Epileptic syndromes frequently start at childhood and therefore it is cruci
al to test new anticonvulsants at immature stages of the nervous system. We
compared the effects of the gamma-aminobutyric acid (GABA) uptake inhibito
r tiagabine [(R)-N-(4,4-bis(3-methyl-2-thienyl)but)3-en-1-yl nipecotic acid
] on low-Mg2+-induced epileptic discharges in brain slices from rat pups (p
5-8) and juvenile animals (p 15-20). In tissue from rat pups, tiagabine sl
ightly reduced epileptiform activity in hippocampal area CAI but had no eff
ect in the entorhinal cortex. In juvenile rats, epileptiforn discharges wer
e unaffected in CA1 bur suppressed by 60% in the entorhinal cortex. While t
iagabine increases its efficacy with age, in-situ hybridisation and PCR ana
lysis show that mRNA coding for the neuronal GABA-transporter GAT-1 is alre
ady present at p 5. We therefore conclude that the increasing efficacy of t
iagabine during ontogenesis is due to functional maturation of GABAergic sy
napses rather than to up-regulation of GAT-1 expression. (C) 1999 Elsevier
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