Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats
Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats
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DOI：
10.1111/j.1460-9568.2004.03101.x
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发表时间：
2004-01-01
影响因子：
3.4
通讯作者：
Satoh, M
中科院分区：
文献类型：
--
作者：
Ozawa, T;Nakagawa, T;Satoh, M
有大量证据表明中枢谷氨酸能系统参与了吗啡依赖。我们先前报道了吗啡依赖和纳洛酮催促戒断大鼠部分脑区胶质谷氨酸转运体GLT-1mRNA表达的变化，以及谷氨酸转运体激动剂对吗啡身体依赖的抑制作用。这些发现支持GLT-1等谷氨酸转运体参与吗啡依赖的可能性。在本研究中，我们观察了重组腺病毒将GLT-1基因转移到蓝斑(LC)对大鼠吗啡身体依赖的影响。我们构建了重组腺病毒，在体内外成功地携带了GLT-1基因。与对照组相比，注射吗啡颗粒前双侧LC内局部过表达GLT-1的重组腺病毒显著抑制了纳洛酮催促吗啡戒断的各种躯体体征。这些结果表明，Lc内的GLT-1对吗啡的身体依赖具有抑制作用。
There is a body of evidence implying the involvement of the central glutamatergic system in morphine dependence. We previously reported changes in the mRNA expression of a glial glutamate transporter GLT-1 in some brain regions of morphine-dependent and naloxone-precipitated withdrawal rats, and inhibition of morphine physical dependence by a glutamate transporter activator in mice. These findings support the possibility that glutamate transporters such as GLT-1 are involved in morphine dependence. In this study, we examined the effects of gene transfer of GLT-1 into the locus coeruleus (LC) by recombinant adenoviruses on morphine physical dependence in rats. We constructed recombinant adenoviruses that successfully delivered the GLT-1 gene in vitro and in vivo. Local overexpression of GLT-1 within the bilateral LC by the recombinant adenoviruses before implantation of the morphine pellet significantly inhibited various somatic signs of naloxone-precipitated morphine withdrawal, compared with the control. These results suggest that GLT-1 within the LC plays an inhibitory role in morphine physical dependence.