Sleep patterns deteriorate over time in chronic corticosterone-treated rats.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Sleep Research

Background:

• Repeated corticosterone (CORT) administration is a validated method for inducing depressive-like behaviors in rodents.
• Previous research indicated a correlation between sleep disturbances and depressive-like behavior following short-term CORT treatment.
• The temporal relationship between sleep alterations and the development of depression under prolonged CORT exposure requires further investigation.

Purpose of the Study:

• To examine the time-dependent relationship between sleep parameter changes and the emergence of depressive-like behavior in rats subjected to extended daily CORT injections.
• To identify specific molecular alterations in the locus coeruleus associated with chronic CORT-induced depression and sleep disruption.

Main Methods:

• Rats received daily subcutaneous injections of CORT (40 mg/kg) for durations of 7, 14, or 21 days.
• Sleep parameters were assessed using electroencephalographic recordings.
• Depressive-like behaviors were evaluated via the sucrose preference and forced swim tests.
• Western blot analysis was employed to quantify protein levels, including tyrosine hydroxylase (TH), glucocorticoid receptor (GR), and FKBP51 in the locus coeruleus.

Main Results:

• Seven-day CORT treatment did not induce significant depressive-like behavior or alter REM sleep, but decreased non-REM sleep duration, increased TH levels, and decreased GR expression in the locus coeruleus.
• Fourteen and 21-day CORT treatments led to increased depressive-like behavior, enhanced REM sleep, shortened REM sleep latency, reduced TH and GR levels, and elevated FKBP51 levels in the locus coeruleus.
• These findings highlight a progressive development of depression-like symptoms and associated sleep disturbances with prolonged CORT exposure.

Conclusions:

• The development of depression following chronic CORT administration appears intrinsically linked to the emergence of sleep disorders.
• Abnormalities in REM sleep, including shortened latency and altered duration, may serve as a hallmark of CORT-induced depression models in rats.
• The noradrenergic system and the glucocorticoid receptor pathway within the locus coeruleus are implicated in the pathophysiology of depression co-occurring with sleep disturbances.