Levetiracetam has no significant γ-aminobutyric acid-related effect on paired-pulse interaction in the dentate gyrus of rats

Abstract

γ-Aminobutyric acid (GABA)ergic mechanisms of the novel antiepileptic drug, levetiracetam ( Keppra®), have been both favored and rejected. Since paired-pulse interaction is accepted in functionally assessing GABAergic mechanisms, we investigated whether levetiracetam affects the paired-pulse inhibition/facilitation of the field potentials, evoked in the dentate gyrus of urethane-anesthesized rats. This model revealed a strong paired-pulse inhibition at 20-ms interstimulus interval, a noteworthy paired-pulse facilitation at 80-ms interstimulus interval, and a moderate paired-pulse inhibition at 500-ms interstimulus interval. Bicuculline (3 mg/kg/h, i.v.) and baclofen (10 mg/kg, i.v.) markedly depressed paired-pulse inhibition at 20-ms interstimulus interval, while clonazepam (1 mg/kg, i.p.), diazepam (10 mg/kg, i.v.), and phenobarbital (40 mg/kg, i.v.) enhanced it. Bicuculline also depressed paired-pulse inhibition at 500-ms interstimulus interval. Bicuculline, baclofen, and diazepam reduced paired-pulse facilitation at 80-ms interstimulus interval. Distinct from these GABA A receptor- and GABA B receptor-related drugs, levetiracetam (17 and 540 mg/kg, i.v.) had no significant effect on either paired-pulse interaction in this model, a result not favoring any major role of GABAergic mechanisms in its antiseizure action.