Methamphetamine Dysregulation of the Central Nervous System and Peripheral Immunity

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 379; no. 3; pp. 372 - 385
• Main Authors: Miller, Douglas R., Bu, Mengfei, Gopinath, Adithya, Martinez, Luis R., Khoshbouei, Habibeh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2021; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Brain - drug effects; Brain - immunology; Central Nervous System - drug effects; Central Nervous System - immunology; Central Nervous System Stimulants - pharmacology; Humans; Immunity, Cellular - drug effects; Immunity, Cellular - immunology; Methamphetamine - pharmacology; Microglia - drug effects; Microglia - immunology; Minireview; BBB; IL; METH; CNS; PKC; TAAR1; TNF; LPS; IFN; MMP; NF-κB; CaMKII; HIV; DAT; ROS; VMAT2; TLR; NK; DC
• ISSN: 0022-3565; 1521-0103; 1521-0103
• DOI: 10.1124/jpet.121.000767

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. 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.