Frequency-dependent enhancement of hippocampal inhibition by GABA uptake blockers

The effects of GABA uptake inhibitors, SKF 89976A and SKF 100330A, on recurrent inhibition were studied in the rat hippocampal slice preparation by the antidromic-orthodromic stimulation test. Population spikes evoked orthodromically by stimulation of the stratum radiatum and recorded in the CA1 pyramidal cell body layer were inhibited antidromically by stimulation of the alveus by a single pulse or by a train of pulses, either at low or at high frequency. Low frequency train conditioning produced less inhibition than a single pulse. The uptake blockers had no effect or slightly enhanced the inhibition produced by single stimuli or low frequency trains. High frequency train conditioning produced more and much longer inhibition than a single pulse. This inhibition was further substantially enhanced and prolonged by the drugs. Frequency-dependent enhancement of inhibition may be responsible for suppression of epileptiform discharges by GABA uptake blockers.