Nabeshima A, Toki S, Saito T, Takahata N
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1995 Aug;15(4):345-53.
We studied the differences in alterations of GABAAergic receptor function between pentobarbital (PB)-dependent female Lewis (LEW) and Wistar-Kyoto (WKY) rats. The 36Cl- influx induced by 10 microM GABA in the PB-dependent WKY was significantly lower than that in the control, while there was no significant 36Cl- influx change in both PB-dependent and control LEW. The additions of PB, flunitrazepam (FZ) and ethanol (EtOH) enhanced the GABA-dependent 36Cl- influx in control rats of both strains. However, the enhancements of 36Cl- influx by PB, FZ, EtOH were not recognized in PB-dependent WKY. On the other hand, the enhancement of GABA-dependent 36Cl- influx was observed only with the addition of PB in PB-dependent LEW. The additions of bicuculline (BIC) and picrotoxin (PIC) inhibited GABA-dependent 36Cl- influx in control rats of both strains. However, inhibition of 36Cl- influx by BIC and PIC was not recognized in the PB-dependent WKY. These results suggest that physical dependence on PB in WKY may cause greater functional alterations of the GABA/benzodiazepine receptor complex than those in LEW, and that these changes in this receptor complex may relate to the difference in the development of physical dependence on PB between the two strains.
我们研究了戊巴比妥(PB)依赖的雌性刘易斯(LEW)大鼠和Wistar-Kyoto(WKY)大鼠之间GABAA能受体功能改变的差异。在PB依赖的WKY大鼠中,10微摩尔GABA诱导的36Cl-内流显著低于对照组,而在PB依赖的和对照的LEW大鼠中,36Cl-内流均无显著变化。添加PB、氟硝西泮(FZ)和乙醇(EtOH)可增强两种品系对照大鼠中GABA依赖的36Cl-内流。然而,在PB依赖的WKY大鼠中未观察到PB、FZ、EtOH对36Cl-内流的增强作用。另一方面,在PB依赖的LEW大鼠中,仅添加PB时观察到GABA依赖的36Cl-内流增强。添加荷包牡丹碱(BIC)和印防己毒素(PIC)可抑制两种品系对照大鼠中GABA依赖的36Cl-内流。然而,在PB依赖的WKY大鼠中未观察到BIC和PIC对36Cl-内流的抑制作用。这些结果表明,WKY大鼠对PB的身体依赖可能比LEW大鼠导致GABA/苯二氮䓬受体复合物更大的功能改变,并且该受体复合物的这些变化可能与两种品系对PB身体依赖发展的差异有关。