Beneficial Effects of Maprotiline in a Murine Model of Colitis in Normal and Reserpinised Depressed Rats.

Mohsen Minaiyan,Parvin Mahzouni,Valiollah Hajhashemi,Mohammad Rabbani,Ehsan Fattahian

doi:10.1155/2014/359841

Abstract

Background. Anti-inflammatory and immunomodulatory activities have been reported for maprotiline, a strong norepinephrine reuptake inhibitor. In addition, some other antidepressant drugs have shown beneficial effects in experimental colitis. Methods. All the animals were divided into normal and depressed groups. In normal rats colitis was induced by instillation of 2 mL of 4% acetic acid and after 2 hours, maprotiline (10, 20, and 40 mg/kg, i.p.) was administered. In reserpinised depressed rats, depression was induced by injection of reserpine (6 mg/kg, i.p.), 1 h prior to colitis induction, and then treated with maprotiline (10, 20, and 40 mg/kg). Treatment continued daily for four days. Dexamethasone (1 mg/kg, i.p.) was given as a reference drug. On day five following colitis induction, animals were euthanized and distal colons were assessed macroscopically, histologically, and biochemically (assessment of myeloperoxidase activity). Results. Maprotiline significantly improved macroscopic and histologic scores and diminished myeloperoxidase activity in both normal and depressed rats while reserpine exacerbated the colonic damage. Conclusion. Our data suggests that the salutary effects of maprotiline on acetic acid colitis are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug.

Highlights

The inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis (UC), affect approximately 12 of every 1000 people in developed countries [1]
These three doses of maprotiline were selected for evaluation in the ulcerative colitis rats
Twenty-four hours after the instillation of 4% acetic acid into the colon, the animals developed bloody diarrhea, weakness, and decreased food intake that resulted in body weight loss during the experiment period

Summary

Background

Anti-inflammatory and immunomodulatory activities have been reported for maprotiline, a strong norepinephrine reuptake inhibitor. In normal rats colitis was induced by instillation of 2 mL of 4% acetic acid and after 2 hours, maprotiline (10, 20, and 40 mg/kg, i.p.) was administered. Depression was induced by injection of reserpine (6 mg/kg, i.p.), 1 h prior to colitis induction, and treated with maprotiline (10, 20, and 40 mg/kg). On day five following colitis induction, animals were euthanized and distal colons were assessed macroscopically, histologically, and biochemically (assessment of myeloperoxidase activity). Maprotiline significantly improved macroscopic and histologic scores and diminished myeloperoxidase activity in both normal and depressed rats while reserpine exacerbated the colonic damage. Our data suggests that the salutary effects of maprotiline on acetic acid colitis are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug

Introduction

Materials and Methods

Behavioral Tests

Discussion