STRIATAL DOPAMINE AND GLUTAMATE RECEPTORS MODULATE METHAMPHETAMINE-INDUCED CORTICAL Fos EXPRESSION
STRIATAL DOPAMINE AND GLUTAMATE RECEPTORS MODULATE METHAMPHETAMINE-INDUCED CORTICAL Fos EXPRESSION
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DOI：
10.1016/j.neuroscience.2009.04.023
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发表时间：
2009-07-21
期刊：
影响因子：
3.3
通讯作者：
Marshall, J. F.
中科院分区：
文献类型：
--
作者：
Gross, N. B.;Marshall, J. F.
甲基苯丙胺 (mAMPH) 是一种精神兴奋药物，可增加整个大脑细胞外单胺的水平。此前已观察到，单次注射 mAMPH 会增加纹状体和大脑皮层中立即早期基因 (IEG) 的表达。此外，这种效应受到多巴胺和谷氨酸受体的调节，因为已发现全身施用多巴胺或谷氨酸拮抗剂可以改变mAMPH诱导的纹状体和皮质IEG表达。然而，由于多巴胺和谷氨酸受体存在于纹状体外和纹状体大脑区域，因此采用全身注射多巴胺或谷氨酸拮抗剂的研究未能定位 mAMPH 诱导的激活的影响。在本实验中，研究了纹状体多巴胺和谷氨酸受体在纹状体和大脑皮层 mAMPH 诱导的基因表达中的作用。 Fos（IEG c-fos 的蛋白质产物）的核表达在接受纹状体内多巴胺或谷氨酸拮抗剂给药的动物的纹状体和皮质中进行了定量。纹状体内输注多巴胺（D1或D2）或谷氨酸[N-甲基-D-天冬氨酸（NMDA）或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）]拮抗剂不仅影响mAMPH诱导的纹状体，而且影响皮质Fos表达。总体而言，拮抗剂的作用在输注半球和非输注半球中均呈剂量依赖性，其中在输注半球中影响更大。最后，单侧纹状体内输注多巴胺或谷氨酸拮抗剂将大鼠的行为从特征性 mAMPH 诱导的刻板行为改变为与输注同侧的旋转。这些结果表明，mAMPH 对纹状体多巴胺和谷氨酸受体的作用调节 mAMPH 诱导的广泛皮质激活。据推测，黑质纹状体末梢释放的多巴胺调节纹状体传出通路内的活动，从而解除丘脑皮质回路的抑制。推而广之，这些结果表明，反复暴露于 mAMPH 可能会影响 mAMPH 滥用者的皮质功能。 (C) 2009 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Methamphetamine (mAMPH) is a psychostimulant drug that increases extracellular levels of monoamines throughout the brain. It has previously been observed that a single injection of mAMPH increases immediate early gene (IEG) expression in both the striatum and cerebral cortex. Moreover, this effect is modulated by dopamine and glutamate receptors since systemic administration of dopamine or glutamate antagonists has been found to alter mAMPH-induced striatal and cortical IEG expression. However, because dopamine and glutamate receptors are found in extra-striatal as well as striatal brain regions, studies employing systemic injection of dopamine or glutamate antagonists fail to localize the effects of mAMPH-induced activation. In the present experiments, the roles of striatal dopamine and glutamate receptors in mAMPH-induced gene expression in the striatum and cerebral cortex were examined. The nuclear expression of Fos, the protein product of the IEG c-fos, was quantified in both the striatum and the cortex of animals receiving intrastriatal dopamine or glutamate antagonist administration. Intrastriatal infusion of dopamine (D1 or D2) or glutamate [N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] antagonists affected not only mAMPH-induced striatal, but also cortical, Fos expression. Overall, the effects of the antagonists occurred dose-dependently, in both the infused and non-infused hemispheres, with greater influences occurring in the infused hemisphere. Finally, unilateral intrastriatal infusion of dopamine or glutamate antagonists changed the behavior of the rats from characteristic mAMPH-induced stereotypy to rotation ipsilateral to the infusion. These results demonstrate that mAMPH's actions on striatal dopamine and glutamate receptors modulate the widespread cortical activation induced by mAMPH. It is hypothesized that dopamine release from nigrostriatal terminals modulates activity within striatal efferent pathways, thereby disinhibiting thalamo-cortical circuits. By extension, these results suggest processes through which repeated exposure to mAMPH might influence cortical function in mAMPH abusers. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.