[Reliable induction of generalized seizures in hippocampal kindling triggered with low-frequency electrical...

To assess the appropriateness of hippocampal low-frequency kindling as an experimental model of epilepsy, we stimulated, bipolarly, left ventral hippocampus of 8 cats with 2 mA biphasic square wave pulses (1 msec duration) once a day. The pulse-interval was set at 300 msec. Recording electrodes were inserted in right ventral hippocampus, bilateral amygdaloid and bilateral globus pallidus. EEG was monitored before, during and after the delivery of stimulation. If the triggering of epileptic afterdischarge was observed on EEG monitoring, the delivery of stimulation was stopped immediately. Generalized convulsive seizures developed in all subjects within a mean of 26.2 days. In all seizures self-sustained epileptic afterdischarge, defined as epileptiform spikes three times the base line amplitude with a frequency greater than the stimulating pulse-interval (300 msec) in the stimulated hippocampus lead, was triggered abruptly. Therefore we could measure the number of stimulating pulses required for the triggering of epileptic afterdischarge, defined as pulse-number threshold, definitely in all cases. At the completion of kindling the pulse-number threshold was measured at 12.3 +/- 0.9 (+/- SE). After five generalized convulsions were induced we tested the stability of the pulse-number threshold and the duration of triggered epileptic afterdischarge. Both the two measures did not change statistically at the interstimulation interval from 24 hrs to 96 hrs. In addition we carried out testing with antiepileptic and antipsychotic drugs. Phenobarbital (10 mg/kg, i.p.) increased the pulse-number threshold and the after discharge duration simultaneously. Haloperidol (3 mg/kg, i.p.), oppositely, decreased the pulse number threshold and the after discharge duration.