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The effect of diazepam on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to membrane preparations from rat cerebral cortex was examined in the presence or absence of GABA. The in vitro addition of diazepam to unwashed membranes preparations (rich in endogenous GABA) decreased [35S]TBPS binding by 41%. On the contrary, diazepam produced an opposite effect (+28%) when GABA had been removed by extensive washes of membranes. Moreover, diazepam increased by 26% [35S]TBPS binding also in unwashed membrane preparations previously incubated with bicuculline. These results suggest that, in absence of gamma-aminobutyric acid (GABA), diazepam may have a paradoxical negative modulatory action on the function of the GABAA receptor-coupled chloride channels.
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