Systemic administration of lithium chloride and tacrine but not kainic acid augments citrulline content of rat brain.
The effects of tacrine (5 mg/kg i.p.) in lithium chloride (LiCl; 12 mEq/kg i.p.)-pretreated (24 h beforehand) animals and of kainate (10 mg/kg i.p.) on brain citrulline, the co-product of nitric oxide (NO) synthesis, were studied in rats. High performance liquid chromatography analysis of whole brain tissue homogenates from rats treated with LiCl and tacrine revealed a significant increase in citrulline content before the onset of seizures. This effect was prevented in a stereoselective manner by N omega-nitro-L-arginine methyl ester (10 mg/kg i.p., given 20 min before tacrine), an inhibitor of NO synthase. By contrast, kainic acid (10 mg/kg i.p.) did not affect significantly brain citrulline during the pre-convulsive period. In conclusion, our data indicate that in rats seizures induced by LiCl and tacrine but not kainic acid are triggered by excessive NO production in the brain.
Bagetta
G
G
Department of Neuroscience, University of Cagliari, Italy.
Rodinò
P
P
Paoletti
A M
AM
Arabia
A
A
Massoud
R
R
Nisticò
G
G
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000378:metabolism*; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018697:Nootropic Agents; D019335:Nitroarginine; D002956:Citrulline; D009569:Nitric Oxide; D013619:Tacrine; D008094:Lithium; D019001:Nitric Oxide Synthase; D007608:Kainic Acid