阿片成瘾中的神经免疫机制

Neuroimmune Mechanism of Opiates Addiction

综述小胶质细胞参与阿片类物质成瘾行为的细胞和分子机制,以及神经免疫抑制剂防治阿片成瘾的研究进展。阿片类物质成瘾是严重的医学和社会问题。目前针对阿片成瘾的研究主要集中在神经元,戒毒药物也主要针对阿片受体,然而其效果有限。神经元不是神经通路的唯一组分,神经小胶质细胞占中枢神经系统细胞总数的10%~15%,然而其作用和功能一度被忽视。阿片能激活Toll样受体4(TLR4),活化小胶质细胞,分泌大量炎症因子,从而调节奖赏信号通路,增加神经元兴奋性,参与成瘾行为的形成和表现。研究调节性神经免疫因子以及它们所造成神经炎症反应,将为理解阿片所造成的大脑功能改变和成瘾行为提供新的思路。

This paper provides a brief review on cellular and molecular mechanism of microglia involving opiates addiction,also introduces prevention and cure of neuro-immuno suppressive agent on opiates addiction. Opiates addiction brings serious medical and social problems. Most researchers concentrate on opiates′ effects on neurons. Current rehabilitation medicines acting on opioid receptor of neurons have limited efficacy. Neurons are not the only components in central nervous system(CNS).Although accounting for 10%-15% of CNS cell,the function of microglia has been neglected. Opioid stimulates Toll-like receptor 4(TLR4),which induces microglia activation and inflammatory factors production. As a result,reward signaling pathway is regulated to increase neuron excitability,leading to drug dependence and addiction. The neuromodulatory properties of the immune factors,together with their essential role in neuroinflammation,provide a new framework to understand how neuroimmune system mediates brain function and addiction behaviors.