Nabeshima A, Saito T, Takahata N
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1995 Jun;15(3):265-74.
Changes in GABAA receptor function were studied in pentobarbital (PB)-dependent rats. Physical dependence on PB in male Lewis rats was induced by the drug-admixed food method. The 36Cl- influx into cerebral cortical synaptoneurosomes induced by 10 microM GABA in the PB-dependent rat was significantly decreased compared with the control. The enhancement of GABA-dependent 36Cl- influx by the addition of PB, ethanol (EtOH) and flunitrazepam (FZ) was not recognized in the PB-dependent group. The addition of picrotoxin and bicuculline had no effect on GABA-dependent 36Cl- influx in PB-dependent rats. In the [3H]muscimol binding assay of low affinity sites of the GABAA receptor, Kd was significantly increased and Bmax was significantly decreased in PB-dependent rats compared with the control. However, these values were similar between PB-dependent and control rats in the study of [3H]FZ binding to benzodiazepine (BZ) receptors. The present study indicates that GABAergic transmission involving GABA-dependent chloride channels was altered in PB dependent rats. This alteration of the GABAA/BZ/chloride channel complex function may be related to the cross-tolerance among barbiturates, BZ and EtOH.
在戊巴比妥（PB）依赖的大鼠中研究了GABAA受体功能的变化。采用药物混合食物法诱导雄性Lewis大鼠对PB产生身体依赖性。与对照组相比，PB依赖大鼠中由10微摩尔GABA诱导的36Cl-流入大脑皮质突触神经小体的量显著减少。在PB依赖组中未观察到添加PB、乙醇（EtOH）和氟硝西泮（FZ）对GABA依赖性36Cl-流入的增强作用。添加印防己毒素和荷包牡丹碱对PB依赖大鼠中GABA依赖性36Cl-流入没有影响。在GABAA受体低亲和力位点的[3H]蝇蕈醇结合试验中，与对照组相比，PB依赖大鼠的解离常数（Kd）显著增加，最大结合量（Bmax）显著降低。然而，在[3H]FZ与苯二氮䓬（BZ）受体结合的研究中，PB依赖大鼠和对照大鼠的这些值相似。本研究表明，在PB依赖大鼠中，涉及GABA依赖性氯通道的GABA能传递发生了改变。GABAA/BZ/氯通道复合体功能的这种改变可能与巴比妥类药物、BZ和EtOH之间的交叉耐受性有关。
