Functional involvement of benzodiazepine receptors in ethanol-induced increases of diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.
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 Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice.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 Ro-15-1788 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.
Katsura
M
M
Department of Pharmacology, Kawasaki Medical School, Okayama, Japan.
Ohkuma
S
S
Tsujimura
A
A
Xu
J
J
Hibino
Y
Y
Ishikawa
E
E
Kuriyama
K
K
D000280:Administration, Inhalation; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D026261:Diazepam Binding Inhibitor; D000431:Ethanol / Q000633:toxicity*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D011963:Receptors, GABA-A / Q000502:physiology*
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D000431:Ethanol