Assessment of seizure susceptibility in pilocarpine epileptic and nonepileptic Wistar rats and of seizure reinduction with pentylenetetrazole and electroshock models.
OBJECTIVE
Pentylenetetrazole (PTZ) and maximal electroshock (MES) models are often used to induce seizures in nonepileptic control animals or naive animals. Despite being widely used to screen antiepileptic drugs (AEDs), both models have so far failed to detect potentially useful AEDs for treating drug-resistant epilepsies. Here we investigated whether the acute induction of MES and PTZ seizures in epileptic rats might yield a distinct screening profile for AEDs.


METHODS
Status epilepticus (SE) was induced in adult male Wistar rats by intraperitoneal pilocarpine injection (Pilo, 320 mg/kg, i.p.). One month later, controls or naive animals (Cont) that did not develop SE postpilocarpine (N-Epi) and pilocarpine-epileptic rats (Epi) received one of the following: phenobarbital (PB, 40 mg/kg), phenytoin (PHT, 50 mg/kg), or valproic acid (VPA, 400 mg/kg). Thirty min later the animals were challenged with either subcutaneous MES or PTZ (50 mg/kg, s.c.).


RESULTS
VPA, PB, and PHT were able to prevent MES in all groups tested (Cont, N-Epi, and Epi groups), whereas for the PTZ model, only the Cont group (naive animals) had seizure control with the same AEDs. In addition, Epi and N-Epi groups when challenged with PTZ exhibited a higher incidence of severe seizures (scores IV-IX) and SE (p < 0.05, Fisher's exact test).


CONCLUSIONS
Our findings suggest that the induction of acute seizures with PTZ, but not with MES, in animals pretreated with pilocarpine (regardless of SE induction) might constitute an effective and valuable method to screen AEDs and to study mechanisms involved in pharmacoresistant temporal lobe epilepsy (TLE).
Blanco
Miriam Marcela
MM
Department of Physiology, UNIFESP, São Paulo, SP, Brazil.
dos Santos
Jair Guilherme
JG
Perez-Mendes
Patrícia
P
Kohek
Silvia R B
SR
Cavarsan
Clarissa Fantin
CF
Hummel
Michele
M
Albuquerque
Cristovão
C
Mello
Luiz E
LE
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000209:etiology; D004569:Electroencephalography; D004597:Electroshock / Q000009:adverse effects*; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology* / Q000517:prevention & control*
D000927:Anticonvulsants; D003292:Convulsants; D010862:Pilocarpine; D010433:Pentylenetetrazole