ABSTRACT
This study addressed the anticonvulsant effects of repeated administration of phenytoin, carbamazepine, phenobarbital, valproate, and ethosuximide in kindled guinea-pigs in order to further substantiate this novel model of partial seizures for the screening of future anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using scores on a sedation/muscle relaxation rating index. In response to suprathreshold stimulation, the anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge duration (ADD) and behavioral seizure severity (SS) during a repeated drug treatment schedule in kindled guinea-pigs. All drugs exerted slight to moderate sedative effects in guinea-pigs on our rating index. We found that phenytoin, carbamazepine, and phenobarbital exhibited effective anticonvulsant properties in kindled guinea-pigs by reducing both ADD and SS. We found that valproate consistently reduced ADD throughout the treatment schedule but failed to significantly reduce SS. Lastly, ethosuximide failed to exhibit effective anticonvulsant properties. Our results indicate that the guinea-pig kindling model correctly predicted the actions of these common anticonvulsant drugs in the treatment of partial seizures. Guinea-pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.
Subject(s)
Anticonvulsants/adverse effects , Brain/drug effects , Epilepsies, Partial/drug therapy , Kindling, Neurologic/drug effects , Action Potentials/drug effects , Action Potentials/physiology , Amygdala/drug effects , Amygdala/physiology , Animals , Brain/physiology , Carbamazepine/adverse effects , Disease Models, Animal , Drug Administration Schedule , Drug Evaluation, Preclinical , Electric Stimulation/adverse effects , Epilepsies, Partial/physiopathology , Epilepsies, Partial/prevention & control , Ethosuximide/adverse effects , Female , Guinea Pigs , Kindling, Neurologic/physiology , Male , Phenobarbital/adverse effects , Phenytoin/adverse effects , Predictive Value of Tests , Reproducibility of Results , Species Specificity , Treatment Outcome , Valproic Acid/adverse effectsABSTRACT
This study addressed the anticonvulsant effects of phenobarbital, valproate, and ethosuximide in the amygdala of kindled guinea pigs to further validate this model for the screening of anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using quantitative locomotor tests, as well as scores on a sedation and muscle relaxation rating index. The anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioral seizure severity (SS) during early and late phases of kindling acquisition, and in kindled guinea pigs. ADD and SS were also measured in response to both threshold and suprathreshold kindling stimulation. All drugs exerted slight to moderate sedative effects in guinea pigs on both the behavioral tests and rating index. We found that phenobarbital exhibited effective anticonvulsant properties in guinea pigs by consistently reducing ADD and SS in response to both threshold and suprathreshold kindling stimulation. Valproate exhibited effective anticonvulsant properties at threshold stimulation and less effective properties at suprathreshold stimulation. Lastly, we found that ethosuximide lacked effective anticonvulsant action at either threshold or suprathreshold kindling stimulation. Our results indicate that the guinea pig kindling model correctly predicted the actions of phenobarbital, valproate, and ethosuximide in the treatment of partial seizures. Guinea pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.
