INFLUENCE OF ETHANOL AND GLUCOCORTICOIDS ON GABA RECEPTORS IN THE CNS

乙醇对神经元细胞具有剂量依赖性的刺激或抑制作用。 CNS;然而，这些作用的机制尚不清楚。 乙醇改变 几种中枢作用GABA能药物的作用，如 苯二氮卓类药物和巴比妥类药物，这表明乙醇 GABA受体。 乙醇对结合具有双相作用， 蝇蕈醇（GABA-A激动剂）对突触体膜中GABA受体的作用 从不同的大脑区域获得。 蝇蕈醇的结合在 浓度范围为1.5 mM至6 mM的乙醇，而 在更高的浓度下增强。 蝇蕈醇结合减少， 发现低水平乙醇的存在是由于配体还原 对GABA受体的亲和力，而在高浓度下增强蝇蕈醇结合， 乙醇浓度增加是由于受体数量增加。 糖皮质激素似乎也直接作用于中枢GABA受体， 以与乙醇相反的剂量依赖性方式。 纳摩尔 浓度的糖皮质激素增强蝇蕈醇结合，而 微摩尔浓度抑制结合。 这些影响是由于 受体对配体的亲和力增加，受体数量减少 分别在低或高水平糖皮质激素的存在下。

Ethanol exerts a dose-dependent stimulatory or inhibitory effect on the CNS; the mechanism of these effects is not, however, clear. Ethanol alters the action of several centrally acting GABA-ergic drugs, such as benzodiazepines and barbiturates, which suggests that ethanol interacts with GABA receptors. Ethanol exerts a biphasic effect on the binding of muscimol (GABA-A agonist) to GABA receptors in synaptosomal membranes obtained from different brain regions. Muscimol binding is inhibited at concentrations of ethanol ranging from 1.5 mM to 6 mM, whereas it is enhanced at higher concentrations. Decreased muscimol binding in the presence of low levels of ethanol was found to be due to reduced ligand affinity to the GABA receptors, whereas enhanced muscimol binding at high ethanol concentrations was due to increased receptor number. Glucocorticoids also appear to act directly on central GABA receptors, but in a dose-dependent manner opposite to that of ethanol. Nanomolar concentrations of glucocorticoids enhance muscimol binding, whereas micromolar concentrations inhibit binding. These effects are due to increased receptor affinity for the ligand and a decreased receptor number in the presence of low or high levels of glucocorticoids, respectively.