Methamphetamine Dysregulation of the Central Nervous System and Peripheral Immunity

Abstract

Methamphetamine (METH) is a potent psychostimulant that increases extracellular monoamines such as dopamine and norepinephrine and affects multiple tissue and cell types in the 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 StatementEmerging 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.

Sex differences in methamphetamine use disorder perused from pre-clinical and clinical studies: Potential therapeutic impacts

“…Repeated METH misuse leads to loss of control over drug use, compulsive use despite negative consequences, and multiple relapse episodes in humans who meet diagnostic criteria for METH use disorder (MUD) ( DSM-5, 2013 ). Multi-system dysfunctions can accompany the misuse of METH even in those who may or may not have met criteria for MUD ( Jayanthi et al, 2021 ; Miller et al, 2021 ). These adverse consequences may include loss of appetite, anxiety, depression, delusional ideations including full-blown paranoia, tactile hallucinations, suicidal ideation, and successful suicides ( Darke et al, 2019 ; Glasner-Edwards et al, 2011 ; Lisa et al, 2019 ; Mahoney et al, 2010 , 2008 ; Polcin et al, 2012 ; Su et al, 2017 ).…”

“…It is important to note that prolonged METH use can also be associated with neurological and neurotoxic damage to the brain ( Bae et al, 2006 ; Bonk et al, 2020 ; Du et al, 2015 ; Hall et al, 2015 ; Kogachi et al, 2017 ; Nie et al, 2021 ; NSDUH, 2019 ; Paknahad et al, 2021 ; Tobias et al, 2010 ). Studies conducted in various animal models have provided some clues to the molecular and biochemical mechanisms involved in METH-induced neurodegenerative changes in the brain ( Jayanthi et al, 2021 ; Miller et al, 2021 ). Nevertheless, there is evidence that METH might also cause its clinical and other deleterious effects in a sex-dependent fashion ( Daiwile et al, 2021 , 2019 ).…”

Effects and associated transcriptomic landscape changes of methamphetamine on immune cells

“…Immune cells are an important part of the immune system, and an increasing number of studies have found them to be impaired in METH abuse [ 23 , 24 , 32 ]. In this study, we constructed models of METH-treated cells of three common immune cells in vitro and evaluated the effects of METH in the resting state of immune cells.…”

Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal

“…As noted in the literature, numerous experimental models have been applied to explore the knowledge regarding the impartments in the nerve system and the immune system from METH exposure and withdrawal (Loftis and Janowsky, 2014;Potula et al, 2018;Miller et al, 2021). Because the exosomes could cross the blood-brain-barrier (BBB) into the bloodstream, making it possible to extract CNS-derived bioactive substances, the peripheral exosomes have been thought to be promising 10.3389/fncel.2022.961131 minimally invasive biomarkers and therapeutic targets for neuronal diseases (Gao et al, 2021;Pineles et al, 2022), multiple lines of evidence indicate that the circulating exosomes might act as the bridge for intercellular communications between neuronal cells (Meng et al, 2020), while contents of these exosomes were closely related to METH addiction status in rats (Li et al, 2018).…”