Can Sertraline and Nortriptyline Protect the Neurons in Submucosal and Myenteric Plexuses of Rat’s Colon Against Stress?

  • Ali Noorafshan
  • Majid Yousefi
  • Leila Hosseini
  • Saied Karbalay-DoustEmail author
Original Article



The colon is partly controlled by myenteric and submucosal plexuses, which respond to stress and lead to some gastrointestinal disorders. These plexuses play roles in irritable bowel syndrome. Patients suffering from this syndrome can be treated with some antidepressants, including sertraline and nortriptyline.


The primary aim of study was to compare the effect of a sertraline and a nortriptyline on the structural changes of the enteric neurons after stress exposure in both sexes. The secondary objectives were to evaluate the effects of stress on the submucosal and myenteric plexuses.


Male and female Sprague-Dawley rats were assigned to four subgroups. The first subgroup received no stress. The other three subgroups received chronic variable stress (CVS) and were given phosphate buffer, sertraline (10 mg/kg/day), or nortriptyline (10 mg/kg/day). After 45 days, the neuron number in their colon plexuses was estimated using the stereologic method.


The number of neurons increased by 40–51% in the submucosal plexus and by 57–69% in the myenteric plexus in the CVS group compared with the control group (p < 0.002) without any sex preference. The increment was significantly higher in the myenteric plexus than in the submucosal plexus (p < 0.05). Moreover, co-treatment of stressed rats with sertraline and nortriptyline could prevent the cellular hyperplasia of the plexuses, with more effective action for sertraline (p < 0.02).


Stress exposure for 45 days induced hyperplasia of the colon’s enteric plexuses in both sexes. However, these drugs could prevent the changes, with a more effective action for sertraline.


Stress Enteric plexus Colon Sertraline Nortriptyline Rat 



This work was performed at the Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. This study was a part of the thesis written by Majid Yousefi and financially supported by the Research Vice-chancellor of Shiraz University of Medical Sciences (approval no. 95-01-01-12986). The authors thank Ms. A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for improving the English in the manuscript and express their appreciation to Rouz Darou Pharmaceutical Co. for their kind provision of sertraline.

Author's contribution

AN designed the study. LH researched and discussed the physiopathology of the syndrome and medication dosage. MY carried out the animal experiments. SK collected the data. AN, LH, and SK drafted and revised the whole manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.

Ethical approval

The animal experiments were approved by the Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (approval no. 95-01-01-12986).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Histomorphometry and Stereology Research CenterShiraz University of Medical SciencesShirazIran
  2. 2.Anatomy Department, School of MedicineShiraz University of Medical SciencesShirazIran
  3. 3.Department of Traditional Medicine, School of MedicineShiraz University of Medical SciencesShirazIran

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