Szmigielski A, Szmigielska H, Wejman I
Department of Pharmacodynamics, Medical University of Lódź, Poland.
Pol J Pharmacol Pharm. 1992 May-Jun;44(3):271-80.
The response of GABA-modulin to various doses of diazepam and muscimol was used as an index of the sensitivity of central benzodiazepine and GABA-A receptors, respectively. Diazepam and muscimol induced a dose-dependent increase in cytosol GABA-modulin activity in rat nucleus accumbens, hippocampus and cerebellum. A single dose of ethanol (1 g/kg po) potentiated the action of diazepam and muscimol. Prolonged treatment with ethanol (5 g/kg/day for 21 days) did not affect the action of diazepam. In contrast, the effect of muscimol was greatly reduced. In the rats pretreated for 21 days with ethanol five times higher doses of muscimol than in control group were necessary to induce a statistically significant increase of GABA-modulin in the cytosol of the nucleus accumbens, hippocampus and cerebellum. Those results show that a single dose of ethanol enhances GABA-ergic transmission, whereas prolonged treatment with ethanol induces subsensitivity of GABA-A but not benzodiazepine receptors in the limbic system and in cerebellum.
将GABA调节蛋白对不同剂量地西泮和蝇蕈醇的反应分别用作中枢苯二氮䓬受体和GABA - A受体敏感性的指标。地西泮和蝇蕈醇可引起大鼠伏隔核、海马和小脑中胞质GABA调节蛋白活性呈剂量依赖性增加。单次给予乙醇（1 g/kg，口服）可增强地西泮和蝇蕈醇的作用。长期给予乙醇（5 g/kg/天，持续21天）不影响地西泮的作用。相反，蝇蕈醇的作用大大降低。在经乙醇预处理21天的大鼠中，与对照组相比，需要五倍于更高剂量的蝇蕈醇才能使伏隔核、海马和小脑中胞质GABA调节蛋白有统计学意义的增加。这些结果表明，单次给予乙醇可增强GABA能传递，而长期给予乙醇会导致边缘系统和小脑中GABA - A受体而非苯二氮䓬受体出现敏感性降低。
