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.

Abstract

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.

• Authors: K Ishige, H Endo, H Saito, Y Ito
• Journal: Neuroscience letters (Neurosci Lett) Vol. 297 Issue 3 Pg. 207-10 (Jan 19 2001) ISSN: 0304-3940 [Print] Ireland
• PMID: 11137764 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Cyclic AMP Response Element-Binding Protein
• GABA Antagonists
• GABA-B Receptor Antagonists
• Phosphinic Acids
• Transcription Factor AP-1
• 3-aminopropyl-cyclohexylmethylphosphinic acid
• Ethosuximide
• DNA

Topics

• Animals
• Anticonvulsants (administration & dosage)
• Cerebellum (metabolism)
• Cerebral Cortex (metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• DNA (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Epilepsy, Absence (drug therapy, metabolism)
• Ethosuximide (administration & dosage)
• GABA Antagonists (administration & dosage)
• GABA-B Receptor Antagonists
• Hippocampus (metabolism)
• Mice
• Phosphinic Acids (administration & dosage)
• Sleep Stages (drug effects)
• Thalamus (metabolism)
• Transcription Factor AP-1 (metabolism)
• Treatment Outcome