Allan A M, Harris R A
Research Service, VA Medical Center, Denver, CO 80262.
Pharmacol Biochem Behav. 1987 Aug;27(4):665-70. doi: 10.1016/0091-3057(87)90192-4.
The effect of ethanol exposure in vitro on the GABA receptor-operated chloride channel was evaluated by monitoring 36Cl- influx in a membrane vesicle suspension (microsacs) prepared from mouse cerebellum. These experiments directly demonstrate ethanol augmentation of muscimol-stimulated chloride flux. DBA/2J mice were made tolerant to and dependent on ethanol by administration of an ethanol containing liquid diet for 7 days. Exposure to physiologically relevant concentrations of ethanol (10-45 mM) in vitro potentiated muscimol stimulation of 36Cl- uptake in control (pair-fed) membranes, but had no effect on cerebellar microsacs from tolerant/dependent mice. Muscimol stimulation of 36Cl- uptake was not different for pair-fed and ethanol-treated mice. Augmentation of muscimol-induced 36Cl- flux by in vitro ethanol was abolished by a single 4 g/kg injection of ethanol. This "acute tolerance" occurred within 5 min and disappeared within 24 hr after ethanol treatment. The reduced sensitivity of ethanol treated (chronic and acute) mice to ethanol potentiation of muscimol stimulated 36Cl- uptake offers a biochemical correlate to the phenomenon of ethanol tolerance. Moreover, the findings suggest that this biochemical tolerance develops rapidly following a single hypnotic dose of ethanol.
通过监测从小鼠小脑制备的膜囊泡悬浮液（微囊）中的³⁶Cl⁻流入，评估了体外乙醇暴露对γ-氨基丁酸（GABA）受体介导的氯离子通道的影响。这些实验直接证明了乙醇增强了蝇蕈醇刺激的氯离子通量。通过给予含乙醇的液体饲料7天，使DBA/2J小鼠对乙醇产生耐受性并产生依赖性。体外暴露于生理相关浓度的乙醇（10 - 45 mM）可增强对照（配对喂养）膜中蝇蕈醇对³⁶Cl⁻摄取的刺激，但对耐受/依赖小鼠的小脑微囊没有影响。配对喂养和乙醇处理的小鼠中，蝇蕈醇对³⁶Cl⁻摄取的刺激没有差异。单次注射4 g/kg乙醇可消除体外乙醇对蝇蕈醇诱导的³⁶Cl⁻通量的增强作用。这种“急性耐受性”在乙醇处理后5分钟内出现，并在24小时内消失。乙醇处理（慢性和急性）的小鼠对乙醇增强蝇蕈醇刺激的³⁶Cl⁻摄取的敏感性降低，为乙醇耐受性现象提供了生化相关性。此外，研究结果表明，这种生化耐受性在单次催眠剂量的乙醇后迅速发展。
