Acute or Chronic Exposure to Corticosterone Promotes Wakefulness in Mice

Author:

Yao Zhen1ORCID,Zhang Bei-Xuan1,Chen Hui1,Jiang Xiao-Wei1,Qu Wei-Min1,Huang Zhi-Li1ORCID

Affiliation:

1. Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China

Abstract

Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, sleep changes in response to elevated corticosterone (CORT), the major glucocorticoid in rodents, remain unclear. Here, we investigated the effects of acute or chronic CORT administration on sleep using electroencephalogram (EEG) and electromyography (EMG) recordings in freely moving mice. Acute CORT exposure rapidly promoted wakefulness, marked by increased episodes and enhanced EEG delta power, while simultaneously suppressing rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, with the latter marked by decreased mean duration and reduced delta power. Prolonged 28-day CORT exposure led to excessive wakefulness and REM sleep, characterized by higher episodes, and decreased NREM sleep, characterized by higher episodes and reduced mean duration. EEG theta activity during REM sleep and delta activity during NREM sleep were attenuated following 28-day CORT exposure. These effects persisted, except for REM sleep amounts, even 7 days after the drug withdrawal. Elevated plasma CORT levels and depressive phenotypes were identified and correlated with observed sleep changes during and after administration. Fos expression significantly increased in the lateral habenula, lateral hypothalamus, and ventral tegmental area following acute or chronic CORT treatment. Our findings demonstrate that CORT exposure enhanced wakefulness, suppressed and fragmented NREM sleep, and altered EEG activity across all stages. This study illuminates sleep alterations during short or extended periods of heightened CORT levels in mice, providing a neural link connecting insomnia and depression.

Funder

STI2030-Major Project

National Natural Science Foundation of China

Program for Shanghai Outstanding Academic Leaders

Shanghai Municipal Science and Technology Major Project

ZJ Lab

Publisher

MDPI AG

Subject

General Neuroscience

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