title: Morphine sensitization in the pentylenetetrazole-induced clonic seizure threshold in mice: role of nitric oxide and μ receptors.
abstract: Behavioral sensitization occurs after repeated administration of μ-opioid receptor agonists following a drug-free period. It seems that the changes in dopaminergic systems induced by μ-opioid receptor agonists play a crucial role in behavioral sensitization to opioids. Nitric oxide also plays a role in some behavioral effects of morphine, including sensitization to the locomotor-stimulating effect. This study investigated whether morphine sensitization appears in seizure threshold and the possible role of μ-opioid receptor and nitric oxide in this sensitization. Sensitization was produced by daily injections of morphine (0.1, 0.5, 1, 5, 15, or 30 mg/kg), followed by a 10-day washout period. Then the challenge test was performed using morphine (0.1, 0.5, 1, 5, 15, or 30 mg/kg) in different groups. To assess clonic seizure threshold, pentylenetetrazole (PTZ) was administered intravenously. Subcutaneous administration of morphine (0.1 and 0.5 mg/kg) induced sensitization in PTZ-induced clonic seizures in mice. Intraperitoneal administration of L-NAME (20 mg/kg), a nonselective inhibitor of nitric oxide synthase, or naltrexone (10 mg/kg), an opioid receptor antagonist, along with morphine inhibited morphine-induced sensitization in PTZ-induced seizure threshold. In conclusion, at low doses, morphine induces sensitization in PTZ-induced clonic seizures in mice probably as a result of the interaction with μ-receptors and nitric oxide.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Centre, Islamic Azad University, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Nazanin
authors.initials: N
authors.lastname: Baradaran
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Siavash
authors.initials: S
authors.lastname: Dehpour
authors.forename: Tina
authors.initials: T
authors.lastname: Kabiri
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000009:adverse effects; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; D009569:Nitric Oxide; D009271:Naltrexone; D009020:Morphine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole