BICUCULLINE ENHANCES THE LATE GABA(B) 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 interpul se interval allowed the separation of an early phase of inhibition (in terpulse interval 5-20 ms), blocked by the GABA(A) receptor antagonist bicuculline (1 mu M; n = 11), and a late phase (interpulse interval 2 00-400 ms) blocked by the GABA(B) 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 i ncreasing the stimulus strength, rather than bicuculline. Orthodromic stimulation leads to synaptic excitation of both pyramidal neurones an d inhibitory interneurones, and may also lead to activation of inhibit ory inputs onto interneurones. Bicuculline could prevent inhibition of the interneurones, and hence enhance the late, GABA(B) receptor-media ted inhibition. Conversely, the therapeutic administration of benzodia zepines would be postulated to enhance the inhibition of inhibitory in terneurones, leading to an iatrogenic decrease in GABA(B) receptor-med iated inhibition.