In the present study, we explored the effects of two-day zolpidem (10 渭M) treatment on GABAA receptors on the membranes of rat cerebellar granule cells (CGCs) using [3H]flunitrazepam binding and semi-quantitative PCR analysis.
Two-day zolpidem treatment of CGCs did not significantly affect the maximum number (Bmax) of [3H]flunitrazepam binding sites or the expression of 伪1 subunit mRNA. However, as shown by decreased GABA [3H]flunitrazepam binding, two-day exposure of CGCs to zolpidem caused functional uncoupling of GABA and benzodiazepine binding sites at GABAA receptor complexes.
If functional uncoupling of GABA and benzodiazepine binding sites at GABAA receptors is the mechanism responsible for the development of tolerance following long-term administration of classical benzodiazepines, chronic zolpidem treatment may induce tolerance.