Secondary generalization in non-kindled rats following acute administration of GABA-complex and adenosine antagonists.
In order to test the GABA hypothesis of kindling, GABA-complex antagonists were administered in a dose-response paradigm to rats that had been implanted with indwelling forebrain electrodes, but not kindled. Focal seizures were then elicited from either the cortex or the amygdala to see whether kindling-like secondary generalization would occur. Norharmane, a benzodiazepine inverse agonist, failed to promote secondary generalization from either the cortex or the amygdala. Bicuculline, a GABAA receptor antagonist, and picrotoxin, a chloride ionophore antagonist, enhanced generalization from both sites and, in amygdala-implanted subjects, appeared to produce a significant acceleration of kindling as well. Aminophylline, an adenosine antagonist tested for purposes of comparison, also enhanced secondary generalization from both sites, and in amygdala-implanted subjects produced long electrographic discharges which sometimes developed into status epilepticus.
Department of Pharmacology, University of Toronto, Ont., Canada.
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Mingo
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WM
Burnham
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000628:Aminophylline / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002243:Carbolines; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004828:Epilepsies, Partial / Q000503:physiopathology*; D018756:GABA Antagonists; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology; D007696:Kindling, Neurologic; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats
D000241:Adenosine; D000628:Aminophylline; D001640:Bicuculline; D002243:Carbolines; D018756:GABA Antagonists; D006247:Harmine; D010852:Picrotoxin; C010262:norharman