Functional involvement of benzodiazepine receptors in ethanol-induced increases of diazepam binding inhibitor (DBI) and its mRNA in the mouse brain

• Published in: Brain research. Molecular brain research. 1998-02, Vol.54 (1), p.124-132
• Main Authors: Katsura, Masashi, Ohkuma, Seitaro, Tsujimura, Atsushi, Xu, Jun, Hibino, Yasushi, Ishikawa, Emiko, Kuriyama, Kinya
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; Benzodiazepine (BDZ) receptor; Biological and medical sciences; Brain Chemistry - drug effects; Brain Chemistry - genetics; Carrier Proteins - drug effects; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; DBI mRNA; Diazepam Binding Inhibitor; Diazepam binding inhibitor (DBI); Ethanol - toxicity; Ethanol inhalation; Ethanol withdrawal; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Male; Medical sciences; Mice; Rabbits; Receptors, GABA-A - physiology; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism; Toxicology
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(97)00330-6

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 Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice.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 Ro15-1788 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.