Katsura M, Ohkuma S, Tsujimura A, Kuriyama K
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
J Pharmacol Exp Ther. 1995 Jun;273(3):1529-33.
Although the molecular mechanisms underlying behavioral responses observed in ethanol (EtOH)-dependent and -withdrawn animals are poorly understood, several lines of evidence have suggested that some of the pharmacological actions of EtOH are mediated via the potentiation of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 The expression of cerebral DBI mRNA significantly increased in EtOH-treated (130% of control) and EtOH-withdrawn (220% of control) mice in comparison with untreated mice, whereas the DBI mRNA level was not altered after a single administration of EtOH (3 g/kg i.p.).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.
尽管目前对乙醇（EtOH）依赖和戒断动物行为反应的分子机制了解甚少，但有几条证据表明，EtOH的一些药理作用是通过增强γ-氨基丁酸（GABA）能传递介导的。在本研究中，检测了急性和慢性EtOH处理对小鼠脑中地西泮结合抑制剂（DBI）mRNA表达的影响，以及苯二氮䓬（BDZ）受体在EtOH诱导的DBI mRNA表达改变中的功能参与。与未处理的小鼠相比，EtOH处理组（对照组的130%）和EtOH戒断组（对照组的220%）小鼠脑内DBI mRNA的表达显著增加，而单次腹腔注射EtOH（3 g/kg）后DBI mRNA水平未发生改变。尽管在停止EtOH后2天内戒断症状消失，但在14天内，EtOH戒断后小鼠大脑皮质中DBI mRNA表达的增加逐渐减少。氟硝西泮（10 mg/kg腹腔注射）与EtOH同时给药完全消除了EtOH诱导的DBI mRNA表达增加。另一方面，β-肌动蛋白mRNA水平不受类似EtOH处理的影响。这些结果表明，长期EtOH处理诱导的脑内DBI mRNA表达变化可能参与了酒精依赖的形成，并且这种变化也可能受BDZ受体的调节。
