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首页> 外文期刊>Genes, brain, and behavior >Do specific NMDA receptor subunits act as gateways for addictive behaviors?
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Do specific NMDA receptor subunits act as gateways for addictive behaviors?

机译：特定的NMDA受体亚基是否充当上瘾行为的网关？

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摘要

Addiction to alcohol and drugs is a major social and economic problem, and there is considerable interest in understanding the molecular mechanisms that promote addictive drives. A number of proteins have been identified that contribute to expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of ionotropic glutamate receptors, have been of particular interest because their physiological properties make them an attractive candidate for gating induction of synaptic plasticity, a molecular change thought to mediate learning and memory. NMDARs are generally inactive at the hyperpolarized resting potentials of many neurons. However, given sufficient depolarization, NMDARs are activated and exhibit long-lasting currents with significant calcium permeability. Also, in addition to stimulating neurons by direct depolarization, NMDARs and their calcium signaling can allow strong and/or synchronized inputs to produce long-term changes in other molecules (such as AMPA-type glutamate receptors) which can last from days to years, binding internal and external stimuli in a long-term memory trace. Such memories could allow salient drug-related stimuli to exert strong control over future behaviors and thus promote addictive drives. Finally, NMDARs may themselves undergo plasticity, which can alter subsequent neuronal stimulation and/or the ability to induce plasticity. This review will address recent and past findings suggesting that NMDAR activity promotes drug- and alcohol-related behaviors, with a particular focus on GluN2B subunits as possible central regulators of many addictive behaviors, as well as newer studies examining the importance of non-canonical NMDAR subunits and endogenous NMDAR cofactors.
机译：对酒精和毒品的成瘾是一个重大的社会和经济问题，并且对理解促进上瘾驱动的分子机制有相当令人兴趣。已经确定了许多蛋白质，这有助于表达上瘾行为。 NMDA受体（NMDARS）是离子级谷氨酸受体的亚类，因为它们的生理特性使其成为突触诱导突触可塑性的有吸引力的候选者，分子变化思想介绍学习和记忆。 NMDAR通常在许多神经元的超极化休息潜力处于非活动状态。然而，鉴于足够的去极化，激活NMDAR并表现出具有显着钙渗透性的持久电流。此外，除了通过直接去极化的刺激神经元之外，NMDAR和它们的钙信号传导可以允许强度和/或同步的输入在其他分子（例如AMPA型谷氨酸受体）中产生可能持续几年时间的长期变化，在长期存储器迹线中将内部和外部刺激绑定。这些记忆可以让突出的药物相关的刺激对未来的行为产生强烈的控制，从而促进上瘾的驱动器。最后，NMDARS本身可以接受可塑性，这可以改变随后的神经元刺激和/或诱导可塑性的能力。该审查将讨论近期和过去的调查结果表明NMDAR活动促进了与酗酒和酗酒相关的行为，特别关注了GLUN2B亚基，作为许多上瘾行为的可能的中央监管机构，以及较新的研究检查非规范NMDAR的重要性亚基和内源性NMDAR辅因子。

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