Devaud L L
Department of Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello, Idaho 83209-8334, USA.
Alcohol Clin Exp Res. 2001 Apr;25(4):606-11.
Neuroadaptations of GABAergic and glutamatergic systems appear to play an important role in both the acute as well as chronic effects of ethanol. Chronic ethanol intake leads to the development of ethanol tolerance and dependence that is associated with a decrease in GABAergic and an increase in glutamatergic function. The present report assessed the involvement of GABA and glutamate transporters in the chronic ethanol-induced adaptations of these two neuronal systems.
Male and female rats were made ethanol dependent by 2-week administration of ethanol in a liquid diet. Levels of GABA (GAT-1, GAT-3) and glutamate (GLT-1, EAAC-1) transporters were assayed by immunoblotting. Transporter function was assessed by [3H]GABA and [3H]glutamate uptake assays.
Ethanol dependence did not alter levels of GABA or glutamate transporters in cerebral cortex compared with pair-fed control values. There were increases in some, but not all, transporter levels in hippocampus and hypothalamus with the development of ethanol dependence. A decreased rate of uptake was observed for GABA in cerebral cortex. There was no change in maximal GABA uptake or in glutamate uptake (Vmax).
These results suggest that alterations in GABA and glutamate transporters have only a limited role in neuroadaptations to chronic ethanol intake in rats. However, the observed alterations were region-specific, supporting the complex responses to chronic ethanol exposure and suggesting that neuroadaptations of GABAergic and glutamatergic systems vary across the brain.
γ-氨基丁酸(GABA)能和谷氨酸能系统的神经适应性似乎在乙醇的急性和慢性效应中均发挥重要作用。长期摄入乙醇会导致乙醇耐受性和依赖性的发展,这与GABA能功能降低和谷氨酸能功能增强有关。本报告评估了GABA和谷氨酸转运体在慢性乙醇诱导的这两种神经元系统适应性变化中的作用。
通过在液体饮食中给予乙醇2周,使雄性和雌性大鼠产生乙醇依赖性。通过免疫印迹法检测GABA(GAT-1、GAT-3)和谷氨酸(GLT-1、EAAC-1)转运体的水平。通过[3H]GABA和[3H]谷氨酸摄取试验评估转运体功能。
与配对喂养的对照值相比,乙醇依赖性并未改变大脑皮层中GABA或谷氨酸转运体的水平。随着乙醇依赖性的发展,海马体和下丘脑的部分(而非全部)转运体水平有所增加。观察到大脑皮层中GABA的摄取速率降低。最大GABA摄取或谷氨酸摄取(Vmax)没有变化。
这些结果表明,GABA和谷氨酸转运体的改变在大鼠对慢性乙醇摄入的神经适应性变化中仅起有限作用。然而,观察到的改变具有区域特异性,支持了对慢性乙醇暴露的复杂反应,并表明GABA能和谷氨酸能系统的神经适应性在大脑中各不相同。