresponsivityinmice
AT holtersabinem arobustandreliablenoninvasivetestforstressresponsivityinmice
AT zimprichannemarie robustandreliablenoninvasivetestforstressresponsivityinmice
AT garrettlillian robustandreliablenoninvasivetestforstressresponsivityinmice
AT deussingjanm robustandreliablenoninvasivetestforstressresponsivityinmice
AT wotjakcarstent robustandreliablenoninvasivetestforstressresponsivityinmice
AT fuchshelmut robustandreliablenoninvasivetestforstressresponsivityinmice
AT gailusdurnervalerie robustandreliablenoninvasivetestforstressresponsivityinmice
AT deangelismartinhrabe robustandreliablenoninvasivetestforstressresponsivityinmice
AT wurstwolfgang robustandreliablenoninvasivetestforstressresponsivityinmice
AT holtersabinem robustandreliablenoninvasivetestforstressresponsivityinmice