Toll-Like Receptor 4: A Novel Target to Tackle Drug Addiction?
Toll-Like Receptor 4: A Novel Target to Tackle Drug Addiction?
复制标题
Toll 样受体 4：解决毒瘾问题的新靶点？
DOI：
10.1007/164_2022_586
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发表时间：
2022
影响因子：
--
通讯作者：
Wu,Ruyan
中科院分区：
文献类型：
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作者：
Liu,Jianfeng;Li,Jun-Xu;Wu,Ruyan
药物成瘾是一种慢性脑疾病，其特征是强迫性的药物寻求和服用行为，尽管会产生重大的负面后果。目前已建立的药物成瘾的神经基础，促进了对这种疾病的理解的实质性进展。然而，长期以来，药物成瘾的非神经机制一直被低估。幸运的是，越来越多的证据表明，神经免疫系统，尤其是Toll样受体4（TLR 4）信号传导，在药物成瘾的不同阶段发挥着重要作用。阿片类药物，精神兴奋剂和酒精等药物激活TLR4信号并增强促炎反应，这与药物奖励相关的行为有关。虽然广泛的研究表明，抑制TLR4减弱了药物相关的反应，但有相互矛盾的发现表明TLR4信号可能不是药物成瘾所必需的。在本章中，将讨论临床前和临床研究，以进一步评估是否TLR4为基础的神经免疫药物治疗可用于治疗药物成瘾。此外，还将讨论TLR 4抑制调节药物相关行为的可能机制。
Drug addiction is a chronic brain disease characterized by compulsive drug-seeking and drug-taking behaviors despite the major negative consequences. Current well-established neuronal underpinnings of drug addiction have promoted the substantial progress in understanding this disorder. However, non-neuronal mechanisms of drug addiction have long been underestimated. Fortunately, increased evidence indicates that neuroimmune system, especially Toll-like receptor 4 (TLR4) signaling, plays an important role in the different stages of drug addiction. Drugs like opioids, psychostimulants, and alcohol activate TLR4 signaling and enhance the proinflammatory response, which is associated with drug reward-related behaviors. While extensive studies have shown that inhibition of TLR4 attenuated drug-related responses, there are conflicting findings implicating that TLR4 signaling may not be essential to drug addiction. In this chapter, preclinical and clinical studies will be discussed to further evaluate whether TLR4-based neuroimmune pharmacotherapy can be used to treat drug addiction. Furthermore, the possible mechanisms underlying the effects of TLR4 inhibition in modulating drug-related behaviors will also be discussed.