Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats.
OBJECTIVE
To evaluate the effects of high-frequency electrical stimulation (HFS) in both ventral hippocampi, alone and combined with a subeffective dose of antiepileptic drugs, during the status epilepticus (SE) induced by lithium-pilocarpine (LP).


METHODS
Male Wistar rats, stereotactically implanted in both ventral hippocampi, were injected with pilocarpine (30 mg/kg, i.p.) 24 h after lithium (3 mEq/kg) administration. One minute following pilocarpine injection, HFS (pulses of 60 mus width at 130 Hz at subthreshold intensities and applied during 3 h) was applied alone or combined with subeffective doses of antiepileptic drugs.


RESULTS
HFS alone reduced the incidence of severe generalized seizures. This effect was not evident when HFS was combined with phenytoin (33.3 mg/kg, i.p.). HFS combined with diazepam (0.41 mg/kg, i.p.) or phenobarbital (10 mg/kg, i.p.) reduced the incidence of severe generalized seizures and mortality rate, and augmented the latency to first forelimb clonus, generalized seizure, and status epilepticus (SE). When combined with gabapentin (46 mg/kg, i.p.), HFS reduced the incidence of severe generalized seizures, enhanced latency to SE, and decreased mortality rate.


CONCLUSIONS
Subeffective doses of antiepileptic drugs that increase the gamma-aminobutyric acid (GABA)ergic neurotransmission may represent a therapeutic tool to augment the HFS-induced anticonvulsant effects.
Departamento de Farmacobiología, Sede Sur del Centro de Investigación y Estudios Avanzados del IPN, Mexico DF, Mexico.
Manola
M
Cuellar-Herrera
Fernando
F
Peña
David
D
Alcantara-Gonzalez
Leticia
L
Neri-Bazan
Luisa
L
Rocha
D000588:Amines / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin; D018021:Lithium Chloride