DECREASED EXPRESSION OF GAMMA-AMINOBUTYRIC-ACID TYPE-A BENZODIAZEPINERECEPTOR-BETA SUBUNIT MESSENGER-RNAS IN BRAIN OF FLURAZEPAM-TOLERANT RATS

The expression of GABA(A)/benzodiazepine beta subunit mRNAs was studie d in cerebral cortex, hippocampus, and cerebellum of flurazepam-treate d rats. Immediately following 4 wk of treatment, beta 2 and beta 3 sub unit mRNAs were significantly reduced in cerebellum and hippocampus, w hereas only beta 2 was decreased in cortex. These decreases had largel y reversed 48 h following flurazepam treatment. After 2 wk of treatmen t, 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. F our hours after an acute flurazepam treatment, the only change was a d ecrease in beta 3 mRNA in hippocampus. These results indicate that the expression of GABA(A) receptor beta subunit mRNAs in different brain regions is differentially regulated during chronic flurazepam treatmen t, and some changes occur within hours after a single large dose.