Anticonvulsant efficacy of gabapentin on kindling in the immature brain.
The anticonvulsant and motor effects of gabapentin (GBP) were evaluated in rat pups aged 16-17 days. Fourteen-day-old rat pups received an implanted stimulating electrode in the amygdala unilaterally. Kindled seizures were produced on day 16 of life by repeatedly applying an electrical current stimulus to the amygdala electrode. Animals received kindling stimulation until they achieved three consecutive generalized convulsions. On day 17, rat pups received one of four doses of GBP 10, 25, 50, or 100 mg/kg. After receiving GBP, rat pups again received electrical stimulation to the amygdala electrode to determine the extent to which GBP prevented the kindled seizure. Anticonvulsant effects were found at doses as low as 10 mg/kg. A separate group of naïve rats received GBP to determine the motor effects of each treatment dose. Impaired motor performance, quantified as time on a balance beam, occurred at doses of >or=50 mg/kg. In summary, our data indicate that in immature rats, GBP exerts an anticonvulsant effect against kindled seizures at doses that do not significantly impair motor performance.
Lado
F A
FA
Department of Neurology, Albert Einstein College of Medicine, Montefiore Medical Center Epilepsy Management Center, Bronx, NY 10461, USA. ladof@ix.netcom.com
Sperber
E F
EF
Moshé
S L
SL
D000085:Acetates / Q000494:pharmacology*; D000367:Age Factors; D000588:Amines; D000679:Amygdala / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D000077206:Gabapentin; D006801:Humans; D007223:Infant; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin