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Updated: Apr 28, 2026

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Stable rat models in constipation with depression and anxiety: evaluation and validation.

Jiali Liu1,2, Shaoliang Li2, Conghui Bian2

  • 1Department of Colorectal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Frontiers in Behavioral Neuroscience
|April 27, 2026
PubMed
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This study developed a reliable rat model for functional constipation (FC) with anxiety and depression. The optimal model involved combining diphenoxylate and chronic unpredictable mild stress (CUMS) throughout the experiment.

Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pharmacology

Background:

  • Functional constipation (FC) is often comorbid with anxiety and depression.
  • Establishing reliable animal models is crucial for studying these conditions.
  • Chronic unpredictable mild stress (CUMS) is a common method for inducing stress-related behavioral changes in rodents.

Purpose of the Study:

  • To establish a reliable rat model of functional constipation (FC) comorbid with anxiety and depression.
  • To investigate the effects of diphenoxylate and CUMS on constipation and behavioral indicators.
  • To determine the optimal timing and duration for establishing this dual-condition animal model.

Main Methods:

  • Thirty-two female rats were divided into control and experimental groups receiving diphenoxylate and CUMS in varying sequences and durations.
Keywords:
CUMSFC with anxiety and depressionanimal modelsapoptosis proteinshippocampus

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  • Constipation and behavioral indicators were assessed post-model establishment.
  • Histological analyses (HE, AB-PAS, Nissl staining) and Western blotting (WB) were performed on brain and colon tissues to examine pathological changes and protein expression (BDNF, Bax, PGP9.5, iNOS).

    • Main Results:

    • The FC throughout CUMS group exhibited decreased synaptic ultrastructure, consistent with FC, anxiety, and depression.
    • Key protein changes included decreased BDNF and PGP9.5, and increased Bax and iNOS.
    • These findings indicate successful induction of the FC with anxiety and depression model.

    Conclusions:

    • The study successfully established a reliable rat model for functional constipation with anxiety and depression.
    • The 'FC throughout CUMS' approach appears optimal for model establishment.
    • This model serves as a valuable reference for future in vivo research on FC, anxiety, and depression.