Evidence for GABAB-mediated mechanisms in experimental generalized absence seizures.
Experimental absence seizures are characterized by the fact that they are exacerbated by both direct and indirect GABA agonists. To date most of the studies that have examined this phenomenon have utilized GABAA agonists. We assessed the effect of a GABAB agonist, baclofen and a specific GABAB antagonist in two pharmacological models of absence seizures in rodent after using either gamma-hydroxybutyrate or pentylenetetrazole to induce the bilaterally synchronous spike wave discharges that typify absence seizures in rodent. Baclofen markedly prolonged and the GABAB antagonist attenuated or blocked the experimental absence seizures in both models. These data suggest a role for GABAB-related mechanisms in the pathogenesis of generalized absence seizures and raise the possibility that GABAB antagonists may have therapeutic potential as antiabsence drugs.
Snead
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Division of Neurology, Childrens Hospital Los Angeles, CA 90027.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000503:physiopathology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; C066430:CGP 35348; D001418:Baclofen