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

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 w...

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Principais autores: Reis, Marina Pádua, Ferreira, Diana Aline Nôga Morais, Tort, Adriano Bretanha Lopes, Blunder, Martina
Formato: article
Idioma:English
Publicado em: Springer Science and Business Media LLC
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Endereço do item:https://repositorio.ufrn.br/handle/123456789/32780
http://dx.doi.org/10.1038/s41598-021-88599-5
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spelling ri-123456789-327802021-06-28T13:45:05Z Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice Reis, Marina Pádua Ferreira, Diana Aline Nôga Morais Tort, Adriano Bretanha Lopes Blunder, Martina Diazepam - Therapeutic use Hypnotics and sedatives Anti-anxiety agents Mice 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 2021-06-28T13:45:04Z 2021-06-28T13:45:04Z 2021-04-29 article PÁDUA-REIS, Marina; NÔGA, Diana Aline; TORT, Adriano B. L.; BLUNDER, Martina. Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice. Scientific Reports, [S.L.], v. 11, p. 9335, abr. 2021. http://dx.doi.org/10.1038/s41598-021-88599-5. Disponível em: https://www.nature.com/articles/s41598-021-88599-5. Acesso em: 28 jun. 2021. https://repositorio.ufrn.br/handle/123456789/32780 http://dx.doi.org/10.1038/s41598-021-88599-5 en Attribution 3.0 Brazil http://creativecommons.org/licenses/by/3.0/br/ application/pdf Springer Science and Business Media LLC
institution Repositório Institucional
collection RI - UFRN
language English
topic Diazepam - Therapeutic use
Hypnotics and sedatives
Anti-anxiety agents
Mice
spellingShingle Diazepam - Therapeutic use
Hypnotics and sedatives
Anti-anxiety agents
Mice
Reis, Marina Pádua
Ferreira, Diana Aline Nôga Morais
Tort, Adriano Bretanha Lopes
Blunder, Martina
Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
description 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 Reis, Marina Pádua
Ferreira, Diana Aline Nôga Morais
Tort, Adriano Bretanha Lopes
Blunder, Martina
author_facet Reis, Marina Pádua
Ferreira, Diana Aline Nôga Morais
Tort, Adriano Bretanha Lopes
Blunder, Martina
author_sort Reis, Marina Pádua
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 Springer Science and Business Media LLC
publishDate 2021
url https://repositorio.ufrn.br/handle/123456789/32780
http://dx.doi.org/10.1038/s41598-021-88599-5
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