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 loweri ng in place the bicuculline-containing micropipette, ucb L059 had no e ffect on PS2 in the absence of bicuculline. Paired-pulse stimulation p roduced marked inhibition of the second PS2 at low interstimulus inter val, an effect which was significantly reduced by bicuculline. Althoug h ucb L059 reduced the effect of bicuculline on both PS(2)s elicited b y paired stimulations, the drug did not alter the reduction by bicucul line of paired-pulse inhibition at low interstimulus interval. These r esults suggest that ucb L059 prevents increases in CA3 neuronal excita bility by bicuculline through a non gamma-aminobutyric acid-ergic mech anism.