Repeated administration of diazepam reduces [3H]Ro 5-4864 binding in cerebral cortex of rats
1992
Binding of [3H]Ro 5-4864 to mitochondrial membrane preparations of rat cerebral cortex was measured after repeated (5 days) IV administration of diazepam (10 mg/kg daily) and clonazepam (2.5 mg/kg daily). The Bmax value for [3H]Ro 5-4864 was significantly reduced in rats treated with diazepam (−49%) but not in those treated with clonazepam. These findings suggest the involvement of peripheral-type binding sites in the development of rapid tolerance to the sedative effects of benzodiazepines. A downregulation of [3H]Ro 5-4864 (−65%) was also observed after repeated administration of Ro 5-4864 (4 mg/kg daily), thus confirming that this compound behaves as an agonist at its own recognition sites.
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