Division of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea.
Neurosci Lett. 2010 May 21;475(3):124-8. doi: 10.1016/j.neulet.2010.03.051. Epub 2010 Mar 25.
In the brain, the stress system plays an important role in motivating continued alcohol use and relapse. The neuropeptide substance P and the neurokinin-1 receptor (NK1R) are involved in the stress response and drug reward systems. Recent findings have shown that the binding of ligands to NK1Rs decreases the self-administration of alcohol in mice. We examined the effect of an artificial microRNA (amiRNA) on the functional expression of NK1R in mouse brains. Lentiviruses expressing either an amiRNA targeting the NK1R (amiNK1R) or a negative control amiRNA (amiNC) were injected into mouse brains. Four weeks after amiRNA injection, we found that amiNK1R decreased the voluntary alcohol consumption compared to mice injected with amiNC. We also observed that NK1R expression was reduced in the hippocampus. RNA interference is an effective approach to regulate the expression of specific behavior-related genes. Our results support the potential use of amiRNA as a therapeutic agent for the treatment of alcohol dependence.
在大脑中，应激系统在激励持续饮酒和复发方面起着重要作用。神经肽 P 物质和神经激肽-1 受体（NK1R）参与应激反应和药物奖励系统。最近的研究结果表明，配体与 NK1R 的结合减少了小鼠对酒精的自我给药。我们研究了人工 microRNA（amiRNA）对 NK1R 在小鼠大脑中功能表达的影响。表达靶向 NK1R 的 amiRNA（amiNK1R）或阴性对照 amiRNA（amiNC）的慢病毒被注射到小鼠大脑中。amiRNA 注射后 4 周，我们发现与注射 amiNC 的小鼠相比，amiNK1R 减少了自愿饮酒量。我们还观察到海马体中 NK1R 的表达减少。RNA 干扰是一种调节特定行为相关基因表达的有效方法。我们的研究结果支持 amiRNA 作为治疗酒精依赖的治疗剂的潜在用途。
