The effects of GABA uptake inhibitors, SKF 89976A and SKF 100330A, on
recurrent inhibition were studied in the rat hippocampal slice prepara
tion by the antidromic-orthodromic stimulation test. Population spikes
evoked orthodromically by stimulation of the stratum radiatum and rec
orded in the CA1 pyramidal cell body layer were inhibited antidromical
ly by stimulation of the alveus by a single pulse or by a train of pul
ses, either at low or at high frequency. Low frequency train condition
ing produced less inhibition than a single pulse. The uptake blockers
had no effect or slightly enhanced the inhibition produced by single s
timuli or low frequency trains. High frequency train conditioning prod
uced more and much longer inhibition than a single pulse. This inhibit
ion was further substantially enhanced and prolonged by the drugs. Fre
quency-dependent enhancement of inhibition may be responsible for supp
ression of epileptiform discharges by GABA uptake blockers.