FUNCTIONAL INVOLVEMENT OF BENZODIAZEPINE RECEPTORS IN ETHANOL-INDUCEDINCREASES OF DIAZEPAM-BINDING INHIBITOR (DBI) AND ITS MESSENGER-RNA IN THE MOUSE-BRAIN

We have attempted to clarify the mechanisms for alcohol (EtOH)-induced elevation of diazepam binding inhibitor (DBI) mRNA and to investigate whether the increase in DBI mRNA is paralleled with that in DBI using EtOH-treated mice and primary cultured neurons. Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice. Simultaneous administration of flun itrazepam (FLN) and Ro15-1788 with EtOH vapor completely abolished the EtOH-induced elevation of DBI mRNA. In addition, the exposure of the neurons for 3 days significantly elevated the expression of DBI mRNA, which was completely inhibited by concomitant exposure of FLN, Ro15-45 13 and Ro15-1788 with EtOH, while muscimol and bicuculline showed no e ffects on the EtOH-induced increase of DBI mRNA expression. These resu lts indicate that functional interaction between EtOH and benzodiazepi ne (BDZ) receptors is a critical role in the increased expression of D BI mRNA. (C) 1998 Elsevier Science B.V.