Alterations in cerebral diazepam binding inhibitor expression in drug dependence - A possible biochemical alteration common to drug dependence

Mechanisms for formation of drug dependence and expression of withdrawal sy ndrome have not fully clarified despite of huge accumulation of experimenta l and clinical data at present. Several clinical features of withdrawal syn drome are considered to be common among patients with drug dependence induc ed by different drugs of abuse. One of them is anxiety. Recent investigatio ns have revealed that diazepam binding inhibitor (DBI), a peptide consistin g of 87 amino acids with molecular weight of about 10 kDa, serves as an inv erse agonist for benzodiazepine (BZD) receptors with endogenously anxiogeni c potential. These lines of data suggest that cerebral DBI expression in br ain may participates in formation of drug dependence and/or emergence of wi thdrawal syndrome. Based on this working hypothesis, we have examined DBT e xpression in the brain derived from mice depended on alcohol (ethanol), nic otine, and morphine to investigate functional relationship between cerebral DBI expression and drug dependence. Cerebral DBI expression significantly increases in animals with drug dependence induced by these drugs, and in th e cases of nicotine- and morphine-dependent mice concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectiv ely, abolished the increase. Abrupt cessation of administration of drugs fa cilitated further increase in DBP expression. Therefore, these alterations in DBI expression have close relationship with formation of drug dependence and/or emergence of withdrawal syndrome, and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse . Finding and elucidation of mechanisms :for common biochemical alterations among drug dependence may provide a clue to clarify mechanisms for formati on of drug dependence and/or emergence of withdrawal syndrome. (C) 2001 Els evier Science Inc. All rights reserved.