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Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABA A ‐receptor function

1990; Wiley; Volume: 101; Issue: 4 Linguagem: Inglês

10.1111/j.1476-5381.1990.tb14167.x

1476-5381

Wendy R. Galpern, Lawrence G. Miller, David J. Greenblatt, Richard I. Shader,

Receptor Mechanisms and Signaling

Chronic benzodiazepine administration has been associated with tolerance and with downregulation of γ‐aminobutyric acid A (GABA A )‐receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. To compare the effects of chronic lorazepam and alprazolam, we have administered these drugs to mice for 1 and 7 days (2 mg kg −1 day −1 ) and determined benzodiazepine receptor binding in vivo with and without administration of CL 218,872, 25 mg kg −1 i.p., and GABA‐dependent chloride uptake in 3 brain regions at these time points. Benzodiazepine binding was decreased in the cortex and hippocampus at day 7 compared to day 1 of lorazepam, with an increase in CL 218,872‐resistant (Type 2) sites in both regions. Maximal GABA‐dependent chloride uptake was also decreased in the cortex and hippocampus at day 7. Binding was decreased only in the cortex after 7 days of alprazolam, with no significant change in Type 2 binding. Maximal GABA‐dependent chloride uptake was also decreased only in the cortex. These data suggest that the effects of chronic benzodiazepine administration on the GABA A ‐receptor may be both region‐specific and receptor subtype‐specific.