Changes in polyamine levels in rat brain after systemic kainic acid administration: relationship to convulsant activity and brain damage.
We have examined the effects of systemic kainic acid (KA) administration (9 mg/kg, i.p.) on rat behavior, brain damage, and polyamine levels and the action of the specific ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) on these effects. KA elicited convulsant activity in 63% of the animals. In the acute convulsant phase (1-3 h after KA), a rapid decline (-39% at 3 h) of spermidine content in frontal cortex was found. After the acute convulsant phase, levels of hippocampal spermidine and spermine were reduced (-70 and -66%, respectively, at 8 h). A dramatic increase of putrescine content (68.1, 1,382, and 336% at 8 h, 24 h, and 9 days, respectively, after KA) was found, associated with histological signs of cortical brain damage (ischemia and necrosis). There was a close relationship between the concentration of putrescine and signs of delayed toxicity (body weight losses) 24 h and 9 days after KA. DFMO partially antagonized the convulsant activity and reduced the increased putrescine levels to approximately 50% of values in KA-treated animals at 24 h but did not change the pattern of histological damage. The role of polyamines in the early and late phases of KA-induced neurotoxicity is discussed.
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Department of Pharmacology, C.S.I.C., Barcelona, Spain.
Artigas
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Serratosa
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Martínez
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001925:Brain Damage, Chronic / Q000139:chemically induced* / Q000473:pathology; D000518:Eflornithine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000494:pharmacology* / Q000506:poisoning; D008297:Male; D009017:Morbidity; D009026:Mortality; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology
D011073:Polyamines; D007608:Kainic Acid; D000518:Eflornithine