Role of ATP-sensitive potassium channels in the biphasic effects of morphine on pentylenetetrazole-induced seizure threshold in mice.
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.
Shafaroodi
Hamed
H
Department of Pharmacology, Tehran Medical Unit, Islamic Azad University, Tehran, Iran.
Asadi
Shahrzad
S
Sadeghipour
Hamed
H
Ghasemi
Mehdi
M
Ebrahimi
Farzad
F
Tavakoli
Sina
S
Hajrasouliha
Amir Reza
AR
Dehpour
Ahmad Reza
AR
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009294:Narcotics; D015221:Potassium Channels; D019806:Cromakalim; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide; D010433:Pentylenetetrazole