Decreased GABA enhancement of benzodiazepine binding after a single dose of diazepam

The GABA and benzodiazepine binding sites on GABA(A) receptors are alloster ically coupled. The in vitro binding of 2 nM [H-3]flunitrazepam to cortical and cerebellar membranes prepared from drug-naive rats was potentiated sim ilar to 1.6-fold by 100 mu M GABA. Potentiation in both regions was signifi cantly reduced 4 or 12 but not 24 h after a single dose of 15 mg/kg diazepa m. 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) recept or gamma 2-subunit gene transcription and alpha 1-, beta 2-, and gamma 2-su bunit steady-state mRNA levels did not appear to be temporally related to a llosteric uncoupling.