Functional involvement of benzodiazepine receptors in ethanol-induced increases of diazepam binding inhibitor (DBI) and its mRNA 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 Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice.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 flunitrazepam (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, Ro15-4513 and Ro-15-1788 with EtOH, while muscimol and bicuculline showed no effects on the EtOH-induced increase of DBI mRNA expression. These results indicate that functional interaction between EtOH and benzodiazepine (BDZ) receptors is a critical role in the increased expression of DBI mRNA.