Gipson Cassandra D, Rawls Scott, Scofield Michael D, Siemsen Benjamin M, Bondy Emma O, Maher Erin E
Department of Family and Community Medicine, University of Kentucky, 741 S. Limestone, BBSRB, Room 363, Lexington, KY, 40536-0509, USA.
Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA.
J Neuroinflammation. 2021 Feb 21;18(1):56. doi: 10.1186/s12974-021-02072-8.
Chronic use of drugs of abuse affects neuroimmune signaling; however, there are still many open questions regarding the interactions between neuroimmune mechanisms and substance use disorders (SUDs). Further, chronic use of drugs of abuse can induce glutamatergic changes in the brain, but the relationship between the glutamate system and neuroimmune signaling in addiction is not well understood. Therefore, the purpose of this review is to bring into focus the role of neuroimmune signaling and its interactions with the glutamate system following chronic drug use, and how this may guide pharmacotherapeutic treatment strategies for SUDs. In this review, we first describe neuroimmune mechanisms that may be linked to aberrant glutamate signaling in addiction. We focus specifically on the nuclear factor-kappa B (NF-κB) pathway, a potentially important neuroimmune mechanism that may be a key player in driving drug-seeking behavior. We highlight the importance of astroglial-microglial crosstalk, and how this interacts with known glutamatergic dysregulations in addiction. Then, we describe the importance of studying non-neuronal cells with unprecedented precision because understanding structure-function relationships in these cells is critical in understanding their role in addiction neurobiology. Here we propose a working model of neuroimmune-glutamate interactions that underlie drug use motivation, which we argue may aid strategies for small molecule drug development to treat substance use disorders. Together, the synthesis of this review shows that interactions between glutamate and neuroimmune signaling may play an important and understudied role in addiction processes and may be critical in developing more efficacious pharmacotherapies to treat SUDs.
长期滥用药物会影响神经免疫信号传导；然而，关于神经免疫机制与物质使用障碍（SUDs）之间的相互作用仍有许多未解决的问题。此外，长期滥用药物会诱发大脑中的谷氨酸能变化，但成瘾过程中谷氨酸系统与神经免疫信号传导之间的关系尚未得到充分理解。因此，本综述的目的是聚焦长期药物使用后神经免疫信号传导的作用及其与谷氨酸系统的相互作用，以及这如何指导SUDs的药物治疗策略。在本综述中，我们首先描述可能与成瘾中异常谷氨酸信号传导相关的神经免疫机制。我们特别关注核因子-κB（NF-κB）通路，这是一种潜在的重要神经免疫机制，可能是驱动觅药行为的关键因素。我们强调星形胶质细胞-小胶质细胞相互作用的重要性，以及它如何与成瘾中已知的谷氨酸能失调相互作用。然后，我们描述以前所未有的精度研究非神经元细胞的重要性，因为了解这些细胞中的结构-功能关系对于理解它们在成瘾神经生物学中的作用至关重要。在此，我们提出一个神经免疫-谷氨酸相互作用的工作模型，该模型是药物使用动机的基础，我们认为这可能有助于小分子药物开发策略以治疗物质使用障碍。总之，本综述的综合分析表明，谷氨酸与神经免疫信号传导之间的相互作用可能在成瘾过程中发挥重要但尚未充分研究的作用，并且可能对开发更有效的药物疗法来治疗SUDs至关重要。
