[Lidocaine increases the granule cell excitability in hippocampal dentate area instead of affecting GABAergic...

Lidocaine is well known to have toxic effects on the central nervous system including the induction of electroencepharographic seizures and convulsions at high doses. Although lidocaine was reported to induce electroencepharographic seizures and behavioral convulsions by decreasing the strength of GABAergic synaptic inhibition, detailed mechanisms underlying the lidocaine-induced seizures remain unclear. To determine whether lidocaine decreases GABAergic inhibition or increases the cellular excitability instead of reducing GABAergic inhibition, in the present study, we examined effects of lidocaine on monosynaptic field potentials in the hippocampal dentate gyrus of urethane-anesthetized rats. Lidocaine (10-15 mg.kg-1, i.v.) decreased significantly the threshold for action potential generation instead of producing a significant decrease in GABAergic paired-pulse inhibition. The results suggest that lidocaine first produces the hyperexcitability of hippocampal neurons, which then decreases the hippocampal GABAergic inhibition by the so-called inhibition failure leading to the induction of seizures.