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Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABA A ‐receptor function
Author(s) -
Galpern Wendy R.,
Miller Lawrence G.,
Greenblatt David J.,
Shader Richard I.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14167.x
Subject(s) - lorazepam , benzodiazepine , gabaa receptor , alprazolam , diazepam , chemistry , pharmacology , endocrinology , hippocampus , receptor , cortex (anatomy) , medicine , anesthesia , biology , biochemistry , neuroscience , psychiatry , anxiety
1 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. 2 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. 3 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. 4 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. 5 These data suggest that the effects of chronic benzodiazepine administration on the GABA A ‐receptor may be both region‐specific and receptor subtype‐specific.