The Effect of L-Arginine on the Memory Impairing Action

of Phenobarbitone in Rats that Convulsed

after the Injection of Picrotoxin

Vanaja Paul*, Leema Reddy and P. Ekambaram

Department of Pharmacology and Environmental Toxicology,

Dr. ALM Postgraduate Institute of Basic Medical Sciences,

University of Madras,

Taramani, Chennai – 600 113

( Received on October 15, 2003 )

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Abstract : Nitric oxide (NO) has been demonstrated to enhance memory formation in experimental animals. However, the effect of NO precursor, L-arginine has never been tested on the memory impairing action of the aniepileptic drug, phenobarbitone independently and concurrently with the convulsant, picrotoxin (PCT). In view of this, in the present study, rats that acquired the shock avoidance task were treated with PCT (5 mg/kg). Twenty four h later these animals were injected with L-arginine (500, 1000 mg/kg) and phenobarbitone (10, 20 mg/kg). Retention of the acquired task was tested 30 min later. The effect of these compounds were correlated with the changes produced by them on the concentration of NO in the brain. PCT and phenobarbitone (20 mg/kg) inhibited memory process independently and concurrently. NO concentration was not altered by phenobarbitone but was decreased in PCT-treated animals. L-arginine (1000 mg/kg) increased the concentration of NO in PCT and phenobarbitone treated animals and prevented these compounds from impairing memory process independently and concurrently. These results lead to a conclusion that L-arginine may be used in combination with phenobarbitone to prevent both the cognitive side effect of the antiepileptic drug and the impairment of memory that is associated with the convulsion disorder.

Key words : nitric oxide           phenobarbitone          picrotoxin          rats