title: Effects of oleuropein on pentylenetetrazol-induced seizures in mice: involvement of opioidergic and nitrergic systems.
abstract: Oleuropein, a well-known olive polyphenol, has been shown to mediate neuroprotection in Alzheimer's disease and cerebral ischemia. We investigated the effects of oleuropein on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice, with diazepam as the standard drug. We also examined the possible involvement of opioidergic/nitrergic pathways in the probable effects of oleuropein. Intraperitoneal (i.p.) administration of different doses of oleuropein (10, 20 and 30 mg/kg) significantly increased the seizure threshold 60 min prior to induction of seizure, in a dose-dependent manner. Administration of naltrexone (10 mg/kg, i.p.), an opioid receptor antagonist, completely reversed the anticonvulsant effects of oleuropein (10 mg/kg). On the other hand, the anticonvulsant effect of oleuropein (10 mg/kg) was blocked by a non-effective dose of nonspecific inhibitor of nitric oxide synthase (NOS), L-NAME (1 and 10 mg/kg, i.p) and a selective inhibitor of neuronal NOS, 7-nitroindazole (30 mg/kg, i.p.). However, the nitric oxide precursor, L-arginine (30 and 60 mg/kg, i.p.) potentiated the anticonvulsant activity of oleuropein (10 mg/kg). A selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) did not change the anticonvulsant activity of oleuropein. It seems that the opioidergic system and constitutive neuronal NOS may be involved in the anticonvulsant properties of oleuropein.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Rahimi
authors.affiliation: Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Delfan
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
authors.forename: Nazgol
authors.initials: N
authors.lastname: Motamed-Gorji
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. dehpour@yahoo.com.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001688:Biological Products; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D057888:Iridoid Glucosides; D039823:Iridoids / Q000009:adverse effects*; D008297:Male; D051379:Mice; D031658:Olea / Q000737:chemistry*; D010433:Pentylenetetrazole / Q000009:adverse effects*; D012640:Seizures / Q000139:chemically induced*
chemical_list: D001688:Biological Products; D057888:Iridoid Glucosides; D039823:Iridoids; C002769:oleuropein; D010433:Pentylenetetrazole
keywords: Mice; Nitric oxide; Oleuropein; Opioid; Pentylenetetrazole; Seizure