A mouse model mimicking human first night effect for the evaluation of hypnotics

Qi Xu; Xin-Hong Xu; Wei-Min Qu; Michael Lazarus; Yoshihiro Urade; Zhi-Li Huang

doi:10.1016/j.pbb.2013.11.029

A mouse model mimicking human first night effect for the evaluation of hypnotics

Pharmacol Biochem Behav. 2014 Jan:116:129-36. doi: 10.1016/j.pbb.2013.11.029. Epub 2013 Dec 4.

Authors

Qi Xu¹, Xin-Hong Xu², Wei-Min Qu³, Michael Lazarus⁴, Yoshihiro Urade⁵, Zhi-Li Huang⁶

Affiliations

¹ State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai, China.
² Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai, China.
³ Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai, China; Institutes of Brain Science, Shanghai Medical College of Fudan University, Shanghai, China.
⁴ International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
⁵ International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Japan.
⁶ State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai, China; Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai, China; Institutes of Brain Science, Shanghai Medical College of Fudan University, Shanghai, China. Electronic address: huangzl@fudan.edu.cn.

PMID: 24316349
DOI: 10.1016/j.pbb.2013.11.029

Abstract

In humans, a first night effect (FNE) is characterized by increased sleep latency and decreased total sleep time in an unfamiliar environment, but the mechanism and treatment options for this universally experienced acute insomnia are unclear. We continuously recorded electroencephalography (EEG) and electromyogram (EMG) and measured plasma corticosterone levels to develop a mouse FNE model by inducing acute insomnia in mice that have been placed in unfamiliar cage environments. The sleep latency of mice 'moved to clean cages' (MCC) was longer than that for mice 'moved to dirty ones' (MDC). As compared to MDC mice, MCC mice showed stronger decreases in the amount of non-rapid eye movement (non-REM, NREM) and REM sleep, with a lower power density of NREM sleep, increased fragmentation and decreased stage transitions from NREM sleep to wake, and higher variation in plasma corticosterone levels. Treatment of MCC mice with zolpidem, diazepam, raclopride, pyrilamine, except SCH23390 shortened NREM sleep latency. In addition, zolpidem significantly increased NREM and REM sleep with the increase in slow wave activity (1.00-2.75 Hz), while raclopride significantly increased NREM and REM sleep without changing the EEG power density in MCC mice, whereas diazepam increased sleep with a drastic decrease in power density of the frequency band between 1.00 and 4.00 Hz, diazepam also increased the frequency band between 9.75 and 24.75 Hz during NREM sleep. These results indicate that a MCC mouse can mimic a FNE phenotype of humans and that zolpidem and raclopride may be useful drugs to prevent acute insomnia, including FNE.

Keywords: BZ; D(1)R; D(2)R; EEG; EMG; FNE; First night effect; H(1)R; Insomnia; KO; MCC; MDC; NREM; REM; Raclopride; Sleep; Zolpidem; benzodiazepine; dopamine D(1) receptor; dopamine D(2) receptor; electroencephalography; electromyogram; first night effect; histamine H1 receptor; knock out; mice moved to clean cages; mice moved to dirty cages; non-rapid eye movement; rapid eye movement.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Corticosterone / blood
Drug Evaluation, Preclinical
Humans
Hypnotics and Sedatives / pharmacology*
Male
Mice
Mice, Inbred C57BL
Models, Animal*
Sleep / drug effects

Substances

Hypnotics and Sedatives
Corticosterone