NMDA receptors in the midbrain play a critical role in dopamine-mediated hippocampal synaptic potentiation caused by morphine
NMDA receptors in the midbrain play a critical role in dopamine-mediated hippocampal synaptic potentiation caused by morphine
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中脑 NMDA 受体在吗啡引起的多巴胺介导的海马突触增强中发挥关键作用
DOI：
10.1111/adb.12010
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发表时间：
2014-05-01
影响因子：
3.4
通讯作者：
Zhu, Bing
中科院分区：
文献类型：
--
作者：
Hu, Ling;Jing, Xiang-Hong;Zhu, Bing
单次暴露于滥用药物在中脑腹侧被盖区（VTA）的多巴胺（DA）神经元的兴奋性突触处产生NMDAR（N-甲基-D-天冬氨酸受体）依赖性突触增强。所有成瘾性药物都可以增加中脑投射区域的DA浓度，包括海马。海马多巴胺释放随后调节海马可塑性和药物相关记忆。利用在体电生理记录技术在麻醉大鼠，我们表明，全身注射吗啡诱导海马突触增强的剂量依赖性方式。内VTA，但不是海马内注射吗啡诱发这种增强。海马多巴胺D1受体（D1 R）参与吗啡诱导的突触增强和条件性位置偏爱（CPP）。此外，VTA和VTA/海马多巴胺能连接中的NMDAR激活对于吗啡诱发的增强和CPP是必不可少的。这些发现表明，在中脑NMDAR信号在调节多巴胺介导的海马突触可塑性药物诱导的联想记忆的关键作用。
A single exposure to drugs of abuse produces an NMDAR (N-methyl-D-aspartate receptor)-dependent synaptic potentiation at excitatory synapses of dopamine (DA) neurons in the ventral tegmental area (VTA) of the midbrain. All addictive drugs can increase DA concentrations in projection areas of the midbrain, including the hippocampus. Hippocampal DA release subsequently modulates hippocampal plasticity and drug-associated memories. Using in vivo electrophysiological recording techniques in anesthetized rats, we show that systemic injection of morphine induced hippocampal synaptic potentiation in a dose-dependent manner. Intra-VTA but not intra-hippocampus injection of morphine evoked this potentiation. Local hippocampal dopamine D1 receptors (D1R) are required in the morphine-induced synaptic potentiation and conditioned place preference (CPP). Moreover, both NMDAR activation in the VTA and VTA/hippocampus dopaminergic connections are essential for the morphine-evoked potentiation and CPP. These findings suggest that NMDAR signalings in the midbrain play a key role in regulating dopamine-mediated hippocampal synaptic plasticity underlying drug-induced associative memory.