Paradoxical role of GABA in a chronic model of petit mal (absence)-like epilepsy in the rat
| Autor: | George G. Bierkamper, Kris Alan Smith |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Atypical absence seizures trans-1 4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride GABA Antagonists Epilepsy Seizures Internal medicine medicine Animals Picrotoxin gamma-Aminobutyric Acid Pharmacology Valproic Acid Dose-Response Relationship Drug Electromyography business.industry Electroencephalography GABA receptor antagonist medicine.disease Clonazepam Rats Disease Models Animal Anticonvulsant Endocrinology Epilepsy Absence Chronic Disease GABAergic Anticonvulsants business Diazepam medicine.drug |
| Zdroj: | European Journal of Pharmacology. 176:45-55 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(90)90130-x |
| Popis: | Neonatal Long-Evans hooded rats were treated with AY-9944, a cholesterol biosynthesis inhibitor, every 6 days for 7 weeks to induce a permanent absence-like epileptic condition. AY-9944-treated rats averaged 50 +/- 15 generalized non-motor seizures per hour of 2-15 s duration as monitored by electrocorticography. Clinically effective anti-absence drugs were observed to reduce seizure occurrence in a dose-dependent manner. Paradoxically, GABA agonists increased seizure occurrence while GABA antagonists decreased seizure occurrence. Evaluation of the benzodiazepines, diazepam and clonazepam, in this model revealed inhibition of seizure activity by GABA-independent mechanisms. Valproic acid produced a biphasic effect suggesting a GABA-independent, antiabsence action at low doses and GABAergic augmentation of seizure occurrence at higher doses. The results of this study support the hypothesis that increased GABAergic stimulation may induce inhibitory seizures in absence epilepsy. |
| Databáze: | OpenAIRE |
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