The role of GABA and excitatory amino acids in the development of the leptazol-induced epileptogenic EEG.
The developing epileptogenic electroencephalogram (EEG), seen during the slow intravenous infusion of leptazol, is sensitive to various anticonvulsant drugs, particularly those known to augment the function of gamma-aminobutyric acid (GABA), such as clonazepam and sodium valproate, which specifically prolong the earlier wave-like (pre-spiking) phases. Thus, whilst antagonism of GABA may be responsible for spiking, the early wave-like phases may be due to GABA released in the cortex as a feedback control to delay spiking. Intravenous infusion of the GABA antagonists, bicuculline and picrotoxin, produced a developing EEG with spiking the first abnormal feature noted and no wave-like phase, like that seen with leptazol. Cortical superfusion of GABA during the infusion of leptazol, enhanced kand prolonged the wave-like phase, whilst bicuculline reduced it. Cortical superfusion of leptazol, picrotoxin or larger concentrations of bicuculline produced spiking but no wave-like activity. When leptazol and GABA were superfused together they produced wave-like activity similar to that seen during infusions of leptazol. Of the excitatory amino acid antagonists, only those active at receptors for N-methyl-D-aspartate (NMDA) influenced the EEG changes induced by leptazol. It is suggested that leptazol produces waves in the EEG by stimulating subcortical pathways to release GABA in the cortex and that spiking occurs as the cortex is further stimulated by GABA antagonism and the release of excitatory amino acids.
D000501:Allylglycine / Q000494:pharmacology; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D018756:GABA Antagonists; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008297:Male; D010433:Pentylenetetrazole; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000501:Allylglycine; D000596:Amino Acids; D001640:Bicuculline; D002998:Clonazepam; D018756:GABA Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D010433:Pentylenetetrazole; D010852:Picrotoxin; D014635:Valproic Acid; D005680:gamma-Aminobutyric Acid