A role for opioid system in the proconvulsant effects of sildenafil on the pentylenetetrazole-induced clonic seizure in mice

作者：Montaser Kouhsari Laleh; Payandemehr Borna; Gholipour Taha; Ziai Pouya; Nabavizadeh Pooneh; Ghasemi Abbas; Bahremand Arash; Ghasemi Mehdi; Dehpour Ahmad Reza^*

来源：Seizure-European Journal of Epilepsy, 2011, 20(5): 409-413.

DOI：10.1016/j.seizure.2011.01.014

• Sildenafil
• Morphine
• Cyclic guanosine monophosphate (cGMP)
• Naltrexone
• Clonic seizure threshold
• Pentylenetetrazole
• Mice

There are several lines of evidence that opioidergic and nitrergic systems could modulate the seizure threshold. We previously have shown that sildenafil had proconvulsant effects in a model of clonic seizure induced by pentylenetetrazole (PTZ) or bicuculline. In the present study, we examined whether the opioid system participates in the action of sildenafil on the PTZ-induced clonic seizures in mice. Sildenafil (1, 5, 10 and 20 mg/kg, i.p.) significantly decreased the seizure threshold in a dose-dependent manner, whereas morphine had both anticonvulsant and proconvulsant effects at low (0.5, 1, and 3 mg/kg, s.c.) and high (60 mg/kg, s.c.) doses. A sub-effective dose of sildenafil (5 mg/kg) combined with a dose of morphine (7.5 mg/kg) which was sub-effective for its proconvulsant effects significantly decreased the seizure threshold. Although naltrexone at 0.5 and 1 mg/kg had no effect on the seizure threshold, it significantly prevented both the proconvulsant effects of sildenafil as well as the anticonvulsant and proconvulsant effects of morphine on the PTZ-induced seizure thresholds. Our data suggested a role for opioidergic system in the proconvulsant effects of sildenafil on the PTZ-induced clonic seizures in mice.

• 出版日期2011-6