Acute or Chronic Exposure to Corticosterone Promotes Wakefulness in Mice

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.

Automated summary

Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, the effects of the major glucocorticoid corticosterone (CORT) on sleep in rodents remain unclear. In this study, acute or chronic administration of CORT in mice resulted in rapid promotion of wakefulness, suppression of REM and NREM sleep, and altered EEG activity. Prolonged CORT exposure led to excessive wakefulness and REM sleep, decreased NREM sleep, and persistent sleep changes even after drug withdrawal. The observed sleep alterations were associated with elevated plasma CORT levels and depressive phenotypes. These findings provide insight into the neural link between insomnia and depression.