HIGH-DOSES OF PENICILLIN DECREASES [H-3] FLUNITRAZEPAM BINDING-SITES IN RAT NEURON PRIMARY CULTURE

Penicillin (PC) neurotoxicity (convulsions and encephalopathy) is cons idered to be due to GABAergic inhibition. The effects of penicillin G( PCG) on [H-3]flunitrazepam (FNZ) binding in rat neuron-enriched primar y cultures was examined to assess the role of the benzodiazepine (BDZ) receptor in the neurotoxicity. PCG application for 24 h induced a sig nificant decrease in [H-3]FNZ binding activity at 10(-3) M, and a decr ease in available receptor number (B(max)) at 10(-2) M, without obviou s cell damage. Pre-application of the BDZ receptor antagonist, Ro-15-1 788, prevented the PC-induced decrease in [H-3]FNZ binding activity. T herefore, PC seems to reduce the number of BDZ receptors through a dir ect effect on this receptor, which is a part of the major inhibitory s ystem in mammalian brain; the GABAergic macromolecular receptor comple x. This decrease in BDZ receptors may play a role in PC-induced neurot oxicity, especially encephalopathy.