[Involvement of GABAergic and NMDA systems in drug-induced convulsions in mice].
Intravenous (iv) pretreatment of muscimol, a GABAA receptor agonist, inhibited the convulsive effect of bicuculline but not that of picrotoxin, whereas phenobarbital, a Cl ion channel blocker, exhibited both effects. These results suggest that the bicuculline-induced convulsion may be due to Cl ion channel blockade secondary to the direct inhibition of GABAA receptors. CPP and MK-801, competitive and noncompetitive NMDA antagonists, respectively, inhibited both the bicuculline- and picrotoxin-induced convulsion, suggesting that these convulsive effects may also involve activation of the NMDA-Ca ion channel complex, which might link to the GABA-Cl ion channel system. Anticonvulsants phenytoin, carbamazepine and diazepam as well as phenobarbital inhibited the convulsive responses of bicuculline and picrotoxin. Therefore, the anticonvulsive effects of these drugs may involve an activation of the GABA-Cl ion channel function. On the other hand, neither the GABA agonist nor anticonvulsants affected NMDA-induced convulsion. These results also provide evidence that the convulsive effects of bicuculline and picrotoxin may be mediated by indirect activation of NMDA systems through their Cl ion channel-blocking action, whereas the convulsive effects of NMDA may involve the activation of NMDA-Ca ion channel function without the GABA-Cl ion channel activities.
Obara
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Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000037:antagonists & inhibitors; D015220:Calcium Channels / Q000187:drug effects; D018118:Chloride Channels / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D010852:Picrotoxin / Q000037:antagonists & inhibitors; D018079:Receptors, GABA / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000927:Anticonvulsants; D001640:Bicuculline; D015220:Calcium Channels; D018118:Chloride Channels; D009118:Muscimol; D010634:Phenobarbital; D010852:Picrotoxin; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate