Tiagabine exerts an anti-epileptogenic effect in amygdala kindling epileptogenesis in the rat.
Tiagabine (TGB) is a novel antiepileptic drug whose anticonvulsant effects are due to inhibition of gamma-aminobutyric acid (GABA) transport mediated by the GABA transporter-1. We have previously shown that TGB is effective in acute amygdala kindled seizures, and consequently we wanted to test the hypothesis that TGB also could suppress the development of kindling epileptogenesis. Rats had stereotaxically implanted stimulating/recording electrodes in the basolateral amygdala and recording electrode in the contralateral occipital cortex. Rats were divided in three groups (n = 8 for each group) intraperitoneally (i.p.) administered vehicle, TGB 7.3 micromol/kg and TGB 24.3 micromol/kg, respectively, 30 min before stimulation. TGB dose-dependently suppressed the development of the behavioral seizure score and afterdischarge (AD) duration recorded from the amygdala and cortex. Vehicle treated animals displayed at the 16th stimulation an average behavioral score of 4.7 +/- 0.2 (mean +/- SEM) compared to 3.9 +/- 0.2 in the 7.3 micromol/kg TGB treated group and 1.4 +/- 0.3 in the 24.3 micromol/kg TGB treated group. Amygdaloid AD in controls on the 16th stimulation was 92 +/- 10 s compared to 56 +/- 12 s in group 2 and 25 +/- 3 s in group 3. Cortical AD was at the same time 92 +/- 10, 55 +/- 13 and 20 +/- 5 s, respectively. Groups 2 and 3 required four and seven further stimulations, respectively, without TGB administration to reach the AD level in the control group. At the 17th stimulation, rats in group 1 were administered TGB 24.3 micromol/kg and displayed an average behavioral score of 0.5 +/- 0.2. Amygdaloid and cortical AD were both 6 +/- 1 s. Tiagabine 24.3 micromol/kg suppresses both the kindling process and the expression of the fully kindled seizure.
Dalby
N O
NO
Novo Nordisk, Health Care Discovery, Måløv, Denmark. nod@novo.dk
Nielsen
E B
EB
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000188:drug therapy*; D007696:Kindling, Neurologic; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000078308:Tiagabine
D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine