title: Effect of anticonvulsant treatment on kainic acid-induced increases in peptide levels.
abstract: The influence of anticonvulsant treatment upon (1) chronically increased seizure susceptibility, (2) on late increases in peptide levels and (3) on seizure-induced brain damage was investigated during various stages of acute kainic acid (10 mg/kg i.p.)-induced seizures. The seizures were interrupted at various stages of the syndrome (50 min to 24 h after injection of the toxin) by injecting thiopental (50 mg/kg i.p.) or the excitatory amino acid antagonist, MK-801 (10 mg/kg i.p.). The increase in neuropeptide Y and somatostatin levels in the frontal cortex could be prevented by early injection of either anticonvulsant (up to 180 min after kainic acid). No protection against the increase in peptide levels was observed when the anticonvulsants were applied later. Kainic acid-induced neuronal damage in the amygdala, with glutamate decarboxylase as a neurochemical marker, was entirely prevented by interrupting seizures up to 2 h after kainic acid. Partial protection (about 40-50%) was even found when the anticonvulsant treatment was applied after the acute syndrome, as late as 8 h after kainic acid injection. Chronically increased seizure susceptibility induced by kainic acid was not prevented, even by early injection (90 min after kainic acid) of the anticonvulsant drugs. The data indicate that (1) the late increase in seizure susceptibility may be initiated early after injection of kainic acid. (2) the late increase in peptide levels may be related to the frequency of acute seizures rather than to a change in seizure threshold or brain damage and (3) even late anticonvulsant therapy may antagonize seizure-induced brain damage in the amygdala.
authors.affiliation: Department of Pharmacology, University of Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Marksteiner
authors.forename: R
authors.initials: R
authors.lastname: Prommegger
authors.forename: G
authors.initials: G
authors.lastname: Sperk
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013004:Somatostatin / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D009478:Neuropeptide Y; D009479:Neuropeptides; D013004:Somatostatin; D016291:Dizocilpine Maleate; D005968:Glutamate Decarboxylase; D007608:Kainic Acid; D010433:Pentylenetetrazole