Nahid Fakhraei1, Nina Javadian1,2, Reza Rahimian3,4, Fatemeh Nili5, Nastaran Rahimi2,3, Shiva Hashemizadeh6, Ahmad Reza Dehpour7,8,9. 1. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Psychiatry and Neuroscience, Faculty of Medicine, CERVO Brain Research Centre, Laval University, Quebec, G1J 2G3, Canada. 5. Department of Pathology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. 6. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 7. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. dehpoura@sina.tums.ac.ir. 8. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. dehpoura@sina.tums.ac.ir. 9. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. dehpoura@sina.tums.ac.ir.
Abstract
PURPOSE: There are several lines of evidence on the protective roles of opioids in gastrointestinal inflammatory conditions. This study aims to distinguish the central and peripheral roles of methadone, a non-selective opioid receptor agonist, in an acute model of ulcerative colitis in male rats. METHODS: Ulcerative colitis was induced by intrarectal administration of acetic acid 4%. Methadone was injected subcutaneously (s.c.), 5 and 10 mg/kg, and intracerebroventricular (i.c.v.), 50 and 300 ng/rat. Opioid antagonists were employed. Methylnaltrexone (MNTX; 5 mg/kg, i.p.), a peripherally acting opioid receptor antagonist, and naltrexone (NTX; 5 mg/kg, i.p. and 10 ng/rat, i.c.v.), a peripherally and centrally acting opioid receptor antagonist were injected before methadone (10 mg/kg, s.c. and or 300 ng/rat, i.c.v.) administration. NTX (5 mg/kg, i.p. and 10 ng/rat, i.c.v.) were administered 30 min prior to administration of methadone (10 mg/kg, s.c. and 300 ng/rat, i.c.v.), respectively. MNTX (5 mg/kg, i.p.) was injected 30 min prior to methadone (10 mg/kg, s.c.). Seventy-two hours following colitis induction, macroscopic and microscopic mucosal lesions, and the colonic levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were determined. RESULTS: Methadone (300 ng/rat, i.c.v.) and Methadone (5 and 10 mg/kg, s.c.) improved the macroscopic and microscopic scores through opioid receptors. Also, a significant reduction in TNF-α and IL-1β was observed. Peripherally and centrally injected NTX significantly reversed methadone 10 mg/kg s.c. anti-inflammatory effects while MNTX could not completely reverse this effect. Moreover, centrally administered methadone (300 ng/rat) showed the anti-inflammatory effect which was reversed by central administration of NTX (10 ng/rat). CONCLUSIONS: The opioid receptors mainly the central opioid receptors may mediate the protective actions of methadone on the experimental model of inflammatory bowel disease in rat.
PURPOSE: There are several lines of evidence on the protective roles of opioids in gastrointestinal inflammatory conditions. This study aims to distinguish the central and peripheral roles of methadone, a non-selective opioid receptor agonist, in an acute model of ulcerative colitis in male rats. METHODS:Ulcerative colitis was induced by intrarectal administration of acetic acid 4%. Methadone was injected subcutaneously (s.c.), 5 and 10 mg/kg, and intracerebroventricular (i.c.v.), 50 and 300 ng/rat. Opioid antagonists were employed. Methylnaltrexone (MNTX; 5 mg/kg, i.p.), a peripherally acting opioid receptor antagonist, and naltrexone (NTX; 5 mg/kg, i.p. and 10 ng/rat, i.c.v.), a peripherally and centrally acting opioid receptor antagonist were injected before methadone (10 mg/kg, s.c. and or 300 ng/rat, i.c.v.) administration. NTX (5 mg/kg, i.p. and 10 ng/rat, i.c.v.) were administered 30 min prior to administration of methadone (10 mg/kg, s.c. and 300 ng/rat, i.c.v.), respectively. MNTX (5 mg/kg, i.p.) was injected 30 min prior to methadone (10 mg/kg, s.c.). Seventy-two hours following colitis induction, macroscopic and microscopic mucosal lesions, and the colonic levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were determined. RESULTS:Methadone (300 ng/rat, i.c.v.) and Methadone (5 and 10 mg/kg, s.c.) improved the macroscopic and microscopic scores through opioid receptors. Also, a significant reduction in TNF-α and IL-1β was observed. Peripherally and centrally injected NTX significantly reversed methadone 10 mg/kg s.c. anti-inflammatory effects while MNTX could not completely reverse this effect. Moreover, centrally administered methadone (300 ng/rat) showed the anti-inflammatory effect which was reversed by central administration of NTX (10 ng/rat). CONCLUSIONS: The opioid receptors mainly the central opioid receptors may mediate the protective actions of methadone on the experimental model of inflammatory bowel disease in rat.
Authors: L A Dieleman; M J Palmen; H Akol; E Bloemena; A S Peña; S G Meuwissen; E P Van Rees Journal: Clin Exp Immunol Date: 1998-12 Impact factor: 4.330
Authors: Carlos Roncero; Begoña Vicente-Hernández; Nerea M Casado-Espada; Lourdes Aguilar; Sinta Gamonal-Limcaoco; María A Garzón; Fernando Martínez-González; Carlos Llanes-Álvarez; Ruth Martínez; Manuel Franco-Martín; Ana Álvarez-Navares Journal: Front Psychiatry Date: 2020-11-25 Impact factor: 4.157