Involvement of glial glutamate transporters in morphine dependence
Involvement of glial glutamate transporters in morphine dependence
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DOI：
10.1196/annals.1307.047
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Satoh, M
中科院分区：
文献类型：
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作者：
Nakagawa, T;Satoh, M
有几条线索的证据表明，参与吗啡依赖的中枢神经系统。从神经末梢释放的细胞外谷氨酸被神经元（EAAC 1和EAAT 4）和神经胶质细胞（GLT-1和GLAST）中的谷氨酸转运体平衡，从而调节谷氨酸能系统并保护神经元免受谷氨酸的兴奋性毒性作用。在这里，我们表明，神经胶质谷氨酸转运蛋白GLT-1可能参与身体和心理吗啡依赖。通过北方印迹分析，胶质细胞谷氨酸转运体GLT-1，而不是GLAST，mRNA的表达减少，在纹状体/中脑核（NAc）和丘脑的吗啡依赖大鼠。皮下注射谷氨酸转运体激活剂可抑制吗啡依赖和吗啡诱导的条件性位置偏爱。侧脑室注射谷氨酸转运体抑制剂对吗啡依赖大鼠促进了纳洛酮诱导的吗啡戒断诱导的躯体体征和条件性位置厌恶的表达。此外，基因转移技术，使用重组腺病毒显示，GLT-1在蓝斑和NAc壳发挥抑制作用，在生理和心理吗啡依赖，分别。这些发现可能为神经胶质谷氨酸转运体GLT-1可能成为预防生理和心理吗啡依赖的新靶点提供证据。
There are several lines of evidence implying the involvement of the central glutamatergic system in morphine dependence. Extracellular glutamate released from nerve terminals is counterbalanced by glutamate transporters in neurons (EAAC1 and EAAT4) and glial cells (GLT-1 and GLAST), thereby modulating the glutamatergic system and protecting neurons from an excitotoxic action of glutamate. Here we show that a glial glutamate transporter GLT-1 could be involved in physical and psychological morphine dependence. By Northern blot analysis, the expression of glial glutamate transporter GLT-1, but not GLAST, mRNA was decreased in the striatum/nucleus accumbens (NAc) and thalamus of morphine-dependent rats. Subcutaneous administration of a glutamate transporter activator suppressed the development of physical morphine dependence and morphine-induced conditioned place preference. Intracerebroventricular administration of a glutamate transporter inhibitor to morphine-dependent rats facilitated the expression of naloxone-precipitated morphine withdrawal-induced somatic signs and conditioned place aversion. Furthermore, gene transfer techniques using recombinant adenoviruses revealed that GLT-1 in the locus coeruleus and NAc shell plays inhibitory roles in physical and psychological morphine dependence, respectively. These findings may provide evidence that a glial glutamate transporter GLT-1 could be a new target for preventing physical and psychological morphine dependence.