Department of Pharmacology, Neuropharmacology Laboratory, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA.
Curr Neuropharmacol. 2023;21(2):235-259. doi: 10.2174/1570159X21666221208142151.
The use of psychostimulant drugs can modify brain function by inducing changes in the reward system, mainly due to alterations in dopaminergic and glutamatergic transmissions in the mesocorticolimbic pathway. However, the etiopathogenesis of addiction is a much more complex process. Previous data have suggested that microglia and other immune cells are involved in events associated with neuroplasticity and memory, which are phenomena that also occur in addiction. Nevertheless, how dependent is the development of addiction on the activity of these cells? Although the mechanisms are not known, some pathways may be involved. Recent data have shown psychoactive substances may act directly on immune cells, alter their functions and induce various inflammatory mediators that modulate synaptic activity. These could, in turn, be involved in the pathological alterations that occur in substance use disorder. Here, we extensively review the studies demonstrating how cocaine and amphetamines modulate microglial number, morphology, and function. We also describe the effect of these substances in the production of inflammatory mediators and a possible involvement of some molecular signaling pathways, such as the toll-like receptor 4. Although the literature in this field is scarce, this review compiles the knowledge on the neuroimmune axis that is involved in the pathogenesis of addiction, and suggests some pharmacological targets for the development of pharmacotherapy.
使用精神兴奋剂药物可以通过改变奖励系统来改变大脑功能，这主要是由于中脑边缘多巴胺能和谷氨酸能传递的改变。然而，成瘾的病因发病机制是一个更为复杂的过程。先前的数据表明，小胶质细胞和其他免疫细胞参与与神经可塑性和记忆相关的事件，这些现象也发生在成瘾中。然而，依赖症的发展与这些细胞的活性有多大关系？虽然机制尚不清楚，但可能涉及一些途径。最近的数据表明，精神活性物质可能直接作用于免疫细胞，改变它们的功能，并诱导各种炎症介质，调节突触活动。这些炎症介质反过来可能参与物质使用障碍中发生的病理性改变。在这里，我们广泛回顾了证明可卡因和安非他命如何调节小胶质细胞数量、形态和功能的研究。我们还描述了这些物质在产生炎症介质方面的作用，以及一些分子信号通路（如 toll 样受体 4）的可能参与。尽管该领域的文献很少，但本综述汇集了与成瘾发病机制相关的神经免疫轴的知识，并为开发药物治疗提出了一些药理学靶点。
