Sumatriptan effects on morphine-induced antinociceptive tolerance and physical dependence: The role of nitric oxide

Hassanipour, Mahsa. and Rajai, Nazanin. and Rahimi, Nastaran. and Fatemi, Iman. and Jalali, Mitra. and Akbarian, Reihaneh. and Shahabaddini, Ali. and Nazari, Amirhossein. and Amini-Khoei, Hossein. (2018) Sumatriptan effects on morphine-induced antinociceptive tolerance and physical dependence: The role of nitric oxide. European Journal of Pharmacology, 835.


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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 morphineinduced physical dependence in mice.

Item Type: Article
Uncontrolled Keywords: Morphine,Sumatriptan,Antinociception,Tolerance,Dependence,Nitric oxide
Subjects: QV pharmacology
Divisions: Faculty of Medicine > Basic Sciences Academic Groups > Department of Physiology
Faculty of Medicine > Department of Clinical Sciences > Department of pharmacology
Reserach Vice-Chancellar Department > Medical Plants Research Center
Depositing User: Users 1 not found.
Date Deposited: 26 Aug 2018 04:12
Last Modified: 26 Aug 2018 04:12

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