Brain Research, 53 (1973) 477-482 477 © Elsevier ScientificPublishing Company, Amsterdam - Printed in The Netherlands Convulsant actions of penicillin: effects on inhibitory mechanisms HARTMUT MEYER AND DAVID PRINCE Max-Planck-Institut fiir Psychiatric, 8000 Munich 40 (G.F.R.) and Department of Neurology, Stanford University School of Medicine, Stanford, Calif. 94305 (U.S.A.) (Accepted January 31st, 1973) Topical application of penicillin to the mammalian cortex produces regularly recurring focal epileptiform discharges (EEG 'spikes' of the electroencephalographer) which have been extensively investigated using intracellular recording techniquesS, 6, 18-20,z3,z4. In spite of these studies, the mode of action of the drug on single cortical neurons is not well understood. In order to avoid problems introduced by anatomical complexities of the mammalian brain, the effects of penicillin upon 'simple' prepara- tions have been examined. Previous reports have described the action of penicillin on isolated neurons of crayfish stretch receptor 2, on excitatory neuromuscular trans- mission in the crayfish tonic abdominal flexor system 7,8, on giant synapses of the squid stellate ganglion 1 and on Mauthner fiber-giant fiber synapse of the hatchet fish 25. To date there is little information available bearing on possible penicillin action on postsynaptic inhibition. The persistence of IPSPs in neurons of neocortex23,24 and archicortexS, 6 after penicillin application does not rule out an effect of the drug on inhibitory potentials (see for example refs. 21 and 22). In order to study further the convulsant action of penicillin, we examined its effect on inhibitory synaptic potentials in the isolated crayfish stretch receptor. Complete abdominal stretch receptors were dissected from large specimens of Astaeusfluviatilis L. and mounted unstretched in a plexiglass chamber which allowed controlled exchange of solutions. The nerve leading to the fast adapting cell, which contains a branch of the inhibitory axon supplying both the fast and the slow adapting cell, was stimulated with suprathreshold pulses using a suction electrode in order to generate isolated inhibitory synaptic potentials in the slow adapting cell by axon reflexlL Another suction electrode was used to stimulate the 'slow' cell antidromically. Glass microelectrodes filled with a mixture of 85 ~ 0.6 M potassium sulfate and 15 1.5 M potassium chloride or with 1.5 M potassium citrate were used to obtain intra- cellular recordings from the soma of the 'slow' cell. The reference electrode was a sintered Ag-AgC1 pellet connected to the bath by means of a Ringer-saturated agar bridge. A bridge circuit permitted simultaneous recording and current pulse injection so that the effects of changes in membrane potential on the IPSP and the reversal potential of IPSP (Eipsp) could be determined. If necessary, the Wheatstone bridge could easily be equilibrated by means of the spike height method 9. Both intracellular