Im. Stanford et al., BICUCULLINE ENHANCES THE LATE GABA(B) RECEPTOR-MEDIATED PAIRED-PULSE INHIBITION OBSERVED IN RAT HIPPOCAMPAL SLICES, European journal of pharmacology, 277(2-3), 1995, pp. 229-234
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.