Repeated administration of CGP 46381, a gamma-aminobutyric acidB antagonist, and ethosuximide suppresses seizure-associated cyclic adenosine 3'5' monophosphate response element- and activator protein-1 DNA-binding activities in lethargic (lh/lh) mice.
To characterize seizure-associated increases in cerebral cortical and thalamic cyclic AMP responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in lethargic (lh/lh) mice, a genetic model of absence seizures, we examined the effects of ethosuximide and CGP 46381 on these DNA-binding activities. Repeated administration (twice a day for 5 days) of ethosuximide (200 mg/kg) or CGP 46381 (60 mg/kg) attenuated both seizure behavior and the increased DNA-binding activities, and was more effective than a single administration of these drugs. These treatments did not affect either normal behavior or basal DNA-binding activities in non-epileptic control (+/+) mice. Gel supershift assays revealed that the increased CRE-binding activity was attributable to activation of the binding activity of CREB, and that the c-Fos-c-Jun complex was a component of the increased AP-1 DNA-binding activity.
Ishige
K
K
Department of Pharmacology, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, 274-8555, Funabashi, Japan. ishigek@pha.nihon-u.ac.jp
Endo
H
H
Saito
H
H
Ito
Y
Y
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000378:metabolism*; D005013:Ethosuximide / Q000008:administration & dosage*; D018756:GABA Antagonists / Q000008:administration & dosage; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D010721:Phosphinic Acids / Q000008:administration & dosage*; D012894:Sleep Stages / Q000187:drug effects; D013788:Thalamus / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D016896:Treatment Outcome
D000927:Anticonvulsants; D017362:Cyclic AMP Response Element-Binding Protein; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D018808:Transcription Factor AP-1; C086109:3-aminopropyl-cyclohexylmethylphosphinic acid; D005013:Ethosuximide; D004247:DNA