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GABA A receptor gene expression in rat cortex: Differential effects of two chronic diazepam treatment regimes
Author(s) -
Arnot Michelle I.,
Davies Martin,
Martin Ian L.,
Bateson Alan N.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1115
Subject(s) - diazepam , gabaa receptor , flunitrazepam , benzodiazepine , pharmacology , receptor , anxiolytic , endocrinology , dosing , medicine , chemistry , in vivo , biology , microbiology and biotechnology
Diazepam is widely prescribed as an anxiolytic but its therapeutic application is limited because with daily use tolerance develops to certain aspects of its pharmacological profile. We compared the effects of two dosing paradigms on GABA A receptor gene expression and benzodiazepine binding characteristics. Equivalent daily doses of 15 mg/kg/day diazepam were delivered either via constant infusion or daily subcutaneous injection for 14 days. The two distinct treatment regimes produced significantly different changes in GABA A receptor α4‐, β2‐, β3‐ and γ1‐subunit mRNA steady‐state levels. Similar changes in the GABA enhancement of flunitrazepam binding and the BZ3/BZ2 subtype ratio determined ex vivo were produced, however, significant differences were found in [ 3 H]‐Ro 15‐4513 binding between cortical tissue from diazepam injected animals compared with diazepam infused animals. Our data suggest that it is the diurnal fluctuations in receptor occupancy that are responsible for the different effects produced by these two dosing regimes. J. Neurosci. Res. 64:617–625, 2001. © 2001 Wiley‐Liss, Inc.