Characterization of GABAergic seizure regulation in the midline thalamus.
This study characterized the role of GABA in the central medial intralaminar nucleus on seizures induced by pentylenetetrazol given systemically. Injections of the direct selective GABAA agonist, piperidine-4-sulfonic acid or the indirect GABAA agonists, flurazepam and pentobarbital, in this region depressed arousal and facilitated myoclonic and clonic seizures induced by pentylenetetrazol but only caused slight inhibition of tonic seizures. In contrast the GABAB agonist (-)baclofen facilitated all three types of seizures. Recording after injection of piperidine-4-sulfonic acid and (-)baclofen revealed marked suppression and slowing of thalamic and cortical electrical activity. Thalamic injections of the GABAA antagonist, bicuculline methiodide, had opposite behavioral effects, causing hyperactivity and episodes of violent running, not accompanied by EEG discharges. When pentylenetetrazol was infused concommitantly there was marked facilitation of the tonic seizures, which occurred without preceding myoclonic of clonic seizures, or EEG spikes. These results demonstrate that GABA-mediated neurotransmission in the central medial intralaminar nucleus can control the threshold of seizures and that GABA agonists and antagonists have opposite effects. It is suggested that the central medial intralaminar nucleus is not a site of origination or spread of seizures, but controls seizures indirectly by regulating the excitability of other structures and that different synaptic mechanisms and anatomical connections mediate effects on different types of seizures.
Miller
J W
JW
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110.
Ferrendelli
J A
JA
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D005479:Flurazepam / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D010880:Piperidines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C023402:piperidine-4-sulfonic acid; D001418:Baclofen; D010424:Pentobarbital; D005479:Flurazepam; D010433:Pentylenetetrazole; D001640:Bicuculline