BICUCULLINE-RESISTANT PAIRED-PULSE INHIBITION IN THE RAT HIPPOCAMPAL SLICE

1 An initial observation that paired-pulse inhibition in hippocampal s lices was increased rather than decreased by bicuculline prompted the present study to explore the mechanism underlying bicuculline-resistan t inhibition. 2 In the presence of bicuculline, paired-pulse interacti ons were dependent on the interpulse interval (i.p.i.) but a medium-la tency inhibition was consistently observed at an i.p.i. of 300 to 500 ms. 3 The medium-latency (300 ms) bicuculline-resistant inhibition pro duced by paired orthodromic stimuli was substantially reduced by 2-hyd roxysaclofen and was probably largely mediated by GABA(B)-receptor act ivation. Paired-pulse inhibition produced by an orthodromic/antidromic stimulation sequence was not affected by 2-hydroxysaclofen suggesting the possibility that the GABA(B)-receptors involved in orthodromic in hibition may be located presynaptically on the Schaffer collateral ter minals rather than on the postsynaptic surface. The medium latency inh ibition was also reduced by baclofen and under some conditions, by ade nosine. 4 In addition to the GABA(B)-component, a hydroxysaclofen-resi stant depression of postsynaptic excitability contributed to bicuculli ne-resistant paired-pulse inhibition at the 300 ms latency.