Prevention of picrotoxin convulsions-induced learning and memory impairment by nitric oxide increasing dose of L-arginine in rats.
Learning and memory processes were tested in adult male rats using a traditional pole-climbing apparatus 30 min after the administration of L-arginine (500 and 1000 mg/kg), the precursor of nitric oxide (NO), and N-nitro-L-arginine methyl ester (L-NAME) (50 and 100 mg/kg), the inhibitor of NO synthesis. The effects of the convulsant (5.0 mg/kg) and a smaller nonconvulsant (2.5 mg/kg) dose of picrotoxin were tested on learning and memory 120 min and 24 h after their administration. The tests were carried out 30 min after L-arginine in animals treated 120 min previously with the convulsant dose of picrotoxin. A dose-dependent enhancement and an inhibition of learning and memory were observed in animals treated with L-arginine and L-NAME, respectively. The convulsant dose of picrotoxin impaired both learning and memory processes. The effect of picrotoxin was reverted following the administration of L-arginine (1000 mg/kg). An interpretation of these results indicates that convulsions induced by picrotoxin produces learning and memory impairment, and that this defect is reversible if NO synthesis is increased in the brain by the systemic administration of L-arginine.
Paul
Vanaja
V
Department of Pharmacology and Environmental Toxicology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, Taramani, Chennai 600 113, India. pgibms@md2.vsnl.net.in
Reddy
Leema
L
Ekambaram
P
P
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007859:Learning Disabilities / Q000139:chemically induced* / Q000523:psychology*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010852:Picrotoxin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000523:psychology*
D001120:Arginine; D003292:Convulsants; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010852:Picrotoxin