DECREASED DIAZEPAM-H-3 BINDING IS A SPECIFIC RESPONSE TO CHRONIC BENZODIAZEPINE TREATMENT

Specific 3H-diazepam binding was measured in rat cortex after 7-10 days of twice daily treatment with large doses of either flurazepam or barbital. Subjective ratings of drug response each day showed that barbital treated rats experienced a degree of ataxia equal to, or greater than, that experienced by the benzodiazepine treated animals. Before performing the binding assay, the membrane preparation was washed 3 times in hypotonic buffer to remove aby residual drug. Flurazepam treatment caused a 16% decrease in maximal 3H-diazepam binding, but no change in binding affinity, confirming previous results. In contrast, barbital treatment caused no change in either binding affinity or in maximal binding. Thus, decreased diazepam binding appears to be a specific response to prolonged receptor occupation, and not part of a more generalized adaptation to chronic CNS depression. © 1979.