Losada M E
Instituto de Investigaciones Farmacológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):669-74. doi: 10.1007/BF00175794.
The acute effects of corticosterone (0.5 and 1 mg/kg, i.p.) upon the GABAergic system have been investigated. While no changes were detected after treatment with corticosterone 0.5 mg/kg, the administration of 1 mg/kg lowered the levels of gamma-aminobutyric acid (GABA) (29%) in the mediobasal hypothalamus either 30 or 60 min after injection in both young (3-4 weeks old) and adult (7-8 weeks old) rats. No changes were found in the frontal cerebral cortex. Only in young rats did the administration of corticosterone (1 mg/kg, 30 min) reduced GABA levels in the corpus striatum (34%). In young rats this dose of corticosterone: 1. did not affect the activity of the enzymes of the metabolism of GABA (GAD and GABA-T); 2. reduced neuronal 3H-GABA uptake in the corpus striatum (30%) and in the mediobasal hypothalamus (46%), and increased it in the frontal cortex (2-fold); 3. enhanced the turnover of GABA (2-fold) in the corpus striatum. These values were unaffected by 0.5 mg/kg. Corticosterone 0.5 and 1 mg/kg did not alter non-neuronal 3H-GABA uptake. These findings show an area-related and age- and dose-dependent response of the GABAergic pathways to acute corticosterone treatment. This is discussed in relation to the age-related sensitivity to the environmental stimuli which cause this release of corticosteroids. The stimulation of GABAergic function which occurs mainly in the corpus striatum as estimated from the increase in its turnover may be related to the postulated anticonvulsant role of corticosteroids.
已对皮质酮(0.5和1毫克/千克,腹腔注射)对γ-氨基丁酸(GABA)能系统的急性作用进行了研究。在用0.5毫克/千克皮质酮处理后未检测到变化,但在幼鼠(3 - 4周龄)和成年鼠(7 - 8周龄)中,注射1毫克/千克皮质酮后30或60分钟,中基底下丘脑的γ-氨基丁酸(GABA)水平降低(29%)。额叶大脑皮层未发现变化。仅在幼鼠中,注射皮质酮(1毫克/千克,30分钟)降低了纹状体中的GABA水平(34%)。对于幼鼠,该剂量的皮质酮:1. 不影响GABA代谢酶(谷氨酸脱羧酶和GABA转氨酶)的活性;2. 降低了纹状体(30%)和中基底下丘脑(46%)中神经元对3H - GABA的摄取,并使额叶皮层中的摄取增加了两倍;3. 增强了纹状体中GABA的周转(两倍)。这些值不受0.5毫克/千克的影响。0.5和1毫克/千克的皮质酮未改变非神经元对3H - GABA的摄取。这些发现表明GABA能通路对急性皮质酮处理存在区域相关、年龄和剂量依赖性反应。这与对导致皮质类固醇释放的环境刺激的年龄相关敏感性进行了讨论。根据其周转增加估计主要发生在纹状体中的GABA能功能刺激可能与皮质类固醇假定的抗惊厥作用有关。