ORIGINAL RESEARCH article
Front. Behav. Neurosci.
Sec. Emotion Regulation and Processing
A Stable Rat Models in Constipation with Depression and Anxiety: Evaluation and Validation
Provisionally accepted
- 1Nanjing University of Chinese Medicine, Nanjing, China
- 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Purpose: The study aimed to establish a model of functional constipation (FC) with anxiety and depression in rat using a compound diphenoxylate combined with chronic unpredictable mild stress (CUMS). It futher investigated constipation and behavioral indicators in different group at various compound diphenoxylate with CUMS durations to determine the optimal time frame for successful model establishment. Method: Thirty-two female rats were randomly assigned to Control, FC before CUMS, FC after CUMS and FC throughout CUMS group. Control: Same amount of regular saline solution, FC before CUMS: Compound diphenoxylate 15 mg/kg 2 weeks + CUMS 5 weeks, FC after CUMS: CUMS 5 weeks + Compound diphenoxylate 15 mg/kg 2 weeks, FC throughout CUMS: CUMS 5weeks with Compound diphenoxylate 10 mg/kg 4 weeks. After model establishment, constipation and behavioral indicators were detected. HE staining was used to observe pathological changes in brain and colon tissue, while AB-PAS was used to observe goblet cell in colon tissue, Nissl staining was used to observe neuron cell in hippocampus. The protein expression of BDNF and Bax in the hippocampus and PGP9.5 and iNOS in the colon were detected by Western Blot. Results: In the FC throughout group, synaptic ultrastructure significantly decreased, aligning with pathological changes indicator of FC with anxiety and depression. The protein expression levels of BDNF, PGP9.5 were markedly decreased and Bax, iNOS were elevated. This study provided a reliable reference for determining the optimal establishment way of FC with anxiety and depression models and for in vivo FC with anxiety and depression animal experiments.
Keywords: Animal Models, apoptosis proteins, CUMS, FC with anxiety and depression, Hippocampus
Received: 18 Nov 2025; Accepted: 09 Jan 2026.
Copyright: © 2026 Liu, Li, Bian, Mi, He, Haihua and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiali Liu
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