Benzodiazepine receptor binding by membranes from brain cell cultures following chronic treatment with diazepam.

Murine brain cells differentiated for 19 days in culture before treatment for 5 days with 10 microM diazepam. Radioligand binding to the benzodiazepine receptors on membranes obtained from these cultures was determined by the filtration assay method. Decreased binding was observed in the membranes from treated cultures relative to untreated cells. However, this decrease appears to be due, at least in part, to competition from residual drug in the assay system despite extensive cell and membrane rinses. These data emphasize the difficulty in ascribing the mechanism of benzodiazepine tolerance observed clinically with chronic treatment to receptor down-regulation as determined by binding assays.