靶向神经小胶质细胞的戒毒治疗策略

鸦片用于镇痛治疗有千余年历史， 其滥用导致药物成瘾， 带来严重的社会和医学问题。关于鸦片等精神活性物质的研究主要围绕 神经元，当前的戒毒药物作用于神经元的阿片受体或离子通道受体，然而其戒毒效果非常有限。神经元不是中枢神经系统中调节神经信号 转导的唯一组分，神经小胶质细胞占中枢神经系统的 10%~15%，然而其作用和功能在很长一段时间被忽视。鸦片、可卡因、冰毒及其他 精神活性物质激活 Toll 样受体 4 (TLR4)，活化小胶质细胞，产生大量炎症因子，从而调节奖赏信号通路，增加神经元的兴奋性，导致药物 依赖和成瘾，因而 TLR4 是开发新型戒毒药物的靶点。综述药物成瘾的小胶质细胞分子机制以及靶向小胶质细胞的治疗药物成瘾的药物发现。

Treatment Strategy for Drug Addiction by Targeting Microglia

Opioids have been used as analgesics for more than one thousand years. However, addiction resulted from the abuse of opioids and other psycho-active substances brings about serious medical and social problems. Most opioids researches concentrate on their effects on neurons. Current rehabilitation medicines act on opioid receptor or ion channel receptor of neurons with limited efficacy. Neurons are not the only components modulating signal transduction in central nerve system (CNS). Although accounting for 10% -15% of CNS, the function of microglia has long been neglected. Opioids, cocaine, ice and other psycho-active substances stimulate Toll-like receptor 4 (TLR4), which induces microg lia activation and pro-inflammatory factors production. As a result, reward signaling pathway is regulated to increase neuron excitability, leading to drug dependence and addiction. Therefore, TLR4 becomes the target of novel types of rehabilitation medicines. Herein we reviewed the molecular and cellular mechanisms utilized by microglia that contribute to drug addiction and highlighted drug discovery of TLR4 inhibitors for treating drug addiction.