title: Role of ATP-sensitive potassium channels in the biphasic effects of morphine on pentylenetetrazole-induced seizure threshold in mice.
abstract: Although several studies have indicated that the opioid receptor agonist morphine exerts biphasic effects on clonic seizure threshold, as yet little is known of the underlying mechanisms in this effect. In the present study, using the specific ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide and the specific K(ATP) channel opener cromakalim, the possible involvement of K(ATP) channels in the effects of morphine on pentylenetetrazole (PTZ)-induced seizure threshold in mice was investigated. Acute administration of lower doses of morphine (1, 3 and 7.5 mg/kg, i.p.) increased and higher doses of morphine (30 and 60 mg/kg, i.p.) decreased the PTZ-induced seizure threshold. Glibenclamide (2.5-5 mg/kg) increased the PTZ-induced seizure threshold. Non-effective dose of cromakalim (0.1 microg/kg) inhibited anticonvulsant effect of glibenclamide (5 mg/kg). Acute administration of non-effective dose of glibenclamide (1 mg/kg) interestingly inhibited both anticonvulsant and pro-convulsant effects of morphine and this effect was significantly reversed by cromakalim (0.1 microg/kg). These results support the involvement of K(ATP) channels in the modulation of seizure threshold by morphine.
authors.affiliation: Department of Pharmacology, Tehran Medical Unit, Islamic Azad University, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Asadi
authors.forename: Hamed
authors.initials: H
authors.lastname: Sadeghipour
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Farzad
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: Sina
authors.initials: S
authors.lastname: Tavakoli
authors.forename: Amir Reza
authors.initials: AR
authors.lastname: Hajrasouliha
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000187:drug effects; D019806:Cromakalim / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005905:Glyburide / Q000008:administration & dosage; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D010433:Pentylenetetrazole; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009294:Narcotics; D015221:Potassium Channels; D019806:Cromakalim; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide; D010433:Pentylenetetrazole