Decreased GABA_Areceptor subunit mRNA concentrations following chronic lorazepam administration

Abstract

Chronic benzodiazepine administration has been associated with alterations in binding and function at the GABAA receptor. To evaluate effects of chronic benzodiazepine exposure on messenger RNA (mRNA) concentrations for several GABAA receptor subunits, we treated mice with lorazepam, 2 mg kg-1 daily for 1-28 days and evaluated mRNAs for the alpha 1 and gamma 2 subunits by Northern hybridization. In cerebral cortex, concentrations of mRNA for the alpha 1 and gamma 2 subunits were unchanged from vehicle or control after 1-10 days of lorazepam. However, after 14 days of treatment mRNA concentrations for both subunits decreased to approximately 50% of control values and remained decreased at 28 days. In contrast, no significant alterations were observed for either subunit mRNA in hippocampus or cerebellum over the same time course. Alterations in mRNAs in cortex occur after the development of tolerance and receptor downregulation in this model.