Increase of diazepam binding inhibitor mRNA levels in the brains of chronically ethanol-treated and -withdrawn mice.
Although the molecular mechanisms underlying behavioral responses observed in ethanol (EtOH)-dependent and -withdrawn animals are poorly understood, several lines of evidence have suggested that some of the pharmacological actions of EtOH are mediated via the potentiation of gamma-aminobutyric acid (GABA)ergic transmission. In the present study, the effects of acute and chronic EtOH treatment on the expression of diazepam binding inhibitor (DBI) mRNA in the mouse brain and the functional involvement of the benzodiazepine (BDZ) receptor in EtOH-induced alteration of the DBI mRNA expression were examined. The expression of cerebral DBI mRNA significantly increased in EtOH-treated (130% of control) and EtOH-withdrawn (220% of control) mice in comparison with untreated mice, whereas the DBI mRNA level was not altered after a single administration of EtOH (3 g/kg i.p.). The increase in the DBI mRNA expression in the mouse cerebral cortex after EtOH withdrawal diminished over 14 days despite the disappearance of withdrawal signs within 2 days after the withdrawal of EtOH. Simultaneous administration of flunitrazepam (10 mg/kg i.p.) with EtOH completely abolished the EtOH-induced increase in DBI mRNA expression. On the other hand, the level of beta-actin mRNA was not affected by similar EtOH treatment. These results indicate that changes in the expression of cerebral DBI mRNA induced by long-term EtOH treatment may be involved in the establishment of alcohol dependence, and such changes may be also regulated by BDZ receptors.
Katsura
M
M
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Ohkuma
S
S
Tsujimura
A
A
Kuriyama
K
K
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D026261:Diazepam Binding Inhibitor; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D002352:Carrier Proteins; D017931:DNA Primers; D026261:Diazepam Binding Inhibitor; D058787:GABA-A Receptor Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D000431:Ethanol