Decreased GABA enhancement of benzodiazepine binding after a single dose of diazepam.
The GABA and benzodiazepine binding sites on GABA(A) receptors are allosterically coupled. The in vitro binding of 2 nM [3H]flunitrazepam to cortical and cerebellar membranes prepared from drug-naive rats was potentiated approximately 1.6-fold by 100 microM GABA. Potentiation in both regions was significantly reduced 4 or 12 but not 24 h after a single dose of 15 mg/kg diazepam. At 24 h after the last of 14 daily doses of diazepam, no differences in GABA potentiation were observed. Diazepam-induced changes in GABA(A) receptor gamma2-subunit gene transcription and alpha1-, beta2-, and gamma2-subunit steady-state mRNA levels did not appear to be temporally related to allosteric uncoupling.
Holt
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Department of Biological Sciences, University of Albany, State University of New York, USA.
Bateson
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Martin
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D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism / Q000494:pharmacology*; D006706:Homeostasis / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018757:GABA Modulators; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D003975:Diazepam