NR2B-containing NMDA receptor is required for morphine-but not stress-induced reinstatement
NR2B-containing NMDA receptor is required for morphine-but not stress-induced reinstatement
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DOI：
10.1016/j.expneurol.2006.08.014
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发表时间：
2007-02-01
影响因子：
5.3
通讯作者：
Cui, Cai-Lian
中科院分区：
文献类型：
--
作者：
Ma, Yao-Ying;Chu, Ning-Ning;Cui, Cai-Lian
已知谷氨酸受体密集分布于前脑奖赏回路中，谷氨酸能传递积极参与药物滥用的奖赏和恢复作用的调节。本研究探讨了n -甲基d -天冬氨酸（NMDA）受体在吗啡条件下位置偏好（CPP）恢复中的作用。我们发现先前熄灭的吗啡（3mg /kg, i.p。）吗啡启动注射（2 mg/kg, i.p.）或急性环境应激源（强迫游泳10分钟）可明显恢复CPP，但24小时食物剥夺引起的应激不能明显恢复CPP。与此同时，恢复后的大鼠伏隔核（NAc）和海马体中NMDA受体2B亚基（NR2B）的蛋白水平升高，但前额叶皮层中没有。全身给予NR2B选择性拮抗剂伊芬地尔3,10 mg/kg, i.p)可减弱吗啡启动注射引起的恢复，但不能通过强迫游泳引起。伊芬普罗地尔（2.0 μ g/大鼠）直接注射到NAc壳或海马背侧ca1区也产生类似的效果。这些结果表明，NAc和海马背侧含有nr2b的NMDA受体在介导吗啡奖励反应的恢复中发挥了重要作用。(c) 2006爱思唯尔公司版权所有。
Glutamate receptors are known to be densely distributed in the forebrain rewarding circuits, and glutamatergic transmission is actively involved in the regulation of rewarding and reinstating effects of drugs of abuse. Here we investigated the possible involvement of the N-methylD-aspartate (NMDA) receptors in the reinstatement of extinguished morphine conditioned place preference (CPP) in rats. We found that previously extinguished morphine (3 mg/kg, i.p.) CPP was markedly reinstated by a priming injection of morphine (2 mg/kg, i.p.) or an acute environmental stressor (forced swim for 10 min), but not by the stress induced by a 24-h food deprivation. Parallel with this, protein levels of the NMDA receptor 2B subunit (NR2B) were elevated in the nucleus accumbens (NAc) and the hippocampus, but not the prefrontal cortex, of reinstated rats. Systemic administration of an NR2B selective antagonist ifenprodil 3, 10 mg/kg, i.p.) attenuated the reinstatement induced by a priming morphine injection, although not by the forced swim. Ifenprodil (2.0 mu g/rat) directly injected into the NAc shell or the CA 1 region of the dorsal hippocampus produced a similar effect. These results indicate that the NR2B-containing NMDA receptors in the NAc and the dorsal hippocampus play a significant role in mediating the reinstatement of rewarding responses to morphine. (c) 2006 Elsevier Inc. All rights reserved.