Related Experiment Video
Updated: May 23, 2026
Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Hormonal and behavioural abnormalities induced by stress in utero: an animal model for depression
S Maccari1, M Darnaudery, O Van Reeth
1Neumsciences du Comportement, Universite‘ de Lille I , 59655 Klleneuve d’Ascq, France. maccari@univ-lillel.fr
Insights
Prenatal stress in rats leads to long-term anxiety, depression-like behaviors, and disrupted circadian rhythms and sleep patterns. These prenatally stressed (PNS) rats show promise as a model for studying human depression.
Area of Science:
- Neuroscience
- Behavioral Biology
- Endocrinology
Background:
- Prenatal stress (PNS) in rats induces lasting neurodevelopmental abnormalities.
- PNS affects the hypothalamo-pituitary-adrenal (HPA) axis and cholinergic systems.
- Maternal stress hormones and anxiety during pregnancy and postpartum mediate these effects.
Purpose of the Study:
- To investigate the impact of prenatal stress on the sleep-wake cycle in adult male rats.
- To explore the link between prenatal stress, circadian rhythm disturbances, and depression-like behaviors.
Main Methods:
- Assessment of sleep-wake parameters in prenatally stressed (PNS) rats.
- Evaluation of circadian rhythm adjustments to light-dark cycle shifts.
- Analysis of depression-like behaviors using the forced swimming test.
Main Results:
- PNS rats displayed altered sleep-wake patterns, notably increased paradoxical sleep.
- PNS rats showed slower resynchronization of activity rhythms after light-dark cycle shifts.
- Depression-like immobility in PNS rats was reduced by tianeptine, melatonin, or a melatonin agonist (S23478).
Conclusions:
- Prenatal stress induces long-term behavioral and circadian rhythm abnormalities in rats.
- PNS rats serve as a valuable model for human depression research.
- Melatonin and its agonists may possess antidepressant-like properties.
Abstract:
Prenatal stress in rats can exert profound influence on the off spring's development, inducing abnormalities such as increased "anxiety", "emotionality" or "depression-like" behaviours.Prenatal stress has long-term effects on the development of the hypothalamo-pituitary-adrenal(HPA) axis and forebrain cholinergic systems. These long-term neuroendocrinological effects are mediated, at least in part, by stress-induced maternal corticosterone increase during pregnancy and stress-induced maternal anxiety during the postnatal period. We have shown a significant phase advance in the circadian rhythms of corticosterone secretion and locomotor activity in prenatally-stressed (PNS) rats. When subjected to an abrupt shift in the light-dark(LD) cycle, PNS rats resynchronized their activity rhythm more slowly than control rats. In view of the data suggesting abnormalities in the circadian timing system in these animals, we have investigated the effects of prenatal stress on the sleep-wake cycle in adult male rats. PNS rats exhibited various changes in sleep-wake parameters, including a dramatic increase in the amount of paradoxical sleep. Taken together, our results indicate that prenatal stress can induce increased responses to stress and abnormal circadian rhythms and sleep in adult rats.Various clinical observations in humans suggest a possible pathophysiological link between depression and disturbances in circadian rhythmicity. Circadian abnormalities in depression can be related to those found in PNS rats. Interestingly, we have recently shown that the increased immobility in the forced swimming test observed in PNS rats can be corrected by chronic treatment with the antidepressant tianeptine, or with melatonin or S23478, a melatonin agonist. Those results reinforce the idea of the usefulness of PNS rats as an appropriate animal model to study human depression and support a new antidepressant-like effect of melatonin and the melatonin agonist S23478.
