Bicuculline enhances the late GABAB receptor-mediated paired-pulse inhibition observed in rat hippocampal slices

The inhibition of CA1 pyramidal neurones in rat hippocampal slices was studied using extracellular recordings of population spike potential responses to paired orthodromic stimulation. Variation of the interpulse interval allowed the separation of an early phase of inhibition (interpulse interval 5–20 ms), blocked by the GABAA receptor antagonist bicuculline (1 ?M; n = 11), and a late phase (interpulse interval 200–400 ms) blocked by the GABAB receptor antagonist phaclofen (1 mM; n = 5) but enhanced by bicuculline (n = 11). Similar enhancement was not observed when conditioning response amplitudes were increased by increasing the stimulus strength, rather than bicuculline. Orthodromic stimulation leads to synaptic excitation of both pyramidal neurones and inhibitory interneurones, and may also lead to activation of inhibitory inputs onto interneurones. Bicuculline could prevent inhibition of the interneurones, and hence enhance the late, GABAB receptor-mediated inhibition. Conversely, the therapeutic administration of benzodiazepines would be postulated to enhance the inhibition of inhibitory interneurones, leading to an iatrogenic decrease in GABAB receptor-mediated inhibition