Anti-inflammatory Effect of Amitriptyline on Ulcerative Colitis in Normal and Reserpine-Induced Depressed Rats.

Depressive disorders are more common among persons with chronic diseases such as inflammatory bowel disease and anti-inflammatory effect of some antidepressants such as amitriptyline has been reported. Acetic acid colitis was induced in both reserpinised (depressed) and non-reserpinised (normal) rats. Reserpinised groups received reserpine (6 mg/kg, i.p.) one hour prior to colitis induction. Then Amitriptyline (5, 10, 20 mg/kg, i.p.) was administered to separate groups of male Wistar rats. All treatments were carried out two hours after colitis induction and continued daily for four days. Dexamethasone (1 mg/kg) and normal saline (1 mL/kg) were used in reference and control groups, respectively. At day five, animals were euthanized and colonic tissue injuries were assessed macroscopically and pathologically. Myeloperoxidase activity as a marker of neutrophil infiltration was also measured in colonic tissues. Results showed that reserpine (6 mg/kg, i.p.) intensified colitic condition. Compared to control, amitriptyline (10, 20 mg/kg) and dexamethasone significantly decreased weight of colon and ulcer index in normal and reserpine-induced depressed rats. Myeloperoxidase activity and pathological assessments also proved anti-inflammatory effect of amitriptyline. Our results suggest that amitriptyline, a tricyclic antidepressant, could reduce inflammatory and ulcerative injuries of colon both in normal and depressed rats. So among the wide spread anti-depressant drugs, amitriptyline is a good choice to treat depression comorbidities in patients with IBD.

Effect of venlafaxine on experimental colitis in normal and reserpinised depressed rats.

Psychological disorders such as depression have more prevalence in inflammatory bowel disease patients and can exacerbate the clinical course of the disease, so anti-depressant therapy may have a potential to positively impact the disease course. On the other hand several antidepressant drugs have shown anti-inflammatory and immunomodulatory properties. Thus, this study aimed to explore the beneficial effects of venlafaxine on experimental colitis in normal and reserpinised depressed rats. Acetic acid colitis was induced in both reserpinised and non-reserpinised rats. Reserpinised groups received reserpine at dose of 6 mg/kg i.p.1 h prior to colitis induction and then treated with venlafaxine at doses of 10, 20, 40 mg/kg given i.p. 2 h after induction of colitis and daily for 4 consecutive days. Non-reserpinised groups treated with 10, 20, 40 mg/kg venlafaxine i.p. 2 h after the induction of colitis and daily for 4 successive days. Dexamethasone (1 mg/kg, i.p.) was used as reference drug. Colonic inflammation was evaluated using macroscopic, histological and myeloperoxidase activity measurements. Results showed that reserpine at dose of 6 mg/kg exacerbated the colitis damage. Compared to acetic acid control, venlafaxine at dose of 40 mg/kg as well as dexamethasone significantly improved colitis parameters in both reserpinised and non-reserpinised animals. Venlafaxine reduced inflammatory injury in this animal model of induced ulcerative colitis. These effects 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.

Evaluation of anti-colitic effect of fluvoxamine against acetic acid-induced colitis in normal and reserpinized depressed rats.

High prevalence of psychological comorbidities such as depression and anxiety in patients with inflammatory bowel disease (IBD) supports the premise that adding an anti-depressant drug with known anti-inflammatory effect to the medical treatment have beneficial effect in the course of the underlying disease. Colitis was induced by intracolonic instillation of 2 ml of 4% v/v acetic acid solution in rats. Anti-colitic effect of fluvoxamine was evaluated in two categories: A: normal rats, B: reserpinized (6 mg/kg, i.p.) depressed rats. In group A, fluvoxamine (2.5, 5, 10 mg/kg, i.p.) was administered 2 h after induction of colitis and in group B: reserpine (6 mg/kg, i.p.) was administered 1 h prior to colitis induction and then fluvoxamine (2.5, 5, 10 mg/kg, i.p.) was administered 2 h after colitis induction. Dexamethasone (1 mg/kg) was used as reference drug. All the treatments continued daily for five days. The effect was assessed on the basis of macroscopic score, biochemical (myeloperoxidase) changes and histopathological studies. Results showed that fluvoxamine (2.5 and 5 mg/kg) and dexamethasone treatment markedly reduced disease severity in both reserpinized and non-reserpinized rats as indicated by reduction in macroscopic and microscopic colonic damages while reserpine adversely exacerbated the colitis damage. Myeloperoxidase activity which was increased following colitis induction was also decreased. The findings of this study elucidate the anti-colitic and anti-inflammatory properties of fluvoxamine and so introduced it as a good candidate to treat depressive symptoms in people comorbid to IBD.

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

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.