Department of Neuroscience, College of Medicine (D.R.M., M.B., A.G., H.K.), and Department of Oral Biology, College of Dentistry (L.R.M.), University of Florida, Gainesville, Florida.
Department of Neuroscience, College of Medicine (D.R.M., M.B., A.G., H.K.), and Department of Oral Biology, College of Dentistry (L.R.M.), University of Florida, Gainesville, Florida
J Pharmacol Exp Ther. 2021 Dec;379(3):372-385. doi: 10.1124/jpet.121.000767. Epub 2021 Sep 17.
Methamphetamine (METH) is a potent psychostimulant that increases extracellular monoamines, such as dopamine and norepinephrine, and affects multiple tissue and cell types in the central nervous system (CNS) and peripheral immune cells. The reinforcing properties of METH underlie its significant abuse potential and dysregulation of peripheral immunity and central nervous system functions. Together, the constellation of METH's effects on cellular targets and regulatory processes has led to immune suppression and neurodegeneration in METH addicts and animal models of METH exposure. Here we extensively review many of the cell types and mechanisms of METH-induced dysregulation of the central nervous and peripheral immune systems. SIGNIFICANCE STATEMENT: Emerging research has begun to show that methamphetamine regulates dopaminergic neuronal activity. In addition, METH affects non-neuronal brain cells, such as microglia and astrocytes, and immunological cells of the periphery. Concurrent disruption of bidirectional communication between dopaminergic neurons and glia in the CNS and peripheral immune cell dysregulation gives rise to a constellation of dysfunctional neuronal, cell, and tissue types. Therefore, understanding the pathophysiology of METH requires consideration of the multiple targets at the interface between basic and clinical neuroscience.
甲基苯丙胺（METH）是一种有效的精神兴奋剂，可增加细胞外单胺类物质，如多巴胺和去甲肾上腺素，并影响中枢神经系统（CNS）和外周免疫细胞中的多种组织和细胞类型。METH 的强化特性是其具有显著滥用潜力的基础，会导致外周免疫和中枢神经系统功能失调。METH 对细胞靶标和调节过程的综合影响导致了吸毒者和 METH 暴露动物模型中的免疫抑制和神经退行性变。在这里，我们广泛回顾了 METH 引起的中枢神经系统和外周免疫系统失调的许多细胞类型和机制。意义陈述：新兴研究已经开始表明，甲基苯丙胺调节多巴胺能神经元的活性。此外，METH 还会影响非神经元脑细胞，如小胶质细胞和星形胶质细胞，以及外周免疫细胞。CNS 中多巴胺能神经元和神经胶质细胞之间的双向通讯以及外周免疫细胞失调的同时破坏，导致一系列功能失调的神经元、细胞和组织类型。因此，理解 METH 的病理生理学需要考虑基础和临床神经科学之间界面的多个靶标。
