Related Experiment Video
Updated: Apr 23, 2026
Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
Sleep in prenatally restraint stressed rats, a model of mixed anxiety-depressive disorder
Jérôme Mairesse1, Gilles Van Camp, Eleonora Gatta
1International Associated Laboratory-Prenatal Stress and Neurodegenerative Diseases, Neural Plasticity Team-UMR CNRS/USTL n 8576 Structural and Functional Glycobiology Unit, University of Lille 1, Lille, France.
Insights
Prenatal restraint stress (PRS) in rats alters circadian rhythms and sleep patterns, leading to anxiety and depression-like behaviors. This study suggests PRS may serve as a valuable animal model for depression research.
Area of Science:
- Neuroscience
- Behavioral Biology
- Endocrinology
Background:
- Prenatal stress can cause lasting developmental changes.
- Prenatal restraint stress (PRS) is linked to anxiety, depression, and altered hypothalamo-pituitary-adrenal (HPA) axis function in adult offspring.
- Circadian rhythms, including sleep-wake cycles, are often disrupted in depression.
Purpose of the Study:
- To investigate the impact of PRS on circadian rhythms and sleep patterns in adult rats.
- To explore the relationship between PRS, HPA axis activity, and depressive/anxiety-like behaviors.
- To evaluate PRS as a potential animal model for depression.
Main Methods:
- Gestation period restraint stress was applied to pregnant rats.
- Adult offspring were assessed for hormonal and behavioral circadian rhythms, including sleep-wake cycles.
- Plasma corticosterone levels, immobility in the forced swimming test, and glutamate release in the ventral hippocampus were measured.
Main Results:
- PRS induced phase advances in circadian rhythms and increased paradoxical sleep.
- Elevated plasma corticosterone levels correlated with increased immobility (depression-like behavior) and paradoxical sleep.
- Anxiety-like behaviors in PRS rats were associated with reduced glutamate release in the ventral hippocampus.
Conclusions:
- Prenatal restraint stress significantly alters circadian rhythms, sleep, and neurobehavioral profiles in adult rats.
- PRS induces a depressive-like state associated with HPA axis dysregulation and anxiety, potentially linked to altered hippocampal glutamate.
- The PRS rat model offers a valuable tool for studying the pathophysiology of depression and developing therapeutic strategies targeting stress-related disorders.
Abstract:
Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the external environment, we studied the effects of PRS on circadian rhythms, including the sleep-wake cycle, that are parameters altered in depression. Using a restraint stress during gestation, we showed that PRS induced phase advances in hormonal/behavioral circadian rhythms in adult rats, and an increase in the amount of paradoxical sleep, positively correlated to plasma corticosterone levels. Plasma corticosterone levels were also correlated with immobility in the forced swimming test, indicating a depressive-like profile in the PRS rats. We observed comorbidity with anxiety-like profile on PRS rats that was correlated with a reduced release of glutamate in the ventral hippocampus. Pharmacological approaches aimed at modulating glutamate release may represent a novel therapeutic strategy to treat stress-related disorders. Finally, since depressed patients exhibit changes in HPA axis activity and in circadian rhythmicity as well as in the paradoxical sleep regulation, we suggest that PRS could represent an original animal model of depression.
