Publication Cover
Chronobiology International
The Journal of Biological and Medical Rhythm Research
Volume 32, 2015 - Issue 2
233
Views
6
CrossRef citations to date
0
Altmetric
Original Article

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice

, , , , , , & show all
Pages 248-254 | Received 04 Jul 2014, Accepted 08 Sep 2014, Published online: 06 Oct 2014
 

Abstract

Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.

Acknowledgements

The authors thank Eliane Dallegrave, Marta Cioato, Fabíola S. Meyer, Roberta Andrejew, Adriana Simon Coitinho and Ricardo Schneider for technical support and Conselho Nacional de Desenvolvimento Científico e Tecnológico (LKP, YT, CLQ, RB, GM, MPH and EE) and CAPES (RL) for fellowships. This study was supported by FIPE/HCPA/UFRGS and PRONEX 10/0031-1.

Declaration of interest

The authors report no conflict of interest.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 61.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 489.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.