[Effects of agonists and antagonists of benzodiazepine, GABA and NMDA receptors, on caffeine-induced seizures in mice].
In mice, tonic convulsive seizure induced by intravenous administration of caffeine (adenosine A1, A2 receptors antagonist) was significantly potentiated by any one of L-PIA (adenosine A1 receptor agonist), NECA (adenosine A2 receptor agonist) and 2-ClAd (adenosine A1, A2 receptors agonist). The caffeine-induced seizure was unaffected by diazepam (benzodiazepine receptor agonist), but was inhibited by Ro 15-1788 (antagonist or partial agonist). beta-DMCM (antagonist or inverse agonist) increased the seizure. Muscimol (GABA-a receptor agonist), baclofen (GABA-b receptor agonist) and AOAA (GABA transaminase inhibitor) did not show significant effect on caffeine-induced convulsion. Bicuculline (GABA-a receptor antagonist) and picrotoxin (chloride channel blocker) significantly potentiated the convulsion at the doses which did not induce it. Caffeine-induced convulsion was potentiated by NMDA with its non-convulsive dose. CPP (competitive NMDA receptor antagonist) and MK-801 (non-competitive NMDA receptor antagonist) significantly inhibited the seizures. These results suggest that caffeine-induced seizure is not caused by blockade of adenosine receptors. Caffeine may act to beta-carboline sensitive benzodiazepine receptor (Type 1) which has no linkage with GABA-a receptor. Furthermore, it is implied that caffeine plays some role at NMDA receptor calcium ion channel complex.
Inano
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Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Japan.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002110:Caffeine / Q000633:toxicity*; D003975:Diazepam / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011983:Receptors, Purinergic; D001569:Benzodiazepines; D009118:Muscimol; D002110:Caffeine; D005442:Flumazenil; D016291:Dizocilpine Maleate; D001418:Baclofen; D003975:Diazepam