Methamphetamine and the brain: Emerging molecular targets and signaling pathways involved in neurotoxicity

Abstract

Methamphetamine (METH) is a psychostimulant drug widely used because of its arousing, euphoric and hallucinogenic properties. Studies have reported that chronic METH abuse causes neurotoxic effects in the central nervous system (CNS), including alterations in dopaminergic terminals, gray matter atrophy, and microgliosis in different parts of the CNS. METH administration leads to enhancement in extracellular dopamine and serotonin. Moreover, METH increases glutamate release and induces excitotoxicity due to dopamine dysregulation. METH use reduces neuronal survival, damages the physiological functions of neurons and induces neurodegeneration, primarily in association with dopamine dependent mechanisms. Moreover, METH increases protein accumulation and mitochondrial damage in the neuronal cells, and inhibits cellular clearance. Studies have reported the destructive effects of METH on diverse functional structures of the brain. This review describes several interrelated mechanisms including neurochemical changes, apoptosis, autophagy, neuroinflammation and oxidative stress, which have been shown to be involved in METH-induced neural damage. Understanding these mechanisms may pave the way for finding new strategies to prevent, manage and treatment the neurotoxic and neurodegenerative pathways involved in METH-induced disorders.

Keywords:

• Methamphetamine
• neurotoxicity
• neuroinflammation
• autophagy
• oxidative stress

Acknowledgements

The present study was a research project with the research code:APRC-0214 ethical code: IR.AJUMS.ABHC.REC.1402.068 in Ahvaz Jundishapur University of Medical Sciences. The authors are very grateful for the support and cooperation of Ahvaz Jundishapur University of Medical Sciences.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data can be made available on request.