Anticonvulsant drugs effective against human temporal lobe epilepsy prevent seizures but not neurotoxicity induced in rats by quinolinic acid: electroencephalographic, behavioral and histological assessments.

ABSTRACT

Intrahippocampal injection of quinolinic acid (QUIN) in rats caused an epileptic-like syndrome reminiscent of human temporal lobe epilepsy. By electroencephalographic (EEG) analysis, the authors assessed whether QUIN seizures were responsive to anticonvulsants effective in the treatment of the human disease. Anticonvulsants used in clinical practice to control partial seizures, such as carbamazepine, diphenylhydantoin, sodium phenobarbital, sodium valproate and diazepam, prevented QUIN-induced EEG seizures, whereas ethosuximide, which is specifically used to control absence attacks, and chlorpromazine, a sedative with no anticonvulsant properties, were ineffective. QUIN seizures showed particular sensitivity to carbamazepine (5 mg/kg) but were resistant to diphenylhydantoin unless a relatively high dose was used (100 mg/kg). None of the effective anticonvulsants completely suppressed EEG paroxysmal events like spikes and fast activity. Animals injected with QUIN displayed chewing, sniffing and rearing; no clear correlation was found between the ability of drugs to prevent QUIN-induced EEG seizures and effects on stereotypies, suggesting that these behavioral signs are not sensitive measures of anticonvulsant activity in this model. The anticonvulsants that protected animals from QUIN seizures did not prevent nerve cell degeneration induced by the excitotoxin, thus indicating that nerve cell death can occur even in the absence of sustained seizure activity. The data show that, in this animal model of epilepsy, the EEG seizure activity is specifically sensitive to anticonvulsants effective in partial epilepsy, thus suggesting that it could be used to test potential new drugs for this human disorder.