4.7 Article

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

期刊

SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

出版社

NATURE RESEARCH
DOI: 10.1038/s41598-021-88599-5

关键词

-

资金

  1. Swedish Research Council (Vetenskapsradet)
  2. Fredrik och Ingrid Thurings Stiftelse
  3. Stiftelse Lars Hiertas Minne
  4. Ahlen-stiftelse
  5. Svenska Lakaresallskapets forskningsfonder
  6. Gunvor och Josef Aners Stiftelse
  7. Emil och Ragna Borjessons Stiftelse
  8. Hjarnfonden
  9. Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
  10. Brazilian National Council for Scientific and Technological Development (CNPq)
  11. Brazilian Coordination for the Improvement of Higher Education Personal (CAPES) through the international cooperation program CAPES/STINT

向作者/读者索取更多资源

The study found that diazepam had no anxiolytic effect on mouse behavior in the elevated plus maze task, and at the highest dose it impaired locomotor activity, likely due to sedation. In contrast, paroxetine significantly reduced anxiety-like behavior without inducing sedative effects. Therefore, preclinical studies screening new anxiolytic drugs should be cautious with the use of diazepam as a potential positive control.
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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据