Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice

Abstract Diazepam has been broadly accepted as an anxiolytic drug and is often used as a positive control in behavioral experiments with mice. However, as opposed to this general assumption, the effect of diazepam on mouse behavior can be considered rather controversial from an evidence point of vie...

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Autores principales:	Marina Pádua-Reis, Diana Aline Nôga, Adriano B. L. Tort, Martina Blunder
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db755120395f4b16a2a42085ff8bd829
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spelling	oai:doaj.org-article:db755120395f4b16a2a42085ff8bd8292021-12-02T16:55:45ZDiazepam causes sedative rather than anxiolytic effects in C57BL/6J mice10.1038/s41598-021-88599-52045-2322https://doaj.org/article/db755120395f4b16a2a42085ff8bd8292021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88599-5https://doaj.org/toc/2045-2322Abstract Diazepam has been broadly accepted as an anxiolytic drug and is often used as a positive control in behavioral experiments with mice. However, as opposed to this general assumption, the effect of diazepam on mouse behavior can be considered rather controversial from an evidence point of view. Here we revisit this issue by studying the effect of diazepam on a benchmark task in the preclinical anxiety literature: the elevated plus maze. We evaluated the minute-by-minute time-course of the diazepam effect along the 10 min of the task at three different doses (0.5, 1 and 2 mg/kg i.p. 30 min before the task) in female and male C57BL/6J mice. Furthermore, we contrasted the effects of diazepam with those of a selective serotoninergic reuptake inhibitor (paroxetine, 10 mg/kg i.p. 1 h before the task). Diazepam had no anxiolytic effect at any of the tested doses, and, at the highest dose, it impaired locomotor activity, likely due to sedation. Noteworthy, our results held true when examining male and female mice separately, when only examining the first 5 min of the task, and when animals were subjected to one hour of restrain-induced stress prior to diazepam treatment. In contrast, paroxetine significantly reduced anxiety-like behavior without inducing sedative effects. Our results therefore suggest that preclinical studies for screening new anxiolytic drugs should be cautious with diazepam use as a potential positive control.Marina Pádua-ReisDiana Aline NôgaAdriano B. L. TortMartina BlunderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marina Pádua-Reis Diana Aline Nôga Adriano B. L. Tort Martina Blunder Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
description	Abstract Diazepam has been broadly accepted as an anxiolytic drug and is often used as a positive control in behavioral experiments with mice. However, as opposed to this general assumption, the effect of diazepam on mouse behavior can be considered rather controversial from an evidence point of view. Here we revisit this issue by studying the effect of diazepam on a benchmark task in the preclinical anxiety literature: the elevated plus maze. We evaluated the minute-by-minute time-course of the diazepam effect along the 10 min of the task at three different doses (0.5, 1 and 2 mg/kg i.p. 30 min before the task) in female and male C57BL/6J mice. Furthermore, we contrasted the effects of diazepam with those of a selective serotoninergic reuptake inhibitor (paroxetine, 10 mg/kg i.p. 1 h before the task). Diazepam had no anxiolytic effect at any of the tested doses, and, at the highest dose, it impaired locomotor activity, likely due to sedation. Noteworthy, our results held true when examining male and female mice separately, when only examining the first 5 min of the task, and when animals were subjected to one hour of restrain-induced stress prior to diazepam treatment. In contrast, paroxetine significantly reduced anxiety-like behavior without inducing sedative effects. Our results therefore suggest that preclinical studies for screening new anxiolytic drugs should be cautious with diazepam use as a potential positive control.
format	article
author	Marina Pádua-Reis Diana Aline Nôga Adriano B. L. Tort Martina Blunder
author_facet	Marina Pádua-Reis Diana Aline Nôga Adriano B. L. Tort Martina Blunder
author_sort	Marina Pádua-Reis
title	Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
title_short	Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
title_full	Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
title_fullStr	Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
title_full_unstemmed	Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
title_sort	diazepam causes sedative rather than anxiolytic effects in c57bl/6j mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/db755120395f4b16a2a42085ff8bd829
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Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice

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