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Altered gamma-aminobutyric acid/benzodiazepine interaction after chronic diazepam exposure
1Yale University School of Medicine, Department of Psychiatry, Abraham Ribicoff Research Facilities, New Haven, CT.
Abstract:
Binding to components of the GABA/benzodiazepine receptor complex was examined in cortical membranes from rats treated for 3 weeks with continuously releasing diazepam pellet implants. Chronic diazepam treatment resulted in a decrease in the ability of GABA to inhibit benzodiazepine inverse agonist binding. The amount of binding of benzodiazepine agonist, antagonist, and inverse agonist to benzodiazepine recognition sites was unaltered by the chronic treatment, as were the potencies of these benzodiazepine ligands in inhibiting agonist (3H-flunitrazepam) binding. Chloride channel binding (35S-TBPS) was also unchanged by chronic diazepam treatment. A change in GABA/benzodiazepine coupling and/or a decreased effectiveness of GABA may be responsible for the desensitization of GABA/benzodiazepine interaction.