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