Microperfusion of picrotoxin in the hippocampus of chronic freely moving rats through microdialysis probes: a new method of induce partial and secondary generalized seizures.

In this study we investigated the threshold and latency of seizures in a new model of chemically induced partial seizures, with or without secondary generalization. We performed repeated experiments with a maximum of 20 between day seizures on each individual rat over a period up to 6 months, with resting intervals ranging from 3 to 15 days depending on the severity of seizures. Seizures were induced by microperfusion of variable doses of picrotoxin starting at 100 microM in each animal and increasing in steps of 25 microM through microdialysis probes introduced in the hippocampus of freely moving rats. The seizures were registered in a Holter-EEG and videotaped. Only one picrotoxin dose was perfused during each experimental session. Threshold was defined as the minimum dose of picrotoxin which induced a type of seizure after a 5 min period of perfusion. Latency was defined as the period from the end of the microperfusion period to the onset of electro-behavioral seizures. Patterns of seizures induced in different experimental sessions showed a dose-dependent variation ranging from arrest behavior (absence-like) to rapidly recurring seizures. A permanent seizure threshold for each type of seizure was observed in repeated experiments within individual rats, but when compared with different animals, significant variations in threshold were observed. A long latency period (14-41 min) was observed, unrelated to threshold or seizure type. Since the method can induce separate seizures with constant seizure threshold in experiment rats over a testing period as long as 6 months, the described method offers a new way to test a large number of antiepileptic drugs on the same animals.