Differential paired-pulse effects of gabazine and bicuculline in rat hippocampal CA3 area

Field potentials were evoked in hippocampal area CA3 of anaesthetised rats by commissural stimulation, in order to study the effect of the prototypic gamma-aminobutyric acid (GABA)A antagonists gabazine (SR-95531; GBZ) and bicuculline methiodide (BMI) on paired-pulse interaction. Prominent paired-pulse inhibition of the orthodromic population spike (PS2) was observed when the interpulse interval (IPI) was < or = 40 ms, while facilitation occurred at IPIs >100 ms. Paired-pulse facilitation was lost at 500 ms. The antidromic population spike (PS1) presented paired-pulse facilitation at low-IPI, which decayed exponentially at increasing IPI. When the recording micropipettes contained millimolar concentrations of either GBZ, or BMI, single stimuli evoked repetitive (epileptiform) orthodromic PS2, of higher amplitude, while the antidromic PS1 was only weakly influenced. BMI reduced, but GBZ enhanced the low-IPI paired-pulse inhibition of the orthodromic PS2. Furthermore, BMI blunted paired-pulse facilitation of the antidromic PS1 at low-IPI, while GBZ caused strong paired-pulse inhibition of PS1 at IPI < or = 60 ms. The differential effects of GBZ and BMI on paired-pulse interaction might reflect different mechanisms of action of these compounds.