Abstract
Fetal mouse cerebral cortex in culture was exposed chronically to diazepam, and benzodiazepine (BDZ) receptor activity was assayed on the intact cell. Results have indicated: (1) minimal evidence of generalized drug toxicity, determined by choline acetyltransferase activity, tetanus labeling, high-affinity uptakes of gamma-aminobutyric acid and beta-alanine, protein, and light microscopy; (2) a significant dose-dependent reduction (down-regulation) of BDZ receptor activity that occurs after chronic exposure to clinically relevant concentrations of the drug; (3) a disproportionate suppression of the neuronal portion of the receptor after both acute and chronic exposure; and (4) recovery patterns of the BDZ receptor that differ substantially after acute versus chronic treatment. The latter finding may partially explain the observed clinical manifestations of drug tolerance and reduced anticonvulsant efficacy after prolonged use of this class of drugs.
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