ArticleBioPsychoSocial medicine2023
Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats.
Article in BioPsychoSocial medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Early life stress and the pathogenesis of visceral hypersensitivity: mechanisms and implications for disorders of gut-brain interaction.Frontiers in cell and developmental biology · 2026Review
- Maternal separation disrupts noradrenergic control of adult coping behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Corticotropin-releasing hormone receptor-1 antagonist attenuates visceral hypersensitivity induced by trinitrobenzene sulfonic acid colitis and maternal separation in rats.BioPsychoSocial medicine · 2025Article
- Understanding Role of Maternal Separation in Depression, Anxiety,and Pain Behaviour: A Mini Review of Preclinical Research With Focus on Neuroinflammatory Pathways.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2025Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundNeonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD).
methodsMale and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS.
resultsIn male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline.
conclusionsThese findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic-pituitary-adrenal axis function depending on sex.
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