Decreased expression of gamma-aminobutyric acid type A/benzodiazepine receptor beta subunit mRNAs in brain of flurazepam-tolerant rats.
The expression of GABAA/benzodiazepine beta subunit mRNAs was studied in cerebral cortex, hippocampus, and cerebellum of flurazepam-treated rats. Immediately following 4 wk of treatment, beta 2 and beta 3 subunit mRNAs were significantly reduced in cerebellum and hippocampus, whereas only beta 2 was decreased in cortex. These decreases had largely reversed 48 h following flurazepam treatment. After 2 wk of treatment, both beta 2 and beta 3 mRNAs were reduced in cerebellum, and beta 3 mRNA was reduced in hippocampus, but neither was changed in cortex. Four hours after an acute flurazepam treatment, the only change was a decrease in beta 3 mRNA in hippocampus. These results indicate that the expression of GABAA receptor beta subunit mRNAs in different brain regions is differentially regulated during chronic flurazepam treatment, and some changes occur within hours after a single large dose.
Zhao
T J
TJ
Department of Pharmacology, Medical College of Ohio, Toledo 43699, USA.
Chiu
T H
TH
Rosenberg
H C
HC
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004361:Drug Tolerance / Q000235:genetics; D005479:Flurazepam / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005479:Flurazepam