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Sumatriptan Effects on Morphine-Induced Antinociceptive Tolerance and Physical Dependence: The Role of Nitric Oxide Publisher Pubmed



Hassanipour M1, 2 ; Rajai N3, 4 ; Rahimi N3, 4 ; Fatemi I1, 2 ; Jalali M1 ; Akbarian R3, 4 ; Shahabaddini A1, 2 ; Nazari A1, 2 ; Aminikhoei H5, 6 ; Dehpour AR3, 4
Authors
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Authors Affiliations
  1. 1. Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  2. 2. Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  6. 6. Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

Source: European Journal of Pharmacology Published:2018


Abstract

Sumatriptan, a 5HT (5-hydroxytryptamine)1B/1D receptor agonist, showed neuroprotection in different studies. The aim of the present study was to investigate the effect of sumatriptan on morphine-induced antinociceptive tolerance and physical dependence. We also investigated the possible role of nitric oxide (NO) on sumatriptan effects. Tolerance was induced by morphine injection (50, 50, 75 mg/kg) three times daily for five days. Antinociceptive latency after acute and chronic treatment with sumatriptan (0.001, 0.01, 0.1 and 1 mg/kg) was measured by hot plate test in morphine-dependent animals. To investigate the possible involvement of NO, different isoforms of nitric oxide synthase (NOS) inhibitors including L-NAME, aminoguanidine and 7-nitroindazole were co-administered with sumatriptan. Nitrite level in mice hippocampus was quantified by Griess method. To examine the role of sumatriptan on physical dependence, three parameters of withdrawal signs were recorded after injection of naloxone (4 mg/kg). Acute treatment with sumatriptan (0.01, 0.1 and 1 mg/kg) attenuated the antinociceptive tolerance (P < 0.001). Chronic injection of sumatriptan (0.001, 0.01 and 0.1 mg/kg), as well, decreased the antinociceptive tolerance (P < 0.001). Moreover, co-administration of NOS inhibitors prevented the effects of sumatriptan. Sumatriptan significantly increased the level of nitrite only after chronic administration. Sumatriptan administration showed no alteration in naloxone-precipitated withdrawal signs. Acute and chronic administration of sumatriptan attenuated morphine antinociceptive tolerance; at least in chronic phase via nitrergic pathway. Our data did not support beneficial effects of sumatriptan on morphine-induced physical dependence in mice. © 2018 Elsevier B.V.
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