An ATP-sensitive potassium channel blocker abolishes the potentiating effect of morphine on the bicuculline-induced convulsion in mice.
ICV bicuculline, a selective GABAA antagonist, dose-dependently induced clonic-tonic convulsions in mice. Coadministration of ICV morphine (mu opioid agonist) significantly potentiated ICV bicuculline-induced convulsions, and this effect of morphine was completely blocked by pretreatment with beta-funaltrexamine (beta-FNA), a mu antagonist. ICV glibenclamide, a selective ATP-sensitive potassium (KATP) channel blocker, at a dose which alone did not affect the convulsive threshold of bicuculline, was capable of blocking the exacerbation of ICV bicuculline-induced convulsions by morphine. The present data further suggest that KATP channels may play a tonic regulatory role in the potentiative effect of morphine on ICV bicuculline-induced convulsions.
Narita
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Takahashi
Y
Y
Suzuki
T
T
Misawa
M
M
Nagase
H
H
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced*; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D015221:Potassium Channels; D009118:Muscimol; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide; D001640:Bicuculline