EPILEPTOGENIC DOSES OF PENICILLIN DO NOT REDUCE A MONO-SYNAPTIC GABA-MEDIATED POSTSYNAPTIC INHIBITION IN THE INTACT ANESTHETIZED CAT

The hypothesis that penicillin (PCN) causes seizures by interfering with γ-aminobutyric acid (GABA)-mediated inhibition was investigated by observing the effect of epileptogenic doses of systemic PCN on the monosynaptic inhibition of Deiters neurons by cerebellar stimuli. After intravenous PCN, typical epileptic spikes in cerebral cortical surface recordings occurred and were correlated with various degrees of hyperactivity and Deiters nucleus. Intracellular recordings in five Deiters neurons with stable penetrations before and after PCN-induced cortical spikes showed no reduction of the evoked monosynaptic inhibitory postsynaptic potential (IPSP). These few long-duration recordings were supported by statistical analysis of IPSP amplitude in small populations of neurons recorded either before or after PCN in 11 cats; no significant trend was seen after PCN. Extracellular unit and antidromic field potential recordings in Deiters nucleus did show alterations of net inhibition after PCN but do not refute the intracellular data. The epileptic effects of PCN on the intact mammalian nervous system may involve mechanisms other than antagonism of GABA-mediated inhibition. © 1979.