Behavioral and Neurochemical Impact of Early Weaning in Rodent Models

Early weaning in rodent models is widely used to mimic adverse developmental conditions, revealing profound and lasting alterations in emotional behaviour, stress responsiveness and neurochemical organisation. Removal of maternal contact and milk during a critical postnatal window provokes exaggerated activation of the hypothalamic–pituitary–adrenal (HPA) axis, elevated circulating corticosterone and deficits in synaptic plasticity. These changes manifest as heightened anxiety‐like and depressive‐like behaviours, cognitive inflexibility and altered social interactions that persist into adulthood. Neurochemically, early‐weaned rodents exhibit reduced expression of brain‐derived neurotrophic factor (BDNF) in key limbic structures, impaired hippocampal neurogenesis and shifts in monoamine transmitter systems. Timing and duration of separation, sex and genetic background modulate the severity and trajectory of these effects. Recent work has also drawn attention to interactions between gut microbiota disturbances and immune alterations as mediators of behavioural dysregulation. Collectively, this body of research underscores the critical importance of early postnatal care for normal neurobehavioural development and provides translational insight into the origins of human mood and stress‐related disorders.

Research from Nature Portfolio

Recent studies have elucidated the molecular underpinnings of anxiety following early weaning. In a mouse model, removal of maternal care within the third postnatal week heightened adulthood anxiety by driving prolonged elevations in corticosterone and dampening BDNF signalling within the prefrontal cortex. Pharmacological blockade of glucocorticoid receptors in this region or administration of a BDNF receptor agonist effectively restored normal exploratory behaviour and reduced stress responses. These findings demonstrate that disrupted glucocorticoid‐BDNF interplay in the prefrontal cortex is a key mechanism by which early separation induces long‐term emotional dysfunction.

Behavioral and Neurochemical Impact of Early Weaning in Rodent Models publication trend

The graph below shows the total number of articles in behavioral and neurochemical impact of early weaning in rodent models across all publications each year (not limited to Nature Index journals).

Technical terms

Early weaning: Premature cessation of maternal milk intake and separation from the dam during the postnatal period.

HPA axis: Hypothalamic–pituitary–adrenal axis, the neuroendocrine system controlling stress responses via glucocorticoid release.

Brain‐derived neurotrophic factor (BDNF): A growth factor important for neuronal survival, synaptic plasticity and cognitive function.

Gut microbiota: The community of micro‐organisms in the gastrointestinal tract that influences neurodevelopment and behaviour.

Corticosterone: The primary glucocorticoid in rodents, released in response to stress and modulating brain function.

References

1. Modulation of gut microbiota composition due to early weaning stress induces depressive behavior during the juvenile period in mice. Animal Microbiome (2024).
2. Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex. Scientific Reports (2019).
3. A Time to Wean? Impact of Weaning Age on Anxiety-Like Behaviour and Stability of Behavioural Traits in Full Adulthood. PLOS ONE (2016).
4. Hormonal and Metabolic Status of Male Rats with Metabolic Syndrome Model Induced by Interruption of Breastfeeding in the Early Postnatal Period. Journal Biomed (2022).
5. Maternal deprivation by early weaning increases corticosterone and decreases hippocampal BDNF and neurogenesis in mice. Frontiers in Behavioral Neuroscience (2009).