Morphine and MK-801 administration leads to alternative N-methyl-D-aspartate receptor 1 splicing and associated changes in reward seeking behavior and nociception on an operant orofacial assay.
Morphine and MK-801 administration leads to alternative N-methyl-D-aspartate receptor 1 splicing and associated changes in reward seeking behavior and nociception on an operant orofacial assay.
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DOI：
10.1016/j.neuroscience.2012.04.032
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发表时间：
2012-07-12
期刊：
影响因子：
3.3
通讯作者：
Caudle, R. M.
中科院分区：
文献类型：
--
作者：
Anderson, E. M.;Del Valle-Pinero, A. Y.;Suckow, S. K.;Nolan, T. A.;Neubert, J. K.;Caudle, R. M.
NMDA受体在阿片类药物诱导的神经系统可塑性变化中发挥重要作用。其NR 1亚基的表达水平被吗啡显著改变，但其选择性剪接没有变化。N1、C1、C2和C2'盒剪接的变化可改变该受体的药理学和调节。对吗啡耐受的大鼠的脑组织进行的蛋白质印迹显示，杏仁核和杏仁核中的N1盒以及杏仁核和背侧海马体中的C1盒的剪接发生了变化。停药三天后，这些区域中的每一个都下调了含C2 '的NR 1亚基。这些不是由于急性剂量的吗啡，并可能代表药物诱导的神经可塑性的长期改变。我们还研究了吗啡耐受性对操作性口面伤害性试验的影响，该试验迫使动物忍受令人厌恶的热刺激以获得甜牛奶奖励。吗啡降低了疼痛敏感性，但也增加了在这项任务中的动机奖励寻求。NMDAR拮抗作用增强了这种奖赏寻求行为，这表明MK-801实际上可能改变吗啡的奖赏和/或动机特性，而不是减弱耐受性。当MK-801和吗啡联合使用时，会产生叠加效应，导致杏仁核、杏仁核和背侧海马体的剪接发生改变。总之，NR 1剪接可能在认知行为方面发挥重要作用，特别是在动机性奖励寻求行为中。
The NMDA receptor plays a large role in opioid-induced plastic changes in the nervous system. The expression levels of its NR1 subunit are altered dramatically by morphine but no changes in its alternative splicing have been reported. Changes in the splicing of the N1, C1, C2, and C2’ cassettes can alter the pharmacology and regulation of this receptor. Western blots run on brain tissue from rats made tolerant to morphine revealed altered splicing of the N1 cassettes in the accumbens and amygdala, and the C1 cassette in the amygdala and the dorsal hippocampus. After three days of withdrawal C2’-containing NR1 subunits were down-regulated in each of these areas. These were not due to acute doses of morphine and may represent long term alterations in drug-induced neuroplasticity. We also examined the effects of morphine tolerance on an operant orofacial nociception assay which forces an animal to endure an aversive heat stimulus in order to receive a sweet milk reward. Morphine decreased pain sensitivity as expected but also increased motivational reward seeking in this task. NMDAR antagonism potentiated this reward seeking behavior suggesting that instead of attenuating tolerance, MK-801 may actually alter the rewarding and/or motivational properties of morphine. When combined, MK-801 and morphine had an additive effect which led to altered splicing in the accumbens, amygdala, and the dorsal hippocampus. In conclusion, NR1 splicing may play a major role in the cognitive behavioral aspects especially in motivational reward seeking behaviors.
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影响因子：
3.6
作者：
BUFFALO, EA;GILLAM, MP;PAULE, MG
通讯作者：
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去极化和CAM激酶IV通过两个必需的RNA元素调节NMDA受体剪接。
影响因子：
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作者：
Lee, Ji-Ann;Xing, Yi;Nguyen, David;Xie, Jiuyong;Lee, Christopher J;Black, Douglas L
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影响因子：
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作者：
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影响因子：
3.4
作者：
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DOI：
10.1152/ajpregu.00406.2010
发表时间：
2011-07-01
影响因子：
2.8
作者：
Katsuura, Yoshihiro;Heckmann, Jennifer A.;Taha, Sharif A.
通讯作者：
Taha, Sharif A.