Abstract

Methamphetamine (METH) is a potent psychostimulant that increases extracellular monoamines such as dopamine and norepinephrine and affects multiple tissue and cell types. 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 have shown to lead 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 system and peripheral immune system.

Significance Statement Emerging research has begun to show that methamphetamine not only regulates dopaminergic neuronal activity, it also affects non-neuronal brain cells, such as microglia and astrocytes as well immunological cells of the periphery. The bi-directional communication between dopaminergic neurons in the CNS and peripheral immune cells becomes dysregulated by a constellation of dysfunctional neuronal and cell types revealing multiple targets that must be considered at the interface between basic and clinical neuroscience.