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 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.