Mechanisms for formation of
drug dependence and expression of withdrawal syndrome have not fully clarified despite of huge accumulation of experimental and clinical data at present. Several clinical features of withdrawal syndrome are considered to be common among patients with
drug dependence induced by different drugs of abuse. One of them is anxiety. Recent investigations have revealed that
diazepam binding inhibitor (
DBI), a
peptide consisting of 87
amino acids with molecular weight of about 10 kDa, serves as an inverse agonist for
benzodiazepine (BZD) receptors with endogenously anxiogenic potential. These lines of data suggest that cerebral
DBI expression in brain may participates in formation of
drug dependence and/or emergence of withdrawal syndrome. Based on this working hypothesis, we have examined
DBI expression in the brain derived from mice depended on alcohol (
ethanol),
nicotine, 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 the cases of
nicotine- and
morphine-dependent mice concomitant administration of antagonists for nicotinic
acetylcholine and
opioid receptors, respectively, abolished the increase. Abrupt cessation of administration of drugs facilitated further increase in
DBI 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 formation of
drug dependence and/or emergence of withdrawal syndrome.