氟西泮耐受听源性惊厥大鼠脑皮质运动区和海马区GABA_A受体亚单位mRNA含量的变化

Modification of GABA _A receptor subunit mRNA content in audiogenic seizure rat cortex and hippocampus following tolerance to flurazepam

目的 :探讨氟西泮耐受的听源性惊厥大鼠中枢GABAA 受体亚单位mRNA含量的改变及意义。方法 :使用腹腔注射氟西泮 2周 ,产生氟西泮耐受性而无依赖性的听源性惊厥大鼠模型。用竞争性定量RT PCR测定大鼠脑皮质运动区和海马区GABAA 受体α1、α3、α5、γ2L和γ2S亚单位mRNA的含量。结果 :氟西泮耐受组大鼠皮质运动区的α1亚单位下降 2 4% ,α3下降 17% ,α5上升 33% ,γ2L下降 35 % ,γ2S下降 45 % ;海马区的α1下降 33% ,γ2L下降 35 % ,γ2S下降 2 7% ,与对照组比较差异均有显著性。结论 :听源性惊厥大鼠的氟西泮耐受机制与中枢GABAA 受体α1、α3、α5。

SUMMARY Objective: To investigate the modification of GABA A receptor subunits in audiogenic seizure rat cortex and hippocampus when rendered tolerant to flurazepam. Methods: Rats were administrated with flurazepam for two weeks, which resulted in tolerance to flurazepam, in the absence of behavioral signs of withdrawal. GABA A receptor subunits α1, α3, α5, γ2L and γ2S were assayed using quantitative competitive RT PCR in rat frontparietal motor(FrPaM) and hippocampus. Results: In FrPaM, the contents of mRNA encoding for α1, α3, γ2L and γ2S were all significantly decreased (24%,17%,35% and 45% respectively),whereas that of α5 was significantly increased (33%) compared with the control. In hippocampus, α1, γ2L, and γ2S mRNA contents were significantly decreased (33%, 35%and 27% respectively). Conclusion: The accomodated change in GABA A receptor subunits α1, α3, α5,γ2L and γ2S in FrPaM and hippocampus may be associated with the mechanism of flurazepam tolerance in audiogenic seizure rats.