Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: an ontogenic study.
OBJECTIVE
To examine antiepileptogenic and antiictogenic potential of retigabine (RTG) under conditions of rapid kindling epileptogenesis during different stages of development.


METHODS
The experiments were performed in postnatal day 14 (P14), P21, and P35 male Wistar rats. After stereotaxic implantation of hippocampal stimulating and recording electrodes, the effects of RTG on baseline afterdischarge (AD) properties were studied. Next, the animals underwent rapid kindling (sixty 10 s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of seizures (kindling acquisition), and responses to test stimulations after kindling (retention) were compared between RTG and vehicle-treated rats. Additionally, the effects of RTG on the severity of seizures in previously kindled animals were examined.


RESULTS
When administered intraperitoneally in doses that induced only mild, or no motor deficits, RTG significantly dampened brain excitability, evident as the increase of AD threshold and shortening of AD duration. During kindling, RTG delayed the development of focal seizures in P14 rats, and prevented the occurrence of full limbic seizures at all three ages. At P14 and P21, but not at P35, pretreatment with RTG prevented the establishment of kindling-induced enhanced seizure susceptibility. Administration of RTG to kindled animals decreased the severity of seizures induced by test stimulation. The effect was most prominent at P14.


CONCLUSIONS
RTG exerted both antiepileptogenic and antiictogenic effects under conditions of rapid kindling model. These effects were apparent during postneonatal, early childhood, and adolescent stages of development.
Mazarati
Andréy
A
Department of Pediatrics, Neurology Division, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752, USA. mazarati@ucla.edu
Wu
Jim
J
Shin
Don
D
Kwon
Young Se
YS
Sankar
Raman
R
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects / Q000528:radiation effects; D002219:Carbamates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D010655:Phenylenediamines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine