Lack of involvement of nitric oxide in the mechanisms of seizures and hippocampal damage produced by kainate and ouabain in rats.
The gross behavioural, electrocortical and neuropathological effects of kainate (10 mg/kg i.p,) and ouabain (1 micrograms, given into one dorsal hippocampus) were studied in rats. The effects of these treatments on nitric oxide synthase (NOS) activity in homogenates of hippocampus and cortex were also studied. Administration of kainate or ouabain produced motor and electrocortical seizures similar for latency to onset (approximately 15 min) and intensity (in all instances 80-100% of the treated rats showed behavioural and electrographic seizures). These effects were accompanied at 24 h by severe damage to all subsectors of the hippocampal formation and this concerned a similar proportion of the treated rats (n = 4-8 per treatment). No significant changes in nitric oxide synthase (NOS) activity were noted in the cerebral cortex and hippocampus of rats receiving injections of kainate and ouabain. In addition, pretreatment with N omega-Nitro-L-arginine methyl ester (300 micrograms, given into one lateral cerebral ventricle 15 min previously) was ineffective in preventing the effects of kainate and ouabain. In conclusion, present data suggest that excessive production of NO is not involved in the mechanisms triggering seizures and neurodegeneration produced by kainate or ouabain.
Bagetta
G
G
Faculty of Pharmacy, Calabria University, Cosenza, Italy.
Iannone
M
M
Palma
E
E
Rodinò
P
P
Granato
T
T
Nisticò
G
G
D000594:Amino Acid Oxidoreductases / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001925:Brain Damage, Chronic / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects*; D007608:Kainic Acid / Q000633:toxicity*; D018021:Lithium Chloride; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D010042:Ouabain / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013619:Tacrine / Q000633:toxicity
D009569:Nitric Oxide; D013619:Tacrine; D010042:Ouabain; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D018021:Lithium Chloride; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester