[Functional involvement of diazepam binding inhibitor (DBI) in the establishment of drug dependence]

In this paper, we have reviewed the possibility of the functional involvement of an endogeneous neuropeptide for benzodiazepine receptors, diazepam binding inhibitor (DBI), in the development of drug dependence and the establishment of its withdrawal symptoms. The cerebral levels of DBI protein and its mRNA significantly increased in alcohol-dependent mice, and alcohol-withdrawal caused further increases of both DBI protein and its mRNA. These increases in the mouse cerebral cortex diminished over 14 days after alcohol-withdrawal. In the cerebrocortical neurons, similar patterns of DBI protein and its mRNA were observed during long-term exposure to alcohol and after its withdrawal. Simultaneous exposures of benzodiazepine receptor agonist, antagonist and inverse agonist with alcohol abolished the alcohol-induced increase in DBI mRNA expression in the neurons. Furthermore, the DBI contents and its mRNA expressions were also increased in the cerebral cortex obtained from nicotine-dependent mice and the neurons after long-term treatment with nicotine. The nicotine-induced increases in DBI content and its mRNA expression in the mouse cerebral cortex and the neurons were completely abolished in the presence of an antagonist for nicotinic acetylcholine receptor. These results suggest that the changes in the levels of cerebral DBI induced by continuous treatments with alcohol and nicotine may be involved in the establishment of dependence by alcohol and nicotine, and such changes may be regulated by the benzodiazepine and nicotinic acetylcholine receptors, respectively.