GABA-B RECEPTORS IN VARIOUS INVITRO AND INVIVO MODELS OF EPILEPSY - A STUDY WITH THE GABA-B RECEPTOR BLOCKER CGP-35348

The effect of the GABA(B) receptor blocker CGP 35348 on epileptic processes in vitro and in vitro was studied. In hippocampal slices of the rat maintained in vitro, CGP 35348 (100-mu-M) induced a moderate increase in the frequency of extracellularly recorded spontaneous epileptiform burst discharges induced in CA3 by penicillin (1.2 mM), bicuculline (5-mu-M) and low Mg2+ (0.1 mM). This effect was observed in 50-75% of the slices. A similar but less consistent increase was also observed in CA1 in bicuculline and low Mg2+. Data obtained by intracellular recordings from CA1 pyramidal cells in the presence of bicuculline (10-mu-M) demonstrated that CGP 35348 (100-mu-M) increased the duration of the paroxysmal depolarization underlying an evoked epileptiform burst and reduced the early component of the afterhyperpolarization which followed the burst. In mice pretreated with isoniazid, CGP 35348 (300 mg/kg, i.p.) significantly increased the number of convulsing mice. However, convulsions induced by submaximal doses of pentylenetetrazol, picrotoxin or strychnine were not facilitated by CGP 35348. We conclude that GABA(B) receptors appear to exert a suppressant effect on various kinds of epileptiform discharges of hippocampal neurons in vitro. In vivo, however, the role of GABA(B) receptors in regulating convulsions is less prominent since only isoniazid-induced convulsions were facilitated by GABA(B) receptor blockade.