Pharmacological evidence indicating a role of GABAergic systems in termination of limbic seizures.
The role of inhibitory systems in the initiation and termination of seizures in limbic circuits of the rat was tested by measuring the time to onset and duration of maximal dentate activation before and after the administration of GABAergic agents. Both 0.1 and 0.3 mg/kg of the GABAA receptor antagonist bicuculline lengthened maximal dentate activation while 0.3 mg/kg was needed to reversibly decrease the time to onset. Picrotoxin, an antagonist at the GABAA receptor/channel complex, lengthened maximal dentate activation, but did not alter the time to onset. Muscimol, a GABAA receptor agonist, shortened maximal dentate activation, but did not lengthen the time to onset. Baclofen, a GABAB receptor agonist (3 and 10 mg/kg), had no effect on the time to onset of maximal dentate activation, while 10 mg/kg baclofen shortened maximal dentate activation. These results demonstrate that agents that have selective action at both GABAA and GABAB synapses alter the duration of maximal dentate activation more than they influence the time to onset of maximal dentate activation and suggest that GABAergic mechanisms are critical in the termination of seizures.
Stringer
J L
JL
Department of Neurology, University of Virginia Medical Center, Charlottesville 22908.
Lothman
E W
EW
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000503:physiopathology; D007473:Ion Channels / Q000187:drug effects; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D001418:Baclofen; D001640:Bicuculline; D018118:Chloride Channels; D058787:GABA-A Receptor Antagonists; D007473:Ion Channels; D008565:Membrane Proteins; D009118:Muscimol; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid