ucb L059, a novel anticonvulsant, reduces bicuculline-induced hyperexcitability in rat hippocampal CA3 in vivo.

Local diffusion of bicuculline from a bicuculline-containing recording micropipette increased the orthodromic field population spike (PS2), elicited upon commissural stimulation in the hippocampal CA3 region of anaesthetized rats. This increase in PS2 was consistently reduced by 5.4 mg/kg of the novel anticonvulsant drug ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide), when injected i.v. 10 min prior to lowering in place the bicuculline-containing micropipette. ucb L059 had no effect on PS2 in the absence of bicuculline. Paired-pulse stimulation produced marked inhibition of the second PS2 at low interstimulus interval, an effect which was significantly reduced by bicuculline. Although ucb L059 reduced the effect of bicuculline on both PS2S elicited by paired stimulations, the drug did not alter the reduction by bicuculline of paired-pulse inhibition at low interstimulus interval. These results suggest that ucb L059 prevents increases in CA3 neuronal excitability by bicuculline through a non gamma-aminobutyric acid-ergic mechanism.